SEARCH RESULTS FOR:

Myocardial Infarction: Findings on History

Yu Yan - MI Findings on History - FINAL.pptx - Myocardial Infarction: Findings on HistoryLegend:Published January 30, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsAuthor: Yan YuReviewers:Sean SpenceTristan JonesNanette Alvarez** MD at time of publication Systolic function(necrotic myocardium cannot contract as well)Reflexive ? in sympathetic activity (to try to maintain CO)Clammy skin? stroke volume (SV), ? cardiac output (CO)Myocardial infarction (tissue necrosis)Note: Myocardial ischemic pain may differ between patients, but recurrences usually feel the same in any given patient.Generalized vasoconstrictionVasoconstriction of skin arteriolesCool skinLocal myocardial inflammationIrritation of T1-T4 sympathetic afferentsIrritation of cardiac branches of vagus nerveSignals enter spinal cord, mixes with T1-T4 dermatomesCrushing, Diffuse L).(Onset: often at rest; crescendo)Activation of reflexive vagal responses (listed below)Weakness, dizziness, nausea, vomitingInflammatory mediators irritates nerves innervating the heart (the cardiac plexus)Cytokines act on hypothalamic T0 regulatorMild fever? Sweating (diaphoresis)Inflammatory cytokines can spread systemicallyBrain perceives nerve irritation as pain coming from T1-T4 dermatomesBlood backs up from the LV, into the left atrium and eventually accumulates in the pulmonary vasculatureHigh pulmonary venous blood pressure forces fluid out of capillaries, into pulmonary interstitium & alveoliRespiratory muscles work harder to ventilate lungsSoggier lung interstitium ? lung complianceDyspnea(Shortness of breath)Fluid compresses airways, ? resistance to airflow 102 kB / 204 words" title="Yu Yan - MI Findings on History - FINAL.pptx - Myocardial Infarction: Findings on HistoryLegend:Published January 30, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsAuthor: Yan YuReviewers:Sean SpenceTristan JonesNanette Alvarez** MD at time of publication Systolic function(necrotic myocardium cannot contract as well)Reflexive ? in sympathetic activity (to try to maintain CO)Clammy skin? stroke volume (SV), ? cardiac output (CO)Myocardial infarction (tissue necrosis)Note: Myocardial ischemic pain may differ between patients, but recurrences usually feel the same in any given patient.Generalized vasoconstrictionVasoconstriction of skin arteriolesCool skinLocal myocardial inflammationIrritation of T1-T4 sympathetic afferentsIrritation of cardiac branches of vagus nerveSignals enter spinal cord, mixes with T1-T4 dermatomesCrushing, Diffuse "Pain" or "tightness": Often retrosternal, with radiation to shoulder, neck, and inner aspect of both arms (R > L).(Onset: often at rest; crescendo)Activation of reflexive vagal responses (listed below)Weakness, dizziness, nausea, vomitingInflammatory mediators irritates nerves innervating the heart (the cardiac plexus)Cytokines act on hypothalamic T0 regulatorMild fever? Sweating (diaphoresis)Inflammatory cytokines can spread systemicallyBrain perceives nerve irritation as pain coming from T1-T4 dermatomesBlood backs up from the LV, into the left atrium and eventually accumulates in the pulmonary vasculatureHigh pulmonary venous blood pressure forces fluid out of capillaries, into pulmonary interstitium & alveoliRespiratory muscles work harder to ventilate lungsSoggier lung interstitium ? lung complianceDyspnea(Shortness of breath)Fluid compresses airways, ? resistance to airflow 102 kB / 204 words" />

process

lower-urinary-tract-infections-complications

Predisposing Factors: Immunocompromised state, diabetes, elderly, female (short urethra), stagnant urine (anatomical variant, obstruction, neurogenic bladder, urinary reflux) Bacterial entry (Less Common): Indwelling catheter, surgical inoculation, hematogenousspread, trauma (Staphylococcus, Enterococcus, Candida) Fecal bacteria access urethra (E. coli, Proteus, Klebsiella) Impairment of body's natural defense systems, or stagnant urine, allow for bacterial accumulation Portal of entry bypasses body's physical defenses (gravity and repetitive outward urine flow) Bacterial fimbriae and pili allow them to ascend urethra and adhere to epithelium Lower Urinary Tract Infection (LUTI): Pathogenesis and clinical findings Suprapubic Tenderness Bacterial colony irritates urinary epithelium Urgency: Sensation of need to urinate quickly or impending incontinence Stimulation of inflammatory response Stimulation of urinary reflex Pathogens use enzymes to reduce nitrate to nitrite Delirium in Elderly Frequency: Repetitive need to urinate Unique response of altered fluid status, electrolytes and mental status, likely as a result of increased inflammatory cytokines Lower Urinary Tract Infection (“Cystitis”): Infection of bladder or distal tract by capable bacteria colonizing epithelium and causing symptoms Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 16, 2014 on www.thecalgaryguide.com Author: Brett Edwards Reviewers: Riley Hartmann Jan Rudzinski Haotian Wang Steve Vaughan* * MD at time of publication Usual Pathogens (“KEEPS”): K – Klebsiella E – E. coli (90%) E – Enterococcus, Enterobacteriaceae P – Proteus, Pseudomonas S – Staph. saprophyticus, Serratia Urine Findings: ↑ Colony Count (>107 CFU/L) ↑ WBC (>10 WBC/μL) (+) Bacterial culture (+) Nitrites, Leukocyte Esterase (+) Foul, turbid urine +/- Hematuria (rare)

lower-urinary-tract-infection-pathogenesis-and-clinical-findings

Predisposing Factors: Immunocompromised state, diabetes, elderly, female (short urethra), stagnant urine (anatomical variant, obstruction, neurogenic bladder, urinary reflux) Bacterial entry (Less Common): Indwelling catheter, surgical inoculation, hematogenousspread, trauma (Staphylococcus, Enterococcus, Candida) Fecal bacteria access urethra (E. coli, Proteus, Klebsiella) Impairment of body's natural defense systems, or stagnant urine, allow for bacterial accumulation Portal of entry bypasses body's physical defenses (gravity and repetitive outward urine flow) Bacterial fimbriae and pili allow them to ascend urethra and adhere to epithelium Lower Urinary Tract Infection (LUTI): Pathogenesis and clinical findings Suprapubic Tenderness Bacterial colony irritates urinary epithelium Urgency: Sensation of need to urinate quickly or impending incontinence Stimulation of inflammatory response Stimulation of urinary reflex Pathogens use enzymes to reduce nitrate to nitrite Delirium in Elderly Frequency: Repetitive need to urinate Unique response of altered fluid status, electrolytes and mental status, likely as a result of increased inflammatory cytokines Lower Urinary Tract Infection (“Cystitis”): Infection of bladder or distal tract by capable bacteria colonizing epithelium and causing symptoms Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 16, 2014 on www.thecalgaryguide.com Author: Brett Edwards Reviewers: Riley Hartmann Jan Rudzinski Haotian Wang Steve Vaughan* * MD at time of publication Usual Pathogens (“KEEPS”): K – Klebsiella E – E. coli (90%) E – Enterococcus, Enterobacteriaceae P – Proteus, Pseudomonas S – Staph. saprophyticus, Serratia Urine Findings: ↑ Colony Count (>107 CFU/L) ↑ WBC (>10 WBC/μL) (+) Bacterial culture (+) Nitrites, Leukocyte Esterase (+) Foul, turbid urine +/- Hematuria (rare) WBCs onsite release enzymes Cytokines released systemically Fever, Malaise, ↑WBC (>11 x 109 cells/L) (Rare in LUTI)

Osteoarthritis (OA): Clinical findings

Osteoarthritis (OA): X-ray features

Diffuse Systemic Sclerosis (Scleroderma)

Takayasu's Arteritis: Pathogenesis and clinical findings

Giant Cell (Temporal) Arteritis: Pathogenesis and investigations

Giant Cell (Temporal) Arteritis: Clinical findings and Complications

Hyperuricemia Pathogenesis and Complications

Gout Pathogenesis and Clinical Findings

Reactive Arthritis

Psoriatic Arthritis: Complications

Psoriatic Arthritis - Pathogenesis and Clinical findings

Ankylosing Spondylitis: Extra-articular Manifestations

Ankylosing Spondylitis: Pathogenesis and Clinical findings

Lupus: Muco-cutaneous manifestations

Pathogenesis of Lupus

Rheumatoid arthritis (RA): X-ray features

Rheumatoid arthritis (RA): Extra-articular manifestations

Rheumatoid arthritis (RA): Pathogenesis and Joint diseases features

Charcot Joint: Pathogenesis and Clinical findings

Osteoarthritis (OA): X-ray features

Degenerative Vs Inflammatory Joint Disease

Hypersensitivity: Definitions

Type I Hypersensitivity: Pathogenesis and clinical findings

Type II Hypersensitivity: Pathogenesis and clinical findings

Type III Hypersensitivity: Pathogenesis and clinical findings

Type IV Hypersensitivity: Pathogenesis and clinical findings

Hypersensitivity Summary

Agammaglobulinemia: Pathogenesis and clinical findings

Acute Otitis Media: Pathogenesis and Clinical Findings (in Children)

Acute Otitis Media: Complications

Endometriosis: Pathogenesis and Complications

Physiology of the Renin-Angiotensin-Aldosterone System (RAAS)

Hypokalemia: Clinical Findings

Yu, Yan - Hypokalemia clinical findings - FINAL.pptx Production of Na+/ K+ transporters in cell membranes ? over timeHypokalemia: Clinical FindingsAuthor: Yan YuReviewers:David WaldnerSean SpenceAndrew Wade** MD at time of publicationLegend:Published May 21, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsPalpitationsExcitable cells (muscle cells, neurons) depolarize less readilyK+ efflux out of all cells in the body, down its concentration gradientCardiac myocytes experience electrical conduction defects? muscle impulse conductionECG shows characteristic changes:? skeletal muscle contractile abilityRMP now more negative; myocytes take longer to repolarize to RMP(0.5 of R-R interval)?Flatter T-Waves ?Inverted T-waves (with more severe hypokalemia)Purkinje fibers repolarize after the rest of the myocardium has done soU-waves (upward ECG deviations after the T-wave)Cells become hyperpolarized: Inside of cells are more negative relative to outside, ? Resting Membrane Potential (RMP)In the Kidney:Generalized Muscle weaknessK+ diffuse out of Proximal Convoluted Tubule & Collecting Duct cells ? cells retain acidic H+ inside (maintains electrical neutrality)? pH within PCT cells ? glutaminase activity, ? glutamine breakdown, producing HCO3-, which enters the blood? blood pH, [HCO3-], & pCO2 (respiratory compensation)Low Plasma [K+]Abnormally long diastole means that ventricles are overfilled. Contraction takes greater force; sensed by patientsDyspnea, fatigue, dizziness, syncope? cardiac output ? perfusion of tissues, i.e. lungs & brainCardiac arrhythmias: PACs, PVCs, Sinus Bradycardia, paroxysmal atrial/junctional tachycardia, VT (i.e. Torsades de pointes), V-Fib? smooth muscle contractile abilityBowel ileus (bloating, anorexia, nausea/vomiting, absent bowel sounds)? pH in collecting duct intercalated cells ? H+ secretion into the tubuleMetabolic alkalosisParalysis, muscle cramps (in severe hypokalemia)Respiratory muscle failure (? tidal volume, ? pCO2, ? pO2), may even cause death!? depolarizations ? adenyl cyclase activity ? ? sensitivity of collecting duct cells to ADH? ability of nephron to concentrate urineNephrogenic Diabetes Insipidus? urine osmolality, Hypernatremia, Polyuria, Polydipsia? # of aquaporins in the collecting duct membrane"Insulin Resistance": ? ability to import K+ from the blood in response to insulinIn skeletal muscle: 117 kB / 307 word" title="Yu, Yan - Hypokalemia clinical findings - FINAL.pptx Production of Na+/ K+ transporters in cell membranes ? over timeHypokalemia: Clinical FindingsAuthor: Yan YuReviewers:David WaldnerSean SpenceAndrew Wade** MD at time of publicationLegend:Published May 21, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsPalpitationsExcitable cells (muscle cells, neurons) depolarize less readilyK+ efflux out of all cells in the body, down its concentration gradientCardiac myocytes experience electrical conduction defects? muscle impulse conductionECG shows characteristic changes:? skeletal muscle contractile abilityRMP now more negative; myocytes take longer to repolarize to RMP("stretches out" the T-wave)! Long QT interval (>0.5 of R-R interval)?Flatter T-Waves ?Inverted T-waves (with more severe hypokalemia)Purkinje fibers repolarize after the rest of the myocardium has done soU-waves (upward ECG deviations after the T-wave)Cells become hyperpolarized: Inside of cells are more negative relative to outside, ? Resting Membrane Potential (RMP)In the Kidney:Generalized Muscle weaknessK+ diffuse out of Proximal Convoluted Tubule & Collecting Duct cells ? cells retain acidic H+ inside (maintains electrical neutrality)? pH within PCT cells ? glutaminase activity, ? glutamine breakdown, producing HCO3-, which enters the blood? blood pH, [HCO3-], & pCO2 (respiratory compensation)Low Plasma [K+]Abnormally long diastole means that ventricles are overfilled. Contraction takes greater force; sensed by patientsDyspnea, fatigue, dizziness, syncope? cardiac output ? perfusion of tissues, i.e. lungs & brainCardiac arrhythmias: PACs, PVCs, Sinus Bradycardia, paroxysmal atrial/junctional tachycardia, VT (i.e. Torsades de pointes), V-Fib? smooth muscle contractile abilityBowel ileus (bloating, anorexia, nausea/vomiting, absent bowel sounds)? pH in collecting duct intercalated cells ? H+ secretion into the tubuleMetabolic alkalosisParalysis, muscle cramps (in severe hypokalemia)Respiratory muscle failure (? tidal volume, ? pCO2, ? pO2), may even cause death!? depolarizations ? adenyl cyclase activity ? ? sensitivity of collecting duct cells to ADH? ability of nephron to concentrate urineNephrogenic Diabetes Insipidus? urine osmolality, Hypernatremia, Polyuria, Polydipsia? # of aquaporins in the collecting duct membrane"Insulin Resistance": ? ability to import K+ from the blood in response to insulinIn skeletal muscle: 117 kB / 307 word" />

Hyperkalemia: Clinical Findings

Yu, Yan - Hyperkalemia clinical findings - Published.pptx Hyperkalemia: Clinical FindingsAuthor: Yan YuReviewers:Alexander ArnoldDavid WaldnerSean SpenceAndrew Wade** MD at time of publicationLegend:Published September 9, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsPalpitationsNotes: Symptoms usually manifest when plasma [K+] > 7.0 mmol/L, but can occur at lower [K+]s when hyperkalemia is acute.ECG changes can, but don't necessarily, correlate with a particular [K+].Initially: Excitable cells (muscle cells, neurons) undergo action potentials more readily? [K+ ] gradient between cells and the blood (K+ tends to stay inside cells, less K+ diffuses out)In the Heart:In Skeletal Muscle:[K+] >5.5 mmol/L :faster myocardial repolarization( 6.5 mmol/L:? atrial conduction; slow signal transmission from SA to AV nodeCells become slightly depolarized: Resting Membrane Potential (RMP) is brought closer to thresholdIn the Kidney:Muscle weakness and even paralysis (respiratory muscle weakness is rare)? reabsorption of Na+ from Cortical Collecting Duct (CCD)CCD lumen remains more positively chargedMetabolic Acidosis(normal anion gap)Over time (when patients become symptomatic): Chronic membrane depolarization desensitizes voltage-gated Na+ channels (slows their opening) ? ? membrane excitability ? ? action potential generation[K+] > 7.0 mmol/L:? ventricular conductionBradycardiaProlonged, abnormal QRSAV blocks[K+] > 9.0 mmol/L:more conduction abnormalitiesPEA with bizarre wide-QRS rhythmV-fibAsystole? urinary H+ secretion by alpha-intercalated cellsHIGH Plasma [K+] (potassium ion concentration)Dyspnea, fatigue, dizziness, syncope? cardiac output ? ? perfusion of tissues, i.e. lungs & brainCardiac arrhythmias: Conduction blocks (AV block, Bundle branch blocks), VT , V-Fib, Bradycardia, Asystole.?? PR interval ?P-wave flattens, eventually disappearsIf severe, QRS & T-waves fuse:Sine-WavesThe higher the [K+], the slower the voltage-gated Na+ channels open, reflected by distinctive ECG changes:If the K+ is due to ? aldosterone effect ? principal cell dysfunctionHigh pH ? glutamate deamination, which normally produces NH4+? NH4+ reaches the thick ascending limb to be converted to NH3Less NH3 diffuses into the collecting duct to be converted to NH4+ through binding with H+ ? ? NH4+ and therefore ? H+ is excretedK+ moves into proximal tubule cells, causing H+ to diffuse out ? Intracellular alkalosis Irregular force and rhythm of cardiac muscle contraction is sensed by the patient? contraction impulse is conductedDefective electrical conduction through cardiac myocytesMore acid (H=) is retained in the body 118 kB / 357 words" title="Yu, Yan - Hyperkalemia clinical findings - Published.pptx Hyperkalemia: Clinical FindingsAuthor: Yan YuReviewers:Alexander ArnoldDavid WaldnerSean SpenceAndrew Wade** MD at time of publicationLegend:Published September 9, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsPalpitationsNotes: Symptoms usually manifest when plasma [K+] > 7.0 mmol/L, but can occur at lower [K+]s when hyperkalemia is acute.ECG changes can, but don't necessarily, correlate with a particular [K+].Initially: Excitable cells (muscle cells, neurons) undergo action potentials more readily? [K+ ] gradient between cells and the blood (K+ tends to stay inside cells, less K+ diffuses out)In the Heart:In Skeletal Muscle:[K+] >5.5 mmol/L :faster myocardial repolarization("squeezes up" T-wave)Tall, peaked T-Waves Short QT interval (<0.5 of RR interval)[K+] > 6.5 mmol/L:? atrial conduction; slow signal transmission from SA to AV nodeCells become slightly depolarized: Resting Membrane Potential (RMP) is brought closer to thresholdIn the Kidney:Muscle weakness and even paralysis (respiratory muscle weakness is rare)? reabsorption of Na+ from Cortical Collecting Duct (CCD)CCD lumen remains more positively chargedMetabolic Acidosis(normal anion gap)Over time (when patients become symptomatic): Chronic membrane depolarization desensitizes voltage-gated Na+ channels (slows their opening) ? ? membrane excitability ? ? action potential generation[K+] > 7.0 mmol/L:? ventricular conductionBradycardiaProlonged, abnormal QRSAV blocks[K+] > 9.0 mmol/L:more conduction abnormalitiesPEA with bizarre wide-QRS rhythmV-fibAsystole? urinary H+ secretion by alpha-intercalated cellsHIGH Plasma [K+] (potassium ion concentration)Dyspnea, fatigue, dizziness, syncope? cardiac output ? ? perfusion of tissues, i.e. lungs & brainCardiac arrhythmias: Conduction blocks (AV block, Bundle branch blocks), VT , V-Fib, Bradycardia, Asystole.?? PR interval ?P-wave flattens, eventually disappearsIf severe, QRS & T-waves fuse:Sine-WavesThe higher the [K+], the slower the voltage-gated Na+ channels open, reflected by distinctive ECG changes:If the K+ is due to ? aldosterone effect ? principal cell dysfunctionHigh pH ? glutamate deamination, which normally produces NH4+? NH4+ reaches the thick ascending limb to be converted to NH3Less NH3 diffuses into the collecting duct to be converted to NH4+ through binding with H+ ? ? NH4+ and therefore ? H+ is excretedK+ moves into proximal tubule cells, causing H+ to diffuse out ? Intracellular alkalosis Irregular force and rhythm of cardiac muscle contraction is sensed by the patient? contraction impulse is conductedDefective electrical conduction through cardiac myocytesMore acid (H=) is retained in the body 118 kB / 357 words" />

Hypocalcemia: Clinical Findings

Yu, Yan - Hypocalcemia - Clinical Findings - FINAL.pptx Hypocalcemia: Clinical FindingsAuthor: Yan YuReviewers:David WaldnerSean SpenceGreg Kline** MD at time of publicationLegend:Published May 7, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsHypocalcemia(serum [Ca2+] <2.1mmol/L)Altered sensory ability of peripheral nervesLess Ca2+ outside cells, with no change in + charges inside cellsPeripheral paraesthesia? Neuronal

Hypercalcemia: Clinical Findings

Nephrotic Syndrome: Pathogenesis and Clinical Findings

Destroys charge barrier to protein filtrationNephrotic Syndrome: Pathogenesis and Clinical FindingsAuthor: Yan YuReviewers:Alexander ArnoldDavid WaldnerSean SpenceStefan Mustata** MD at time of publicationLegend:Published August 19, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsExcessive (3.5g/day*? Ability of blood to retain fluids within vessels ? fluid leaks into extra-vascular spaceInjury to glomerular endothelium and epitheliumImmune complexes deposit into glomerulusDamaged glomerulus ? abnormally permeable to proteins within the blood ? plasma proteins are thus excessively filtered out? Oncotic pressure signals liver to ? albumin synthesis, only to have it filtered out by the kidneys? anabolic activity of liver ? ? lipoprotein synthesisHyperlipidemia*:(? serum LDL, VLDL, and TGs)Lipiduria(lipid/fatty casts; "Maltese cross" sign under polarized light)Since counter-balancing anticoagulant proteins are lost, clotting factors (i.e. 1, 7, 8, 10) now have more activityThrombo-embolic diseaseBlood becomes hyper-coagulable? Lipids are filtered into renal tubules, end up in urineMembranoproliferative Glomerulonephritis (MPGN)Lupus Glomerulonephritis Post-infectious GlomeruloneprhitisIgA NephropathyDamages podocytes on epithelial side of glomerulus ("podocyte effacement"; foot processes flattening)Diabetes MellitusChronic hyperglycemia damages glomeruliDeposition of Immunoglobulin light chains in glomerulusAmyloidosisAnasarca(If generalized)Peri-orbital edema (classic sign)Focal Segmental Glomerular Sclerosis (FSGS)Membranous GlomeruloneprhitisAntibodies attack podocytes, thickening glomerular basement membraneOverflow of immunoglobulin light chains into urine (More filtered than can be reabsorbed)Proteinuria >3.5g/day*The Anion Gap is mostly due to the negative charge of plasma albumin? Anion GapNotes: The four classic features (*) of Nephrotic Syndrome are PEAL (Proteinuria (>3.5 g/day), Edema, hypo-Albuminemia, and hyperLipidemia)For each 10 g/L drop in albumin below 40:Add 2.5 to the calculated anion gap (AG) to get the "correct" AG valueAdd 0.2 mmol/L to total calcium or get an ionized calcium, which is unaffected50% of serum Ca2+ is albumin-bound, so total serum calcium ? Serum total Ca2+ does not reflect ionized Ca2+ ? Blood oncotic pressure" title="Destroys charge barrier to protein filtrationNephrotic Syndrome: Pathogenesis and Clinical FindingsAuthor: Yan YuReviewers:Alexander ArnoldDavid WaldnerSean SpenceStefan Mustata** MD at time of publicationLegend:Published August 19, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsExcessive ("Nephrotic-range") loss of albumin in the urineHypo-albuminemia*Loss of anti-coagulant proteins (Antithrombin, Plasminogen, and proteins C and S) in urineMinimal Change Disease (MCD)"Underfill" edema*Proteinuria >3.5g/day*? Ability of blood to retain fluids within vessels ? fluid leaks into extra-vascular spaceInjury to glomerular endothelium and epitheliumImmune complexes deposit into glomerulusDamaged glomerulus ? abnormally permeable to proteins within the blood ? plasma proteins are thus excessively filtered out? Oncotic pressure signals liver to ? albumin synthesis, only to have it filtered out by the kidneys? anabolic activity of liver ? ? lipoprotein synthesisHyperlipidemia*:(? serum LDL, VLDL, and TGs)Lipiduria(lipid/fatty casts; "Maltese cross" sign under polarized light)Since counter-balancing anticoagulant proteins are lost, clotting factors (i.e. 1, 7, 8, 10) now have more activityThrombo-embolic diseaseBlood becomes hyper-coagulable? Lipids are filtered into renal tubules, end up in urineMembranoproliferative Glomerulonephritis (MPGN)Lupus Glomerulonephritis Post-infectious GlomeruloneprhitisIgA NephropathyDamages podocytes on epithelial side of glomerulus ("podocyte effacement"; foot processes flattening)Diabetes MellitusChronic hyperglycemia damages glomeruliDeposition of Immunoglobulin light chains in glomerulusAmyloidosisAnasarca(If generalized)Peri-orbital edema (classic sign)Focal Segmental Glomerular Sclerosis (FSGS)Membranous GlomeruloneprhitisAntibodies attack podocytes, thickening glomerular basement membraneOverflow of immunoglobulin light chains into urine (More filtered than can be reabsorbed)Proteinuria >3.5g/day*The Anion Gap is mostly due to the negative charge of plasma albumin? Anion GapNotes: The four classic features (*) of Nephrotic Syndrome are PEAL (Proteinuria (>3.5 g/day), Edema, hypo-Albuminemia, and hyperLipidemia)For each 10 g/L drop in albumin below 40:Add 2.5 to the calculated anion gap (AG) to get the "correct" AG valueAdd 0.2 mmol/L to total calcium or get an ionized calcium, which is unaffected50% of serum Ca2+ is albumin-bound, so total serum calcium ? Serum total Ca2+ does not reflect ionized Ca2+ ? Blood oncotic pressure" />

Signs and Symptoms of Hypovolemia

Placental Abruption

Contraindications to Inducing Vaginal Delivery

Active Phase Problems: Pathogenesis and Management

Normal Signs of Placental Detachment

Yu Yan - Normal signs of placental detachment - FINAL.pptx Normal placental detachment in labor: Key SignsDisruption of blood vessels connecting the placenta with the uterusSemi-detached placenta being dragged out of uterus will pull the uterine fundus down with itThe umbilical cord is of limited length and is attached to the placentaLegend:Published September 5, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsAuthor: Yan YuReviewers:Kayla NelsonRadhmila ParmarAlina Constantin** MD at time of publicationWhen placenta fully detaches, the elastic fundus muscle

Methods to Improve Fetal Oxygenation

Yu Yan - Methods to improve fetal oxygenation - FINAL.pptx Methods used to improve fetal oxygenation during laborMother's great vessels are less compressed by the fetus? Involuntary uterine contractions in mother? oxygenation of mother's bloodInfusing more fluid into uterus shifts uterine structures and ? their cushioning? Blood volume and counteracts the hypotensive effect of epiduralsChange maternal position from supine to left lateral decubitusStop or ? Oxytocin to motherIV fluid bolus to motherAdminister O2 to motherAmnio-infusionLegend:Published September 5, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsAuthor: Yan YuReviewers:Kayla NelsonRadhmila ParmarAlina Constantin** MD at time of publicationImproved maternal circulation? amount of oxygen able to be passed to fetusCord may become de-compressed from original sites of compressionMay improve fetal oxygenation Suspect fetal hypoxiaIf cord is prolapsed, can push it back inVaginal exam for cord prolapseRelieves cord pressure, restores cord blood flowIf cord compression suspectedAtypical Fetal Heart Rate (FHR) pattern (i.e. variable decelerations, mild tachycardia, mild ? in HR variability)? Mechanical stress on the fetus, to allow better perfusion of fetusImproved perfusion of maternal organs, including the uterus/fetusNote: if these methods do not restore normal FHR, perform scalp stimulation and scalp pH to better assess fetal hypoxia)Normal FHR pattern 91 kB / 187 words

Post-Partum Hemorrhage

Upper Urinary Tract infection (UUTI): Pathogenesis and Clinical Findings

adrenaline

Asthma: Findings on Investigations

COPD: Pathogenesis

COPD: Clinical Findings

COPD: Findings on Investigations

COPD: Complications

Bronchiectasis: Findings on Chest X-Ray and CT Scan

Cystic Fibrosis

Posterior-Anterior Chest X-Ray

Lateral Chest X-Ray

Coronal CT

Axial CT

Infant Respiratory Distress: Clinical findings

Foreign Body Aspiration

Types of Burns - Summary of Causes and Clinical Findings

Saif

Deep Partial Thickness Burns: Pathogenesis and Clinical Findings

Pericardial Effusion and Tamponade: Pathogenesis and Clinical Findings

Atherosclerosis - Pathogenesis

Atherosclerosis - Complications

Complications of Myocardial Infarction

myocardial-infarction-findings-on-investigations

Yu Yan - MI Findings on Investigations - FINAL.pptx Myocardial Infarction: Findings on InvestigationsAuthor: Yan YuReviewers:Sean SpenceTristan JonesNanette Alvarez** MD at time of publicationTissue ischemia disrupts normal cardiac electrical conduction(detected on serial ECG)Acute, trans-mural myocardial ischemiaIschemia of sub-endocardial myocardiumMyocardial infarctionNote: Both types of ST-segment changes are non-specific: they can indicate Myocardial Infarctions , but can also be false positives (i.e. caused by left ventricular hypertrophy, bundle branch blocks, and other non-myocardial ischemic causes)If ischemia progresses to tissue infarctionPathologic Q-waves (localizes to site of ischemia)Tissue necrosis ? Local myocardial inflammation2-4 hours after MI: troponin proteins released into blood3-8 hours after MI:Creatinine-kinase MB-isozymes released into blood? serum Cardiac Troponins: cTnT, cTnI(Sensitive and most specific serum marker for myocardial necrosis)Relatively faster clearance from circulation? serum CK-MB(less sensitive and specific for myocardial necrosis than Troponins)ST-segment depression(non-localizing)Inflammatory cytokines can spread systemicallyStimulation of neutrophil and monocyte migration towards area of inflammation? WBC count (on CBC)? C-Reactive Protein (CRP)Dead, damaged cardiac myocytes release inner contents into the bloodRelatively slower clearance from circulationSerum CK-MB levels normalize within 3 daysSerum Troponin levels normalize within 14 daysNote: Measuring both CK-MB and Troponins gives a timeline to the MI. For instance, if CK-MB is normal but Troponins are high, it means the MI happened >3 days but <14 days ago.ST-segment elevation(localizes to site of ischemia)Legend:Published January 30, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplications 104 kB / 212 words

myocardial-infarction-findings-on-physical-exam

Yu Yan - MI Findings on Physical Exam - FINAL.pptx Myocardial Infarction: Findings on Physical Exam Author: Yan YuReviewers:Sean SpenceTristan JonesNanette Alvarez** MD at time of publication Systolic function(necrotic myocardium cannot contract as well) Diastolic compliance (necrotic myocardium does not relax as well to accommodate blood)Necrosis of papillary muscles:S4(4th heart sound)? Force of ventricular contractionsMitral valve regurgitationBlood

MI Findings on History

Dilated Cardiomyopathy

Myocarditis

Restrictive Cardiomyopathy

Hypertrophic Cardiomyopathy

Left Heart Failure - Pathogenesis

Right Heart Failure

Left Heart Failure

Left Heart Failure - Physical Exam Findings

Left Heart Failure - Findings on History

pericarditis

Aortic Dissection

Aortic Stenosis - Pathogenesis and Clinical Findings

Aortic Regurgitation

Mitral Stenosis

Atrial Flutter

Ventricular fibrillation

1st Degree AV block

Second Degree Heart Block - Mobitz Type II - Pathogenesis and clinical findings

Atrial Fibrillation - Clinical Findings

atrial-fibrillation-complications

Yu Yan - AFib Clinical Findings - FINAL.pptx Atrial Fibrillation: Clinical FindingsAbnormal electrical signals in fibrillating atria can propagate to ventricles before ventricles have fully recovered from their previous contraction.Uncoordinated, irregular atrial contraction? Diastolic ventricular filling timeLegend:Published January 22. 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsAuthor: Yan YuReviewers:Rob SchultzSean SpenceNanette Alvarez** MD at time of publicationNo discrete

Second Degree Heart Block - Mobitz Type I (Wenckebach) - Pathogenesis and Clinical Findings

Third Degree (Complete) AV Block - Pathogenesis and Clinical Findings

Atrial Flutter (1)

Cardiogenic Shock

Distributive Shock

Obstructive Shock

Drugs used to treat shock

JVP-Physical Exam Features

jvp-kussmals-sign-explained

Yu Yan - JVP explained - FINAL.pptx Myocardium of right ventricle becomes fibrotic and stifferKussmaul's sign: JVP increases with inspirationJugular Venous Pressure (JVP): Kussmal's Sign explainedExcessive pericardial fluid compresses heart walls on all sidesLegend:Published January 7, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsAuthor: Yan YuReviewers:Sean SpenceJason BasermanJason Waechter** MD at time of publication? Right ventricle wall complianceConstrictive pericarditisRight ventricle prevented from fully expanding ? ability of the right ventricle to accommodate higher venous returnBackup of venous blood into right atrium and preceding internal jugular veinsRestrictive cardiomyopathyInflamed, fibrotic pericardium restricts expansion of heartRight ventricle myocardial infarct Cardiac tamponade (rare)InspirationMore venous blood tries to enter the low-pressure thoracic cavity via the right ventricle? pressure in thoracic cavity JVP should return to normal within 3 respiration cyclesJugular Venous Pressure (JVP): Physical Exam FeaturesExerts less force against vesselsTilting the head of the bed:Low pressure, & the thinner walls of the internal jugular veins, are less able to keep lumen open when compressedLegend:Published January 7, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsAuthor: Yan YuReviewers:Sean SpenceJason BasermanJason Waechter** MD at time of publicationBlood in internal jugulars settles to bottom of the vein (analogy: half-full tube of water is turned vertically)Visible waves in the JVP correspond to stages of the cardiac cycleNon-palpableBiphasic waveform? JVP The Jugular Venous Pressure (JVP) Blood pressure in the internal jugular veinsV-waveA-waveRight atrial contractionBlood passively fills right atrium during ventricular systole? JVP? JVPIn: ? intrathoracic pressurePressing hard on abdomen (overlying the liver), or doing a valsalvaFacing lower afterload, Right heart more readily pumps blood into pulmonary circulation? abdominal pressure? venous blood forced up into right atriumVenous blood pressure is normally very lowOccludableNote: Since the internal jugular veins are continuous with the right atrium, the JVP is a reliable estimate of right atrial blood pressure (Central Venous Pressure). The JVP on the right side is a better

Pulsus Paradoxus

Yu Yan - Pulsus Paradoxus - FINAL.pptx Lungs are hyperinflated, and vascular beds are more expanded? BP on inspiration (<10mmHg)Pulsus ParadoxusThrombi in the pulmonary arteries ? blood filling pulmonary vasculatureLegend:Published January 21, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsAuthor: Yan YuReviewers:Sean SpenceLaura CraigNanette Alvarez** MD at time of publication? ? ? forward blood flow from lungs into left heartWith cardiac pathology external to myocardium(Cardiac tamponade, or rarely with constrictive pericarditis)? Right heart filling, ? blood flow into lung vesselsMore blood returns to R heart ? more blood enters and pools in pulmonary vasculature? blood returns to the left heart, ? its fillingWith obstructive lung diseases (i.e. COPD)With vascular pathology (rare):InspirationNormally:? lung volume ? ? intra-vascular volume within pulmonary blood vessels ? ? lung capacitance for blood, ? R heart afterloadPulsus Paradoxus:Exaggerated ?in systolic BP on inspiration (>10mmHg)? left heart stroke volume/cardiac outputOn inspiration, ? ? ? blood enter lungs and pools within pulmonary vasculature? ? ? left heart stroke volume/cardiac outputAbnormally:On inspiration, as pulmonary intra-vasculature volume expands and blood pools within, flow into the left heart ? ? ? Pulmonary embolism? venous return to R heartVena cava obstructionBy thrombi, or external compression by masses/ fibrosis (from obesity, pregnancy) As ? blood fills R heart on inspiration, external constraints on myocardium ? cardiac expansion, interventricular septum is pushed into LVThere is no room in the pericardial sac for the LV to expand and maintain normal end diastolic volume (i.e. ? LV filling) 98 kB / 233 words

Complications of Measles Pathogenesis and Clinical Findings

Retroviral Infections Mechanisms of oncogenesis

Superficial Partial Thickness Burns - Pathogenesis and Clinical Findings

Complications of Burns

Acne Vulgaris

Androgenic Alopecia

Distinguishing between Benign and Malignant Pigmented Lesions

Seborrheic Keratosis

Basal Cell Carcinoma (BCC)

Squamous Cell Carcinoma (SCC)

Varicella Zoster (Chicken Pox)

Herpes Zoster (Shingles)

Pemphigus Vulgaris

Bullous Pemphigoid

Actinic Keratosis

Lichen Planus

Herpes Simplex Virus (HSV)

Herpes Simplex Virus (HSV)

1-and-2-syphilis-pathogenesis-and-clinical-findings

Scabies

DM I pathogenesis

Pathogenesis of Diabetes mellitus DM), Type II

Yu, Yan - DM I and II pathogenesis - Ready for Faculty.pptx Over many years, as insulin resistance worsens, Beta-cells

Diabetic Ketoacidosis

DKA

Diabetic Polyneuropathy

GDM Complications

Hypoglycemia - Pathogenesis

Hypoglycemia - Clinical Findings and Complications

Diabetic Hypoglycemia

Yu, Yan - Diabetic Hypoglycemia - Clinical Findings - FINAL.pptx ? Epinephrine(Released within seconds as [glucose] falls further) Growth hormone, ? Cortisol (if hypoglycemia persists for minutes)Glucagon should ? when [glucose] falls. But here, glucagon release is inhibited by 1) diabetic auto-immune destruction of Alpha cells & 2) the high insulin.43210Plasma Glucose concentration (mmol/L)Liver should ? glycogenolysis & gluconeogenesisPeripheral vaso-constrictionPlasma [glucose] stays lowActivation of sympathetic (adrenergic) receptors across body, triggering Neurogenic symptomsPlasma [glucose] ?Excess subcutaneous insulin or insulin-secretagogue ?? [insulin] in the bloodOver time: [insulin] in the DM patient depends only on how much was injected or how much secretagogue was consumed; not on the body's physiological state.[Insulin] stays high in excessively-treated DM patientsPlasma [glucose] normally ?, but...High insulin transports plasma glucose into cells!In pts with existing diabetic autonomic neuropathy, epi-nephrine secretion will already be ?Brain does not get enough glucose, ? neuron function ? Neuroglycopenic symptomsTx: glucose intake![Glucose] returns to normalIf no glucose intake:Hypoglycemia-unawareness: No autonomic Sx felt so hypoglycemia not treated early ? pts present later on with more severe hypoglycemia and neuroglycopenic sxBrain cells kept chronically euglycemic due to GLUT1 receptor over-expression (despite rest of body being hypoglycemic)With many hypoglycemic events over time:Brain feels no need to ? glucose, so it ? autonomic epinephrine secretion!This is the normal sequence of hormone responses to ?ing plasma glucose levels.But this normal hormonal response will be blunted over time if there is 1) continued hypoglycemia dampening the sympathetic nervous system, and 2) long-standing diabetic neuropathy! (To be explained later in this flow chart)Abbreviations: [ ] = concentrationTx = TreatmentDM = Diabetes mellitusDiabetic Hypoglycemia: Pathogenesis and Clinical FindingsConfusionCan't concentrateWeaknessSlurred speech? coordination (staggering, etc)SeizuresComa, deathAdrenergic symptoms (epinephrine-mediated):Anxiety, irritability, trembling, pallor (skin vasoconstriction), palpitations, ? systolic BP, tachycardia Cholinergic symptoms(Acetylcholine-mediated):Sweating, hunger, tingling, blurry visionNote: In pts w/out DM, endogenous insulin secretion normally stops when blood [glucose] drops to <4mmol/LAuthor: Yan YuReviewers: Peter Vetere, Gillian Goobie, Hanan Bassyouni** MD at time of publicationLegend:Published June 14, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsMany hypoglycemic events over time blunt epinephrine secretion further.Hypoglycemia unawareness can be reversedIf pt stays hypoglycemia-free for >6 weeks, brain restores its ability to detect low glucose levels? peripheral glucose delivery and uptake (saving more glucose for the brain)Lack of glucagon effect reinforces hypoglycemia 124 kB / 361 words

Acquired Disorders of Reduced Bone Strength - Pathogenesis

Primary Hypertriglyceridemia

Hypothyroidism

Hashimoto

Thyroiditis

Hyperfunctional

Central Adrenal Insufficiency - Pathogenesis and Clinical Findings

Clinical Findings of Androgen Deficiency

Yu, Yan - Androgen Deficiency - FINAL.pptx Hypogonadism in Males:Clinical Findings of Androgen Deficiency? secretion volume from seminal vesicle and prostateAuthor: Yan YuReviewers:Peter VetereGillian GoobieHanan Bassyouni** MD at time of publicationLegend:Published June 18, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplications? effect of testosterone on the brain? Libido(sensitive, but less specific)? [testosterone] : [estrogen] ratio at the male breast? ejaculate volume(a sensitive and specific sign)Gynecomastia (palpable breast tissue, not fat, directly under nipple)Fatigue,low mood, irrtabilityHot flashes, sweats(Can be nocturnal; occur only when hypogonadism is severe)Vasomotor neural response of unknown causeFewer spontaneous erections (i.e. in the morning)Lack of androgens (i.e. testosterone, DHT) in men past the age of pubertyIn advanced stages of the disease, after years of hypogonadism:(thus, less commonly seen)Low Bone Mass Density (BMD)Less testosterone to be converted into estrogen in bone? muscle bulk and strengthSmall, soft testicles(<4cm long on orchidometer)Lack of hormones to stimulate and maintain testicular hyperplasia/growthLoss of androgenic hair (on face, midline, and pubic area)Vertebral fracture (height loss), or other fragility fracturesIf sexual development is incomplete from puberty:Note: These clinical findings apply to many disorders, including:-Andropause-Hypopituitarism (suspect if other hormone abnormalities & Sx of mass lesion like visual field loss, diplopia, and headache exist)-Testicular Failure (if Hx of chemo, radiation, excess alcohol, and chronic liver disease)-Klinefelter's (if assoc. tall and eunuchoid stature, breast enlargement and cognitive deficiency - XXY)-Kallman's (if assoc. anosmia, and tall/eunuchoid stature)-Drugs (e.g. ketoconazole, anabolic steroids, spironolactone, digoxin, marijuana)Testosterone's inhibitory effect on estrogen is not enough to prevent breast growthDeficiency in testosterone during puberty delays fusion of epiphysesTall, eunuchoid statureNote: any disease involving an increase in aromatase activity (hyperthyroidism, cirrhosis, HCG-secreting tumors) will also cause relative estrogen excess & subsequent gynecomastia. 111 kB / 272 words

Hypocalcemia - Clinical Findings

Yu, Yan - Hypocalcemia - Clinical Findings - FINAL.pptx Hypocalcemia: Clinical FindingsAuthor: Yan YuReviewers:David WaldnerSean SpenceGreg Kline** MD at time of publicationLegend:Published May 7, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsHypocalcemia(serum [Ca2+] <2.1mmol/L)Altered sensory ability of peripheral nervesLess Ca2+ outside cells, with no change in + charges inside cellsPeripheral paraesthesia? Neuronal

Hypercalcemia - Clinical Findings

Yu, Yan - Hypercalcemia - Clinical Findings - FINAL.pptx Hypercalcemia: Clinical FindingsAuthor: Yan YuReviewers:David WaldnerSean SpenceGreg Kline** MD at time of publicationLegend:Published May 7, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsHypercalcemia(serum [Ca2+] > 2.5mmol/L)Na+ channels on neuronal membranes become more resistant to opening (resists Na+ influx)Cognitive dysfunctionIf precipitation occurs in the urinary tract...Fatigue? contractility of GI tract smooth muscle? K+ movement out of TAL epithelial cells into the tubule lumen Alters charge balance across the cell membraneCa2+ precipitates with PO43- throughout the bodyDetected by the Ca-Sensing-Receptor (CaSR) on Thick Ascending Limb (TAL) epithelial cells? neuronal action potential generationSluggish neuronal activity...? appetiteConstipationFlank painInhibit insertion of Renal Outer Medullary K+ (ROMK) channels on TAL's luminal membrane? K+ in TAL lumen to drive Na+/Cl- reabsorption through the Na-K-Cl Cotransporter (NKCC)? Na/Cl in tubule lumen ? osmotically draws water into lumen? drinking (polydipsia)? Urine volume (polyuria)Rationale for the CaSR-pathway: ECF has enough Ca2+, no need for more K+ to be excreted into the tubule lumen to create a more + charge there that drives Ca2+ reabsorptionBehavior compensates to prevent dehydrationKidney stones (nephrolithiasis)Constantly feeling full because of reduced GI motilityCa2+ directly inhibits the insertion of aquaporin channels in the collecting duct membraneLess water reabsorbed into the renal vasculatureMore water remains in the tubule filtrateMuscle Weakness...in central nervous system:...at neuromuscular junction:A rhyme to help you recall the manifestations of one specific cause of hypercalcemia, primary hyperparathyroidism:Bones (Calcium levels are high often due to ? resorption from bones)Stones (? Calcium-containing kidney stones)Groans (GI and skeletal muscle issues) Psychic Moans (Cognitive dysfunction from neuronal disturbances)Note: sick/ICU patients have ? serum albumin, due to ? synthesis from a sick liver. Their lab Ca2+ values can be

Etiologies and Physical Historical Signs of Upper GI Bleed

Infectious Large Bowel Diarrhea

Acetaminophen Overdose

Gall Bladder Disorders

Cholelithiasis

Cholestasis

signs of chronic liver disease

cirrhosis

Ascites Clinical Findings

AscitesComplications

viral hepatits

A1ATDeficiency

Hepatitis A (HAV) Infections

Hereditary hemochromatosis

Auto-immune Hepatitis

Primary Biliary Cirrhosis (PBC)

Primary Sclerosing Cholangitis (PSC)

Achalasia Pathogenesis and clinical findings

Gastroesophageal Reflux Disease (GERD) Pathogenesis and Clinical Findings

TRALI

Transfusion Associated Circulatory Overload (TACO)

Essential Thrombocytosis (ET)

Pathogenesis of thrombocytosis

Heparin Induced Thrombocytopenia

Immune thrombocytopenic purpura

hodgkin lymphoma - pathogenesis and clinical findings

Clinical Features to Describe Abnormal Lymph Nodes

Acute Myeloid Leukemia

Pathophysiology behind the leukemias

Multiple Myeloma

Overview of blood cell malignancies

Suspected Deep Vein Thrombosis

APS

TTP HUS

Polycythmia Vera

Polycythmia Overview

G6PD Deficiency

Sickle cell disease signs

Sickle cell disease

Hemolytic Anemia Signs and Symptoms

Anemia of Chronic Disease

Vitamin B12 Deficiency

Folate Deficiency

Pathogenesis of Beta Thalassemia

Beta Thalassemia Signs Symptoms Treatment

Alpha Thalassemia Pathogenesis

Iron Deficiency Anemia

CNVII_Bells Palsy

Trigger Finger

Dupuytren

Gonorrhea Pathogenesis

Cauda Equina Syndrome

Myelopathy

Radiculopathy

Spondylosis

Disc Herniations

Presentation of increased ICP

Pathogenesis of SAH

Side Effects of Opioid Medications

Non Neural Complications of Stroke

Giant Cell (Temporal) Arteritis - Pathogenesis and investigations

Giant Cell (Temporal) Arteritis - Clinical findings and Complications

Migraines and Auras Pathogenesis and Clinical Findings

Pain Pathways in the Head

Bacterial Meningitis Complications

Bacterial Meningitis Clinical Findings

Bacterial Meningitis Pathogenesis

Basal Ganglia in Huntingtons Disease

Huntingtons Disease Pathogenesis and Clinical Findings

Parkinsons Disease

Basal ganglia pathways

Lower Motor Neuron (UMN) Disease

Upper Motor Neuron (UMN) Disease

Dupuytren

Trigger Finger

Acute Compartment Syndrome

Chronic Exertional Compartment Syndrome

Patellofemoral Syndrome

Developmental Dysplasia of the Hip (DDH)

Adhesive Capsulitis

Scoliosis -Pathogenesis and Clinical Findings

Cauda Equina Syndrome

Myelopathy

Radiculopathy

Disc Herniations

Spondylolysis _and_Spondylolisthesis Pathogenesis and Clinical Findings

Representative X-ray appearance of a primary benign bone tumor

Benign Primary Bone Tumors - Pathogenesis of X-ray appearance

Representative X-ray appearance of a primary malignant bone tumor

Malignant Bone Tumors - Pathogenesis of X-ray appearance

MSK tumors complications

Avascular Necrosis - Pathogenesis and Clinical Findings

Pagets Disease Complications

Fracture Healing (and disruptors of this process)

Falls

Alcohol Use Disorder

SNRIs

Bupropion

SSRIs

MDD

BipolarDisorder

OCD

Panic Disorder

PTSD

Social Anxiety

Pathogenesis of Anxiety Disorders

Yu, Y - Pathogenesis of Anxiety Disorders FINAL.pptx Stress hormones interact with brain and body in various complicated mechanismsAnxiety Disorders: Pathogenesis of AnxietyPhysiological arousalAuthor: Yan YuReviewers:Sara Meunier JoAnna FayDex ArnoldMargaret Oakander* MD at time of publicationLegend:Published October 28, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsGenetics (Positive family history)Sense of foreboding or apprehensionActivation of hypothalamus-pituitary-adrenal cortex axisPredisposition to anxiety: Imbalance and/or abnormal functioning of norepinephrine, serotonin, dopamine, and gamma-aminobutyric acid (GABA) Female gender (may be related to hormonal factors, less internal locus of control, greater reporting rates)Other biological theories (under investigation)Prefrontal Cortex modulation of amygdala impairedUnpleasant tensionAmygdala maladaptively activates fear response? Cortisol releaseChronic activation of stress hormones over time causes death of neurons in the hippocampusAnxiety Disorders:A maladaptive emotional state causing fear, worry, and excessive stress, characterized by:Perceived environmental threatHippocampus and Cingulate Gyrus abnormally process threatActivation of autonomic nervous system and adrenal medulla? Epinephrine releaseHippocampus shrinks in sizeAbility of hippocampus to normally integrate environmental stimuli is further compromisedMood dysregulationMemory impairmentStrong association between anxiety disorders and depressionMeasurable ? in Brain-Derived Neurotrophic factor (BDNF)BDNF value correlates with the degree of neuronal loss in the hippocampus 97 kB / 173 words

3rd gen anti-psychotics

2nd generation antipsychotics

1st gen antipsychotics

Schizophrenia Pathogenesis and Clinical Findings

Yu, Y - Schizophrenia Pathogenesis and Clinical Findings FINAL.pptx Schizophrenia: Pathogenesis and Clinical FindingsDelusions(Fixed, false beliefs out of keeping with cultural background)? dopaminergic transmission in mesocortical projection? dopaminergic transmission in mesolimbic projection Author: Yan YuReviewers:Sara Meunier Briana CassettaJoAnna FayPhilip Stokes** MD at time of publicationLegend:Published November 5, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsGenetics (50% monozygotic twin risk, 6-13% 1st degree relative risk)Speech disorganization or senselessness (Tangentiality, derailment, word salads)Dopaminergic neurons here project into the limbic system, responsible for behaviors and emotions.SchizophreniaDopamine Hypothesis(predominant theory)Other biological theories (under investigation)High

DSM - Axis to Formulation

Complications of Measles Pathogenesis and Clinical Findings

Kawasaki Disease

Physiologic Neonatal Jaundice

Group A Streptococci Pharyngitis Pathogenesis and Clinical Findings

AcuteOtitisComplications

Acute Otitis Media - Pathogenesis and Clinical Findings (in Children)

Asthma Exacerbation - Pathogenesis and Clinical Findings in Children

Tetralogy of Fallot-Pathogenesis & Clinical Findings

Transposition of the Great Arteries-Pathogenesis & clinical findings

21-Hydroxylase Deficiency-Pathogenesis and clinical findings

Hallux Valgus pathogenesis and clinical findings - August 15 2015

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) - Pathogenesis and Clinical Findings

Urticaria- Pathogenesis and Clinical Findings

High Anion Gap Metabolic Acidosis Pathogenesis

Underfill Edema Pathogenesis

Edema Pitting vs Non-pitting

Childhood Immunization Schedule-Why we immunize

Gastroenteritis-Pathogenesis and clinical findings

Hyperopia - Pathogenesis and Clinical Findings

Myopia - Pathogenesis and clinical findings

Presbyopia - Pathogenesis and clinical findings

Trachoma - Pathogenesis and clinical findings

Acute Infectious Mononucleosis-Pathogenesis and clinical findings

Age Related Macular Degeneration - Pathogenesis and clinical findings

Posterior Vitreous Detachment - Pathogenesis and clinical findings

FINAL - CREST Syndrome Pathogenesis and clinical findings

Eosinophillic Esophagitis -Kattab Yaman - Final For Publication

Raynaud Phenomenon Pathogenesis and Clinical Findings

Chan Richard - Underfill Edema - Final 210915

Pre-Renal Acute Kidney Injury Pathogenesis

Pre-Renal Acute Kidney Injury Pathogenesis

High-AG Metabolic Acidosis Pathogenesis

Astigmatism Pathogenesis and Clinical Findings

Amblyopia Pathogenesis and clinical findings

Chemical Eye Injury Pathogenesis and clinical findings

Femoral Head Fracture Pathogenesis and clinical findings

PPROM - Pathogenesis and clinical findings

Septic arthitis pathogenesis and clinical findings

Family Med Slides Vitamin D Deficiency

Malignant Hyperthermia-Pathogenesis and clinical findings

Retinopathy of Prematurity - Pathogenesis and clinical findings

Orthostatic Hypotension-Pathogenesis and clinical findings

Stroke - Pathogenesis

Breast Cancer - Clinical findings

Splenomegaly - Pathogenesis and clinical findings

Chondrocalcinosis Calcium Pyrophosphate Dihydrate Deposition Disease

Graves' Disease Pathogenesis & Clinical Findings

sjogrensyndrome

Systemic Lupus Erythematosis SLE Musculoskeletal Manifestations

Hashimoto's Thyroiditis Natural History and Clinical Findings

Hashimoto's Thyroiditis Pathogenesis and Clinical Findings

Lacrimal Drainage System - Physiology

Ventricular Septal Defect (VSD)-Pathogenesis and clinical findings

Transfusion-associated Graft Versus Host Disease - Signs and Symptoms

Multiple sclerosis (MS)

Cataracts - pathogenesis and clinical findings

Keloid scar - pathogenesis and clinical findings

Overuse Tendinopathy -Pathogenesis and clinical findings

Wolff Parkinson White - Pathogenesis and clinical findings

Autonomic Dysreflexia - Pathogenesis and clinical findings

Acute Spinal Cord Injuries - Pathogenesis and clinical findings

Retinoblastoma - Pathogenesis and clinical findings

Alopecia Areata - Pathogenesis and clinical findings

Seasonal Affective Disorder - Pathogenesis and clinical findings v2

Yu, Y - Schizophrenia Pathogenesis and Clinical Findings - March 26 2016

Anterior Shoulder Dislocation - Pathogensis clinical and radiographic findings

Anterior Shoulder Dislocation - Pathogensis clinical and radiographic findings

Allergic Rhinitis - Pathogenesis and clinical findings

Allergic Rhinitis - Pathogenesis and clinical findings

Olfactory Dysfunction - Pathogenesis and clinical findings

Tinnitus

Acute Otitis Externa

Psoriasis: Pathogenesis and clinical findings

InfectiousFoodPoisoning

1st gen antipsychotics Translated

First Generation Anti-Psychotics: Mechanisms and Side Effects

Anti-Psikotik Generasi Kedua: Mekanisme dan Efek Samping

2nd generation antipsychotics Translated

Anti-Psikotik Generasi Kedua (Atipikal): Mekanisme dan Efek Samping

Anti-Psikotik Generasi Ketiga: Mekanisme dan Efek Samping

1st gen antipsychotics Translated

2nd generation antipsychotics Translated

1st gen antipsychotics Translated

3rd gen anti-psychotics Translated

Schizophrenia Pathogenesis Translated

Pathogenesis of Anxiety Disorders Translated

SAD Gangguan Afektif Musiman Translated

PTSD Translated

Panic Disorder Translated

OCD Translated

Bipolar Disorder Translated

MDD Translated

SSRIs Translated

Bupropion Translated

SNRIs Translated

Thacker, J - Social Anxiety Translated

DSM - Axis to Formulation Translated

Alcohol Use Translated

Seasonal Affective Disorder: Pathogenesis and clinical findings

Seasonal Affective Disorder: Pathogenesis and clinical findings

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Isolated Neutropenia

Chorioamnionitis: Risk factors, pathogenesis and clinical findings

Placental Complications During Labour

Placental Complications During Labour

Acute Rheumatic Fever- Pathogenesis and Clinical Findings

Opioid Receptor Agonists

Pharmacokinetics Basic Principles

Pharmacodynamics Basic Principles

Opioid Receptor Agonists

Peds Sexual Abuse

Peds Sexual Abuse

Onset of Labour- Pathophysiology

Stages of Labour- Mechanisms

Dilatation and Curettage - Complications

myasthenia-gravis-final

horner-syndrome

Focal Seizures in the adult: Pathogenesis and Clinical Findings

Macrosomia: Maternal Complications

Pediatric Uncompensated Shock: pathogenesis and clinical findings

Type 1 Respiratory Distress Syndrome

acute-closed-angle-glaucoma

aids-and-cmv-retinitis

keratoconus

onchocerciasis

primary-open-angle-glaucoma

secondary-glaucoma

opioid-withdrawal

keratoconus

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allergic-contact-dermatitis

Nephritic Syndrome: Pathogenesis and clinical findings

nephritic-syndrome

nephritic

Opioid Receptor Agonists

refeeding syndrome

Breast Cancer Risk Factors Causes and Types

Hyperosmolar Hyperglycemic State

Hyperosmolar Hyperglycemic State (HHS) Note: HHS is only seen in Type II DM patients! Note: In patients with either DKA or HHS, always look for an underlying cause (i.e. an infection) Author: Yan Yu Reviewers: Peter Vetere Gill Goobie Hanan Bassyouni* * MD at time of publication Alters total body water & ion osmosis Inadequate insulin production, insulin resistance, non- adherence to insulin Tx Relative Insulin deficit Stresses that ↑ Insulin demand: infections, pneumonia, MI, pancreatitis, etc) Hyperglycemia (Very high blood [glucose], higher than in DKA) When blood [glucose] > 12mmol/L, glucose filtration > reabsorption, ↑ urine [glucose] Glucosuria Glucose in filtrate promotes osmotic diuresis: large- volume urine output Polyuria Dehydration (↓ JVP, orthostasis: postural hypotension/ postural tachycardia, ↑ resting HR) Some insulin still present, but not enoughsome glucose is utilized by muscle/fat cells, some remain in the blood Cells not “starved”, but still need more energy ↑ release of Catabolic hormones: Glucagon, Epinephrine, Cortisol, GH Body tries to ↑ blood [glucose], to hopefully ↑ cell glucose absorption Hypothalamic cells sense low intra-cellular glucose, triggering feelings of hunger Polyphagia Note: the presence of some insulin directly inhibits lipolysis; thus, in HHS there is no ketone body production, and no subsequent metabolic acidosis and ketouria (unlike in DKA). If ketones are detected in an HHS patient it’s likely secondary to starvation or other mechanisms. ↓ ECF volume, ↑ ECF osmolarity (i.e. hypernatremia) ↑ Gluconeogenesis ↑ Glycogenolysis (in liver) ↓ Protein synthesis, ↑ proteolysis (in muscle) ↑ Gluconeogenic substrates for liver If the patient doesn’t drink enough water to replenish lost blood volume If pt is alert and Electrolyte imbalance water is accessible Water osmotically leaves neurons, shrinking them Neural damage: delirium, lethargy, seizure, stupor, coma ↓ renal perfusion, ↓ GFR Renal Failure (pre-renal cause; see relevant slides) Polydipsia Note: in HHS, body K+ is lost via osmotic diuresis. But diffusion of K+ out of cells may cause serum [K+] to be falsely normal/elevated. To prevent hypokalemia, give IV KCl along with IV insulin as soon as serum K+ <5.0mmol/L. But ensure patient has good renal function/urine output first, to avoid iatrogenic hyperkalemia! Note: Electrolyte imbalances (i.e. hyperkalemia, hypernatremia) are worsened by the acute renal failure commonly coexisting with DKA/HHS Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 3, 2016 on www.thecalgaryguide.com

cholesteatoma-nov-4-2016_final-edits

Ketamine

Neurotransmitters and Pharmacology behind Nausea and Vomiting

Neurotransmitters and Pharmacology behind Nausea and Vomiting

Neurotransmitters and Pharmacology behind Nausea and Vomiting

pathogenesis-of-neuropathic-pain

bn-pathogenesis

bn-signs-and-symptoms

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Small Bowel Bacterial Overgrowth: Pathogenesis and clinical findings

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Shoulder Dystocia: Pathogenesis and Clinical Findings

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NSAIDs Final

NSAIDs Final

induction-of-labour-indications-and-contraindications

Stress Fracture v.5

Placenta Accreta

GDM: Risk factors and pathogenesis

BPH Final

BPH Final

ASPD FINAL

BPD FINAL

NPD FINAL

Lithium FINAL

AF FINAL

generalized-seizures-definitions

generalized seizures definitions

Lateral Medullary Syndrome FINAL

Subdural hematoma FINAL

Staphylococcus Scalded Skin Syndrome FINAL

Manion contraception MOAs

Manion contraception MOAs2

Common meds contra in Preg

Non hormonal

Vasa Previa

ASPD FINAL

hypertension-in-pregnancy-overview-of-definitions

Yu Yan - Pre-eclampsia pathogenesis - publish

Yu Yan - Pre-eclampsia Maternal Complications - publish

Yu Yan - Pre-eclampsia Fetal Complications - publish

Altered Metabolism in the ICU

Altered Metabolism in the ICU- Pathogenesis and clinical findings

Mental Status Exam

Addiction Long-term Consequences

Addiction Pathogenesis

Non-accidental Burns

SLE-GI Manifestations

Testicular Torsion

Acquired Hydrocephalus

Kawasaki Disease

Secondary Hemostasis: Coagulation Cascade

systemic-lupus-erythematosus-gastrointestinal-manifestations

Systemic Lupus Erythematosus: Gastrointestinal Manifestations Abbreviations: • APLA Phospholipid — Anti-Antibodies 1— Production of auto-antibodies APLA in circulation promotes blood coagulation —01• Thrombosis of vessels in the pancreas Micro-thrombi of vessels in the liver Liver infarcts Thrombosis of vessels in the small intestine Acute Pancreatitis Death of liver cells release contents into blood stream Thrombus in the hepatic vein • Vascular Damage Mesenteric Vasculitis/Ischemia Budd Chiari Syndrome Damage to Auerbach's Plexus 11` Liver Enzymes 1` in capillary permeability Abnormal release of inflammatory cytokines 1 Inflammation in esophageal muscles Protein-Losing Enteropathy Ascites Note: The gastrointestinal manifestations of systemic lupus erythematosus are due to multifactorial and complex causes, some of which are unknown. Legend: Pathophysiology Mechanism Impaired motor innervation Authors: Joseph Tropiano Reviewers: Zaini Sarwar Harjot Atwal Liam Martin* * MD at time of publication Abnormal production of immune complexes Immune complex deposition in blood vessels Immune complex deposition in smooth muscle Inflammatory reaction in the GI tract Immune complex mediated vasculitis Chronic ischemia of bowel smooth muscle Muscular damage Myopathy or neurogenic pathology of the GI muscles GI muscle damage not severe enough to inhibit peristalsis completely Esophageal Motility Disorders Dysphagia Sign/Symptom/Lab Finding Complications Hypomotility Dysmotility

Critical Care Malnutrition

esophageal-gastric-varices

Esophageal/Gastric Varices: Pathogenesis and clinical findings Schistosomiasis Schistosoma species enter the body through the skin and circulate to liver Eggs lodge in terminal portal venules causing inflammation and fibrosis • 1` resistance through fibrosed and inflamed sinusoids Cirrhosis Liver disease activates hepatic stellate cells causing hepatic fibrosis • I` resistance through fibrosed and distorted sinusoids • 1` portal inflow due to splanchnic vasodilation Veno-Occlusive Disease Budd-Chiari Syndrome Endothelial damage Hypercoagulable in the sinusoids leads to clotting states* cause factor deposition in thrombosis of hepatic sinusoids hepatic veins 1` resistance t resistance through through hepatic occluded distal veins occluded sinusoids by thrombus ► Intra Hepatic Portal Hypertension Post Hepatic Portal Portal Vein Thrombosis Hypercoagulable states* cause thrombosis of portal vein Infiltrative Lesion • Primary or secondary malignancy localized to the portal vein Splenic Vein Thrombosis Pancreatitis leads to inflammation and thrombosis of the splenic vein 1 resistance through '1' resistance through 1` resistance through portal vein occluded portal vein occluded by splenic vein occluded by thrombus malignancy by thrombus Pre Hepatic Portal Hypertension Hypertension *Hypercoagulable states such as thrombophilia, malignancy, or connective tissue disease Portal esophageal/gastric Esophageal/Gastric blood flow backed anastomoses up into Varices As variceal pressure 1` vessels swell 4— Blood loss from circulation 1 vessel J, wall thickness 1 vessel size tension Dilation of veins in submucosa Blood oxidized and vomited or passed through GI Authors: Bigger Varices Variceal rupture Upper GI bleed Gabriel Burke Reviewers: Vadim lablokov Laura Byford-Richardson Meredith Borman* * MD at time of publication • Red Wale Mark or Cherry Red Spot Blood loss too rapid to be oxidized before emesis or passage of GI (visualized on endoscopy) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications • Venous drainage of spleen backed up into gastric anastomoses Tachycardia and hypotension Anemia Death Melena Coffee ground emesis Hematemesis Bright red blood per rectum

localized-pitting-edema

Localized Pitting Edema: Pathogenesis Central venous catheter insertion -11I• Insufficient venous valves Foreign body irritates the endothelium, causing endothelial injury 1` pro-fibrotic gene activation & pro-inflammatory factors Smooth muscle proliferation & thickening of the venous endothelial layer Central vein stenosis 1` in venous blood pooling, causing venous congestion -1111. Venous insufficiency 1` in venous blood • pressure Extrinsic compression (i.e. tumor) Authors: Sunny Fong Reviewers: Joseph Tropiano Adam Bass* * MD at time of publication Central vein thrombosis Deep vein thrombosis T in venous pressure is transmitted to the capillaries 1` in capillary hydrostatic pressure T in fluid extravasation from plasma into the interstitial space distal to site of obstruction or insufficiency Localized Pitting Edema: Edema fixed at a specific anatomical site Venous obstruction causes'` blood pooling distal to site of obstruction Starling's Equation: Net filtration gradient = LpS x ((Pap — Pint) Olcap LpS = Porosity or permeability of the endothelial layer Pup = Capillary hydrostatic pressure Pint = Interstitial hydrostatic pressure ncap = Capillary oncotic pressure flint = Interstitial oncotic pressure Note: An increase in net filtration gradient (eg. Increased capillary hydrostatic pressure or decreased capillary oncotic pressure) can lead to the formation of edema

Neurotransmitters-and-Pharmacology-behind-Nausea-and-Vomiting - IN

Neurotransmiter dan Farmakologi Mual dan Muntah Integrasi sensorik penglihatan, penghiduan, nyeri, takut, cemas, dsb. /(` TIK (tumor atau edema) 2 Pusat lebih tinggi di SSP (korteks serebri, batang otak, hipotalamus, talamus) Penyakit gerak atau labirin, menyebabkan ketidakcocokan sinyal antara sistem visual, vestibular, and proprioseptif Obat-obatan (cth. kemoterapi, opiat, antibiotik) Gangguan metabolik (cth. Gagal organ, hiperkalsemia) toksin (cth. Dari bakteri penyebab keracunan makanan) Peregangan (akibat stasis gaster, obstruksi organ berongga, tumor, konstipasi, atau distensi kapsuler organ padat — liver, pankreas) Kompresi (dari organ sekitar, tumor, atau asites) Jejas jaringan (dari peradanga, invasi tumor, kemoterapi, radiasi) Legenda: Sistem vestibular (telinga dalam) Zona Pemicu Kemoreseptor (CTZ) (terletak di daerah ventrikel 4 tanpa sawar darah otak, secara konstan menyaring bahan kimia di darah) Mekanisme kompleks dan belum dimengerti (mungkin dimediasi oleh banyak NT) Tx: bicara dan dengarkan pasien, teknik relaksasi; lini-2: benzodiazepin untuk depresi SSP global, non-spesifik Stimulasi langsung pusat muntah via efek massal Tx: kortikosteroid, to 4, peradangan + tx penyebab (cth. pembedahan) Sinyal mual/muntah ke pusat muntah dimediasi oleh Histamin (H1) dan Asetilkolin Muskarinik (ACh) T Tx: antagonis H1/ACh (cth. dimenhidrinat), Lini-2: antagonis ACh (cth. scopolamin) Sinyal mual/muntah ke pusat muntah dimediasi Serotonin (5-HT) dan Dopamin (D2) Tx: antagonis 5-HT (cth. ondansetron), antagonis D2 yang menembus sawar darah otak (cth. metoklopramid, bukan domperidon) + berhenti/kurangi obat penyebab Kebanyakan m ua I a kibat stasis Tx: antagonis D2 gastrokinetik(cth. domperidon — saluran makan atas /lambung penetrasi SSP kurang - & metoklopramid. catatan: keduanya dikontraindikasikan pada obstruksi GI) + dimediasi Dopamin (D2) di CTZ tx penyebab Patofisiologi Mekanisme Saluran GI (termasuk liver & mesenterium) Tanda/Gejala/Penunjang Sinyal mual/muntah ke pusat muntah dimediasi terutama oleh Serotonin (5-HT) dan Dopamin (D2) Tx: antagonis 5-HT (cth. ondansetron), antagonis D2 gastrokinetik (cth. metoklopramid, domperidon), fenotiazin antagonis D2 (i.e. haldol) + tx penyebab Komplikasi Penulis: Yan Yu* Penyunting: Laura Byford-Richardson Russell Loftus* Penerjemah: M Harmen Reza S* * MD (dokter) pada saat publikasi Catatan: Kebanyakan jalur neurotransmiter pada mual/muntah masih belum diketahui. Tatalaksana yang tercantum di sini hanya bertujuan untuk menjelaskan prinsip umum terapi lini pertama. Terapi terapan pada pasien akan bergantung kepada diagnosis spesifik dan presentasi klinis. Pusat Muntah Koordinasi refleks muntah (dijelaskan di slide

chronic-hypertensive-retinopathy-pathogenesis-and-clinical-findings

Chronic Hypertensive Retinopathy: Pathogenesis and clinical findings Risk Factors for 1° HTN (ex. 1` Age, FHx, Ethnicity, Diet, Smoking, 1` Alcohol use, Stress, 1` Salt intake, 1` BMI, 1, Exercise) • 1° HTN Retinal Detachment Vitreous Hemorrhage Central/Branch Retinal Artery/Vein Occlusions Risk Factors for 2° HTN (ex. Hyperaldosterone, Cushing's, Acromegaly, Chronic Kidney Disease, Obstructive Sleep Apnea, Diabetes Mellitus, Hypo/Hyper-thyroid, Adrenal Hyperplasia, Renal Artery Stenosis) 2° HTN Ophthalmic Artery Hypertension ,17 Stage 1: Mild/vasoconstrictive Stage 2: Moderate/sclerotic Stage 3: Severe/exudative Stage 4: Malignant Abbreviations: • HTN — Hypertension • BRB — Blood-retinal barrier • RPE — Retinal pigment epithelium Legend: Pathophysiology Mechanism Acute and chronic vasospasm Authors: Graeme Prosperi-Porta Reviewers: Stephanie Cote Usama Malik Johnathan Wong* * MD at time of publication Diffuse and focal arterial narrowing and vascular tortuosity Atherosclerosis and hyalinization causes arteriolar wall thickening resulting in a diffuse light reflex appearing red-brown coloured Thickening of the arteriolar wall and/or sclerotic thickening at the arteriole/venule crossing compresses the underlying venule BRB breakdown causes dot/blot hemorrhages in the inner retina and flame hemorrhages in the nerve fiber layer Serum proteins and lipids leakage from damaged BRB appears as white or yellow areas with sharp margins Occlusion of the terminal retinal arterioles causes fluffy white ischemic lesions in the inner retinal nerve fiber layer Hyper-pigmented patches surrounded by a hypo-pigmented ring due to RPE clumping around atrophic areas in the choroid Sign/Symptom/Lab Finding lschemia of optic disc arterioles causes optic nerve swelling and blurred disc margins. Leakage of optic disc arterioles causes hemorrhage and disc edema. Complications Copper Wiring AV nicking Retinal Hemorrhages Yellow Hard Exudates Cotton-wool Spots Elschnig's Spots Papilledema

central-retinal-artery-occlusion-pathogenesis-and-clinical-findings

Central Retinal Artery Occlusion: Pathogenesis and clinical findings Inflammatory Disease: Cardiogenic Embolism: Hypercoagulable state: Hematologic Disease: (i.e. GCA, SLE, GPA) (i.e. Valvular, arrhythmias, congenital defects) (i.e. OCP, Protein C&S deficiency, ATIII deficiency) (i.e. leukemia/lymphoma, sickle cell, polycythemia) Endothelial cell damage Abnormal blood flow 1` coagulation and/or 1 blood viscosity and creates hypercoagulable state causing localized stasis 4, anti-coagulation inflammation Abbreviations: • GCA — Giant Cell Arteritis • SLE — Systemic Lupus Erythematosus • GPA — granulomatosis with polyangitis • OCP — Oral contraceptive pill • ATIII — Anti-thrombin Ill Thrombus formation Blockage of central retinal artery Central Retinal Artery Occlusion (CRAO) Authors: Graeme Prosperi-Porta Reviewers: Stephanie Cote Usama Malik Johnathan Wong* * MD at time of publication Carotid Artery Atherosclerosis Atherosclerotic plaque dislodges from carotid artery The retina becomes pale 4, perfusion of retinal Slow retinal artery blood Acute retinal edema Ganglion cells and axons from NI, perfusion arterioles due to upstream flow allows for caused by ischemia results death due to ischemia CRAO segmentation of the blood column in a blurred appearance of the retina results in disc pallor seen months after CRAO The choroidal vessels supplying the macula via the posterior ciliary artery become more prominent within a background of retinal pallor

Fragile X Syndrome

Attention Deficit Hyperactivity Disorder (ADHD)

Oppositional Defiant Disorder (ODD)

Conduct Disorder (CD)

Down Syndrome

infectious-esophagitis-pathogenesis-and-clinical-findings

Infectious Esophagitis: Pathogenesis and clinical findings HIV/AIDS Radiation therapy Chemotherapy Organ Transplant Antibiotics I/Esophageal motility Tir CD4+ T cells 4,Monocyte and Corticosteroid and granulocyte precursors anti-TNF therapy • • Immunosuppression Note: Bacterial causes of infectious esophagitis are difficult to isolate as they are often polymicrobial in nature and derived from normal oral flora. Cytomegalovirus Infection of endothelial cells and fibroblasts I, Protective flora 4, Pathogen clearance Authors: David Deng Reviewers: Peter Bishay Vadim lablokov Kirles Bishay* MD at time of publication Mechanical stricture Inflammation Ulceration ,..,4 Dysphagia Infectious Viral Bacterial infection infection esophagitis • Fungal infection Odynophagia (i.e. Candida) Herpes Simplex Infection of squamous cells and macrophages Colonization facilitated by use of antacid therapy Nuclear Large Superficial Squamous Macrophage inclusion bodies esophageal ulceration ulcers cell inclusion bodies aggregation Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Spores and pseudohyphae seen on biopsy • Invas.on of underlying blood vessels • White plaques over erythematous base '1' neutrophils due to inflammatory response

The Neuroanatomy and Physiology of Emotion

The Neuroanatomy and Physiology of Emotion Basal Ganglia • The Prefrontal Cortex (PFC) Processes higher order emotions that 1— require recall, reason, and decision making (e.g., embarrassment) Integrates sensory information from the viscera in response to the inciting • environmental object or event with information from the amygdala Emotional feeling (i.e., conscious experience of emotion) Thalamus Emotionally salient environmental stimulus Sensory input (e.g., vision, touch, smell, hearing, taste) Hypothalamus ► (major output of the limbic system) Olfaction* Primary and Association Cortices • Amygdala Processes lower order emotions that have fast, automatic, and conditioned responses (e.g., fear) Participates in formation and retrieval of emotionally relevant memories from neocortical areas, attaching emotional significance to sensory input Hippocampus (key for memory consolidation and retrieval) ► Motor, Endocrine and Visceral systems Notes: • The structures involved in emotions are defined as the limbic system • The thalamus, basal ganglia and PFC together form the corticostriatalthalmocortical loop which comprises the major emotional processing pathway in the brain • The Prefrontal Cortex (PFC) includes the orbitofrontal cortex (OFC), dorsolateral prefrontal cortex and anterior cingulate cortex • *Olfaction is the only sense that bypasses the thalamus and connects directly to the primary olfactory cortex Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Authors: Andrea Moir Reviewers: Erika Russell Usama Malik Brienne McLane* * MD at time of publication Autonomic Nervous System (ANS) The ANS automatically and unconsciously responds to the emotional stimulus (e.g., 11` HR, blushing) Physical response to emotional stimulus Visceral sensation Sensory receptors are stimulated by the ANS response and transmit this information to the somatosensory and insular cortices

Serotonin Syndrome Pathogenesis and Clinical Findings

Serotonin Syndrome: Pathogenesis and Clinical Findings Serotonergic Agents SSR1s, SNRIs, MOAIs, TCAs, atypical antidepressants, antibiotics, mood stabilizers (valporate, lithium), opioids, antiemetic agents, triptans, weight loss agents, drugs of abuse (e.g. cocaine, amphetamines) Therapeutic drug use • Drug interactions (esp. combo of serotonergic agents) Serotonin Syndrome Variable combination of mental status changes, autonomic instability, and neuromuscular hyperactivity ranging from mild to life-threatening with an abrupt onset (within minutes to hours) after medication ingestion and most cases resolving within 24 hours of cessation of offending medication Intentional self-poisoning Excessive serotonergic activity at 5-HT receptors centrally (brainstem) and peripherally serotonin synthesis and release serotonin reuptake and metabolism IN receptor agonism and sensitivity 4, Drug-induced changes in the relative ratio of non-serotonergic neurotransmitters (e.g. increase in noradrenaline) Altered Mental Status Anxiety, confusion, agitation, hypervigilance, pressured speech, delirium, coma Autonomic Instability Shivering, diaphoresis, fever, diarrhea, tachycardia, mydriasis, hypertension Authors: Preeti Kar Reviewers: Erika Russell Usama Malik Aaron Mackie* * MD at time of publication Notes: The Hunter Serotonin Toxicity Criteria is used to make a clinical diagnosis • History of serotonergic agent taken within past 5 weeks + any of the following clinical features: • Spontaneous clonus • Inducible clonus and either agitation or diaphoresis • Ocular clonus and either agitation or diaphoresis • Tremor and hyperreflexia • Hypertonia, temperature > 38 °C, and either ocular clonus or inducible clonus Neuromuscular Hyperactivity Hyperreflexia, muscle rigidity (esp. lower extremities), myoclonus, tremor, incoordination, trismus*, opisthotonus*, ocular clonus*, seizures *Notes: • Trismus or lockjaw, is the reduced opening of the jaw • Opisthotonus is an abnormal body position where the person is usually rigid and arches their back, with their head thrown backwards • Ocular Clonus is rhythmic or equal movements of both eyes; should be distinguished from nystagmus which has a fast and slow component Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Abbreviations: • 5-HT = serotonin • SSRI = selective serotonin reuptake inhibitors • SNRI = selective noradrenaline reuptake inhibitors • MOAI = monoamine oxidase inhibitors • TCA = tricyclic antidepressants

Side Effects of ACEi/ARBs During Pregnancy

Side Effects of Methimazole During Pregnancy

Side Effects of NSAIDs During Pregnancy

Side Effects of Valproic Acid During Pregnancy

Side Effects of Warfarin During Pregnancy

Pediatric Parasomnias and Nightmares: Pathogenesis and clinical findings

Hemolytic Disease of the Fetus and Newborn

Trigeminal Neuralgia

Mallory-Weiss Tear

Unconjugated Neonatal Hyperbilirubinemia - Complications

pathogenesis-of-select-causes-of-constipation-in-adults-and-in-elderly

Pathogenesis of Select Causes of Constipation in Adults and in Elderly Authors: Reviewers: Lina Cadili Peter Bishay Joseph Tropiano Kirles Bishay* *MD at time of publication Mechanical Metabolic Endocrine Neurological Myogenic Pelvic Floor IBS-C Drugs (ex. Bowel (ex. (ex. (ex. Multiple (ex. Dyssynergia (ex. Opioid Obstruction, Stricture) Hypercalcemia) Hypothyroid-ism) Sclerosis) Scleroderma) Analgesics) Mechanical I`Ca2+ = 4, Na+ Thyroid Demyelination Collagen Puborectalis Disturbance in obstruction in permeability in hormone of CNS neurons deposits into muscle and the gut-brain the bowel neurons deficiency colonic mucosa, leading to external anal sphincter fail interaction fibrosis of the gut wall to relax Interrupted 4, Excitability Possible Dysfunction of Narrowed Mechanism flow of bowel contents and tone of bowel smooth mechanisms: hormone autonomic nerves that anorectal angle and unknown, many Atrophy of the muscle receptor supply smooth muscle '`pressure of pathways changes, involuntary wall of the colon anal canal neuromuscular disorders, myopathy from bodily functions 1, Peristalsis of infiltration of 4, Ability of the Evacuation Visceral the bowel colon to contract of feces is hypersensitivity Abbreviations: the intestinal wall 4, Digestion less effective and 4, colonic and colonic motility motor • IBS-C: Irritable Bowel Syndrome with predominant constipation • CNS: Central Nervous System 4, Peristalsis of response after a meal the bowel Opioids bind to Lt-opioid receptors on gut wall Inhibition of excitatory neural pathways within the enteric nervous system 1, Peristaltic contractions 1 l• Colonic transit time

1st gen antipsychotics (Slovenian translation) - FINAL VERSION

Antipsihotiki prve generacije: mehanizem delovanja in neieleni utinki antagonisti dopaminskih D2 receptorjev zavirajo delovanje DA na D2 receptorjih po celotnih mo2ganih t antipsihotiki prve generacije (tudi tipicni ali klasicni antipsihotiki) primera: haloperidol, klorpromazin antagonisti ACh M1 receptorjev zavirajo delovanje ACh po celem telesu (v ustih, prebavilih, o6eh, mo2ganih) zaprtje suha usta zamegljen vid kognitivna upolasnjenost Legenda: antagonisti histaminskih H1 receptorjev zavirajo delo-vanje histami-na v mo2ganih zaspanost porast tel. teie antagonisti adrenoceptorjev dilatacija gladkih miSic v stenah arteriol - te2ave pri vzdrievanju krvnega tlaka ortostatska hipotenzija mezolimbiZna pot VTA 4 limbicni sistem mezokortikalna pot VTA prefrontalna skorja tuberoinfundibularna pot hipotalamus 4 hipofiza nigrostriatna pot substanca nigra 4 striatum 1 ekstrapiramidni simptomi (EPS) avtorica: Sara Meunier pregledala: Yan Yu, Aaron Mackie* * dr. med. ob objavi 4, pozitivnih simptomov terapevtski ueinek 4, odziv nagrajevalne poti negativnih simptomov 11• kognitivnih simptomov teiave s pozornostjo in u6enjem blokada DA vodi v izlaanje prolaktina iz adenohipofize prevedel in priredil: Jan Kejiar, dr. med., specializant psihiatrije pregledala: doc. dr. Brigita Novak Sarotar, dr. med., spec. psih. 4, halucinacij 4, blodenj otopelost anhedonija 4. zanimanja za socialne stike amenoreja galaktoreja okrajgave: VTA - ventral no tegmental no podraje DA - dopamin ACh - acetilholin tardivna diskinezija Nenormalni asimetri6ni gibi obraznih mrgic, jezika in/ali udov, povzro6eni s kroni6no dopaminsko blokado. Letna incidenca pribliino 5 %, potencialno ireverzibilna! patofiziologija mehanizem iatrogeni parkinsonizem pojav zobatega kolesa, nestabilnost v drii, tremor v mirovanju, bradikinezija/akinezija znak/simptom/laboratorijska najdba akutna distonija kra migic vratu, okrog ob, jezikageljusti akatizra obL'utek motorie'nega nemira zaplet Objavljeno 15. junija 2017 na www.thecalgaryguide.com.

2nd gen antipsychotics (Slovenian translation) - FINAL VERSION

Antipsihotiki druge generacije: mehanizem delovanja in neieleni utinki antipsihotiki druge generacije (atipibi antipsihotiki): primeri: klozapin, olanzapin, kvetiapin, risperidon, paliperidon itd. antagonisti dopaminskih D2 receptorjev zavirajo delovanje DA na D2 receptorjih po celotnih mo2ganih antagonisti serotoninskih 2A receptorjev zavirajo delovanje 5-HT na 5-HT2A receptorjih po celotnih mo2ganih antagonisti serotoninskih 2C receptorjev klozapin, olanzapin, kvetiapin antagonisti ACh M1 receptorjev zavirajo delovanje ACh po telesu (v ustih, prebavilih, o6eh, mo2ganih) antagonisti aradrenoceptorjev v oiilju dilatacija gladkih migic v stenah arteriol antagonisti histaminskih H1 receptorjev zavirajo delovanje histamina po telesu sano-presnovni kink' mehanizem neznan Legenda: patofiziologija mehanizem Pomni: posledica velikih razlik v afiniteti za receptorska vezavna mesta so svojevrstni terapevtski in varnostni profili atipicnih a nti psi hoti kov. Kloza pi n med vsemi velja za najud nkovitejSega, a i ma tudi najve6 neZelenih uC'inkov, vkljUuja agranulocitozo (0,5-2 %). Tako predstavlja terapijo drugega izbora, potrebno je red no spremljanje bolnikove krvne slike. mezolimbiEna pot DA blokada > 5-HT blokado nigrostriatna pot 5-HT blokada > DA blokado 4, pozitivnih simptomov terapevtski ueinek blokada 5-HT vodi v sprokanje DA v striatumu tubero- blokada 5-HT zavre sprokanje infundibularna pot prolaktina v adenohipofizi mezokortikalna pot blokada 5-HT2c receptorjev stimulira sprokanje DA in NA v prefrontalni skorji zamegljen vid kognitivna upolasnjenost sposobnost vzdrievanja krvnega tlaka omotica apetit T tel. tee ortostatska hipotenzija tveganje za debelost trigliceridi na tee inzulinska odpornost —■ diabetes tipa 2 znak/simptom/laboratorijska najdba 4, halucinacii blodeni avtorica: Sara Meunier pregledala: Yan Yu, Aaron Mackie* * dr. med. ob objavi prevedel in priredil: Jan KejZar, dr. med., specializant psihiatrije pregledala: doc. dr. Brigita Novak Sarotar, dr. med., spec. psih. 4, ekstrapiramidnih simptomov (EPS)* 4, hiperprolaktinemije* prokognitivni in antidepresivni ainki 4, kognitivnih simptomov* 4, negativnih simptomov* * Glede na anti-psihotike prve generacije, glej ustreznogradivo! okrajgave: 5-HT - serotonin DA - dopamin NA - noradrenalin ACh - acetilholin visoko presnovno tveganje: klozapin, olanzapin zmerno presnovno tveganje: risperidon, kvetiapin nizko presnovnotveganje:antipsihotikitretjegeneracije 1 tveganje za diabeti6no ketoacidozo pri bolnikih z visokim tveganjem tveganje za srbo-iilne dogodke tveganje za prezgodnjo smrt zaplet Objavljeno 15. junija 2017 na www.thecalgaryguide.com.

3rd gen antipsychotics (Slovenian translation) - FINAL VERSION

Antipsihotiki tretje generacije: mehanizem delovanja in neieleni utinki antipsihotiki tretje generacije (atipithi antipsihotiki) primer: aripiprazol delni agonist dopaminskih D2 receptorjev Veie se na D2 receptor, se hitro sprosti in znova veie. Ta ponavljajoc vzorec receptorske vezave molekulam DA v sinapsah ne pusti, da bi se vezale na D2 receptorje. 4, prepre6uje vikk DA zaradi preve6 stimuliranih receptorjev in primanjkljaj DA zaradi premalo stimuliranih receptorjev

Alcohol Use Disorder (Slovenian translation) - FINAL VERSION

Sindrom odvisnosti od alkohola: patogeneza in kliniene najdbe genetika 54-% tveganje pri enojagnih dvogkih; 28-% tveganje pri dvojagnih dvogkih psiholoKki dejavniki anamneza antisocialnega vedenja, nizka samopodoba, impulzivnost, druge teiave z duSevnim zdravjem okoljski dejavniki stresno Zivljenje, prevzemanje vzorcev od starkv ali vrstnikov sindrom odvisnosti od alkohola kot odziv na ponavljajoL'e se izpostavitve, jetra aktivnost encimov, npr. nevroanatomske •••11 deregulacija 2ivthih alkoholne dehidrogenaze, • nepravilnosti (v prefrontalni ki razgrajujejo etanol prenagalcev (glutamata, GABA-e, serotonina) sprokanje endogenih opioidov skorji in mezolimbibem dopaminskem sistemu) etanol dose2e dano koncentracijo v krvi hitreje (tj. v 6asa) toleranca (zmanjgana ob'6utljivost na ainke etanola) /1` vnos etanola za dosego enakih u6inkov socialna okrnjenost nezmoZnost izpolnjevanja obvez (na delu, v Soli, doma) nadaljevanje (zlo)rabe kljub druZbenim problemom, povzro6enih z alkoholom kljuthih druthenih, poklicnih in rekreativnih aktivnosti • tvegana uporaba substance ponavljajo6e se raba alkohola v 'gkodIjivih situacijah nadaljevanje rabe navkljub poznavanju posledic Pomni: v DSM-5 sta prej lo6eni entiteti zloraba alkohola in odvisnost od alkohola zdruZeni v motnjo rabe alkohola (an. alcohol use disorder). Zloraba alkohola je bila prej definirana kot pitje navkljub ponavljajo6im se druZbenim in medosebnim teZavam ter teZavam z zakonom, odvisnost pa je predstavljala „podaljSek

BMR (Slovenian translation) - FINAL VERSION

Bipolarna motnja razpoloienja: patogeneza in kliniene najdbe genetika 85-% tveganje pri enojagnih neravnovesja iivenih prenagalcev dvoj6kih, 5- do 12-% tveganje zlasti serotonina, noradrenalina pri sorodnikih v prvem kolenu in dopamina nepravilnosti v moig. poteh deregulacija frontalnih in limbi6nih poti maniEna epizoda najmanj 1 teden ali indikacija za sprejem • ( A privzdignjeno/ekspanzivno/razdrailjivo razpoloienje k cilju usmerjenega vedenja/agitacija potrebe po spanju odkrenljivost vrveiavost pospegen govor evforije velilavosti I` razdrailjivosti tveganja Legenda: patofiziologija mehanizem inhibicije nadzora custvenih poti bipolarna motnja razpoloienja motnje homeostaze custev 4, nihanja razpoloienjskih stanj raznolik potek bolezni pri razliCnih bolnikih evtimi'a o6itna obdobja normalnega razpolo2enja Primarni cilj zdravljenja je vzdr2evati to fazo! okoljski dejavniki (travmatski dogodki, 2ivljenjski stresorji) ) Pomni: • Bipolar motnja tipa 1: maniba epizoda in/ali depresivna epizoda: priblrino 10 epizod manije in depresije v 2ivljenju bolnika v primeru nezdravljene bolezni • Bipolar motnja tipa 2: hipomaniba epizoda in depresivna epizoda • hipomaniba epizoda predstavlja bla2jo obliko manije, tj. brez funkcionalne okrnjenosti, brez psihotibih simptomov, brez hospitalizacije in v trajanju vsaj 4 zaporednih dni znak/simptom/laboratorijska najdba avtorici: Briana Cassetta, Sara Meunier pregledali: Yan Yu, Alexander Arnold, Philip Stokes* * dr. med. ob objavi prevedel in priredil: Jan Kejiar, dr. med., specializant psihiatrije pregledala: doc. dr. Brigita Novak Sarotar, dr. med., spec. psih. depresivna epizoda najmanj 2 tedna depresivno razpoloienje socialnega urriika obEutkov krivde, tesnobe brezupa samomorilnih misli in vedenja anhedonija teiave s pozornostjo A v spanju, utrujenost A tel. teie, apetita psihomotorna agitira nost ali upolasnjenost zaplet Objavljeno 30. junija 2017 na www.thecalgaryguide.com.

Bupropion (Slovenian translation) - FINAL VERSION

Bupropion (atipiEni antidepresiv): Mehanizem delovanja in neieleni utinki potenten antidepresiv v monoterapiji all kot dodatno zdravilo pri zdravljenju razpoloienjskih motenj okrajgave: 5-HT - serotonin DA - dopamin DAT - prenagalec DA NA - noradrenalin NAT - prenagalec NA SSRI - selektivni zaviralec ponovnega privzema 5-HT Legenda: bupropion farmakologija antidepresivni udnki uporaben pri zdravljenju NAT), ki proizvaja aktivne metabolite. Natan'6en mehanizem delovanja (se) ni znan. znak/simptom/laboratorijska najdba DA in NE posledi6no ostaneta v sinapsah dlje Casa in okrepita 2iv6ni prenos neieleni udnki glavobol suha usta 4, tel. tee nespeEnost slabost zaprtie tahikardija epileptiEni napadi faringitis omotica hipertenziia agitacija prevedel in priredil: Jan Kejiar, dr. med., specializant psihiatrije pregledala: doc. dr. Brigita Novak Sarotar, dr. med., spec. psih. eliminacija poteka preko jeter in ledvic prilagoditev odmerka v primeru bolezni jeter in/ali ledvic bupropion lahko inhibira jetrni citokrom P4502D6 in povzrod interakcije med zdravili kontraindiciran pri boleznih, ki zmanIgajo epileptogeni prag: anoreksija/bulimija nervoza, epilepsija, odtegnitev alkohola, odtegnitev benzodiazepinov zaplet Objavljeno 30. junija 2017 na www.thecalgaryguide.com. " title="Bupropion (atipiEni antidepresiv): Mehanizem delovanja in neieleni utinki potenten antidepresiv v monoterapiji all kot dodatno zdravilo pri zdravljenju razpoloienjskih motenj okrajgave: 5-HT - serotonin DA - dopamin DAT - prenagalec DA NA - noradrenalin NAT - prenagalec NA SSRI - selektivni zaviralec ponovnega privzema 5-HT Legenda: bupropion farmakologija antidepresivni udnki uporaben pri zdravljenju "zmaniganega pozitivnega afekta" nima pomembnelgih 5-HT udnkov povzraa spolne disfunkcije v primerjavi s SSRI; lahko celo odpravi omenjeni neieleni udnek (povzraen s strani SSRI) dodatek pri zdravljenju odvisnosti od nikotina preko T iive'nega prenosa DA v nagrajevalni poti energije preko T 2ivbega prenosa NA patofiziologija mehanizem farmakokinetika farmakodinamika avtorica: JoAnna Fay, Sara Meunier pregledala: Jojo Jiang, Alexander Arnold, Aaron Mackie* * dr. med. ob objavi Nizkoafiniteten zaviralec ponovnega privzema DA in NA (DAT>NAT), ki proizvaja aktivne metabolite. Natan'6en mehanizem delovanja (se) ni znan. znak/simptom/laboratorijska najdba DA in NE posledi6no ostaneta v sinapsah dlje Casa in okrepita 2iv6ni prenos neieleni udnki glavobol suha usta 4, tel. tee nespeEnost slabost zaprtie tahikardija epileptiEni napadi faringitis omotica hipertenziia agitacija prevedel in priredil: Jan Kejiar, dr. med., specializant psihiatrije pregledala: doc. dr. Brigita Novak Sarotar, dr. med., spec. psih. eliminacija poteka preko jeter in ledvic prilagoditev odmerka v primeru bolezni jeter in/ali ledvic bupropion lahko inhibira jetrni citokrom P4502D6 in povzrod interakcije med zdravili kontraindiciran pri boleznih, ki zmanIgajo epileptogeni prag: anoreksija/bulimija nervoza, epilepsija, odtegnitev alkohola, odtegnitev benzodiazepinov zaplet Objavljeno 30. junija 2017 na www.thecalgaryguide.com. " />

PTSD (Slovenian translation) - FINAL VERSION

Posttravmatska stresna motnja (PTSM): patogeneza in kliniene najdbe predbolezenski dejavniki genetika 30-% varianca* skupen vpliv preteklih iivljenjskih stisk veda oUutijivost za dukvne travme **Op. prey.: nepristranskost pozornosti (an. attentional bias) se nanak na podyrknost oz. nagnjenost Elovekovih zaz-nav k vplivu njegovih trenutnih misli. VeE v skupni bibliografiji psihologov A. Tverskyja in D. Kahnemana. Legenda: travmatski dogodek obaitki nemod in/ali izgube nadzora (npr. v okolikinah vojne, naravnih katastrof, spolnega napada, poroda) intenziven Zustveni odziv ob du§evni travmi strah, nema ali groza posttravmatska stresna motnja (PTSM) nevrokemijske nepravilnosti spremembe v prenosu kortizola, GABA-e, dopamina prekomerna Zustvena vzburjenost anksioznost posttravmatski dejavniki pomanjkanje druibene podpore stresni dejavniki v iivljenju avtorica: Briana Cassetta pregledali: Sara Meunier, Yan Yu, Margaret Oakander* * dr. med. ob objavi prevedel in priredil: Jan Kejiar, dr. med., specializant psihiatrije pregledala: doc. dr. Brigita Novak Sarotar, dr. med., spec. psih. *Op. prey.: z narakanjem variance se ve6a fenotipska raznolikost v populaciji. moteni spoznavni procesi pove6ana odzivnost amigdale nepristranskostpozornosti** zoper sign ale ogroknosti inhibicija hipokampusa vodi v drobljenje spomina pove'Cana opreznost pretirana bojazijivost teiave s pozornostjo podoiivljanje duKevnih travm, npr. v obliki noZnih mor ali „iivega

Lipid Physiology Slide

LIPID PATHWAY BASICS: Absorption, Transport and Storage of Triglyceride and Cholesterol Exogenous (Dietary) Lipid Supply Small Intestine: Absorption of dietary triglycerides and cholesterol Lymph, then Plasma: Chylomicrons (ApoC2 , ApoB48 ) Transport of dietary Triglycerides and Cholesterol Peripheral Tissues: Triglyceride uptake and Chylomicron metabolism via Lipoprotein Lipase receptors (in presence of ApoC2) Plasma: Chylomicron Remnants (ApoE) Liver: Chylomicron Remnant uptake via surface LDL receptors and LRP1 (in presence of ApoE) Note: Key component carrier lipoproteins are indicated in bold parentheses. i.e. (ApoC2). _DL are Density Lipoproteins which can be High (HDL), Intermediate (IDL), Low (LDL), and Very Low (VLDL) Deficiencies in these lipoproteins often result in inability to shuttle lipids and ensuing hyperlipidemias. Endogenous Triglyceride Supply Liver: Synthesis of VLDL from FFAs, ApoB100, and Cholesterol Plasma: VLDL (ApoB100, ApoC2, ApoE) Transport of endogenous triglycerides and Cholesterol Peripheral Tissues: Triglyceride uptake and VLDL cleavage via Lipoprotein Lipase receptors (in presence of ApoC2) Endogenous Cholesterol Supply Plasma: IDL (ApoE ) Transport of Cholesterol and Triglycerides to Liver Liver: IDL uptake via surface LDL receptors (in presence of ApoE) IDL metabolism to LDL via Hepatic Lipase Plasma: LDL (ApoB100, Apo E) Transport of Cholesterol Peripheral Tissues: Cholesterol uptake via surface LDL receptors (in presence of ApoB100) Author: David Lincoln Reviewers: Harjot Atwal Usama Malik Dr. Alexander A-C Leung* * MD at time of publication Reverse Cholesterol Transport Plasma: Immature HDL (ApoAl) Nascent in plasma • Peripheral Tissues: Cholesterol export via surface ABCA1/ABCG1 transporters Abbreviations: • ABCA1 - ATP-Binding Cassette Transporter Al • ABCG1 - ATP-Binding Cassette Transporter G1 • FFAs - Free Fatty Acids • LCAT - Lecithin Cholesterol Acetyl Transferase • LRP1 - LDL Receptor-related protein • SRB1 - Scavenger Receptor B1 Plasma: Mature HDL (ApoAl) Free cholesterol is esterified via LCAT. Some cholesterol remains in plasma via CTEP-mediated transfer of Cholesterol to lower density lipoproteins (i.e. VLDL, IDL) Liver: Cholesterol ester uptake into liver via SRB1 Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September, 24,2017 on www.thecalgaryguide.com

Subtrochanteric Femur Fracture

Subtrochanteric Femur Fracture: Pathogenesis and clinical inical findings lack Yu gm: Annalise Alaboo Major trauma s Osteo l: porosis Atypical femur fracture si: Reza Ojaghi '1,Usama Malik Dr. Richard Buckley. • moottime of publication An excess amount of Low energy Bisphosphonate force is transferred to forces exerted suppresses bone the femur( e.g. fall onto the remodeling from height in lateral side of elderly, motor vehicle the weakened ii accident in young fem.-Lb..Microscopic pm*/ low level foll) damage Notes: weakens the ------------___________L_____---------- hone • Subtrochanteric region span, cm .tally from the lesser Subtrochanteric trochorder • Major haumas is most Femur Fracture common in young and low energy fall fractures in elderly Mechanical instability Pain with motion Point tenderness Inability to beercei ht Gluseus maxlmus and minimus force vectors Abduction Displaced proximal femur Psoas force vector Pirifo o Non-union of fracture External rotation Legend: Pa.ophysiolo. Mechanism sign/Symptom/Lab Finding Complications Published September, Mk 201, on envie thecelgeigguide CO. rum

Ovarian Torsion

Non-Hodgkin Lymphoma

Pelvic Inflammatory Disease

Pituitary Mass Effects

Pituitary Mass Effects Note: pituitary tumors are almost always a benign adenoma. Pituitary adenomas are very common -approximately 1 in 6 individuals. These are usually asymptomatic and are found incidentally. Symptomatic pituitary adenomas that require treatment are much less common and affect approximately 1 in 1000 individuals. Pituitary tumor Note: typically (but not always) the anterior hormones will be lost in the following order; GH, LH, FSH, TSH, ACTH, PRL. This order (with the exception of prolactin) is the order of least-essential to most-essential hormones needed for survival. A good mnemonic to remember the order the hormones are is, 10mm on MRI) vomiting Giant adenoma Extension into hypothalamus —1■• Damage to hypothalamic cells Hypothalamic (>40mm on MRI) dysfunction Obstruction of dopamine Superior tumor growth Impingement of the optic chiasma Bitemporal Loss of pituitary hemianopsia hormones ICP Suprasellar extension Occlusion of ventricles Obstruction of CSF Flow Hydrocephalus Lateral tumor growth Impingement of cranial nerves 3, 4, 5 (V1/V2) and 6 4 Pituitary stalk impingement Diplopia Inferior tumor growth Erosion into sphenoid sinus CSF leak into throat Post-nasal Obstruction of ADH drip Communication between sinus and brain Migration of bacteria from sinus flora Hyper-Diabetes Meningitis prolactinemia insipidus Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 1 2017 on www.thecalgaryguide.com " title="Pituitary Mass Effects Note: pituitary tumors are almost always a benign adenoma. Pituitary adenomas are very common -approximately 1 in 6 individuals. These are usually asymptomatic and are found incidentally. Symptomatic pituitary adenomas that require treatment are much less common and affect approximately 1 in 1000 individuals. Pituitary tumor Note: typically (but not always) the anterior hormones will be lost in the following order; GH, LH, FSH, TSH, ACTH, PRL. This order (with the exception of prolactin) is the order of least-essential to most-essential hormones needed for survival. A good mnemonic to remember the order the hormones are is, "Go Look For The Adenoma Please". Legend: Note: for pituitary masses of all sizes, it is important to determine whether the pituitary tumor is secreting (70%) or non-secreting (30%) as secreting tumors can be targeted with medication. The most common secreting tumors secrete prolactin (most common), growth hormone, and ACTH. Authors: Chris Oleynick Reviewers: Amyna Fidai Laura Byford-Richardson Joseph Tropiano Hanan Bassyouni* * MD at time of publication Microadenoma Small size is unlikely to cause mass effects (<10mm on MRI) Asymptomatic Macroadenoma Large size may press on surrounding structures, causing mass effects Headaches Stretching of the meninges Activation of mechanoreceptors Nausea and (>10mm on MRI) vomiting Giant adenoma Extension into hypothalamus —1■• Damage to hypothalamic cells Hypothalamic (>40mm on MRI) dysfunction Obstruction of dopamine Superior tumor growth Impingement of the optic chiasma Bitemporal Loss of pituitary hemianopsia hormones ICP Suprasellar extension Occlusion of ventricles Obstruction of CSF Flow Hydrocephalus Lateral tumor growth Impingement of cranial nerves 3, 4, 5 (V1/V2) and 6 4 Pituitary stalk impingement Diplopia Inferior tumor growth Erosion into sphenoid sinus CSF leak into throat Post-nasal Obstruction of ADH drip Communication between sinus and brain Migration of bacteria from sinus flora Hyper-Diabetes Meningitis prolactinemia insipidus Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 1 2017 on www.thecalgaryguide.com " />

Acute Chest Syndrome (Sickle Cell Disease)

tetanus

tetanus

Anaphylaxis - Pathogenesis

Ischemia: Pathogenesis of Cellular Injury and Death

Ischemia: Pathogenesis of Cellular Injury and Death 4, Cardiac Output Obstruction of Blood Flow 4, Oxygen Carrying Capacity Inadequate oxygenation of body tissues • lschemia • 4, oxygen availability to body tissues with inadequate oxygen supply • Hypoxia/Anoxia 4, cellular oxidative phosphorylation Authors: Tiffany Yuen Reviewers: David Lincoln Erin Davison Usama Malik Dr. P. Timothy Pollak* * MD at time of publication Anaerobic respiration • vir Failure to resynthesize energy-rich phosphates & phosphocreatine Catabolism of ATP -> AMP Altered ATP-dependent ionic membrane pump Intracellular accumulation of intracellular Ca2+ intracellular hypoxanthine & H2O Conversion of hypoxanthine Activation of phospholipases & Cellular Edema production of free fatty acids -> toxic oxygen species Reperfusion and re-introduction Phospholipases and free fatty acids degrade cellular membranes of molecular oxygen Legend: Pathophysiology Mechanism Cellular Injury and/or Cellular Death Sign/Symptom/Lab Finding Complications 4, pH Lactic acidosis • 1` Fe decompartmentalization Mitochondrial injury 1` free-radicals NADH degradation 4, ATP levels Nuclear damage

Hepatitis C (HCV) Infections: Explaining Serology Patterns

Hepatitis C (HCV) Infections: Explaining Serology Patterns Seroconversion occurs on average 8-9 weeks after exposure to antigen H CV RNA Negative Anti-HCV Antibody Positive2 HCV RNA Positive4 1 HCV Screen Anti-HCV Antibody Negative Suspected acute HCV3 HCV RNA will be positive in blood within 1-3 weeks after exposure No risk factors; likely no HCV exposure HCV RNA Negative No HCV exposure HCV cleared spontaneously or with treatment or false positive antibody test6 Acute HCV (15%) 5Chronic HCV (85%) HCV RNA negative 12 or 24 weeks after stopping therapy (SVR12 or SVR24) Abbreviations: SVR12: sustained virologic response after 12 weeks SVR24: sustained virologic response after 24 weeks Hepatocellular Carcinoma Cirrhosis Decompensation (ascites, variceal bleeding, encephalopathy) 7 Liver Transplant Death Authors: Emma Boyce Sarah Lacny Reviewers: Peter B i s h ay Joesph Tropiano Yin Chan* * MD at time of publication Notes: 1Indications for HCV screen: born between 1945-1965, ↑ALT/AST, IVDU, received blood or organ transplant before 1992, received clotting factors before 1987, HIV infected or multiple sexual partners, tattoos and piercings (especially if done in prison), dialysis patients, Egyptian background 2There is no HCV vaccine; an anti-HCV positive test result indicates exposure to the virus 3Seve re l y immunocompromised, hemodialysis, possible exposure, clinical manifestations 4Assess genotype and viral load (HCVRNA), symptoms, and potential exposures to diagnose chronic versus acute HCV 5Acute HCV infection is defined as the first 6 months following exposure 6The anti-HCV antibody does not protect against future infections 7Liver transplant recipients have an 80% chance of developing a recurrent HCV infection Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published NOVEMBER 12, 2017 on www.thecalgaryguide.com

Hepatitis C (HCV) Infection: Explaining Serology Patterns

Hepatitis C (HCV) Infections: Explaining Serology Patterns Seroconversion occurs on average 8-9 weeks after exposure to antigen H CV RNA Negative Anti-HCV Antibody Positive2 HCV RNA Positive4 1 HCV Screen Anti-HCV Antibody Negative Suspected acute HCV3 HCV RNA will be positive in blood within 1-3 weeks after exposure No risk factors; likely no HCV exposure HCV RNA Negative No HCV exposure HCV cleared spontaneously or with treatment or false positive antibody test6 Acute HCV (15%) 5Chronic HCV (85%) HCV RNA negative 12 or 24 weeks after stopping therapy (SVR12 or SVR24) Abbreviations: SVR12: sustained virologic response after 12 weeks SVR24: sustained virologic response after 24 weeks Hepatocellular Carcinoma Cirrhosis Decompensation (ascites, variceal bleeding, encephalopathy) 7 Liver Transplant Death Authors: Emma Boyce Sarah Lacny Reviewers: Peter B i s h ay Joesph Tropiano Yin Chan* * MD at time of publication Notes: 1Indications for HCV screen: born between 1945-1965, ↑ALT/AST, IVDU, received blood or organ transplant before 1992, received clotting factors before 1987, HIV infected or multiple sexual partners, tattoos and piercings (especially if done in prison), dialysis patients, Egyptian background 2There is no HCV vaccine; an anti-HCV positive test result indicates exposure to the virus 3Seve re l y immunocompromised, hemodialysis, possible exposure, clinical manifestations 4Assess genotype and viral load (HCVRNA), symptoms, and potential exposures to diagnose chronic versus acute HCV 5Acute HCV infection is defined as the first 6 months following exposure 6The anti-HCV antibody does not protect against future infections 7Liver transplant recipients have an 80% chance of developing a recurrent HCV infection Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published NOVEMBER 12, 2017 on www.thecalgaryguide.com

Medical Conditions Causing Mania or Mania-Like Episodes: Pathogenesis

Medical Conditions Causing Mania or Mania-Like Episodes: Pathogenesis Bipolar Disorder Combination of individual, genetic, and environmental factors Abnormalities of amine neurotransmitter systems and impairment of neuroplasticity and cellular resilience, particularly frontal and limbic circuitry 4, Inhibitory control of frontal and limbic emotional circuitry Multiple Sclerosis Immune-mediated demyelination alters normal neurotransmitter pathways B12 deficiency Lack of B12 as a cofactor for methionine synthesis Downregulation of S-Adenosyl methionine (SAM) pathway 4, myelin synthesis and neurotransmitter regulation Altered Thyroid Activity Corticosteroid Use 7), 4, thyroid activity 4, central serotonin activity 4, postsynaptic beta-adrenergic receptor activity 4, in catecholamine (including dopamine) transmission Adrenocortical hormones t Dopamine D2 receptor numbers (hypothesis) Note: Mania is defined as at least 1 week of abnormally and persistently elevated, expansive, or irritable mood, and abnormally and persistently increased goal-directed activity or energy By definition, a manic episode is not caused by drugs/medication or a medical illness, therefore those with a non-psychiatric underlying cause are mania-like episodes. Note as well that the conditions listed are not an exhaustive list Legend: Pathophysiology Mechanism Manic episodes precipitated by Dopamine D2 receptor overactivity and 4, serotonergic regulation (hypothesis) Additional environmental precipitating factors including lack of sleep, social stress, or change Mania or Mania-like Episode Sign/Symptom/Lab Finding Complications Authors: Emily Ower Reviewers: Alexa Scarcello Usama Malik Dr. Lauren Zanussi* * MD at time of publication

Left Heart Failure: Pathophysiology (Neurohormonal Activation)

Left Heart Failure: Pathophysiology (Neurohormonal Activation) Frank Starling Mechanism • The Frank Starling mechanism of the heart represents the relationship between preload (EDV) and SV • As preload (EDV) increases, SV increases, because higher volumes of blood in the ventricles stretch the cardiac fibers and increases cardiac contraction during systole. However, volume overload causes reduced SV. Myocardial Dysfunction: • Left ventricular Compensatory 4, SV 4A, CO 4 Mechanisms 4, BP Important equations: • BP = CO x SVR • CO = SV x HR Cardiac hemodynamics: • Stroke volume is affected by three factors 1) Preload (end-diastolic volume (EDV)) 2) Afterload (resistance to LV ejection) 3) Contractility (inherent strength of contraction of LV myocytes) Definition of heart failure: • Myocardial dysfunction (systolic or diastolic) results in decreased CO, such that the heart cannot meet the body's metabolic demands or can only do so at elevated filling pressures Anti-diuretic hormone (ADH) activation: Arginine 4, BP 4 carotid sinus Vasopressin --• and aortic arch (V2) receptor baroceptors activation activation 4 I` ADH release RAAS System: 4, BP 4 t release of renin from the juxtaglomerular kidney cells due to renal hypoperfusion SNS System: In response to CO, 4 SNS t release of (catecholamines) norepinephrine and epinephrine Adrenal Glands: Aldosterone release Angiotensin II Type 1 receptor activation al receptor activation 13, receptor activation —• Renal Collecting Ducts: t H2O retention Renal Distal —• Tubules: t Na+ & H2O retention Heart: Activation of fibroblasts 4 collagen synthesis and hypertrophy Blood Vessels: Peripheral vasoconstriction 4 SVR Heart: Chronic p, receptor activation 4 Ca2+ overload myocyte apoptosis Heart: Increase HR to maintain normal CO Maladaptive Response: t preload (EDV), —• volume overload Abbreviations: • SV — Stroke volume • CO — Cardiac output • SVR — Systemic vascular resistance • BP — Blood pressure • RAAS — Renin-Angiotensin-Aldosterone System • SNS — Sympathetic nervous system tin systemic and pulmonary congestion via the Frank-Starling Mechanism Maladaptive 1` resistance Response: t BP, —• against LV afterload ejection 4 4, SV Maladaptive Response: Adverse LV remodelling Maladaptive Response: t myocardial oxygen demand and 4, diastolic time 4, contractility —• of the heart 4, coronary blood flow 4 myocardial ischemia Physical signs and symptoms of congestive heart failure (see relevant slide) Authors: Sunny Fong Reviewers: —• I Jack Fu Usama Malik Dr. Jason Waechter* *MD at time of publication

Primary Spontaneous Pneumothorax: Pathogenesis and clinical findings

Primary Spontaneous Pneumothorax: Pathogenesis and clinical findings Thoracic Tall, thin endometriosis males Genetic Factors (i.e. FLCN mutations, HCY, MFS, CTD) Malnutrition Smoking Structurally compromised lung parenchyma Notes: • PSPs usually occur at rest • Respiratory symptoms vary in severity • Suspect thoracic endometriosis in young women with recurrent PSPs that coincide with menstruation • *Pathophysiology of tension pneumothorax is described in a separate slide Air leaks into the subcutaneous tissue Subcutaneous emphysema Authors: Lauren Hampton Reviewers: Kening (Midas) Kang Natalie Morgunov Sadie Kutz Usama Malik Leila Barss* * MD at time of publication Thoracic Ischemia endometriosis Mechanical forces of respiration create blebs Inflammation disrupts mesotheial and/or bullae ~ cell layer of the visceral pleura 47 Spontaneous rupture of blebs or bullae 47 Sudden onset pleuritic chest pain 71r Primary spontaneous pneumothorax: Presence or introduction of air in the pleural space in a patient WITHOUT diagnosed or clinically apparent lung disease Tachycardia Abbreviations: Communication occurs between the alveoli and pleural space • FLCN- Folliculin gene • HCY- Homocystinuria • MFS- Marfan syndrome Alveolar pressure > pleural pressure • CTD- Connective tissue disease • PSP- Primary spontaneous Air from the lungs enters the pleural space pneumothorax • V/Q- ventilation/perfusion Air separates the chest from /1` intrapleural pressure • Sp02- oxygen saturation the lung parenchyma Small areas of lung collapse Blood flow to areas of On affected side: under un-opposed intrinsic atelectasis is maintained -• Si, chest wall expansion elastic recoil while ventilation 4, t resonance to percussion Si, or absent tactile fremitus Si, or absent breath sounds 4, lung compliance Shunting and V/Q mismatch Pleural line on chest x-ray 1` work of breathing Tension pneumothorax* Accessory muscle use, 4• Sp02, Sudden onset dyspnea, Tachycardia Hypotension, Juglar venous Tachypnea distension, Pulsus paradoxus

Anksiozne motnje: patogeneza tesnobe

Anksiozne motnje: patogeneza tesnobe ienski spol (morda v povezavi s hormonskimi dejavniki, manj notranjega „lokusa

Depresivna epizoda/motnja: patogeneza in klinične najdbe

Depresivna epizoda/motnja: patogeneza in kliniene najdbe Legenda: genetika 10 do 15-% tveganje z obolelim sorodnikom v prvem kolenu, 50-% tveganje z obolelim enojagninn bratom monoaminska hipoteza zni2ani konc. NA in 5-HT v mo2ganih, doka-zani z obdukcijskimi studijami, mehanizmom delovanja antidepresivov in PET slikanjem • Freudova teorija jeza in agresija zaradi medosebne izgube usmerjeni navznoter Beckov kognitivni model triada negativnih misli o sebi, svojem svetu in svoji prihodnosti; ponavljajai se vzorci depresivnega razmigljanja; okrnjena obdelava podatkov v mo2ganih psiholaki in • avtorica: JoAnna Fay pregledali: Sara Meunier, Jojo Jiang, Alexander Arnold, Philip Stokes* * dr. med. ob objavi prevedel in priredil: Jan Kejiar, dr. med., specializant psihiatrije pregledala: doc. dr. Brigita Novak Sarotar, dr. med., spec. psih. revkina in dru2bena izklju6enost neugodni 2ivljenjski dogodki (npr. zloraba, izguba, bolezen, laitev) pomanjkanje tesnih, zaupnih odnosov druibeni dejavniki Prevalenca 10-15 % pri 2enskah in 5-12 % pri mogkih. Razmerje med 2enskami in mc&imi 2:1. Pogosteja pri razvezanih, laenih in samskih ter tistih z nizkim druThenoekonomskim stanjem. depresivna epizoda/motnja simptomi (po DSM 5 merilih) prisotni tekom istega dvotedenskega obdobja in pomenijo odklon od premorbidne ravni funkcioniranja drugi simptomi pomanjkanje libida tesnoba razpolo2enje '6ez dan niha (ang. diurnal variation) huje pozimi (sezonska depresivna motnja) halucinacije (psihotiCna depresija) blodnje (psihotiena depresija) anhedonija (izguba zanimanj/u2itkov) depresivno razpolo2enje nejeknost ali povaan apetit s pridrdienimi spremembami telesne te2e (4, ali 1`) anergija (utrujenost) nespanost ali preva spanja okrajgave: 5-HT - serotonin NA - noradrenalin nastop v mesecu po porodu (poporodna depresija) obC'utki niC'vrednosti ali pretirane krivde psihomotorit'na upaasnjenost ali agitiranost upad spoznavnih sposobnosti (zlasti motnje pozornosti) ponavljajae se misli na smrt/samomor

Obsesivno-kompulzivna motnja: patogeneza in klinične najdbe

obsesivno-kompulzivna motnja -111, Obsesivno-kompulzivna motnja: patogeneza in kliniene najdbe psihologka hipoteza kognitivno-vedenjski model: iz nefunkcionalnih preprr6anj o okoligdnah all drailjajih izhajajae '6ustvene motnje; izogibajae/kompulzivno vedenje vzdr2uje neustrezna preprr6anja in tesnobo biolake hipoteze serotonin: preobaitljivost postsinaptithih serotoninskih receptorjev 4 moten nadzor nad anksioznostjo strukturni model: morda je krivo okrnjeno funkcioniranje moig. poti v orbitalnih, frontalnih in/all subkortikalnih predelih genetika —27 do 47-% dednost pri gtudijah na dvojacih obsesije neielene/vsiljive misli, ideje, podobe all impulzi, ki vdirajo v bolnikovo zavest potreba po ohranjanju reda in simetrije tabuizirane misli o spolnosti/nasilju/ bogokietnosti obEutek krivde in odgovornosti za Iastno gkodo ali Kkodo drugih neielene ideje o bacilih in umazaniji Legenda: bolnik jih skuga potladti/ublaiiti avtorica: Jenna Thomas pregledali: Sara Meunier, Van Yu, Margaret Oakander* * dr. med. ob objavi prevedel in priredil: Jan KejZar, dr. med., specializant psihiatrije pregledala: doc. dr. Brigita Novak Sarotar, dr. med., spec. psih. kompulzije nuje, ki bolnika silijo v izvajanje odtnih vedenjskih all psihibih ritualov z namenom zmanjganja obsesivne anksioznosti all distresa v povezavi s pretedmi posledicami prepri6anja so navadno nekongruentna (neskladna) z bolnikovim vrednostnim sistemom (

Panična motnja: patogeneza in klinične najdbe

PaniEna motnja: patogeneza in kliniene najdbe druibeni dejavniki - vzgoja in navezanost na dojeaka - otrcae bolezni/zloraba - dolgotrajen stres ali travma - zloraba psihoaktivnih snovi biologki dejavniki - moten nadzor nad osjo hipotalamus-hipofiza-skorja nadledvibic - nepravilnosti v iiv6nem prenosu GABA-e psiholoKki dejavniki - trdna prepriEanja/strah pred fizitho ali psihitho skodo s strani telesnih obEutkov - nevrotska osebnostna struktura genetika: —30 do 40-% dednost paniEna motnja panithi napadi se najpogosteje zgodijo neodvisno od zunanjih spralcev telesni simptomi tahikardija, hiperventilacija, 6ezmerno potenje, drgetanje, slabost, kratka sapa, bole6ine v prsih, palpitacije hiperventilacija 4 dihalna alkaloza omotica, otopelost, kratka sapa 4, konc. GABA-e v limbibem sistemu inhibicije amigdale fiziologko: aktivacija simpatibega 2ivbega sistema 4 Pomni: zdraystvena stanja ali psihostimulansi, ki povzraajo simptome, podobne tistim pri panibih napadih, lahko slednje povzraijo ali opon8ajo (npr. astma, KOPB, sCano-iilne bolezni, hipoglikemija, kitnibe bolezni). izogibajoEe vedenje izogibanje okolikinam, ki poustvarjajo telesne ob6utke, podobne panithemu napadu (telesna vadba, u2ivanje kofeina ali alkohola, obisk savne) Legenda: patofiziologija mehanizem kognitivno: bolnik si telesne obEutke razlaga kot katastrofibe 4 povet'anje vzburjenja avtorica: Jenna Thomas pregledali: Saara Meunier, Yan Yu, Margaret Oakander* * dr. med. ob objavi prevedel in priredil: Jan Kejiar, dr. med., specializant psihiatrije pregledala: doc. dr. Brigita Novak Sarotar, dr. med., spec. psih. -1110 psiholoKki simptomi nenadzorovan strah pred simptomi/izgubo nadzora/smrtjo obt'utek izgubljanja stika z realnostjo vzdrievalno vedenje varovalno vedenje npr. posedovanje pomirjeval, iskanje najbli2je bolnignice (z namenom oUutka varnosti v primeru panibega napada) znak/simptom/laboratorijska najdba pogosto pridruiene druge dugevne bolezni: • anksiozne motnje (npr. generalizirana anksiozna motnja, posttravmatska stresna motnja, obsesivno-kompulzivna motnja) • ponavljajoea se depresivna motnja • bipolama motnja razpoloienja prilakovanje vnoviZnega napada vsiljive misli in skrbi o tern, kdaj/kje se bo zgodil naslednji panibi napad in kakgne bodo posledice (srannota, nev'nosti)

Sezonska depresivna motnja: patogeneza in klinične najdbe

Sezonska depresivna motnja: patogeneza in kliniene najdbe Legenda: okoljski dejavniki v zimskih mesecih je izpostavljenost soncu zaradi vremena in krajih dni manik hipoteza faznega premika: dnevno-nobi ritem neusklajen s ciklom svetlega in temnega dela dneva genetika pogosteje pri 2enskah in v primeru dukvnih bolezni v dru2inski anamnezi melatoninska hipoteza: zmanjgana izpostavljenost soncu povzrod pove'6ano izlaanje melatonina pridruiene bolezni depresivna epizoda/motnja (v 100 %), sindrom kasne zaspanosti, odvisnost od alkohola nevrologki dejavniki nenormalen serotoninergibi prenos serotoninska hipoteza: zni2ana konc. serotonina v zimskih mesecih sezonska depresivna motnja avtorica: Luxey Sirisegaram pregledala: Paul Adamiak, Phillip Stokes* * dr. med. ob objavi prevedel in priredil: Jan Kejiar, dr. med., specializant psihiatrije pregledala: doc. dr. Brigita Novak Sarotar, dr. med., spec. psih. I simptomi (po DSM 5 merilih) 2 depresivni epizodi v zadnjih 2 letih z nakazanim casovnim vzorcem pojavljanja hipersomnija hiperfagija sla po u2ivanju ogljikovih hidratov porast telesne te2e patofiziologija mehanizem sezonske posebnosti sezonski vzorec pojavljanja pri depresivni epizodi/motnji popolne remisije all obrati faze v dolaenem delu leta ni povezave s specifithim sezonskim psihosocialnim stresorjem (npr. pove6anim obsegom dela v slu2bi) znak/simptom/laboratorijska najdba simptomi, po katerih se loEi od depresivne epizode/motnje sezonski vzorec pojavljanja (torej v specifibem delu leta) sezonske depresivne epizode morajo po 'gtevilu presegati ne-sezonske depresivne epizode

Shizofrenija: patogeneza in klinične najdbe

Shizofrenija: patogeneza in kliniene najdbe genetika (50-% tveganje pri enojagnih druge biolo§ke dvoi6kih, 6 do 13-% pa v primeru dopaminska hipoteza teorije (zaenkrat obolelega sorodnika v prvem kolenu) (prevladujaa teorija) predmet raziskav) visoka stopnja izraianja Zustev • (ang. expressed emotion): iivljenje v okolju s pogostimi negativnimi komentarji na raC'un bolnika (I` tveganje za relaps) shizofrenija nepravilnosti v 2ivthem prenosu nevrotransmitorjev (predvsem dopamina) v razlithih predelih mo2ganov dopaminergibega dopaminergiC'nega prenosa v mezolimbibi poti dopaminergibi nevroni te6ejo do Iimbicnih struktur in so odgovorni za nadzor nad razpolo2enjem in 6ustvi moten prenos dopamina v tej poti naj bi bil kriv za pozitivne simptome shizofrenije prenosa v mezolimbiC'ni poti avtorica: Yan Yu pregledali: Sara Meunier, Briana Cassetta, JoAnna Fay, Philip Stokes* * dr. med. ob objavi prevedel in priredil: Jan Kejiar, dr. med., specializant psihiatrije pregledala: doc. dr. Brigita Novak Sarotar, dr. med., spec. psih. Pomni: • Ceravno smo vzroke za shizofrenijo sprva iskali v biologkih dejavnikih, zdaj vse bolj prepozna-vamo vlogo tako psihologkih (npr. kognitivnih stereotipov) kot druibenih dejavnikov (npr. stresa ali osame) v njeni etiologiji. • pri shizofreniji lahko odkrijemo tudi nevropsihologke primanjkljaje: motnje spomina, psihomotorike in pozornosti ter te2ave s psihi6no prilagodljivostjo. • Genetske modifikacije C4 gena naj bi ravno tako igrale va2no vlogo v etiologiji bolezni, saj v 6asu adolescence povzro6ajo pove6ano zmanjgevanje gtevila sinaps (nova hipoteza). dopaminergibi nevroni te6ejo do razlibih predelov mo2g. skorje (npr. moten prenos dopamina v tej frontalnega re2nja) in so odgovorni poti naj bi bil kriv za negativne za migljenje, odlaanje, tvorbo simptome shizofrenije jezika in razpolo2enje negativni simptomi (okrnjeno izraianje 6ustev, 6ustvena otopelost, osiroma§en govor, brezvoljnost, ‘iY miselna zavrtost, nedruiabno vedenje) blodnje (nespremenljiva, zmotna prepriEanja, odstopajoEa od bolnikovega kulturnega ozadja) Legenda: patofiziologija mehanizem ha lucinacije (zaznave brez dra2ljajev; obiC'ajno pri shizofreniji a kustiC'n e) dezorganiziran/nesmisein govor (tangencialni odgovori, ohlapne asociacije, besedna solata) znak/simptom/laboratorijska najdba hudo dezorganizirano vedenje, vkljauja katatonijo (neodzivnost na zunanje dra2ljaje)

Serotoninski sindrom: patogeneza in klinične najdbe

Serotoninski sindrom: patogeneza in kliniene najdbe serotoninergiEne snovi SSRI, SNRI, MAOI, TCA, atipieni antidepresivi, antibiotiki, stabilizatorji razpololenja (valproat, litij), opioidi, antiemetiki, triptani, zdravila za izgubo tel. te2e, ilegalne psihoaktivne snovi (npr. kokain, amfetamini) terapevtska raba 1 interakcije (se posebej pri kombinacijah serotoninergikov) namerna samozastrupitev serotoninski sindrom raznolika kombinacija sprememb v psihiZnem stanju, vegetativne nestabilnosti in iivZnomigiZne hiperaktivnosti, ki sega od blage do iivljenje ogroiajoL'e z nenadnim nastopom (v nekaj minutah do urah) po administraciji zdravil(a), v vecini primerov pa se razregi v <24 urah po prekinitvi jemanja odgovorne snovi prekomerna serotoninergitha aktivnost 5-HT receptorjev centralno (v moiganskem deblu) in periferno sinteza in privzem in T receptorski agonizem sprogEanje 5-HT presnova 5-HT in ok'utljivost z zdravili povzraene spremembe v relativnem razmerju ne-serotoninergithih nevrotransmitorjev (npr. pove6anje konc. noradrenalina) spremenjeno psihreno stanje tesnoba, zmedenost, agitacija, hipervigilnost, dolgoveznost, delirij, koma vegetativna nestabilnost mrzlica/drgetanje, 6ezmerno potenje, vraina, driska, tahikardija, ra8irjene zenice, hipertenzija avtorica: Preeti Kar pregledali: Erika Russell, Usama Malik, Aaron Mackie* * dr. med. ob objavi prevedel in priredil: Jan Kejiar, dr. med., specializant psihiatrije pregledala: doc. dr. Brigita Novak Sarotar, dr. med., spec. psih. Pomni: za klinicno postavitev diagnoze uporabljamo Hunterjeva merila serotoninske toksiZnosti: - zgodovina jemanja serotoninergithih snovi v preteklih 5 tednih + kateri koli od naslednjih pogojev: • spontani klonus • inducirani klonus in bodisi agitacija bodisi L'ezmerno potenje • aesni klonus in bodisi agitacija bodisi L'ezmerno potenje • tremor in hiperrefleksija • hipertonija, tel. temperatura >38 °C in bodisi aesni klonus bodisi inducirani klonus ihgnomigiZna hiperaktivnost hiperrefleksija, mR

Zaviralci privzema serotonina in noradrenalina (SNRI): mehanizem delovanja in neželeni učinki

Zaviralci privzema serotonina in noradrenalina (SNRI): mehanizem delovanja in neieleni utinki zaviralci privzema serotonina in noradrenalina predstavnika: venlafaksin, duloksetin konc. 5-HT in NA v 02S/P2S farmakologija farmakokinetika farmakodinamika nenadna prekinitev jemanja zdravila ali vnos avtorici: JoAnna Fay, Sara Meunier pregledali: Jojo Jiang, Alexander Arnold, Jessica Asgarpour, Aaron Mackie* iz krvnega obtoka jih odstranijo jetra zavirajo prenagalec za privzem NA (NET) in prenaalec za privzem 5-HT (SERT) 5-HT in NA ostaneta v sinapsah dlje in podaVata oz. okrepita iiv6ni prenos odtegnitev namerno predoziranje nenamerno povzrocene interakcije nepri6akovan odziv na terapevtski odmerek prekometna v aktivnost 02S/P2S sindrom 1` 5-HT omotica 5-HT serotoninski omotica driska nejegZnost nespeEnost nespanost slabost utrujenost glavobol vegetativna * iivEnomiKiEne kognitivne hiperaktivnost nepravilnosti spremembe vrtoglavica potencialno iivljenje ogroiajoE spolne hipertenzija olesni klonus agitacija motn'e porast tahikardija tremor akatizra tel. tee raigir-ene hiperrefleksija zenice migiEni klonus Legenda: patofiziologija mehanizem znak/simptom/laboratorijska najdba 1` NA slabost Zezmerno potenie * dr. med. ob objavi prevedel in priredil: Jan Kejiar, dr. med., specializant psihiatrije pregledala: doc. dr. Brigita Novak Sarotar, dr. med., spec. psih. v primeru ietrnih bolezni in/ali saasne rabe zaviralcev/sproncev CYPD26 ie potrebna prilagoditev odmerka izboljganje depresivne in anksiozne simptomatike 1 blokada ponovnega privzema 5-HT in NA v sinapsah pa u6inka SNRI ne pojasni v celoti posredno SNRI povzro6ijo sproManja nevrozaMitnih proteinov, denimo BDNF, ki bi naj imel po podatkih §tudij protivnetno delovanje za dosego kliniEnega uZinka ie potrebnih 3-8 tednov all veZ zdravlienia okralgave in opombe: 5-HT— serotonin NA— noradrenalin BDNF — mo2ganski nevrotrofiEni faktor 025 — osrednji 2ivEni sistem P2S — periferni 2ivEni sistem *vegetativen — nanagajoE se na avtonomni 2ivEni sistem

Socialna anksiozna motnja: patogeneza in klinične najdbe

Socialna anksiozna motnja: patogeneza in kliniene najdbe nevrobiologki dejavniki 1

Selektivni zaviralci privzema serotonina (SSRI): mehanizem delovanja in neželeni učinki

Selektivni zaviralci privzema serotonina (SSRI): mehanizem delovanja in neieleni utinki selektivni zaviralci privzema serotonina predstavniki: citalopram, escitalopram, fluoksetin, paroksetin, sertralin farmakologija Pomni: dolo6eni SSRI z ve6jo verjetnostjo povzro6ajo nekatere od na'gtetih neielenih ainkov. Zmanigamo jih lahko z zamenjavo z drugim SSRI, postopnim titriranjem odmerka ali razdelitvijo dnevnega odmer-ka. Antidepresivi lahko zvgajo tveganje za samomor pri mlajsih od 24 let, pri starelgih od 31 let pa ga lahko znilajo. farmakokinetika farmakodinamika iz krvnega obtoka jih odstranijo jetra zavirajo privzem 5-HT in povzraijo sinaptibe konc. 5-HT avtorici: JoAnna Fay, Sara Meunier pregledali: Jojo Jiang, Alexander Arnold, Aaron Mackie* * dr. med. ob objavi prevedel in priredil: Jan Kejiar, dr. med., specializant psihiatrije pregledala: doc. dr. Brigita Novak Sarotar, dr. med., spec. psih. v primeru jetrnih bolezni je potrebna prilagoditev odmerka lahko zavrejo jetrne encime citokroma P4502D6 in povzraijo interakcije med zdravili tel. teie omotica 4 5-HT ostane v sinapsah dlje in podaVa oz. okrepi 2iv6ni prenos izboVanje depresivne in anksiozne simptomatike spolne motnje vrtoglavica nejeknost namerno predoziranje nenadna prekinitev jemanja zdravila ali I, vnos blokada ponovnega privzema 5-HT v sinapsah pa u6inka SSRI ne pojasni v celoti prekometna aktivnost 5-HT v 02S/P2S nenamerno povzro'6ene interakcije konc. 5-HT v O2S/P2S posredno SSRI povzraijo sprokanja nevrozakitnih proteinov, denimo BDNF, ki bi naj imel po podatkih gtudij protivnetno delovanje nepriakovan odziv na terapevtski odmerek serotoninski sindrom odtegnitveni sindrom potencialno iivljenje ogroiajoE 1 vegetativna * iivEnomiKiEne nepravilnosti kognitivne spremembe omotica tremor za dosego kliniEnega uEinka je potrebnih hiperaktivnost slabost none more 3-8 tednov ali veE zdravljenja okrajgave in opombe: 5-HT— serotonin BDNF — nnoiganski nevrotrofi6ni faktor 025 — osrednji 2ivcni sistem P2S — periferni iivcni sistem *vegetativen— nanagajo6 se na avtonomni iivcni sistem hipertenzija olesni klonus agitacija Eezmerno

Nevroanatomija in fiziologija čustev

Nevroanatomija in fiziologija tustev bazalni gangliji prefrontalna skorja obdeluje 6ustva vgje-ga reda, ki zahtevajo priklic, razum(sko) presojo in sposobnost odloCanja (npr. sramota) senzorne informacije iz notranjih organov kot odziv na spralne okoljske objekte ali dogodke integrira z informacijami iz amigdale Zustveni obEutki (npr. zavestne izkugnje Zustev) 1— talamus Zustveno izstopaja okoljski drailjaj zaznave (npr. vid, sluh, tip, oku'ganje, vonjanje) avtorica: Andrea Moir pregledali: Erika Russell, Usama Malik, Brienne McLane* * dr. med. ob objavi hipotalamus (glavna izhodna [ang. output] struktura limbibega sistema) voh* prim. in asociacijski predeli mo2g. skorje • amigdala obdeluje 6ustva niijega reda, torej tista s hitrimi, samodejnimi in pogojevanimi odzivi (npr. strah) sodeluje pri tvorbi in priklicu C'ustveno pomembnih spominov iz neokortikalnih podrodj, torej zaznavi pripi§e neko Custveno vrednost hipokampus (kljaen za utrditev in priklic spominov) motorl6ni, endokrini in visceralni sistemi prevedel in priredil: Jan Kejiar, dr. med., specializant psihiatrije pregledala: doc. dr. Brigita Novak Sarotar, dr. med., spec. psih. avtonomni zivcni sistem (A2S) A2S se samodejno in podzavestno odziva na okoljske dra2ljaje (npr. s '(` frekvence sr6nega utripa ali zardevanjem) telesni odziv na Zustveni drailja( Pomni: • Strukture, ki sodelujejo pri C'ustvovanju, se imenujejo limbiEni sistem. • Talamus, bazalni gangliji in prefrontalna skoraj skupaj tvorijo kortiko-striato-talamo-kortikalno zanko, ki predstavlja glavno pot za obdelavo C'ustev v moiganih. • Prefrontalna skorja vkljue'uje orbitofrontalno skorjo, dorzolateralno prefrontalno skorjo in sprednjo cingulatno skorjo. • *Voh je edini cut, cigar vlakna zaobidejo talamus in se stekajo neposredno v primarno olfaktorno skorjo.

Diabetic Foot: Pathogenesis and clinical findings

Classification of Pelvic Ring Fractures: Mechanisms, Clinical Features and Complications

Classification of Pelvic Ring Fractures: Mechanisms, Clinical Features and Complications Limb-length discrepancy >2.5cm. SI of Types of Pelvic Fractures (Young-Burgess Classification) Ring • Instability with External rotation of rotational force on each leg(s) iliac crest' • vectors LC Scrotal, labial or 15 or S1 dermatomal perinea! hematoma parasthesia2 Flank hematoma Vertical Shear (VS) Axial shear force (i.e. fall)3 Loss of rectal tone or Perinea! lacerations Anterior Posterior Compression (APC) Lateral Compression (LC) perirectal sensation De-gloving injuries Direct/indirect AP force causing diastasis of pubic symphysis (i.e. MVC, cyclist)3 *Combination APC Grade Lateral compressive force, causing inward rotation of pelvis (i.e. MCV rollover, pedestrian vs auto)3 Grade 1 Rami ipsilateral LC Grade • Gross hematuria VS Vertical displacement, anterior & posterior through SI joint APC Grade 1 LC Grade 3 Type 1 or 2 injury on the side of trauma + APC on the opposite side of trauma Pubic symphysis diastasis < 2.5cm APC Grade 2 of two can 3 of above occur Sacral on the unilateral 2 Pubic symphysis diastasis Anterior SI diastasis, posterior ligaments intact. Disruption sacrospinous and sacrotuberous ligaments compression fracture side of trauma with or bilateral rami fractures fracture and posterior ilium fracture dislocation APC 2 + disruption of posterior SI ligaments and possible vascular injury Abbreviations: SI = Sacroiliac Notes: *1- Low sensitivity *2- Most Common *3- Common Mechanisms Authors: Meaghan Mackenzie Reviewers: Annalise Abbott Usama Malik Dr. Prism Schneider* * MD at time of publication Complications Chronic Instability Urogenital Injuries (posterior urethral tear, bladder rupture) NW. Venous thromboembolism Neurologic Injury (L5 and S1)

Open Fractures: Mechanisms, Clinical Features and Complications

Open Fractures: Mechanisms, Clinical Features and Complications Inability to weight bear Limb length discrepancy • Loss of sensation distally Deformity Gustilo-Anderson Classification Type I Wound < 1cm Typically 10 cm 4, Extensive contamination Extensive comminution Type IIIA Adequate soft tissue for bone coverage Legend: Pathophysiology Mechanism Complications Open wound Contusion/Blisters Compartment syndrome Bone tenting or protruding through a wound Loss of distal pulses Amputation Type IIIC Vascular injuries, possible amputation • Type IIIB ++ soft tissue damage with periosteal stripping Sign/Symptom/Lab Finding Non- union Deep Vein Thrombosis Delayed union Infection Authors: Meaghan MacKenzie Reviewers: Annalise Abbott Usama Malik Dr. Prism Schneider* * MD at time of publication " title="Open Fractures: Mechanisms, Clinical Features and Complications Inability to weight bear Limb length discrepancy • Loss of sensation distally Deformity Gustilo-Anderson Classification Type I Wound < 1cm Typically "inside out" injury Yir Minimal comminution Type II Wound 1-10 cm 4, Possible tissue contamination Moderate comminution Note: • Open fractures can occur with low risk mechanism, typically with diseased bone Legend: *Motor cycle/car crashes, pedestrian vs. car, gun shot Direct, high energy force* Open Fractures Fractures with varying degrees of comminution Type Ill Yir Wound >10 cm 4, Extensive contamination Extensive comminution Type IIIA Adequate soft tissue for bone coverage Legend: Pathophysiology Mechanism Complications Open wound Contusion/Blisters Compartment syndrome Bone tenting or protruding through a wound Loss of distal pulses Amputation Type IIIC Vascular injuries, possible amputation • Type IIIB ++ soft tissue damage with periosteal stripping Sign/Symptom/Lab Finding Non- union Deep Vein Thrombosis Delayed union Infection Authors: Meaghan MacKenzie Reviewers: Annalise Abbott Usama Malik Dr. Prism Schneider* * MD at time of publication " />

Bronchogenic Carcinoma - Pancoast Tumors Pathogenesis and clinical findings

Bronchogenic Carcinoma - Pancoast Tumors Pathogenesis and clinical findings Abbreviations: • NSCLC- Non Small Cell Lung Cancer • SCLC — Small Cell Lung Cancer • RLN — Recurrent Laryngeal Nerve • SVC — Superior Vena Cava • RA — Right Atrium • STM — Superior Tarsal Muscle Chest pain Pleural rubs Shoulder pain SCLC (less common) Endothoracic fascia 1— Parietal pleura • 1— Upper ribs Large Cell Carcinoma Adenocarcinoma Squamous Cell Carcinoma Primary Bronchogenic Carcinoma Pancoast tumor: Local/metastatic growth in ipsilateral lung apex Disruption of structures adjacent to superior pulmonary sulcus NSCLC (more common) Invasion of airways ► causing obstruction (later stages) Author: Bradley Stebner Daniel Meyers Midas (Kening) Kang Reviewers: Natalie Morgunov Sadie Kutz Usama Malik Kerri Johannson* *MD at time of publication Notes: • Pancoast Tumor: Malignant lesion occupying the superior pulmonary sulcus (lung apex) Bronchogenic carcinoma: primary malignant neoplasm arising from epithelium of bronchus or bronchiole Pancoast tumors can be caused by primary or metastatic pulmonary neoplasms (described here) as well as infectious foci Hemoptysis Compression of C8 and T1 nerves • Disruption of paravertebral sympathetic chain Shoulder • Weakness in intrinsic Horner's • 4, sympathetic to to iris muscle Syndrome 4, sympathetic radial to eccrine sweat gland Pain (ulnar hand muscles nerve) 4, sympathetic innervation STM Paresthesia in 4th /5th digits and arm/forearm medial Ptosis Mi o sis Anhidrosis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Compression of SVC SVC Syndrome • 4, venous return to RA 4, Cardiac output to lungs Dyspnea Disruption of RLN 1 Hoarse voice 4, venous drainage from upper thoracic cavity Retention of fluid in upper limb •)r Facial and limb swelling

Polycystic Ovarian Syndrome

Nitrous Oxide

GABAAreceptor activation Activation of GABAAreceptor benzodiazepine binding site causes ↑ chloride influx Possible activation of Ca M - N O S- cG M P-PKG pathway (exact mechanism unknown) Anxiolysis Myeloneuropathy Encephalopathy Subacute Combined Degeneration of spinal cord Peripheral Neuropathy Hyperhomocysteinemia Megaloblastic Anemia Irreversible inhibition of methionine synthase Modulation of nociception Stimulation of neurons in PAG of midbrain causes release of E O Ps and/or DY N s Activation of opioid receptors in GABA-ergicnuclei of pons causes inhibition of inhibitory GABA-ergicpathway Activation of descending noradrenergic system in spinal cord posterior grey column Inhibition of primary afferent and second-order neuron nociception Analgesia Authors: Parthiv Amin Reviewers: Billy Sun Joseph Tropiano Michael Chong* * MD at time of publication Abbreviations •CaM-calmodulin •cGMP-cyclic guanosine monophosphate •DYN-dynorphin •EOP-endogenous opioid peptide •GABA-γ-aminobutyric acid •N2O-nitrous oxide •NDMA-N-methyl-D-aspartate •NOS-nitric oxide synthase •PAG-periaqueductal grey area •PKG-protein kinase Nitrous Oxide NDMA receptor antagonism: Inhibition of the N D M A glutamate receptor Closure of NDMA receptor channel Inhibition of ionic currents ↓ central nervous system excitability Anesthesia Quick Facts 1°Use: Anesthesia Adjuvant 2°Use: Analgesia, Dental Sedation, Anxiolytic Route of Admin.: Inhalation Metabolism: None Excretion: 1°=Lung (exhalation) Min. Alveolar Conc.: >100% @1atm = Incomplete Anesthetic Vitamin B12 Inactivation: N2O irreversibly oxidizes Vitamin B12 (cobalamin) Pyramidal Cell Vacuole Reaction: Swelling of endoplasmic reticulum and mitochondria Reversible pyramidal cell neurotoxic vacuole reaction in posterior cingulate / retrosplenial cortex Neurotoxicity Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January,07, 2018 on www.thecalgaryguide.com

Hyperthyroidism

Primary Hyperthyroidism: Pathogenesis and clinical findings Abbreviation: TH — Thyroid hormones RAAS— Renin-angiotensin-aldosterone system TSH — Thyroid stimulating hormone '`Stimulating TSH receptor antibodies Graves Disease Toxic adenoma and/or multinodular goiter 1123 De Novo 4— synthesis of TH uptake Persistent 4, TSH Proptosis T3/T4 Lid retraction Conjunctivitis t osmotic pressure behind eyes Pretibial myxedema Tachycardia Palpitations Bruit over thyroid 4, exercise tolerance t cardiac output Legend: Pathophysiology Mechanism t local synthesis of glycosaminoglycan hyaluronic acid in dermis and subcutis TH production independent of TSH Acute thyroidits Damage to thyroid follicular cells Y Primary Hyperthyroidism 4 RAAS activation • erythropoietin synthesis Sign/Symptom/Lab Finding Release of stored TH t sympathetic stimulation T sweating thermogenesis Viral infection Authors: David Deng Reviewers: Amyna Fidai Hamna Tariq Joseph Tropiano Karin Winston* * MD at time of publication 4, 1123 uptake Transient 4, TSH T3/T4 Gut hypermotlity --* CNS overstimulation Diarrhea, t bowel movement t weight loss Heat intolerance t appetite Nervousness Hyperkinesia Hyperreflexia Tremor Poor attention Note: Although rare, gestational diseases can lead to thyrotoxicosis due to excess secretion of hCG, which is structurally similar to TSH. Secondary hyperthyroidism due to excess TSH production by the pituitary can also occur. Complications I Published MONTH, DAY, YEAR on www.thecalgaryguide.com 0 GS' I 4;

Hyperthyroidism

Growth Hormone Excess

4 GH Excess: Pathogenesis and Clinical Findings 4, joint spaces Macroadenoma (>1cm) Somatotroph adenoma in anterior pituitary Microduplications in chromosome Xq26.3 4— Plain film CT/M RI GH secretion 1\ frequency and amplitude ► GH excess Imaging 4— Acromegaly/Gigantism Stimulation/ repression of other hormones Authors: David Deng Reviewers: Amyna Fidai Hamna Tariq Joseph Tropiano Karin Winston * MD at time of publication intracranial Pressure Headache 4— 4, visual confrontation 4, visual acuity Bitemporal hemianopsia Abbreviations: • GH: Growth hormone • GHRH: Growth hormone releasing hormone • FSH: Follicle stimulating hormone • LH: Luteinizing hormone • TSH: Thyroid stimulating hormone Legend: 4-- Local IGF-1 overproduction Median nerve edema Connective tissue Carpal tunnel overgrowth syndrome Acne 4 Coarse features Hyperhydriosis Pathophysiology Mechanism Hypertrichiosis Macrognathia 1— Enlarged hands and feet Sign/Symptom/Lab Finding Excess insulin secretion \I, insulin receptor numbers and affinity Acanthosis Nigricans Impaired glucose tolerance Cardiovascular disease Weight gain Cardiac arrhythmia Valvular damage ejection fraction ► HTN Notes: • Acromegaly and gigantism share the same pathophysiology but differ mainly in terms of time of onset of GH excess. GH excess prior to growth plate fusion 4 gigantism. GH excess after growth plate fusion 4 acromegaly. • Other rare causes of acromegaly include GHRH hypothalamic tumors and ectopic secretion of GHRH by neuroendocrine tumors. Complications Published January 28, 2018 on www.thecalgaryguide.com

Asthma Acute Exacerbation: Pathogenesis and Treatment

Asthma Acute Exacerbation: Pathogenesis and Treatment Viral URI Allergen Pollution Other Triggers Activation of immune system: Epithelial chemokine activation, lymphocyte activation, macrophage activation, t leukotriene production Inflammation of lower airway • Dyspnea Air flows past inflamed airways causes t irritation Cough and wheezing Release of inflammatory mediators Mucosal edema causing turbulent air flow 7Ir Wheezing Notes • Asthma: Airway hyper-responsiveness causing airflow obstructions • Acute Exacerbation (Asthma): An episode of increased symptoms due to decreases in airflow Abbreviations • PCO2: Partial pressure of CO, in arterial blood • PEF: Peak expiratory flow • SABA: Short-acting beta-2 agonists • Sp02 : Blood oxygen saturation level Mild to moderate exacerbation: PEF 50% of predicted Titrate O2 toSpO2, 92%, give SABA & steroids ■ Good response: symptoms resolved, PEF > 80% [Treat at home with SABA as needed and steroids Dyspnea Bronchoconstriction 1` Residual volume and 1` PCO2 Respiratory failure 1` Air trapping causes '1' intra-alveolar pressure Severe exacerbation: PEF 50% of predicted Educate patient regarding medications, Loss of Pulsus inhaler technique & [consciousness paradoxus follow up with primary care provider I Legend: Pathophysiology Mechanism Titrate O2 to402 93%, give SABA, steroids & magnesium sulfate Sign/Symptom/Lab Finding {Worsening symptoms and/or respiratory failure: Do not delay intubation, send to ICU, give SABA, steroids & magnesium sulfate Authors: Luke Gagnon Reviewers: Midas (Kening) Kang Usama Malik Lian Szabo* * MD at time of publication 4, Delivery of oxygen rich air to alveoli 4, Oxygenation of blood Drowsy and confused Central cyanosis • Tachycardia Pneumothorax [Depending on 1 severity: Observation or place chest tube

Bronchiectasis Pathogenesis and clinical findings

Bronchiectasis: Pathogenesis and clinical findings Acquired immunodeficiency Lymphoma, HIV, transplant Autoimmune Lupus, inflammatory bowel disease, rheumatoid arthritis Congenital/Genetic Cystic fibrosis, A1AT deficiency, Marfan, immunoglobulin deficiency, Kartagener syndrome, Young syndrome Endobronchial obstruction Neoplasm, foreign body, lymph node compression Other Inhalation exposure (smoke, ammonia), MAC complex infection, COPD, allergic bronchopulmonary aspergillosis, chronic infections Irreversibly dilated bronchi Chronic bronchial infection and inflammation 1 Easily collapsible airways I Bronchiectasis (persistent and progressive damage to lungs) Chronic cough (mucopurulent) Defect in immunity and/or mucus clearance Persistent bacteria in airway (commonly Pseudomonas/Staph aureus) Inflammatory response Rhinosinusitis Abbreviations: • A1AT — Alpha-1-antitrypsin • COPD — Chronic Obstructive Pulmonary Disease • HIV — Human Immunodeficiency Virus • MAC — Membrane Attack Complex • VQ— Ventilation/Perfusion ratio Legend: Pathophysiology Mechanism Fever Sign/Symptom/Lab Finding Failure to thrive (children) Authors: Rebecca (Becky) Phillips Reviewers: Midas (Kening) Kang Usama Malik Eric Leung* * MD at time of publication Notes: • Can be focal (single lobe/segment) or diffuse (both lungs) • Mainly in elderly • 1% prevalence in children Tissue damage Epithelial destruction of airways Further impairment of bacterial clearance Persistent inspiratory adventitious sounds (crackles > wheezing) Complications Structural damage to bronchial walls Obstructive pulmonary function tests Hemoptysis Chest pain VQ mismatch and 4, gas exchange 4, oxygenation Digital clubbing (rare) Fatigue Dyspnea Cyanosis (uncommon)

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) Pathogenesis

Chronic Thromboembolic Pulmonary Hypertension (CTEPH): Pathogenesis Acute Pulmonary Thromboembolic Event Mechanical breakdown, Fibrinolysis —5%: Incomplete thrombus resolution after 2 years (Etiology unknown) * Clot resolution (>90%) Hypothesis 1: Increased hypercoagulability Hypothesis 2: Impaired clot lysis Hypothesis 3: Impaired angiogenesis Hypothesis 4: Inflammatory thrombosis • Associated with 1` levels of • Fibrin more resistant to • Impaired VEG-F function (unknown if cause or effect) plasma Factor VIII plasmin-mediated lysis • Ventriculoatrial shunts • Infected pacemaker wires • Splenectomy • Inflammatory bowel disease Unresolved thromboemboli incorporates into blood vessel wall by fibrosis leading to fibrothrombotic organization Authors: Dinusha T. Senaratne Reviewers: Midas (Kening) Kang Usama Malik Natalie Morgunov* Lian Szabo* * MD at time of publication Legend: Webs, bands and slow blood flow In-situ thrombosis expanding the fibrotic thrombus and branch occlusion Abbreviations: BP: Blood pressure PE: Pulmonary embolism PH: Pulmonary hypertension RAD: Right atrial dilatation RHF: Right heart failure RVHD: Right Ventricular hypertrophy/dilatation RVP: Right ventricular pressure VEGF: Vascular endothelial growth factor Proliferation of vascular and inflammatory cells proximal to lesion sites Adaptive vascular remodeling BP in patent vessels of the pulmonary vasculature For signs and symptoms refer to PH slide ■ Progressive PH CTEPH (Chronic Thromboembolic pulmonary hypertension): Chronic occlusion of the pulmonary arteries due to intraluminal fibrosis of thromboembolic material from unresolved PE clots Pathophysiology Mechanism Progressive'(` RVP causes RAD and RVH/D Sign/Symptom/Lab Finding Progressive RHF Complications For signs and symptoms refer to RHF slide

Lung cancer clinical findings and paraneoplastic syndromes

Lung cancer: clinical findings and paraneoplastic syndromes Note: most presentations of lung cancer are very subtle with non-specific symptoms and signs (i.e. fever, weight loss, general malaise) Obstruction of proximal airway Inability to clear inhaled pathogens Postobstructive pneumonia Cough, fever, dyspnea Local tumor growth Spread of tumor to pleural surface Chest Pleural discomfort effusion • Obstruction or compression at local site Uncontrolled abnormal cell growth in one or both lungs 4 Lung Cancer Airway invasion Hemoptysis Lambert-Eaton syndrome (Production of auto-antibodies against Calcium channels) Muscle weakness I` effort to Compression at the Compression Superior vena ventilate the laryngeal nerve of brachial cava lungs nerve plexus compression Impaired innervation to the vocal cords Dyspnea Shortness of Arm/shoulder/ Face/arm breath Voice hoarseness neck pain edema Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Authors: Yoyo Chan Reviewers: Midas (Kening) Kang Usama Malik Leila Barss* * MD at time of publication Tumor secretes biologically active substances Paraneoplastic Syndromes 4 Associated symptoms with malignant diseases TGF131 extracellular matrix protein Fingers clubbing PTHrP T calcium release from bones Hypercalcemia Serum calcium >2.6 mmol/L ADH 1 SIADH T water reabsorption 1 Hyponatremia Serum sodium <135mEq/L Abbreviations: • ACTH: Adrenocorticotropic hormone • ADH: Anti-diuretic hormone • PTHrP: Parathyroid hormone-related protein • SIADH: Syndrome of inappropriate antidiuretic hormone production • TGFI31: Transforming growth factor beta 1 1` ACTH cortisol release and production Cushing's syndrome (symptoms and signs caused by prolonged cortisol exposure) Muscle weakness, hyperglycemia, severe hypokalemia

Impetigo Pathogenesis and clinical findings

Impetigo: Pathogenesis and clinical findings Early: Single erythematous macule developing into vesicle or pustule Late: vesicular lesion and pustules with

Pressure Ulcers Pathogenesis and clinical findings

Depth unknown (slough/eschar covers wound bed and obscures depth) Must remove slough/eschar to determine stage -110. Kennedy terminal ulcer (often precedes death) —1111. Pressure Ulcers: Pathogenesis and clinical findings Bed, wheelchair, stretcher, car seat External physical compression Involuntary muscle movement, passive repositioning of torso Shear forces (dermis/epidermis fixed through contact with a surface while deeper tissues are moved; vessels angulate and thrombose, creating undermining of ulcer) Inability to move well, aging skin (loss of elasticity, blood flow, and subcutaneous fat) Friction (person dragged across surface, damaging stratum corneum) Bowel/bladder incontinence, diaphoresis, wound drainage Moisture (skin maceration) 4, in movement (coma, neuro injury, post-surgery, etc.) Limited mobility Unrelieved pressure greater than arterial capillary pressure (>32 mmHg, with more rapid ulcer formation at higher pressures; normal range 12-32 mmHg) Disrupts blood supply and deprives tissues of oxygen and nutrients Pressure Ulcer (local injury to skin and/or underlying tissues, often over bony prominence) Authors: Rebecca (Becky) Phillips Reviewers: Gurleen Chahal Usama Malik Laurie M. Parsons* * MD at time of publication Notes: • More common in ages 65+ • Risk factors: diabetes, peripheral arterial disease, immunodeficiency, steroid therapy, smoking, dementia, poor nutrition, sensory deficit, circulatory disturbance, prolonged immobility • Grading system from National Pressure Ulcer Advisory Panel Pear- or butterfly-shaped sacral ulcer Stage I (non-blanchable erythema of intact skin; heralds impending ulcer) May be warmer, painful, edematous, indurated, or discolored compared to surrounding tissue Legend: Stage II (partial thickness skin loss) Erosion, serum-filled blister, or shallow ulcer with red-pink wound bed Pathophysiology Mechanism Stage III (full thickness skin loss; damage to subcutaneous tissue but not underlying fascia) * Exposed subcutaneous fat. May have slough, undermining, or tunneling (nose bridge, ear, occiput, and malleolar ulcers will appear shallow due to absence of subcutaneous tissue) Sign/Symptom/Lab Finding Stage IV (full thickness tissue loss) Bone, tendon, or muscle exposed. Slough or eschar may be present. Often have undermining or tunneling Complications Bacterial invasion via contiguous spread (commonly S. Aureus and coagulase-negative staphylococci) Osteomyelitis

Benign Prostatic Hyperplasia: Pathogenesis and medications

Benign Prostatic Hyperplasia: Pathogenesis and medications Aging Testosterone Testosterone metabolized into DHT by type II 5- a-reductase in prostate DHT binds to androgen receptor in prostate cell nuclei Hyperplasia of the prostate Prostate encapsulated by fibromuscular tissue, therefore grows inwards Prostatic urethral compression and bladder outlet obstruction Legend: a-1 blockers (e.g. tamsulosin) Note: MoA not fully established PDE-5 inhibitors (e.g. tadalafil) Bladder and prostate smooth-muscle a-1 receptor antagonism —110. Relaxation of bladder outlet and prostate smooth-muscle Authors: Michael Korostensky Reviewers: Alex Tang Usama Malik Dr. Jay Lee* * MD at time of publication Acronyms: 5-ARI = 5-a reductase inhibitors COX = cyclooxygenase DHT = dihydrotestosterone GnRH = gonadotropin-releasing hormone LUTS = lower urinary tract symptoms PDE-5-mediated cGMP degradation in prostate smooth-Improved urinary outflow muscle and associated vascular supply Relaxation of prostate smooth-muscle MoA = mechanism of action NSAID = nonsteroidal anti-inflammatory drugs PDE-5 = phosphodiesterase-5 -NO 5-ARIs (e.g. dutasteride) LHRH receptor antagonists (e.g. cetrorel ix) P3-adrenergic agonists (e.g. mirabegron) anticholinergics (e.g. oxybutynin) NSAIDs 1` Bladder pressures Pathophysiology Mechanism 5-a-reductase activity 1, Conversion of testosterone into DHT 4, Progression of LUTS 1, Testosterone secretion from testicular Leydig cells 1, LH secretion from pituitary GnRH antagonism DHT production Relaxation of detrusor Bladder muscle 1` capacity Improved LUTS Acetylcholine antagonism at muscarinic receptors Relaxation of bladder outlet smooth-muscle 1` volume to first detrusor contraction 4, Prostaglandin release Analgesia and 4, Prostatic ,f, COX activity ► inflammation —110. Bladder smooth-muscle hyperplasia (detrusor thickening) /1` Sensitivity (i.e. overactive detrusor) -1110. 1, Volume to first detrusor contraction LUTS

Erectile Dysfunction: Pathogenesis

Erectile Dysfunction: Pathogenesis Abbreviations: • CBC - Complete Blood Count • cGMP - cyclic Guanosine Mono-Phosphate • CVD - Cardiovascular Disease • HbA1c - Hemoglobin A1c • mm-millimeter • NO - Nitric Oxide Organic Erectile Dysfunction Gradual, all circumstances, older, nocturnal/AM erection absent Mixed Psychogenic and Organic Erectile Dysfunction Vasculogenic Erectile Dysfunction Hypertension, smoking, hyperlipidemia, diabetes, cardiovascular disease, iatrogenic Endothelia cell damage and I` small vessel disease (penile artery diameter 1-2 mm) 1. Assess CVD Disease risk* a. I% Blood pressure b. I% Fasting glucose or HbA1c c. TG's & cholesterol 1. Penile duplex sonography 2. Cavernosometry Legend: Endocrinologic Erectile Dysfunction Hypogonadism, hyperprolactinemia, hyperthyroidism, alcoholism, iatrogenic .J, circulating free testosterone • 1. 4, 7 AM free testosterone* 2. l• Thyroid Stimulating Hormone 3. l• Prolactin 4. l• Follicle Stimulating Hormone 5. l• Luteinizing Hormone 4, release of NO and cGMP levels within corpora cavernosa and smooth muscle relaxation Pathophysiology Mechanism Neurogenic Erectile Dysfunction Neurologic disease, trauma, iatrogenic, diabetes mellitus Central (cerebral or spinal cord); peripheral (afferent/sensory neuropathy) or efferent (autonomic neuropathy) 4, parasympathetic nerve firing 4, NO release Psychogenic Erectile Dysfunction • Sudden onset, sporadic (circumstantial), younger, nocturnal/AM erection present • Anxiety, depression, strained relationship, lack of sexual arousal, psychological disorder Possible mechanisms include an imbalance of central neurotransmitters, over inhibition of spinal erection center by the brain, and sympathetic overactivity 1. Abnormal Nocturnal penile 1. Normal Nocturnal penile tumescence and rigidity* tumescence and rigidity* Erectile Dysfunction -• (persistent or recurrent inability to achieve an erection sufficient to achieve desired sexual performance) Sign/Symptoni/Lab Finding Complications Authors: Braden Milian Reviewers: Alex Tang Usama Malik Jay C. Lee* * MD at time of publication

Mixed Urinary Incontinence Pathogenesis and clinical findings

Mixed Urinary Incontinence: Pathogenesis and clinical findings Abbreviations: • BOO — Bladder Outlet Obstruction • BPH — Benign Prostatic Hyperplasia • CNS — Central Nervous System • IAP — Intra-abdominal pressure • OAB — Over-Active Bladder • PVR — Post Void Residual • SUI —Stress Urinary Incontinence • UTI — Urinary Tract Infection • UUI — Urge Urinary Incontinence Mixed Urinary Incontinence 47 Urinary leakage accompanied by both urgency and t intra-abdominal pressure Urgency Urinary Incontinence (UUI) 4, Urinary leakage preceded by a sudden, strong urge to void Overflow Incontinence vir Overfilling of the bladder from obstruction; BOO (tumour, stone, BPH, urethral or bladder neck stricture) Detrusor Overactivity Ilr OAB (idiopathic), CNS lesion (neurogenic), inflammation/ infection (cystitis, UTI), diabetes mellitus 4. Bladder Wall Compliance Progressive t in intravesicle pressure during bladder filling pushing urine from the bladder Authors: Braden Millan Reviewers: Alex Tang Usama Malik Jay C. Lee* * MD at time of publication Stress Urinary Incontinence (SUI) + Episodic involuntary urinary leakage with sudden l• in intra-abdominal pressure 4. Urethral hypermobility, intrinsic sphincter deficiency, or a poorly coapting urethra 4, 4, Pelvic floor muscle and ligament strength causing 4. tone of vesicoureteral sphincter unit; 4, urethral strength and associated striated and smooth muscle; iatrogenic Legend: Failure to Void Weak Stream (+ dribbling), Intermittent, Straining, '1` PVR if a complication of urinary retention; obstruction visible on cystoscopy Failure to Store Frequency, Urgency, Nocturia, Dysuria if SUI or UUI not caused by obstruction Pathophysiology Mechanism Urodynamic Studies SUI — 4, urethral closure pressure with 11` IAP/Bladder Volume and urinary leakage UUI — involuntary detrusor contraction and/or detrusor sphincter dyssynergia Incontinence, 4, Quality of Life, UTI's

Penyembuhan Luka Akut: Patogenesis dan Temuan Klinis

Penyembuhan Luka Akut: Patogenesis dan Temuan Klinis Tusuk Lecet Remuk Cedera Kulit Akut Iskemia Tekanan berlebih suplai darah dan oksigenasi • Kerusakan Kulit Utuh Gangguan struktur dan fungsi jaringan dermis, epidermis dan subdermal Note: Kernampuan penyembuhan luka bergantung pada: • Asal Trauma • Adanya Infeksi • Adanya Benda Asing • Iskemia Jaringan • Vaskularitas • Tingkat edema atau peningkatan tekanan jaringan Legenda: Infla• masi (pada lapisan kulit terganggu) • 0 — 7 hari Proliferasi (kolagen, matriks ekstrasel & pembuluh darah) 4 - 14 hari Remodeling ► (.j, pemb. darah & kolagen tersusun) Lapisan Epidermis Batas Dermis-Epidermis Lapisan Dermis Vasokonstriksi transien Pembentukan sumbat platelet Jejas endotel dan subendotel mengaktivasijalur koagulasi Sel mast melepaskan histamin merespon iritan Penulis: Amanda Eslinger Penyunting: Heena Singh Yan Yu Laurie Parsons* Penedemah: M Harmen Reza S* * MD (dokter) pada saat publikasi Inflamasi I Proliferasi I Remodeling Perdarahan berkurang atau berhenti karena sumbat hemostatik (hemostasis) Permeabilitas pemb. kecil terhadap neutrofil & makrofag Aktivasi komplemen memicu sel endotel sekitar untuk melepaskan prostaglandins TGF-8*, dibentukselama fase inflamasi, menarikfibroblas ke daerah luka Klot Menyatukan Ujung luka Perdarahan Leukosit proliferasi dan menyapu kotoran dan bakteri 1 Suplai vaskuler dan vasodilatasi di daerah luka Makrofag melepaskan transforming growth factor beta (TGF-8) * -110. 1' Tekanan hidrostatik mendorong cairan dari pembuluh jaringan sekitar Fibroblas& makrofag menstimulasi pertumbuhanjaringan dan angiogenesis yang menggantikan sumbat hemostatik. Akhirnya, reepiteliasisasi terjadi 8 — 365+ hari Patofisiologi Mekanisme Kolagen tipe 1 yang mengalami tautan silang secara luas menggantikan kolagen yang berserakan yang tersusun pada fase proliferasi Tanda/Gejala/Hasil Lab Komplikasi Luka Sembuh kadar —* protein dalam kolagen Eritema Edema Keropeng Penyembuhan Luka Parut (Scar)

Penyembuhan Fraktur: Tahapan dan Faktor Pengganggu

Penyembuhan Fraktur: Tahapan dan Faktor Pengganggu Stabilitas absolut pada lokasi fraktur: ujung tulang bersentuhan langsung, dan tidak ada pergerakan di antara tulang. Cth: fiksasi interna, fiksasi eksterna Penyembuhan tulang primer (direk) (osifikasi intramembran) Penyembuhan tulang tahap inflamasi, kalus halus, and kalus keras Penulis: Spencer Montgomery Penyunting: Yan Yu Dr. Gerhard Kiefer* Penerjemah: M Harmen Reza S* * MD (dokter) pada saat publikasi Legenda: Fraktur Catatan: Penyembuhan fraktur melibatkan campuran antara jalur penyembuhan primer dan sekunder Tahap Inflamasi (0-7Hari) Stabilitas relatif pada lokasi fraktur: (pergerakan pada ujung tulang) - e.g. bidai, paku intramedular, traksi Penyembuhan tulang sekunder (indirek) (osifikasi endokondral) Kerusakan pembuluh darah lokal 4 hematoma 4 4, perfusi/02 ke tulang 4 osteonekrosis pada garis fraktur 4 terbentuk inflamasi lokal Pergerakan pada lokasi fraktur ++ nyeri Tahap Kalus Halus (mgg 1— 3) Tahap Kalus Keras (mgg 3 — bin 3) Remodeling (bin — thn) Patofisiologi Mekanisme • 1Kondrosit menyusun tulang rawan di lokasi hematoma, menjembatani kedua ujung tulang 4 nyeri berkurang 1 Osteoblas mengendapkan Ca3(PO4)2 ke matriks tulang rawan, membentuk kalus,1` stabilitas lokasi fraktur Faktor yang dapat mengganggu penyembuhan fraktur Tembakau Memperlama waktu penyembuhan, mekanisme belum jelas. Tiga hipotesis: 1) Nikotin: 4, aliran darah, dapat bersifat toksik pada osteoblas 2) Karbon Monoksida: 4, 02 ke lokasi fraktur 3) Hidrogen Sianida: menginhibisi metabolisme oksidatif pada tingkat sel Penyalahgunaan alkohol Memperlama waktu penyembuhan, mekanisme tidak diketahui Kortikosteroid & AINS jangka panjang Menghalangi respon inflamasi yang membatu penyembuhan Remodeling tulang oleh pasangan Osteoklas-osteoblas : mengikir kalus agar tulang dapat mencapai bentuk efisien, sepanjang jalur gaya mekanisnya Tanda/Gejala/Penunjang Komplikasi Kuinolon Menyebabkan pembentukan kalus imatur Defisiensi Vitamin C Mengurangi pembentukan kolagen (Vit C adalah kofaktor kunci sintesis kolagen) Diabetes Produksi kalus lemah (studi hewan) Rifampicin & gentamycin topikal Toksik terhadap osteoblas Hipotiroidisme Menginhibisi osifikasi endokondral (studi hewan) Defisiensi Vitamin D Kurangnya absorpsi Ca2+ & Fosfat dari saluran cerna, 4, mineralisasi tulang.

RICE: Mekanisme Aksi

RICE: Mekanisme Aksi Rest: (penghentian beban atau gerakan yang membebani) Ice (diaplikasikan pada lokasi cedera) Compression (pembalutan lokasi cedera) Elevation (tungkai dinaikkan lebih tinggi dari jantung) Mengurangi aliran darah ke jaringan Mekanisme belum dipahami Tekanan mekanis pada lokasi cedera _110, pengiriman PMN dan makrofag ke lokasi luka Mencegah jejas lanjutan terhadap jaringan yang terkena beban mekanis produksi sitokin (bahan-bahan proinflamasi) seperti TNF-a, PDGF, (3- FGF, EGF, dan TG F-(3 Inflamasi Penulis: Matthew Roberts Penyunting: Alexander Arnold Amanda Eslinger Bradley Jacobs* Penerjemah: M Harmen Reza S* * MD (dokter) pada saat publikasi • ► Cairan berlebih terdorong kembali ke kapiler dan limfe Gravitasi pengembalian darah vena menuju sirkulasi sistemik Abbreviations: • PMN- Netrofil Polimorfonuklear • TNF-a- Tissue Necrosis Factor-Alpha • PDGF- Platelet Derived Growth Factor • 13-FGF- Basic Fibroblast Growth Factor • EGF- Epidermal Growth Factor • TGF-13- Transforming Growth Factor Beta Legenda: Patofisiologi Mekanisme 4, Edema (akumulasi cairan di ruang interstisial) *Note: Penyembuhan cedera merupakan keseimbangan antara mengontrol nyeri dan inflamasi yang cukup untuk memulai aktivitas. Tujuan utama RICE adalah untuk menurunkan inflamasi. Aktivitas itu sendiri menimbulkan nyeri dan inflamasi, namun merupakan faktor penting dalam proses rehabilitasi. Tanda/Gejala/Penunjang ► 4, Nyeri 1% Rentang gerak (Range of motion), dan juga fungsi 1 Inisiasi olahraga rehabilitatif spesifik dini untuk memperbaiki rentang gerak, kekuatan dan propriosepsi Tekanan pada lokasi cedera akan menyebabkan robekan mikro pada jaringan lalu menginduksi inflamasi dan perbaikan* Otot, tendon, tulang, atau ligamen yang cedera menjadi lebih kuat Penyembuhan dini

Hemostasis Sekunder: Kaskade Koagulasi

Hemostasis Sekunder: Kaskade Koagulasi Jalur intrinsik: F12 F12a *1* Fll F11a F9* F9a* Faktor kontak: Kolagen HMWK, prekallikrein Jalur Bersama (common): F8a Ca 2+ F5a Protrombin (F2*) Uji Laboratorium Rutin: • PT — Lama terbentuknya sumbatan setelah aktivasi jalur ekstrinsik • INR — PT yang dinormalisasi • PTT — Lama terbentuknya sumbatan setelah aktivasi jalur intrinsik Jalur ekstrinsik: Jejas pada jaringan Kerusakan sel endotel vaskuler akan memaparkan sub-endothelial Tissue Factor (Faktor jaringan) F10* F10a* Ca2+ Ca2+ • Faktor jaringan (Tromboplastin) F7a* Kompleks faktor jaringan — F7a* ► Trombin (F2a*) Fibrinogen (F1) Defisiensi jalur intrinsik Ca2+ ► Fibrin (Fla) Koagulasi Pembentukan sumbatan (clot) Fibrin Defisiensi jalur Defisiensi jalur ekstrinsik bersama Penulis: Christina Schweitzer Penyunting: David Lincoln Yan Yu* Lynn Savoie* Penerjemah: M Harmen Reza S* * MD (dokter) pada saat publikasi Abbreviations: • PT — Prothrombin Time • INR - International Normalized Ratio • PTT — Partial Thromboplastin Time • F — Coagulation Factor (Faktor koagulasi) • a —Activated coagulation factor (Faktor koagulasi teraktivasi) • N— Normal • HMWK — High molecular weight kininogen • * — bergantung Vitamin K (untuk info lebih lanjut, lihat slide Vitamin K Deficiency) Jembatan keledai (tidak diterjemahkan): • PT = Ekstrinsik: Play Tennis outside • PTT = Intrinsik: Play Table Tennis Inside • Faktor intrinsik — TENET: Twelve, Eleven, Nine, Eight, Ten • Faktor jalur bersama — 10/5=2, 2/2=1 (F10, 5, 2, 1) • Faktor bergantung Vitamin K— 1972: F10, 9, 7, 2 Jalur intrinsik, ekstrinsik & bersama normal N PT, l• PTT 1` PT, N PTT t PT, t PTT N PT, N PTT Perdarahan Memanjang

Fisiologi sistem Renin-Angiotensin-Aldosteron (RAAS)

Angiotensinogen \*. Renin • Angiotensin I LACE • Angiotensin II Fisiologi sistem Renin-Angiotensin-Aldosteron (RAAS) Hipoperfusi Ginjal Regangan baroreseptor pada dinding arteriol aferen Hipotensi/ Hipovolemia 9 Pengiriman NaCI ke Makula Densa 9 Tekanan dirasakan oleh Baroreseptor Jantung & Arteri Katekolamin di sirkulasi Aktivitas saraf simpatis pada arteriol aferen Stimulasi reseptorn-adrenergik pada arteriol aferen Keseimbangan Glomerulotubuler (Mekanisme intrinsik ginjal diluar RAAS) *Hanya sebagian dari mekanisme tersebut Angiotensin II 4 konstriksi arteriol eferen 01% Tekanan hidrostatik glomerulus Jumlah cairan yang disaring + Konsentrasi sisa protein darah di glomerulus Darah kental bergerak dari glomerulus menuju kapiler peritubuler it pada kapiler peritubuler 9 Tekanan hidrostatik peritubular Legenda: Patofisiologi Mekanisme Pelepasan Renin oleh sel-sel Jukstaglomerular pada arteriol aferen 4 berujung pada T Angiotensin II Sekresi aldosterone dari korteks adrenal 1 Insersi KNaE pada Sel Prinsipal di DK ■ Aktivitas transporter NHE3 di dalam PCT Reabsorpsi Na ke dalam darah, menarik H2O ke dalam darah melalui osmosis Reabsorpsi H2O langsung ke dalam sirkulasi darah (via aliran gradien tekanan onkotik dan hidrostatik H2O) Tanda/Gejala/Penunjang Komplikasi Author: David Waldner Reviewers: Yan Yu Sean Spence Sophia Chou* Penerjemah: M Harmen Reza S* * MD (dokter) pada saat publikasi Hati secara normal mensintesis angiotensinogen dengan laju basal, melepaskannya ke dalam sirkulasi darah: Vasokonstri ksi arteri sistemik Tekanan darah Daftar singkatan: • ACE: Angiotensin Converting Enzyme (disintesis oleh Ginjal dan Paru) • DK: Duktus Kolektivus • PCT: Tubulus Konturtus Proksimal • NHE3: Sodium Hydrogen Exchanger (Antiport) 3 • KNaE: Kanal Natrium (Sodium) Epitel • n:Tekanan onkotik

Gradien pO2 Alveolus-arteri: Mengapa ada, dan mengapa penting

Gradien pO2Alveolus-arteri: Mengapa ada, dan mengapa penting Singkatan kunci: • p02: tekanan parsial 02, atau 15 mmHg) selalu menjadi tanda patologis (lihat slide terkait) Penulis: Yan Yu Penyunting: Steven Liu Amogh K. Agrawal Juri Janovcik* Penerjemah: M Harmen Reza S* * MD (dokter) pada saat publikasi Catatan: Gradien A-a yang terlalu tinggi menjadi indikasi adanya masalah dengan difusi udara antara alveolus & kapiler pulmoner " title="Gradien pO2Alveolus-arteri: Mengapa ada, dan mengapa penting Singkatan kunci: • p02: tekanan parsial 02, atau "konten 02". • Pa02: tekanan parsial 02 di arteri. Diukur secara langsung via analisa gas darah (AGD) arteri. • PA02: tekanan parsial 02 di Alveolus. (Tidak dapat langsung diukur, harus melalui perhitungan). Secara teori, pada kapiler paru yang bersebelahan dengan alveolus: 02 berdifusi dari alveolus menuju kapiler paru, dan tidak ada 02 yang hilang dari darah sampai darah mencapai arteri sistemik— maka harusnya Pa02 setara dengan PA02. 1 Tetapi dalam realitanya Darah di dalam kapiler paru sejak awal tidak sepenuhnya teroksigenasi Gravitasi menyebabkan lebih banyak darah menuju basis (dasar) paru, sehingga menyebabkan terlalu banyak darah untuk dapat sepenuhnya teroksigenasi oleh alveolus Darah yang kurang teoksigenasi dari basis paru menurunkan keseluruhan p02 darah Catatan: beberapa patologi respiratorik dapat memiliki gradien A-a normal (lihat slide terkait) Legenda: Definisi Penjelasan Darah yang kurang teroksigenasi dari vena sistemik bercampur dengan darah yang teroksigenasi dari paru ("Venous admixture"): Drainase vena dari sirkulasi bronkial bercampur dengan darah yang teroksigenasi pada kapiler paru Beberapa vena pada sirkulasi koroner bermuara menuju atrium kiri, bukan menuju sinus koroner/atrium kanan .111••••■• Maka dari itu, konten 02 darah ketika mencapai arteri sistemik (Pa02) lebih rendah dibandingkan dengan konten 02 pada alveolus (PA02) PA02 - Pa02 = "gradien" p02 antara alveolus dan arteri sistemik Gradien A-a normal: <15 mmHg Tanda/Gejala/Penunjang Gradien A-a tinggi (>15 mmHg) selalu menjadi tanda patologis (lihat slide terkait) Penulis: Yan Yu Penyunting: Steven Liu Amogh K. Agrawal Juri Janovcik* Penerjemah: M Harmen Reza S* * MD (dokter) pada saat publikasi Catatan: Gradien A-a yang terlalu tinggi menjadi indikasi adanya masalah dengan difusi udara antara alveolus & kapiler pulmoner " />

Gradien pO2 Alveolus-arteri: Penjelasan rumus (Penjelasan ringkas)

Gradien pO2Alveolus-arteri: Penjelasan rumus (Penjelasan ringkas) Untuk penjelasan fisiologis mengenai mengapa terdapat gradien A-a, silahkan lihat:

Gradien pO2 Alveolus-arteri: Penjelasan rumus (Penjelasan secara ilmiah)

Gradien pO2Alveolus-arteri: Penjelasan rumus (Penjelasan secara ilmiah) Untuk penjelasan fisiologis mengenai mengapa terdapat gradien A-a, silahkan lihat:

Acetylcholinesterase Inhibitors

1 .1-- ► Hypotension ► Nausea/ Vomiting Authors: Sunny Fong Reviewers: Joseph Tropiano Billy Sun Melinda Davis, MD Quick Facts Primary indication in the OR = Used as a reversal agent against non-depolarizing neuromuscular blockers post-surgery Route of Administration = IV Metabolism & Excretion = hepatic clearance and renal excretion See Anticholinerqics slide for reversal of parasympathetic effects due to acetylcholinesterase inhibitors Abbreviations ACh — Acetylcholine NDNMBs — Non-depolarizing neuromuscular blockers Acetylcholinesterase Inhibitors E.g. Neostigmine, Pyridostigmine, Physostigmine 4, Breakdown of ACh in neuromuscular junctions ACh available to compete with NDNMBs to bind to post-synaptic nicotinic receptors on muscles Reversible enzymatic inhibition of acetylcholinesterase ACh available to compete with NDNMBs to bind to pre-synaptic nicotinic receptors on neurons Normal neuromuscular junction function re-established 1` Positive feedback for continued ACh release Reversal of neuromuscular block 1 Excess dose leads to depolarizing block of the nicotinic receptors Flaccid skeletal muscle paralysis Respiratory paralysis & failure 1 4, Breakdown of ACh in rest of body 1` Stimulation of muscarinic receptors various organ systems Muscarinic (parasympathetic) effects Salivation Peristalsis ► Bradycardia Bronchoconstriction Bronchial Secretions Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications I Published March 3, 2018 on www.thecalgaryguide.com 0€3,0 BY NC SA

Anticholinergics

po Authors: Sunny Fong Reviewers: Joseph Tropiano Billy Sun Melinda Davis (MD) Anticholinergics E.g. Atropine, Glycopyrrolate, Scopolamine Abbreviations ACh — Acetylcholine SA — Sino-atrial Quick Facts Primary indication in the OR = Combined with acetylcholinesterase inhibitors to prevent over-activation of the parasympathetic nervous system Route of Administration = IV Muscarinic (parasympathetic) effects Competitive antagonism at muscarinic receptors in various organ systems 4, Binding sites for ACh at muscarinic receptors Blockage of muscarinic ► receptors in SA node (esp. atropine) ► Smooth muscle relaxation in the bronchial airways 4, Respiratory tract mucosal ► secretions (esp. glycopyrrolate, scopola mine) ► Pupillary dilation Tachycardia Bronchorelaxation Respiratory tract clearing Mydriasis ► 4, Secretion of salivary glands —■ Dry mouth ► 4, Intestinal motility and peristalsis ► 4, Ureter and bladder tone Constipation Urinary retention Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications I Published March 3, 2018 on www.thecalgaryguide.com 0 0 4SI 0 I' it En

non-depolarizing-neuromuscular-blocks-ndnmbs

Authors: Sunny Fong Reviewers: Joseph Tropiano Billy Sun Melinda Davis, MD Non-Depolarizing Neuromuscular Blockers (NDNMBs) Eg. pancuronium, rocuronium, atracurium, vecuronium Abbreviations NDNMBs — Non-Depolarizing Neuromuscular Blockers ACh — Acetylcholine Quick Facts 1° Indication = Skeletal muscle paralysis to facilitate tracheal intubation, and used during indicated surgeries or mechanical ventilation Route of Administration = IV Metabolism & Excretion = Redistribution, hepatic clearance/renal excretion (extent varies greatly by drug). NOT degraded by acetylcholinesterase or pseudocholinesterase See Acetylcholinesterase Inhibitors slide for reversal of NDN M Bs Competitive antagonism at post-synaptic nicotinic receptors on muscles Competitive antagonism at the pre-synaptic nicotinic receptors on neurons Vagolytic effect (esp. pancuronium) Anaphylactic/ anaphylactoid reactions 4, Binding sites for ACh at post-synaptic nicotinic receptors on muscles 4, Binding sites for ACh at pre-synaptic nicotinic receptors on neurons Blockage of vagal muscarinic receptors in sinoatrial nodes IgE antibodies attach to ammonium ion components of NDNMBs Non-immunologic mast cell degranulation (esp. atracurium) 4, Muscle cell depolarization 4, Positive feedback for continued ACh ► release in response to high frequency stimulation Skeletal muscle paralysis Tetanic fade, Train-of-Four fade 4, —• Parasympathetic Tachycardia effects on heart Release of histamine from mast cells and basophils Bronchospasm Hypotension Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications I Published March 3, 2018 on www.thecalgaryguide.com 0€3,0 BY NC SA

Propofol

Authors: Ryden Armstrong Reviewers: Billy Sun Joseph Tropiano Melinda Davis, MD Propofol Abbreviations GABA – Ga mma-a minobutyric acid Quick Facts 1° Indication = Induction and maintenance of general anesthesia, sedation Route of Administration = IV Metabolism & Excretion = Redistribution, hepatic conjugation/ renal clearance Legend: Pathophysiology Mechanism Allosterically increases binding affinity of inhibitory neurotransmitter GABA for GABAA receptor i Prolonged opening of chloride channel 1 Hyperpolarization of nerve membrane Inhibitory effect on CNS I Induction/maintenance of general anesthesia Sign/Symptom/Lab Finding Injection site pain Can pre-treat with intravenous local anesthetic (lidocaine) 4, Cerebral metabolic rate CNS —÷ 4, Cerebral oxygen consumption 4, Intra-cranial pressure 4, Systemic vascular resistance Hypotension ► Cardiovascular --■ —■ (with no change 4, Preload in heart rate) 4, Contractility Respiratory / ♦ Hypercapnia 4, Hypoxic and --■ hypercapnic Hypoxia respiratory drive ♦ Apnea 4, Upper airway reflexes Complications I Published MARCH 3, 2018 on www.thecalgaryguide.com Lac.).T2

Succinylcholine

Authors: Billy Sun Reviewers: Joseph Tropiano Melinda Davis, MD Succinylcholine (Depolarizing Neuromuscular Blocker) Abbreviations ACh — Acetylcholine SA — Sino-atrial Quick Facts 1° Indication = Skeletal muscle paralysis to allow tracheal intubation with the advantage of faster onset (30s-60s) and shorter duration (<10min) than non-depolarizing neuromuscular blocking agents Route of Administration = IV Metabolism & Excretion = redistribution and metabolism by pseudocholinesterase in blood plasma and liver No reversal of succinylcholine available Contraindicated in patients with traumatized, denervated, or immobilized muscles due to risk of cardiac arrest from hyperkalemia. Agonist at nicotinic ACh receptors in muscles Generates action potential Not affected by synaptic acetylcholinesterase (unlike ACh) Continuous end-plate depolarization Inactivation of sodium channels Prevention of repolarization and additional action potentials Skeletal muscle paralysis Succinylcholine mimics ACh in structure ♦ Fasciculation ♦ Myalgia 1` Serum lc (esp. in patients with muscle trauma/denervation/ immobilization) 1 Hyperkalemia Malignant Hyperthermia (See Slide) Agonist at nicotinic receptors in parasympathetic ganglia, sympathetic ganglia, and muscarinic receptors in SA node of heart Parasympathetic effect (low dose succinylcholine) 4, Heart rate 4, Contractility Cardiac arrest 1 Sympathetic effects (high dose succinylcholine) t Heart rate t Contractility Catecholamine release Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications I Published March 3, 2018 on www.thecalgaryguide.com 0€3,0 BY NC SA

Volatile Gases

Authors: Billy Sun Reviewers: Joseph Tropiano Melinda Davis, MD Volatile Gases e.g. desflurane, sevoflurane, isoflurane Abbreviations GABA — Gamma-aminobutyric acid CNS — Central nervous system NDNMB — Non-depolarizing neuromuscular blocking agents Quick Facts 1° Indication = Facilitates induction and maintenance of general anesthesia Route of Administration = Inhalation Metabolism & Excretion = Minimal metabolism, excretion by exhalation Legend: Pathophysiology Mechanism Potentially interacts with GABA activated chloride channels to induce hyperpolarization and CNS depression Potentially inhibits excitatory presynaptic channel activity mediated by neuronal nicotinic, serotonergic, and glutaminergic receptors Loss of Consciousness 4-- Potentially interacts with two-pore domain potassium channels to alter resting membrane potential of neurons Specific mechanism of action unclear Amnesia CNS 4, Cerebral metabolic rate 4, Cerebral oxygen consumption Sign/Symptom/Lab Finding Cardiovascular 4, Systemic vascular resistance Hypotension Tachycardia Prolong QT interval (esp. sevoflurane) Respiratory 4, Hypoxic and hypercapnic respiratory drive 4, Tidal volume 4, Alveolar ventilation Hypercapnia 1 t Respiratory rate Musculoskeletal Neuromuscular blockade and potentiation of NDNMBs Muscle Relaxation Malignant Hyperthermia (See Slide) Complications I Published March 3, 2018 on www.thecalgaryguide.com 0 0 IS 0 riL - H

non-depolarizing-neuromuscular-blocks-ndnmbs

Authors: Sunny Fong Reviewers: Joseph Tropiano Billy Sun Melinda Davis, MD Non-Depolarizing Neuromuscular Blockers (NDNMBs) Eg. pancuronium, rocuronium, atracurium, vecuronium Abbreviations NDNMBs — Non-Depolarizing Neuromuscular Blockers ACh — Acetylcholine Quick Facts 1° Indication = Skeletal muscle paralysis to facilitate tracheal intubation, and used during indicated surgeries or mechanical ventilation Route of Administration = IV Metabolism & Excretion = Redistribution, hepatic clearance/renal excretion (extent varies greatly by drug). NOT degraded by acetylcholinesterase or pseudocholinesterase See Acetylcholinesterase Inhibitors slide for reversal of NDN M Bs Competitive antagonism at post-synaptic nicotinic receptors on muscles Competitive antagonism at the pre-synaptic nicotinic receptors on neurons Vagolytic effect (esp. pancuronium) Anaphylactic/ anaphylactoid reactions 4, Binding sites for ACh at post-synaptic nicotinic receptors on muscles 4, Binding sites for ACh at pre-synaptic nicotinic receptors on neurons Blockage of vagal muscarinic receptors in sinoatrial nodes IgE antibodies attach to ammonium ion components of NDNMBs Non-immunologic mast cell degranulation (esp. atracurium) 4, Muscle cell depolarization 4, Positive feedback for continued ACh ► release in response to high frequency stimulation Skeletal muscle paralysis Tetanic fade, Train-of-Four fade 4, —• Parasympathetic Tachycardia effects on heart Release of histamine from mast cells and basophils Bronchospasm Hypotension Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications I Published March 3, 2018 on www.thecalgaryguide.com 0€3,0 BY NC SA

Succinylcholine

Clavicular Fracture: Pathogenesis and clinical findings

Clavicular Fracture: Pathogenesis and clinical findings Multisystem Repetitive stress Fall onto shoulder Fall on outstretched Direct blow from trauma (e.g. MVC) (e.g. rowing) (87%) hand (6%) an object (7%) • • Acute fracture Stress fracture Proximal third Group III (2.8%) Undisplaced fracture • Shape of clavicle undergoes minimal change Legend: Middle third (mid-shaft) Group I (69%) Clavicular Fracture Displaced medial and lateral segments Sternocleidomastoid muscle pulls the medial segment up •••-•••11 Anterior Shoulder Pain Pathophysiology Mechanism Distal third Group II (29%) Fracture is medial or lateral to the coracoclavicular ligaments Pectoralis muscle and weight of arm pulls the lateral segment down and towards midline Sign/Symptom/Lab Finding Complications Lateral Shoulder Pain Authors: Jack Fu Reviewers: Reza Ojaghi Usama Malik Aaron J. Bois* * MD at time of publication Notes: • There is no correlation between the mechanism of injury and the site of fracture (i.e., which

Pediatric Pneumonia: Pathogenesis and clinical findings

Pediatric pneumonia: Pathogenesis and clinical findings Immunological: immunization status, immune compromise Environmental: second-hand smoke, air pollution Hospitalization: length of stay, recent antibiotics, mechanical ventilation Neonates, immunocompromise, underlying lung disease (ciliary dysfunction, Cystic Fibrosis, bronchiectasis) Exposure to pathogen: inhalation, hematogenous, direct, aspiration Susceptible host and/or virulent pathogen Infection and proliferation of pathogen in lower respiratory tract/parenchyma Pediatric pneumonia: Inflammatory response to proliferation of microbial pathogens at the alveolar level Authors: Nicola Adderley Reviewers: Midas (Kening) Kang Usama Malik Eric Leung* * MD at time of publication Notes: • Additional findings in pediatric pneumonia may include nausea, otitis, headache • Viral pathogens most common in children <2yrs; bacterial pathogens most common in children >2yrs • Interstitial pattern: suspect Mycoplasma pneumoniae, Influenza A + B, Parainfluenza • Lobar pattern: suspect S. pneumonia, H. influenzae, Moraxella, S. aureus Local inflammatory response: neutrophils recruited to site of infection (LOBAR or INTERSTITIAL PATTERN, depending on pathogen) by epithelial cytokine release At-- Irritation of contiguous structures and/or referred pain (mechanism unclear) Acute abdominal pain Accumulation of plasma exudate (from capillary leakage at sites of inflammation), cell-debris, serous fluid, bacteria, fibrin Irritation of airways and failure of ciliary clearance to keep up with fluid buildup Cough Legend: Crack es, 4• breath sounds Pathophysiology Mechanism Fluid buildup in spaces between alveoli (INTERSTITIAL PATTERN) Interstitial opacity on CXR Fluid buildup in alveoli (LOBAR PATTERN) J, efficiency of gas exchange (I` diffusion distance in INTERSTITIAL, J, surface area in LOBAR) Lobar consolidation on CXR Sign/Symptom/Lab Finding Complications Hypoxemia Systemic inflammatory response: Cytokine release (eg. TNF, IL-1) 1` respiratory drive • Tachypnea Disruption of hypothalamic thermoregulation Fever/chills Respiratory accessory muscle use (chest indrawing, paradoxical breathing, muscle retractions)

Radiological findings of child abuse

Non-Accidental Head Trauma

Duchenne Muscular Dystrophy

Acquired Inguinal Hernias: Indirect + Direct

ACQUIRED INGUINAL HERNIAS: Indirect + Direct Developmental Breakdown of collagen Aging, smoking, vitamin deficiency, I` protease activity, malnutrition • Failure of process vaginalis to close; in O's this is shown via internal inguinal ring failure to close Collagen deficiency Long-term Ehlers-Danlos and Marfan syndrome glucocorticoid use Weakening of connective tissues Thinning of skin and soft tissues intraabdominal pressure Pregnancy, chronic cough, constipation, abdominal masses or fluid Authors: Jeffery Lindgren Peter Bishay Reviewers: Brandon Hisey Vadim lablokov Usama Malik Dr. Sylvain Coderre* * MD at time of publication Stretching of musculoaponeurotic structures weakening of the abdominal fibromuscular tissue Quick facts: *If the hernia is not incarcerated or strangulated, then an elective surgical repair is indicated *There is no clinical test to differentiate direct and indirect inguinal hernias • CT 8 x more likely than 'Z? for abdominal hernia • cy 20x more likely to require surgical repair •indirect the most common hernia in CT + INDIRECT ► INGUINAL HERNIA Abdominal contents protrude though the inguinal ring 'I` pain w. straining, heavy lifting More pain at the end of the day Bulge in the groin +/- pain DIRECT INGUINAL HERNIA Abdominal contents protrude through Hasselbach's triangle* *Hasselbach's triangle, also known as the inguinal triangle, is defined by linea semilunaris (medial), inferior epigastric vessels (suprlateral) and the inguinal ligament (inferior boarder) Herniated contents become entrapped Groin erythema Pain on palpation Strangulation Vomiting • l• pain (SURGICAL ► Incarceration EMERGENCY) (SURGICAL Yir Fever EMERGENCY) Necrosis Compromise of vascular supply • Pain, Sepsis, fistula, abscess Bowel perforation formation

Celiac Disease: Pathogenesis and clinical findings

Celiac Disease: Pathogenesis and clinical findings Associated with other autoimmune disorders (i.e. DM1, thyroiditis, RA, SLE, Addison's) Genetic predisposition -■ (Northern European, Down's syndrome, Associated with HLA DQ 2,8) Note: *The anti-TTG antibody is an IgA anti-body, therefore if the patient is IgA-deficient, absence of anti-TTG does not rule out celiac Anti-TTG in serum* Anti-TTG reacts with TTG in skin Deposition of anti-TTG in renal glomeruli Dermatitis herpetiformis Chronic Kidney Disease Small Bowel Biopsy: Crypts of bowel become enlarged (hyperplasia) with architectural change, villous shortening Legend: Pathophysiology Mechanism Exposure to prolamins (proteins found in wheat, rye, oats, barley) TTG alters prolamin Altered protein fits more easily into HLA HLA activates adaptive immunity IgA generated against prolamin-TTG Wheat prolamin (gliandin) interacts with and activates zonulin signalling Gut epithelium becomes more porous Large dietary proteins in epithelium disrupt tight junctions Author: Matthew Harding Yan Yu Peter Bishay Reviewers: Dean Percy Jason Baserman Usama Malik Kerri Novak* * MD at time of publication Inflammation of Intestinal epithelium Inflammation disrupts structure of bowel mucosa Mechanism Unknown Lymphocytes migrate to site of inflammation Extraintestinal Complications: Arthropathy Ataxia (gluten associated) Infertility Mild Hepatitis Villi of intestine atrophy Risk of Microscopic Colitis (50x) Malabsorption Extraintestinal manifestations: Chronic watery Fatigue Failure to thrive, weight loss Anemia (Fe, B12, folate) Peripheral neuropathy (B12, Ca) Ataxia (Ca) Dysrhythmia (Ca, K) Osteoporosis (Vit D, Ca) diarrhea + Intestinal manifestations steatorrhea: Pale, foul-smelling Abdominal bloating Steatorrhea (fat in stool) Diarrhea

Celiac Disease: Complications

Celiac Disease: Complications Autoimmune response to dietary gluten in genetically predisposed individuals 4 Celiac Disease Note: most common presentation with minor symptoms and iron deficiency Modified gluten peptides activates HLA-DQ2 and DQ8 receptors on T cells Activation of B cells to produce anti-tTG2 autoantibodies 1 tanti-tTG2 Release of pro-inflammatory cytokines Villous Atrophy along duodenum and/or jejunum Loss of brush border Loss of enterokinase Defective mucosal barrier enzyme (failure to produce trypsin) Carbohydrate Protein Fat Secretory maldigestion maldigestion malabsorption diarrhea Legend: Fermentation by gut bacteria 1 Gas production Bloating Fat retained in stool Steatorrhea Abdominal pain Pathophysiology Mechanism Sign/Symptom/Lab Finding Growth Retardation Authors: Yoyo Chan Reviewers: Peter Bishay Usama Malik Sylvain Coderre* * MD at time of publication IgA response Autoimmune IgA deposits Lymphocyte response in sub-epidermal skin layer against enamel Dermatitis Herpetiformis (Chronic pruritic blisters) Nutritional deficiency Dental enamel hypoplasia Vitamin D and calcium deficiency Zinc, selenium Folate Iron Osteoporosis deficiency deficiency deficiency Anemia t Risk of miscarriages

Orofacial Clefts cleft lip cleft palate

Cerebral Palsy clinical findings

Developmental Coordination Disorder

Sudden Infant Death Syndrome SIDS Triple Risk Model

Aplastic Anemia: Pathogenesis and Clinical Findings

Feedback Loops Growth Hormone

Kallmann Syndrome and Normosmotic Idiopathic Hypogonadotropism: Pathogenesis and Clinical Findings

Kallmann syndrome (KS) and Normosmic Idiopathic Hypogonadotropic Hypogonadism (nIHH): Pathogenesis and clinical findings Authors: Danielle Lynch Reviewers: Nicola Adderley Josephine Ho* * MD at time of publication Abbreviations: GnRH – gonadotropin- releasing hormone LH – luteinizing hormone FSH - follicle stimulating hormone Notes: • 4 male : 1 female • KS, nIHH, and isolated anosmia exist on a spectrum • KS has X-linked recessive, autosomal dominant, autosomal recessive, oligogenic, and idiopathic forms • KS and nIHH are also associated with gene- specific features such as cleft lip/palate, oculomotor synkinesis, hearing loss, and unilateral renal aplasia • Diagnosis typically occurs around pubertal age, but may be earlier in males if micropenis and cryptorchidism are present at birth Mutations in KAL1, NELF, and PROKR2 Abnormal olfactory bulb development Mutations in FGFR1, FGF8, PROK2, PROKR2, HS6ST1, CHD7, WRD11, and SEMA3A or idiopathic Mutations in GNRH1, KISS1, KISS1R, TAC3, TACR3 Impaired migration of olfactory neurons from olfactory bulb to hypothalamus Impaired migration of GnRH neurons from olfactory bulb to hypothalamus Impaired GnRH neuron activity Kallmann syndrome (idiopathic hypogonadotropic hypogonadism with anosmia) Normosmic idiopathic hypogonadotropic hypogonadism Anosmia Olfactory bulb aplasia Abnormal /absent olfactory bulb on MRI ↓ GnRH ↓LH and ↓FSH Delayed or absent puberty Infertility ↓estrogen In males: ↓testosterone Cryptorchidism Delayed epiphyseal plate closure Micropenis (5-10%) Uninhibited long bone growth ↑ length hands, arms, legs Delayed bone age (hand/wrist x-ray) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 29, 2018 on www.thecalgaryguide.com

Posterior Cruciate Ligament (PCL) Injury Pathogenesis and Clinical Findings

Posterior Cruciate Ligament (PCL) Injury: Pathogenesis and Clinical Findings Sport-related Hyperextension Injury Motor Vehicle Collision (MVC) Fall on flexed knee Dashboard injury PCL Injury +ve Posterior draw test +ve Lachman or +/- Varus & Valgus Stress Test +/- McMurray 1 Multiligamentous injury Notes: • The PCL is an important stabilizer in the knee and is the primary resistor of posterior translation of the tibia on the femur. • Isolated PCL injuries are uncommon and are often asymptomatic and acutely undiagnosed. Legend: Pathophysiology Mechanism Isolated PCL injury +ve Posterior draw test -ye Lachman -ye Varus & Valgus Stress Test -ye McMurray Chronic PCL deficiency and Knee Instability 1 1` Dynamic Stabilization with quadriceps tendon 1 Post-traumatic patellofemoral pain or arthritis Sign/Symptom/Lab Finding Authors: Luc Wittig Reviewers: Reza Ojaghi Usama Malik Dr. R. Buckley* * MD at time of publication Classification of PCL Injuries Partial: Translation < 10 mm on posterior drawer test with the knee in neutral rotation. Some sort of end point is present. Complete isolated PCL: Posterior drawer test is positive with the knee in neutral rotation and is diminished with the knee in internal rotation. Combined PCL: The PCL is injured in conjunction with other structures, such as the ACL, posterolateral corner, and medial side.

Feedback Loop: Adrenocorticotropic Hormone (ACTH)

Feedback Loop: Adrenocorticotropic Hormone (ACTH) Authors: Rhiannon Brett Reviewers: Andrea Kuczynski Bernard Corenblum* * MD at time of publication Posterior Pituitary Gland ADH - - - Hypothalamus CRH + Anterior Pituitary Gland ACTH, MSH, other hormones produced from POMC ACTH + Adrenal Cortex Activate ACTHR Activate cAMP Activate PKA Activate Zona Fasciculata Cortisol Abbreviations: CRH: Corticotropin Releasing Hormone ADH: Anti-diuretic Hormone ACTH: Adrenocorticotropic Hormone MSH: Melanocyte Stimulating Hormone POMC: Pro-Opiomelanocortin ACTHR: ACTH Receptor cAMP: Cyclic Adenosine Monophosphate PKA: Protein Kinase A DHEA(S): Dehydroepiandrosterone (sulfonated form) F: Female M: Male Excess: hirsutism, acne, oily skin, oligo- or amenorrhea, virilization in F Deficiency: symptoms not typically seen due to gonadal production Note: Activate Zona Reticularis Activate Zona Glomerulosa (minor effect) Excess: central obesity, hirsutism, violaceous striae, weakness Deficiency: weight loss, fatigue, weakness, nausea/vomiting, diarrhea DHEA(S) Aldosterone Specific to primary adrenal insufficiency: ↑ pigmentation, hyperkalemia • Virilization is a red flag for an androgen- secreting tumor Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 2, 2018 on www.thecalgaryguide.com

Feedback Loop- Thyroid Stimulating Hormone (TSH)

Feedback Loop: Thyroid Stimulating Hormone (TSH) Authors: Josh Kariath Reviewers: Andrea Kuczynski Bernard Corenblum* * MD at time of publication Stress Excess: heat intolerance, tremor, proximal muscle weakness, palpitations, systolic HTN, brisk reflexes, weight loss, ↑ appetite, ↑ bowel movements Deficiency: cold intolerance, firm gland of any size, fatigue, depression, weight gain, constipation, delayed relaxation of DTRs, diastolic HTN Cortisol - + + Cold Hypothalamus TRH TRH travels down hypophyseal stalk through portal vessels Anterior Pituitary Gland - TSH TSH travels through the blood Thyroid Gland (Follicle) + T3 T4 Converted into T3 in all target tissues ↑ BMR - Abbreviations: TRH: Thyrotropin Releasing Hormone HTN: Hypertension DTRs: Deep Tendon Reflexes TSH: Thyroid Stimulating Hormone I2: iodine CO: Cardiac Output T3: Triiodothyronine T4: Thyroxine CNS: Central Nervous System SNS: Sympathetic Nervous System BMR: Basal Metabolic Rate - Diet I2 Excess: no real disorders Deficiency: goiter ↑ CO, ↑ contractility, ↓ resistance Hormone metabolism, bilirubin metabolism Heart Liver Bone growth Bone ↑ SNS activation, temperature homeostasis CNS Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 2, 2018 on www.thecalgaryguide.com

Anaphylaxis: Signs and Symptoms

Giant Cell Arteritis: Pathogenesis and Clinical Findings

Acute Hemolytic Transfusion Reaction: Signs and Symptoms

Anaphylaxis: Treatments

Glucocorticoid Induced Osteoporosis: Pathogenesis and Clinical Findings

intrauterine-growth-restriction-iugr-pathogenesis

Intrauterine Growth Restriction (IUGR): Pathogenesis Authors: Ricki Hagen Reviewers: Jaimie Bird Sarah McQuillan* * MD at time of publication Abbreviations: • DM: diabetes mellitus • HTN: hypertension • IUGR: intrauterine growth restriction • SGA: small for gestational age • SLE: systemic lupus erythematosus • TORCH: Toxoplasmosis, Others, Rubella, CMV, HSV Maternal Factors Maternal-Fetal Factors Placental malformations (Ex. previa, accreta, infarction, abnormal implantation, ischemia) Gestational HTN/ Preeclampsia Multiple gestation Gestational DM Fetal Factors Structural anomalies (often comorbid with cytogenetic disorders) Congenital infections (Ex. TORCH) Inborn errors of metabolism Chromosomal disorders/ genetic syndromes Multiple unclear intrinsic fetal mechanisms Note: Teratogenic medications (Ex. Warafin, Valproic Acid, Folic Acid Antagonists) High altitude living Smoking, ETOH and/or drug use Malnutrition/ Low pre-gestational weight Multiple unclear extrinsic fetal mechanisms Medical conditions (Ex: chronic HTN, cyanotic heart disease, severe chronic anemia, kidney disease) Autoimmune conditions (Ex. Type 1 DM, SLE) Decreased uteroplacental blood flow Nutrient supply to fetus compromised Reduction of total body mass, bone mineral content, and muscle mass Blood flow redirected away from vital organs to brain, placenta, heart and adrenal glands Reduction of overall fetal size to increase survival IUGR Failure to reach genetically determined growth potential • IUGR is not synonymous with SGA • Constitutional SGA is due to paternal and maternal factors such as height, weight, ethnicity, and parity; it is not associated with increased risk for infant mortality or morbidity Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October, 30, 2018 on www.thecalgaryguide.com

fetal-alcohol-spectrum-disorder-pathogenesis-and-clinical-findings

Fetal Alcohol Spectrum Disorder: Pathogenesis and clinical findings Authors: Preeti Kar Reviewers: Nicola Adderley Chandandeep Bal* Danielle Nelson* * MD at time of publication Genetic Factors Disadvantaged prenatal and/or postnatal environment Maternal factors (age, metabolism, stress, other substance use) Maternal alcohol consumption during pregnancy (greatest risk with binge drinking and daily/chronic intake) Prenatal alcohol exposure to fetus via placenta-umbilical transport Notes: Fetal Alcohol Spectrum Disorder with Sentinel Facial Features (confirmed or unknown PAE) Fetal Alcohol Spectrum Disorder without Sentinel Facial Features • There is no known safe amount of prenatal alcohol exposure (PAE). Although PAE below the threshold of >7 drinks/week or > 2 binge episodes (one binge episode is >4 drinks in one sitting) has not been associated with neurodevelopmental effects, there is insufficient objective evidence to deem this level of alcohol exposure safe. Sentinel Facial Features (confirmed PAE) Alcohol exposure between Alcohol acts directly as a teratogen Vasoconstriction of placental-umbilical unit ̄ blood flow and ̄ oxygen delivery to fetus Notes (continued): • A multidisciplinary team is necessary for an accurate and comprehensive diagnosis and subsequent recommendations. Canadian Guidelines for diagnosis, 4-digit code, the APP Toolkit, University of Washington Lip- Philtrum Guide are different methods of assessing and diagnosing patients. • While not specific to FASD, congenital abnormalities (e.g. heart defects, renal problems, auditory/visual impairments, skeletal defects) and growth deficits (prenatal and/or postnatal height or weight ≤ 10th percentile) are often associated with this disorder. Smooth philtrum Thin upper lip day 15 and 22 of & indirectly via its metabolites pregnancy (most often) Neuronal cell death & disruption of migration & proliferation Altered signaling, neurotransmitter imbalance, & neural connectivity Evidence of impairment in 3+ neurodevelopmental domains Small palpebral fissures (≥2 SDs below the mean for age & sex or < 3rd percentile) Language Memory Attention Motor skills Cognition Affect regulation Academic achievement Executive function (including hyperactivity & impulsivity) Neuroanatomy/ Neurophysiology (e.g. seizure disorder, abnormal brain structure as seen on brain imaging, microcephaly (head circumference ≤ 10th percentile)) Adaptive behavior, social skills, or social communication Failure to reach age-appropriate milestones, challenges at school, aggression, delinquency, mental health challenges, substance use disorders Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 30, 2018 on www.thecalgaryguide.com

Hydrocephalus: Clinical Findings

Hydrocephalus: Clinical Findings in Pediatrics Authors: Andrea Kuczynski Reviewers: Nicola Adderley Naminder Sandhu* * MD at time of publication Edema and ischemia in periventricular brain tissue Abbreviations: CSF: Cerebrospinal fluid ICP: Intracerebral pressure CN: Cranial nerve LOC: Level of consciousness Notes: • Communicating hydrocephalus is less common than obstructive • Normal pressure hydrocephalus is very rare in children • Additional focal neurological signs may be present if the etiology is a space-occupying lesion Pressure distorts unclosed sutures Rapid head growth, bulging fontanelle, splaying of the cranial sutures Blockage of CSF flow and drainage (Obstructive Hydrocephalus) ↓ or insufficient CSF absorption (Communicating Hydrocephalus) Hydrocephalus Enlargement of CSF pathways Neuroimaging: ventriculomegaly CSF accumulation ↑ ICP Compression of blood vessels and altered cellular metabolism Delayed neuronal migration (neonates) Periventricular white matter tract damage (variable) Seizures, developmental anomalies (e.g. learning disability, impaired speech) Compression of brainstem cranial nerve nuclei and/or tracts Distortion of meninges and blood vessels Headache (worse in the morning), nausea/vomiting Midbrain/brainstem dysfunction (as hydrocephalus worsens) Lethargy/↓ LOC, neck stiffness Irritable, feeding difficulty Upward gaze palsy (Setting Sun sign) Papilledema, CN 6 palsy Infant Older Child Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 30, 2018 on www.thecalgaryguide.com

Orbital Cellulitis: Pathogenesis and clinical findings

Orbital Cellulitis: Pathogenesis and clinical findings Authors: Amanda Marchak Reviewers: Jaimie Bird Dr. Rupesh Chawla* * MD at time of publication Staphylococcus aureus, Streptococcus pyogenes Note: Orbital cellulitis is an extremely serious infection. If not caught and treated early, it can lead to death. CT should be performed if suspected. Involves the orbit Panopthalmitisb Endopthalmitisc Blindness Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenza Local infection or break in skin Eye surgery or trauma Direct inoculation Sinusitis (more common) Periorbital cellulitis1,2 Hematogenous spread Contiguous spread of infection Pathogens reach orbital tissue (posterior to the orbital septum) Spreads to periorbital tissue (anterior to the orbital septum) Localized inflammation Conjunctival chemosisa Eyelid and periorbital edema Pain on palpation Induration Warmth Orbital Cellulitis Inflammation of orbital tissue Proptosis Spreads to surrounding structures Subperiosteal abscess Brain abscess Cavernous sinus thrombosis Meningitis Subdural empyema Orbital abscess Notes: Impinges on ocular muscles Impaired extra- ocular movements Pain with eye movement or opthalmoplegia Definitions: Impinges on nerves Afferent pupillary defect Decreased visual acuity Exposes cornea Corneal drying and scarring a. Chemosis: Edema of the bulbar conjunctiva b. Panopthalmitis: inflammation of all coats of the eye including intraocular structures. c. Endopthalmitis: inflammation of the interior of the eye. 1. See slide on Periorbital Cellulitis for how sinusitis can lead to the development of periorbital cellulitis 2. The micro-organism responsible for periorbital cellulitis varies depending on how the pathogen was introduced to the system. Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 5, 2018 on www.thecalgaryguide.com

Periorbital Cellulitis: Pathogenesis and Clinical Findings

Periorbital Cellulitis: Pathogenesis and Clinical Findings Authors: Amanda Marchak Reviewers: Jaimie Bird Dr. Rupesh Chawla* * MD at time of publication Staphylococcus aureus, Streptococcus pyogenes (most common organisms) Note: Also referred to as preseptal cellulitis Dacryoadenitisa Conjunctivitisb Acute chalazionc Dacryocystitisd Hordeolume Streptococcus pneumoniae, Moraxella catarrhalis, non-typable Haemophilus influenza (most common organisms) Abrasion Insect bite Burns Trauma Local infection Contiguous spread of infection Sinusitis Otitis media Hematogenous spread Local break in skin Micro-organisms enter Definitions: Note: Eye exam should reveal normal: - extra-ocular movements and globe position - pupillary reflex and visual acuity If any are abnormal, the presentation is no longer considered periorbital cellulitis, as the infection has likely spread beyond the preseptal compartment/orbital septum. If the eye cannot be assessed, the patient NEEDS a CT scan. Pathogens reach dermis and subcutaneous periorbital tissue Periorbital Cellulitis a. Dacryoadenitis: infection of the lacrimal glands b. Conjunctivitis: inflammation of the conjunctiva c. Chalazion: a benign, painless bump or nodule inside the upper or lower eyelid which results from healed internal hordeolums that are no longer infectious. d. Dacryocystitis: an infection of the lacrimal sac, secondary to obstruction of the nasolacrimal duct at the junction of lacrimal sac. e. Hordeolum: localized infection or inflammation of the eyelid margin involving hair follicles of the eyelashes or meibomian glands. Spreads beyond preseptal compartment/orbital septum Involves the orbit Orbital cellulitis See slide on Orbital Cellulitis: Pathogenesis and clinical findings Localized inflammation Pain on palpation Induration Warmth Eyelid and periorbital edema Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 5, 2018 on www.thecalgaryguide.com

Child Abuse: Risk Factors and Possible Indicators

Child Abuse: Risk Factors and Possible Indicators Authors: Alexa Scarcello Reviewers: Jaimie Bird Dr. Jenn D’Mello* * MD at time of publication Note: Child abuse is most frequently missed when parents are upper or middle class, Caucasian, & married Parental Factors Low education Substance abuse Mental illness Unwanted pregnancy Personal hx of abuse Child Factors Behavioral problems Medical problems Male gender Young (non-verbal), especially <1 year old ↑ Risk Note: Special Indicators for Sexual Abuse Definition: Child Abuse • Any act or omission by a parent or caregiver that results in actual or potential harm to a child • Includes physical, sexual, & emotional abuse, or neglect Family Factors Unrelated caregiver Low SES Single parent Domestic violence Social isolation Indicators on History Indicators on Physical Exam Injury blamed on pet or sibling Delays in seeking treatment Frequent visits to different healthcare providers for injuries Self-inflicted injury not compatible with child’s development Child described as “difficult” Hx of injury changes with time History not compatible with injury Extensive physical injury with hx of minor trauma • • • • • Regressive behaviour Difficulty sleeping Sexually inappropriate behaviour Sudden change in behaviour School difficulties Burns (esp. immersion) Frenulum tear in infants Bruising: Pattern, Location (esp. face), Number, Shape (esp. ligature marks, instrumentation), Age of child (“those who don’t cruise don’t bruise”) Abusive head trauma See “Non-accidental Head Trauma” slide Fractures (esp. posterior rib, shearing/twisting forces) Evidence of injury with no hx of trauma Suspicion of child abuse Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 5, 2018 on www.thecalgaryguide.com

Circle of Willis: Anatomy and Physiology

Circle of Willis: Anatomy and Physiology Authors: Josh Kariath Reviewers: Andrea Kuczynski Gary Klein* * MD at time of publication Supplies midline cortical structures, lower extremity region of homunculus Anterior Cerebral Artery (ACA) *Anterior Communicating Artery (Acomm) Note: • Circle of Willis architecture serves as collateral circulation; i.e. there are alternative pathways for blood to travel in event of narrowing or occlusion of an artery • * signifies common sites of aneurysm. These are junction sites that may become weak over time • Anterior circulation: ICA, ACA, MCA; Posterior circulation: PCA, VA • Findings from occlusion depend on the extent of occlusion and will present with contralateral findings • The cerebellar arteries are not included on this diagram Supplies 2/3 of the lateral portions of frontal, temporal and parietal lobes, specifically UE and facial regions of the homunculus Middle Cerebral Artery (MCA) Supplies midbrain, thalamus, occipital lobe Vertebral Arteries (VA) Supplies brainstem, cerebellum, spinal cord, posterior portion of brain Posterior Cerebral Artery (PCA) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 5, 2018 on www.thecalgaryguide.com Basilar Artery (BA) Supplies cerebellum, brainstem, occipital lobe *Posterior Communicating Artery (Pcomm) Internal Carotid Arteries (ICA)

Mastoiditis: Pathogenesis and clinical findings

Mastoiditis: Pathogenesis and clinical findings Authors: Amanda Marchak Reviewers: Nicola Adderley Jim Rogers Emily Ryznar Danielle Nelson* * MD at time of publication Acute Otitis Media (AOM) Distal middle ear is physically connected to mastoid air spaces Pathogens spread from middle ear to the mastoid air spaces Mucosa lining the mastoid becomes inflamed Mastoiditis 1 Infection persists Accumulation of pus in mastoid cavities ↑ pressure Formation of abscess cavities Dissection of pus into adjacent areas Infection spreads Into intracranial compartment See slide on Acute Otitis Media (AOM): Pathogenesis and Clinical Findings in Children Post- operation Trauma Infection Notes: 1. Most common suppurative complication of AOM Tenderness, erythema, swelling and fluctuance over the mastoid process Inflammation spreads to external auditory canal Cranial Nerve VII anatomically near mastoid Cranial Nerve VIII anatomically near mastoid air space Destroys bony septae b/t air cells (visible on CT) Mastoid abscess Swelling of external auditory canal Mastoid inflammation disrupts nerve Mastoid inflammation disrupts nerve Petrositis Facial nerve palsy Sensorineural hearing loss Labyrinthitis Osteomyelitis of the calvaria Into adjacent bones Underneath the periosteum Subperiosteal abscess Pinna is pushed out and of the temporal bone Into the neck beneath the attachment of the sternocleidomastoid and digastric muscles forward Dural venous thrombosis Temporal lobe abscess Meningitis Epidural abscess Subdural abscess Cerebellar abscess Bezold abscess Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 5, 2018 on www.thecalgaryguide.com

Scarlet Fever: Pathogenesis and clinical findings

Scarlet Fever: Pathogenesis and clinical findings Authors: Amanda Marchak Reviewers: Nicola Adderley Jim Rogers Danielle Nelson* * MD at time of publication Note: GAS pharyngitis can be left untreated, but scarlet fever MUST be treated. Enters systemic circulation Delayed type hypersensitivity response See slide on Type IV Hypersensitivity: Pathogenesis and Clinical Findings Abbreviations: GAS – Group A Streptococci SPE – Streptococcal Pyogenic Exotoxin SSA – Streptococcal Superantigen Group A Streptococci Infection1 5-15 years old2 Adhesins, including lipoteichoic acid and M protein, within GAS cell wall facilitates regional adherence to pharyngeal epithelial cells GAS releases SPE A, B and C, and SSA Stimulation of T-cells and mononuclear cells General inflammatory response White strawberry tongue3 Coating sluffs off after 2-3 days Red strawberry tongue4 Complications: See slide on Group A Streptococci Pharyngitis: Pathogenesis and Clinical Findings Scarlatiniform rash (sandpaper feel) 0-1 days post- pharyngitis Pastia’s lines5 1-2 days post- pharyngitis Appears on upper trunk and axillae 3-4 days post- pharyngitis Spreads to remainder of body, sparring face6, palms and soles 7-10 days post- pharyngitis Fades Desquamation7 Otitis media, sinusitis, pneumonia, bacteremia, osteomyelitis, meningitis, arthritis, erythema nodosum, hepatitis, acute poststreptococcal glomerulonephritis, and acute rheumatic fever Fine maculopapular rash Blanchable with Non-pruritic and pressure painless Notes: 1. While the majority of infections are cases of GAS pharyngitis, rarely, it is possible to develop scarlet fever from a GAS skin infections. 2. Scarlet fever is most common in patients of this age group although, rarely, it can occur in adults. 3. White strawberry tongue is characterized by a white coating on the tongue through which edematous lingual papillae project. 4. Red strawberry tongue is characterized by a beefy red, edematous tongue covered in edematous lingual papillae. 5. Prominent erythema and petechiae in the body folds, especially the antecubital fossae and axillary folds. They tend to appear before the rash and persist through the desquamation phase. 6. Typically, the rash does not occur on the face, although facial flushing may be noted. When this occurs, there is perioral sparring. 7. Desquamation tends to occur ~1 week after the rash fades, most severely effecting the hands and feet, and lasts 2-6 weeks. While a classical presentation, not everyone gets it. Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 5, 2018 on www.thecalgaryguide.com

Sinusitis: Pathogenesis and clinical findings

Sinusitis: Pathogenesis and clinical findings Authors: Amanda Marchak Reviewers: Nicola Adderley Jim Rogers Danielle Nelson* * MD at time of publication Abbreviations URTI – Upper respiratory tract infection Nasal obstruction/ congestion Hyposmia Headache Facial pain/pressure Maxillary tooth pain Ear pain/ fullness Osteomyelitis of frontal bone Chemical irritants Cystic Fibrosis Direct toxic effect on cilia Viral URTI Allergies Inflammation of paranasal sinuses Edematous passageways Septal deviation Adenoid hypertrophy Polyps Turbinate hypertrophy Tumors Foreign body Dysfunctional cilia Congenital and/or craniofacial abnormality Obstruct sinus ostia Cilia unable to clear mucus from sinuses Mucus unable to drain through ostia Post-nasal drip Mucus overflows from the sinuses Cough Mucus accumulates in sinuses Occupies a larger volume Applies ↑ pressure to sinus walls Mucopurulent discharge Bacterial1 overgrowth in sinuses Bacterial infection spreads to adjacent structures Halitosis Pharyngitis Throat clearing Dental root infection Immunodeficiency Note: Irritates the back of the throat Perforation of the Schneiderian membrane2 Passage of bacteria into the sinuses Fever Fatigue Subperiosteal orbital abscess Orbital abscess Orbital edema ↑ susceptibility to bacteria 1. The most common bacteria are Streptococcus pneumoniae, Haemophilus influenza, and Moraxella catarrhalis. Staphylococcus aureus and Group A Streptococcus may be seen, but are less common. However, in cases of dental root infection, oral anaerobes become more common, while Pseudomonas species are associated with foreign bodies. 2. The Schneiderian membrane is the membranous lining of the maxillary cavity. Cavernous sinus thrombosis Meningitis Cerebral abscess Subdural abscess Epidural abscess Periorbital or orbital cellulitis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 5, 2018 on www.thecalgaryguide.com

Tonsillitis: Pathogenesis and clinical findings

Tonsillitis: Pathogenesis and clinical findings Group A Streptococci (GAS) infection1,2 Authors: Amanda Marchak Reviewers: Nicola Adderley Jim Rogers Danielle Nelson* * MD at time of publication Viral pathogen1 5-15 years3 Pathogen colonizes the nasopharynx Pathogen colonizes oropharynx4 ** ↑ vascular permeability Leakage of protein and fluid into surrounding tissue Inflammatory cytokine release Inadvertent cellular injury and hemolysis Tonsillar petechiae and erythema Systemic inflammatory cytokines disrupt hypothalamic regulation Fever White blood cell (WBC) activation WBCs infiltrate site of infection WBCs kill pathogen Accumulation and deposition of cellular debris and products of inflammatory response Tonsillar exudate Note: *When GAS is the pathogen, cytokine release and WBC activation is secondary to the release of exotoxins by GAS. Swelling and irritation ↑ lymph drainage to regional nodes Enlarged anterior cervical nodes Cough Note: It is extremely important to distinguish between viral tonsillitis and bacterial tonsillitis. Viral tonsillitis is usually self-limited while GAS tonsillitis can be associated with a number of complications. Notes: Tonsillar tissue Tonsillar edema Nasal tissue6 Nasal congestion Coryza Nasal discharge irritates back of throat Complications5: Peritonsillar abscess, neck abscess, otitis media, sinusitis, pneumonia, scarlet fever, bacteremia, osteomyelitis, meningitis, arthritis, erythema nodosum, hepatitis, acute poststreptococcal glomerulonephritis, acute rheumatic fever, and toxic shock syndrome 1. In general, viral tonsillitis is more common than GAS infection. However, in the absence of cough and coryza (acute, isolated tonsillitis), GAS is more common. 2. While GAS is the most bacterial cause of tonsillitis, it can be caused by other pathogens. 3. GAS tonsillitis is most common in patients of this age group although, rarely, it can occur in adults. 4. When GAS colonizes the oropharynx, the primary location of infection determines how it’s identified. • tonsils primarily effected = tonsillitis • pharynx (throat) primarily effected = pharyngitis (See slide on Group A Streptococci Pharyngitis: Pathogenesis and Clinical Findings) • both = pharyngotonsillitis 5. The listed complications are the result of exotoxins entering systemic circulation or the bacterial infection extending beyond the tonsils. 6. While viral tonsillitis tends to be associated with more upper respiratory tract symptoms, clinical signs and symptoms are NOT reliable for diagnosing GAS tonsillitis. Throat swab or rapid antigen detection test are the standards for diagnosis. Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 5, 2018 on www.thecalgaryguide.com

Stomach Acid Reducing Medications - Mechanisms of Action

Dependent Personality Disorder Slide - Pathogenesis and clinical findings

Obsessive-Compulsive Personality Disorder Slide - Pathogenesis and clinical findings

Brain Death: Pathogenesis assessment and clinical findings

Benefits of Breast Milk: Mechanism of Action

Major Depressive Disorder: Complications

Note: the complications associated with MDD are due to interlocking biological, psychological, and social factors, in which causality across conditions is challenging to establish. This slide is a simplified framework that assumes MDD as an antecedent condition, without assuming causality. Major Depressive Disorder: Complications Confounding social factors in childhood and adolescence that lead both to early depression and to adulthood adverse outcomes Complications due to symptoms and pathophysiology of MDD Individual factors such as deviant peer Dysregulation of Difficulty concentrating and involvement the other undefined factors can hypothalamic-pituitary-adrenocortical axis lead to cognitive impairment and impaired memory performance Educational High levels of circulating underachievement cortisol that cross to placenta during pregnancy Early parenthood • High placental cortisol correlated with low birth weight Coronary Artery Altered Disease autonomic Complicated tone pregnancy: Impaired recovery from Low birth weight other medical illnesses Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Family environment of parental absenteeism, parental substance abuse, parental educational underachievement, or abusive behaviors Recurrent episodic nature of MDD Development of negative cognitive and behavioural patterns Author: Emily Ower Reviewers: Alexa Scarcello Usama Malik Dr. Lauren Zanussi* * MD at time of publication Recurrent Depressive Episodes Social patterns of school absenteeism, unemployment, and/or continued deviant peer involvement Social isolation and inter-personal challenges Higher incidence of smoking Self-medication through substances Substance abuse or dependence Psychomotor Retardation Complications More passive approach to managing challenges Ruminative and worry thought patterns Anxiety Disorder Low Energy Heightened effort required to recover from illness compared to general population

Avoidant Personality Disorder - Pathogenesis and clinical findings

Measures of Population Health

Employment as a Determinant of Health

Menopause contraindications to hormone replacement therapy

Phenylketonuria (PKU): Pathogenesis and clinical findings

Phenylketonuria (PKU): Pathogenesis and clinical findings Authors: Hamna Tariq Reviewers: Chandan Kaur Bal Nicola Adderley Rebecca Sparkes* * MD at time of publication Abbreviations: PAH – phenylalanine hydroxylase BH4 – tetrahydrobiopterin Phe – phenylalanine Tyr - tyrosine LAT-1 - L-amino acid transporter 1 LNAA – large neutral amino acids NT – neurotransmitter Biallelic mutations in PAH gene on chromosome 12q23.2 Loss of activity/deficiency of PAH Inability to convert Phe to Tyr Buildup of Phe and its metabolites ↑ transport of Phe via LAT-1 at the blood brain barrier Phe outcompetes LNAA for binding sites on LAT-1 ↓ LNAA transport ↓ cerebral protein synthesis and ↓ NT synthesis White matter lesions, oxidative damage, hypomelination & demyelination Sources of Phe Dietary protein Breakdown into amino acids ↓ Tyr and derivatives ↓ melanin Fair skin and hair Notes: Endogenous recycling of amino acid stores Phe oxidized to phenylacetate Musty odor to urine, sweat and breath • Autosomal recessive inborn error of metabolism; clinical severity depends on residual PKU activity • This slide denotes clinical features of classical PKU in untreated patients. Symptoms develop within a few months of birth only if untreated. • PAH, using a BH4 cofactor, converts Phe to tyrosine, which is necessary to produce epinephrine, norepinephrine, dopamine and melanin. (Rare inherited disorders of BH4 synthesis/recycling cause elevated Phe and neurologic symptoms.) • PKU is screened for at birth in most developed nations. • In early-diagnosed, continuously treated patients, ID, microcephaly and neurologic features are not expected, but there is still an increased incidence of behavioral, emotional and social problems ↑ brain [Phe] Behavioral, emotional & social problems (ADHD, mood disorders, aggression, ↓ self-esteem, ↓ social competency, ↓ autonomy) Intellectual disability (↓ language, memory & learning skills, executive function, IQ, school performance) Neurological findings (tremor, shaking, seizures, poor coordination) Microcephaly Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 19, 2018 on www.thecalgaryguide.com

Feedback Loop: Prolactin (PRL)

Feedback Loop: Prolactin (PRL) Authors: Nicola Adderley Reviewers: Andrea Kuczynski Bernard Corenblum* * MD at time of publication Abbreviations: TRH: Thyrotropin Releasing Hormone DA: Dopamine GnRH: Gonadotropin Releasing Hormone FSH: Follicle Stimulating Hormone LH: Luteinizing Hormone Note: • PRL levels exhibit diurnal, menstrual, and age-related variation • TRH has a stimulatory effect on PRL release; however, dopamine is the principal regulator of PRL secretion Alveolar Cells of Breast Ducts Milk production and release Lactation TRH Suckling stimulus (via spinal afferents) + + Hypothalamus + (arcuate nucleus) DA - Anterior Pituitary Gland Lactotrophs Uterus, immune cells, breast tissue, prostate PRL Hypothalamus ↓ GnRH secretion ↓ FSH/LH ↓ estradiol in females, ↓ testosterone in males Limbic System ↓ libido Immune System Organs Promotes proliferation and maturation of immune cells Oxytocin Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 19, 2018 on www.thecalgaryguide.com

Vesicoureteric reflux (VUR): Pathogenesis and clinical findings

Vesicoureteric reflux (VUR): Pathogenesis and clinical findings Authors: Nicola Adderley Reviewers: Emily Ryznar *Lindsay Long * MD at time of publication Abnormal function Abnormal anatomy Neurogenic bladder (e.g. cerebral palsy, constipation, spinal injury, iatrogenic) Non-neurogenic bladder (neuropsychological) Lower urinary tract abnormality (posterior urethral valves, meatal stenosis) Bladder outlet obstruction ↑ pressure distorts UVJ Upper urinary tract abnormality (ureters) UVJ abnormality Incomplete closure of UVJ during bladder contraction Abbreviations • UVJ - ureterovesicular junction • UTI – urinary tract infection Failure of bladder sphincter to relax during bladder contraction Vesicoureteric reflux (VUR): Back flow of urine from the bladder into one or both ureters +/- kidneys Migration of lower urinary tract bacteria to kidneys Bacterial invasion of renal parenchyma Upper UTI (pyelonephritis) Incomplete emptying of bladder during Abnormal ↑ pressure in bladder Bladder dilates Dilated bladder on U/S urination Bacteria in bladder are not cleared during urination voiding habits ↑ bladder capacity Renal scarring ↓ functional renal tissue *Chronic kidney disease (↓ GFR, hypertension, proteinuria) Flank tenderness Fever, dysuria, urgency, frequency Lower UTI (cystitis) Urinary stasis Cloudy, foul- smelling urine Urethral stricture Notes Urgency, dysuria, frequency • First febrile UTI in an infant should trigger a work-up for VUR • High likelihood of spontaneous resolution • *Late complication of severe VUR Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 19, 2018 on www.thecalgaryguide.com

IVH Intraventricular Hemorrhage in Preterm Infants - Pathogenesis

Intraventricular Hemorrhage in Preterm Infants: Pathogenesis Authors: Alexa Scarcello Reviewers: Nicola Adderley Jennifer Unrau* * MD at time of publication Abbreviations: CBF: cerebral blood flow GM: germinal matrix Germinal matrix: highly cellular and richly vascularized layer of the developing brain responsible for neuron and glial development in fetus; involutes by term Prematurity <32wk Birth weight <1500g Mechanical ventilation Pneumothorax Neonatal transport Extensive resuscitation Use of hyperosmolar fluids Risk factors in preterm infants Coagulopathy Hemodynamic instability Respiratory distress syndrome Immature basal lamina Few pericytes Decreased glial fibers Poorly developed structural support of blood vessels Blood vessels within GM are simple, endothelial-lined vessels larger than mature capillaries Impaired autoregulation of cerebral blood flow due to prematurity of brain development Inability to maintain constant cerebral blood flow during changes in systemic pressure (pressure passive system) ↑ susceptibility to ischemia/reperfusion injury GM capillary network is prone to hemorrhage Hemorrhage in germinal matrix capillary bed, which drains into venous system Intraventricular Hemorrhage hemorrhage in periventricular subependymal germinal matrix Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 20, 2018 on www.thecalgaryguide.com

Prader Willi syndrome: pathogenesis and clinical findings

Anticonvulsants as Mood Stabilizers: Mechanism and Side-effect

Anticonvulsants as Mood Stabilizers: Mechanism and Side-effect Anticonvulsants as Mood Stabilizers Examples: Valproate, Carbamazepine, Lamotrigine Pharmacology Mild anticholinergic effect Drowsiness, dry mouth, blurred vision, constipation Allergic reaction Benign rash Pharmacokinetics —■ Cleared from circulation by liver —■ Pharmacodynamics Block voltage sensitive sodium channels Failure to clear reactive metabolites • T-cell mediated cytotoxic reaction to drug antigens Potentially life threatening –Stevens-Johnson Syndrome • NI, Glutamate and aspartate release or I` GABA neurotransmission Authors: Usama Malik Reviewers: Sina Marzoughi Aaron Mackie* * MD at time of publication Dose adjustments needed in setting of liver disease and specific CYP450 inhibitors/inducers Excessive blockage of VSSCs Abrupt discontinuation or 4, intake Inhibition of dopaminergic activity Neurologic effect Systemic effect 1 1 • Withdrawal seizure, relapse of bipolar disorder Notes: • Valproate relies on CYP450 2C9/2C19, Carbamazepine relies on CYP450 34A, and Lamotrigine relies on glucuronidation • Lamotrigine and Carbamazepine are excreted renally • Valproate act on nonspecific VSSCs while lamotrigine and carbamazepine mostly act on alpha unit VSSC • Exact mechanism for some of the side-effects is unknown Legend: Pathophysiology Mechanism Dose-dependent tremor, ataxia, asthenia Sedation, dose-Nausea, vomiting, dependent tremor, diarrhea, dizziness, diplopia, hyponatremia, rash, ataxia, asthenia, pruritus, weight gain, headache alopecia (unusual), thrombocytopenia Abbreviations: • VSSCs: Voltage-Sensitive Sodium Channels

Benzodiazepine (BZD) withdrawal: clinical findings and complications

Benzodiazepine (BZD) withdrawal: clinical findings and complications Abrupt cessation of chronic ingestion of BZDs Administration of BZD antagonist (flumazenil) on patients who have developed -* tolerance/dependence to BZD Withdrawal Seizure Negative physiological reactions BZD intake inhibition a mygd to f, • of a la Withdrawal symptoms Benzodiazepine Withdrawal GABA receptor activity (less inhibition alleviated by ingesting BZD Tolerance GABA BZD intake Conformational changes in the GABA receptor 1, receptor's Withdrawal Insomnia Pro-excitatory 4— state of excitatory neurotransmitters) 4— to the agent activity affinity for the agent A Activation of ACC and OFC Feelings of fear Activation of PAG Behavioural response of fight or flight Legend: Pathophysiology Mechanism Activation of hypothalamus '1` Cortisol CAD, T2DM, Stroke Sign/Symptom/Lab Finding Activation of PBN V t RR, SOB, Asthma, or a sense of being smothered Activation of LC t Sympathetic Activity t BP, t HR variability, tremor, and diaphoresis Authors: Usama Malik Reviewers: Sina Marzoughi Aaron Mackie* * MD at time of publication Notes: • The onset of withdrawal can vary according to the half-life of the BZD involved. Symptoms may be delayed up to three weeks in BZDs with long half-lives, but may appear as early as 24 to 48 hours after cessation of BZDs with short half-lives. Abbreviations: • ACC: Anterior Cingulate Cortex • BP: Blood Pressure • CAD: Coronary Artery Disease • HR: Heart Rate • LC: Locus Coeruleus • MI: Myocardial Infarction • OFC: Orbitofrontal Cortex • PAG: Periaqueductal Gray • PBN: Parabrachial Nucleus • RR: Respiratory Rate • SOB: Shortness of Breath • T2DM: Type 2 Diabetes I` atherosclerosis, cardiac ischemia, MI, or sudden death

Benzodiazepines: Mechanism of Action and Side Effects

Benzodiazepines: Mechanism of Action and Side Effects BZDs are sedative-hypnotic agents. Examples: Lorazepam, Diazepam, Clonazepam, Alprazolam. Pharmacology Pharmacokinetics Absorbed by GI tact and metabolized by liver Pharmacodynamics 1 BZD bind to site on GABA-A receptor Dose adjustment if liver disease or older age Interaction with inhibitors of CYP 3A4 Authors: Usama Malik Amy Fowler Reviewers: Aaron Mackie* * MD at time of publication Accumulation of metabolites vir 4, LOC Note: • GABA is the principal inhibitory neurotransmitter in the brain and plays an important regulatory role in reducing the activity of many neurons Amygdala-centered circuit regulates fear while CSTC regulate worry Lorazepam, Oxazepam, and Tamazepam are not metabolized by the liver, and excreted by the kidney. Muscle relaxant 1 Binding triggers influx of Cl- ions leading to hyperpolarization of membrane • • 4, seizures, hypnotic spinal activity cord firing of neurons 4, cerebral Abbreviations: • BZD: Benzodiazepines • GABA: Gamma aminobutyric acid • CSTC: Cortico-Striato-Thalamo-Cortical NI, cortex activity • Respiratory amygdala-centered CSTC circuit activity Adverse Effects Depression circuit activity Overdose 4, fear, 4, panic Anxiolytic Anterograde Ataxia, slurred Dependence, Rare unless co-and 4, phobia amnesia, speech, tolerance ingestion with other CNS depressant confusion weakness

Schizotypal Personality Disorder (SPD): Pathogenesis and clinical findings

Schizotypal Personality Disorder (SPD): Pathogenesis and clinical findings Genetics Environmental Neurobiological Changes Neurotransmitter /1` prevalence among first-More common among Significant atrophy of the Imbalance degree relatives of people with lower (predominantly left) lateral Dysfunction in synaptic probands with incomes and those never temporal lobe. Certain subregions dopamine degradation, Schizophrenia. Genes associated with married, divorced, separated, or widowed. of the prefrontal cortex have been shown to be enlarged. usually due to gene catechol-0- schizophrenia are also risk factors for Schizotypal PD. Volume 1, of specific temporal lobe subregions. methyltransferase (COMT). Cognitive-perceptual • Magical thinking Belief in paranormal or supernatural phenomena, such as superstitions, telepathy, weird fantasies Unusual Perceptions Seeing a halo or aura, presence of unseen force, or bodily illusions Ideas of Paranoia/ Reference Suspiciousness Believing Can range from coincidences persistent and have strong overt hostility, personal guardedness to significance pleasant and agreeable compliance Schizotypal Personality Disorder Oddness/ disorganized ► Interpersonal Lack Close Friends Deficit in finding social interactions gratifying, a form of social anhedonia Constricted affect Eccentric behavior Unusual thinking or or appearance speech Unconventional or Speech and thought idiosyncratic process can be hygiene, attire, or vague, unelaborate, social behaviors circumstantial, metaphorical, or stereotyped but not grossly incoherent or blocked Social Anxiety Unrelenting, situationally generalized, unconditional, and does not tend to lessen with familiarity Clinically significant impaired functioning Authors: Usama Malik Reviewers: Sina Marzoughi Aaron Mackie* * MD at time of publication Notes: • Cluster A Personality Disorder • 4.2CY : 3.7g - frequently diagnosed in fragile X syndrome • 3.9-4.6%of adults • More than half of these patients have at least one episode of major depression SPD Mnemonic: ME PECULIAR • Magical thinking Experiences unusual perceptions • Paranoid / suspicious ideation • Eccentric behavior or appearance • Constricted or inappropriate affect • Unusual thinking or speech • Lacks close friends • Ideas of reference • Anxiety in social situations • Rule out psychotic or pervasive developmental disorders • Dx: present in a variety of contexts causing marked social impairment

Boutonniere Deformity: Pathogenesis and Complications

Boutonniere Deformity: Pathogenesis and Complications Laceration of extensor surface of PIP Authors: William F Hill Marshall Thibedeau Reviewers: Emily Ryznar Brett Byers* *MD at time of publication Rheumatoid Arthritis Hand trauma Hyperflexion of PIP Dislocation of PIP Central Slip Rupture Unopposed lumbrical and interossei pull on lateral bands Stretching of triangular ligament Volar subluxation of lateral bands Lateral band contraction Hyperextension of DIP Erosion of connective tissue Synovial inflammation Avulsion of central slip insertion Triangular ligament prevent bowstringing of the lateral bands during finger flexion EDC inserts dorsally on to extensor aponeurosis Interossei and lumbricals travel from volar aspect of palm with action dorsal to the axis of rotation Aponeurosis gives rise to central slip and lateral bands Elson test for central slip rupture: • Flexion of PIP 90 degrees over edge of table • Extend affected phalanx against resistance • Positive if DIP becomes extended and rigid • From exaggerated lateral band action Abbreviations: PIP proximal interphalangeal joint EDC: extensor digitorum communis IPJ: interphalangeal joint DIP: distal interphalangeal joint ROM: range of motion Flexion of PIP Boutonniere Deformity Shortening of collateral ligaments and volar plate of PIP joint Premanent contracture and fibrosis of IPJs Permanent deformity ↓ ROM in PIP extension Osteoarthritis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 4, 2018 on www.thecalgaryguide.com

menstrual-cycle-physiology-ovarian-cycle-brief-overview

Menstrual Cycle Physiology: Ovarian Cycle – Brief Overview Authors: Kristin Milloy Reviewers: Emily Ryznar Andrea Kuczynski Bernard Corenblum* * MD at time of publication Follicular Phase Selection of dominant follicle Luteal Phase Ripening of corpus luteum Corpus luteum forms following ovulation LH supports corpus luteum function until natural atrophy or pregnancy occur Progesterone produced Inhibit FSH/LH release from pituitary Atrophy of corpus luteum if embryo does not implant FSH from pituitary stimulates granulosa cells ↑ FSH receptors ↑ sensitivity to FSH Follicle with most FSH receptors selected LH from pituitary ↑ androgens from theca cells Aromatase ↑ estrogen ↑ LH receptors ↑ sensitivity to LH Prepare for ovulation from LH surge LH surge Note: • LHandFSHare required for follicular development and continued growth until ovulation Abbreviations: FSH: follicle stimulating hormone LH: luteal hormone Convert androgens to estrogen Ovulation Release of dominant follicle Day 1 Day 7 Day 14 Day 21 Day 28 Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 21, 2018 on www.thecalgaryguide.com

Complex Regional Pain Syndrome: Pathogenesis and clinical findings

Complex Regional Pain Syndrome: Pathogenesis and clinical findings Authors: Calvin Howard Reviewers: Sina Marzoughi Scott Jarvis* * MD at time of publication Central nervous system lesion Unknown Mechanism ACE inhibitors Trauma with at most minor nerve lesion i.e. surgery, nerve compression, fracture, tissue trauma, ischemia, sprain Neurogenic inflammation Sympathetic dysregulation Acute Phase Proinflammatory cytokine profile Central and peripheral nociceptive sensitization Chronic Phase Central sensorimotor dysregulation ↓ Perfusion of cortex & ↓ cortical grey matter volume of limbic and sensorimotor areas ↑ Perfusion to motor cortex ↓ Grey matter volume in cortical pain regions ↓ Connectivity of sensorimotor planning/control regions Complex Regional Pain Syndrome 1 (Formerly Reflex Sympathetic Dystrophy) Sensory: Hyperalgesia or allodynia Sudomotor: Edema, sweating changes, asymmetric sweating Vasomotor: Temperature asymmetry, altered skin colour Motor/trophic: Decreased range of motion, motor dysfunction, trophic changes Definitions: • Hyperalgesia: Heightened sensation of pain • Allodynia: Pain caused by normally non-painful stimuli • Sudomotor: Relating to the sweat glands • Vasomotor: Relating to the muscle within vasculature • Trophic: Relating to growth and atrophy of cells • Cytokine: Molecules that recruit inflammatory cells Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 20, 2018 on www.thecalgaryguide.com

Microangiopathic Hemolytic Anemia: Pathogenesis and clinical findings

Microangiopathic Hemolytic Anemia: Pathogenesis and clinical findings Authors: Jocelyn Law Reviewers: Naman Siddique Emily Ryznar Lynn Savoie* * MD at time of publication Atypical HUS Mutation or antibody attack of complement proteins HELLP Anti-angiogenic factors in maternal blood Damaged placental vasculature Typical HUS STEC releases Shiga Toxin Malignant Hypertension DIC (See DIC Slide) ↓ Inhibition of complement Immune inflammatory ↑ Pressure in ↑ Extrinsic clotting pathway activation TTP (See TTP-HUS Slide) Disruption of endothelial cell activation perfusion/ischemia response metabolism vasculature ↑Thrombin Deficient Placental under- renal afferent ↑ Complement pathway activation MAC-mediated cell lysis Cytokine release Endothelial injury Shear stress on endothelium production ↑ Fibrin clot production and deposition in small vessels ADAMTS13 protease enzyme ↓ Cleavage and ↑ accumulation of VWF multimers Abbreviations: • HELLP - Hemolysis, Elevated Liver Enzymes, Low Platelets • HUS - Hemolytic-Uremic Syndrome • DIC - Disseminated Intravascular Coagulation • TTP - Thrombotic Thrombocytopenic Purpura • MAC - Membrane Attack Complex • STEC - Shiga Toxin-Producing Escherichia coli • VWF - Von Willebrand Factor Pro-thrombotic Environment (see Virchow’s Triad Slide) Platelet aggregation Mechanical obstruction of the vessel lumen Hypercoagulable state Thrombocytopenia ↑ RBC production in bone marrow ↑ Reticulocytes Hemoglobin released from damaged RBCs Shearing of RBCs Anemia Binds to haptoglobin Conversion to bilirubin in liver ↓ Free haptoglobin ↑Indirect bilirubin Shistocytes Jaundice Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 13, 2018 on www.thecalgaryguide.com

Neurogenic Claudication: Pathogenesis and Clinical Findings

Neurogenic Claudication: Pathogenesis and Clinical Findings Mechanical Authors: Heather Yong Reviewers: Calvin Howard Emily Ryznar *Dr. Bradley Jacobs * MD at time of publication Spinal Impingement of stenosis spinal nerves Spinal stenosis: Abnormal narrowing of the spinal canal. The lumbosacral area is most prone to stenosis. compression Vascular compromise Edema, ischemia Symptomatic spinal nerves Neurogenic Claudication: Note: How to distinguish between neurogenic and vascular claudication Symptoms within the dermatomal distribution (pain, parasthesia) and myotomal distribution (weakness, cramping) of the impaired spinal nerve when walking or standing. Relieved with rest. Symptoms distributed along the dermatome and myotome Neurogenic • Position dependent • Dermatomal distribution • Proximal to distal progression Vascular • Exercise dependent • Sclerotomal distribution • Distal to proximal progression Hip extension Buckling of ligamentum flavum and overlapping of adjacent vertebral laminae and facets ↓ canal size ↑ compression Worsening of symptoms Myotomal: weakness, cramping Dermatomal: pain, paraesthesias Modification of symptoms with movement and position Exercise ↑ vasodilation of spinal arteries ↑ compression Hip flexion Stretching of ligamentum flavum, reduction of overlap of adjectent vertebral laminae and facets, enlarged foramina ↑ canal size ↓ compression Slow relief of symptoms (>30 min) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 7, 2018 on www.thecalgaryguide.com

Atopic Dermatitis: Pathogenesis and Clinical Findings

Rosacea: Pathogenesis and Clinical Findings

Hepatic Encephalopathy: Pathogenesis and Clinical Findings

Hepatic Encephalopathy: Pathogenesis and Clinical Findings Nicholls Chan Doherty Cheng portal systemic bypass congenital bypasses liver surgery blood flow delivery of toxins severe liver damage cirrhosis, acute liver failure decreased hepatocellular function toxin metabolism disordered metabolism and protein synthesis muscle atrophy extra-hepatic ammonia removal electrolyte dysregulation conversion NH4+ NH3

Hypernatremia Physiology

Hypernatremia: Physiology Unreplaced H2O loss Hypodipsia H2O shift into cells Severe exercise, electroshock induced seizures Transient ↑ cell osmolality Na+ overload Inappropriate IV hypertonic solution, salt poisoning Abbreviations: H2O: Water GI: Gastrointestinal DM: Diabetes Mellitus DI: Diabetes Insipidus Na+: Sodium ion IV: Intravenous ADH: Antidiuretic Hormone LOC: Level of Consciousness Skin Sweat, burns GI Vomiting, bleeding, osmotic diarrhea Fluid [Na+] < serum [Na+] ↑ H2O loss compared to Na+ loss Renal DM, Mannitol, Diuretics Absent thirst mechanism Hypothalamic lesion impairs normal drive for H2O intake Nephrogenic ↑ renal resistance to ADH H2O Deprivation Test + no AVP response ↓ access to H2O DI Central ↓ ADH secretion H2O Deprivation Test + AVP response ↑ [Na+] 10- 15 mEq/L within a few minutes Weakness, irritability, seizures, coma ↑ thirst, ↓ urinary frequency and volume Note: Hypernatremia Serum [Na+] > 145 mmol/L Intracranial hemorrhage Headache, vomiting, ↓ LOC • Plasma [Na+] is regulated by water intake/excretion, not by changes in [Na+]. • Effects on plasma [Na+] of IV fluids or loss of bodily fluids is determined by the tonicity of the fluid, not the osmolality. Authors: Mannat Dhillon Reviewers: Andrea Kuczynski Kevin McLaughlin* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 11, 2019 on www.thecalgaryguide.com

Hyponatremia- Physiology

Hyponatremia: Physiology Authors: Mannat Dhillon Reviewers: Andrea Kuczynski Kevin McLaughlin* * MD at time of publication Abnormal Renal H2O Handling (hypo-osmolar serum) AKI/CKD Heart failure ↓ renal blood flow ↓ glomerular filtration GFR < 25 mL/min, ↓ urine dilution ↑ H2O retention Note: • Plasma [Na+] is regulated by water intake/excretion, not by changes in [Na+]. • Artifactual hyponatremia can be differentiated by a normal or hyperosmolar serum. Appropriate ADH secretion ↓ EABV Hypovolemia: losses via GI, renal, skin, 3rd spacing, bleeding Hypervolemia: heart failure, cirrhosis ↑ Na+/H2O absorption at PCT ↓ EABV, ↑ H2O retention Urine [Na+] < 20 mmol/L Hereditary: tubular disorders (Bartter, Gitlemann syndromes). Thiazide diuretics Inappropriate: SIADH, hypothyroidism, AI Normal EABV Anti-diuresis Primary polydipsia, eating disorder ↑ H2O or ↓ solute intake ↓ Osmoles Impaired desalination Block NCC ↑ H2O retention ↑ Na+/K+ excretion Hyponatremia Serum [Na+] < 135 mmol/L Urine osmolality > 100 mmol/L Urine osmolality < 100 mmol/L Cerebral edema, ↑ intracranial pressure, vasoconstriction If hypovolemic: ↓ JVP, ↓ blood pressure Lethargy, altered mental status Abbreviations: AKI: Acute Kidney Injury CKD: Chronic Kidney Disease GFR: Glomerular Filtration Rate H2O: Water PCT: Proximal Convoluted Tubule EABV: Effective Arterial Blood Volume NCC: Na+/Cl- Co-Transporter SIADH: Syndrome of Inappropriate ADH Secretion AI: Adrenal Insufficiency Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 11, 2019 on www.thecalgaryguide.com

Coronary anatomy on ECG- Localizing Ischemia

Coronary arteries Coronary anatomy on ECG- Localizing Ischemia interventricular atrioventricular myocardial infarction sinoatrial st-elevation myocardial infarction two arteries that originate from the root of the aorta behind the cusps (aortic sinus) of the aortic valve left posterior left CA anterior aortic sinus right CA myocardium right coronary artery posterior descending right atrium ventricle SA AV nodes inferior MI leads II III aVF bradycardia heart blocks problems posterior MI V1 V4 leads anterolateral left main circumflex descending septum ventricle apex anteroseptal occlusion dominant T wave flattening inversion transmural reciprocal depression limb leads precordial leads

Patent Ductus Arteriosus (PDA)- Pathogenesis and Clinical Findings

Patent Ductus Arteriosus (PDA)- Pathogenesis and Clinical Findings Sun Bishay Gagnon Adderley Ryznar waechter circulating PGE2 low arterial oxygen content genetic factors char syndrome patent birth aortic pressure pulmonary artery pressure continuous flow from aorta to pulmonary artery via the PDA left to right shunt continuous flow murmur precordial activity S1 S2 accentuated pulse volume load dilation dysfunction left atrium ventricle displaced apex dynamic left ventricular impulse grade pulmonary blood flow systemic blood flow exercise intolerance wide systemic pulse pressure pulmonary artery pressure vascular changes resistance difficulty feeding infants failure to thrive heart failure respiratory distress pulmonary hypertension reversal of shunt adult complications eisenmenger syndrome clubbing cyanosis

Arterial Insufficiency- Signs and symptoms

Arterial Insufficiency- Signs and symptoms Adderley gagnon Waechter atheroma thrombus artery vessel diameter hardening blockage artery embolism left atrium thrombus plaque rupture resistance to flow circulation to tissues distal to occlusion narrowing tissue perfusion positive Allen's test ABI absent pulses cool extremity pallor dependent robor O2 availability muscle cell metabolic needs exercise demand supply transient ischemia anaerobic metabolism lactic acid buildup muscles intermittent claudication reproducible cramp-like pain alleviated by rest blood velocity poiseuille's law turbulent flow bruits over time arterioles maximally vasodilator and desensitized to pro-vasodilatory stimuli loss ability compensate reduced vessel diameter chronic limb ischemia atrophic changes hair loss muscle atrophy thin shiny skin nail thickening fungus critical limb ischemia end stage chronic thrombo-embolic event stroke ischemic limb ischemic clotting cascade initiated tissue necrosis pain at rest ulcers big toe heel underside foot gangrene amputation nerve infarction hyporeflexia paraesthesia thromboembolic

Venous insufficiency- Signs and symptoms

Venous insufficiency- Signs and symptoms vein veins blood flow interruption venous system valve incompetence reflux venous obstruction venous return backflow blood hypertension hydrostatic transmural pressure in postcapillary vessels capillary dilatation vessel permeability extravasation RBCs interstitial hemoglobin released degraded hemosiderin deposits hemosiderosis brown discolouration high pressure superficial venous circulation varicose veins tortuous dilated superficial veins distended veins compress somatic nerves achy pain protein-rich exudate edema peripheral ankle edema tissue perfusion metabolic exchange stasis dermatitis dermal fibrosis lipodermatosclerosis fibrotic thickened skin pruritus chronic inflammation risk of thrombus local ischemia embolus skin integrity venous ulcer risk of infection Adderley gagnon Waechter

Takotsubo Cardiomyopathy- Pathogenesis and clinical findings

Takotsubo Cardiomyopathy- Pathogenesis and clinical findings emotional physical stresses other neurologic endocrine drug brain natriuretic peptide coronary artery disease takotsubo catecholamine release stimulation Beta receptors ionotropic effect alpha receptors coronary vessels metabolic contraction band necrosis edema inflammatory cell infiltration localized fibrosis coronary vasospasm microvascular dysfunction decrease oxygen supply relative to demand hypo-contraction ballooning left ventricular apex chest pain troponin BNP elevation ST ECG changes absence of obstructive CAD transient left ventricle systolic dysfunction dyskinetic apex Mitral regurgitation ventricular thrombus cardiac output low dyspnea syncope heart failure cardiogenic shock echocardiogram apex Gu gagnon Ryznar Waechter

Meralgia paresthetica- Pathogenesis and Clinical Findings

Meralgia paresthetica- Pathogenesis and Clinical Findings spine pelvis abdominal surgery pregnancy obesity pressure on lateral femoral cutaneous nerve belts tight waistbands diabetes mechanical iatrogenic idiopathic metabolic injury neuropathy carpal tunnel compression injury sensation sensory symptoms dysesthesias tingling burning stinging stabbing negative straight leg raise test pain on palpation lateral inguinal ligament anterior superior iliac spine Shah Hill Ryznar Bryan

Simple Febrile Seizure- Pathogenesis and clinical findings

Simple febrile seizure pathogenesis clinical findings infection HHV6 influenza virus child hippocampus fever 38 exogenously elevated brain temperature GABA receptor mutation sodium channel fever increased production mediators physiologic familial sporadic ion channels elevated temperature glutamate GABA excitability and synchronization of activity generalized tonic-clonic activity no focal signs <15 minutes normal EEG MRI complex focal signs eye deviation head turning status epilepticus beyak Howard Klein

Reactive Neutrophilia- Pathogenesis and Clinical Findings

reactive neutrophilic pathogenesis clinical findings infection inflammation malignancy drugs emotional stimuli stress smoking hyposplenism asplenia rheumatoid arthritis Crohn's epinephrine retinoic acid glucocorticoids anxiety exercise heat stroke surgery neutrophils neutrophil bone marrow demarginalization splenic sequestration neutrophilic ANC peripheral blood smear absolute neutrophil count left shift bands metamyelocytes myelocytes toxic granulations dohle bodies brenneis Siddique savoie ryznar

Hypoxemia- Pathogenesis and clinical findings

Hypoxemia- Pathogenesis and clinical findings interstitial lung disease pulmonary hypertension thickening of interstitium vasculature diffusion across alveolar membrane diffusion limitation exertional desaturation PE AVM pneumonia atelectasis cardiac defects airways disease inefficient blood flow ventilated areas blood bypasses aerated alveolar tissue V:Q mismatch R L shunt negligible significant improvement paO2 response 100% O2 Central drugs coma hypothyroidism peripheral damaged lung structure chest wall disorders minute ventilation alveolar gas exchange altitude barometric pressure driving pressure diffusion across membranes inspired a-a gradient hypoxemia tissue hypoxia cyanosis anaerobic metabolism organ brain anoxic angina

Bronchopulmonary Dysplasia (BPD)- Pathogenesis and clinical findings

Bronchopulmonary Dysplasia (BPD)- Pathogenesis and clinical findings Adderley Mitchell antenatal post-natal prematurity intrauterine growth restriction genetic predisposition maternal smoking chorioamnionitis pregnancy induced hypertensive disorders post natal mechanical ventilation sepsis O2 toxicity patent ductus arteriosus insult to lungs pro inflammatory cytokines disruption pulmonary vascular alveolar development reduced pulmonary vascular resistance vascular growth and altered vasoreactivity dysmorphic capillary beds remodelling of pulmonary arteries artery hypertension suboptimal repair abnormal remodelling interstitial fibrosis diffuse haziness interstitial thickening cxr impaired pulmonary gas exchange hypoxia signs of respiratory distress retractions wheezes crackles DLCO airway resistance obstructive lung disease FEV1 separation and alveolar hypoplasia functional alveoli surface area gas exchange

Neuromuscular Junction (NMJ)- Physiology and pharmacology

Neuromuscular Junction (NMJ)- Physiology and pharmacology calcium ion ions voltage gated ca2+ channels acetylcholine ACh receptors nicotinic SNARE protein complex AChR receptor sodium muscle specific kinase action potential voltage gated Ca2+ channels activated release presynaptic terminal binds

Biliary Atresia (BA)- Pathogenesis and clinical findings

Biliary Atresia (BA)- Pathogenesis and clinical findings Intrauterine environment genetic factors abnormal bile duct development toxic inflammatory response viral immunologic injury to bile duct epithelia pathophysiology poorly understood histology consistent with obstruction on liver biopsy biliary atresia progressive idiopathic fibre-obliterative disease extra-hepatic biliary tree biliary obstruction on intra-operative cholangiogram (diagnostic) partial complete bile duct obstruction delivery of bile acids to small intestine pressure in bile duct absorption of fat and soluble vitamins vitamin K+ deficiency coagulopathy INR PTT bruising petechiae acholic pale stool failure to thrive elimination of bilirubin conjugated direct bilirubin jaundice pruritus excreted urine dark urine diaper yellow pressure bile duct GGT backs up in liver cholestatic hepatitis firm enlarged liver fibrosis cirrhosis ALT AST Horwitz Adderley McKenzie

Inflammatory-Cascade-Pathogenesis-and-Clinical-Findings

Sepsis, and Septic Shock- Pathogenesis and Clinical Findings

Sepsis, and Septic Shock: Pathogenesis and Clinical Findings Authors: Daniel J. Lane Simonne Horwitz Reviewers: James Rogers Emily Ryznar Braedon McDonald* Christopher Doig* *MD at time of publication Sepsis Pathogen (Bacteria, Fungi, Virus, or Parasite) Comorbidities Immunosuppression or ↑ susceptibility (e.g. splenectomy) Pathogen virulence Invasion and host immune avoidance Vulnerable infection site ↑ likelihood of spread of infection & mortality Genetics ↑ Sensitivity of innate immune response Community acquired Hospital acquired Infection of host Innate immune response Fever, Leukocytosis/ Leukopenia, Left Shift/ Bandemia Compensatory response Tachypnea, Altered Level of Consciousness, Hypotension ↓ perfusion and oxygen delivery to organs Dysregulated Host Response Pro- and anti-inflammatory response Life-threatening organ dysfunction caused by a dysregulated host response to infection The Sequential Organ Failure Assessment (SOFA) or quick SOFA (qSOFA) Scores may be used to assess mortality risk Respiratory ↓ PaO2 / FiO2 (mmHg) Nervous ↓ Level of consciousness Septic Shock Cardiovascular ↓ Mean Arterial Pressure Organ Dysfunction Liver ↑ Bilirubin Kidney ↑ Creatinine, Acute oliguria Coagulation Thrombocytopenia, ↑ INR or aPTT Require vasopressors to ↑ mean arterial pressure Persistent hypotension despite adequate fluid resuscitation ↓ Mean Arterial Pressure (< 65 mmHg), ↑ Lactate (> 2 mmol/L) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 12, 2019 on www.thecalgaryguide.com

adrenergic-agonists-for-treating-hypotensionlow-blood-pressure

Side effects Authors: Arsalan Ahmad, Lance Bartel, Yan Yu* Reviewers: Billy Sun, Mackenzie Gault, Melinda Davis* *MD at time of publication Legend: Published February 19, 2019 on www.Pathophysiology Mechanism Sign/Symptom/Lab Finding thecalgaryguide.com Epinephrine Norepinephrine High Dose Low Dose Adrenergic Agonists for Treating Hypotension/Low Blood Pressure (BP) β1-receptor activation on cardiac myocytes ↑ contractility α1-receptor activation on the smooth muscle of blood vessel walls ↑ intra-cellular Ca2+ in these cells, ↑ their contraction Ephedrine Direct effect Indirect effect ↑ release of endogenous norepinephrine from the adrenal medulla (see above) Mimics epinephrine (see above) Primary Indications: anaphylaxis, cardiac arrest Primary Indications: Hypovolemic states (e.g. blood loss), Low systemic vascular resistance states (e.g. sepsis, Anesthesia-induced hypotension) Primary Indications: mainly used in Anesthesiainduced hypotension ↑ intracellular Ca2+ ↑ rate of myocyte contraction Phenylephrine ↑ Cardiac Output ↑ heart rate ↑ strength of myocyte contraction ↑ arterial wall tone ↑ stroke volume Pushes more blood to flow back to heart (↑ preload) ↑ systemic vascular resistance (SVR) More blood in ventricles stretch myocytes more optimally for ↑ contractility (Frank Starling Law) ↑ venous wall tone ↑ Blood Pressure Nonspecific activation of α and β receptors on other areas of the body (e.g. on the autonomic nervous system) as well as on cardiac myocytes Hypertension Cardiac Dysrythmias: e.g. palpitations, ventricular fibrillation Tremors Cardiac arrest All four drugs

Hyperkalemia- Physiology

Hyperkalemia: Physiology ↓ Renal Excretion ↑ Intake ↓ Intracellular Shift Acute and chronic kidney disease; CHF Principal Cell Dysfunction (TTKG < 7) ACEi/ARB; AI; heparin Hypovolemia (TTKG > 7) ↓ EABV ↓ distal flow of Na+ and H2O Urine [Na+] < 20 mmol/L Cell lysis ↑ osmolarity H2O efflux Solvent drag β2 inhibition α1 stimulation Digoxin ↓ A NAGMA ↓ insulin ↓ NHE1 activity Diabetic nephropathy; NSAIDs ↓ A: ↓ R K+ sparing diuretics; voltage- dependent RTA ↓ Na+/K+ ATPase activity ↓ GFR ↓ A: ↑ R ↑ A: ↑ R ↓ CCD K+ secretion ↑ K+ availability ↑ K+ release ↓ intracellular K+ influx Chronic: Desensitize voltage- gated Na+ channels and ↓ membrane excitability ECG: Peaked T-waves, ↑ PR interval, flat/absent P-wave, ↑ QRS, QRST “sine wave” Hyperkalemia Serum [K+] > 5.1 mmol/L Acute: ↑ extracellular [K+] makes the RMP less (-) Abbreviations: A: Aldosterone AI: Adrenal Insufficiency CCD: Cortical Collecting Duct CHF: Congestive Heart Failure EABV: Effective Arterial Blood Volume H+: Hydrogen ion K+: Potassium ion Na+: Sodium ion NAGMA: Normal Anion Gap Metabolic Acidosis NSAIDs: Non-steroidal anti-inflammatory drugs Note: Muscle weakness or paralysis, ↓ urinary acid excretion R: Renin RTA: Renal Tubular Acidosis RMP: Resting Membrane Potential TTKG: Transtubular Potassium Gradient • Pseudohyperkalemia should always be excluded; can be caused by thrombocytosis, leukocytosis or improper blood withdrawal technique. Authors: Mannat Dhillon Joshua Low Reviewers: Andrea Kuczynski Kevin McLaughlin* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 6, 2019 on www.thecalgaryguide.com

Torsades de Pointes (TdP)- Pathogenesis and Clinical Findings

Torsades de Pointes (TdP): Pathogenesis and Clinical Findings Drugs (e.g. Class 1A [quinidine], Class III [sotalol, amiodarone], TCAs, erythromycin, quinolones, anti-histamines) Sinus bradycardia, AV block Metabolic abnormality (hypo K+/Ca2+/Mg2+) Primary heart disease: ischemic, congestive heart failure, cardiomyopathy Acquired long QT syndrome Congenital long QT syndrome ↓ repolarizing current/ ­ depolarizing current in cardiomyocytes Mutated cardiac ion channels Author: Nicola Adderley Reviewers: Luke Gagnon Emily Ryznar *Saman Rezazadeh *George Veenhuyzen MD at time of publication* ↓ repolarizing current in cardiomyocytes ­ QTc interval Prolonged ventricular action potential duration Early after depolarization (EAD) triggering PVC Torsades de Pointes Illustrated changes to action potential: Normal cardiac action potential EAD Abbreviations: TCAs: tricyclic antidepressants AV: atrioventricular QTc: QT interval, corrected for heart rate PVC: premature ventricular contraction VF: ventricular fibrillation SR: sinus rhythm Polymorphic ventricular tachycardia initiated by PVC in the setting of QT interval prolongation and maintained by functional re-entry Non-sustained TdP Asymptomatic, palpitations, syncope (length-dependent) Illustrated changes to ECG Strip: OR Sinus rhythm restored Degeneration to VF Sudden cardiac death Prolonged repolarization Triggered beat (PVC) A BCDE A. Prolonged QT interval B. PVC C. PVC triggers TdP D. Non-sustained TdP E. Return to SR Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 10, 2019 on www.thecalgaryguide.com

Shoulder Dystocia: Complications

Failure of spontaneous restitution after delivery of head Shoulder Dystocia: Risk factors, mechanisms and complications Macrosomia Post-dates (>42 weeks) Previous shoulder dystocia Size discrepancy between fetal shoulders and maternal pelvis Multiparity Maternal diabetes Inadequate uterine tone (over distension of uterus, prolonged 2nd stage) and birth canal trauma from complicated delivery **Attempts to disimpact and/or deliver a macrosomic fetus Traction to head can lead to stretching and tearing of brachial plexus nerves Intentional or incidental fracture of the fetus’: Dysfunctional or prolonged labour and/or contractions ↓ oxygenation to fetus Authors: Danielle Hubbert Risk Factors: *Up to 50% have no risk factors = Obstetrical Emergency that is challenging to predict Mark Diaz Fetal death Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 12, 2019 on www.thecalgaryguide.com Prolonged 2nd stage of labour Maternal obesity Operative vaginal delivery Fetal anterior shoulder becomes impacted against maternal pubis symphysis and fails to deliver spontaneously with normal efforts Clavicular fracture Erbs palsy (C5-6) Klumpke palsy (C8-T1) (rarely permanent) Episiotomy or 3rd-4th degree perineal tears Postpartum hemorrhage Hypoxia/asphyxia (see PPH slide) Turtle sign – fetal head retracts tight against perineum Uterine rupture Antepartum Risks Intrapartum Risks Cord Compression Weakened and distended musculature Fetal Complications Maternal Complications Clavicle, to ↓ diameter of shoulders Humerus, when sweeping posterior arm across chest Humeral fracture Reviewers: Dalynne Peters Angela Deane Ingrid Kristensen* *MD at time of publication

Primary Myelofibrosis pathogenesis and clinical findings

Primary Myelofibrosis: Pathogenesis and clinical findings Legend: Published March 30, 2019 on www.Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications thecalgaryguide.com Author: Tony Gu Reviewers: Naman Siddique Sonia Cerquozzi* Man-Chiu Poon* * MD at time of publication Definitions: Constitutive activation – Constant expression of gene Extramedullary hematopoeisis – red blood cell production outside of bone marrow Somatic mutations in genes that drive cancerous replication (e.g., JAK2, CALR, MPL) within hematopoietic stem cells Non-driver mutations in other myeloid genes (e.g., LNK, CBL, TET2, ASXL1, IDH) Constitutive activation of cellular proliferation pathways ↑ cell signaling ↑ gene transcription and expression Cellular proliferation and resistance to apoptosis Proliferation of abnormal megakaryocytes ↑ neutrophil engulfment by megakaryocytes ↑ growth factor release by megakaryocytes Stimulation of fibroblasts Stimulation of endothelial cells New blood vessel formation ↑ osteoprotegerin Unbalanced osteoblast proliferation Osteosclerosis Fibrosis of the bone marrow Anemia Bleeding and bruising Infections Fatigue and pallor Bone pain Increased cell turnover Tumor lysis syndrome Cachexia, night sweats, fever/chills, malaise Expanding marrow pushing against bone Extramedullary hematopoiesis Hepatomegaly Portal hypertension Splenomegaly ↑ LDH Thrombocytosis Leukocytosis Secretion of coagulation inducing cytokines Arterial and venous thromboembolism ↓ blood cell production & leukoerythroblastosis Thrombocytopenia Leukopenia ↑ K+, PO4 2-, uric acid ↓ Ca2+ Bone pain Periostitis Immature granulocyte and erythroid precursors with blasts ↑ cytokine production (+) ↑ sequestration of blood cells Disseminated intervascular coagulation (see MAHA slide) Definitions: Periostitis – Inflammation of the membrane surrounding bone Osteosclerosis – Abnormal hardening and increased in density of bone

Hemorrhoids - Pathogenesis and Clinical Findings

INTERNAL Hemorrhoids - Found proximal to the dentate line - Visceral innervation Behavioural or Genetic Predisposition I.e. hereditary bowel/rectal problems or shared habits and practices (unclear mechanism) Increased Intra-Abdominal Pressure I.e. pregnancy, constipation, chronic straining, lifting, cirrhosis Hemorrhoids: Pathogenesis and clinical findings Dilations originate from inferior hemorrhoidal venous plexus Vascular cushions engorge along anal canal Legend: Published March 30, 2019 on www.Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications thecalgaryguide.com Authors: Aleeza Manucot Reviewers: Yoyo Chan Sean Doherty Dr. Sylvain Coderre* * MD at time of publication Supporting tissues of anal cushions weaken, disintegrate, or deteriorate Inflammatory reaction occurs, involving vascular wall and connective tissue Thrombosis Pain ↑ mucus secretions or fecal soiling of prolapsing hemorrhoids Cushion epithelium erodes via damage from compression Painless rectal bleeding Bleeding without prolapse Prolapse with spontaneous reduction Prolapse requiring manual reduction Irreducible 1st degree 2nd degree 3rd degree 4th degree Infarction and thrombosis Acute severe pain Anal cushions prolapse (downwardly slide) into rectum or open space Dentate line: divides the upper two thirds and lower third of the anal canal EXTERNAL Hemorrhoids - Found distal to the dentate line - Somatic innervation Somatic nerve receptors activated Sebaceous glands ↑ secretions around area of hemorrhoid Itching Perianal irritation Swelling Inflammation creates prothrombotic state Hemorrhoids

gastroesophageal-reflux-disease-gerd-complications

Gastroesophageal Reflux Disease (GERD): Complications Esophageal stricture disease Esophagitis Esophageal adenocarcinoma Barrett’s esophagus GERD Reflux of gastric content into distal esophagus Damage to squamous esophageal epithelium Legend: Published March 30, 2019 on www.Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications thecalgaryguide.com Authors: Wendy Wang Reviewers: Yoyo Chan Sean Doherty Dr. Sylvain Coderre* * MD at time of publication Squamous esophageal epithelium undergoes metaplasia to become columnar epithelium This predisposes cells to premalignant changes (dysplasia) Collagen is deposited where ulcers heal Asthma/Chronic Cough Chronic Laryngitis Laryngeal and Tracheal Stenosis Extra-esophageal Complications Esophageal Complications Airway becomes irritated Fibroblasts proliferate and deposit granulation tissue in airway Tissue deposition leads to narrowing of laryngeal and tracheal space Damage to pharyngeal lining and airway Esophageal tissue repeatedly exposed to stomach acid Pro-inflammatory cells and cytokines are recruited to the area Definitions: • Metaplasia: abnormal change in the nature of a tissue • Pro-inflammatory cells and cytokines: Mediators of inflammation. Examples of cells include macrophages and T cells, cytokines include IL-17, IL-2, IL-4 Over time, collagen fibers contract Bronchoconstriction ↑ vagal tone ↑ bronchial reactivity Cough sensory nerve endings are stimulated Vagal reflex is activated Activation of cough center in brainstem ↑ inflammation of squamous epithelium Ulcers form in esophagus

autosomal-dominant-polycystic-kidney-disease-adpkd

Autosomal Dominant Polycystic Kidney Disease (ADPKD): Pathogenesis, Clinical Findings, and Complications Author: Yan Yu* Reviewers: David Waldner* Sean Spence* Andrew Wade* * MD at time of publication Legend: Published April 14, 2019 on www.Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications thecalgaryguide.com One theory (mechanism unclear): these mutations in the polycystin gene result in dysfunctional Ca2+ channels on epithelial cells PKD1 mutation (~78%) Abnormal Ca2+ entry disrupts intracellular Ca2+ signaling In the Kidney: all segments of the nephron develop cysts: sacs of flattened epithelium filled with proteinaceous fluid, replacing normal parenchyma with dysfunctional tissue PKD2 mutation (~15%) Expansive cell proliferation Low urine Osmolality (< 500 mmol/kg) Abnormally expandable basement membranes PKD3 mutation (rare) ↑ fluid secretion 95% inherited, autosomal dominant mutations 5% spontaneous mutations In adults, the same pathophysiology occurs in epithelial tissue throughout the body When pH of urine <5.5, uric acid is in its protonated form & is less soluble àprecipitates uric acid stones Nephrolithiasis Urine accumulates within cysts Cyst growth Pyelonephritis Damaged tubules leak proteins into filtrate Proteinuria Flank pain Inability to concentrate urine Low urine specific gravity (<1.010) ¯ NH3 production, ↑ acidity of renal tubule (¯ pH) Activates nociceptors Cyst hemorrhage Urine stasis à precipitation of CaOxalate stones within cysts Multiple Renal Cysts (bilaterally, in cortex and medulla, on Ultrasound) In the Brain: expansion & weakening of cerebral arterial walls “Berry Aneurysms” 9- 12% (ask about this on Family Hx!) In many organs: epithelial tissue expansion & fluid secretion In the Heart: abnormal valve collagen matrix Valve prolapse & regurgitation Liver (90%), spleen/pancreas (5-10%), thyroid (rare) cysts In seminal vesicles: Cyst formation disrupts sperm motility Infertility In GI tract: Cyst formation Herniations, diverticuli Dysfunctional collecting ducts Abdominal mass (enlarged kidneys) (may be palpable) Blood leaks into renal tubules Hematuria (isomorphic) Bacteria accumulate in the static urine Dysfunctional proximal tubules Unknown mechanisms à ¯ urine citrate àmore urine Ca2+ binds to oxalate than to citrate à↑ Ca- Oxalate stones Note: PKD1 mutations have more severe prognosis than PKD2 mutations (earlier disease onset, larger cysts) Vessels tear more easily Stretches renal capsule Cysts compress renal vasculature ¯ Glomerular perfusion To ↑ perfusion à kidneys activate RAAS Hypertension

Rickets and Osteomalacia: Pathogenesis and Clinical Findings

Hypocalcemia Rickets and Osteomalacia: Pathogenesis and clinical findings Abnormal Vitamin D Metabolism: Deficiency, hereditary disorders of synthesis or vitamin D receptor Fractures Proximal muscle weakness, manifesting often as gait disturbances Osteomalacia: Occurs after epiphyseal closure Bone mineralization defect (Osteopenia with reduced mineralization) Shear forces bend the osteopenic bone Short stature Diffuse skeletal pain (bone tenderness) Osteopenia reduces bone density and cause fractures with minimal force applied If hypophosphatemic, production of ATP and other high energy molecules declines Unequally distributed forces and muscle/tendon tension stimulate nociceptors Legend: Published November 26, 2012 on www.Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications thecalgaryguide.com Calcification inhibitors (excess exposure to Al, Fluoride, etidronate) Lack, or reduced function, of mineralization enzymes (like ALP) Lack of bone mineral components: 1. Phosphate: renal tubule disorders, vit D or Phosphate deficiency, ↑FGF23 2. Calcium: severe deficiency (infants) Rickets: Occurs before epiphyseal closure Epiphyseal plates do not fuse, impairing bone growth Bowed legs Cartilage in epiphyseal plates cannot become ossified Disruption in calcium ion homeostasis ↓ GI absorption of Ca2+ into blood ↓ Kidney reabsorption of Ca2+ into blood ↓ energy available to muscle Author: Payam Pournazari Reviewers: Yan Yu Spencer Montgomery David Hanley* * MD at time of publication

Polyarteritis Nodosa (PAN): Pathogenesis and Clinical Findings

Polyarteritis Nodosa (PAN): Pathogenesis and clinical findings Environmental triggers Infectious/viral agents (commonly Hepatitis B) Medical Comorbidities Malignancies (most commonly hairy-cell leukemia) Immunogenetic Predisposition: patient is genetically predisposed to a dysregulated immune response Fever ↑ ESR and CRP Postulate 1 Viral antigen-antibody complexes deposit in vasculature, causing lesions and activating cellular inflammatory response Authors: Nela Cosic, Yan Yu* Reviewers: Sean Doherty Martin Atkinson* * MD at time of publication Palpable or necrotic purpura Malignant Hypertension Renal Insufficiency Myocardial ischemia Heart failure Diffuse myalgias Postulate 2 Viral replication causes direct injury to vascular endothelial cells ↑ Anti- endothelial cell autoantibodies (AECA) Altered cytokine profile (↑TNF-α, IL-1β, IFN-α, IL- 2)à↑ T-cell mediated immune response Weight metabolism Loss Autoimmune attack on various areas of the body Malaise and/or Arthralgias (knees, ankles, elbows, wrists) Orchitis: Testicular pain, erythema and/or swelling Small intestine perforation GI Manifestations Non-specific abdo pain GI hemorrhage Peripheral sensory changes: Distal mononeuropathy multiplex Polyarteritis Nodosa (PAN) Focal segmental necrotizing leukocytoclastic vasculitis of medium or small-sized arteries Inflammation of arteries damages the vascular endothelium of those arteries Inflammation predisposes formation of arterial thromboses Blockage of arteriesà tissue ischemia and possible necrosis (tissue cell death) ↑ basal Arterial aneurysms Inflamed subcutaneous arteries Inflamed renal artery àluminal narrowing and reduced blood flow to kidneys Inflamed coronary artery à luminal narrowing, occlusion, thromboses Segmental inflammation of muscular arteries, stimulating surrounding nociceptors. Muscle ischemia develops long-term. Ischemia/necrosis of the testicles Ischemia/necrosis of the small intestine Ischemic vasculitic nerve damage: Immune complex deposition within vessel walls of arteries traveling with nerves leads to persistent vascular inflammation and ischemia of associated nerve Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 18, 2019 on www.thecalgaryguide.com

dermatomyositis-dm-and-polymyositis-pm-pathogenesis-and-clinical-findings

Dermatomyositis (DM) and Polymyositis (PM): Authors: Merna Adly, Yan Yu* Reviewers: Nela Cosic Sean Doherty Martin Atkinson* * MD at time of publication Pathogenesis and clinical findings Immunogenetic and Cellular Predisposition Genetic polymorphisms cause dysregulated immune response, cytokine profile, and protein expression in muscle cells Demographics F:M, 2:1 Bimodal age distribution: - Juvenile: 7 years of age (mean) - Adult: 52 years of age (mean) Malignancy Tumor cells increase systemic inflammatory response, leading to increase of autoantigens associated with DM ↑ in DM-associated autoantibodies (Ex. Anti-Mi-2/ Anti-Jo-1) Autoantibodies bind to DNA or RNA in muscles, provoking a systemic inflammatory response ↑ chemokine and cytokine release in endothelial vasculature of muscles Perivascular Capillary necrosis inflammation Lack of blood supply to the myofibers causes endofascicular hypoperfusion and muscle ischemia Muscle tissue damage: Inflammatory infiltrates destroy cellular components of muscle (endoplasmic reticular, myofiber, and keratinocytes) Environmental triggers Infectious agents (ex. Picornavirus) or drugs (ex. statins) provoke immune response Elevated Antinuclear Antibodies Anti-Jo-1 Anti-OJ Anti-Mi2 Anti-SRP Anti-EJ Anti-PL12 Anti-PL7 These processes occur in the skin on the dorsum of the hands, forming hyperkeratotic flat red papules These processes occur in the upper & lower eyelids, causing red-purple discoloration +/- swelling Perifascicular atrophy (Observed on histology) Weaker GI tract musculature Weaker pulmonary musculature Weaker cardiac musculature Dermatomyositis only: Gottron Papules Heliotrope Rash Damaged muscle cells release their internal cellular enzymes into the bloodstream Elevation of muscle enzyme levels in serum: Creatinine kinase (CK), lactate dehydrogenase (LD), aldolase, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) Muscle Biopsy Findings Muscle necrosis, fiber regeneration, diffuse CD8+ T lymphocytes infiltrates Bilateral Muscle Weakness Subacute development, primarily deltoids and hip flexors affected Dysphagia Aspiration, respiratory compromise Atrioventricular defects, tachyarrhythmias, dilated cardiomyopathy Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 18, 2019 on www.thecalgaryguide.com

DiGeorge Syndrome: Pathogenesis and Clinical Findings

DiGeorge Syndrome: Pathogenesis and clinical findings Authors: Danielle Lynch Reviewers: Meghan Jackson, Sean Doherty Yan Yu*, Luis Murguia Favela* * MD at time of publication Note: *TBX1 is most strongly associated with the signs of DiGeorge syndrome, however 30-40 genes reside in the deleted region (e.g. DGCR8 & COMT), though their role is less well understood. Abbreviations: • PA-VSD – pulmonary atresia with ventricular septal defect • TBX1 – T-box Protein 1 • VSD – ventricular septal defect Heterozygous deletion at chromosomal region 22q11.2 The region’s main gene product, TBX1*, exhibits haploinsufficiency: even a heterozygote for this gene product, producing half the normal quantities of TBX1, is insufficient to produce a normal phenotype Abnormal pharyngeal arch development Hypoplastic / aplastic thymus ↓ T cells (lymphopenia) Craniofacial malformations (e.g. tracheomalacia, horizontal Eustachian tubes, cleft palate) Impaired ear and sinus drainage Abnormal conotruncus development Heart defects (e.g. interrupted aortic arch, tetralogy of Fallot, PA-VSD/VSD, truncus arteriosus) Hypoplastic parathyroid glands Hypocalcemia Seizures (usually neonatal onset) Memory Aid: CATCH-22 Cyanotic congenital heart disease Abnormal facies Thymic hypoplasia Cognitive impairment Hypoparathyroidism, hypocalcemia 22q11.2 deletion Abnormal T cell regulation and development Compromised cytotoxic T cells Susceptibility to intracellular pathogens Compromised helper T cells ↓ communication with memory B cells ↓immunoglobulins (progressive hypogammaglobulinemia) Susceptibility to extracellular pathogens Autoimmunity and Atopy Note: There is phenotypic variability in DiGeorge Syndrome. Other features include: thin upper lip, upslanted palpebral fissures, prominent nose, low-set ears, small mouth, hearing impairment, long tapered fingers, scoliosis, vertebral malformations, learning disabilities, and failure to thrive. Viral Infections Bacterial Infections Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 21, 2019 on www.thecalgaryguide.com

Molluscum Contagiosum: Pathogenesis and Clinical Findings

Molluscum Contagiosum: Pathogenesis and clinical findings Authors: Kara Hawker Reviewers: Taylor Woo Sean Doherty Dr. Laurie Parsons* * MD at time of publication 4 main subtypes of molluscipox virus (MCV): • MCV I *more prevalent than other subtypes except in immunocompromised individuals • MCVII • MCV III • MCVIV Abbreviations: - MCV: Molluscum contagiosum virus - NF-KB: nuclear factor kappa-light- chain-enhancer of activated B cells (a transcription factor regulating genes responsible for innate & adaptive immune responses) Sexually active adults: abdomen, genitals, inner thighs Children: face, trunk, limbs Immunosuppression Active Atopic Dermatitis Hot, humid climates Crowded living conditions Risk factors for infection Direct skin-to-skin contact with infected host Contact with contaminated objects Molluscipox virus infection of epidermal keratinocytes Virus replicates in cytoplasm of epithelial cells Cytoplasmic inclusion bodies form, multiply & push nucleus to edge of cell Rupture and discharge of virus-packed inclusion bodies MCV-released proteins inhibit NF-KB activation Suppress host immune response to infection Single or multiple, 2-6 mm, pearly white, discrete papules with central umbilication containing white, waxy curd-like core appearing on any cutaneous surface Papule contains caseous plug Squeezing the papule produces white cheesy fluid Transmission of MCV to conjunctiva of eye Scratching or removing lesions by curettage and cautery Staphylococcus aureus infects lesion Neutrophils & macrophages phagocytose bacteria Immunosuppression Impaired T-cell immunity fails to defend against MCV infection Conjunctivitis Scarring Abscess Widespread lesions Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 21, 2019 on www.thecalgaryguide.com

acute-somatic-pain

Acute Somatic Pain: Pathophysiology Acute tissue damage, from three types of causes: Mechanical (eg: sharp pin) Thermal (eg: hot stove) Chemical (eg: inflammation) Nociceptors activated at site of injury (1st order sensory neurons) Nociceptive fibres (A∂ and C) carry noxious sensory information to the ipsilateral dorsal horn of the spinal cord Excitatory neurotransmitters are released and stimulate 2nd order sensory neurons 2nd order sensory neurons immediately cross the midline of the spinal cord, and ascend up the opposite side’s anterolateral (aka spinothalamic) tracts, terminating in various locations: Authors: Lisa Murphy Yan Yu* Reviewers: Mackenzie Gault Melinda Davis* * MD at time of publication Nociceptors: neurons that detect noxious or painful stimuli and carry this information to the spinal cord. There are two major types: A∂ fibres: myelinated, initial “sharp, fast” feeling C fibres: unmyelinated, delayed, “dull, burning” feeling To hypothalamus 2nd order neuron synapses in the hypothalamus Hypothalamic neurons coordinate the body’s visceral response to pain 2 nd To thalamus order neuron terminates in thalamus To brainstem 2nd order neuron synapses in brainstem’s reticular formation To midbrain 2nd order neuron synapses in periaqueductal gray area (PGA) in the midbrain In the thalamus, 2nd order sensory neurons synapse with 3rd order sensory neurons, which carry the signal to the cerebral cortex Stimulates descending pathways to modulate the incoming pain signal Decreased or increased perception of pain Pain localization and sensation Emotional and behavioural response ↑ Heart Rate Nausea Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 25, 2019 on www.thecalgaryguide.com

Small Bowel Infarction

Small Bowel Infarction: Pathogenesis and clinical findings Authors: Yan Yu Reviewers: Dean Percy Danny Guo Erin Stephenson Maitreyi Raman* * Indicates faculty member at time of publication Important Notes: • Bowel infarction is a rare cause of acute abdominal pain • Small bowel infarction is more common than colonic due to the small intestine’s single blood supply (SMA) versus the colon’s dual blood supply (SMA and IMA) • With decreased perfusion colonic tissue tends to suffer from ischemia rather than more serious infarction • Colonic ischemia presents with pain, diarrhea, and rectal bleeding Abbreviations • SMA - Superior mesenteric artery • IMA - Inferior mesenteric artery Atrial fibrillation Blood stasis in left atria of heart more prone to coagulation Embolism occluding SMA Hypertension, dyslipidemia, smoking, diabetes, + family hx Atherosclerosis (of SMA) Thrombosis in the superior mesenteric artery ↓ Arterial perfusion of the small intestine (↓ O2 delivery to bowel tissue) Ischemia of bowels Infarction of bowels Venous trauma ↓ blood flow and endothelial injury hypercoagulable state Mesenteric venous thrombosis, backing up arterial blood Food in the intestine ↑ demand for blood in gut Death of cells under visceral peritoneum stimulates autonomic nerves Post-prandial abdominal pain Severe central abdominal pain Small bowel infarction from SMA occlusion is commonly pain progressive, and out of proportion with the patient’s physical exam findings Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published June 15, 2019 on www.thecalgaryguide.com

Crohn's Disease

Inflammatory Bowel Disease: Clinical findings in Crohn’s Disease Authors: Yan Yu Amy Maghera Reviewers: Jennifer Au Danny Guo Jason Baserman Jessica Tjong Kerri Novak* * MD at time of publication Behavioural Factors: Smoking, over-sanitation Genetic Susceptibility Environmental Factors Diet, bacteria/viruses, drugs, vitamin D Systemic immune response primarily against the GI tract. (Unclear mechanism, mediated by cytokine release and neutrophil inflammation) Inflammation of the GI tract lining - Inflammation is “transmural”, spanning the entire thickness of the intestinal wall from luminal mucosa to the serosa. - The inflammation occurs anywhere in the GI tract from the oral mucosa to the anal mucosa (from ‘gums to bum’) in skip lesion pattern. Atrophy, scarring of the intestinal villi Inflammatory cytokines destroy the mucosa epithelial cells of the GI tract wall, causing cell apoptosis and ulceration ↑ permeability of the blood vessels supplying the GI tract wall Chronic inflammation impairs healing responses Dysregulated wound healingàexcess extracellular matrix deposition Fibrosis leads to scar tissue and thickening of all layers of the GI tract Strictures Inflammation is systemic, affecting: Joints Arthropathy Erythema Impaired absorption of nutrients Weight loss Prolonged GI bleeding Anemia Transporter proteins responsible for Na+ reabsorption gradually disappear from the epithelium More sodium (and thus water) is retained in the GI tract lumen Microperforations can penetrate through the intestinal wall Anal fistulae (“holes” connecting the anus to the skin, bladder, peritoneum, small bowel, etc.) Continued inflammation and/or infection can lead to: Leakage of fluid out of capillaries into the GI tract Luminal edema and swelling Narrowing of GI lumenàbowel obstruction Skin Mouth Eyes Liver nodosum, pyoderma gangreno- sum >5 canker sores Uveitis Iritis, scleritis Sclerosing cholangitis ↓ fat absorption Fatty acids (negatively charged) bind Ca2+, freeing oxalate from Ca2+ ↑ oxalate absorbed into blood & filtered by kidney Calcium oxalate kidney stones Diarrhea Abdominal cramping and pain (see Bowel Obstruction page for full mechanism Anal abscesses Inflammatory masses Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published June 15, 2019 on www.thecalgaryguide.com

Hemophilia

Hemophilia: Pathogenesis and clinical findings Authors: Sean Spence Reviewers: Jennifer Au Yan Yu Erin Stephenson Lynn Savoie* * Indicates faculty member at time of publication Platelets not affected Normal platelet count X-Linked Recessive pattern of inheritance Almost exclusively male disease Epidemiology: • Hemophilia A and B have a combined incidence of 1:5000 live male births • Hemophilia A accounts for approx. 85% of cases • Hemophilia B (Christmas Disease) accounts for approx. 15% of cases • Factor levels below 1% of normal constitutes severe disease, 1-5% moderate disease, and 5-40% mild disease • The more severe the disease, the greater the odds of “spontaneous” bleeds occurring Genetic defect on the X chromosome affecting the factor VIII or factor IX gene Deficiency of functional factor VIII (Hemophilia A) or factor IX (Hemophilia B) in blood Insufficient clotting action when faced with a bleeding challenge Factor VIII/IX deficiency slows intrinsic clotting pathway Factor VIII/IX not part of extrinsic clotting pathway ↑PTT Normal PT Uncontrolled bleeding Occurs across entire body Hemarthrosis (bleeding in joints) Intramuscular hematoma Dental bleeds Intracranial hemorrhage GI/GU bleeds, etc. Chronic hemophilia arthropathies (main contributor to disability and reduced QoL) In severe patients, repeated joint bleeds common Recurrent bleeding into joints damages cartilage Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published June 15, 2019 on www.thecalgaryguide.com

Signs and Symptoms of Pulmonary Embolism

Signs and Symptoms of Pulmonary Embolism Authors: Dean Percy Yan Yu Reviewers: Tristan Jones Julia Heighton Man-Chiu Poon* Lynn Savoie* * MD at time of publication Notes • One of the most under- diagnosed conditions, typically asymptomatic, with tachycardia often being the only sign • Consider DVT and PE as one disease: if PE is suspected, look for signs and symptoms of DVT • Absence of DVT does not rule out PE Virchow’s Triad: hypercoagulable state, venous stasis, vessel injury (*see Suspected DVT) Deep Vein Thrombosis – popliteal, femoral, iliac veins Clot migrates to IVCàright atrium of heartàright ventricleàpulmonary vasculature Large clots (saddle emboli) are lodged in pulmonary arteries Small clots are lodged in pulmonary arterioles Saddle embolus (pulmonary artery obstruction) Back-up of blood into right heart Right heart strain ↓ CO2 delivery to the lungs for exhalation Less CO2 exhaled, CO2 builds up in the blood, triggers medullary chemoreceptors to ↑ respiratory rate Well-ventilated (V) areas of lung do not receive adequate blood supply (Q); vice versa V/Q mismatch On V/Q scan Signals brain to ↑ heart rate Ischemic tissue becomes inflamed and adheres to pleura Pleural friction rub Sandpaper-like sound heard on auscultation Pleuritic chest pain Focal, localized chest pain that occurs with each breath Clot ↓ pulmonary arterial/arteriolar blood flow ↓ delivery of deoxygenated blood to alveoli for oxygenation Low O2 in blood (↓ O2 saturation) is detected by aortic/carotid chemoreceptors Signals brain to ↑ respiratory rate If circulation to lung periphery is cut off, sub-pleural lung tissue can become ischemic and infarct Irritation of somatic sensory nerve endings on the parietal pleural membrane Pain stimulates adrenergic response Tachycardia Dyspnea/shortness of breath (SOB) Most sensitive indicator of PE, but not very specific Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published June 15, 2019 on www.thecalgaryguide.com

Hemolytic Anemia - Pathophysiology

Hemolytic Anemia: Pathophysiology behind the Normocytic Anemia Note • Extreme bone marrow compensation for hemolysis (↑ RBC synthesis/reticulocytosis) may result in slightly macrocytic anemia (because reticulocytes have larger volumes than RBCs) Defects in the RBC’s environment Defects in RBC membranes Ex. Hereditary Spherocytosis: mutation causing deficiency of RBC structural proteins like ankyrin or spectrin RBC membranes become weakened and form blebs that break off ↓ RBC surface area while volume remains constantà RBC becomes spherical Spherocytes in spleen trapped and phagocytosed by splenic macrophages (extravascular hemolysis) Defects in RBC internal contents (thalassemia, hemoglobinopathies, and metabolic defects) Ex. Sickle Cell Disease: point mutation in hemoglobin (Hgb) structure (GluàVal) Inappropriate Hgb polymerization in low oxygen environments due to mutationàRBC becomes rigid, forms a sickle shape Inflexible RBCs become trapped in the spleen’s sinusoid membranes àphagocytosed by splenic macrophages (extravascular hemolysis) Infection triggers immune system activation Autoimmune processes TTP/HUS (abnormal platelet aggregation blocking blood vessels) Production of abnormal antibodies and immune complexes targeted against RBC surface antigens Immunoglobulin-bound RBCs are marked for destruction by the immune system (by either the cell- mediated or complement- mediated pathways) DIC (fibrin deposition blocking blood vessels) Artificial heart valve RBCs are sheared when they flow past an abnormal surface Rate of hemolytic RBC destruction > rate of bone marrow RBC synthesis (reticulocytosis) ↓ total number of RBCs in the body (despite normal RBC production/volume) Normocytic anemia Authors: Yan Yu Katie Lin Man-Chiu Poon* Reviewers: Andrew Brack Julia Heighton JoyAnne Krupa Lynn Savoie* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published June 15, 2019 on www.thecalgaryguide.com

Wilson's Disease

Wilson Disease: Pathogenesis and clinical findings Authors: Sean Spence Reviewers: Danny Guo Yan Yu Crystal Liu Natalie Arnold Sam Lee* * MD at time of initial publication Autosomal Recessive mutation in ATP7B gene, defect in hepatic Cu transport protein Impaired Cu transport from liver into bile, ↓ Cu incorporation into apoceruloplasmin (protein responsible for carrying Cu in the blood) Hepatic Cu accumulation, deposition in hepatocyte lysosomes Hepatocyte injury (speculated mechanism: free radicals) Cu leak from damaged hepatocytes Epidemiology: • Autosomal Recessive condition with prevalence of 1:30,000 • 60% of cases present initially with neurologic Symptoms • Fulminant cases present with acute liver failure and massive hemolysis, treated with liver transplant ↓ ceruloplasmin release ↓ serum ceruloplasmin Early asymptomatic liver dysfunction Cu movement into bloodstream Cu deposition in vulnerable tissues Abbreviations: • Cu - Copper • AST - Aspartate Aminotransferase • ALT - Alanine Aminotransferase ↑ AST, ALT, and Bilirubin ↑ Serum free Cu (total usually low due to low ceruloplasmin) Eyes: Kayser-Fleischer rings CNS: Neurologic disease, Psychiatric disease MSK: Arthropathies Kidney: Fanconi syndrome, Kidney stones Chronic hepatitis, Cirrhosis with hepatic insufficiency, Portal hypertension, Hemolysis, Acute Liver Failure Continued hepatocyte injuryà progressive liver damage Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published June 17, 2019 on www.thecalgaryguide.com

chronic-myeloid-leukemia

Chronic Myeloid Leukemia (CML): Pathogenesis and Clinical Presentation Translocation of a Chr 9 segment onto Chr 22, creating a Philadelphia chromosome (Chr 22) containing the BCR-ABL1 fusion gene Mutations from ionizing radiation Other genetic abnormalities Authors: Yan Yu Katie Lin Reviewers: Jennifer Au Crystal Liu Danielle Chang Lynn Savoie* *Indicates faculty member at time of initial publication These genetic abnormalities accumulate in the earliest cell of the blood cell differentiation sequence: the pluripotent hematopoietic stem cell Hematopoietic stem cell division in the bone marrow becomes unregulated 1. Chronic Stage (85% of clinical presentation): Hematopoietic stem cell division/differentiation in the bone marrow results in ↑ production of multiple blood cell lines (detectable on CBC, but patients are usually asymptomatic at this stage) Acquired ↑ genetic abnormalities 2. Accelerated Stage More and more immature precursor cells (”blasts”) divide and accumulate in bone marrow (where 10-19% of blood cells are “blasts”.) Blasts start to spill over into the peripheral blood Acquired ↑ genetic abnormalities 3. Blast crisis (transformation into AML/ALL) Neoplastic blast cells have filled up the bone marrow (where >20% of blood cells are blasts). More blasts spill out into the peripheral blood. Multifactorial causes, most Weight loss, malaise, fever/ with unclear mechanisms Neoplastic division of platelet precursor cells Neoplastic division of WBC precursor cells, especially neutrophil precursors Dividing “blasts” limit the space and resources available for RBC synthesis chills, night sweats Thrombocytosis Leukocytosis: · Neutrophilia, basophilia, & eosinophilia · “Left shift”: ↑ neutrophil & band production · Disorderly WBC differential: i.e. “myelocyte bulge” Trapping of WBC’s in the spleen enlarges the spleen Splenomegaly: · Left upper quadrant pain · Early satiety (large spleen compresses the stomach) · Associated hepatomegaly (if spleen is overfilled & WBCs spill over into liver) Anemia ↓ oxygenation of blood means blood is less red & body tries to compensate Pallor Dyspnea Tachycardia High turnover of these cancerous cells → excess cell lysis Release of intracellular contents (uric acid, K+, LDH) into plasma · Hyperkalemia · High (LDH) Hyperuricemia Gout Acute Kidney Injury Expanding marrow pushing on bone Bone marrow expands into sternum Bone pain Sternal tenderness Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published June 15, 2019 on www.thecalgaryguide.com

Secondary Polycythemia

Secondary Polycythemia: Pathogenesis Authors: Noriyah Al Awadhi, Yan Yu, Peter Duggan* Reviewers: Crystal Liu, Kara Hawker, Paul Ratti, Man-Chiu Poon*, Lynn Savoie* * MD at time of initial publication Chronic lung disease (ILD, COPD) Poor lung function Renal artery stenosis ↓ blood flow to kidney Kidney senses ↓ O2 High affinity Hb or CO poisoning Hb does not easily unload O2 Tissues become hypoxic Tumors (e.g. renal, hepatic, lung) Secretes EPO in an unregulated way, as a “paraneoplastic syndrome” High altitude Obstructive sleep apnea Episodic airway obstruction during sleep Intermittent hypoxia Cyanotic heart disease Shunting of blood Venous and arterial blood mixes Poorly oxygenated blood ↓ O2 partial pressure ↑ EPO production independent of O2 (inappropriate response) ↑ EPO production due to hypoxia (appropriate response) Abbreviations: • Hb- Hemoglobin • EPO- Erythropoietin • ILD- Interstitial Lung Disease • COPD- Chronic Obstructive Pulmonary Disease “Endogenous causes” of high EPO Secondary Polycythemia “Exogenous causes” of high EPO Testosterone therapy Iatrogenic EPO (results in ↑ EPO synthesis administration within the body) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published May 5, 2019 on www.thecalgaryguide.com

Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia (ALL): Pathogenesis and Clinical Presentation Authors: Yan Yu, Katie Lin Reviewers: Crystal Liu, Kara Hawker, Jennifer Au, Lynn Savoie* * MD at time of initial publication Note: ALL is much rarer than AML and is usually seen in children Accumulation of genetic abnormalities in immature lymphoid precursor cells (B/T cell precursors) Neoplastic lymphoid precursor cells (“blasts”) divide and accumulate in bone marrow Abundance of blasts displaces other blood precursors from marrow, inhibiting their development/differentiati on After neoplastic blasts fill up bone marrow, they spill out into blood High turnover of these cancerous cells Multifactorial causes, most with unclear mechanisms Expanding marrow pushing on bone Pancytopenia on CBC 20% of marrow is blasts (on bone marrow aspirate and/or biopsy) Neoplastic blasts continue to divide and accumulate in lymph nodes and spleen (can occur, but not that common) Blasts detected as white blood cells on CBC High rate of cell lysis Weight loss, malaise, fever/chills, night sweats Bone pain (worse than that felt in AML, especially in children) ↓ in neutrophils ↓ in RBCs ↓ in platelets, reduced blood clotting ability Lymphadenopathy Splenomegaly May cause leukocytosis, despite pancytopenia Release of intracellular contents (uric acid, K+, LDH) into plasma Greater chances of infection Anemia Fatigue, shortness of breath, pallor Easy bruising and petechiae on skin Hyperuricemia Hyperkalemia High [LDH] Tumor lysis syndrome Acute kidney injury Gout Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published May 5, 2019 on www.thecalgaryguide.com

Ulcerative Colitis

Inflammatory Bowel Disease: Clinical Findings in Ulcerative Colitis Authors: Yan Yu Amy Maghera Reviewers: Jennifer Au Danny Guo Jason Baserman Crystal Liu Danielle Chang Kerri Novak* * MD at time of initial publication Inflammation is systemic, affecting: Environmental Factors Diet, bacteria/viruses, drugs Genetic Susceptibility Behavioral Factors: In UC, smoking and appendectomy are actually protective (unknown reason) Immune response against the GI tract. (Unclear mechanism, but thought to be mediated by cytokine release and neutrophil infiltration) Inflammation of the GI tract epithelial lining - Starting at the rectum and moves up the colon and is continuous (does not invade the small intestine) - Inflammation affects the mucosal and submucosal only Diarrhea, abdo pain and cramping causing avoidance of food Weight loss Apoptosis of GI tract mucosa Transporter proteins responsible for Na+ reabsorption gradually disappear from the epithelium Ulceration, into the anus, and more severe Prolonged Bleeding - GI and anus Anemia, often iron deficiency Inflammation ↑ permeability of the blood vessels supplying the GI tract wall Fluid leak out of capillaries into GI tract wall, causes edema and swelling Swelling narrows the GI tract lumen, causing bowel obstruction Inflammation, ulceration, or infection at the anus (all involve the RECTUM!) Anal irritation stimulates autonomic and somatic nerves leading up to the brain, causing the pt to want to defecate Tenesmus, urgency, frequency (feeling or urgency to defecate, but little stool is produced) Joints Skin Arthroplasty/ joint pain Erythema nodosum, pyoderma gangrenosum Mouth >5 canker sores More sodium (and thus water) is retained in the GI tract lumen Bloody Diarrhea, usually bloody due to anal bleeding and ulceration bleeding Abdominal Cramping and pain (see Bowel Obstruction page for full mechanism) Eyes (uvea, iris, sclera) Liver Blood Uveitis Iritis, scleritis Sclerosing Cholangitis Autoimmune hemolytic anemia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published May 5, 2019 on www.thecalgaryguide.com

HBV Serology

HBV Serology: First Principles and Pattern Interpretation Authors: Sean Spence, Kelly Burak* Reviewers: Crystal Liu, Kara Hawker, Dean Percy, Yan Yu, Sam Lee* * MD at time of initial publication HBsAg HBV Core antigen Marker of HepB infection at some point Anti-HBsAg Denotes immunity HBeAg Anti-HBeAg Presence denotes current HBV infection (chronic or acute) Anti-HBcAg IgM acute/recent infection Anti-HBcAg IgG chronic/remote infection (Due to vaccination or past exposure) Marker of active viral disease and patient infectiousness Detected in chronically infected patients or patients who have cleared infection Never infected, never immunized - - - - - - Chronic infection/carrier + +/- + - +/- +/- Acute infection + + - - + - Natural immunity (past infection) - - + + - +/- Immunized - - - + - - Historical Notes: • HBeAg was previously used as a marker of viral replication • Presence of Anti-HBeAg antibodies indicates that the antigen has been cleared, representing seroconversion and a halt to viral replication • HBV DNA is the current clinical marker of viral replication, and can be used to assess viral load in the body Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published May 5, 2019 on www.thecalgaryguide.com

Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukemia: Pathogenesis and clinical findings Authors: Yan Yu Katie Lin Reviewers: Jennifer Au Natalie Arnold Crystal Liu Lynn Savoie* * MD at time of publication Accumulation of genetic abnormalities in more mature lymphoid cells (usually B-cells) Clonal division of neoplastic B lymphocytes within lymph nodes With continued cell division, B- cells spill over into the peripheral blood Neoplastic B cells fail to die and continue to divide within lymph nodes over time Neoplastic B cell precursors infiltrate the spleen and the bone marrow A small % of CLL patients undergo Richter’s transformation, in which their disease evolves into Diffuse Large B-cell Lymphoma Notes: • CLL is the most common adult leukemia in developed nations. • Prevalence of CLL ↑ with age, occurring most often in older people Slow process of neoplastic cell division Patients are most commonly asymptomatic at initial presentation Multifactorial causes, most Weight loss, malaise, fever/chills, night with unclear mechanisms B-cell are detected as lymphocytes on a CBC Lack of functional B cells ↓ body’s ability to produce antibodies for immune response Neoplastic cells accumulate in lymph nodes sweats Lymphocytosis (B cell count >5x109/L for at least 3 months) Hypogammaglobulinemia Lymphadenopathy ↑ risk for infection, especially by encapsulated bacteria normally killed by antibodies Hypercellular bone marrow (on bone narrow biopsy) Splenomegaly ↑ sequestration of platelets and RBCs ↓ in RBCs ↓ in platelets Anemia Thrombocytopenia (reduced blood clotting ability) Fatigue, shortness of breath Easy bleeding, easy bruising, petechiae Abundance of B-cell precursors in marrow inhibits the development/differentiation of other cell types Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published June 30, 2019 on www.thecalgaryguide.com

perforated-viscous

Perforated “Viscous” (aka. GI tract; bowels): Author: Yan Yu Reviewers: Michael Blomfield, Tony Gu, Dean Percy, Danny Guo Maitreyi Ramran* * MD at initial time of publication Chest X-Ray (CXR) Pathogenesis and Clinical Findings Diverticulitis Crohn’s disease Peptic ulcer (H. pylori infection, NSAID use, ICU stress, etc) Appendicitis Malignant neoplasm Irritates visceral peritoneum, stimulates autonomic nerves Severe inflammation causes destruction of GI tract mucosa Over time, Perforation of the GI tract wall Bowel contents (air, fluids) released into peritoneal cavity Massive peritoneal inflammation Diagnostic investigations if a GI perforation is suspected Dull diffuse abdominal pain Severe, Sharp abdominal pain with peritoneal signs Abdominal X-ray Irritation of parietal peritoneum, stimulates somatic nerves • Abdominal X-ray • Intra-peritoneal air will coat the GI tract surfaces, giving them a faint white outline under X-ray • Chest X-ray of upright patient (Diagnostic) • Intra-peritoneal air will rise above the peritoneal fluid when pt is upright, accumulating under the right hemi-diaphragm. • Note: air under left hemi-diaphragm = normal gastric bubble • CT? Most patients with suspected GI perforation will get a CT scan, but this is not the diagnostic gold standard (and access to CT can be limited, especially in rural settings) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published June 30, 2019 on www.thecalgaryguide.com

acanthosis-nigricans-pathogenesis-and-clinical-findings

Acanthosis Nigricans: Pathogenesis and clinical findings Authors: Laura Chin Reviewers: Taylor Woo Crystal Liu Laurie Parsons* * MD at time of publication Medications E.g. systemic glucocorticoids, injected insulin, oral contraceptives Hyperinsulinemia Insulin inhibits IGFBP 1&2 secretion Genetic Syndromes E.g. Down syndrome, Rabson- Mendenhall syndrome, congenital generalized lipodystrophy Defects in insulin receptor or anti-insulin receptor antibody production Insulin Resistance ↑ IGFR1 binding Type 2 Diabetes Mellitus Polycystic Ovarian Syndrome Obesity Neoplasms E.g. gastric carcinomas Excess IGF-1, TGFα, and FGF production TGFα is structurally similar to EGFα TGFα can bind to EGFR ↑ EGFR binding Inheritable Mutations E.g. FGFR3 activating mutation ↑ free IGF-1 ↑ FGFR binding Moist environment and rubbing of intertriginous skin Skin inflammation and thinning Bacterial or yeast infection Erosions Malodour Dermal keratinocyte and fibroblast growth and differentiation of neck and intertriginous areas, occasionally mucosal surfaces Hyperkeratosis Abbreviations: • IGF-1 – insulin-like growth factor • IGFR1 – insulin-like growth factor receptor-1 • IGFBPs – insulin-like growth factor binding proteins • FGFR – fibroblast growth factor receptor • TGFα – transforming growth factor-alpha • EGFα – epidermal growth factor-alpha • EGFR – epidermal growth factor receptor Hyperpigmentation Crusting Velvety plaques Pain Pruritis Pus Acanthosis Nigricans Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 14, 2019 on www.thecalgaryguide.com

HELLP syndrome pathogenesis and clinical findings

HELLP Syndrome: Pathogenesis and clinical findings Authors: Natalie England Reviewers: Bishwas Paudel Crystal Liu Monica Kidd* * MD at time of publication Aberrant placental development and function (mechanism still under investigation) Abnormal maternal immune tolerance of placentation in early pregnancy Polymorphisms of FasL and receptor gene ↑levels of placental FasL in maternal circulation Lesions in membrane separating maternal and fetal circulation Release of inflammatory products from placenta into maternal circulation Systemic maternal inflammatory response (activation of coagulation and complement pathways) Microvascular endothelial activation, dysfunction, and damage Widespread platelet aggregation and agglutination ↓ amount of platelets measurable on complete blood count Low platelets HELLP Syndrome RBCs are sheared as they flow through damaged vessels Microangiopathic hemolytic anemia (MAHA) Lab findings indicative of hemolysis: normocytic anemia, high LDH & bilirubin, low haptoglobin Microthrombin in hepatic circulation Damage to hepatocytes Elevated liver enzymes Hemolysis, Elevated Liver Enzymes, Low Platelets Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 14, 2019 on www.thecalgaryguide.com

Lyme Disease Pathogenesis and Clinical Findings

Lyme Disease: Pathogenesis and clinical findings Authors: Victoria Chang Reviewers: Taylor Woo Crystal Liu Yan Yu* Richard Haber* * MD at time of publication Abbreviations: • OspC – outer surface protein C of B. burgdorferi Tick bite from Borrelia burgdorferi infected Ixodes pacificus (western black-legged tick in British Columbia, Canada) Tick bite from Borrelia burgdorferi infected Ixodes ricinus (tick from European countries) Tick bite from Borrelia burgdorferi infected Ixodes scapularis (Deer tick/black-legged tick in SE Canada and NE United States) Binding of OspC (a surface protein expressed by B. Burgdorferi) to human plasminogen allowing the spirochete to spread from bite site to other host organs and tissues B. burgdorferi spreads through skin and other tissues via bloodstream in human host. If tick bite lasts 36-72 hours or more, this is sufficient time for ticks to transmit the infection. (<36 hours of tick attachment results in a lower rate of infection: 1.2% -1.4%) Lyme Disease A vector-borne, infectious multi-system disease with highest risk in late spring and summer by the spirochete Borrelia burgdorferi Early Disease Stage (<30 days) Macrophages and T-cells produce ↑ inflammatory (TNF- α, IFN-γ) and ↑ anti-inflammatory cytokines, causing eosinophils to concentrate adjacent to the tick bite site Early Disseminated Disease Stage (<3 months) B. burgdorferi attach to host cell integrins Pro-inflammatory response with production of matrix glycosaminoglycans and extracellular matrix proteins which have an affinity to attack collagen fibrils on the heart, nerves, and joints 1. Multiple erythema migrans 2. Meningitis 3. Meningoradiculoneuritis 4. Cranial nerve palsies 5. Carditis 6. Borrelial lymphocytoma Late Disease Stage (>3 months) Ongoing and repeated innate and adaptive host immune response to B. burgdorferi Chronic inflammatory state results in synovial hypertrophy, vascular proliferation, and ↑ mononuclear cell infiltrate in large joints Large joint arthritis (most commonly affecting the knees) Erythema migrans (a slowly expanding red skin patch with partial central clearing resulting in a “target clearing lesion” appearance) at site of tick bite Systemic inflammatory response after dissemination of the spirochete to body tissues and organs Flu-like symptoms (fever, chills, muscle aches, headache, fatigue, joint aches, swollen lymph nodes) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 24, 2019 on www.thecalgaryguide.com References • David A. Wetter and Colin A. Ruff. CMAJ August 09, 2011 183 (11) 1281; DOI: https://doi.org/10.1503/cmaj.101533 • https://www.canada.ca/en/public-health/services/diseases/lyme-disease/causes-lyme-disease.html • Borrelia burgdorferi Infection-Associated Surface Proteins ErpP, ErpA, and ErpC Bind Human Plasminogen. Catherine A. Brissette, Katrin Haupt, Diana Barthel, Anne E. Cooley, Amy Bowman, Christina Skerka, Reinhard Wallich, Peter F. Zipfel, Peter Kraiczy, Brian Stevenson. Infection and Immunity Dec 2008, 77 (1) 300-306; DOI: 10.1128/IAI.01133-08 • https://www.uptodate.com/contents/what-to-do-after-a-tick-bite-to-prevent-lyme-disease-beyond- the-basics • Murray, T. S., & Shapiro, E. D. (2010). Lyme disease. Clinics in laboratory medicine, 30(1), 311–328. doi:10.1016/j.cll.2010.01.003 • Weedon, David. Weedon's Skin Pathology E-Book: Expert Consult-Online and Print. Elsevier Health Sciences, 2009.

intraventricular-hemorrhage-in-preterm-infants-clinical-findings-and-complications

Intraventricular hemorrhage (IVH) in preterm infants: Clinical findings and complications Authors: Alexa Scarcello Reviewers: Nicola Adderley, Emily Ryznar, Yan Yu*, Jennifer Unrau* * MD at time of publication Volpe Grading Grade I: germinal matrix hemorrhage with no or minimal IVH (<10% of ventricular area) Grade II: IVH (10-50% of ventricle) Grade III: IVH (>50% of ventricle; usually distends lateral ventricle) Grade IV/Intra-parenchymal echodensity (IPE): periventricular hemorrhagic infarction Inflammation/dysfunction of arachnoid villi ↓ absorption of CSF 2° to obstruction of arachnoid villi Communicating hydrocephalus (IVH grades II-IV) Venous congestion Venous infarction Periventricular hemorrhagic necrosis Destruction of periventricular motor tracts Cerebral palsy Rapid significant blood loss ↓ intravascular blood volume Hypotension ↓ bloodflow to the brain to support brain function Intraventricular Hemorrhage (IVH) hemorrhage in periventricular subependymal germinal matrix Ultrasound: blood in germinal matrix, ventricles, or cerebral parenchyma Sudden ↓ hematocrit Blood irritates contiguous structures Variable neurologic findings; including altered level of consciousness, hypotonia, apnea, etc Neuro- developmental abnormalities (varying severity) See slide - Hydrocephalus: Clinical Findings in Pediatrics This mechanism leads to three different possible clinical manifestations: 1. Silent Presentation (most common) 2. Stuttering/Saltatory Course: non-specific findings - hypotonia, apnea, altered level of consciousness, bradycardia, and ↓ Spontaneous movements 3. Catastrophic Deterioration (least common) Stupor or coma, decerebrate posturing, seizures, bradycardia, metabolic acidosis, bulging fontanelles, abnormal pupillary reflexes, inappropriate ADH secretion Notes • Incidence & severity are inversely proportional to gestational age • 50% occur within 1st day of life, 90% by 3rd day • As explained in the flow chart, the postnatal clinical presentations of IVH fall into three categories (1-3) • Symptoms of catastrophic bleeds are uncommon and usually caused by rapid significant blood loss with subsequent neurologic findings 2° to meningeal irritation, inflammation, and potential mass effect/acute hydrocephalus; severe bleeds may also occur in the absence of clinical findings attributable to IVH Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 27, 2019 on www.thecalgaryguide.com

Vitamin K Deficiency

Vitamin K Deficiency: Pathogenesis and Clinical Findings Author: Sean Spence Reviewers: Michael Blomfield, Tony Gu, Tristan Jones, Yan Yu Man-Chiu Poon* Lynn Saviole* * MD at initial time of publication Dietary Deficiency Small bowel bacterial overgrowth Antibiotic use Disruption of normal flora ↓ Gut flora synthesis Vitamin K Deficiency ↓ vitamin K dependent gamma carboxylation of clotting factors II, VII, IX, X Gastrointestinal mucosal diseases (e.g., Celiac disease) Pancreatic insufficiency Cholestasis Malabsorption Exposure to vitamin K antagonists (e.g., warfarin) Inhibition of vitamin K epoxide reductase ↑ bleeding tendency Gastrointestinal tract bleeds Intracranial bleeds Hemarthoses (bleeding into joints) Easy bruising Petechiae, purpura Heavy menstrual bleeds Prolonged PT/INR Note: PT/INR is more sensitive and validated for warfarin monitoring ↓ Activity of intrinsic clotting pathway Prolonged PTT ↓ Activity of extrinsic clotting pathway Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published July 27, 2019 on www.thecalgaryguide.com

Normocytic Anemia

Normocytic Anemia: Causes, Signs, and Symptoms Authors: Katie Lin Yan Yu Reviewers: Andrew Brack Jessica Tjong Man-Chiu Poon* Lynn Savoie* * MD at time of publication Aplastic anemia: hypo-proliferation of bone marrow RBC precursors Anemia of Chronic Disease Splenomegaly ↑ RBC sequestration within enlarged spleen Acute bleeding Hemolysis (infection, autoimmune, RBC structural defects) ↓ RBC production ↑ RBC destruction/elimination Normocytic Anemia: [Hgb] <120g/L in females, <140g/L in males, with the RBC mean corpuscular volume (MCV) still within the normal range: 80-100 fL RBCs that ultimately end up in the blood are still qualitatively normal/functional; there is a quantitative shortage of these RBCs in the blood relative to body needs Spurious/False normocytic anemia: Any fluid overload state (pregnancy, heart failure, kidney disease, etc.) can ↑ plasma volume which can dilute RBCs and cause apparent anemia, but the mean volume of each RBC is still normal Normocytic Anemia Heart needs to work faster to pump sufficient oxygenated blood to tissues ↑ Heart rate Reduced oxygen- carrying ability of blood Patient feels oxygen- deprived, needs to inhale more oxygen as compensation Dyspnea (shortness of breath) ↑ Respiratory rate (RR) Not enough oxygen being delivered to body tissues, including brain Fatigue Reduced absolute number of RBCs means less RBCs to color the blood red Pallor (especially conjunctival and palmar) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published July 27, 2019 on www.thecalgaryguide.com

Appendicitis

Appendicitis: Pathogenesis and Clinical Findings Authors: Yan Yu Wayne Rosen* Reviewers: Wendy Yao Laura Craig Noriyah AlAwadhi* * MD at time of publication Dull, crampy, diffuse peri- umbilical pain Pt may develop fever, diarrhea, constipation, vomiting or anorexia as inflammation worsens Focal, intense, persistent RLQ pain, abdominal guarding and peritoneal signs (i.e. percussion and rebound tenderness Epidemiology Dx of healthy adults: • Men > women • Commonly 10-30 years old, can present at any age • Most common cause of acute abdomen (5% prevalence in all ethnicities) The appendix is anatomically located in the RLQ; appendicitis may be confused with disorders of surrounding structures: Gynecological Diseases • RuleoutpregnancywithHCG pregnancy test • Rupturedovariancyst • Ectopicpregnancy • Mittelschmerz(mid-cycle pain) Gastro-intestinal Diseases • Meckel’sdiverticulum (presents identically to appendicitis; surgically located 2 feet from ileocecal valve; mostly seen in children) • Diverticulitis(presentsasleft sided appendicitis) Non-GI Abdominal Issues • Mesentericadenitisinkids <15: swollen mesenteric lymph nodes • Renalcolic Obstruction of appendiceal lumen (by fecalith, fibrosis, neoplasia, foreign bodies or lymph nodes in kids) Appendix distension and spasms ↑ lumen pressure, ↓ blood flow to appendix Ischemia, tissue necrosis, loss of appendix structural integrity Bacterial invasion of the appendix wall, causing transmural inflammationandnecrosis Stretching of visceral peritoneum, stimulation of autonomic nerves T9-T10 Progression of inflammation over several days (variable length of time) Irritation of parietal peritoneum, stimulation of somaticnerves If appendix not surgically removed Perforation of colon wall, causing peritonitis, abscesses or death Note: Symptoms hugely variable. Only 30% present with classic history. Diagnosis is mostly clinical. Further investigations: CBC: Leukocytosis (due to inflammatory response) CT: Gold standard test. Thickened visceral membrane with enhancing (white) rim due to ↑ blood flow Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published July 27, 2019 on www.thecalgaryguide.com

Acute GI Related Abdominal Pain

Acute GI-Related Abdominal Pain: Pathogenesis and Characteristics Authors: Yan Yu Wayne Rosen* Reviewers: Laura Craig Danny Guo Julia Heighton Maitreyi Raman* * MD at time of publication Peritoneal cavity Visceral peritoneum (innervated by autonomic nerves) Bowel stretching, pulling, contracting Abdominal pain type: Diffuse, non-localized Dull, crampy, periodic Not associated with movement Patient may writhe around, trying to get rid of the pain Mesentery Intestinal lumen Parietal peritoneum (innervated by somatic nerves) Cross-section of the GI tract Cuts, structural damage, and inflammation in the bowel Important Notes • Acute abdominal pain can also result from non- gastrointestinal causes, such as kidney stones, female reproductive tract issues, and urinary tract issues. For simplicity’s sake, only the GI-related acute abdominal pain disorders are listed here. • The DDx of visceral abdominal pain is broad. Please consult relevant sections of the Calgary Black Book for the DDx. • Keep in mind that visceral abdominal pain can also be caused by the “acute abdomen” diseases (if the diseases are presenting in their initial phases). • • • • • • Abdominal pain type: Sharp, well-localized Excruciatingly painful, persistent Associated with movement of bowels Patient often lies still to avoid abdominal vibration Peritoneal signs Abdominal guarding, pain with abdominal vibration (coughing, shaking, percussion, palpation) Transition from diffuse to localized pain can indicate disease progression (e.g. from visceral to parietal peritoneal inflammation) Note: bowel obstruction may or may not present as acute abdominal pain Bowel Infarction Appendicitis Diverticulitis Acute Cholecystitis Acute Pancreatitis Perforated Ulcer DDx of an “acute abdomen”: A sudden, non-traumatic disorder of the abdomen that needs urgent diagnosis and treatment. Each topic will be further explored in their respective slides. Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published July 27, 2019 on www.thecalgaryguide.com

Operative vaginal delivery Complications of Vacuum

Complications of operative vaginal delivery (vacuum) Vacuum Authors: Alexa Scarcello Reviewers: Claire Lothian, Crystal Liu, Yan Yu*, Ron Cusano* * MD at time of publication Maternal trauma to surrounding structures to fit operative device Traction and torsion on flexion point of fetal head, between anterior and posterior fontanelles Pressure of device directly on fetal scalp Pop-offs of vacuum cup Rapid decompression and compression forces Separation of underlying structures Bleeding between skull and periosteom of neonate Cephalohematoma ↑ breakdown of RBCs ↑ release of hemoglobin Hemoglobin breakdown à↑ release of bilirubin into the bloodstream Potential interference with spontaneous rotation of trunk ↑ risk of shoulder dystocia Delivery during shoulder dystocia may traumatize infant’s shoulder Brachial plexus injury Head injury leads to potential ocular trauma Retinal hemorrhage Hyperbilirubinemia Fetal scalp lacerations Tentorial tears Intracranial bleeding Perineal lacerations 1° Lacerations: skin, subcutaneous tissue, vaginal epithelium 2° Lacerations: into superficial perineal muscles 3° Lacerations: extending to rectal sphincter 4° Lacerations: extending to rectal mucosa Urethral injury Rupture of emissary veins (connections between dural sinus and scalp veins) Blood accumulation between epicranial aponeurosis and periosteom Subgaleal hemorrhage Large space in between these tissue layers ↑ capacity for blood accumulation here Hypovolemia Death Factors independent of operative device Notes: • • Vacuums are now used more often (compared to forceps) due to ↓ maternal trauma Caution in use if fetus <34wks Jaundice Less operator experience Higher fetal station Poor head Rotation Longer active 2nd stage ↑ complication rate Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Aug 4, 2019 on www.thecalgaryguide.com

Ataxia Telangiectasia Pathogenesis and Clinical Findings

Ataxia-telangiectasia: Pathogenesis and clinical findings Genetics: Autosomal Recessive, with a defect on gene region 22 and 23 on Chromosome 11q Authors: Merna Adly Reviewers: Kara Hawker Crystal Liu Yan Yu* Laurie Parsons* * MD at time of publication Truncation and loss of the ATM protein, a serine/threonine protein Kinase Impaired ability to phosphorylate ATM, a key protein involved in the activation of the DNA damage checkpoint Impaired DNA damage and apoptosis signals Impaired ATM concentration ability at DNA damaged sites Failure to activate apoptosis in specific neural regions Genomically-damaged cells incorporated into the developing nervous system Progressive spinocerebellar granular neural cell damage and Purkinje Cell degeneration Cerebellar Ataxia (at 12-18 months); involuntary muscle contractions, hypotonia, IQ decline, and abnormal eye movement Loss of ATM leads to mitotic defects and arrest in gamete genetic recombination process Gonadal dysgenesis and delayed puberty DNA damage to tumor suppressors such as p53 and BRCA1 Impaired signaling of downstream cell cycle regulators Impaired genome stability and increased disposition to cancer ↑ Acute Lymphocytic Leukemia of T cell origin (in children) and Chronic Lymphoblastic Leukemia (in adults) Impaired recombination of DNA in immune cells Thymic hypoplasia; humoral & cellular immunodeficiency ↓ or absent functional immunoglobulins IgA, IgE, and IgG2 that function to prevent respiratory infections Respiratory infections with bronchiectasis and pneumonia Cells less able to undergo apoptosis in response to ionizing radiation Accumulation of DNA defects in the cells of sun exposed areas such as skin, hair, and conjunctiva Mucocutaneous telangiectasia on the bulbar conjunctiva and ears between 2-6 years of age May progress to involve periorbital skin, trunk, extremities, body folds, and other mucosal surfaces Sterility DNA damage and genomic instability Premature melanocyte stem cell differentiation Premature graying of skin and hair Abbreviations: • ATM – Ataxia-telangiectasia mutated protein • p53 – Tumor protein 53 • BRCA 1 – Breast cancer susceptibility protein. • IgA, IgE, IgG2 – Immunoglobulins Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 4, 2019 on www.thecalgaryguide.com

Diverticulosis and Angiodysplasia

Diverticulosis and Angiodysplasia: Pathogenesis and Clinical Features Diverticulosis Author: Yan Yu Reviewers: Jason Baserman, Jennifer Au Paige Shelemey, Tony Gu Kerri Novak* * MD at time of publication Abnormal Angiogenesis vWF Deficiency Older Ageà weakening the circular muscles strutting the colon High intracolonic pressure (i.e. from peristalsis pushing against colonic waste that’s low in fiber and harder to move) Angiodysplasia Autoimmune Diseases Unclear Mechanisms These patients tend to have “arterial-venous malformations” that rise up to the mucosa of the lower GI tract Irritation of these malformations leads to bleeding into the GI tract lumen Lower GI bleed (occult, slow, asymptomatic, large- volume blood loss, usually associated with iron deficiency anemia) Renal Failure Older Age Gradual expansion over time thins the diverticular wall Capillaries within diverticuli burst and leak blood into the colon lumen Lower GI bleed (usually stops by itself) Colon wall forms little outpouchings (diverticuli) Stretching of colonic serosa stimulates somatic sensory nerves innervating the colon Bloating, cramping (But most often PAINLESS) Trapping of feces in the colonic diverticuli Bacteria have more time to metabolize the undigested materials, producing gas Flautulence Irregular defecation Both conditions share similar features: • Both are common, and their prevalence increases with age • Are relatively benign and most are easy to treat (80% stop w/o intervention) • Both present without pain in a previously-well patient • Together, account for 50-80% of lower GI bleeds (diverticulosis > angiodysplasia) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published August 4, 2019 on www.thecalgaryguide.com

Erythema Nodosum pathogenesis and clinical findings

Erythema Nodosum: Pathogenesis and clinical findings Authors: Merna Adly Reviewers: Taylor Evart Woo Crystal Liu Yan Yu* Laurie Parsons* * MD at time of publication Epidermal layer Dermal-Epidermal Junction Dermal layer Subcutaneous Fat Layer Phase 1-5. Septal Fibrosis made of inflammatory cells, such as T lymphocytes, histocytes and eosinophils Genetic Dysregulation Infections (Ex. Streptococcal Pharyngitis) ~28-48% of cases Medications (Ex. Birth Control Pills, Sulfa drugs) ~3-10% of cases Malignancy (ex. Lymphoma) Autoimmune conditions (ex. Sarcoidosis and Inflammatory Bowel Disease) ~11-25% of cases Pregnancy ~1-3% of cases Antigenic Stimuli / Bacteria / Viruses / Chemical Agents all could trigger the following process: Phase 1. Neutrophils Infiltrate the fibrous septa between fat lobules in the subcutaneous fat Phase 2. Neutrophils release reactive oxygen species, leading to oxidative tissue damage and inflammation Phase 3. Opening of inter-endothelial junction and the migration of more inflammatory cells into the septal venules, including macrophages, histocytes, and eosinophils Phase 4. Macrophages secrete inflammatory cytokines, which stimulates the proliferation of more helper T cells (Th1) Phase 5. Th1 cells secrete more cytokines, leading to the further release of Th1 cytokines and mediating the immune complexes deposition in the septal venules of the subcutaneous fat (panniculitis). The Th1 immune reaction is called Type IV Delayed Hypersensitivity Reaction Phase 6. Activated macrophages produce hydrolytic enzymes and transform into multi- nucleated giant cells, called Miescher’s Radial Granulomas. These consist of small, well defined aggregations of small histocytes arranged radially around a small cleft of variable shapes in the septal venules of the subcutaneous fat Phase 1-4. Lesions are red tender nodules, poorly defined, vary in size from 2-6 cm, and usually on shins ( 1st week) Fat Lobules T lymphocytes Macrophages Note: we’ve done extensive research and can’t figure out why erythema nodosum happens mostly on the shins. If you have an answer, please email us! Phase 5. Lesions become tense, hard, and painful; and they change in color into bluish or livid. (2nd week) Phase 6. Lesions become fluctuant as in abscess, but do not ulcerate. Lesions fade to a yellowish color Epidermal layer Dermal-Epidermal Junction Dermal layer Subcutaneous Fat Layer Phase 6. Miescher’s Radial Granulomas Fat Lobules T lymphocytes Macrophages Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 25, 2019 on www.thecalgaryguide.com

Colorectal Carcinoma pathogenesis and clinical findings

Colorectal Carcinoma: Pathogenesis and clinical findings Obstipation Nausea & vomiting Tenesmus Rectal pain Hematochezia Hydronephrosis (swelling of kidney) ↓ appetite Local bleeding Abdominal Abscess Weight loss Acute blood loss Iron deficiency anemia Classification of tumours/abnormal growths: 1. Adenoma–abenigntumorfromglandular structures 2. Carcinoma–cancerarisingfromtheepithelial tissue of the skin or the lining of internal organs 3. Sarcoma–cancerarisingfromconnectivetissue Mechanical bowel Obstruction Ribbon (thin) stool In rectum Mass effect Tumor ↓ bowel lumencaliber Backed up contents mayberegurgitated Cancerinvadesrectal sphincters, muscles, vessels&nerves Compressing ureters, urine backs up into kidney Compressing stomach Abdominal distension/pain Invades blood vessels Inflammatory Bowel Disease Smoking Abdominal radiation Tubular adenomas (pre- cancerous polyps) Obesity Local growth of tumor Cell line mutations Idiopathic Uncontrolled cell division in the colon and rectum Hereditary syndromes Colorectal Carcinoma (Develops over time) Outside bowel serosa Bowel perforation Bowel to bowel/local organ fistulisation Host immune cells release cytokines to combat cancer Bowel contents leak Metabolic abnormalities, ↑energy use Tumor Spread Mechanisms: 1. Hematogenous 2. Lymphatic 3. Contiguous 4. Transperitoneal Tumor cells spread distally Friable vessels supply tumor Metastatic Disease Vessels Rupture Occult bleeding & melena (black stools) depletes stores of iron Authors: Karly Nikkel Reviewers: Michael Blomfield Tony Gu Yan Yu* Edwin Cheng* * MD at time of publication Tumors develop in liver, lungs, brain, peritoneum and lymph nodes Hematochezia (passage of fresh blood in stool) Slow, chronic blood loss Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 25, 2019 on www.thecalgaryguide.com

iga-vasculitis-henoch-scholein-purpura-pathogenesis-and-clinical-findings

IgA Vasculitis (Henoch-Schönlein purpura) : Pathogenesis and clinical findings Authors: Mia Koegler Nela Cosic Reviewers: Crystal Liu Yan Yu* Martin Atkinson* * MD at time of publication Infectious Agents 50% have preceding upper respiratory tract infections, i.e., influenza virus or Group A Strep Drugs I.e., antibiotics (penicillin, erythromycin), NSAIDs and biologics (tumor necrosis factor α inhibitors) Immunogenetic and cellular predisposition Various genetic polymorphisms alter cell- mediated immune response, IgA levels elevated in 50% of people ↑ Circulating galactose-deficient IgA1 (GD-IgA1). Deficiency in galactosylation of IgAà↓ IgA serum clearanceàadhesion of IgA complexes, which then deposit into the endothelial lining of blood vesselsàattraction of various inflammatory cells to the area: Formation of Secretion of Interleukin 8 (IL8) - cytokine that induces Neutrophils infiltrate Activation of complement immune complexes neutrophilic chemotaxis and macrophage phagocytosis the tissue site factors (C3, C4) Leukocytoclastic vasculitis (histopathologic term for small vessels inflamed by neutrophilic autoimmune response) Inflamed cutaneous vessels become enlarged in clusters Symmetrical palpable purpura (red/purple, non- blanchable papules) distributed on lower limbs and buttocks areas Cutaneous small vessel vasculitis (100%) Inflamed gastric vessels - hemorrhage and edema within bowel wall Gastrointestinal (85%) Colicky abdominal pain (commonly in the periumbilical region), nausea, vomiting Gastrointestinal GI bleeding (hematemesis, melena), Intussusception Glomerular mesangial proliferation and inflammation ↑ mast cell deposition in joints Joints (60-85%) Arthralgia's (common), arthritis (especially knees and ankles) Arthralgia often transient. No permanent sequelae Sympathetic nervous system activation Glomerulosclerosis, tubulointerstitial and podocyte damage Renal tissue ischemia ↑ Na sensitivity in renal tubules (↑ Na and water retention) Renal (10-50%) Increased renin secretion HTN, nephrotic/nephritic syndrome, renal insufficiency Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 1, 2019 on www.thecalgaryguide.com

Negative-Pressure-Pulmonary-Edema

Negative Pressure Pulmonary Edema: Pathophysiology Authors: Mackenzie Gault Reviewers: Arsalan Ahmad Melinda Davis* * MD at time of publication Notes: ET tube: Endotrachial tube Laryngospasm: spasm of vocal cords; may occur on extubation CXR: Chest X-Ray Hypoxia Detected by peripheral chemoreceptors Sympathetic stimulation ↓ ventilation to lungs Airway Obstruction Involuntarily biting ET tube or laryngospasm most common Patient tries to inspire forcefully against obstruction Highly negative intrathoracic pressure Acute ↑ in systemic venous return to right heart ↑ pulmonary blood volume ↑ pulmonary arterial + capillary pressure ↓ pulmonary interstitial pressure ↑ trans-capillary pressure gradient Fluid pushed out of pulmonary capillaries into the interstitium Negative Pressure Pulmonary Edema: Fluid in lungs caused by highly negative intrathoracic pressure alveolus capillary interstitium Frothy pink sputum CXR: diffuse bilateral infiltrates ↓ PO2 ↓ O2 Sats Fluid surrounds alveoli ↓ diffusion of alveolar O2 into pulmonary capillaries If severe: pressure and fluid build-up damages capillary and alveolar walls Fluid & red blood cells from capillaries enter alveoli and are coughed up Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 1, 2019 on www.thecalgaryguide.com

Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome (TTP-HUS): Pathogenesis and clinical findings

Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome (TTP-HUS): Pathogenesis and clinical findings Thrombotic Thrombocytopenic Purpura Hemolytic Uremic Syndrome Shiga toxin from E. coli 0157:H7 infection Acquired ADAMTS13 auto-antibodies Pregnancy/Post-partum Unclear mechanism Failure to cleave large vWF multimers Accumulation of large vWF multimers (Usually broken down by ADAMTS13) Platelet aggregation and formation of platelet thrombi Widespread microthrombi occluding blood vessels causing tissue damage/necrosis Congenital ADAMTS13 mutation Triggering event ADAMTS13 deficiency Drug dependent antibodies target platelets Direct tissue toxicity (unclear mechanism) ADAMTS 13 Inhibition Widespread hemolysis Shut down of complement regulatory genes Uninhibited membrane attack complex formation Drugs (Quinine, Chemotherapy) Abbreviations: • vWF – von Willebrand Factor • ADAMTS13 (vWF cleaving protein) – A Disintegrin And Metalloprotease with a ThromboSpondin type 1 motif, member 13. Formation of fibrin strands Microangiopathic Hemolytic Anemia (schistocytosis) Cellular damage due to fibrin deposit (intravascular, non- autoimmune hemolysis) ↑ serum indirect bilirubin ↑ serum lactate dehydrogenase ↓ serum haptoglobin Authors: Sean Spence Nicole Burma Reviewers: Tristan Jones Yan Yu Man-Chiu Poon* Lynn Savoie* * MD at time of publication Uncontrolled platelet activation and consumption Thrombocytopenia Reduced clotting ability Purpura Central Nervous System (CNS) Confusion, severe headache, focal neurological findings Heart Patchy necrosis of myocardium Arrhythmia, Sudden Cardiac Death Kidney Glomerular damage à↓ GFR + protein leakage into urine Proteinuria, Acute Kidney Injury (AKI) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 1, 2019 on www.thecalgaryguide.com

Acute-diverticulitis

Acute Diverticulitis: Pathogenesis and clinical findings Authors: Yan Yu Wayne Rosen* Reviewers: Laura Craig Noriyah AlAwadhi Danny Guo Erica Reed Maitreyi Raman* * MD at time of publication These regions are perceived in the Left lower quadrant (LLQ) of the abdomen. • PersistentLLQpain,abdominal guarding and peritoneal signs • Constipation/obstipation No bleeding (unlike diverticulosis) Dehydration (low JVP, ↑ resting HR, orthostatic hypotension) Inherent weakness in the muscle layers of the colonic wall Low Fiber diet ↑ Stool transit time (↓colonic motility) Stool build-up, ↑ pressure in colonic lumen Epidemiology • Diagnosis of developed nations, total prevalence = 15% • More prevalent with ↑ age: • 30-50% by age 60 • 70% by age 80 Diverticula most commonly form in the descending and sigmoid colon Triggers cytokine release Irritationofparietal peritoneum → stimulation ofsomaticnerves Inflamed vessels are more permeable & leak fluid from the blood into the colon Mucosal and submucosal layers of the colon wall herniates through the circular muscle layer, creating colonic diverticula Continued stress on diverticula causes micro-perforations → bacterial infection Inflammation of diverticula reaches parietal peritoneum Clotting of blood in the blood vessels feeding diverticula Continued inflammation of diverticula causes complications over time Fever Complete bowel perforation (medical emergency) Fistulae (through bladder, vagina, skin or gut) Colonic fibrosis → GI strictures, colonic obstruction Abscesses Further Investigations: • CBC: leukocytosis (due to inflammatory response) • CT = Gold Standard Diagnostic test: shows inflamed diverticuli as well as complications (i.e. free air in peritoneum due to microperforations) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published September 1, 2019 on thecalgaryguide.com

virchows-triad-and-deep-vein-thrombosis-dvt

Suspected Deep Vein Thrombosis (DVT): Authors: Dean Percy Yan Yu Reviewers: Tristan Jones Ryan Brenneis Man-Chiu Poon* Maitreyi Raman* * MD at time of publication Pregnancy, Oral Contraceptives (OCP) Pathogenesis and Complications Platelet Activation Increased clot formation Hypercoagulable State ↑ ability for the blood to coagulate upon stimulation Inherited Disorders Congenital defect in coagulation (ie. Factor V Leiden, Factor II mutation, Protein S/C deficiency) ↑ blood clotting ability Estrogen promotes hypercoagulability, especially in presence of other risk factors Notes: • Venous thrombus causes pulmonary embolism, arterial thrombus causes stroke • Previous DVT is risk factor for current DVT Trauma/Surgery Malignancy Abnormal release of coagulation-promoting cytokines Systemic injuryà activation of coagulation cascade Hypertension Bacteria Artificial Valve Physically damages blood vessel walls Adhere/invade vessel wall Abnormal surface Vessel Injury Exposes tissue factor on damaged cells and subendothelium for vWF binding Virchow’s Triad Venous Stasis Low blood flow rate over site of vessel injury, concentrating blood clotting factors at that site Fat contains more aromatase, converts more androgens to estrogen Sedentary lifestyle, poor venous return Obesity Clot formation typically occurs in leg veins Deep, large veins allow for blood pooling (stasis, hypercoagulability) Venous return from legs often against gravity (stasis) Valves in leg veins prone to backflow (stasis) ↓ muscle motion = ↓ venous blood flow Fracture, immobilization, bedrest, long vehicle/airplane ride Destruction of vein valve by clot Venous Insufficiency Clot prevents blood from returning to heart. Blood accumulating in the leg results in unilateral leg edema and venous inflammation (redness, warmth, tenderness) 1. 2. 3. Clot embolizes to the lungs Thromboembolus -*Pulmonary embolism (acute life threatening complication) -Chronic thromboembolic pulmonary hypertension Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published September 1, 2019 on thecalgaryguide.com

Acute-Pancreatitis

Acute Pancreatitis: Pathogenesis and Clinical Findings Authors: Yan Yu Reviewers: Laura Craig Noriyah AlAwadhi Ryan Brenneis Maitreyi Raman* * MD at time of publication Associated signs due to intra- abdominal hemorrhage from an unknown mechanism (classically associated with pancreatitis, but happens in <1% of cases): Note: It is not enough to just diagnose “acute pancreatitis”. Full management requires determining underlying etiology with further work-up. Alcohol ↑ Toxic metabolites within pancreas and Spincter of Oddi Spasms Gallstones Migration to common bile duct blocks Sphincter of Oddi Hypertriglyceridemia Unknown mechanism (rare) Idiopathic Further investigations: CBC: Cell counts elevated, due to sever hypovolemia Serum [Lipase]: Gold Standard Diagnostic Test; rupture of pancreatic cells releases lipase into circulation Pancreatic secretions back up, ↑ pressure within pancreas Hypercalcemia (Rare; Ca2+ depositions in bile ducts block outflow of pancreatic secretions) Since pancreas is retroperitoneal, somatic nerves in the parietal peritoneum are directly stimulated Inflammation triggers cytokine release Inflamed pancreas irritates adjacent intestines, causing ileus Inflamed, more permeable blood vessels leak fluid into pancreas • • Cullen’s sign (bruising in peri-umbilical region) Grey-Turner’s sign (bruises along both flanks) Sudden, severe epigastric pain (with peritoneal signs), radiates to the center of the back Fever, nausea/vomiting (general signs of inflammation) Diminished bowel sounds Profound dehydration (flat JVP, hypotension, tachycardia, oliguria) – may happen, not always 1. Pressure compresses pancreatic blood vessels, causing tissue ischemia. 2. Activation of inactive proteases (zymogens) digesting pancreatic tissue Necrosis (death) of pancreatic cells Inflammation self- perpetuates Massive systemic inflammatory response 2 main complications, usually detected on CT; may happen, but not always 1. Pancreatic pseudocyst (enlargement of the pancreas due to fluid accumulation) 2. Pancreatic necrosis/abscesses (death of a part of the pancreas) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-published September 1, 2019 on thecalgaryguide.com

Peptic Ulcer Disease

Peptic Ulcer Disease: Pathogenesis and clinical findings H. pylori (gram negative rod bacteria) Toxin release Inflammatory response Inhibition of H+ detection in gastric antrum H+ over-secretion NSAID use (including ASA +/- other anti- platelet agents) Ischemia Zollinger–Ellison Syndrome (↑ acid secretion due to gastrin secreting tumor) Stress (in ICU setting) Crohn’s disease Cancer (adenocarcinoma, SCC, lymphoma) ↑ Mucosal Injurious Substances: Acid: Gastrin, Histamine, AChàpromote acid secretion in parietal cell Toxins: drugs (for instance, NSAIDs) directly toxic to gastric epithelial cells, drugs that reduce platelet adhesion/plug Authors: Dean Percy Yan Yu Reviewers: Sean Spence, Jason Baserman Paige Shelemey, Tony Gu, Kerri Novak* * MD at time of publication COX-1 inhibition Decreased prostaglandins ↑ H+ production, ↓ gastric mucous production Toxicity to Gastric epithelial cells ↓ Gastroprotective Factors: • Mucous: barrier between cells and HCl • Blood flow: removes H+, supports mucosal cells • Epithelial cells: physical barrier, HCO3- buffer • Prostaglandins: ↓ H+ secretion, ↑ mucous • • production Erosion of Mucosa Erosion proceeds into blood vessels Irritation of somatic innervation (T5-T8) Bleeding into stomach Bleeding into esophagus Hematemesis (Vomitting Blood) Blood passes through GI tract, becomes oxidized by HCl & digestion Melena (black, tarry, foul- smelling stool) Blood gets oxidized by HCl but moves back into esophagus ‘Coffee-ground’ Emesis Notes: Dyspepsia, Epigastric Pain Nausea • COX-2 inhibitors not always effective for gastroprotection • In elderly patients and patients on NSAIDs, mucosal erosion can be silent (asymptomatic) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published September 22, 2019 on thecalgaryguide.com Mechanism not well understood

Rapid Sequence Induction and Intubation (RSII): Clinical Approach

Rapid Sequence Induction and Intubation (RSII): Clinical Approach Authors: Sandy Ly Reviewers: Wendy Yao Melinda Davis* * MD at time of publication Reversible with Sugammadex (selective relaxant binding agent) Responds to acetylcholinesterase Reversible with acetylcholinesterase inhibitors Not immediately reversible due to high dose Classical RSII Modified RSII Induction Agent e.g. Ketamine or Propofol (2 mg/kg) Inhibitory effect on central nervous system Cricoid pressure (10 lbs pressure posteriorly) Esophagus at the level of the cricoid obstructed Reduced gastric regurgitation Succinylcholine (2 mg/kg) acts similar to Ach Depolarize end plate nicotinic receptors in skeletal muscle Non-competitive with no antagonist Rapid skeletal muscle paralysis (<30 seconds) with short duration (<10 minutes) Irreversible Preoxygenation with 100% O2 displaces nitrogen. Functional residual capacity (2.5L) is filled with O2 Oxygen consumption (250 mL/min) Extend time to desaturation (Ideal condition: 10 minutes) Gastric distension with use of bag valve mask ventilation (positive pressure) High dose Rocuronium (1 mg/kg) competitively antagonizes Ach Decreased Ach binding on nicotinic receptors in skeletal muscle Rapid skeletal muscle paralysis (<60 seconds) with long duration (>45 minutes) Quick Facts Induction of anesthesia Abbreviations Ach – acetylcholine See other pathways for more detailed pathophysiology • • • RSII is used in patients with increased risk of gastric aspiration. Cricoid pressure is NOT THE SAME as BURP (backward, upward, rightward pressure). Other induction agents possible (e.g. etomidate). Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 22, 2019 on www.thecalgaryguide.com

Priapism

Priapism: Pathogenesis Post-cavernosal venous occlusion ↑ nitric oxide from cavernous nerve plexus and cavernosal sinus endothelia Impaired detumescence (erection-ending) pathways Post-cavernosal venous drainage is mechanically obstructed e.g. sickle cell disease, dialysis etc. Ischemic (Low-flow): Inadequate venous function Blood pools in corpora cavernosa Cavernosal cell metabolism uses O2 and releases CO2 into pooled blood Trabecular smooth muscle relaxes Cavernosal artery smooth muscle relaxes Lack of norepinephrine action on penile SM Post-cavernosal venules are compressed against tunica albuginea Trabecular smooth muscle and cavernosal artery smooth muscle do not contract ↑ pressure in corpora ↑PCO2 ↓pH Acidosis ↓PO2 Tissue hypoxia Tissue damage Irreversible fibrosis leading to erectile dysfunction Priapism Prolonged erection lasting more than 4 hours; in absence of sexual stimulation; not relieved by ejaculation Trauma to penis or adjacent areas Authors: Arsalan Ahmad Reviewers: Alec Mitchell Darren Desantis* Yan Yu* * MD at time of publication Cavernosal artery is damaged Excessive, unregulated arterial blood flow into corpora cavernosa Pain Non-ischemic (High-flow): Uncontrolled arterial flow ↑ volume of blood in corpora ↑ pressure in corpora Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 22, 2019 on www.thecalgaryguide.com

Infantile Colic

Infantile Colic: Pathogenesis & Clinical Findings Gastrointestinal (GI) factors ↑ bile acid wasting ↓ bile acid production in immature in immature gut enterohepatic circulation ↓ bile acid availability Psychosocial factors Infant temperament Over/understimulation Parental variables (e.g. parental stress) Collectively, these factors influence the infant’s reactivity to adverse stimuli and the caregiver’s perception of whether crying is problematic. Other biologic factors Poor feeding techniques: under/ overfeeding, swallowing air, infrequent burping Altered gut motility GI discomfort Infantile Colic Dietary intolerances: cow’s milk protein, lactose ↑ gas production and gut distension ↓ mucosal barrier function Loss of bacteriostatic effects of bile acids Immature enteric nervous system Intestinal microbial imbalance ↑ intestinal permeability ↑ systemic inflammation Altered central and enteric neuronal function via microbiota-gut-brain axis Altered perception of pain and other GI stimuli Crying for no apparent reason that lasts > 3 hours/day and occurs ≥ 3 times/week for > 3 weeks in an otherwise healthy infant < 3 months old. There must be normal growth, development, and physical exam. Colic itself is a benign, self-limiting condition that resolves with time. Facial flushing or grimacing Tense or distended abdomen Drawing up of legs Clenching of fingers Stiffening of arms Arching of back Distress expressed via behaviour Loud, high- pitched, urgent cry ↑ risk of non- accidental trauma GI factors directly affect infant’s behaviour Hypothesized role of immature CNS regulation of circadian rhythm ↑ parental stress Immature regulation of behaviour Episodes cluster in evening and/or late afternoon ↑ risk of post- partum depression Paroxysmal crying Inconsolable Authors: Simonne Horwitz Nicola Adderley Reviewers: Crystal Liu Yan Yu* Danielle Nelson* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 28, 2019 on www.thecalgaryguide.com

Macrosomia-Fetal-Complications

Macrosomia: Overview of Fetal Complications 1Macrosomia Authors: Brielle Cram Reviewers: Nicola Adderley, Crystal Liu, Yan Yu*, Danielle Nelson* * MD at time of publication (A fetus larger than 4000- 4500 grams) Size discrepancy between fetal shoulders and maternal pelvic inlet Anterior shoulder becomes impacted behind the symphysis pubis during delivery Shoulder Dystocia (↑risk in infants of diabetic mothers – see slide on Gestational Diabetes) Injuries acquired as a result of the birthing process in an infant with shoulder dystocia ↑ incidence of preterm birth Surfactant deficiency Respiratory Distress Syndrome Umbilical cord compression ↓ delivery of oxygenated blood to fetus Hypoxia/Asphyxia Infant gasping Perinatal aspiration of stained amniotic fluid Meconium Aspiration Syndrome ↑ incidence of cesarean deliveries ↓ duration/absence of labour ↓ release of maternal epinephrine and glucocorticoids ↓ activation of epithelial sodium channels on type II pneumocytes Delayed resorption of fetal lung fluid Transient Tachypnea of the Newborn Notes ↑ oxygen demands Fetal hypoxia ↑ production of erythropoetin Polycythemia Neonatal Jaundice Maternal diabetes ↑ intrauterine exposure to excessive nutrients and glucose 2Fetal Hyperinsulinism ↑ glucose utilization and suppression of hepatic glucose production Termination of the maternal glucose supply at delivery Hypoglycemia Brachial Plexus Injury Clavicular Fracture Humeral Fracture 1. Complications of macrosomia ↑ with birth weight. Risk of stillbirth ↑ above 5 kg 2. Most common in the setting of poorly controlled maternal diabetes; however, hyperinsulinism may be absent if macrosomia is secondary to a different etiology (e.g. post-term fetus, genetic conditions). Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 22, 2019 on www.thecalgaryguide.com

intrauterine-devices-iuds-mechanism-of-action

Intrauterine Devices (IUDs): Mechanisms of Action Authors: Danielle Chang Reviewers: Mirna Matta Crystal Liu Aysah Amath* * MD at time of publication Intrauterine Device (IUD) Contraceptive device that sits in the fundus of the uterus Two Types Copper T-shaped polyethylene with fine copper wrapped around the vertical stem and arms Releases copper in the uterus Progesterone Releasing IUD made of plastic containing levorgestrel (synthetic progesterin, progesterone receptor agonist) Releases levorgestrel in the uterus Stimulate progesterone receptors May inhibit ovulation through negative feedback on hypothalamus (not consistent evidence) Foreign body reaction in endometrium IUD creates local lysosomal activation and uterine inflammatory response Mechanism not fully understood Spermicidal High copper concentrations toxic to sperm Alters sperm mobility Decreases chance of fertilization Suppresses endometrium Thickening of the cervical mucus Barrier to sperm penetration Disturbs function of endometrium Changes uterine environment Thins the endometrium Decreases number of blood vessels to the endometrium Suppresses proliferation Atrophies endometrial glands Sloughing of the endometrium Inflammatory reaction against blastocyst if fertilization occurred Hostile environment for implantation Decreased menstrual blood loss and eventual amenorrhea Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 12, 2019 on www.thecalgaryguide.com

X-linked Severe Combined Immunodeficiency (SCID)

X-linked Severe Combined Immunodeficiency (SCID): Pathogenesis & clinical findings Abbreviations: • Ig: Immunoglobulin • IL: Interleukin • NK: Natural Killer • Th2: T helper 2 cell • Treg: T regulatory cell ↓ IL-15 signaling ↓NK cell differentiation and proliferation ↓ or absent NK cells in the blood, bone marrow and peripheral lymphoid tissues Impaired innate immune system Chronic Stress Response Mutation of the IL2-RG gene encoding the interleukin receptor common gamma chain located on the X-chromosome ↓ IL-2 signaling ↓T cell proliferation Sequence analysis shows mutated, duplicated or deleted IL2-RG gene ↓ IL-7 signaling Global ↓ in lymphocyte survival Absent thymic shadow on X-ray ↑ susceptibility to fungal infections Complete defect in cell mediated and humoral immunity ↓ antibody responses to vaccinations ↑ susceptibility to extracellular pathogens, most notably bacteria Authors: Kyo Farrington Reviewers: Paul Adamiak Jessica Tjong Louis Girard* *MD at time of publication ↓ IL-4 signaling ↓Th2 differentiation ↓T cell help for B cell activation and class switching Dysfunctional B cells Genetic Predisposition ↓ Treg development ↑ risk of developing an autoimmune disease ↓ T cell response to mitogens or anti-CD3 stimulation ↓ or absent T lymphocytes in the blood, bone marrow and peripheral lymphoid tissues ↑ susceptibility to viral infections (often gastrointestinal ones like rotavirus and/or enterovirus) Chronic diarrhea Hypoplastic lymphoid tissues (I.e. tonsils, adenoids, lymph nodes) Hypermetabolic State Failure to thrive ↓ antibody production in response to antigen exposure ↓ IgA, IgM and IgG serum concentrations Note: IL2-RG gene encodes the interleukin receptor common gamma chain, which is a sub-unit common to the receptor complexes for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. The bolded/italicized cytokines contribute most to the pathophysiology of X-linked Severe Combine Immunodeficiency (SCID). Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published October 12, 2019 on www.thecalgaryguide.com

Ischemic Colitis

Ischemic Colitis: Pathogenesis and clinical findings Superior and inferior mesenteric arteries (SMA and IMA) supply blood to colon Surgical repair of aorta Borders of SMA and IMA collaterals at the splenic flexure and rectosigmoid junction are vulnerable to ischemia (“watershed” areas) Atherosclerosis and narrowing of mesenteric arteries Low flow state (e.g., CHF, hypotension, arrhythmia) Underlying CAD/PVD Atrial fibrillation, endocarditis Embolic arterial occlusion of SMA and/or IMA Trauma, infection, clotting abnormalities Mesenteric vein thrombosis Vascular risk factors (e.g., smoking, hypertension) Thrombotic arterial occlusion of SMA and/or IMA Endograft coverage of IMA Nonocclusive hypoperfusion Inadequate blood flow to meet the cellular metabolic needs in the colon Ischemic Colitis Tachypnea Tachycardia Hyperthermia Hypotension Ischemic period Loss of oxygen and nutrients to bowel Reperfusion period Influx of O2àreacts to produce more oxygen free radicals Lipid peroxidation Systemic inflammatory response syndrome* Nausea and vomiting Abdominal pain (generally left sided) Peritonitis Leukocytosis Systemic shock (inadequate perfusion to tissue) Author: Audrey Caron Michael Blomfield Reviewers: Tony Gu Yan Yu* Edwin Cheng* * MD at time of publication Systemic shock (inadequate perfusion to body tissue) Hematochezia (Bloody stool) Gangrene (tissue death) Hemorrhage Tissue damage/cell death (starting from mucosa and submucosa going outwards to serosa) Mucosal ulceration Colonic inflammation Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 10, 2019 on www.thecalgaryguide.com

Incisional-Hernia

Incisional Hernia: Pathogenesis and clinical findings Penetration of abdominal wall from prior surgery, in combination with: Dead and injured cells from incision Small blood vessels rupture Plasma seeps out of vessels and collects together Nutritional deficiency ↓ absorption of fat soluble vitamins Chronic illness Cirrhosis Diabetes Malignancy Immuno- suppressive therapy Ascites Heavy lifting Multiple complex mechanisms (including hyper- glycemia & immune dysfunction) that ↑ risk of infection Post-op wound Infection Obesity Chronic constipation Chronic cough Pregnancy ↓ clotting factors Vigorous cough Severe Hypertension Seroma Post-op hematoma Bulging fluid separates High risk Sutures unsuitable Poor surgical for tension technique ↑ intraabdominal pressure Fascial Incision separates Notes: fascial incision surgeries* High Risk Surgeries* Connective tissue disorder Suboptimal fascial closure • • • Emergency surgeries Midline incisions Acute abdominal surgeries ↓ wound healing/collagen synthesis Fascial defect at previous incision site Incisional Hernia: Protrusion of tissues through prior fascial incision • Deep wound infection = most common cause of incisional hernias • Diagnosis on physical exam +/- CT scan if patient is obese • Treatment = surgery Bulge at prior incision site Palpable fascial defect Bowel and other abdominal contents protrude through defect Mechanical bowel obstruction (see relevant slide) Constipation /obstipation Contents unable to be pushed back through defect (incarceration) Vascular supply is compromised to herniated contents Contents become ischemic (strangulated) Prolonged pressure on skin & bowel over time Ulceration & ischemia ↓ blood flow to skin layers Discoloration of skin Bulge ↑ with coughing/straining Ulcers extend through bowel wall Authors: Karly Nikkel Meaghan Ryan Reviewers Michael Blomfield Tony Gu Yan Yu* Edwin Cheng* *MD at time of publication Colo-enteric fistula Bowel Perforation Abdominal Pain Abdominal Distension Nausea/ Vomiting Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 13, 2019 on www.thecalgaryguide.com

Endometritis

Endometritis: Pathogenesis and clinical findings Prolonged rupture of membranes > 24 hours between amnion rupture and delivery ↑Time for vaginal flora to ascend into the uterus Assisted vaginal delivery Use of forceps or vacuum Multiple digital vaginal exams Manual examination of the vagina to assess cervical dilation Internal monitoring Intrauterine device to monitor the fetus or contractions Group B Streptococcus colonization Opportunistic bacteria present in the normal vaginal flora of up to 30% of women Bacterial Vaginosis Overgrowth of anaerobic bacteria with associated decrease in protective Lactobacillus species Foreign bacterial ascension into the uterus Sepsis Cesarean delivery ↑ Exposure of vaginal flora to the uterus Introduction of bacteria directly into the uterus Spread of infection to myometrial and parametrial layers of uterus Authors: Gabrielle Wagner Reviewers: Danielle Chang Crystal Liu Aysah Amath* * MD at time of publication ↑ Susceptibility to bacterial invasion of the uterine lining Endometritis Postpartum infection of the uterine endometrial lining Activation of innate Fever, immune response Inflammation of uterus Leukocytosis Accumulation of WBCs within vaginal discharge Purulent or foul-smelling lochia (vaginal discharge) Uterine tenderness Pelvic and/or abdominal pain Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 26, 2019 on www.thecalgaryguide.com

Hydrocele

Hydrocele: Pathogenesis and clinical findings Non-communicating Communicating Congenital patent processus vaginalis Communication between peritoneal cavity and the scrotum Free flow of peritoneal fluid into tunica vaginalis Authors: Luc Wittig Ryan Brenneis Reviewers: Alec Mitchell Darren Desantis* * MD at time of publication Notes: • Hydroceles are typically asymptomatic. • Communicating hydroceles may produce a cough impulse or decrease in size after laying down. Localized infection or trauma Previous varicocelectomy or inguinal surgery Impaired fluid drainage Imbalance between secretion and absorption of fluid in tunica vaginalis Testicular or scrotal malignancy Spermatic cord can still be felt above the testicle & accumulated fluid Accumulation of fluid within tunica vaginalis Hydrocele Increased scrotal fluid volume Increased volume stretches layers of the scrotum Scrotal swelling and heaviness Increased pressure on the testicular structures Accumulated fluid allows light to disperse through the scrotum Fluid motion can occur with external pressure on scrotum Positive fluctuation Compression/ irritation of nerves and pain sensitive structures Scrotal discomfort Longstanding compression of vascular supply, ↓ nutrients to testicles Positive pinch test (done to rule out hernia) Transillumination Testicular Atrophy Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 26, 2019 on www.thecalgaryguide.com

Varicocele

Varicocele: Pathogenesis and clinical findings Authors: Luc Wittig Ryan Brenneis Reviewers: Alec Mitchell Darren Desantis* * MD at time of publication Notes: • 90% present as left sided. • Primary varicocele ache and scrotal venous distention can be relieved by superincumbent positioning (increases venous return). • Small varicoceles can be identified by preforming the Valsalva maneuver (decreases venous return). • Unilateral right varicoceles are uncommon and should be investigated for underlying pathology causing obstruction. Primary Anatomically: the left spermatic vein drains into the left renal vein Nutcracker Effect: The left renal vein can get pinched by the abdominal aorta and superior mesenteric artery Backup of blood in left renal vein ↑ pressure in left spermatic vein Secondary Renal cell carcinoma or retroperitoneal masses Inferior vena cava thrombus External compression of spermatic vein Obstruction of blood flow ↑ spermatic vein pressure Vein valve leaflet failure & retrograde bloodflow back towards testicle Dilation of pampiniform plexus and scrotal vein plexus Varicocele ↑ scrotal blood volume ↑ volume in a closed space ↑ pressure and distension of scrotal layers ↑ scrotal vein plexus pressure Compliant veins distend, becoming visible through scrotum Blood heats up the structures it flows through Scrotal hyperthermia Unsuitable environment for spermatogenesis Loss of germ cell mass Bag of Worms Sign Dull ache/heaviness Decreased fertility Testicular atrophy Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 26, 2019 on www.thecalgaryguide.com

Aphasia

Aphasia (Wernicke’s and Broca’s): Pathogenesis and clinical findings Authors: Davis Maclean Reviewers: Heather Yong Tony Gu Yan Yu* Scott Jarvis* *MD at time of publication Ischemic stroke (common) Local Invasion (e.g. by a tumour, Head infection, or hemorrhage) Trauma Intracerebral Hemorrhage Dementia (e.g. Fronto- temporal Dementia) Episodic occurrences (e.g., migraine, epilepsy) Damage to language-dominant cerebral hemisphere (the left hemisphere, for the majority of humans): Damage affecting Broca’s Area in the Inferior frontal gyrus (area 44 & 45) Damage affecting Wernicke’s Area in the posterior part of the superior temporal gyrus (area 22) Localization: Inferior frontal gyrus, superior sylvian fissure Blood supply: superior division M2 branch middle cerebral artery Localization: Posterior perisylvian region, temporal lobe Blood supply: inferior division M2 middle cerebral artery Sensory speech areas still intact (posterior superior temporal lobe) Intact comprehension (intact hearing & reading) Impaired function of Broca’s Area ↓ output or generation of speech/ text If function of nearby motor areas is also impaired Contralateral hemiparesis (face, arm > leg) If function of other nearby areas is also impaired Impaired naming and repetition Motor speech areas still intact (inferior frontal lobe) Fluent (but non-sensical) speech output Impaired function of Wernicke’s Area Impaired compre- hension (i.e. cannot understand speech or text) Loss of sensory speech input to motor areas Errors in word usage, tense, structure If function of nearby sensory areas is impaired Contralateral sensory deficits Broca’s Aphasia Wernicke's Aphasia (Expressive language impairment: non-Fluent) Notes/Definitions: (Receptive language impairment/Fluent: the person can talk but their speech is nonsensical) • Dysarthria ≠ Aphasia (Dysarthria: disruption to neurons controlling the muscles that produce sounds, resulting in slurred/disjointed speech. Aphasia: acquired deficit in language comprehension or generation/output usually due to disruption of neurons in the cerebral cortex.) • “Global” aphasia affects both receptive and expressive language. Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 1, 2020 on www.thecalgaryguide.com

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A1AT-Deficiency

α1AT Deficiency: Pathophysiology and Clinical Findings Authors: Sean Spence Reviewers: Danny Guo Yan Yu Merna Adly Crystal Liu Sam Lee* * MD at time of publication Abnormal α1-Anti-Trypsin (α1AT) allele(s) Accumulation of mutant α1AT protein as ordered polymers in endoplasmic reticulum of hepatocytes ↓ α1AT inhibition of Hepatocyte Injury tissue proteases (Mechanism unclear) ↓ release from hepatocytes Cirrhosis, chronic hepatitis, hepatocellular carcinoma ↓ lung elasticity, ↓ ability for lung to expel air on expirationà gas trapping, hyperinflation, airway collapse over time Role of Genetics: Low serum α1AT In the skin: Subcutaneous proteases > Anti- proteases Unopposed proteolysis in subcutaneous tissues Panniculitis (Rare, most cases associates with ZZ Genotype) Lung Proteases > Anti-proteases àproteolytic destruction of lung parenchymaàpanacinar emphysema (accelerated by smoking) Stigmata of chronic liver disease (ascites, jaundice, spider nevi, petechiae, etc.) Symptoms of chronic obstructive pulmonary disease (COPD): barrel chest/High residual volume (RV), low vital capacity (VC), wheezes on auscultation, etc) – see relevant slide Degree of α1AT deficiency dependent on genotype: • MM gives normal α1AT levels • MZ genotype produces levels ~ 35% of normal • ZZ genotype produces severe deficiency ( <10% of normal) • Null phenotype is completely deficient of α1AT N.B. Heterozygotes almost never develop phenotypic α1AT deficiency syndromes. Even some homozygotes don’t manifest the disease. Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published January 12, 2020 on www.thecalgaryguide.com

Viral-Hepatitis

Viral Hepatitis: Pathogenesis and clinical findings Infection with a virus that targets the Authors: Sean Spence Tyler Anker Yan Yu Reviewers: Dean Percy Crystal Liu Sam Lee* * MD at time of publication liver, e.g. HAV, HBV, HCV, HDV, HEV Hepatocytes are invaded & damaged Foreign particles and tissue damage activate immune systemàliver inflammation Lysis (bursting) of hepatocytes Infection with chronic viruses (HBV and HCV) persist over time and additional symptoms may develop RUQ pain/tenderness If infection is prolonged or severe, inflammation becomes systemic Release of hepatocyte’s cellular contents into the bloodstream Infection with acute viruses (HAV and HEV) resolve over time, and the symptoms above normalize Notes: • HDV can only infect people with concomitant HBV infection • HAV and HBV vaccines are the only ones that currently exist • Not all patients with viral hepatitis will develop each of these symptoms. The presentations vary. Fever, nausea, vomiting ↑ serum ALT, AST ↓ Hepatic metabolic activity (e.g. reduction of gluconeogenesis) ↓Serum Glucose ↓ Synthesis of plasma proteins (albumin, clotting factors, etc) ↓ Albumin, ↑ INR Abbreviations: • HAV - Hepatitis A Virus • HBV - Hepatitis B Virus • HCV - Hepatitis C Virus • HEV - Hepatitis E Virus • RUQ - Right Upper Quadrant • ALT - Alanine Aminotransferase • AST - Aspartate Aminotransferase • INR - International Normalized Ratio ↓ Bilirubin clearance from blood, bilirubin ends up under the skin Jaundice Portal Hypertension Encephalopathy, Splenomegaly, Esophageal Varices, Ascites, Caput Medusae, Edema Encephalopathy, Muscle Wasting, Metabolic Bone Disease, Terry’s Nails, Ascites, Bruising, Clubbing, Edema Spider Nevi, Altered Hair Patterns, Testicular Atrophy, Gynecomastia, Palmar Erythema Progressive deterioration in liver function, possibly ending up in cirrhosis. (See slide on “Cirrhosis: pathogenesis and complications” for more details on mechanisms and full explanations.) Hepatic Insufficiency Hyperestrogenism Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published January 12, 2020 on www.thecalgaryguide.com

Multiple-Myeloma

Multiple Myeloma: Pathogenesis and clinical findings Plasma cell populations in the body normally produce non-clonal (a diverse array of) immunoglobulins Normal SPEP: no spike in the gamma (γ) region Notes: • MGUSismuchmorecommon than MM! • “Plasmacell”:Blymphocytes that produce antibodies/ immunoglobulins Stimulation by specific antigens Genetic changes/mutations accumulate over time in one type of plasma cell Abbreviations/Definitions: • SPEP - Serum Protein Electrophoresis • Ig – Immunoglobulin • Monoclonal – “of one specific genetic strain or subtype” One type of plasma cell starts to proliferate abnormally Monoclonal Gammopathy of Undetermined Significance (MGUS) (Premalignant, mild monoclonal plasma cell proliferation; asymptomatic) In 1-2% of cases, further cytogenetic changes over time stimulate further proliferation of this plasma cell line Multiple Myeloma (MM) (extensive monoclonal B lymphocyte proliferation, causing end organ damage) Slightly more monoclonal plasma cells will produce slightly more monoclonal Immunoglobulins Small spike in the gamma (γ) region of the SPEP (less prominent compared to the spike in MM) More monoclonal plasma cells result in far greater amounts of monoclonal immunoglobulins being secreted Large spike in gamma (γ) region of the SPEP Ig light chains accumulate in the tubules of kidney nephrons Light chain casts obstruct tubules Renal Insufficiency (↓GFR) Osteoblasts ↑ expression of RANK-ligand (RANKL, an apoptosis regulator), and ↓ expression of Osteoprotegerin (OPG, a decoy receptor for RANKL) ↑ osteoclast activity vs osteoblast activityàbone loss Clonal plasma cells overrun normal bone marrow, crowding out production of red blood cells, ↓ red blood cell counts Anemia Authors: Tristan Jones, Tyler Anker, Yan Yu Reviewers: Jennifer Au, Crystal Liu, Man- Chiu Poon*, Lynn Savoie* * MD at time of publication Damaged bones hurt, & become more brittle Bony pain, pathologic fractures Osteolytic bone lesions Osteoclasts release calcium from bone and into blood Hypercalcemia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 12, 2020 on www.thecalgaryguide.com

Pathophysiology-Behind-the-Leukemias

Pathophysiology Behind the Leukemias Authors: Yan Yu, Katie Lin Reviewers: Jennifer Au Merna Adly Crystal Liu Lynn Savoie* * MD at time of publication Point Mutation (in DNA) Chromosomal Abnormality (duplication, loss, recombination error) Combinations of these genetic defects causes reduced tumor suppressor gene expression and/or increased oncogene expression Initiating Mutational Event ALL Any combination of mutations, chromosomal alterations, or other genetic abnormalities that creates a neoplastic cell (incapable of regulating cell growth/division). AML CLL CML Translocation between Chr 9 and Chr 22à Philadelphia chromosome ( abnormal Chr 22) àBCR-ABL1 oncogene (along with other genetic abnormalities) • In White Blood Cells and their precursors: Lack of cell growth inhibition and / or apoptosis. • Over stimulation of cell division/growth Neoplastic blood cell incapable of regulated cell division Neoplastic cells uncontrollably divide in a monoclonal way: one neoplastic cell originates all successive cells Genes regulating differentiation/maturation disrupted, affected neoplastic cells are incapable of further differentiation/maturation Genes regulating maturation remain intact (affected neoplastic cell is capable of further differentiation/maturation) Some neoplastic cells take time to mature furtheràless rapid disease progression (more indolent disease); cells don’t die CLL: Chronic Lymphoid Leukemia Note: Although it is tempting to group the leukemias together for study purposes, it is best to learn the 4 main types of leukemias independently of one another, as they have a uniquely different pathophysiology and clinical presentation Specific mutations cause slower disease progression CML: Chronic Myeloid Leukemia Degeneration during CML’s ”blast crisis” Specific mutations cause rapid division and buildup of existing neoplastic cells àAcute/rapid disease progression. ALL: Acute Lymphoblastic Leukemia AML: Acute Myeloid Leukemia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published January 19, 2020 on www.thecalgaryguide.com

Aqueous-Humor-Production-and-Drainage

Aqueous Humor Production and Drainage: Physiology Authors: Natalie Arnold, Graeme Prosperi-Porta Reviewers: Paige Shelemey, Crystal Liu, Bill Stell* * MD at time of publication Blood plasma passes through fenestrated capillary walls in the ciliary body Anterior ciliary body produce aqueous humor (AH) through combined hydrostatic pressure + active transport AH enters the posterior chamber AH flows around the lens through the pupil into the anterior chamber Temperature gradient cause aqueous humor to flow convectively: downwards at the cornea (colder, fluid denser); upwards at lens (warmer) Abbreviations: • AH – Aqueous Humor • TM – Trabecular Meshwork Provides nutrition, removes wastes, and transports neurotransmitters to the avascular lens and cornea. Circulates inflammatory cells to avascular structures Maintains structural integrity of ocular structures via intraocular pressure (10-21 mmHg) AH leaves the anterior chamber via two pathways located near the limbus Limbus Trabecular Meshwork Pathway (~60-80 % of flow) AH passes through the TM layers: Uveal, corneoscleral, and juxtacanalicular Flows into Schlemm’s Canal Flows through internal outflow channels into the external outflow channels, aqueous veins, intrascleral venous plexus, and the deep scleral venous plexus Drains into the episcleral and conjunctival veins Uveoscleral Pathway (~20-40 % of flow) AH enters uveal meshwork and anterior ciliary body Flows in suprachoroidal space Passes outward through the sclera Enters the scleral, and conjunctival veins Drains back into systemic venous circulation Inflow Trabecular Outflow Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 19, 2020 on www.thecalgaryguide.com

Innate-Immune-Response

Innate immune response: Pathogenesis and clinical findings Authors: Erin Stephenson Reviewers: Jessica Tjong Crystal Liu Nicola Wright* * MD at time of publication Pathogens overcome chemical barriers (e.g., lysozyme, low pH) Pathogens overcome physical barriers (e.g., epithelium, cilia) Trauma Damage-associated molecular patterns Pathogen-associated molecular patterns Examples of tissue-resident macrophages: • Alveolar macrophages – Lung • Histiocytes – Connective tissue • Kupffer cells – Liver Recognition by pattern recognition receptors (e.g., toll-like receptors) • Mesangial cells – Kidney • Microglial cells – Brain • Osteoclasts – Bone Microbe engulfed and exposed to oxidative burst Microbes destroyed Pus Pro-inflammatory chemokines Recruitment of circulating granulocytes and monocytes Pro-inflammatory cytokines (e.g., IL-1β, TNFα, IL-6) Tissue-resident macrophage activation Antimicrobial proteins Unresolved infection/ inflammation Antigen presented to T cells Recruitment of adaptive immune response Enhanced immune responses Acute phase protein production by liver (i.e., C- reactive protein) Prostaglandin production in the hypothalamus Fever Endothelial tight junctions on vasculature disrupted Intravascular fluid leak into extravascular space Edema Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 19, 2020 on www.thecalgaryguide.com

vomiting-pathogenesis

Vomiting: Pathogenesis Authors: Julena Foglia Reviewers: Varun Suresh Matthew Harding Haotian Wang *Yan Yu *Eldon Shaffer *MD at time of publication Intracranial: Trauma, Infection, Tumor, Stroke ↑ Intracranial pressure Mechanism Unknown Irritation of GI mucosa: Inflammation, Distention, Chemotherapy, Radiation Activates receptors in gut mucosa GI Disease: Upper: GERD, PUD, Cancer Lower: Ischemia, obstruction, IBD Mechanical pharyngeal stimulation Signal travels via vagal and sympathetic afferent nerves Metabolic: Pregnancy, Diabetes, Uremia, Thyroid disease, Hypercalcemia Pain, Smells, Foul Sights, Memories Sensory inputs to cortical region Cerebral Cortex Vomiting (Emetic) Center Toxins circulating in bloodstream: Chemotherapy, Opioids Offending substance travels through circulation and binds to receptors in the CTZ, outside the blood brain barrier Abbreviations: GERD: Gastroesophageal Reflux Disease PUD: Peptic Ulcer Disease IBD: Inflammatory Bowel Disease CTZ: Chemoreceptor Trigger Zone CNX: Cranial Nerve Ten H1: Histamine Receptor M1: Muscarinic Receptor Disrupted inner ear balance: Motion Sickness Activation of H1 & M1 receptors in vestibular center traveling via Cerebellum Stimulates Solitary Tract Nucleus (Medulla) (Medulla) Vagus Nerve (CNX) and enteric nervous system activation, resulting in: Gastric relaxation, ↓ pylorus tone, retrograde duodenal peristalsis Downward diaphragm contraction, abdominal & chest wall muscles contract: ↑ intra-gastric pressure Vomiting (Forceful expulsion of material from stomach and intestines) Upper and lower esophageal sphincter relaxation and glottis closure Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-published February 16, 2020 on www.thecalgaryguide.com

Pseudogout

Pseudogout: Pathogenesis and clinical findings Authors: Usama Malik Yan Yu* Reviewers: Jennifer Au Stephanie Nguyen Martin Atkinson* * MD at time of publication Familial chondrocalcinosis Overactivity of the NTPPPH enzyme and mutations in the ANKH gene,↑ pyrophosphate production Hyperparathyroidism ↑ levels of parathyroid hormone produced, ↑ gut Ca2+ absorption Hemochromatosis Clearance of calcium pyrophosphate dihydrate (CPPD) crystals from joints is inhibited by iron Hypomagnesia The relative absence of magnesium impairs pyrophosphatase activity, reduces pyrophosphate breakdown Hypophosphatasia Defective mineralization of calcium and phosphorous in bones Idiopathic (vast majority of cases) Mechanism unknown ↑ serum concentrations of Ca2+ or Pyrophosphate Enhanced mineralization in chondrocytes (cells that make cartilage) Abbreviations • NTPPPH nucleoside triphosphate pyrophosphohydrolase • CPPD – Calcium Pyrophosphate Dihydrate Notes: • There are different types of calcium pyrophosphate crystal deposition (CPPD) disease. This slide only covers “pseudogout”. • Pyrophosphate (PPi) = 2 phosphate molecules = P2O74− • Pyrophosphate is made from the breakdown of Adenosine triphosphate (ATP): ATP -> AMP + PPi Once in cartilage, high levels of either calcium ions or pyrophosphate can result in them binding together, forming CPPD crystals Aggregated CPPD crystals shed into synovial fluid Neutrophils enter joint to phagocytose the crystals and release pyrophosphatase enzyme Repeated crystal precipitation into joint space over time (subacute process) CPPD crystals collect on collagen fibers in articular cartilage Chondrocalcinosis, seen on high-resolution ultrasound and/or x-ray CPPD crystals exhibit unique properties on polarizing microscopy Inflammatory cascade Positively birefringent (crystals appear blue parallel to axis of polarizer) PAINFUL, warm, swollen joint (sudden onset) ↑ C-reactive protein (CRP); erythrocyte sedimentation rate (ESR) Knees and wrist subjected to more trauma over a person’s lifetime Knee > Wrist >>> any other joint affected Wearing down of joint cartilage over time Rapidly progressive osteoarthritis (see osteoarthritis slide) Subchondral sclerosis & cysts, joint space narrowing, and osteophytes seen on x-ray bone loss, hemarthrosis Nerve damage over time “Charcot-like” joint: severe weightbearing to areas that joint destruction/deformity, Painless joint Lack of sensation can cause tolerate it poorly Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 16, 2020 on www.thecalgaryguide.com

C5-C9-deficiency

C5-C9 deficiency: pathophysiology and clinical findings Authors: Heather Yong Reviewers: Jessica Tjong, Crystal Liu, Yan Yu*, Nicola Wright* * MD at time of publication Normal complement response The complement pathway is a non- specific response to bacterial pathogens Bacterial infection Classical, alternative, or lectin pathway activation Complement cascade MAC formation on bacterial surface C5b, C6, C7, C8, C9 Complement proteins create trans- membrane channels within bacterial cell walls/cell membranes Critical bacterial proteins leak out of the cell, breakdown of entire cell Primary (hereditary) causes Secondary (acquired) causes All are autosomal recessive Biologic therapy ex. eculizumab Absence or suboptimal functioning of Abbreviations: • MAC: Membrane Attack Complex • CH50: Classic Hemolytic Complement Test • AH50: Alternative Hemolytic Complement Test • CNS: Central Nervous System • CSF: Cerebrospinal Fluid ≥1 terminal complement proteins C5-C9 deficiency Inability to form MAC ↑ susceptibility to systemic Neisseria infection Commonly N. meningitidis Rarely N. monorrhoeae Nasopharyngeal colonization of N. meningitidis, ↑ susceptibility to bacteremia CH50 ± AH50 assay No lysis Note: Total complement activity assay <10% activity C5, C6, C7, C9 <50% activity C8 Varied bactericidal action via other complement proteins • Risk of invasive meningococcal disease is 1000-10000X higher in C5-C9 deficiency than in the general population • Reason is unknown • C5-C9 deficient patients are not at greater risk for contracting other gram (-) infections • Clinical meningitis in C5-C9 deficiency is less severe and fatality is rare Bacterial lysis Especially gram (-)ve bacteria like Neisseria Bacteria cross the blood-brain barrier, causing swelling and damaging brain tissue Fatigue, fever, headache, altered mental status, etc. Inflammation of CSF and meninges Activation of dura and pia mater fibres Headache, neck stiffness Bacteria release toxins Damage to surface blood vessels Maculopapular rash Exact mechanism unknown Recurrent meningitis CNS damage due Sepsis to recurrent meningitis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 16, 2019 on www.thecalgaryguide.com

tinea-capitis-tinea-corpora-and-tinea-pedis

Tinea capitis, tinea corpora, and tinea pedis: Pathogenesis and Clinical Findings Authors: Kara Hawker Reviewers: Crystal Liu Yan Yu* Laurie Parsons* * MD at time of publication Injured skin Scars Burns ↑ CO2 content Factors favoring fungal invasion Factors predisposing host’s skin to infection ↑ environmental humidity Note: Infections caused by dermatophytes are referred to as “tinea” or “ring-worm” infections due to their characteristic ringed lesions Fungi most commonly causing dermatophytic infections (in order): 1. Trichophyton 2. Epidermophyton 3. Microsporum Direct contact with infected humans, animals, or inanimate objects Dermatophyte invades uppermost, non-living, keratinized layer of skin, the stratum corneum Dermatophyte produces enzyme keratinase Keratinase catalyzes degradation of keratin proteins in the skin Dermatophyte burrows deeper into skin Keratinocytes release inflammatory cytokines in reaction to dermatophyte antigens Dermatophyte moves outwards, away from site of infection, to new areas around the initial site Classic pink-to-red ringed lesion, with central healing Tinea corporis Scaling of skin (such as between the toes: “maceration”) Invasion of hair follicle Hair shaft breaks Alopecia (loss of hair) Pruritis(itchiness) Erythema (redness) Induration (swelling) Heat Local inflammatory response in skin Tinea capitis Tinea pedis Infection of the foot (aka. Athlete’s foot) Infection of the scalp Infection of the trunk and extremities of the body Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 17, 2020 on www.thecalgaryguide.com

Brain-Neoplasms

Brain Neoplasms: Pathogenesis and clinical findings Authors: Steven Chen, *Yan Yu Reviewers: Calvin Howard, Heather Yong, Tony Gu, *Scott Jarvis * MD at time of publication Metastatic Lesions (e.g., primary tumour from breast, lung, gastrointestinal, prostate) Mutagen exposure (e.g., radiation, carcinogens) Errors of DNA replication Acquired cell mutations leading to uncontrolled cell division in the brain Inherited diseases (e.g., neurofibromatosis, tuberous sclerosis) Primary Brain Tumours (e.g., gliomas, meningiomas, pituitary adenomas) Brain Neoplasms Tumors in the brain arising from brain tissue itself (primary) or from non-brain tissue (metastatic) Tumor produces vascular endothelial growth factor (VEGF) which generates new vessels (angiogenesis) Tumor occupies intracranial space ↑Intracranial pressure Tumor irritates grey matter Seizures Headaches Papilledema Tumor outgrows and disrupts its blood supply Cerebral ischemia and/or necrosis Critically located tumors may damage specific neural pathways Tumor invades, infiltrates, or replaces normal brain parenchyma Friable blood vessels within tumor àeasy bleeding Brain hemorrhage Disrupted blood- brain barrier ↓ blood vessel integrity à ↑ serum leaks out Edema Injury to localized brain regions; symptoms vary depending on location of brain affected: ↑ penetration of substances (e.g., drugs, toxins) Mass pressing on surrounding structures (mass effect on brain) Frontal lobe damage Personality change Cerebellar damage Ataxia Occipital lobe damage Visual deficits If adjacent to 3rd/4th ventricles, tumor will impede flow of cerebrospinal fluid Obstructive Hydrocephalus Stretching of meninges; activation of mechanoreceptors affecting the chemoreceptor trigger zone Vomiting Nausea Brain tissue pushed down beyond the tentorium cerebelli, squeezing on brain stem Brain Herniation Note: Clinical findings tend to be similar for primary brain tumors and intracranial metastases. Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 17, 2020 on www.thecalgaryguide.com

Umbilical-Cord-Prolapse

Umbilical Cord Prolapse: Pathogenesis and clinical findings Prematurity or PPROM PROM Membranes rupture before contractions Lack of contractions to help move fetus into optimal position rupture of Low birth weight Smaller fetal size relative to maternal pelvis and amniotic fluid Mal- presentation Fetus not in optimal (head down) position for delivery e.g. transverse presentation Abnormal placentation Poly- hydramnios If membranes are ruptured, there is a large volume of fluid that may push the umbilical cord through the cervix Multiple gestation (second twin) Multiparity Multiple fetuses distend uterus ↑ laxity of the uterus ↑ space for cord to come down Smaller fetal size Fetus has not shifted into optimal delivery position ↑ space for fetus to move around in once first twin delivered Placenta implanted near or over cervical opening Large intrauterine space ↑ risk of mal- presentation Abbreviations: • PROM: Premature The fetus does not adequately block the cervical opening Umbilical cord comes out through the cervix before the fetus does Umbilical Cord Prolapse Obstetrical emergency: Umbilical cord descends through the cervix before or alongside the fetus Authors: Gabrielle Wagner Reviewers: Danielle Chang, Crystal Liu, Yan Yu*, Aysah Amath* * MD at time of publication membranes • PPROM: Preterm premature rupture of membranes Visible or palpable umbilical cord Cord compression Presenting part of the fetus compresses the cord as the fetus descends through the birth canal Umbilical vasospasm Exposure of the cord to cold or touch causes arterial vasospasms within the cordà↓ blood flow to fetus Ante/intrapartum Fetal hypoxia Post-Partum Neonatal hypoxic-ischemic Cerebral Neonatal encephalopathy palsy death Complicated variable fetal Prolonged fetal heart rate decelerations bradycardia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 17, 2020 on www.thecalgaryguide.com

mechanisms-of-opioid-analgesia-in-the-peripheral-nervous-system

Mechanisms of opioid analgesia in the peripheral nervous system Authors: Davis Maclean Reviewers: Heather Yong Tony Gu Yan Yu* Carlos Camara- Lemarroy* * MD at time of publication Exposure to opioid Natural Naturally occurring extracted from opium poppy (e.g. morphine) Exogenous Opioids derived from external source Semi-synthetics Synthesized from natural sources (ex. heroin) Synthetics Entirely created via synthesis (ex. fentanyl) Endogenous Opioids produced naturally in the body Released in response or in anticipation of to painful stimuli Endorphins Enkephalins Dynorphins Inhibition of adenyl cyclase ↓ conductance of presynaptic Ca2+ channels ↑ conductance of postsynaptic K+ channels ↓Activity and production of cAMP Activation of G- protein coupled receptors ↓ neuro- transmitter release Inhibition of postsynaptic neuron Blockage of nerve transmission Binding to opioid receptor subtypes in nervous tissues mu (μ), kappa (k) delta (δ) - Majority of clinically relevant analgesic effects relate to mu (μ) receptor ↓ Release of Substance P and Glutamate in the dorsal horn of spinal cord ↓ Peripheral nociceptive signaling to thalamus and other brain areas Inhibition of pain transmission to brain Inhibition of GABA- releasing neurons in Periaqueductal grey (PAG) area Activation of descending inhibitory pathways from PAG Other/Systemic Side Effects (For complete list and mechanism see Calgary Guide – Side effects of Opioids Abbreviations: cAMP (cyclic Adenosine mono-phosphate) – Cellular signaling molecule GABA (gamma-Aminobutyric acid) – Inhibitory neurotransmitter Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 4, 2020 on www.thecalgaryguide.com

pharmaceuticals-under-investigation-by-who-for-treating-covid-19-proposed-mechanisms

Pharmaceuticals under investigation by WHO for treating Author: Hannah Yaphe Reviewers: Davis Maclean, Timothy Fu, COVID-19 (Corona Virus Disease 2019): Yan Yu*, Stephen Vaughan* * MD at time of publication Note: This slide is based on literature available up to 03/30/2020. Medicines shown here are those included in the WHO SOLIDARITY trial, which were selected based on in vitro work and clinical data from MERS and SARS. Mechanisms are preliminary and there is insufficient data to support or refute the use of these agents for COVID- 19. Research is ongoing. Viral replication is terminated Fewer new cells infected ↓ activation of inflammatory and immune responses Improvement or halt in progression of clinical signs of infection* *See slide on pathophysiology and clinical findings of COVID19 Proposed Mechanisms COVID-19 Viral Replication Pathway Virus adheres to Angiotensin Converting Enzyme 2 (ACE-2) receptor on body cells Endocytosis of virus in clathrin coated vesicles Vesicles mature through endolysosomal pathway Virus membrane fuses with mature endolysosome releasing viral RNA into cytosol Viral RNA uses host cell ribosomes to make new viral proteins like RNA-polymerase Viral RNA-polymerase incorporates nucleotides from the host cell New viral RNA is produced Viral RNA and proteins packaged into new viral particles Viral particles released from cell Chloroquine or Hydroxychloroquine (CQ, HCQ) Weak basicity leads to ↑ pH of endosomes and lysosomes N-terminal glycosylation of ACE-2 in Golgi is inhibited Abnormal ACE-2 receptor expressed on cell surface Viral membrane cannot fuse with immature endosome Altered virus- ACE-2 interaction impairs entry into host cell Viral contents are not released Interferon-β (IFNβ) (Given with LPV/RTV) Ritonavir (RTV) (given with LPV) Inhibition of CYP450, a drug metabolizing enzyme ↓ degradation of Lopinavir (LPV) ↑ plasma half life and duration of action of LPV Binding to interferon receptor Impaired maturation of endosomes Activation of JAK/STAT pathway Transcription of IFN- regulated genes ↑ expression of antiviral and immunomodulatory proteins Antiviral effects may ↑ response to LPV/RTV (mechanism uncertain) Remdesivir (RDV) RDV is phosphorylated to RDV-triphosphate (RDV-TP) Lopinavir (LPV) Inhibition of viral 3- chymotripsin-like protease Inhibition of viral replication (multiple mechanisms) RDV-TP competes with ATP for binding to viral RNA polymerase Viral protein precursors are not cleaved into mature viral proteins Incorporation of RDV-TP terminates growing RNA Newly formed viral particles can’t infect new cells Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 30, 2020 on www.thecalgaryguide.com

GI-changes-during-pregnancy

Physiologic Changes in Pregnancy: Gastrointestinal (GI) Tract Pregnancyàhormonal and physical changes in the body Mechanisms poorly understood ↑ human chorionic ↑ estrogen ↑ progesterone gonadotropin (hCG) ↑ uterus size Uterus rises into abdominal cavity ↑ intra-gastric pressure ↑ backup of stomach contents Nausea & vomiting In the extreme case: Hyperemesis gravidarum (extreme vomiting causing weight loss, dehydration, ketosis) Liver displaced upwards Liver edge generally not palpable on exam ↑ blood pressure in veins within the abdomen Veins around rectum & anus stretch under pressure ↑ blood flow to the gum tissue ↑ tendency for gingival bleeding & ulceration Gingivitis ↑ neo- vascularization in lesions on skin Pyogenic granuloma of pregnancy (shiny red papule with a raspberry-like surface) Mechanism poorly understood Ptyalism (excessive salivation) Difficulty swallowing excess saliva ↑ gallbladder stasis Biliary sludge given time to solidify within gallbladder Gallstones ↓ mobilization of intracellular calcium within smooth muscle cells Smooth muscle relaxation in tissues such as the gallbladder & GI tract Changes in taste perception Dysgeusia Cultural influences and psychological factors Change in diet and dietary cravings ↓ lower esophageal sphincter tone Retrograde transport of gastric contents into esophagus Gastroesophageal reflux ↓ GI motility Delayed gastric and intestinal emptying Stool builds up in colon, and hardens as water is resorbed Constipation Pooling of blood within rectal veins àvenous thrombosis Hemorrhoids Fragile veins, more easily torn Rectal bleeding Change in gut microbiome Authors: Simonne Horwitz, Yan Yu* Reviewers: Claire Lothian, Crystal Liu, Ronald Cusano* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 29, 2020 on www.thecalgaryguide.com

Fecal-Incontinence

Fecal Incontinence: Pathogenesis and complications Note: The majority of fecal incontinence is multifactorial in cause Authors: Timothy Fu Reviewers: Chronic bowel straining Difficult vaginal delivery Direct internal anal sphincter impairment (controls ~70% of anal resting tone) ↓ anal resting tone Aging: Degene- ration of muscle fibers Movement disorders (e.g. arthritis, Parkinson’s); aging is a risk factorà ↓ mobility ↓ timely access to bathrooms Inflammation of colon (e.g., Ulcerative colitis, Radiation proctitis) ↓ capacity of rectal smooth muscle to stretch ↓ capacity to store stool ↑ urgency of defecation ↑ reflex relaxation of internal anal sphincter Chronic diarrhea, diarrhea- predominant irritable bowel syndrome, laxatives Yan Yu* Erika Dempsey* * MD at time of publication Stretch injury of Pelvic surgery Chronic constipation Build up of solid, immobile mass of stool in the rectum Loose stool is able to flow around impacted stool, exiting anal canal (overflow diarrhea) Sensory neuro- pathy (e.g. Diabetes) Altered mental conditions (e.g. stroke, dementia) pudendal nerve (innervating the pelvic muscles and external anal sphincter) Local neuronal damage Impaired pelvic muscle and external anal sphincter motor control Pelvic trauma Rectal prolapse Direct external anal sphincter impairment ↑ Stool volume ↑ Loose stools Rectal hyposensitivity (↓ perception of rectal distension) Patient fails to sense rectal fullness and voluntarily releases their external anal sphincter Voluntary external anal sphincter contraction is no longer sufficient in closing the anus Loose stool is more prone to escape through anal canal compared to solid stool Continence mechanisms are impaired Fecal Incontinence: The unintentional loss of solid or liquid stool Skin Skin Continence mechanisms are intact, but overwhelmed or ignored infection Skin erythema erosion Inability to control what is widely considered a basic, fundamental bodily process ↑ caretaker burden Social stigma ↑ skin contact with acidic irritant (stool) ↑ rate of institutionalization, (e.g., admission into long-term care) ↓ confidence, sense of agency ↑ stress, anxiety Skin inflammation ↓ social activity, work ↓ help-seeking ↓ treatment Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 2, 2020 on www.thecalgaryguide.com

Placenta-Previa

Placenta Previa: Pathogenesis and Clinical Findings Authors: Wendy Yao, Yan Yu* Reviewers: Danielle Chang, Crystal Liu, Aysah Amath* * MD at time of publication Note on Physical Exam: • Do not perform bimanual exam during vaginal bleed until placenta previa is ruled out (2nd trimester onwards) • If patient presents with bleeding, a pelvic exam = risk of damaging placentaàmore bleeding • Use transvaginal ultrasound to confirm location of placenta Previous C/S Multiple gestation Maternal smoking Placenta Previa Presence of placental tissue that extends over the internal cervical os. (Pathogenesis unknown; preceding textboxes are risk factors only) Previous placenta previa Increased maternal age Increased parity Total placenta previa Placenta completely covers the cervix Partial placenta previa Placenta covers cervix partially Marginal placenta previa Placenta near the edge of the cervix Diagnosed early in pregnancy on routine abdominal ultrasound at 18-20 weeks Stretching of lower segment of uterus during 3rd trimester OR Alternate scenario: One scenario: This stretching elongates the space between the cervix and the placenta, relocating the stationary lower edge of the placenta away from the cervical os Placenta previa resolves on its own Reassuring: Placenta >2cm from cervical os on ultrasound This stretching fails to move the placental away from the cervical os Previa persists as uterus changes in preparation for labour: Thinning of the lower segment of the uterus Uterine contractions Shearing forces to the placental attachment site Painless bright red vaginal bleeding (90%) ↑ risk of clinically significant hemorrhage Cervix becomes thinner (effaced) and opens (dilates) Bleeding limits oxygen delivery to placenta, injuring placental tissue Tissue injuryàActivates intracellular G-protein signalling pathways Release of stored intracellular calcium àmyometrial contraction Uterine contraction and bleeding (10%) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 2, 2020 on www.thecalgaryguide.com

Humoral-Immunity

Humoral immunity: Pathogenesis and clinical findings Authors: Erin Stephenson Reviewers: Jessica Tjong Crystal Liu Yan Yu* Nicola Wright* *MD at time of publication Memory B cells are long-lived detectors Memory B cells sequester in storage sites (e.g. lymph nodes, spleen) or circulate in the blood Memory B cells proliferate and differentiate into plasma cells in response to re- exposure to antigen ↑ Rate and amplitude of secondary immune response on repeat exposure Antigens (Ag) are produced from pathogens (bacteria, viruses, fungi, parasites) or the patient (via trauma, tumor, metabolism), & circulate in plasma, lymph, or other tissue Clonal expansion (proliferation of the activated B cells) ↑ WBCs (lymphocytosis) Autoimmune disease if B cells recognize self-antigen T cell-dependent Ag: Ag-presenting cells (such as dendritic cells or macrophages) present Ag to CD4+ helper T cells and activate them. Activated helper-T cells then stimulate B cells T cell-independent Ag: Ags such as peptides, carbohydrates and lipids may be directly recognized by B cells, triggering their activation Complement: Circulating serum complement proteins detect and bind Ag. Ags tagged with C3 complement fragment bind B cell co-receptor complex and enhance B cell activation. Abbreviations: Ab – Antibody Ag – Antigen Ig – Immunoglobulin WBC – White Blood Cell Naïve B cells Activated B cells (in secondary lymphoid organs, such as the spleen or lymph nodes) Plasma cells first produce IgM Cytokines and T cells stimulate Ig class switching of B cells (changing the heavy chain constant regions of the Ig molecule) Ig production switches from IgM to IgG, IgA, IgE, or IgD IgG is the most common Ig in immune reactions. IgA concentrates at mucosa, IgE degranulates mast cells, IgD helps mature B cells. Differentiation (into memory B cells or plasma cells) Plasma cells produce antibodies, which contribute to immunity in 3 ways: Opsonization: Abs coat pathogens, helping recognition by phagocytes Neutralization: Abs bind to pathogen surface molecules that are needed to invade host cells, thereby neutralizing them Activate Complement: Abs activate complement proteins via the classical pathway (see Complement Activation slide) Clearance of pathogen by adaptive immune response ↑ Serum Ig Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 2, 2020 on www.thecalgaryguide.com

Diabetic-Nephropathy

Diabetic Nephropathy: Pathogenesis Type I or Type II Diabetes ↑ Glucose uptake & glycolysis in glomerular & tubular cells Poor glycemic control = ↑ Glucose load ↑ Proximal tubule reabsorption of Na via Na/glucose co-transporter ↓ NaCl to distal tubule Activation of tubulo- glomerular feedback at macula densa to kidney ↑ Activation of renin- angiotensin system (RAS) ↑ Intrarenal angiotensin II ↑ Advanced glycation end products (AGE) Shunting of glucose through non- glycolytic pathways (e.g. polyol) Activation of Protein Kinase C (PKC) pathway Excessive production and accumulation of glycolytic intermediates (e.g. sorbitol, hexosamine, succinate) hyperglycemia Succinate via GPR91 ↑ Free radical production (oxidative stress) Activation of cellular signalling, transcription factors and cytokines (e.g. TGF-β-Smad-MAPK, IGF-1, NF-κB) ↑NADPH oxidase activity ↑Blood volume ↑ Blood pressure ↑ Renal perfusion Relative afferent arteriole dilatation, efferent arteriole constriction Initial ↑ in glomerular filtration rate (GFR) Podocyte loss/injury Authors: Steven Chen Shannon Gui Yan Yu* Reviewers: Julia Heighton Ryan Brenneis Sophia Chou* * MD at time of publication Initial glomerular hyperfiltration at time of diagnosis ↓ Production of matrix metallo- proteinases Aberrant extracellular matrix (ECM) protein expression and accumulation Sheer stress to glomeruli à pressure-induced damage ↑ Glomerular basement membrane permeability to proteins like albumin ↓ Extracellular matrix regulation “Metabolic Pathway” Mesangial matrix expansion Kimmelstiel- Wilson lesions (pink hyaline nodules due to accumulation of damaged proteins) Tubular fibrosis Scarred glomeruli are less able to effectively filter blood ↓ in glomerular filtration rate (GFR) Albuminuria Usually occurs after ~5 years from time of diagnosis in T1DM; can occur at time of diagnosis in T2DM Abbreviations IGF: Insulin-like growth factor MAPK: Mitogen-activated protein kinases NADPH: Nicotinamide adenine dinucleotide phosphate NF-κB: Nuclear factor kappa-light-chain- enhancer of activated B cells TGF-β: Transforming growth factor-β Protein endocytosis into tubular cells causing inflammation “Hemodynamic Pathway” Diabetic Nephropathy Overt diabetic nephropathy may take upwards of 15-25 years to develop Note: The mechanisms presented here have been simplified. The cross- talk and signaling between the metabolic and hemodynamic factors do not manifest in a step-wise fashion, but rather occur in parallel. Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 3, 2020 on www.thecalgaryguide.com

Infarctus du myocarde: Antécédents médicaux

Infarctus du myocarde: Antécédents médicaux Infarctus du myocarde (nécrose 8ssulaire) Auteur: Yan Yu Traductrice: Olivia Genereux Réviseurs: Sean Spence Tristan Jones Nanette Alvarez* Marie Giroux* *MD au moment de publication Sang du ventricule gauche reflue à l’oreille[e gauche et finalement s'accumule dans le système vasculaire pulmonaire Haute pression du système vasculaire pulmonaire force fluide hors des capillaires et dans l'interstitium pulmonaire et les alvéoles Inflammation myocardique locale Médiateurs inflammatoires irritent les nerfs cardiaques (plexus cardiaque) ̄ Fonc8on systolique (myocarde nécro6que ne peut pas se contracter suffisamment) Invasion généralisée des cytokines inflammatoires Cytokines agissent les régulateurs de température hypothalamique Fièvre légère Irritation des nerfs sympathiques afférents (T1-T4) Signal entre moelle épinière, a/n dermatomes T1-T4 Cerveau perçoit irritation des nerfs comme douleur des dermatomes T1-T4 Douleur écrasante, pression, oppression de la poitrine: Souvent rétrosternale, avec radiation à épaule, cou et l'intérieur des deux bras (D>G) (Apparition: au repos, crescendo) IrritaNon des branches cardiaques du nerf vague AcNvaNon réponse vasovagale Fatigue, étourdissements, nausée, vomissement ↓ volume systolique (VS) ↓ debit cardiaque (DC) ­ Activité sympathique (pour essayer de maintenir DC) ­ Sueurs (diaphorèse) Peau moite VasoconstricNon généralisé Vasoconstriction des artérioles de peaux Peau froide Interstitium pulmonaire mou ↓ compliance pulmonaire d Fluide compresse les voies respiratoires, ↑ résistance au flux d’air Abrévia8ons: • a/n – au niveau À Noter: Douleur myocardique ischémique peut présenter différemment entre les patients, mais les symptômes récurrents habituellement présentent les mêmes pour un patient donné. Muscles respiratoires travaillent plus fort pour venNler les poumons Essoufflement (difficulté à respirer) Légende: Physiopathologie Mécanisme Signe/Symptôme/Résultats de Laboratoire Complications Publié Janvier 20, 2013 sur www.thecalgaryguide.com

Marfan-Syndrome

Marfan Syndrome: Pathogenesis and Clinical Findings Inherited or acquired mutation in TGFBR1/2 gene (TGF-β receptor) Dural ectasia (widening of the dural sac) Diminished and disorganized dural elastic fibres Abnormalities in connective tissues Tear in the aortic intima (innermost layer of aorta) Aortic dissection Type A (tear in ascending aorta) > Type B (tear in descending aorta) Back pain Sensory and motor deficits Ectopia lentis (lens dislocation) Development of lung bullae and blebs Rupture of bullae/blebs Pneumothorax ** Abnormal properties of lens + cornea ** Scoliosis ** Myopia Tall stature Chest wall (pectus) Inherited (autosomal dominant) or de novo mutation in FBN1 gene Distortion of neural roots Thinning of ciliary zonules of the eye Weakness and rupture of alveolar tissue Production of aberrant or reduced fibrillin-1 Formation of unstable microfibrils in extracellular matrix of connective tissues ** inactivate TGF-β1 ↑ production of matrix metalloproteinases ↑ cellular signaling cascades ↑ production of growth factors in the endocardium Cell proliferation and apoptosis suppression in mitral valve leaflets Change in valvular architecture Mitral prolapse Mitral regurgitation ↑ degradation of extracellular matrix Thinning of the aortic media Weakness of the aortic wall Inability of fibrillin- 1 to sequester and ↑ TGF-β1 signalling Abbreviations • TGF-β: Transforming growth factor beta (a cytokine) Notes **The underlying mechanisms are unclear Authors: Tony Gu Reviewers: Amanda Nguyen Davis Maclean Yan Yu* Michelle Keir* * MD at time of publication Aortic root dilation Aortic valve leaflets stretched outwards, unable to fully close Aortic regurgitation Aneurysmal dilation of the abdominal & thoracic aorta Aortic rupture Stroke Blood enters and pressurizes a ‘false lumen’ Obstruction of aortic branches End organ malperfusion ** deformities ** Joint hypermobility Thumb sign: Thumb tip extends from palm of hand when thumb is folded into closed wrist Wrist sign: thumb and fifth finger of the hand overlap when grasping opposite wrist Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published June 28, 2020 on www.thecalgaryguide.com

GU-changes-in-pregnancy

Physiologic Changes in Pregnancy: Renal & Genitourinary Pregnancy ↑ estrogen ↑ angiotensin synthesis in liver Renin-angiotensin- aldosterone system activation ↑ aldosterone ↑ plasma volume ↑ glomerular filtration rate (GFR) Mechanism unclear, possibly 1) ↑ circulating anti- angiogenic factorsà ↑ permeability of glomerular basement membrane, or 2) ↑ plasma volumeà↓ oncotic pressure of plasma at the glomerulus Proteinuria > 300 mg/day, abnormal in pregnancy ↑ hCG level Dilation of renal vasculature ↑ renal vascular & interstitial volume ↑ filtration surface area Overwhelming load of glucose to proximal tubule ↑ urine output ↑ relaxin secreted by placenta Mechanism not well understood ↓ osmotic threshold for ADH release & thirst ↑ ADH secretion & ↑ oral hydration Incomplete reabsorption of glucose Glucosuria Encourage bacterial growth in the urine Urinary tract infection (e.g. cystitis, pyelonephritis) ↑ serum progesterone Uterine rotation as uterus enlarge due to presence of large bowel Ureter compression (R > L) Ureterovesical reflux (back-flow of urine into the ureters/kidneys) Dilatation of ureters (R > L) (hydroureter) & renal pelvis (hydronephrosis) Progesterone competes with aldosterone ↓ sodium reabsorption ↓ plasma sodium concentration Hyponatremia of pregnancy* (pathological if < 130 mEq/L) *Despite factors favoring sodium excretion, there is a net retention of sodium during pregnancy from adaptation of the renal tubules ↑ urinary stasis ↑ excretion of creatinine and urea in urine ↓ serum creatinine and urea ↓ ureteral toneà ↑potential for ureter dilation Mechanism not well understood ↓ peristalsis of ureters ↑ urinary frequency (voiding > 7x/day) ↑ nocturia (voiding ≥ 2x/night) ↓ oncotic pressure of plasma intra-vascularly àwater leaves blood, enters interstitial tissue, and stays there in gravity-dependent regions of the body Pedal +/- ankle edema Author: Simonne Horwitz Reviewers: Claire Lothian, Crystal Liu, Ronald Cusano*, Candace O’Quinn*, Yan Yu* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published June 28, 2020 on www.thecalgaryguide.com

Retinal-Detachment-Pathogenesis

Retinal Detachment: Pathogenesis Authors: Natalie Arnold, Davis Maclean Reviewers: David Sia*, Yan Yu* * MD at time of publication Ocular Trauma Proliverative retinal diseases - retinal conditions involving neovascularization, e.g. diabetic retinopathy Vitreoretinal disease - disease of the back of the eye (retina and the vitreous fluid around it) e.g. macular degeneration Formation of fibrous tissue bands in vitreous cavity Bands contract and exert a tractional (pulling) force on the retina Retina is pulled off the choroid layer at the back of the eye by tractional forces, without a retinal tear Tractional Retinal Detachment (TRD): Retina is pulled off the choroid layer at the back of the eye in the absence of retinal tears Posterior Vitreous Detachment For complete pathogenesis and clinical findings see: Calgary Guide – Posterior Vitreous Detachment: Pathogenesis and Clinical Findings Note: Not every retinal tear leads to retinal detachment Parts of the gel- like vitreous humour detach from the retina ↑ Age Vitreous gel liquification Vascular Damage Optic disc Anomalies Degenerative Conditions During rotational eye movement, the vitreous humour moves within the vitreous cavity Strong tractional forces transmitted to retina through remaining attachments Retinal Tear: Physical defect in the retina associated with vitreous traction Defect held open by vitreoretinal traction Defect in retina allows vitreous fluid to gain access into sub retinal space Tumour/ Malignancy Idiopathic Rhegmatogenous Retinal Detachment (RRD): Accumulation of sub retinal fluid due to a tear in the retina allowing liquid vitreous gel to get underneath the retina Separation of the retina from choroid layer at the back of the eye Inflammatory/Infectious Conditions ↑ Permeability of choroid or retinal blood vessels Fluid leaks out of retinal/choroid blood vessels Accumulation of fluid beneath retina and without retinal tear or vitreous traction Exudative Retinal Detachment (ERD): Fluid accumulation in subretinal space in the absence or tears or traction from the vitreous Retinal Detachment: Sight threatening condition, considered ocular emergency See Calgary Guide slide: Retinal Detachment: Clinical findings Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 11, 2020 on www.thecalgaryguide.com

Retinal-Detachment-Clinical-Findings

Retinal Detachment: Clinical Findings See Calgary Guide slide: Retinal Convex elevation (in rhegmatogenous and exudative retinal detachment) Concave elevation (in tractional retinal detachment) Authors: Natalie Arnold, Davis Maclean Reviewers: David Sia*, Yan Yu* * MD at time of publication Rhegmatogenous retinal detachment starts from periphery = curtain pattern of vision Relative afferent pupillary defect: Affected pupil dilates when light moved from unaffected eye to affected eye Lower intraocular pressure Vitreous hemorrhage Detachment: Pathogenesis Elevation of retina on fundus examination Retinal Detachment: Separation of the retina from choroid layer at the back of the eye If involving retinal tears and/or posterior vitreous detachments: Retinal Tear: only present in Rhegmatogenous Retinal Detachments Posterior Vitreous Detachment: usually seen in Rhegmatogenous Retinal Detachments (See Calgary Guide - Posterior vitreous detachment) Separation of retina from the underlying choroid As the choroid contains blood vessels feeding the retina, retinal cells are deprived of blood and become ischemic Death of photoreceptors Light detected by fewer melanopsin retinal ganglion cell photoreceptors Loss of function in detached retina Smaller percentage of action potentials travel to dorsal midbrain Vision Loss Retinal pigment epithelium cell proliferation and formation of contractile membrane (scar tissue) in vitreous Proliferative vitreoretinopathy Communication between vitreous and exposed choroid Physical defect in the retina involves tearing of blood vessels within the retina ↑ outflow of fluid by active pumping through Retinal Pigment Epithelium (small layer of cells between the sensory retina and choroid) Blood released into the neurosensory retina blocks light’s pathway to retina Blood directly block light from stimulating photoreceptors on retina Retinal pigment epithelial cells released Shafer’s sign: (pigment in anterior vitreous seen with slit lamp) Released cells directly block light from stimulating photoreceptors on retina Floaters: Small circles, dots or lines in field of vision Aggregation of Collagen II fibers and blood released from optic disc during posterior vitreous detachment Tractional forces from vitreous movement are transmitted to areas where vitreous remains attached to the retina Collagen fibers cast shadow on the retina Fibers directly block light from stimulating photoreceptors on retina Vitreoretinal traction causes physical Photopsia stimulation of photoreceptors in the retina (Flashes) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 11, 2020 on www.thecalgaryguide.com

preterm-labour-pathogenesis-maternal-complications

Preterm Labour: Pathogenesis & Maternal Complications Cervical Procedures Removing part of the cervix Ex. Cone biopsy, cervical LEEP Genitourinary Infections E.g. Urinary tract infection, bacterial vaginosis, chorioamnionitis, abnormal vaginal flora ↑ bacterial colonization of fetal membrane ↑ bacterial enzymes and immune reactions Antepartum Hemorrhage ↑ risk placental abruption ↑ decidual tissue factor release Activates coagulation cascade ↑ thrombin ↑ proteases Substance Use Smoking or cocaine use Vasoconstriction in uterine circulation, endothelial dysfunction Placental hypoperfusion and ischemia ↑ fetal ACTH ↑ placental prostaglandins Maternal Stress Malnutrition, depression, trauma- related disorders, work-related stress ↑ cortisol ↑ placental corticotropin releasing hormone Uterine Abnormalities Mullerian duct anomalies: congenital abnormalities in uterine shape Septate uterus: ridge of tissue dividing uterus into two horns Intracavitary leiomyoma: benign mass inside uterus ↑ Uterine volume Maternal Genome Family hx or personal hx of preterm birth, previous preterm premature rupture of membrane ↓cervical stroma & ↑cervical scarring ↓ cervical glandsà ↓ mucous production ↑risk of infection ↑ inflammation ↑prostaglandins Cervical collagen degradation Rapid growth exceeds blood supply Ischemia & necrosis of fetal tissue ↑prostaglandins and cytokines ↓ functional volume of uterine cavity Multifetal pregnancy, poly- hydramnios ↓tensile strength and plasticity Uterine stretch Upregulation of oxytocin receptors Genes for ↑ risk Mechanism unknown Cervical Insufficiency Pathologic cervical dilation and/or effacement (thinning) Authors: Skye Russell Reviewers: Danielle Chang, Crystal Liu, Yan Yu*, Nicholas Papalia* *MD at time of publication Digest and weaken amniotic membrane Preterm Premature Rupture of Membranes ↑ myometrial sensitivity to oxytocin Uterine contractions Preterm Labour Uterine contractions and cervical change occurring <37wk gestational age ↑ Risk of future preterm labour and preterm birth Abbreviations: • LEEP – Loop electrosurgical excision procedure • ACTH – adrenocorticotropic hormone Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 12, 2020 on www.thecalgaryguide.com

Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu disease)

Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu disease): Pathogenesis and Clinical Findings Inherited or de novo mutation in the ACVRL1, ENG, or Smad4 genes Abnormal signalling within the transforming growth factor ß (TGF-ß) pathway Unclear mechanismsàInability of vascular mural cells to stabilize and remodel newly formed blood vessels Excessive proliferation of endothelial cells and ensuing overgrowth of blood vessels Authors: Tony Gu Reviewers: Brian Rankin Yan Yu* Laurie Parsons* * MD at time of publication Formation of friable telangiectasias (small dilated vessels apparent near the surface of skin or mucous membranes) Formation of Arteriovenous malformations (AVMs): Direct connection between arteries and veins without intervening capillary bed Nasal telangiectasias Epistaxis (nosebleeds) Gastrointestinal telangiectasias Gastrointestinal bleeding Mucocutaneous telangiectasias Cerebral AVMs Hepatic AVMs Left to right shunting of blood Heart works harder to perfuse tissues Heart failure Pulmonary AVMs Rupture High flow left to right shunting of blood (the steal effect) Cerebral ischemia No oxygenation at capillaries Hypoxemia ↑ erythropoietin production Secondary polycythemia No filtering from capillaries Hemorrhage, shock, death Venous emboli enter arteries (paradoxical embolism) Stroke Venous bacteria enter arteries Cerebral abscess Iron deficiency anemia ↓ serum iron is associated with ↑ coagulation factor VIII levels (mechanism unclear) Venous thromboembolism Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 28, 2020 on www.thecalgaryguide.com

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acute-pancreatitis-complications

Acute pancreatitis: Complications Inflammation causes vasodilation and vasculature leakage Mild, (85%): Interstitial edematous pancreatitis Local accumulation of fluid in the pancreas <2 weeks after onset Acute peripancreatic fluid collection (not encapsulated) Walled off by fibrous & granulation tissue >2 weeks after onset Pancreatic pseudocyst (completely encapsulated) Peritoneal irritation à pain Large cyst can (very rarely) compress surrounding bowel Acute Pancreatitis Inflammatory cytokines are released from damaged pancreas If recurrentàchronic pancreatitis (see relevant slide) Inflammation damages pancreatic exocrine cellsàInappropriate release of pancreatic enzymes into surrounding tissue & vasculature àdigesting pancreatic parenchyma Authors: Nissi Wei, *Yan Yu Reviewers: Dean Percy, Miles Mannas, Varun Suresh, Brandon Hisey, *Kerri Novak, *Sylvain Coderre * MD at time of publication complete resolution (most cases) Necrotic tissue is vulnerable to infection (esp. Gram neg GI bacteria) inflammation & necrosis activate cytokine cascade Severe, necrosis (15%): Necrotizing pancreatitis Local infection Severe pancreatic inflammation shifts body fluid into retroperitoneal spaceàintravascular volume depletion Systemic Inflammatory Response Syndrome (SIRS) (see relevant slide) Organ failure (may be sole feature on presentation) Stagnant fluid can more easily become infected Infection spreads to bloodstream Cardiac failure Hypovolemic shock Renal failure Local accumulation of fluid & necrosis in the pancreas < 4 weeks after onset: Acute necrotic collection (not encapsulated) Walled off by fibrous & granulation tissue > 4 weeks after onset walled-off necrosis (completely encapsulated) When treated with excess fluid resuscitation: Intra- abdominal hypertension Respiratory failure (ARDS) Disseminated intravascular coagulation (DIC) Bowel obstruction Gastric outlet (see relevant slide) obstruction Infected pancreatic necrosis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 20, 2016, updated September 7, 2020 on www.thecalgaryguide.com

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Pulmonary Hypertension

Pulmonary Hypertension: Pathogenesis and Clinical Findings Left heart disease (heart failure, myocardial infarction) ↓ contractility and/or diastolic relaxation ↓ left ventricle cardiac output Backup of blood in left ventricle and atrium Backup of blood in pulmonary vasculature ↑ pulmonary capillary wedge pressure– estimate of blood pressure in left atrium Chronic Anemia ↓ plasma hemoglobin content ↓ oxygen carrying capacity per unit blood Compensatory ↑ in heart rate to maintain tissue oxygen supply ↑ cardiac output Lung disease (chronic obstructive pulmonary disease) Tissue breakdown and ↓ lung elasticity Chronic thromboembolism Pulmonary vessel disease (pulmonary arterial hypertension, scleroderma) Vascular obstruction/fibrosis ↓ lungs’ ventilation ability ↓ surface areaà↓ gas exchange Lung vasculature undergo reflexive, localized vaso- constriction, to shunt blood to better ventilated areas Chronic hypoxemia ↓ local alveolar partial pressure of oxygen ↓ blood vessel compliance ↑ Pulmonary vascular resistance (PVR) Impaired gas exchange across thickened vessel walls ↓ blood partial pressure of O2 and ↑ partial pressure of CO2 Insufficient O2 provision & CO2 removal from tissues Reflexive mechanisms trigger harder & faster breathing to compensate Vascular fibrosis due to chronically increased pressures ↓ circulation of blood to left heart and ↓ filling of left ventricle ↓ left ventricle cardiac output Elevated blood pressure in the lung arteries Pulmonary Hypertension ↑ right-ventricle afterload (pressure against which the heart contracts to eject blood) ↓ right ventricle cardiac output ↑ residual volume in right heart after cardiac contraction Backup of blood in systemic circulation ↑ blood volume in venous system Myocardial hypertrophy develops over time (eccentric & concentric) ↑ tissue volume ↑ myocardial oxygen demand Myocardial ischemia (supply/demand mismatch) ↑ risk of chest pain in times of ↑ oxygen demand Peripheral edema Formation of aberrant conduction pathways and ectopic electrical foci Dysrhythmias Palpitations ↓ tissue perfusion Fatigue Dyspnea ↓ brain perfusion Syncope Authors: Grant E. MacKinnon Davis Maclean Hannah Yaphe Reviewers: Yan Yu* Jason Weatherald* * MD at time of publication ↑ volume and blood pressure in capillaries Fluid pushed from vessels into interstitial space of tissues Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 8, 2020 on www.thecalgaryguide.com

insuffisance-du-coeur-gauche-la-pathogenese

Insuffisance du coeur gauche: La pathogénèse Cardiomyopathies dilatées Régurgitation mitrale et aortique Infarctus du myocarde Hypertension artérielle sévère Sténose aortique avancée Tamponnade cardiaque Ischémie myocardique Cardiomyopathie hypertrophique Fibrose du myocarde Cardiomyopathie restrictive Note concernant la physiologie cardiaque: • Le volume d’éjection systolique dépend des éléments suivants: • 1) précharge cardiaque (volume télédiastolique) • 2) postcharge cardiaque (résistance à l’éjection du ventricule gauche) • 3) contractilité (la force de contraction des myocytes du ventricule gauche) • Fraction d’éjection= volume d’éjection systolique/volume télédiastolique • Le % du volume télédiastolique du ventricule gauche éjecté lors de la systole • Fraction d’éjection normale = 55-75% Dégénération des myocytes et presence de fibrose interstitielle Surcharge volumique chronique à causant une dilatation et hypertrophie du ventricule gauche Myocytes nécrotiques et non fonctionnels ̄ de la contractilité du ventricule gauche Dilatation, hypertrophie et fibrose du ventricule gauche Dysfonction systolique: Le ventricule gauche ne peut se comprimer/ou se vider, aussi ̄ de la fraction d’éjection Insuffisance cardiaque gauche ̄ Volume d’éjection systolique, reduction du débit cardiaque: le sang n'est donc pas pompé suffisamment au niveau de la circulation systémique pour répondre aux besoins métaboliques corporels. Le sang est donc reflué au niveau des poumons, ce qui provoque une congestion pulmonaire. Il en résulte alors des symptômes et des signes de diminution du débit cardiaque (insuffisance cardiaque antérograde) et de congestion (insuffisance cardiaque rétrograde). (voir les diapositives correspondantes) ↑ résistance à l'éjection du ventricule gauche (↑ la postcharge) ̄ relaxation du ventricule gauche et ̄ de l’entrée du sang lors de la diastole ↑ de la rigidité de la paroi ventriculaire gauche ̄ volume télédiastolique du ventricule gauche Dysfonction diastolique: Le ventricule gauche ne peut alors pas se dilater/se remplir adéquatement même si la fraction d'éjection est préservée Surcharge chronique de la pression du ventricule gauche Note: L'insuffisance cardiaque gauche est la manifestation la plus importante (stade ultime) de nombreuses pathologies cardiaques. Emma Hofland-Burry Jean-François Lemay* Auteurs: Yan Yu Editeurs: Sean Spence Jason Baserman Nanette Alvarez* Jean-François Lemay* * MD au moment de la publication Traductrice/Traducteur: Voir les diapositives correspondantes pour une description plus détaillée de chacun de ces diagnostics Légende: Pathophysiologie Mécanisme Signe/Symptôme/Trouver laboratoire Complications Publié le 10 Janvier 2013 à www.thecalgaryguide.com

insuffisance-cardiaque-gauche-resultats-de-lanamnese

Insuffisance cardiaque gauche: résultats de l'anamnèse Lourdeur abdominale (congestion hépatique, ascite) ↑ de la pression hydrostatique veineuses forçant un écoulement liquidien dans les tissus interstitiels, surtout au niveau des zones dépendantes de la gravité Oedème de la cheville Insuffisance du ventricule gauche Débit cardiaque réduit (“insuffisance cardique antérograde”): le sang n'est pas suffisamment pompé au niveau de la circulation systémique pour répondre aux besoins métaboliques corporels Congestion pulmonaire (“insuffisance cardiaque rétrograde”): Le sang reflue du ventricule gauche vers l'oreillette gauche causant ainsi une accumulation dans le système pulmonaire vasculaire Activation sympathique (pour essayer d' ↑ le débit cardiaque) Tachycardie, palpitations et diaphorèse Perfusion tissulaire limitée (i.e. au niveau musculaire) Faiblesse et fatigue Une pression artérielle pulmonaire veineuse élevée force l’evacuation des fluides des capillaires vers l'interstitium et les alvéoles pulmonaires La congestion pulmonaire reflue le sang vers le cœur droit, et ultimement vers la circulation veineuse systémique Ce fluide est dépendant de la gravité ; il s'installe dans les lobes pulmonaires inférieurs. Progressivement, les vaisseaux sanguins des lobes pulmonaires supérieurs (qui sont alors mieux ventilés) se dilatent par réflexe, ce qui ↑ les échanges gazeux (

insuffisance-cardiaque-gauche-les-resultats-de-lexamen-physique

Insuffisance cardiaque gauche: les résultats de l’examen physique Lesoreillettes cardiaques se contractent contre un ventricule gauche rigide en fin de diastole Dysfonction diastolique ̄Débit cardiaque: Insuffisance ventriculaire gauche Il y a une augmentation de la quantité de sang dans le ventricule gauche suivant la systole, avec ­ pression télédiastolique du ventricule gauche Le sang reflue au niveau des poumons, ­ la pression vasculaire pulmonaire B4 Si le ventricule gauche est dilaté (i.e. en cas de cardiomyopathie dilatée) Dysfonction systolique ̄ Perfusion tissulaire (au niveau cerebral, renal etc.) Vasoconstriction périphérique àdetournement limité du volume d’ejection systolique vers les organes principaux Extrémités froides, cyanose périphérique ̄ Du débit urinaire ̄ De l’état de conscience Hypoxie tissulaire ­ la respiration anaérobique, ­ production d’acide lactique (acidose) Les centres respiratoires tentent de compenser Expulsion des fluides des capillaires vers les alvéolesà oedème pulmonaire transudatif La congestion vasculaire et les alvéoles oedématiées compriment les voies respiratoires, provoquant une turbulence du flux d'air Un flux d'air turbulent est entendu lors de l'auscultation Respiration sifflante (wheezing) Flux turbulent dans le ventricule gauche distendu au début de la diastole B3 Choc de la pointe diffuse ̄ Du flux sanguin artériel pendant la systole ̄ Tension artérielle en systole ­ De la tension artérielle lors de la diastole ̄ Pouls cardiaque Fermeture des valves pulmonaires avec une force supérieure à la normale ­ B2 pulmonaire ̄ De l’oxygenation sanguine Le transsudat obstrue les petites voies aériennes et alvéolaires Si le ventricule gauche est en surcharge de pression ou si hypertrophié (i.e. sténose aortique, hypertension sévère) Choc de la pointe soutenue ­ De l'activité du système sympathique (pour tenter de rétablir le débit cardiaque) Pendant l'inspiration, de petites zones de compartiments aériennes s'ouvrent Crépitements pulmonaires (ils sont généralement bilatéraux et surtout au niveau de la base pulmonaire) Auteur: Yan Yu Editeurs: Sean Spence, Jason Baserman, Nanette Alvarez* Traductrice/Traducteur: Emma Hofland-Burry, Jean-François Lemay* *MD au moment de la publication ­ Activité des glandes sudoripares Diaphorèse ­ Activité cardiaque Tachycardie ­ Fréquence respiratoire Tachypnée Remarque: l'insuffisance cardiaque gauche étant la cause principale de l'insuffisance cardiaque droite, elle peut également se présenter par des signes d'insuffisance cardiaque droite. Les autres caractéristiques de l'insuffisance cardiaque gauche dépendent de la cause sous-jacente. Si la pression vasculaire artérielle pulmonaire est chroniquement élevéeàporvequera un surmenage prolongé de la function du ventricule droit: Insuffisance cardiaque droite: Le patient présente des conséquences directes de sa congestion veineuse systémique: œdème périphérique (i.e.cheville), épanchements pleuraux, congestion hépatique/ascites (s.v.p. voir la diapositive correspondante) Publié le 10 Janvier 2013 à www.thecalgaryguide.com

Essential Tremor

Essential Tremor (ET): Pathogenesis and clinical findings Most common tremor in adults Authors: Davis Maclean Evan Allarie Reviewers: Hannah Yaphe Gary Klein* Yan Yu* * MD at time of publication ↑ Age Unknown environmental factors Oscillatory network hypothesis: diffuse oscillating neuronal activity in thalamic, inferior olivary and cerebellar networks ↑ activity in the cerebellothalamocortical circuit Alternating contractions of antagonistic muscles Involuntary rhythmic/oscillatory movements with generally constant frequency and variable amplitude Indeterminate cerebellar and locus coeruleus (pons) pathology 3 non-mutually exclusive mechanisms proposed Polygenic genetic predisposition (up to 70% have family history) Approximately 50% of cases are associated with an autosomal dominant inheritance pattern – specific gene has yet to be identified GABAergic hypothesis: ↓ GABA (Gamma amino butyric acid – Inhibitory neurotransmitter) activity in cerebellar and locus coeruleus circuits Neurodegeneration hypothesis: Possible cerebellar degeneration (this hypothesis is currently controversial and requires more evidence) Potential neuro- degenerative process May lead to difficulty with gait and mild cognitive impairment seen in a minority of ET patients Alcohol binds to GABA receptors in the cerebellum ↑ neuronal inhibition Bilateral and symmetric tremor ↓ activity in overactive (cerebellar) tremor circuits Alcohol consumption ↓ tremor in majority of patients Issues with writing, cooking, eating, occupational duties or other instrumental activities of daily living Pathologic changes in the brain affect both sides of the motor system Unknown mechanism Typically involves the hands and arms but may present or progress to involvement of head, voice, legs, face, jaw and trunk Embarrassment or other social consequences Slowly progressive tremor of 6-12Hz frequency Tremor is persistent and visible Postural tremor (evident during sustained anti-gravity postures), and/or a kinetic tremor (evident during voluntary movement) Tremor becomes apparent when holding outstretched arms against gravity Tremor typically increases at the end of goal directed movement Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 19, 2020 on www.thecalgaryguide.com

Cellulitis

Cellulitis: Pathogenesis, clinical findings and complications Authors: Tegan Evans, Spencer Yakaback Reviewers: Brian Rankin, Timothy Fu, Laurie Parsons*, Yan Yu* * MD at time of publication Cracked skin Surgery Normal Skin Epidermal layer Dermal-Epidermal Junction Dermal layer Subcutaneous fat Resident skin flora: Coagulase-negative Staphylococci* Transient skin flora: Staphylococcus aureus* Streptococcus pyogenes Gram negative bacteria Fungi Pathogen in deep dermis and subcutaneous fat *most common pathogens Break in skin barrier (may not be obvious) and entry of pathogen Risk Factors: Immunocompromised Host: -Diabetes mellitus+ -Lymphedema -Malnourishment -Older patient+ -Obesity+ -Peripheral vascular disease General Infection Risk: -History of cellulitis+ +highest risk factors Risk Factors for MRSA Cellulitis: Increased exposure to MRSA: -Contact sports -Crowded living conditions -Health care workers -Indigenous descent -Sharing towels, equipment Increased susceptibility: -Immunodeficiency -Young age Direct inoculation (e.g. trauma) Organism virulence overwhelms host defense mechanisms (related to risk factors) Cellulitis: A bacterial infection in which pathogens penetrate deep dermis and/or subcutaneous fat Cytokines activate immune response Accumulation of pus (bacteria, white blood cells, dead skin) Abscess formation Infection spreads to nearby lymph nodes Lymphadenitis Infection spreads through lymph vessels Ascending lymphangitis Local inflammatory response in skin Pain Warmth Edema Erythema (redness) with indistinct margins Vesicles and bullae Organisms penetrate blood vessels Bacteremia (presence of bacteria in blood) Systemic inflammation Distant spread to bone Osteomyelitis Distant spread to endocardium (inner lining of heart chambers and valves) Endocarditis Fever Malaise Chills Sepsis (rarely) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 27, 2020 on www.thecalgaryguide.com

pertussis-pathogenesis-clinical-findings-and-complications

Pertussis: Pathogenesis, clinical findings and complications Authors: Morgan Sosniuk Yan Yu* Reviewers: Jessica Tjong Crystal Liu Timothy Fu Luis Murguia-Favela* * MD at time of publication Bordetella pertussis bacterium enters the airway via droplets B. pertussis binds to ciliated epithelial cells and multiplies, colonizing the nasopharynx B. pertussis produces multiple toxins (e.g. “pertussis toxin”, “tracheal toxin”) which damage mucosal cells Pertussis toxin produces cyclic AMP (cAMP) and disrupts normal intracellular signalling, impairing the immune response initially Pertussis (“Whooping Cough”) Respiratory syndrome consisting of severe fits of paroxysmal coughing and stridor Nasopharyngeal swab produces positive culture and/or positive PCR result (either is diagnostic) Initial immune dampening allows the bacteria to take hold and begin replicating. During this “incubation period”, the bacteria has not yet replicated to the point of causing symptoms. 1. Catarrhal Stage (5-10 days) After a few days, continued damage to nasopharynx epithelial cells stimulates the immune system to ↑ its response once again 2. Paroxysmal Stage (1-2 weeks) Tracheal cytotoxin released by B. pertussis impairs normal cilia function and ciliary beating in the trachea 3. Convalescent stage (2 weeks - months) Immune defenses successfully eliminate the majority of B. pertussis from the respiratory tract ↑ mucus production from goblet cells of the respiratory epithelium Mucus blocks airway, prevents air entry Collapsed lung Rarely, areas of chest or abdominal wall are weakened, allowing contents to bulge out Hernia ↑ proinflammatory cytokine production Mild fever Cold-like symptoms Mild dry cough, runny nose, sneezing, nasal congestion ↓ fluid clearance from the respiratory tract Fluid in the trachea narrows tracheal diameter “Whooping” cough Severe, rapid and sequential coughing fits, followed by characteristic “whooping” sound on inspiration due to a stridor from a narrower trachea Fluid build up in the lungs Environment more susceptible to co-infection Other bacteria colonize the lungs Pneumonia Paroxysmal coughing fits ↓ in frequency and number Cough may sound louder (mechanism unknown) but overall symptoms ↓ Some B. pertussis still remain Residual cough flares This stage may be prolonged in unvaccinated individuals who eliminate the bacterium more slowly Intense cough can break ribsàsharp rib ends puncture lungàair leaks out ↑ pressure on bladder If weak urethral sphincters: Urinary incontinence Cough ↑ intra- abdominal pressure If dripping mucus triggers gag reflex while a cough is contracting abdominal muscles: Vomiting Coughing fits disrupt regular inspiration and ↓ oxygenation Hypoxia If hypoxia is profound enough to affect brain Seizures Abdominal muscles tire from coughing, and coughing fits make it difficult to sleep Extreme fatigue Rarely, violent coughing causes trauma to head Intracranial hemorrhage Vertebral or carotid dissection Cerebral ischemia Coma or death Notes: • B. pertussis is a Gram- negative strict aerobe • An effective vaccine exists to prevent infection by B. pertussis • Pertussis most commonly infects children <18 months prior to completion of scheduled vaccination series, or adolescents with ↓ immunity Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 4, 2020 on www.thecalgaryguide.com Include a sentence! When sending in the final draft of a slide, please include in the email a sentence that describes the slide that you've produced in detail. This will help us boost the relevance of the slide with search engines. E.g., Disease X presents with symptom Y due to pathophysiology Z Pertussis presents with fits of severe paroxysmal coughing due to impaired mucociliary clearance.

Creutzfeldt-Jakob-Disease

Creutzfeldt-Jakob Disease: Pathogenesis and clinical findings Author: Skye McIntosh Reviewers: Heather Yong Tony Gu Davis Maclean *Scott Jarvis *Gary Klein *Yan Yu * MD at time of publication Familial (5-15%): Autosomal dominant inheritance of pathologic prion protein (PRNP) genes Sporadic (85%) Pathologic prion protein (PrPSc) form spontaneously from normal prion protein isoforms (PrPc) Acquired (<1%) Variant: consuming bovine spongiform encephalopathy (BSE) infected beef (mad cow disease) Iatrogenic: related to medical intervention (e.g instruments contaminated with PrPSc) Note: The normal prion protein isoform (PrPc) is expressed predominantly in neurons. It is not intrinsically pathological. Presence of PrPSc kickstarts an “autocatalytic” process by which existing PrPSc converts more normal prion protein (PrPc) into pathological protein. Pathological prion proteins (PrPSc) enter host Astrogliosis: ↑ astrocyte cells infiltrate and occupy the space of lost neurons Vacuolation or spongiform changes: clusters of small vacuoles in synaptically dense cortical areas Pathologic prion proteins (PrPSc) are insoluble and aggregate within neurons Mechanism unknown Neuronal loss Creutzfeldt-Jakob Disease Fatal infectious brain disorder causing neuronal death Diffuse brain atrophy Exact mechanism unknown Frontal lobe atrophy The frontal lobes are responsible for executive function and personality Occipital lobe atrophy The occipital lobes are responsible for interpreting vision Basal ganglia atrophy The basal ganglia is responsible for sequencing voluntary movements Loss of inhibitory cortical neurons Hyper-excitable cortical neurons Myoclonus: quick involuntary muscle jerks Cerebellar atrophy The cerebellum is responsible for coordination and fine correction of movements Gait Slurred Extensive neuronal loss in the brainstem reticular activating system Coma Impaired control of respiratory muscles Pneumonia and respiratory failure ~ 75% mortality within 1 year Rapidly progressive dementia Anxiety, depression Visual hallucinations Double vision Bradykinesia: Tremor Rigidity: ↑ muscle tone ataxia speech Incoordination Personality changes Irritability slow movements Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 4, 2020 on www.thecalgaryguide.com

Epidural-Hematoma-Findings-on-CT

Acute Epidural Hematoma: Findings on CT Authors: Davis Maclean Evan Allarie Viesha Ciura* Reviewers: Yan Yu* * MD at time of publication Image Credit: Alberta Health Services Repository Epidural Hematoma: Collection of blood in the potential space between the inner layer of the skull and outer layer of the dura mater See Calgary Guide - Epidural Hematoma: Pathogenesis and clinical findings Generally (75%) occurs beneath the pterion (location where frontal, sphenoidal, temporal and parietal bone meet) The expansion of the hematoma (collection of blood) is limited by cranial sutures (firm attachments of the dura) Multiple bony connections decrease stability in this region Pterion region of the skull is the thinnest portion of the skull Hematoma has limited range to expand in anterior posterior direction High rate of fractures in this area from skull trauma The middle meningeal artery traverses under the temporal bone and pterion, and is susceptible to injury from fractures in this area Hematoma near or under temporal bone Hematoma must expand medially, or inwards, towards brain parenchyma Biconvex hyperintensity Can lead to brain herniation (See Calgary Guide: Brain Herniation Types and Clinical Findings) Estimating Size of Hematoma (A x B x C)/ 2 • A= Maximum hemorrhage diameter at largest point of hematoma • B= Measurement of diameter 900 to Measurement A • C= The number of CT slices where hematoma is visible multiplied by thickness of CT slices CT or MRI? • CT is rapidly available in most North American emergency departments and is the best imaging modality for detecting acute intracranial hemorrhage. Increased pressure can cause shift of brain structures Midline structures shifted away from hematoma (Midline shift) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 14, 2020 on www.thecalgaryguide.com

Pathogenesis-of-Female-Infertility

Pathogenesis of Female Infertility Author: Simonne Horwitz Reviewers: Claire Lothian, Hannah Yaphe, Yan Yu*, Nicole Paterson* * MD at time of publication Extreme stress, eating disorder, excessive exercise, intracranial tumor, or hyperprolactinemia* ↓ Gonadotropin releasing hormone (GnRN) from hypothalamus ↓ release of Luteinizing hormone (LH) & Follicle stimulating hormone (FSH) by pituitary ↓ release of estrogen by ovaries Anovulation (oocyte is not released) Fewer follicles available to ovulate * Causes of Hyperprolactinemia include: prolactinoma (prolactin-producing tumor), hypothalamic infiltrate or mass, chest wall irritation, hypothyroidism, renal or liver disease (↓ prolactin clearance), dopamine antagonists that ↑ prolactin secretion (antipsychotics, anti- depressants, anti-emetics) Polycystic ovary syndrome (see PCOS: Pathogenesis and Clinical findings) ↑ androgen production & ↑ estrogen earlier in the menstrual cycle ↓ FSHà↓ follicle growth ↑ rate of follicle depletion Oocyte not available every month for fertilization Premature ovarian insufficiency due to unexplained causes, chemotherapy, radiation, autoimmune ovarian destruction, Turner’s & Fragile X Syndromes Damage in germ cells that accumulates over a woman’s lifetime Age-related changes in quality of granulosa cells surrounding oocyte Genetic damage accumulates, such as ↑ rates of meiotic nondisjunction (failure of chromosomes to separate during gamete cell division) Tubal occlusion or ↓ transport of oocyte tubal cilia dysfunction through fallopian tube ↓ quality of oocytes Normal transport of oocyte & sperm through fallopian tube is impaired ↓ facilitation of sperm transportation Inhibits normal zygote implantation Chlamydial or gonorrhoeal pathogens Previous tubal surgery or ectopic pregnancy surgery tissue removal ↓ transport of oocyte through fallopian tube Female Infertility Previous abdominal infection or surgery Endometriosis Congenital malformations or trauma / surgery to cervix Uterine leiomyomata (benign smooth muscle monoclonal tumor) or polyp Intrauterine procedures Pelvic adhesions (scar-like tissue that tether together abdominal organs) may distort the shape and normal anatomy of the fallopian tube Ectopic endometrial cells implant & Local inflammatory response grow along pathway of egg/sperm further ↓ egg/sperm mobility Inability of cervix to produce normal mucus, and/or sperm physically unable to enter the cervix Submucosal or intracavitary component disrupts uterine lining Trauma to basalis layer of endometrium Intrauterine scarring or synechiae (adhesions) ↓ vascularization & endometrial regrowth Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 25, 2020 on www.thecalgaryguide.com

Anesthetic-Considerations-Aortic-Stenosis

Anesthetic Considerations: Hemodynamic Goals (“CRRAP Goals”) for Patients with Aortic Stenosis Undergoing Non-Cardiac Surgery CRRAP Goals: Contractility, Rate, Rhythm, Afterload, Preload Pathophysiology Driving Anesthetic Management Hemodynamic Anesthetic Intervention (CRRAP) Goals Author: Ryan Brenneis Reviewers: Stephen Chrusch Hannah Yaphe Yan Yu* Karl Darcus* * MD at time of publication Aortic stenosis = Narrow aortic valve opening Notes: -Cardiac Output = Heart Rate x Stroke Volume -Stroke volume has 3 determinates: 1. Contractility 2. Afterload 3. Preload If the patient’s heart cannot ↑ contractility to maintain cardiac output... ↑ resistance to forward blood flow àheart must ↑ its contractility (↑ the forcefulness of its contractions) to overcome this resistance Applying ↑ force over time causes left ventricle to undergo concentric hypertrophy Contractility deteriorates over time Heart rate must compensate for maintaining cardiac output Coronary Perfusion Pressure = Diastolic BP (DBP) – Left Ventricular End Diastolic Pressure (LVEDP) ↑ cardiac muscle massà↑ myocardial metabolism and oxygen demand ↑ left ventricular wall stiffnessà↓ LV filling while relaxed (diastolic dysfunction) Intraoperative ↓ in contractility compromises cardiac output Bradycardia ↓ cardiac output Tachycardia ↓ filling time of left ventricle (↓ preload) Coronary perfusion occurs during diastole Coronaries require a high DBP to maintain perfusion Tachycardia ↓ perfusion time Hypotension ↓ coronary perfusion pressure Possible myocardial ischemiaà ↓ blood pumped into vessels 40% of LV preload supplied from atrial kick Loss of atrial kick with arrhythmias à↓ cardiac output Note: Aortic stenosis severity (see slide on aortic stenosis) and the type/risk of surgery guide the hemodynamic consequences and need for intervention Adequate intravascular volume required to passively fill stiff ventricle Contractility ↓ use of negative inotropic Maintain drugs, e.g. calcium channel contractility blockers (“Inotrope”: drug that alters heart’s contractility) Rate Keep heart rate above 60 bpm Keep heart rate below 80 bpm Consider transcutaneous pacing, anticholinergics, & sympathetic agonists ↑ anesthetic depth, consider beta blocker (e.g. Esmolol) Afterload Maintain a Mean Arterial Pressure >70mmHg Consider sympathomimetic drugs to treat hypotension Monitor blood pressure closely via arterial line Consider increasing anesthetic depth for severe hypertension Rhythm Maintain Sinus Rhythm Consider presurgical placement of defibrillator pads & crash cart Amiodarone ready & available during operation, to terminate any arrhythmias Preload Maintain Euvolemia Possible use of transesophageal echo to monitor preload Ensure adequate venous access- consider central venous catheter and large bore IV’s Legend: Pathophysiology Mechanism Goal Anesthetic Intervention Published October 25, 2020 on www.thecalgaryguide.com

Tumour-Lysis-Syndrome

Tumour Lysis Syndrome High sensitivity to treatment Highly proliferative malignancy with ↑cell-turnover Large tumour mass Author: Joshua Yu Reviewers: Hannah Yaphe Davis Maclean Tejeswin Sharma Yan Yu* *Peter Duggan *ManChiu Poon *Lynn Savoie *Juliya Hemmett * MD at time of publication High serum phosphate High serum Advanced uric acid Age Volume depletion Pre-existing renal disease Patient risk factors Initiation of cancer treatment Massive tumour cell lysis and release of cellular contents into circulation overwhelms homeostatic mechanisms Tumour properties (hematologic malignancies most common) Though rare, aggressive tumours can spontaneously lyse without treatment Intracellular potassium released into bloodstream Intracellular phosphate released Hyperphosphatemia ↑ serum phosphate Intracellular lactate dehydrogenase (LDH) released ↑ serum LDH Intracellular nucleic acids released Nucleic acids metabolized to uric acid Hyperuricemia ↑ serum uric acid Hyperkalemia ↑ serum potassium (see Hyperkalemia: clinical findings) Uric acid (a crystallizing substance) ↑ precipitation of calcium phosphate ↑ filtration of poorly soluble uric acid into acidic environment of renal tubules Serum phosphate binds serum calcium, forming solid calcium phosphate precipitate crystals High levels of calcium phosphate ↑ uric acid precipitation Uric acid precipitates as crystals and deposits in kidney tubules and collecting ducts Tubular injury and/or intraluminal obstruction Endothelial dysfunction in renal vasculature Renal inflammation, vasoconstriction, and impaired renal vascular autoregulation Decreased renal filtration Acute Kidney Injury (see Acute Kidney Injury Overview) Crystal deposition in the heart Depletion of soluble calcium Hypocalcemia Calcium phosphate crystals deposit in kidneys Main mechanism of Acute Kidney Injury Cardiac Arrythmias ↓ serum calcium (see Hypocalcemia: clinical findings) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 25, 2020 on www.thecalgaryguide.com

Small-Bowel-Obstruction-findings-on-X-Ray

Small Bowel Obstruction: Findings on X-Ray Authors: Evan Allarie Shelley Spaner* Reviewers: Davis Maclean Yan Yu* * MD at time of publication See Calgary Guide – Mechanical Bowel Obstruction and Ileus: Pathogenesis and clinical findings Bowel contents cannot pass the obstruction Buildup of bowel contents (gas, fluid) proximal to the obstruction Gas rises above the fluid If exclusively or mostly accumulation of fluid (and not gas) occurs Any small amounts of gas/air present (not enough to create an air-fluid level) will rise and become trapped in valvulae conniventes (small bowel folds) Small bowel loops are anatomically central compared to large bowel Bowel contents physically push on the bowel walls, dilating them Dilated bowel loops are “central” in location on the x-ray Dilated bowel loops (>3cm) Valvulae Conniventes Visible: Anatomical folds of the small bowel that becomes more apparent when small bowel is distended & allows differentiation from large bowel Air-fluid level (on erect/upright study) - Dark area above level = Gas/Air - Bright/white area below level = Fluid ‘Gasless’ abdomen (not seen here): Refers to the lack of gas/air (dark on X-ray) in the bowel loops - only fluid (bright/white on X- ray) is seen in bowel loops String of pearls sign (not seen here): Small gas bubbles seen arranged in a “string of pearls” pattern instead of a large air fluid level Image Credit: Alberta Health Services Repository Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 25, 2020 on www.thecalgaryguide.com

Calcium-Oxalate-Kidney-Stones

Multiple-Sclerosis-on-Brain-MRI

Classic Findings of Multiple Sclerosis (MS) on Brain MRI Authors: Evan Allarie Davis Maclean Viesha Ciura* Reviewers: Yan Yu* * MD at time of publication infiltrates in the infratentorial region Note: variation in findings exist. The findings shown here are not exhaustive but are some of the most common areas implicated on brain MRI in MS. Most common sites that lesions are observed are: juxtacortical regions, periventricular, infratentorial, spinal cord, and the optic nerve. However lesions can occur anywhere there is myelin in the CNS. Active inflammation and destruction allows for gadolinium contrast to cross the blood- brain barrier, which can be visualized as a marker of active inflammation in MS Classic optic nerve (CN II) lesion seen in optic neuritis. Gadolinium enhancement (↑ signal intensity of lesion after gadolinium injection) in this T1 image demonstrates active inflammation Image Credits: Dr. Viesha Ciura For further pathogenesis, see the Calgary Guide slide: Multiple Sclerosis (MS): Pathogenesis and Clinical Findings Inflammation within the central nervous system (CNS) T-cell, B-cell, and macrophages infiltrate CNS Infiltration occurs through veinsàlocal inflammation Perivenular infiltrates around the medullary veins (perpendicular to ventricles) Inflammation and blood-brain barrier destruction ↑ extravascular inflammatory fluid around lesions, which appears hyperintense/bright Loss of neuronal/axonal density in affected region, replaced by gliosis over time Lesions extend out around veins, creating characteristic ovoid lesions Classic hyperintense T2/FLAIR perpendicular periventricular plaques following the medullary veins – ‘Dawson’s Fingers’ Middle cerebellar peduncle T2/FLAIR hyperintense lesion in classic location for MS Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 25, 2020 on www.thecalgaryguide.com

Uterine-Fibroids

Uterine Fibroids (Leiomyomas): Pathogenesis and clinical findings Early Menarche (onset of period) ↑ estrogen exposure in Obesity ↑ adipose tissue ↑ conversion of androgens into estrogen Ethnicity (African) ↑ amount of aromatase enzymes Family History Complex chromosomal rearrangements Myometrial Injury Hypoxia of myometrial cells Low Parity Lack of protective pregnancy-induced remodeling to myometrium Note: Approximately three-quarters of women have fibroids. Of these, only about one-quarter become symptomatic. Fibroids generally decrease in size after menopause and symptoms improve. Intracavitary Fibroid projects into uterine cavity ↑ Endometrial Surface Area ↑ endometrium to proliferate and lose during menstruation Age 40-50 lifetime Estrogen stimulates proliferation of uterine smooth muscle cells Benign proliferation of monoclonal myometrial (uterine wall/muscle) cells into discrete masses Uterine Fibroids (Leiomyomas) Benign tumours originating in and consisting of uterine muscle tissue Fibroids can be located in different areas of the uterus, including the following locations Authors: Emilee Anderson Reviewers: Danielle Chang Crystal Liu Yan Yu* Aysah Amath* * MD at time of publication Subserosal Fibroid grows adjacent to perimetrium into uterine muscle Enlarged uterus or pelvic mass on bimanual exam Irregularities in uterine cavity Transformation of normal myocytes into abnormal myocytes Submucosal Fibroid grows adjacent to endometrium into uterine muscle Intramural Fibroid is within the thickness of the myometrium Pedunculated Fibroid extends into pelvic cavity or uterine cavity on a stalk Spherical mass on ultrasound Fibroid ↑ intra-abdominal pressure and puts pressure on adjacent organs Enlarged Uterine/Pelvic Mass Repeat shedding over time Iron Deficiency Anemia Pelvic Pain Compression of stomach Fibroid takes up space Enlarged Abdomen Fibroid puts pressure on the cervix Dyspareunia Fibroid compress the bladder Urinary incontinence Fibroid compress the bladder outlet Difficulty with voiding Fibroid compress rectum Constipation Embryo cannot implant Infertility and/or recurrent pregnancy loss Menorrhagia Dysmenorrhea Sensation of abdominal fullness Early Satiety Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 5, 2020 on www.thecalgaryguide.com

Bronchiolitis-updated

Bronchiolitis: Pathogenesis and clinical findings Viral pathogen, most commonly respiratory syncytial virus (RSV) - but can be others such as rhinovirus, adenovirus, parainfluenza, influenza, and coronaviruses - initially colonizes the nasopharyngeal mucosa Virus travels via the epithelium to the lower airways to the terminal bronchioles (small airways) Authors: Nick Baldwin Rebecca Lindsay Reviewers: Kayla Nelson, Yan Yu Timothy Fu, Danielle Nelson* *MD at time of publication Upper airway mucosal inflammation Bronchiolitis (bronchiole inflammation) Apnea (cessation of breathing; via unknown mechanism, potentially apnea reflex) RSV-fusion protein facilitates fusion of the virus to the host cell and directs viral penetration as well as facilitates fusion of the infected cell with its healthy neighbors Forms syncytia (multinucleated cells) Cytokines are released into circulation ↑ thermo- regulatory set- point at the hypothalamus Mild Fever Copious coryza (nasal discharge) Protein and fluid leak into nasopharyngeal interstitium ↑ Capillary permeability Protein and fluid leak into the bronchiole interstitium, accumulating around airway walls Airway wall becomes thickened, more readily apparent on x-ray Peribronchial cuffing (X-ray finding: bronchi appear like thickened ‘cuffs’ when viewed head-on) Inflammation stimulates the upregulation of mucous secreting goblet cells ↑ mucous production Mucous within alveoli ↑ intra- alveolar surface tensionà collapsing alveolar walls During inspiration, air enters the collapsed alveoli if airway is not yet occluded ↑ intra-alveolar pressure causes the alveoli to suddenly pop open Inspiratory crackles on auscultation Syncytia slough off the bronchial epithelium into airways Airways become narrower and occlude Disruption of the ciliated epithelial cells (which transport mucous out of the airways and into the pharynx, to be swallowed or evacuated) ↓ mucous clearance from airways Excess airway mucous triggers cough reflex Cough Interstitial edema Nasal Congestion Air is absorbed distal to occlusion (gas trapping) When all air is absorbed, alveoli collapse (resorptive atelectasis) ↓ gas exchange between blood and air in remaining alveoli ↓ O2 saturation & ↑ CO2 content of blood Narrower airways, especially during expiration, causes audible turbulent airflow Wheeze on auscultation Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published November 29, 2020 on www.thecalgaryguide.com

mrna-vaccines-against-coronavirus-disease-2019-covid-19-production-and-mechanism-of-action

mRNA Vaccines against Coronavirus Disease 2019 (COVID-19): Production and Mechanism of Action Vaccine Production The “spike protein” is known to be a major viral surface Authors: Ryan Brenneis, Yan Yu* Reviewers: Davis MacLean, Hannah Yaphe, Timothy Fu, Stephen Vaughan* * MD at time of publication References 1. ACS Nano 2020, 14, 10, 12522–12537, Publication Date: October 9, 2020, https://doi.org/10.1021/acsnano.0c07197 2. NEJM 2020, Publication Date: December 10, 2020, DOI: 10.1056/NEJMoa2034577 3. Expert Review of Vaccines 2017, 16, 9, 871-881, Publication Date: 2017, DOI: 10.1080/14760584.2017.1355245 4. NEJM 2020, 383, 2439-2450, Publication Date: December 17, 2020, DOI: 10.1056/NEJMoa2027906 5. NEJM 2020, 383, 2427-2438, Publication Date: December 17, 2020, DOI: 10.1056/NEJMoa2028436 6. BMJ 2000, 321, 7271, 1237-1238, Publication Date: November 18, 2000, DOI: 10.1136.bmj.321.7271.1237 Notes: SARS-CoV-2 (RNA virus causing COVID-19) collected from an infected patient (ie. with a nasopharyngeal swab) Various reagents are added to the sample containing both human cells and viral constituents Reagents cause cell/viral membrane lysisàspilling cell contents, viral particles, and viral RNA Fats, proteins, and carbohydrates removed through various washing reagents, leaving nucleic acids (like RNA) Reverse transcriptase polymerase chain reaction produces complementary DNA (cDNA) from viral RNA cDNA library allows for SARS-CoV-2 genome to be mapped through whole-genome sequencing technology SARS-CoV-2’s spike protein DNA sequence is identified, and is used as a template to create synthetic viral spike protein mRNA Extra RNA bases are added to this mRNA strand to promote its stabilityàresulting RNA strand is now called “nucleoside-modified RNA” (“modRNA”) antigen (substance that elicits an immune response) from studies of other coronaviruses (e.g. SARS- CoV-1 and MERS-CoV) Pfizer/BNT162b2 vaccine contents: Moderna mRNA-1273 vaccine: Note: Lipid nano- particles are spherical hollow “balls” made of an outer lipid membrane plus other emulsifiers and membrane stabilizers. Lipid nanoparticles are capable of engulfing smaller molecules (like RNA) and merging with normal cell membranes Spike protein modRNA is then isolated (using a series of precipitation, extraction, and chromatography methods) Final modRNA lipid nanoparticle vaccine is now created and ready for intramuscular injection The modRNA vaccine is injected intramuscularly into a healthy person 2nd dose after 3-4 weeks needed to strengthen the immune response (to a level exceeding the immune response in patients recovered from Covid-19), boosting vaccine efficacy especially in older individuals4,5 Lipid nanoparticle fuses with human cells’ phospholipid membranes via endocytosis, releasing modRNA into the cell’s cytosol modRNA is translated by human ribosomes naturally found in the cell’s cytosol, producing viral spike protein components • • Foreign substance can cause local tissue inflammation The spike proteins encoded by the modRNA of each of the two vaccines are similar It is the proprietary lipid nanoparticle formulation (unknown to the public) that is unique to each vaccine Pain, redness, swelling at injection site (Transient) Proprietary Pfizer/ BioNTech lipid nanoparticle The modRNA encodes a full-length spike protein modified with two proline amino acids (for stability and immunogenicity)2 The modRNA encodes a full-length spike protein modified with two proline amino acids (for stability)1 Proprietary Moderna lipid nanoparticle Encapsulating this modRNA within Pfizer/ BioNTech’s lipid nanoparticle creates the 162b2 vaccine This specific formulation requires colder storage temperatures (-700C) Encapsulating this modRNA within Moderna’s lipid nanoparticle creates the mRNA-1273 vaccine This specific formulation can be stored at slightly warmer temperatures (-200C) Muscles are preferred injection sites as they have greater blood supply than other body tissues Vaccine Action Able to bring in immune cells faster to process foreign antigens6 Able to drain away foreign vaccine material fasterà minimizing local reactions6 Cell-mediated Immunity Spike protein degraded by intracellular enzymes into fragments Humoral Immunity Natural cellular processes release spike protein components from the cell into the bloodstream Spike protein components are engulfed by antigen presenting cells (dendritic cells, B cells, macrophages), fragmented, & bound to unique MHC Class II proteins MHC Class II proteins bring spike protein fragments to the antigen presenting cell’s surface, to present them to circulating naïve CD4+ (helper) T cells Some naïve helper T cells are able to successfully bind to the spike protein-MHC Class II protein complexes Binding activates these spike-protein specific helper T cells Spike protein fragments bound by MHC Class I proteins MHC Class I proteins bring spike protein fragments to the human cell surface MHC Class I proteins present spike protein fragments to naïve CD8+ T cell Naïve CD8+ T cells that able to bind to the spike protein-MHC Class I protein complex become activated, and travel to the lymphatic system to mature MHC = Major Histocompatability Complex; cell surface proteins key to immune function CD = Cluster of Differentiation; glycoproteins on T cell surfaces that are co-receptors and facilitate T cell binding to antigens/MHC complexes. They also distinguish the types of T cells. Some of these T-Cells mature into cytotoxic T cells that now recognize the viral spike protein Cytotoxic T-cells bind to human cells infected with SARS-CoV-2 expressing spike protein or spike protein fragments Cytotoxic T cell releases enzymes perforating infected cell, causing cell death to occur Immune system identifies and destroys human cells infected with SARS-CoV-2, slowing viral spread Other T cell’s can mature into memory T cells (stimulated by cytokines released by helper T cells) Memory T cells travel to lymphatic tissue, awaiting activation from future exposure to spike protein More rapid cell-mediated immune response to future SARS-CoV-2 infection (immunity) Activated helper T cells specific to the viral spike protein secrete cytokines to stimulate immune activity Systemic cytokine releaseàsystemic reactions like fever, chills, fatigue, myalgias (Transient) Some B cells mature into plasma cells that produce IgG antibodies against the viral spike protein Antibodies to spike protein mark SARS-CoV-2, allowing immune system to destroy virus Eradication of SARS-CoV-2 in extracellular compartments Activated helper T cell interacts with naïve B cells in lymphatic tissue Some B cells mature into memory B cells specific to SARS-CoV- 2 spike protein Future exposure to spike protein re-activates memory B cell in lymphatic tissue & creates plasma cells, producing antibodies more rapidly Rapid humoral immune response to future SARS-CoV-2 infection (immunity) Legend: Pathophysiology Mechanism Sign/Symptom/Clinical Finding End Result Published December 19, 2020 on www.thecalgaryguide.com

generalized-absence-seizures-petit-mal

Typical Absence (Petit Mal) Seizure Hyperventilation: A common trigger of absence seizures in pediatric patients with existing absence seizures ↑ respirationà↑ CO2 expelled from body & blood ↓ acidic CO2 levels in bloodà↑ blood pH (↓ blood acidity) Predisposes neurons to fire spontaneously and asynchronouslyà↓ seizure threshold Pathogenesis of absence seizure is complex and not yet fully elucidated, but evidence supports the cortical focus theory: Hyperexcitable focal neurons on cerebral cortex send activation signals down to thalamocortical neuron network Activated neurons in thalamus interact with cortical neurons to produce rhythmic oscillatory neuronal firing (brain waves) between these two regions of the brain Abnormal rhythmic and bilaterally synchronous activation of the cerebral cortex during wakefulness Between seizures (inter-ictal) Inter-ictal changes in neuronal firing patterns and connectivity in sensorimotor cortices (mechanism unclear) First degree relative with absence epilepsy Genetic predisposition/idiopathic (>90%) No single identified cause such as a structural lesion or single genetic mutation Multiple gene mutations that predispose to epilepsy when occurring together Authors: Alyssa Federico, Davis Maclean, Erika Russell, Harjot Atwal Reviewers: Ario Mirian, Shaily Singh*, Kim Smyth*, Yan Yu* * MD at time of publication Monogenetic mutation (<10%) Single gene mutation predisposing to epilepsy Mutations involve genes encoding voltage-gated calcium channels and gamma aminobutyric acid (GABA) receptors, which are important in regulating thalamocortical activity Absence Seizure: Brief lapse of consciousness with a vacant stare lasting 3-10 seconds, without convulsions or loss of motor tone. May occur up to 100 times per day. Seizure features (ictal phase) Absence seizures generally occur in the context of an epilepsy syndrome and present in childhood Childhood absence epilepsy: Most common form of pediatric epilepsy, characterized by absence seizures Juvenile absence epilepsy: Characterized by absence seizures +/- generalized tonic-clonic seizures Juvenile myoclonic epilepsy: Characterized by myoclonic seizures +/- absence seizures Post-seizure (post-ictal) Mechanisms unclear Consciousness regained immediately after seizure No post-ictal symptoms No memory of event Neuropsychiatric symptoms (poor attention, memory, mood, cognition) seen in 60% of children Smooth/rapid transition to seizure No aura (warning sign) prior to seizures Seizure activity directly or indirectly impairs communication between neural networksà alters activity of brain structures involved in maintaining awareness Some simple response to internal or external stimuli may remain intact (mechanisms unclear) Automatisms: Eye movements (fluttering), oral (lip smacking, swallowing, chewing), manual (finger tapping, scratching) Brain wave oscillations generated in the thalamus EEG findings: Generalized 3 Hz spike-wave activity with maximum amplitude in both frontal lobes Impaired awareness Inhibition of response to external stimuli Impaired school performance and social interactions Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 2, 2021 on www.thecalgaryguide.com

Primary-Aldosteronism

Primary Aldosteronism: Clinical findings Note: This condition is also known as “Primary Hyper-Aldosteronism” or “Conn’s Syndrome” Authors: Samin Dolatabadi Reviewers: Amanda Henderson, Hannah Yaphe, Yan Yu*, Hanan Bassyouni* Juliya Hemmett* * MD at time of publication ↑ Expression of Cl-/HCO3- exchanger in the basolateral membrane of intercalated cell of cortical collecting duct ↑ HCO3- reabsorption into bloodstream ↑ Autonomous aldosterone secretion from zona glomerulosa of adrenal cortex (e.g. aldosterone producing adenoma) ↑ Serum aldosterone level ↑ Circulating aldosterone activates mineralocorticoid receptors on cardiac myocytes ↑ Transcription of proinflammatory and profibrotic genes in cardiac myocytes Cardiac fibrosis and hypertrophy In the rest of the body, K+ moves from intracellular to extracellular environment (down it's concentration gradient) to compensate for decreased serum K+ Loss of positively charged K+ànegative intracellular chargeàcells take up H+ to remain electrostatically neutral ↑ Expression of epithelial sodium channels in principal cells of cortical collecting duct ↑ Na+ reabsorption from cortical collecting duct into blood vessels + Water follows Na into the blood vessels to balance the osmotic pressure between the blood and the renal tubules ↑ blood volume within the volume- constrained space of blood vessels ↑ Activation of Na+/K+ ATPase in principle cells of cortical collecting duct Removal of positively charged Na+ from tubular lumenà lumen becomes electronegative versus the interstitial space & inside tubular epithelial cells Positively charged K+ follows the electrical gradient and is secreted into tubular lumen ↓ Serum K+ concentration ↑ Expression of H+ ATPase in the apical (luminal) membrane of intercalated cell of cortical collecting duct H+ is secreted into cortical collecting duct → renal loss of H+ from the body Metabolic Alkalosis (blood becomes more basic; ↑ serum pH) Hypertension Muscle weakness, fatigue, polyuria ↓ pH in intercalated cell ↓ pH in cells of proximal convoluted tubule ↑ loss of H+ through kidneys H+ secretion into cortical collecting duct ↑ H+ ATPase activity in intercalated cell Activation of glutaminase in proximal convoluted tubule HCO3- pumped into blood ↑ production of HCO3- (product of glutamine breakdown) ↑ breakdown of glutamine Hypokalemia (See Hypokalemia: Clinical Findings slide) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 16, 2020 on www.thecalgaryguide.com

Maternal-complications-after-labor-and-vaginal-delivery

Maternal complications of labour and vaginal delivery Author: Yan Yu Reviewers: Kayla Nelson, Radhmila Parmar, Jemimah Raffe-Devine, Alina Constantin* * MD at time of publication Labour and vaginal delivery Detachment of placenta disrupts uterine blood vessels Intense pressure on vaginal walls during fetal passage and/or use of forceps or vacuumà physical damage vagina and perineum Urinary tract catheterization during labour Foreign tube inserted into bladder allows easier colonization of bladder & urinary tract by bacteria Urinary Tract Infections Passage of fetus distends pubo-vesicular and pubo- rectalis sling muscles Urethra /rectum no longer kinked enough to prevent high intra-abdominal pressures from forcing out urine or feces Stress incontinence (of bladder & bowel; usually temporary) Scar tissue forms at site of placental detachment After complete hemostasis (cessation of bleeding) and vessel healing, scar tissue is shed from uterus Lochia (vaginal discharge/ bleeding) & eschar (scar tissue) shedding Placental tissue may be retained in the uterus Uterus fails to contract fully to seal off uterine blood vessels Post-partum hemorrhage (See relevant slide) Foreign substances trigger systemic inflammatory response in mother Disseminated Intravascular Coagulation, DIC (see relevant slide) Rarely, torn blood vessels let amniotic fluid (with fetal cells & meconium) enter maternal circulation Amniotic fluid embolism (clumps of foreign fetal cells and meconium in maternal circulation) Viscous amniotic fluid can block maternal blood vessels Obstructing blood flow out of lungs Blood backs up before lungsàless preload for heart Damaged tissue & blood in the uterus Ample nutrients for bacteria to infect uterus Endometritis Uterine pain, radiating throughout the abdomen Pulmonary edema Hypotension Perineal tears (1st-4th degree); Hemorrhoids Perineal Pain Unilateral leg pain & swelling Dyspnea, Cough If profound Cardiac arrest Tissue damage activates blood coagulation factors ­ Coagulation in areas of hemostasis (e.g. veins) Deep Vein Thrombosis Post-partum fever (see relevant slide) Cardiovascular collapse Lack of perfusion to heart Note: Post-partum depression is commonly seen in at least 10% of newly-delivered mothers. Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Initially published September 5, 2013 on www.thecalgaryguide.com Updated and re-published January 23, 2021

Beta-Blockers-Mechanism-of-Action-and-Side-Effects

Beta-Blockers: Mechanism of Action and Side Effects Two classes of “Beta-Blockers” are used clinically: Non-cardio-selective: binds Cardio-selective: binds largely beta-1 and beta-2 receptors to beta-1 receptors Authors: Tegan Evans, Davis Maclean, Yan Yu* Reviewers:, Amanda Nguyen, P. Timothy Pollak*, Sean Spence* * MD at time of publication Beta blockers bind to beta 1 and/or beta 2-receptors of various tissues throughout body, and thus competitively inhibit binding of sympathetic adrenergic molecules (such as catecholamines from the adrenal medulla, e.g. epinephrine) to these receptors, ↓ their normal adrenergic tone Beta-2 receptor antagonism Beta-1 receptor antagonism Lungs Eyes Central nervous system Heart Kidneys ↓ cAMP (intracellular messenger) productionàcomplex, tissue-specific intracellular mechanisms resulting in a variety of effects in different tissues: Throughout body tissue Epinephrine (via cAMP) indirectly ↑ the activity of the Na+/K+ pump on cell membranes (a pump that moves 3 Na+ out of cells per 2 K+ moved into cells) Blocking epinephrine from binding the beta-2 receptor and producing cAMPà↓ activity of Na+/K+ pump à↓K+ moved into cells ↑ proportion of K+ now resides in extracellular fluid, detectable in serum (total body K+ remains the same) Hyperkalemia (see Calgary Guide: Hyperkalemia – Clinical findings) Blocking sympathetic hormonesà↓ relaxation of smooth muscle circumferentially wrapped around airways ↑ resting airway muscle toneà bronchoconstriction ↑ resistance to airflow Wheezing, dyspnea, chest tightness Exacerbation of underlying airway disease (e.g. asthma) ↓ ciliary epithelium’s production of aqueous humor (fluid that fills anterior chamber of the eye) Reduced intraocular pressure Blocking adrenergic response mediated by epinephrine and norepinephrine (e.g. the physiologic “fight- or-flight” response to stress) ↓ tremor, irritability, anxiety ↓ ability to produce adrenergic symptoms in response to hypoglycemia Hypoglycemia unawareness Coronary perfusion pressure = diastolic blood pressure in aorta – LV end diastolic pressure ↓ inotropy (contractility of cardiac muscle) ↓ chronotropy (heart rate and conduction velocity) ↓ renin releaseà↓ creation of angiotensin II & aldosterone + ↓ reabsorption of Na and H2O in nephron ↑ urinary Na+ & H2O loss ↓ total blood volume Decompensation of acute heart failure Dizziness and fatigue Hypotension (Blood pressure = cardiac output x systemic vascular resistance) ↓ O2 demand of myocardial tissue Bradycardia Inability to ↑ heart rate in response to stress (e.g. shock, sepsis) ↓ stroke volume ↓ cardiac output Beta blockers ↓ diastolic blood pressure, & thus may ↓ coronary perfusion pressure Before giving beta blockers, ensure blood pressure isn’t too low Otherwise, may worsen acute myocardial ischemia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Jan 14, 2021, updated Feb 7, 2021 on www.thecalgaryguide.com

Adenovirus-Vector-Vaccines-Against-COVID19-Production-and-Mechanism-of-Action

Adenovirus Vector Vaccines Against COVID-19: Production and Mechanism of Action Johnson & Johnson Adenovirus type 26 (Ad26), a mild human adenovirus, is isolated Previous exposure to Ad5 or Ad26 may have sensitized immune system to the adenovirus vector1 Potential for human adenovirus vaccine to fail due to previous exposureàimmunity not built against spike protein CanSino Adenovirus type 5 (Ad5), a mild human adenovirus, is isolated Oxford/AstraZeneca Chimpanzee adenovirus AZD1222 (ChAdOx1), previously shown to be safe & to elicit an immune response in humans2, is isolated Vaccine Production SARS-CoV-2 (virus causing COVID-19) synthetic DNA library sequenced from viral RNA using reverse transcriptase polymerase chain reaction and whole genome sequencing technology Spike protein DNA sequence isolated from SARS-CoV-2 genome A promoter sequence is added to the spike protein DNA sequence, allowing human RNA polymerase to recognize and transcribe the spike protein DNA when introduced into human cells Recombinant genetic technology inserts the modified spike protein DNA into a plasmid: a circular piece of DNA that acts as a shuttle allowing for the insertion of new genes (such as the spike protein gene) into host genomes (like the adenovirus vector DNA genome) Adenoviral DNA isolated using various lytic & washing reagents (chemicals that break open cell membranes and remove non- nucleic acid cellular materials) Adenoviral DNA sequenced using whole genome sequencing, then modified as follows: Chimpanzee virus negates possibility of previous immunity to the viral vector1 Chimpanzee viral vector more likely to successfully generate immune response to the spike protein E1 region of adenoviral genome E3 region of adenoviral genome deleted to create deleted to block viral replication3 room for insertion of SARS-CoV-2 spike protein DNA3 Adenovirus used in the final vaccine cannot replicate within human cells and cannot cause human disease References 1. ACS Nano 2020, 14, 10, 12522–12537, Publication Date: October 9, 2020, https://doi.org/10.1021/acsnano.0c07197 Modified adenoviral DNA genome is reinserted into The viral vector & the spike protein plasmid are mixed together, and DNA recombination the adenovirus particle, creating the “viral vector” technology inserts the spike protein gene from the plasmid into the adenovirus DNA2 Adenovirus containing transcribable SARS-CoV-2 spike protein DNA is introduced into a special cellular culture, allowing the virus to replicate despite its modified DNA2, 3 Authors: Ryan Brenneis, Yan Yu* Reviewers: Davis MacLean, Hannah Yaphe Stephen Vaughan* * MD at time of publication 2. Nature 2020, 586, 578–582, Publication Date: October 20, 2020, https://doi.org/10.1038/s41586- 020-2608-y 3. Frontiers in Immunology 2018, 9, 1963, Publication Date: September 19, 2018, doi: 10.3389/fimmu.2018.01963 4. NPJ Vaccines 2020, 5, 69, Publication Date: July 27, 2020, doi: 10.1038/s41541-020-00221-3 5. The Lancet 2020, Publication Date: Dec. 8, 2020, https://doi.org/10.1016/S0140-6736(20)32623-4 6. BMJ 2000, 321, 7271, 1237-1238, Publication Date: November 18, 2000, DOI: 10.1136.bmj.321.7271.1237 7. NEJM 2021, Publication Date: Jan. 13, 2021, DOI: 10.1056/NEJMoa2034201 Adenovirus containing transcribable SARS-CoV-2 spike protein DNA is isolated and concentrated to a high enough level for administration as a vaccine Adenoviruses have an outer protein layer (called a capsid) to protect its DNA DNA is more stable than mRNA due to deoxyribose sugar backbone and intermolecular bonds between strands Enhanced stability compared to mRNA lipid nanoparticle vaccines Can be stored at 2-8°C for up to 3-6 months Muscles are preferred injection sites as they have greater blood supply than other body tissues Immune cells arrive faster to The viral vector vaccine is injected intramuscularly into a healthy person process foreign antigens6 Foreign substance can cause local tissue inflammation Pain, redness, swelling at injection site (Transient) Note: The Johnson and Johnson vaccine may be 90% effective after a single dose7 Foreign vaccine material drains away fasterà minimizing local reactions6 2nd dose after 28 days recommended to strengthen the immune response (to a level exceeding the immune response in patients recovered from Covid-19), boosting vaccine efficacy especially in older individuals5 Vaccine Action Cell-mediated Immunity Spike protein degraded by intracellular enzymes into fragments Adenovirus surface antigens interact with human cellular receptors, allowing viral entry into human cell via endocytosis3 Adenovirus vector travels to cell nucleus, merges with nuclear envelope and injects its DNA (including the spike protein DNA) into the nucleus RNA polymerases in the nucleus transcribe the viral DNA, making messenger RNA (mRNA) for SARS-CoV-2 spike protein mRNA is transported back into the cytosol & translated by ribosomes naturally found there, producing full length SARS-CoV-2 spike protein Humoral Immunity Natural cellular processes release spike protein components from the cell into the bloodstream Spike protein components are engulfed by antigen presenting cells (dendritic cells, B cells, macrophages), fragmented, & bound to unique MHC Class II proteins MHC Class II proteins bring spike protein fragments to the antigen presenting cell’s surface, to present them to circulating naïve CD4+ (helper) T cells Some naïve helper T cells are able to successfully bind to the spike protein-MHC Class II protein complexes Binding activates these spike-protein specific helper T cells Spike protein fragments are bound by MHC Class I proteins MHC Class I proteins bring spike protein fragments to the human cell surface MHC Class I proteins present spike protein fragments to naïve CD8+ T cell Naïve CD8+ T cells that able to bind to the spike protein-MHC Class I protein complex become activated, and travel to the lymphatic system to mature3 MHC = Major Histocompatability Complex; cell surface proteins key to immune function CD = Cluster of Differentiation; glycoproteins on T cell surfaces that are co-receptors and facilitate T cell binding to antigens/MHC complexes. They also distinguish the types of T cells. Some of these T cells mature into cytotoxic T cells that now recognize the SARS-CoV-2 spike spike protein Cytotoxic T cells bind to human cells expressing spike protein or spike protein fragments (e.g. future COVID-19 infection) Cytotoxic T cells release enzymes perforating infected human cells, causing cell death to occur Immune system can now more quickly identify & destroy human cells showing signs of COVID-19 infection Some T cell’s can mature into memory T cells (stimulated by cytokines released by helper T cells) Memory T cells travel to lymphatic tissue, awaiting activation from exposure to spike protein in the future More rapid cell-mediated immune response to future SARS-CoV-2 infection (immunity) Activated helper T cells specific to the viral spike protein secrete cytokines to stimulate immune activity Systemic cytokine releaseàsystemic reactions like fever, chills, fatigue, myalgias (Transient) Note: Duration of cellular/ humoral immunity is unknown Some B cells mature into plasma cells that produce IgG antibodies against the viral spike protein Antibodies to spike protein mark SARS-CoV-2, allowing immune system to destroy virus Eradication of SARS-CoV-2 in extracellular compartments Activated helper T cell interacts with naïve B cells in lymphatic tissue Some B cells mature into memory B cells specific to SARS-CoV- 2 spike protein Future exposure to spike protein re-activates memory B cell in lymphatic tissue & creates plasma cells, producing antibodies more rapidly Rapid humoral immune response to future SARS-CoV-2 infection (immunity)3 Legend: Pathophysiology Mechanism Sign/Symptom/Clinical Finding End result Published February 11, 2021 on www.thecalgaryguide.com

Potassium-Sparing-Diuretics-Mechanism-of-Action-and-Side-Effects

Potassium-Sparing Diuretics: Mechanism of Action and Side Effects Potassium-Sparing Diuretics Authors: Samin Dolatabadi, Yan Yu* Reviewers: Jessica Krahn, Timothy Fu, Juliya Hemmett* * MD at time of publication Epithelium Sodium Channel Blockers (Amiloride and Triamterene) Inhibit Na+ channels (involved in Na+ reabsorption) in the luminal membrane of the principal cells in the cortical collecting duct Aldosterone Antagonists (Spironolactone and Eplerenone) Competitively blocks mineralocorticoid receptors and ↓ aldosterone effect in the renal tubules and throughout the body ↓ aldosterone effectà↓ expression of basolateral Na+/K+ pumps & luminal epithelium Na+ channels on the principal cells of cortical collecting duct Spironolactone’s molecular structure is similar to that of steroid hormonesàspironolactone can also block androgen receptors Anti-androgenic effects (due to ↓ androgen function in reproductive organs, skin, and on brain centers) Triamterene can form triamterene crystals and granular casts (unclear mechanism) ↓ Na+ reabsorption by principal cells ↓ in serum Na+ concentration: Hyponatremia ↓ K+ pumped out into the tubule by principal cells Crystals & casts obstruct tubular lumen → inflammation (unclear mechanism) Triamterene crystals are directly cytotoxic to tubular cells Only ~2-5% of Na+ filtered by the glomerulus is normally reabsorbed in the cortical collecting ductàthe ↑ in Na+ retained in cortical collecting duct is mild Water follows Na+ to maintain a balanced osmotic pressureà↑ in water in cortical collecting duct available for excretion ↑ positive charges in lumen relative to surroundings generates an electropositive tubular lumen Unfavorable electrical gradient ↓ secretion of positive charged ions into electropositive lumen ↓ libido Menstrual abnormalities (in women) ↓ acne Gynecomastia (in men) ↓ secretion of K+ ↑ in serum K+ concentration: Hyperkalemia Cardiac Arrythmias (See relevant slide on Hyperkalemia: Clinical Findings) Interstitial inflammation and tubular injury Drug-induced Nephrotoxicity Mild Diuresis ↓ blood volume ↓ Blood pressure/ Hypotension ↓ secretion of H+ ↑ in serum H+ concentration: Metabolic Acidosis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 15, 2021 on www.thecalgaryguide.com

Avascular-necrosis-of-the-femoral-head

Avascular Necrosis (AVN) of the Femoral Head: Findings on X-Ray Blood supply to the subchondral bone is disrupted (for full pathogenesis, see Calgary Guide slide Avascular Necrosis: Pathogenesis and clinical findings) Hypoxia at boneàOsteocyte (primary bone cell) apoptosis Authors: Daniel Cusano, Evan Allarie, Reviewers: Yan Yu* Davis Maclean, Shelley Spaner* *MD at time of publication ↓ local osteoprotegerin (OPG) production OPG acts to 1) inhibit osteoclast formation, & 2) bind and sequester RANKL, a chemical that stimulates osteoclast activation & proliferation ↓ OPGà↑ osteoclast activation & proliferationà↑ bone resorption Areas that absorb ↑ X-ray radiation appear brighter on X-ray RANKL - Receptor activator of nuclear factor kappa-Β ligand Basic X-Ray Physiology Bone absorbs more X-ray radiation than other tissues in the body (e.g fat and muscle) Areas of ↓ bone density are darker: described as (radio)lucency on X-ray Areas of ↑ bone density are whiter: described as sclerotic on X-ray Image Credit: Alberta Health Services Repository ↓ Production of vascular endothelial growth factor (VEGF), which normally maintains & builds healthy bone & vasculature (via a multifactorial process) Osteopenia: generalized ↓ in bone density, visualized as ↑ radiolucency (darkness) of bone Bone demineralization and collagen matrix destruction Scattered Cysts: radiolucent areas of resorbed bone The femoral head’s trabecular bone is normally more porous (less dense) than the overlying cortical boneàosteopenia affects trabecular bone first, structurally weakening the femoral head Osteoclast activity, and a shift in the balance of multiple cell signaling factorsàcompensatory activation of osteoblasts (bone forming cells) Altered femur structure changes associated joint alignments (e.g. in hip, knee) Repetitive microtrauma and abnormal frictional forces in affected joints Degenerative arthritis: joint space narrowing, osteophytes, acetabular degeneration (late, chronic findings not pictured here) For examples, see Calgary Guide slide Osteoarthritis (OA): X-Ray Findings Fracturing of trabecular bone underneath the cortical bone of the femoral head Fracture creates a curved space between subchondral trabecular bone and overlying subchondral cortical bone Continued net resorption of bone & subcortical fracturingà overlying cortical bone collapses Flattening of femoral head (late, chronic finding; not pictured here) Deposition of collagen matrix and bone re-mineralization Patchy Sclerosis Dense (white) areas of bone deposition Crescent Sign Subcortical lucency indicative of fracture there (atypical outside of instances of avascular necrosis) • X-ray provides a fast and inexpensive imaging modality compared to MRI, however X-ray sensitivity varies from 41- 71% and is best suited to detect more advanced disease • MRI sensitivity is higher at 71-100% across different studies, with the added benefit of being able to detect internal bone changes earlier than X-ray Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 26, 2021 on www.thecalgaryguide.com

AAA-Pathogenesis

Abdominal Aortic Aneurysm (AAA): Pathogenesis Different parts of the aorta have different embryologic origins Atherosclerosis Hypertension Age > 65 Progressive deterioration of aorta structural integrity over life span Connective Tissue Disease Structurally abnormal protein or protein organization in aorta Autoimmunity Infection (e.g Chlamydia, Mycoplasma pneumoniae, Helicobacter pylori, human cytomegalovirus, herpes simplex virus) Antigens (substance that causes immune response) on virus or bacteria resemble local proteins in abdominal aorta Antibodies produced in response to infection inappropriately target host cells in the aorta Antibodies tag cells in the abdominal aorta for destruction by T-lymphocytes Immune-mediated destruction of aorta Smoking Genetics Unclear mechanisms Subacute (not clinically detectable) inflammation of aortic tissue Inflammatory cytokines are released and immune cells are recruited ↑ pressure on aorta and other vessel walls Infiltration of vessel wall by lymphocytes and macrophages Production of enzymes that break down elastin & collagen proteins (which provide most tensile strength to aorta) Aorta susceptible to damage Degradation of aortic connective tissue Biomechanical stress on vessels Authors: Olivia Genereux Davis Maclean Reviewers: Jason Waechter* Amy Bromley* Yan Yu* *MD at time of publication The exact mechanisms are complex, debatable, and an area of intensive research – the 3 mechanisms and associated pathophysiology presented here are generally thought to be the main causes of abdominal aortic aneurysms Infrarenal aorta has poorly developed vaso vasorum (dedicated blood supply to vessel wall) Infrarenal aorta relies solely on nutrient diffusion from aortic blood that crosses abdominal aorta Infrarenal aortic wall has fewer “lamellar” units (fibromuscular units) than other regions of the aorta Infrarenal aorta is less elastic & less able to distribute stress Loss of smooth muscle cells & thinning of tunica media Destruction of elastin in tunica media Normal layers of the aortic wall ↓ aortic tensile strength (ability to withstand stretching) Aorta expands and dilates due to internal pressure Tunica Intima (inner-most tissue layer of aorta) Tunica Media (layers of elastic tissue (elastin) and muscle fibers) Adventitia (thin outermost collagenous layer) (longitudinal section) Aortic aneurysms are usually infrarenal (85%) Abdominal Aortic Aneurysm Infrarenal aorta more prone to ischemia and has impaired repair potential Abnormal, irreversible dilation of a focal area of abdominal aorta (area of aorta between diaphragm & aortic bifurcation) to twice the diameter of adjacent normal artery segment Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published February 27, 2021 on www.thecalgaryguide.com

AAA-Clinical-Findings-and-Complications

Abdominal Aortic Aneurysm (AAA): Clinical Findings and Complications AAA = Abnormal, irreversible dilation of a focal area of abdominal aorta (area of aorta between diaphragm & aortic bifurcation) to twice the diameter of adjacent normal artery segments Asymptomatic, non-ruptured aneurysm: Most AAAs are asymptomatic until rupture or days before impending rupture Asymptomatic AAAs are only detectable on imaging or by palpation Given their structural weakness, AAAs are at risk of rupture (risk ↑ with ↑ size of aneurysm) Ruptured AAA: a medical emergency Aorta lies in between the peritoneal and retroperitoneal space Symptomatic, non-ruptured aneurysm: rarely, an unruptured AAA can cause symptoms or complications (0.1%-1% of AAAs) Authors: Olivia Genereux, Davis Maclean, Yan Yu* Reviewers: Jason Waechter*, Amy Bromley*, Sandeep Aggarwal*, Gregory Samis* *MD at time of publication Posterior aortic wall rupture Retroperitoneal hemorrhage Sudden and severe abdominal and/or back pain Anterior aortic wall rupture Peritoneal hemorrhage Peritoneal space is larger and holds larger volumes of blood Peritoneal hemorrhages are large (entire blood volume can pool in the peritoneal space in minutes) Prior to rupture, the adventitia (thin outermost collagenous layer of the aorta) may dilate significantly Adventitia is the only layer of the aorta that contains sensory innervation à nociceptors there can be activated by adventitia dilation Very rarely (0.1%), areas of stagnant blood flow within the AAA allow for blood & clotting factors to accumulate Thrombi (blood clots) develop in these aneurysms Thrombi may dislodge and travel (embolize) to distal vasculature, cutting off blood- flow to these areas This process (referred to as tamponade) is crucial in preventing catastrophic blood loss, allowing for a window of opportunity for treatment Compensated Hypovolemic Shock: Low blood pressure & poor organ perfusion, but blood loss has temporarily stopped. This state of shock is compatible with life if patient is otherwise healthy (e.g. no coronary artery disease) ↓ space for blood to accumulate in the retroperitoneal space (compared to the peritoneal space) Rapid pressure ↑ in retroperitoneal space overcomes the pressure in aorta Since blood will only travel from areas of ↑ pressure to areas of ↓ pressure, this pressure gradient prevents further blood loss from ruptured aorta Massive hemorrhage due to high blood flow volume through aorta Hypotension and rapid progression to hypovolemic shock Abdominal and/or àorgan ischemia back pain The most common symptom of a symptomatic non- ruptured aneurysm, and may be the first sign of an impending aneurysm rupture Death within minutes (rare) If low blood pressure is now (inappropriately) treated with fluid resuscitation, the blood pressure will ↑ Differential pressure gradient is reversed (aortic blood pressure > pressure in retroperitoneal space) Bleeding into retroperitoneal space resumes Decompensation of hypovolemic shock Possible death Kidney ischemia Lower limb ischemia Time exists to transfer patient to tertiary care center for surgical treatment Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published February 28, 2021 on www.thecalgaryguide.com

Cubital-Tunnel-Syndrome-Ulnar-Neuropathy

Cubital Tunnel Syndrome (Ulnar Neuropathy): Pathogenesis and clinical findings Osteoarthritis Rheumatoid arthritis Diabetes mellitus (see Calgary Guide slide on Diabetic Neuropathy) Degenerative bone & joint changes Autoimmune damage to joints Abnormal bone structure/lesions Idiopathic Hyperglycemia causes nerve damage (complex mechanisms) Elbow trauma Repetitive elbow flexion Authors: Chris Oleynick Alexandros Mouratidis Yan Yu* Reviewers: Annalise Abbott Sean Crooks Davis Maclean Hannah Koury Jeremy LaMothe* Ian Auld* * MD at time of publication Inflammation or edema in cubital tunnel (space between medial epicondyle of humerus and olecranon of ulna) where ulnar nerve is found ↓ size of the cubital tunnelà↑ pressure on internal contents (e.g. ulnar nerve) Axonal conduction is interrupted Myelin sheath is damaged ↓ blood supply to nerve Weakness of adductor pollicus longus (works to adduct thumb) ↑ compensatory activity of flexor pollicis longus with pinching ↓ activity of hypothenar muscles (which move the 5th digit) ↓ activity of 5th digit palmar interosseus muscles (which adduct the 5th digit) Cubital Tunnel syndrome: compression neuropathy Paresthesia Abnormal sensations of skin (“pins & needles”, tingling, burning, and/or numbness) in ulnar nerve sensory distribution ulnar nerve ↓ activity of muscles innervated by ulnar nerve (medial forearm flexors, hypothenar muscles, interossei muscles, adductor pollicis longus) + Tinel sign over cubital tunnel (tapping at medial elbow causes discomfort and/or paresthesia) Weak pinch & ↓ grip strength + Froment’s sign (thumb hyperflexion compensates for weak pinch) Hypothenar atrophy + Wartenburg’s sign (involuntary, excess abduction of 5th digit) of the Altered sensation in areas innervated by ulnar nerve (medial forearm and wrist, 5th digit, and medial half of 4th digit) + elbow flexion test (flexing elbow & extending wrist further ↓ volume of the cubital tunnelà paresthesia in ulnar nerve sensory distribution Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications First published January 12, 2017, re-published February 28, 2021 on www.thecalgaryguide.com

acute-mca-territory-ischemic-stroke-findings-on-non-contrast-ct

Acute MCA-Territory Ischemic Stroke: Findings on Non-Contrast CT See Calgary Guide slide – Ischemic Stroke: Pathogenesis Middle cerebral artery (MCA) strokes are generally caused by emboli (blood clot that travelled from elsewhere in the body) and less commonly caused by thrombus (blood clot that has developed locally in the MCA) Embolism (or thrombus) occludes flow through the MCA Acute embolism (or thrombus) is more dense than surrounding tissue Acute embolism (or thrombus) material attenuates (absorbs more X-rays) more than surrounding tissue (results in area of brightness) Hyperdense MCA sign ↓ blood supply to MCA vascular territory (e.g. basal ganglia or insula) ↓ oxygen for aerobic metabolism (produces large amounts of ATP) ↓ ATP production in area of ischemia ↓ energy for ATP-dependent Na+/K+ pumps (that move Na+ out of cells) in affected neurons (grey matter) Neurons have a higher metabolic rate than other nervous system cells (e.g oligodendrocytes that make myelin) and thus are more vulnerable to hypoperfusion and ischemia As grey matter contains more neurons than white matter, grey matter is more vulnerable to hypoperfusion and ischemia Grey matter shows changes on CT earlier than does white matter Normal grey versus white matter on CT On CT, structures that are more dense (e.g. bone, tissues) absorb more X-raysà brighter. Less dense regions (e.g. water, fluids, fat) absorb less X-raysàdarker. Authors: Evan Allarie Davis Maclean Viesha Ciura* Yan Yu* Reviewers: Katie Lin* Aravind Ganesh* Gary Klein* *MD at time of publication ↓ extra-cellular Na+ concentration Na+ in extracellular space is replenished via capillaries Water follows the Na+ out of the capillaries ↑ intra-cellular Na+ concentration Change in osmotic gradientàwater moves from extracellular space into cells ↑ water content inside & around affected neurons (grey matter) Affected grey matter looks darker on CT (more similar to white matter) White matter contains more fatty myelin (lower density than grey matter)à appears darker on CT Normal insular ribbon (difficult to see here): grey matter usually seen lateral to red line shown here Grey matter, with more neurons, has a higher densityà appears brighter on CT Normal basal ganglia: Lentiform nucleus (putamen + globus pallidus) outlined here Loss of grey-white differentiation throughout MCA vascular territory Difficult to see on this window (adjustable brightness of image) but is present on this scan and easily seen at different window levels Areas with the least collateral circulation (e.g. basal ganglia or insula) show findings first Insular ribbon sign (loss of insular ribbon) Disappearing basal ganglia sign (loss of visible basal ganglia) Comparison to normal anatomy helps outline pathologic findings Comparison to normal anatomy helps outline pathologic findings Images presented here are multiple CT images from the same patient with a large MCA territory ischemic stroke (Image credit: Alberta Health Services Repository) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 7, 2021 on www.thecalgaryguide.com

Achilles-Tendon-Rupture

Achilles Tendon Rupture: Pathogenesis and Clinical Findings Achilles tendon ruptures are multifactorial, and may arise from any one or combination of the factors below Authors: Alyssa Federico, Joseph Kendal Reviewers: Davis Maclean, Hannah Koury , Amanda Eslinger, Maninder Longowal, Dave Nicholl, Mehul Gupta, Gerhard Kiefer*, Yan Yu*, Jeremy LaMothe* * MD at time of publication Aging Iatrogenic factors E.g. use of fluoroquinolone antibiotics,or local or systemic corticosteroids Exact mechanisms remain unclear Exercise related factors Vascular compromise Any process that impairs blood flow to the Achilles tendon (e.g. peripheral artery disease) Impaired ability to heal from microtrauma Mechanical factors Abnormal biomechanics: bowleg, flatfoot, excessive supination, obesity, change in terrain Participation in vigorous exercise Excessive heat generation (hyperthermia) in Achilles tendon induces changes in the extracellular matrix Intra-tendinous collagen degeneration, disorientation, and thinningàcompromised Achilles tendon integrity Sudden shear stress and high tension in an already weakened Achilles tendon, stretching it beyond its capacity Haglund’s deformity: enlargement of the calcaneal postero- superior tuberosity Bony enlargement rubs on soft tissue and causes inflammation of Achilles tendon ↓ tendon strength from changes in extracellular matrix Episodic participation or sudden ↑ in exercise Irregular use renders Achilles tendon weaker Microtrauma to the and less flexible Achilles tendon on Achilles Tendon Abnormal loading Sudden, forced dorsiflexion of foot Eccentric contraction of the gastrocnemius-soleus complex The gastrocnemius muscle normally attaches to Achilles tendon to control plantar flexion of the foot With the Achilles tendon ruptured, contraction of the gastrocnemius muscle cannot induce plantar flexion Achilles tendon rupture Achilles tendon innervated by the sural nerve and tibial nerve Pain over rupture site (e.g. “like being kicked in the back of the leg”) Antalgic gate: abnormal gait developed to avoid pain while walking High tension at the origin and insertion points of the tendon causes the ends of the tear to separate The Achilles tendon contains blood vessels. Rupturing the tendon also ruptures the blood vessels withinàblood leaks out into tendon rupture site Bruising and swelling over rupture site ↓ resting ankle plantar flexion (Observed in prone position with knees flexed at 90 degrees) Passive contraction (e.g. squeezing) of the gastrocnemius does not cause plantar flexion + Thompson (calf squeeze) test Weak ankle plantar flexion Lack of push-off in gait Audible “pop” at time of injury Palpable gap between rupture ends Difficulty ambulating ↓ muscle use over time Calf atrophy Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published March 21, 2021 on www.thecalgaryguide.com

epidural-hematoma-pathogenesis-and-clinical-findings

Epidural Hematoma: Pathogenesis and clinical findings Head trauma (e.g., accidents, falls, assaults) Authors: Krusang Patel Yan Yu* Reviewers: Davis Maclean Austin Laing Gary Klein* * MD at time of publication General force of trauma transiently disturbs structures involved in consciousness (e.g., axonal injury from shear force) Initial Loss of Consciousness (LoC) Patient awakens as initial insult to the brain has subsided, not enough to permanently affect consciousness, and normal action potentials resume Briefly regain consciousness (Lucid Interval), until: Pressure stimulates emetic (vomiting) centers in the medulla Nausea Pressure interrupts area in parietal cortex responsible for up-down spatial orientation Dizziness Pressure compresses brain tissue Headache Most (75%) occurs beneath the pterion (location where frontal, sphenoidal, temporal and parietal bone meet) Multiple bony connections ↓ stability in this region Pterion region of the skull is the thinnest portion of the skull Middle Meningeal Artery located under temporal bone & pterion This area of skull susceptible to traumatic fractures Fracture lacerates the Middle Meningeal Artery Bleeding into the epidural space, where Middle Meningeal Artery runs Blood accumulates in the epidural space, but not yet to the extent that consciousness is affected Blood continues to build up in the epidural space Suture lines (attaches dura to the overlying bone) limit hematoma expansion anteriorly and posteriorly - Hematoma can only expand medially (inwards) towards brain parenchyma More blood accumulatesà ↑ intracranial pressure (ICP) EPIDURAL HEMATOMA: Collection of blood in the epidural space between the inner layer of the skull and outer layer of the dura mater For more information on imaging findings of Epidural hematoma, see Calgary Guide slide - Acute Epidural Hematoma: Findings on CT Cerebellar tonsil (located on the underside of the cerebellum) herniates through foramen magnum, an opening in the base of the skull Cerebellar tonsil compresses brainstem Brainstem (controls functions like breathing, swallowing, blood pressure, and consciousness) loses function Coma or Death Uncus (processes emotions) on baso-medial surface of temporal lobe herniates through tentorial notch, an opening between supra and infratentorial spaces Uncus compresses oculomotor nerve (CN III), needed for ocular movement Muscles for ocular movement (except lateral rectus and superior oblique) and parasympathetic innervation to the pupil are unable to function Eye pulled down and out and pupillary dilation Intracranial pressure becomes greater than mean arterial pressure ICP compresses arterioles in brain ↓ cerebral blood flow Activates α1 adrenergic receptors (part of sympathetic nervous system) Arteries in the body constrict to divert blood flow to the brain Hypertension Cushing’s Triad Baroreceptors in aortic arch detect ↑ blood pressure Stimulates vagus nerve (part of parasympathetic nervous system) Vagus nerve releases acetylcholine, binding M2 muscarinic receptors on SA node membrane, inhibiting sympathetic activity and slowing SA node activity Bradycardia ↑ ICP compresses respiratory centers in the medulla ↓ Respiration Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 11, 2021 on www.thecalgaryguide.com

COVID-Public-Health-Control-Measures

Public Health Control Measures in Response to COVID-19 Authors: Davis Maclean, Yan Yu*, Carol Fenton* Reviewers: Hannah Yaphe, Timothy Fu, Jia Hu* * MD at time of publication COVID-19 An infectious disease caused by the SARS-CoV-2 virus Virus replicates in infected patients, and is released in respiratory droplets when infected people cough, sneeze or talk R0 for COVID-19 = 2-2.5 (in comparison, R0 for influenza = 1.28) R0 = Average # of people that one contagious person will infect when all are susceptible to infection. NOTE: R0 for COVID-19 ↑↑ in indoor, poorly ventilated, crowded settings. People infected by SARS-CoV-2 are more likely to pass the virus onto others than people infected by other viruses (e.g. flu) ↑ Production of ventilators ↑ Available hospital beds & staff (e.g. cancel elective surgeries, discharge inpatients earlier) ↑ Supply of personal protective equipment (higher- grade masks like N95 respirators, goggles, gowns, gloves) Hospital administration response Epidemic curve with no intervention Smaller respiratory droplets (aerosols) containing the virus can remain airborne Wear a high-quality, well- fitting face mask (with minimal gaps between mask & face) in public, especially indoors Some infected individuals can rapidly infect large numbers of other people ↑ Sick/critically ill patients Acute care (e.g. hospital) system risks becoming overwhelmed by patient volume Risk of insufficient medical & protective equipmentàrisk of nosocomial viral spread # of cases Larger respiratory droplets containing the virus can travel ~2 meters Maintain physical distance of 2 meters from other people Unmet health needs Capacity of health system Time Once settled on a surface, the virus may remain viable for up to 72 hours, but can be destroyed by soap or ethanol Frequently wash hands and surfaces (soap + water or ethanol-based hand rub) Infection can occur if virus contacts mucous membranes Avoid touching mouth, nose, eyes & facemask; get vaccinated against the virus After host is infected, virus has a incubation period up to 14 days. Host is infectious for ~10 days after symptom onset, as long as all symptoms other than cough have resolved Individual-level prevention measures Protection measures needed Remove source of infection (e.g. mandatory mask policies; closing borders to travel) 14 day quarantine for returning travelers & close contacts of COVID patients; minimum 10 day isolation for symptomatic patients ↓ Crowding & time spent indoors (e.g. closing schools, limiting hospital/long term care visitation, cancelling indoor mass gatherings) ↑ mortality among elderly and those with co-morbidities Improving indoor ventilation (e.g. opening windows), ↑ air filtration Break chain of infection ↑ Surveillance & testing for COVID-19 Contact tracing, isolating close contacts & those exposed Assessment of population to identify at-risk groups (e.g. ↑ protection of elderly) and to continuously inform public measures (e.g. assess whether interventions are working) Disaster and emergency management (e.g. coordinate with emergency experts and first responders) Research/Evaluation: developing and appraising the evidence to optimize the response (e.g. best use of masks and supplies, develop treatments & vaccines) Public health control measures Community (e.g. out-of-hospital) measures to reduce the number of people infected and hospitalized. Goals include 1) removing the infection sources, 2) breaking the chain of transmission, and 3) protecting unexposed individuals ↑ Resources for urgent and critical patient care Limit viral spread within communities Cases spread over longer time # of cases ↑ capacity of health system End goal: Minimize serious illness and overall death in the population Time Legend: Pathophysiology Public Health Intervention Result Complications First published April 2, 2020; updated May 1, 2021 on www.thecalgaryguide.com

Bacterial-Osteomyelitis

Bacterial Osteomyelitis: Pathogenesis and clinical findings Authors: Mehul Gupta Reviewers: Stephen Vaughan* Yan Yu* * MD at time of publication Iatrogenic: Penetrating medical procedure introduces bacteria directly to bone Systemic immune reaction Macrophages, neutrophils and dendritic cells are activated by recognizing bacterial pathogen associated molecular patterns (PAMPs) Trauma: Penetrating injury or open fracture introduces bacteria directly to bone Hematogenous: Blood carries bacteria from distant site of infection to bone Contiguous: Neighboring site of infection seeds bacteria directly to bone Bacterial Osteomyelitis Innate Immune cells and local mast cells release vasoactive cytokines Capillaries dilate to ↑blood flow to affected area and become more permeable to allow for exit of immune cells and plasma contents Localized Immune response Poorly understood mechanismsàinnate immune systems unable to clear the bacteria in some individualsàchronic infection Immune cells produce pyrogenic intermediates (i.e. PGE2, IL-6, and IL-1) Pyrogenic intermediates travel through the bloodstream to the hypothalamus and alters the body’s thermal setpoint Fever Immune cells produce inflammatory cytokines (i.e. TNFα and IL6) Systemic inflammatory cytokines result in the production of Non-specific acute- phase reactants High Serum CRP and ESR Warmth Erythema Progressive blood vessel occlusion by immune cellular and bacterial debris causing infarct and necrosis of bone More permeable capillaries allow plasma to leak into surrounding periosteal tissue More permeable capillaries allow macrophages and neutrophils to exit the capillaries at the site of infection Immune cells phagocytize bacteria, producing an of opaque off-white fluid Pus Immune cells sequester necrotic bone tissue into a regional abscess within medullary bone Sequestrum seen as localized opacity on CT or late X-ray imaging ↑ Osteoclast activity to remove damaged medullary bone and ↑ Osteoblast activity to reform new bone Osteoclasts and osteoblasts remodel and deposit new bone in area surrounding necrotic tissue Swelling ↑ Periosteal fluid applies ↑ pressure to surrounding nerve endings Bone Pain manifesting as refusal to use limb New layer of bone formed Positive Bone Scan in area of infection Abbreviations: • IL – Interleukin • PGE2 – Prostaglandin E2 • TNFα – Tumor necrosis factor alpha Involucrum / Periosteal Reaction: seen as regional luminance surrounding sequestrum on CT or late X-ray imaging Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 21, 2021 on www.thecalgaryguide.com

Thyroïdite

Thyroïdite : Pathogénie et résultats cliniques Authors: Jaye Platnich Reviewers: Matthew Harding Mark Elliott Hanan Bassyouni* * MD at time of publication Hypertrophie ferme et diffuse de la glande thyroïde (douloureuse dans le cadre d'étiologies subaiguë, radique et infectieuse) Symptômes généraux de l’hyperthyroïdie Post-natal Médicaments/ Radiation Thyroïdite bactérienne Subaigüe (post-virale) Abbréviations: • TSH- Hormone stimulant de la thyroïde Inflammation de la glande thyroïde Plusieurs méchanismes Brianna Ghali Sylvain Coderre* Phillippe Couillard* Translator: Infiltration de la glande thyroïde avec des globules blancs Destruction immunitaire de la glande thyroïde ↑ libération de T4 et T3 stockés par glande thyroïde endommagée durant 2-6 semaines (phase hyperthyroïde) ↓ sécrétion de T4 et T3 de la glande thyroïde endommagée durant des semaines-mois (phase hypothyroïde) Souvent une résolution à un état euthyroïde (normal), mais peut aussi rester dans un état hypothyroïde ↑ T4/T3 inhibe la libération de la TSH par la ↓ sécrétion TSH Réaction inflammatoire altère la fonction folliculaire normale (production T4/T3 et importation d’iode) glande pituitaire ↓ Absorption de l'iode par la glande thyroïde ↓ Capture de l'iode radioactif à la scintigraphie de médecine nucléaire Plusieurs méchanismes Symptômes généraux de l’hypothyroïdie ↓ T4/T3 stimule la liberation de la TSH par la ↑ sécrétion TSH Dommage altère la fonction folliculaire normale, (production T4/T3 et importation d’iode) glande pituitaire ↓ Absorption de l'iode par la glande thyroïde ↓ Capture de l'iode radioactif à la scintigraphie de médecine nucléaire Légende: Pathophysiologie Méchanisme Signes/Symptômes/Résultats labo Complications Publié June 19, 2013 on www.thecalgaryguide.com

VITT

Vaccine Induced Thrombosis and Thrombocytopenia (VITT): Pathogenesis and Clinical Findings Current leading theory: COVID-19 viral vector vaccines (Johnson and Johnson and AstraZeneca) contain an anionic molecule (currently unspecified), which binds to the cationic platelet factor 4 (PF4) molecule in the bloodstream, forming vaccine/PF4 complexes Authors: Brooke Fallis Reviewers: Yan Yu* Katie Lin* * MD at time of publication Spleen macrophages remove antibody/platelet complexes from circulation Fewer unbound platelets in circulation detected on complete blood count (CBC) Thrombocytopenia: Platelets <150x!

Lambert-Eaton-Myasthenic-Syndrome-Pathogenesis-and-Clinical-Findings

Lambert-Eaton Myasthenic Syndrome: Pathogenesis and Clinical Findings Authors: Alexandros Mouratidis Dmitriy Matveychuk Ario Mirian Reviewers: Austin Laing Davis Maclean Michal Krawcyzk Harjot Atwal Chris White* Yan Yu* * MD at time of publication Acquired autoimmunity: mechanism unknown, possibly associated with other autoimmune diseases A paraneoplastic syndrome of small cell lung cancer (SCLC) in >50% of patients Tumour membrane expresses voltage-gated calcium channels (VGCCs), which normally exist on neurons and function in neurotransmission Note: A paraneoplastic syndrome is a condition that arises due to cancer elsewhere in the body; possibly an immune response against tumour cells Positive anti-VGCC IgG on serology ↓ Stimulation of salivary glands à↓ production of saliva ↓ Nitric oxide & prostaglandin production by cavernosal endothelial cellsàImpaired vasodilation of penile arteries ↓ Acetylcholine-induced gastric motility ↓ Acetylcholine available to mediate muscle reflexes ↑ Variability in action potential initiation along muscle fibers Immune response to foreign cancer cells triggers production of antibodies against VGCCs on the cell surfaces of presynaptic neurons Antibodies bind VGCCs, blocking Ca2+ Antibodies bind, cross-link, and from entering presynaptic neurons ↓ Ca2+ influx into the presynaptic neuron during its depolarization internalize VGCCsà↓ VGCC on neuron surface Xerostomia (dry mouth) Erectile dysfunction Constipation ↓ Deep tendon reflexes Unstable motor unit action potentials on electromyography ↓ Baseline compound muscle action potentials (CMAPs: summated action potentials of all motor endplates in one muscle) on nerve conduction studies Since intracellular Ca2+ mediates neurotransmitter vesicle fusion with the presynaptic membrane, ↓ Ca2+ influx ↓release of neurotransmitters like acetylcholine into the synaptic cleft However, with repeated stimulation of the presynaptic neuron (e.g. exercise), there is ↑ Ca2+ accumulation within the axon terminal, allowing for more neurotransmitter vesicle fusion with the presynaptic membrane ↑ Acetylcholine available to mediate muscle reflexes With high frequency repetitive nerve stimulation, ↑ number of compound CMAPS can be generated ↓ Acetylcholine release into synapses leading to autonomic nerves ↓ Acetylcholine release into neuromuscular junction Autonomic dysfunction ↑ Deep tendon reflex amplitude Temporary improvement in muscle strength ↓ Number of muscle fibers activated by each action potential Post-activation facilitation: Repeated stimulation improves symptoms Larger proximal muscles involved in movement (i.e. walking) do not recruit sufficient number of muscle fibers for proper function Can affect any muscle group, but muscles involved in speech, swallowing, and periocular muscles are often afflicted Gait disturbance Symmetric skeletal muscle weakness Dysarthria (difficulty speaking) Dysphagia (difficulty swallowing) Ptosis (drooping of upper eyelid) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published July 18, 2021 on www.thecalgaryguide.com

Corneal-Abrasion

Corneal Abrasion: Pathogenesis and clinical findings Mechanical Trauma / Foreign Body (fingernail scratch, dust, sand, debris in eyelid) Trichiasis (Misdirected eyelashes directly abrading the ocular surface) ↓ tear production (See Calgary Guide - Dry eye pathogenesis) ↓ quantity or quality of tear film Any condition causing incomplete or inadequate eyelid closureà↑ exposure of eye surface to atmosphere (Bell’s palsy, proptosis/ exophthalmos) ↑ Tear evaporation ↓ lubrication of eye surface Dryness and desiccative damage to ocular surface structures ↓ protective barriers against mechanical or foreign body damage Infection of epithelial defect by pathogens Damage deepens to inner layers of the cornea Immune response causes white blood cells to accumulate Pathogen and immune cells obstruct blood flow, causing tissue necrosis Infectious corneal ulcer Any condition affecting the trigeminal nerve and/or peripheral corneal nerves (e.g. Herpes zoster/simplex infection, diabetes, medications, surgery) Tight lens ↓ O2 reaching cornea Corneal epithelium hypoxiaà cellular damage Contact Lens use Extended use Lens dehydrates Corneal epithelium adheres to lens and is removed with the lens Neurotrophic keratopathy (corneal damage secondary to loss of innervation) ↓ stimulation of the cornea by neurotransmitters (complex and multifactorial) ↓ Blinking (if bilateral) Area of defect stained bright green under cobalt-blue filtered light Impaired sensory innervation of the corneaàImpaired Reflex Tearing ↓ adhesion between corneal epithelium and Bowman’s layer Trauma from insertion or removal of contact lens Previous traumatic abrasion with damage to Bowman’s layer or inadequate epithelial adherence (e.g. corneal dystrophy) Spontaneous erosion (occurs without antecedent injury or foreign body) ↓ structural integrity of corneal epithelium Fluorescein dyes the exposed Bowman’s layer (inner corneal layer between epithelium and stroma) Corneal Epithelial Damage (the transparent portion of the eye that covers the anterior portion of the eye and covers the pupil iris and anterior chamber) Corneal Abrasion: Focal area of epithelial loss - outermost layer of cornea (damage may extend to the bowman's layer below as well) Abrasions that overlay the pupil Epithelium (outermost portion on cornea) Bowman’s layer Stroma Descemet’s membrane Endothelium Cornea (cross section) Layers of the cornea Concurrent damage to other anterior segment structures in trauma Can induce traumatic uveitis Irritation and spasms of the iris/ciliary body muscle complex Light stimulus induces further movement of irritated/inflamed structures Damaged tissues & ensuing inflammatory responseà Inflammatory mediator release Conjunctival injection (vasodilation of vessels in the conjunctiva) Red eye Damage to corneal nerves stimulates corneal nociceptors Pain/ Foreign body sensation prevent light entry through the pupil Acute vision loss Hyperalgesia (lowered peripheral nerve threshold for firing while damaged tissues are healing, during which normally non- noxious stimuli like light, wind or temperature change - can induce pain) Nociceptors stimulate afferent neurons in trigeminal nerve, which then activates efferent neurons in the facial nerve Stimulation of the lacrimal gland Tearing Anterior chamber of the eye Photophobia (Light sensitivity or light-induced pain/ discomfort) – Pathophysiology is complex and multifactorial Authors: Yejun Hong, Davis Maclean Reviewers: Mehul Gupta, Adam Muzychuk*, Victor Penner*, Yan Yu* *MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 19, 2021 on www.thecalgaryguide.com

Fat-Embolism-Syndrome

Fat Embolism Syndrome: Pathogenesis and clinical findings Panniculitis (conditions causing inflammation of subcutaneous fat) Non-trauma related (rare) Long bone fracture Pelvic fracture Orthopedic Trauma Intraosseous access Soft tissue injuries Chest compressions Bone marrow transplant Pancreatitis Diabetes mellitus Fat from bone marrow is disrupted and leaks into bloodstream via damaged blood vessels Fat globules obstruct dermal capillaries Capillaries rupture Blood leaks into the skin Petechial rash Non-Orthopedic Trauma (less common) Fat from injured adipose tissue is released from adipocytes into bloodstream Metabolic disturbance mobilizes stored fat and moves it into circulation Fat Embolism Syndrome the presence of fat globules in circulation Fat globules damage blood vessel walls Platelets stick to damaged areas Platelet aggregation ↑ circulating free fatty acids ↑ inflammatory cytokines (TNF, IL1, IL6) ↑ serum C Reactive Protein (an acute phase reactant) C reactive protein binds to lipid vesicles in circulation ↑ formation of lipid complexes in the blood Obstruction of cerebral vasculature ↓ blood flow and oxygen delivery to brain tissue Neurological findings: ranging from ↓ level of consciousness to seizures Notes: Large quantities of fat globules can obstruct pulmonary vasculature Blood clots form throughout the body Disseminated intravascular coagulopathy Back up of blood into right heart àRight ventricular dysfunction ↓ pulmonary arterial blood flow à↓ gas exchange in the lungs Higher CO2 & lower O2 levels in blood àdetected by chemoreceptors Chemoreceptors stimulate respiratory centre in the brain to ↑ rate of respiration Dyspnea / Tachypnea Authors: Tabitha Hawes Reviewers: Hannah Koury, Alyssa Federico, Davis MacLean, Mehul Gupta, Yan Yu*, Jeremy Lamothe* * MD at time of publication • Underlined findings indicate classic triad of symptoms (petechial rash, neurologic findings, dyspnea/tachypnea) • Clinical presentation of fat embolism syndrome is variable and may present with any or all of these findings ↓ pumping of blood into systemic circulation Hypotension Obstructive shock Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 19, 2021 on www.thecalgaryguide.com

Complications-Accouchement-Vaginale

Complications maternelles de l’accouchement par voie vaginale Autheur: Yan Yu Rédacteurs: Kayla Nelson, Radhmila Parmar, Jemimah Travail et accouchement par voie vaginale Pression intense sur les parois vaginales pendant le passage du fœtus et/ou utilisation de forceps ou d'un aspirateur endommagent le vagin et le périnée. Raffe-Devine, Alina Constantin* Traducteurs: Brianna Ghali, Philippe Couillard* * MD at time of publication Le détachement du placenta perturbe les vaisseaux sanguins de l'utérus. Sondage des voies urinaires pendant le travail Un tissu cicatriciel se forme au niveau du décollement du placenta. Après l'hémostase complète (arrêt du saignement) et la cicatrisation des vaisseaux, le tissu cicatriciel est éliminé de l'utérus. Lochies (pertes/ saignements vaginaux) et perte d'escarres (tissu cicatriciel) Le tissu placentaire peut être retenu dans l'utérus. L'utérus ne se contracte pas complètement pour fermer les vaisseaux sanguins utérins. Hémorragie post- partum (Voir la diapositive correspondante) Les substances étrangères déclenchent une réaction inflammatoire systémique chez la mère Coagulation intravasculaire disséminée, CIVD (voir diapositive correspondante) Dans de rares cas, des vaisseaux sanguins déchirés laissent le liquide amniotique (contenant des cellules fœtales et du méconium) pénétrer dans la circulation maternelle. Embolie de liquide amniotique (amas de cellules fœtales et de méconium dans la circulation maternelle) Le liquide amniotique visqueux peut bloquer les vaisseaux sanguins maternels Obstruction de la circulation du sang dans les poumons Bas debit cardiaque avec reduction de la précharge. Tissus endommagés et sang dans l'utérus Des nutriments pour que les bactéries infectent l'utérus. Endométrite Douleur utérine, irradiant dans tout l'abdomen Œdème pulmonaire Hypotension Manque de perfusion au cœur Arrêt cardiaque Le passage du fœtus distend les muscles pubo- vésiculaires et pubo-rectaux. L'urètre/ rectum ne sont plus suffisamment courbés pour empêcher les fortes pressions intra- abdominales de forcer l'urine ou les selles. Incontinence de stresse (de la vessie et des intestins ; généralement temporaire) Remarque: la dépression post-partum est couramment observée chez au moins 10 % des mères qui viennent d'accoucher. Déchirures périnéales (1er-4e degré) ; Hémorroïdes Douleur périnéale Douleur et gonflement unilatéral de la jambe Dyspnée, Toux Les lésions tissulaires activent les facteurs de coagulation du sang. ­ Coagulation dans les zones d'hémostase (par exemple, les veines) Thrombose veineuse profonde La fièvre du post- partum (voir la diapositive correspondante) L'insertion d'un tube étranger dans la vessie facilite la colonisation de la vessie et des voies urinaires par les bactéries. Infections des voies urinaires Si grave Effondrement cardio-vasculaire Légende: Pathophysiologie Méchanisme Signe/Symptôme/Résultat Laboratoire Complications Publié 19 juin 2013 à www.thecalgaryguide.com

Hypertriglycéridémie primaire

Hypertriglycéridémie primaire : Pathogénie et résultats cliniques Traduction: Brianna Ghali Philippe Couillard* Autheur: Gillian Goobie Rédacteurs: Peter Vetere Yan Yu Hanan Bassyouni* * MD au moment de la publication Acronymes: LPL = lipoprotéine lipase TG = triglycérides CM = chylomicrons LDL = lipoprotéine de basse densité VLDL = lipoprotéine de très basse densité FFA = acides gras libres CV = cardiovasculaire MC=maladie coronarienne Déficit en lipoprotéine lipase (LPL) La LPL présente dans le cœur, les muscles squelettiques, les tissus adipeux et d'autres tissus est incapable d'éliminer les TG des CM et des VLDL. Hyperlipidémie combinée familiale Surproduction de TG-riches VLDL, LDL et/ou ApoB100 Dysbétalipoprotéinémie familiale Mutation de ApoE (l'apoprotéine responsable de l'élimination des CMs et VLDLs de la circulation) VLDLs & CMs riches en TG s’accumulent dans le sang Hypertriglycéridémie Primaire versus Secondaire: - L'hypertriglycéridémie primaire est due à une cause génétique. -L'hypertriglycéridémie secondaire est due à une cause médicale ou à un mode de vie acquis. Mécanismes inconnus du risque ↑ CV, distincts du risque d'athérosclérose associé à l'hypercholestérolémie. MC Prématurée (âge d'apparition avant 50 ans chez les hommes et 55 ans chez les femmes) Remarque : les signes les plus pathognomoniques de l'hypertriglycéridémie sont les xanthomes éruptifs et la lipémie rétinienne. La diffusion de la lumière par les TG sanguins fait paraître les vaisseaux de la rétine blanc au fond d’oeil Lipemia Retinalis La lipase pancréatique libère les FFA des CM et des VLDL. La concentration plasmatique des FFA dépasse la capacité de fixation de l'albumine. Les AGF s'accumulent dans le pancréas, provoquant une inflammationàla lyse des cellules pancréatiques et la libération d'enzymes digestives pancréatiques. Pancréatite (le risque de pancréatite augmente considérablement avec un taux de TG >10mmol/L) Des niveaux excessifs de CM et de TG traversent les vaisseaux sanguins pour atteindre le derme ou la cornée. TGs engloutis par les macrophages dermiques or cornéens (histiocytes) Xanthomes éruptifs (papules jaunes de 1 à 3 mm généralement observées sur les tendons et surfaces d'extension comme les coudes, les genoux, les fesses, ainsi que sur le dos, la poitrine et les extrémités proximales). Légende: Pathophysiologie Méchanisme Signe/Symptôme/Résultat Laboratoire Complications Publié 19 juin 2013 à www.thecalgaryguide.com

Nodule-thyroïdien

Nodule(s) thyroïdien(s) hyperfonctionnel(s): Pathogénie et résultats cliniques Traduction: Radiation Tabagisme ↑ Âge Génétiques Brianna Ghali Philippe Couillard* Autheur: Jaye Platnich Rédacteurs: Amogh Agrawal Alexander Arnold Hanan Bassyouni* *MD au moment de publication ADN endommagée et mutée La mutation du récepteur de la TSH dans le tissu thyroïdien entraîne une activation constitutive (une activation indépendante de la TSH) ↑ Signalisation de la protéine G (spécifiquement Gs alpha) Le tissu thyroïdien affecté devient hyperfonctionnel et indépendant des mécanismes normaux de la régulation. ↑ Production et sécrétion de T4 et T3 à partir du nodule hyperfonctionnel. ↑ T4/T3 supprime la production de TSH par la glande pituitaire Abbréviations: • TSH - Hormone de stimulation de la thyroïde Note: Les nodules thyroïdiens hyperfonctionnels sont très rarement malins : plus de 98 % de ces nodules sont bénins. La capacité à capter l'iode et à produire de la T4 et de la T3 suggère un niveau de différenciation cellulaire rarement atteint par les cellules malignes. Prolifération localisée des cellules folliculaires de la thyroïde. ↑ Capture de l'iode radioactif et du technitium-99 par le tissu thyroïdien hyperfonctionnel. Variety of mechanisms (see hyperthyroidism slide) ↓ Stimulation du tissu thyroïdien normal par la TSH Nodule(s) palpable(s) sur la glande thyroïde Captation de l'iode radioactif montre une ↑ quantitative de l'activité thyroïdienne. La scintigraphie thyroïdienne au technitium 99 permet de visualiser qualitativement le ou les nodules hyperactifs (

Physiology-of-the-Normal-ECG-Waveform-Lead-II

Start of ECG waveform Physiology of the Normal ECG Waveform (Lead II) ECG Waveform (Lead II) A group of pacemaker cardiomyocytes in the right atrium (the Sino-Atrial (SA) node) rely on slow Ca2+ channels on their surface to spontaneously reach depolarization threshold Depolarization wave travels through the atria, contracting atrial myocytes (thus causing atrial contraction) AV node relays conduction to Bundle of His, which delays the depolarization Depolarization conducts down the ventricular septum via the bundle branches, towards the apex At the apex, depolarization conducts up the Purkinje fibers within the ventricular walls, towards the base of the heartàventricular contraction During ventricular contraction, repolarization starts in the atria àatrial relaxation Re-polarization proceeds to ventricles, and occurs from the epicardium to the endocardium, with a net direction from the apex towards the base of the heart Depolarizations occur at regular intervals of 60-100 beats per minute Normal heart rate Regular cardiac rhythm Authors: Davis MacLean, Mehul Gupta, Amanda Nguyen, Yan Yu* Reviewers: Luke Gagnon, Paige Shelemey, Katie Lin* * MD at time of publication Regular intervals of P- waves followed by QRS complexes (60- 100 P-waves/min, 60- 100 QRS/min) – ”normal sinus rhythm” R Depolarization moves towards Lead II, thus causing upward deflection on ECG. Atria have less myocytesàsmaller depolarizationà smaller upward deflection on ECG Lead II Normal P Wave Flat segment between P-wave and QRS Depolarization directed inferior and left (compared to patients' vertical axis), in the direction of Lead IIà upward deflection on ECG Lead II Depolarization is now directed away from Lead IIàdownward deflection on ECG Lead II Electrical signal from atrial repolarization is too weak to stand out and is “buried” in the QRS Ventricular myocytes are contractedàno net movement of electrical charge Normal R wave Normal S wave Q Normal QRS Complex S Note: for simplicity, we will only use Lead II to explain the direction of ECG deflections. However, the same principle applies to all leads: Depolarization moving towards the leadàupward deflection on ECG Depolarization moving away from the leadàdownward deflection on ECG Absence of any ECG components representing atrial relaxation • • PR Interval Represents time between start of atrial depolarization to start of ventricular depolarization SA node to atrial and AV node depolarization takes 120-200 milliseconds (ms) No ECG deflection occurs Isoelectric ST segment (Interval between end of ventricular depolarization and beginning of repolarization) QRS Width Represents time required for ventricular depolarization Depolarization spreads along fast conduction pathways of bundle branches and Purkinje fibers Rapid conduction results in ventricular depolarization in 60- 110 ms “Narrow” QRS <110 ms QT Interval Represents time required for ventricular depolarization and repolarization Without the influence of factors including genetics, electrolyte abnormalities, or drugs, the QT segment is of a normal length Normal adult QT interval: <440ms in males and <460ms in females The opposite charge (re-polarization) is now moving away from the positive electrode of Lead II An upward deflection in Lead II is produced, but is slower and smaller in amplitude compared to the QRS, which reflects the slower repolarization process Normal T Wave End of waveform Lead number and orientation Base Apex Note: • Q Waves: Small Q-waves can be seen in lead II and are non- pathologic as they represent the left to right depolarization of the ventricular septum. Larger Q waves are pathologic and are usually indicative of previous infarct/ischemia. • Axis: For an explanation of how to tell the Axis from an ECG, please consult the relevant Calgary Guide slide on the subject. Note: Normally, the apex of the heart points down and to the left of the body, in the direction of leads I, II, and aVF. Since QRS deflections on ECG reflect the direction of ventricular depolarization, an upward QRS deflection in these leads means the heart’s apex is pointed in a normal direction (normal “axis”). Action potential conduction velocity is slowed at AV node PR interval is 120-200 ms (normally) Normally, each action potential travels through the AV node to the ventricular conducting system to cause ventricular depolarization If abnormal conduction through AV node or down the ventricular septum: Heart Block Legend: Pathophysiology Mechanism Normal Findings ECG Components Published July 31, 2021 on www.thecalgaryguide.com

Dry-Eye-Syndrome-Pathogenesis

Dry Eye Syndrome (Keratoconjunctivitis sicca): Pathogenesis The Pathophysiology of Dry eye disease is complex and an area of active investigation – The mechanism and causes presented here represented the highest yield causes and mechanism for students Post laser eye surgery Disruption of corneal nerves ↓ corneal sensitivity Damage to trigeminal nerve, the sensory innervation of the eye (due to: Herpes Zoster, tumor, trauma, etc) Blepharitis (eyelid inflammation) Many medications can cause dry eye via multiple mechanisms presented here (e.g. ↓ corneal sensitivity, Meibomian gland dysfunction, lacrimal gland atrophy) Sex Hormones (e.g. androgens & estrogens) play a complex and poorly understood role in mediating dry eye disease (net effect is that women are more often affected by dry eye) Obstructed meibomian glands Eyelid damage Gland atrophy These items represent general causes of meibomian gland dysfunction – exact causes are numerous, their pathophysiology is beyond the scope of this slide Contact lens (long term use) Corneal nerve adaptation to chronic mechanical stimulation Autoimmune disease (e.g. Sjögren's syndrome) Chronic inflammatory infiltration of the lacrimal gland (and salivary gland) Autoimmune Lymphocytic infiltration Inflammatory cytokine release Autoantibody production Cell death and apoptosis Lacrimal gland degeneration Meibomian gland dysfunction (Located along the eyelid margins, these glands produce meibum, an oily substance that prevents evaporation of the tear film) ↓ meibum secretion Loss of lipid layer covering the eye, ↓ the barrier that blocks evaporation of tear film Tear Film instability Lifestyle Extended reading or TV or electronic device uses Exposure Keratopathy (any condition causing dryness due to incomplete or inadequate eyelid closure, e.g. Bell’s Palsy) ↓ activity of the afferent portion of corneal reflex arc (responsible for reflex tearing: tearing in response to irritation of the eye) Mechanical damage to goblet cells secrete mucins – a substance that lubricates the eye and preserves tear film ↓ blink rate ↑ time and area ↓ normal reflex tearing for evaporation Dry climate Wind exposure Infiltrative diseases (e.g. sarcoidosis) Lacrimal gland infiltration ↓ Lacrimal gland secretion of the the watery aqueous layer of the tear film (Aqueous deficient dry eye) Deficient or unstable tear film (Evaporative dry eye) ↑ tear evaporation Direct damage to lacrimal gland (e.g. infection or trauma of the eye) Authors: Davis Maclean, Yan Yu*, Michael Penny, O.D. Reviewers: Natalie Arnold, Saleel Jivraj, O.D., Adam Muzychuk*, Victor Penner* *MD at time of publication Hyperosmolar Tear Film (hyperosmolarity = ↑ solutes and ↓ solvent) (Further) Tear Film instability Corneal and conjunctival epithelial cells dry out, including goblet cells (which secrete mucins – a substance that lubricates the eye) Inflammatory immune response àRecruitment and activation of CD4+ (Helper) T-Cells, further produce cytokines Further irritation and damage to ocular surface structures (cornea, conjunctiva and Meibomian glands) and lacrimal glands See Calgary Guide: “Dry Eye Syndrome (Kerato- conjunctivitis sicca):Clinical Findings” for signs and symptoms Dry Eye Syndrome (Keratoconjunctivitis sicca): A multifactorial disease of the ocular surface and tears characterized by loss of tear film homeostasis, tear film hyperosmolality and inflammation Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 7, 2021 on www.thecalgaryguide.com

Dry-Eye-Syndrome-Clinical-Findings

Dry Eye Syndrome (Keratoconjunctivitis sicca): Clinical Findings If dry eye is chronic or severe (e.g Sjögren’s syndrome) corneal ulcerations or scarring may occur Impaired visual acuity/ Blindness (does not improve with lubrication) See Calgary Guide: “Dry Eye Syndrome (Keratoconjunctivitis sicca): Pathogenesis” for explanation of etiology and pathogenesis Dry Eye Syndrome (Keratoconjunctivitis sicca): Disease of the ocular surface and tears characterized by loss of tear film homeostasis, tear film hyperosmolality and inflammation Tear film instability & hyperosmolarity Ocular surface inflammation: Immune cell (specifically T-Cell) destruction of corneal and conjunctival epithelium ↓ quantity and/or quality of tear film Inflammatory factors vasodilate conjunctival vessels, making the eye look redder in appearance Conjunctival injection Red eye Corneal surface irregularities Light rays pass through disrupted tear film and ocular surface structures as they enter the eye Degraded image quality as light passes through the eye Impaired visual acuity (improves with lubrication) ↓ lubrication over the eye surface ↑ friction on the eye during blinking or when opening eyes after sleep May cause corneal abrasion (See Calgary Guide: Corneal Abrasion) ↑ stimulation of corneal and conjunctival nerve endings Irritation and damage to corneal and conjunctival cells ↑ stimulation of nerve endings Chronic inflammation surrounding corneal nerves in conjunctiva and epithelium can lead to decreased neuronal firing thresholds (Neurosensory dysfunction / hyperalgesia) ↑ activity of the afferent portion of corneal reflex arc (responsible for reflex tearing: tearing in response to irritation of the eye) Foreign body sensation (scratching / feeling as if a foreign body, like a grain of sand, is in the eye) Minor (typically non-painful stimuli) may cause pain due to hypersensitive corneal nerves Corneal neuropathic pain (pain not fully explained by ocular surface changes, often resistant to standard treatments, sometimes still present following ocular surface anaesthesia if central pathways affected) Pain with temperature change and wind exposure Exact mechanism unknown Photophobia Burning sensation Paradoxical reflex tearing (↑ tearing, which does not improve dry eye due to altered tear composition, poor surface coverage or overflow of temporary tearing out of the eye Authors: Michael Penny, O.D. Davis Maclean Yan Yu* Reviewers: Natalie Arnold Saleel Jivraj, O.D. Adam Muzychuk* Victor Penner* *MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 6. 2021 on www.thecalgaryguide.com

medial-collateral-ligament-mcl-injury

Medial Collateral Ligament (MCL) Injury Previous MCL injury Ligament healing requires adequate blood supply to bring oxygen and nutrients to the site of injury Incomplete healing of MCL due to poor blood supply Authors: Alyssa Federico Reviewers: Hannah Koury, Mehul Gupta, Yan Yu*, Alexander Rezansoff* * MD at time of publication Sports involving significant twisting or torsion of a planted lower extremity (soccer, basketball, tennis, skiing) Tibial rotation External rotation of tibia while foot is planted on the ground High-energy trauma Contact sports (wresting, hockey, football, rugby, soccer) Contact trauma External (valgus) force on flexed knee ↓ stability and resistance to contact trauma and tibial rotation Grade 1 Mild injury Grade 2 Moderate injury Grade 3 Severe injury Similar forces affect surrounding structures in the knee MCL injuries commonly co-occur with anterior cruciate ligament and medial meniscus injuries Medial knee innervated by the saphenous nerve (branch of the femoral nerve) MCL Injury Classified into three grades, each with characteristic findings MCL is located outside of the knee joint capsule Microscopic tear (<10% of collagen fibers torn) Incomplete tear (>10% of collagen fibers) Complete tear of MCL Normal valgus laxity (0-5 mm) at 30° knee flexion with perceived endpoint ↑ valgus laxity (5-10 mm) at 30° knee flexion with a perceived endpoint Significantly ↑ valgus laxity (>10 mm) at 0° and 30° knee flexion with no endpoint ↓ stability and resistance to valgus stress + Valgus stress test with 0° and/or 30° of knee flexion Excessive valgus laxity, medial joint opening and/or medial knee pain MCL stretched beyond capacityàtears collagen fibres in the ligament Medial knee pain Medial knee tenderness on palpation MCL bleedingà blood accumulates below the skin Bruising on medial aspect of knee Localized, extra- articular swelling at site of injury Soft tissue swelling on medial aspect of knee Audible “pop” at time of injury Knee instability from extreme laxity Favouring the injured side to avoid pain while walking Antalgic gate Stiffness and inability to bend or straighten the knee Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 14, 2021 on www.thecalgaryguide.com

lateral-collateral-ligament-lcl-injury

Lateral Collateral Ligament (LCL) Injury Previous LCL injury Ligament healing requires adequate blood supply to bring oxygen and nutrients to the site of injury Incomplete healing of LCL due to poor blood supply Authors: Alyssa Federico Reviewers: Mehul Gupta Yan Yu* Alexander Rezansoff* * MD at time of publication Sports involving high velocity pivoting or jumping (tennis, gymnastics, soccer, basketball, skiing, football, hockey) High-energy trauma Contact sports (wresting, hockey, football, rugby, soccer) Hyperextension Knee joint extended beyond normal range Similar forces affect other structures in the knee LCL injuries commonly co- occurs with anterior cruciate ligament, posterior cruciate ligament, and posterolateral corner injuries Lateral knee innervated by the posterior articular branches of tibial nerve ↓ stability and resistance to varus force and hyperextension Varus force Extreme force placed on medial knee Contact trauma Direct blow causing varus force and hyperextension LCL stretched beyond physiologic capacityàtears collagen fibres in the ligament Grade 1 Mild injury Grade 2 Moderate injury Grade 3 Severe injury Microscopic tear (<10% of collagen fibers torn) Incomplete tear (>10% of collagen fibers) Complete tear Knee instability from extreme laxity Normal varus laxity (0-5 mm) with a perceived endpoint ↑ varus laxity (5-10 mm) with a perceived endpoint Significantly ↑ varus laxity (>10 mm) with no endpoint ↓ stability and resistance to varus stress + Varus stress test with 0° and 30° of knee flexion Excessive varus laxity, lateral joint opening and/or lateral knee pain LCL Injury Classified into three grades, each with characteristic findings LCL is located outside of the knee joint capsule Lateral knee pain Lateral knee tenderness on palpation LCL bleedingà blood accumulates below the skin Bruising on lateral aspect of knee Localized, extra- articular swelling at site of injury Soft tissue swelling on lateral aspect of knee Audible “pop” at time of injury Favouring the injured side to avoid pain while walking Antalgic gate Varus thrust: visible lateral movement of the knee upon weight bearing on ambulation (lateral shift of the head of the fibula and upper tibia) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 14, 2021 on www.thecalgaryguide.com

Congenital-Thrombophilia

Congenital Thrombophilia: Pathogenesis and Complications Authors: Brian Yu Chieh Cheng, Yan Yu* Reviewers: Mehul Gupta, Hannah Yaphe, Tejeswin (Jovey) Sharma, Man-Chiu Poon* *MD at time of publication Group I Hereditary deficiencies of coagulation inhibitors Group II Hereditary disorders with ↑ levels or function of coagulation factors Antithrombin (AT) deficiency AT inhibits thrombin & activated coagulation e.g. factor X (FXa) Autosomal dominant mutation of the SERPINC1 gene causes ↓ production of AT ↓ AT concentrations allows thrombin & FXa to promote secondary hemostasis Protein C (PC) deficiency Protein S (PS) deficiency Factor V Leiden Autosomal dominant point mutation of the Factor V gene Single nucleotide substitution (G1691A) results in mutated form of FVa protein FVa becomes resistant to aPC & PS inactivation FVa is broken down at ↓ rate Prothrombin mutation Autosomal dominant point mutation of the Prothrombin gene Single nucleotide substitution (G20210A) of the gene’s 3’ untranslated region Accumulation of prothrombin mRNA & protein copies of prothrombin ↑ concentration of prothrombinà ↑ conversion to thrombin ↑ clotting factor quantity or function due to mutations intrinsic to these clotting factors Activated Protein C (aPC) & PS combine to inhibit activated clotting Factors V & VIII (FVa & FVIIIa) Autosomal dominant mutation of the PROC & or PROS1 gene ↓ production of PC and/or PS ↓ aPC & PS concentrationsà less breakdown of FVa & FVIIIa, ↑ blood’s clotting ability ↑ clotting factor function due to ↓ inhibition or breakdown of clotting factors Congenital Thrombophilia An inherited abnormality / imbalance of blood coagulation factors that increases the risk of thrombus formation ↑ generation of thrombin ↑ clotting tendency, especially in veins where blood flow is slower/prone to stasis (see Calgary Guide slide on Virchow’s Triad) Venous Thromboembolism Deep Vein Thrombosis Pulmonary Embolism Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 15, 2021 on www.thecalgaryguide.com

epithelial-ovarian-cancer-pathogenesis-and-clinical-findings

Epithelial Ovarian Cancer: Pathogenesis and clinical findings Authors: Brian Yu Chieh Cheng, Yan Yu* Reviewers: Mehul Gupta, Hannah Yaphe, Sarah Glaze* * MD at time of publication See Epithelial Ovarian Cancer Risk Factors slide BRCA1 or BRCA2 mutationà faulty double strand DNA repairà↑ mutations & loss of controlled cell division Asymptomatic serous tubal intraepithelial carcinoma (STIC) lesions of the fallopian tube fimbria develop overtime STIC cells may break off from the fallopian tube & become trapped during inclusion cyst formation As part of the ovarian cycle, the coelomic epithelium (CE) of the ovary is ruptured & repaired after ovulation Incomplete repair of the CE results in invagination of the rupture site, forming a benign cortical inclusion cyst CE cells trapped during cyst formation undergoes metaplasia to tubal or other types of epithelium Endometriosis Endometriosis causes endometrial tissue to start growing on ovarian CE Endometrial cells trapped during cyst formation progresses to endometrioma or “chocolate cysts” Immune cell infiltration & cytokine release inside the ovary results in dysregulated inflammation Cancer cells proliferate in distant organs, invading & destroying native cells Organ failure Metastatic spread to liver, lung, brain & lymph nodes Lymphadenopathy Systemic immune activation ↑ metabolic consumption ↑ capillary surface area & permeability Fatigue & weight loss ↑ fluid entry into Ascites peritoneal cavity Further somatic mutation accumulation leads to malignant transformation of epithelium Tumor growth stimulates new blood vessel formation to supply itself with nutrients & O2 Omental / peritoneal seeding of cancer cells Early-stage disease Asymptomatic Epithelial Ovarian Cancer In late-stage disease, tumor may secrete a glycoprotein called mucin 16, also known as CA-125 (sensitive but non-specific biomarker for ovarian cancer) ↑ serum CA-125 levels Cancer cells proliferate inward & eventually ruptures the ovary Cancer cells are released into the peritoneal cavity Tumor growth in local organs (bladder/uterus) progresses to symptomatic cancer ↑ tumor volume & local tumor spread directly disrupts neighboring structures Pelvic/abdominal pain Palpable pelvic/abdominal mass Altered urinary frequency Compression of colon/bladder Change in bowel habits Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 15, 2021 on www.thecalgaryguide.com

covid-19-pathophysiology-and-clinical-findings

COVID-19 (Corona Virus Disease 2019): Pathophysiology and Clinical Findings Authors: Ryan Brenneis, Yan Yu* Reviewers: Ciara Hanly, Yonglin Mai (􏰄􏰁􏰃)*, Stephen Vaughan* * MD at time of publication -Respiratory failure -Septic shock -Multiple organ dysfunction Critical Respiratory droplet production (cough, sneeze, talking, breathing) by human host or animal vector infected with SARS-CoV-2 Note: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the name of the betacoronavirus (a positive sense, single stranded RNA virus). COVID-19 is the name of the disease caused by this virus. rate, ↓ oxygen saturation -Bilateral interstitial infiltrates on Chest X-ray, progressively worsening Small droplets (<5μm in diameter) are aerosolized and become airborne Inhalation of aerosolized particles that are suspended in air Patient exposed to the virus (SARS-CoV-2) Droplet contacts the mucus membranes (eyes, nose, mouth) of recipient Live viral particles can adhere to inanimate objects called fomites (e.g. doorknobs) Symptoms are on a continuum -Worsening dyspnea: ↑ respiratory -Fever -Cough -Myalgia, fatigue -Nausea/vomiting -Diarrhea -Loss of taste/smell Recipient touching infected fomite subsequently touches any of their mucus membranes Mild Moderate Severe Virus spreads in the body via 1) mucus membrane spread to surrounding cells and 2) entering the blood Virus adheres to angiotensin-converting enzyme 2 (ACE-2) receptor on body cells, mimics ACE-2, & gains access into cell COVID-19 Symptomatic infection with SARS-CoV-2 Viral proliferation in cells of tissues with more ACE-2 receptors: lungs (type II pneumocytes); vasculature (endothelial cells), kidneys (proximal tubular epithelium), heart (myocardium), GI tract (enterocytes) Cell death and ↑ in inflammatory cytokines triggers immune response Neutrophils move to lungs, release reactive oxygen species and cytokines Alveolar/capillary damage Fluid accumulates in interstitium and alveoli ↑ Distance for O2 to diffuse from alveoli to capillaryà ↓ blood O2 saturation Cytokines induce the hypothalamus to release prostaglandins ↑ body temperature set point to fight infection Virus disassembles, releasing viral RNA, which uses host cell’s ribosomes to make new viral proteins like RNA-polymerases Newly made viral RNA-polymerases use cell’s own nucleotides to synthesize new viral RNA Bilateral ground-glass opacities (CT lung) & interstitial infiltrates on Chest X-ray Dyspnea Airway irritation Cough Myocardial cell damage ↑ Troponin ↑ skeletal muscle cell damage Viral RNA & proteins packaged into new viral particles New virus assembled and released from cell, killing the cell and contributing to disease symptoms Average incubation period (time from initial infection to symptom onset) is 4-5 days; can be up to 14 days Heart tries to compensate for Fever Myalgia hypoxemiaà↑ cardiac output Arrhythmogenic and strain on myocardium state Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 22, 2020, updated Aug 18, 2021 on www.thecalgaryguide.com

cystic-fibrosis-findings-on-chest-x-ray-and-lung-window-ct-scan

Cystic Fibrosis: Findings on Chest X-Ray and Lung Window CT Scan CFTR mutationàabnormal transmembrane Cl- transport in exocrine tissueà Author: Sean Kennedy Reviewers: Matthew Harding, Amogh Agrawal, Yan Yu, Ciara Hanly, Aman Wadhwani, Zesheng Ye (􏰃􏰄􏰁), Mark Montgomery* * MD at time of publication Collapsed alveoli appears white on x-ray Peribronchial Cuffing secretions become more viscous. (See relevant slide for CF pathogenesis.) As early as at birth, secretions collect in bronchial lumen, delaying mucociliary clearance Mucus plugs and obstructs bronchial lumen Air trapped distal to obstruction and cannot leave lungs Lung Hyperinflation Diaphragm domes below 10th posterior rib and 6th anterior rib on PA CXR Flattened hemidiaphragm, enlarged retrosternal space on lateral CXR With time, pulmonary capillaries gradually absorb gases in alveoli distal to obstruction àalveolar collapse (Atelectasis) Collapsed alveoli more solid and radiodense than airà↓X-ray penetration Adjacent structures may shift towards atelectasis on CXR In first few years of life, retained bronchial secretions serve as nidus for recurrent bacterial colonization and infection Late findings at 10- 30 years oldà secretion accumulation blocks inhaled air to affected lung segments àchronic hypoxia Inflammatory response (cytokines, nitric oxide and radical oxygen species) leads to bronchial and peribronchial destruction Hypoxia induces pulmonary capillary vasoconstriction Some airways are blocked more than others Leakage of fluid into bronchial walls & peri- bronchial regions. Inflammatory cytokines destroy elastic components of bronchi Accumulation of inflammatory exudate in bronchi Pulmonary artery hypertension à Blood backs up in pulmonary arteries Some segments of lung underventilated Fluid around bronchial walls is more radiodense than air à↓X-ray penetration àappears white Bronchiectasis: dilated, thickened, untapered bronchi on CXR/CT Fluid/mucus in bronchi is more radiodense than air, thus appearing white on imaging Edematous bronchi viewed end on are thickened and appear ring-like on CT/CXR Tramlines (AKA Tramtracking) Bronchus wider than corresponding blood vessel on CXR/CT Advanced bronchiectasis is saccular in appearance Mucus-filled bronchi form tubular opacities giving appearance of white fingers on CXR/CT Signet Ring Sign Bronchiectatic Cavities Mucoid Impaction (AKA Finger in glove sign) ↑ Blood dilates pulmonary arteries Blood backs up in right ventricle, dilating it Pulmonary arteries look wider on CXR. Main pulmonary artery >30 mm diameter on CT Right Ventricle Enlargement on CXR/CT Underventilated lung segments appear as lower intensity (darker) than normal ventilated segments which appear as normal intensity (brighter) Mosaic Changes on CT(non- contrast Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published June 13, 2013, updated Aug 18, 2021 on www.thecalgaryguide.com

asthma-pathogenesis

Asthma: Pathogenesis Author: Yan Yu Reviewers: Jason Baserman Jennifer Au Ciara Hanly Yonglin Mai (􏰁􏰃􏰄) Naushad Hirani* * MD at time of publication Genetic factors (i.e. HLA gene mutations, defects in bronchial airway epithelium) Environmental factors (i.e. excess hygiene, fewer siblings, antibiotics within the first two years) Asthma: Defined as airway hyper-responsiveness causing variable and reversible airflow obstruction Atopy: predisposition to allergic hyper-sensitivity in airways First exposure to triggers* sensitizes helper T cells Stimulation of B-cells to produce IgE, which binds to mast cell surfaces Activated Helper-T cells & IgE-sensitized mast cells now line the airways Triggers of airway hyper- responsiveness include: Upper respiratory tract infections (URTIs) Allergens (pollen, animal dander, dust, mold, etc) Air pollution, cigarette smoke, other chemicals Drugs (aspirin, NSAIDs, Beta- blockers) Cold air Exercise Early response (0-2 hrs) Delayed response (3-4 hrs) Allergens cross-link IgEs on mast cells Activated mast cells & helper T cells release cytokines Mast cells release histamines, leukotrienes, and other inflammatory mediators Induce maturation of granular WBCs like eosinophils Eosinophils migrate into: Vascular permeabilityà edema of airway mucosa Goblet cell hyperplasia à­ mucus secretion Bronchial smooth muscle contraction Airway obstruction Second exposure to triggers Asthma Airways Bronchiole constriction Eyes Conjunctivitis Nose Rhinitis Note: Delayed response presents within 3-4 hrs, peaks within 6-8 hrs, and resolves within 24 hrs Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Dec 17, 2012, updated Aug 19, 2021 on www.thecalgaryguide.com

disseminated-intravascular-coagulation

Disseminated Intravascular Coagulation (DIC): Pathogenesis and clinical findings Authors: Emily Wildman Mehul Gupta Sean Spence Yan Yu* Reviewers: Kiera Pajunen Wendy Yao Tristan Jones Man-Chiu Poon* Lynn Savoie* * MD at time of publication Sepsis Microorganisms express pathogen- associated molecular patterns (PAMPs) Severe Trauma Damaged endothelial cells release damage- associated molecular patterns (DAMPs) Solid and Hematologic Malignancies Cancer cells express tissue factor and release procoagulants Immune cells recognize DAMPs and PAMPs and begin expressing tissue factor and releasing procoagulants Systemic activation of coagulation cascade Activation of coagulation cascade results in the factor X mediated conversion of large quantities of prothrombin (factor II) to its active form, thrombin (factor IIa) Thrombin cleaves fibrinogen (factor I) circulating in blood to an activate form known as fibrin (factor 1a) ↓ Serum fibrinogen Diffuse coagulation causes imbalances between coagulation and anticoagulation pathways Consumption of coagulation factors (including platelets, fibrinogen, prothrombin, factor V, factor VIII) exceeds rate of production Fibrin, in conjunction with platelets, form widespread thrombi within vasculature Fibrin thrombi accumulate in the microvasculature and shear transiting red blood cells Microangiopathic hemolytic anemia (MAHA) ↑ thrombi formation ↑ fibrinolysis, a parallel process that naturally degrades fibrin thrombi Relative deficiency of coagulation factors leads to a bleeding diathesis (tendency to bleed) despite widespread clots ↑ Prothrombin time (PT) ↑ Partial thromboplastin time (PTT) ↑ D-dimer Fibrin thrombi ↑ Fibrin degradation products Platelets are used up forming thrombià less free platelets in circulation ↓ Platelets on Complete Blood Count accumulate in microvasculature of major organs Deposition of thrombi occlude blood flow resulting in ischemia of organ parenchyma Lack of coagulation factors can predispose spontaneous hemorrhage in various organs Multiple organ dysfunction syndrome (MODS) - (renal failure, hepatic dysfunction, stroke, pulmonary disease) Clinical manifestations of bleeding, including petechiae (pinpoint red spots on skin), ecchymoses (bruising), weeping wound sites, bleeding mucous membranes Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications First published Aug 7, 2012, updated July 27, 2019 & Aug 29, 2021 on www.thecalgaryguide.com

convulsions-febrile

Convulsions fébrile simple : Pathogenèse et résultats cliniques Traducteurs: Autheurs: Catherine Beyak Rédacteurs: Calvin Howard Gary Klein * MD à la publication Augmentation de la production de médiateurs de fièvre (IL-1β) Brianna Ghali Eddy Lang* Infection (souvent HHV6 ou la grippe) chez l'enfant (généralement âgé de 6 mois à 6 ans) Température cérébrale élevée de manière exogène (par example un bain chaud) Mutation de la sous-unité du transporteur sodium Synthèse de l'IL-1β dans l'hippocampe Fièvre ≥380C Mutation du récepteur GABAA Conditions physiologiques Susceptibilité génétique familiale ou sporadique aux températures élevées La température élevée a un impact sur les canaux ioniques ↑ glutamate et/ou ↓ GABA ↑ excitabilité et synchronisation de l'activité Crise fébrile simple Convulsions fébrile complexes L'étiologie sous-jacente diffère de celle des crises fébriles simples. Signes focaux pendant la crise (déviation des yeux, rotation de la tête, etc.) Prolongée >15 min État épileptique fébrile Une ponction lombaire doit être envisagée pour exclure une infection grave, c'est-à- dire une méningite. Crise tonico-clonique généralisée unique sans signes focaux d'une durée de <15 minutes EEG et IRM normaux (l'IRM n'est généralement pas indiquée) Légende: Physiopathologie Mécanisme Signe/Symptôme/ Résultat Laboratoire Complications Publié 21 janvier 2019 à www.thecalgaryguide.com

Localisation-des-AVC

Accident vasculaire cérébral ischémique : Déficits par localisation Autheurs: Andrea Kuczynski Rédacteurs: Sina Marzoughi Usama Malik Andrew Demchuk* Traducteurs: Brianna Ghali Eddy Lang* * MD à la publication ↓ perfusion (ischémie) dans l'ACA ↓ perfusion (ischémie) dans l'ACM M1-ACM M2-ACM ↓ perfusion (ischémie) dans l’ACP ↓ perfusion (ischémie) dans l’ABV ↓ perfusion (ischémie) dans l’AB Faiblesse et perte sensorielle controlatérale dans la membre inférieure Abréviations: ACA : artère cérébrale antérieure AB : artère basilaire ACM : artère cérébrale moyenne ACP : artère cérébrale postérieure UE : membre supérieur Lésion de l’hémisphère gauche Aphasie Déficits de la perception visuelle et Lésion de l’hémisphère droite négligence (agnosie du côté gauche) ABV : artère basilaire vertébrale Aucune hémianopsie homonyme Hémiparésie et déficits sensoriels controlatéraux, déficits du champ visuel, aphasie, agnosie, apraxie, agraphie. Affect seulement la member supérieur et le visage Aphasie expressive de Broca (moteure) Hémianopsie homonyme controlatérale Aphasie réceptive de Wernicke (sensorielle) Perte sensorielle, perte de mémoire, hémianopsie homonyme controlatérale, alexie. Problèmes des nerfs crâniens : dysarthrie (IX, X), diplopie, paresthésie du visage (VII), syndrome de Foville. Déficits moteurs : Syndrome de Millard-Gubler, syndrome de Raymond, syndrome de Wallenburg, ataxie. Perte sensorielle unilatérale ou bilatérale (↓ sensation de la position et des vibrations). Problèmes des nerfs crâniens : regard dysconjugué (III, IV, VI), hypoalgésie faciale ipsilatérale (V), paralysie faciale motoneurone inférieure unilatérale (VII), vertiges, dysarthrie (IX, X). Déficits moteurs : hémiparésie controlatérale, quadriplégie. Hypoalgésie du membre controlatéral Définitions : Agnosie : incapacité à traiter les informations sensorielles. Agraphie : incapacité à communiquer par écrit Alexie : difficulté de lecture Aphasie : trouble du langage Apraxie : déficit de la planification motrice Ataxie : anomalie de la démarche Aphasie de Broca : incapacité de produire du langage Diplopie : vision double Dysarthrie : troubles de l'élocution. Syndrome de Foville : ataxie cérébelleuse ipsilatérale, syndrome de Horner, parésie du regard conjugué et hémiparésie controlatérale, paralysie faciale, douleur et hypoesthésie thermique. Hémianopsie : perte du champ visuel Hypoalgésie : diminution de la sensibilité à la douleur Syndrome de Millard-Gubler : lésion de la protubérance dorsale. Aphasie de Wernicke : discours fluide, compréhension affectée Syndrome de Wallenburg : déficits sensoriels du membre controlatéral, du visage ipsilatéral. Légende: Pathophysiologie Méchanisme Signe/Symptôme/Résultat Laboratoire Complications Publié 3 février 2018 à www.thecalgaryguide.com

Pneumoconioses

Pneumoconioses: Pathogenesis and Clinical Findings Authors: Austin Laing Reviewers: Yan Yu* Tara Lohmann* * MD at time of publication Bronchogenic carcinoma and mesothelioma Inhalation of asbestos (Asbestosis) Inhalation of carbonaceous dust (Carboconiosis) Inhalation of metal dust (Metaloconiosis) Inhalation of silica dust (Silicosis) “-Coniosis”: disease which comes from inhaling dust particles Internalized asbestos fibers disrupt cellular processes through a complex series of theorized mechanisms Inhaled dust particles (1-5μm in size) are trapped and deposited in the alveolar airspaces Alveolar macrophages ingest dust particles, which activates the macrophages and sometimes causes apoptosis Activated macrophages create an inflammatory microenvironment by releasing pro-inflammatory cytokines, chemokines and reactive oxygen species Inflammatory products (e.g. reactive oxygen species) damage alveolar epithelial cells, causing activation and release of inflammatory cytokines into the alveolar space Inhaled dust particles, inflammatory products & other pro- tussive mediators activate airway vagal afferent receptors Activated receptors stimulate the cough center located in the medulla oblongata Cough Alveolar capillaries vasoconstrict in response to hypoxia à↑ Pulmonary vascular resistance Pulmonary Hypertension Right heart must pump blood into lungs against higher pressure àcardiomyocyte growth (via sarcomeres formed in parallel within myofibrils)àconcentric hypertrophy of right heart Cor Pulmonale (right heart failure due to pulmonary hypertension) Asbestos fibers accumulate in the airspace and translocate to the pleural surface Macrophage apoptosis: ↓ alveolar macrophages Fibroblasts are recruited to the alveolar wall and are activated Activated fibroblasts produce and deposit collagen in the extracellular space between alveoli Thickening of tissue between alveoli and capillaries ↑ the diffusion distance of atmospheric and blood gasses ↓ Diffusion of CO2 from blood to alveoli and ↓ diffusion of O2 from alveoli to blood ↑ Respiratory rate to maintain minute ventilation due to ↓ lung volumes and diffusion limitations Dyspnea and Exertional Hypoxemia ↓ Innate immune response in the lungs Chest X-Ray: Nodular and reticulonodular opacities are seen in varying lung regions depending on the underlying inhaled dust Excessive collagen deposition ↓ lung compliance and ↓ lung expansion ↓ Diffusing capacity for carbon monoxide (DLCO) on pulmonary function test ↓ Arterial oxygen contentà ↑ deoxyhemoglobin and ↓ oxyhemoglobin ↑ Deoxyhemoglobin within the vasculature causes the skin and mucous membranes to appear blue Cyanosis ↑ Risk of respiratory infections. Mycobacterial infections (e.g. tuberculosis) associated primarily with silicosis ↓ Inhalation volume ↓ Expiratory volume Hypoxemia ↓Total lung capacity (TLC) and ↓ residual volume (RV) on pulmonary function test ↓Forced vital capacity (FVC) and ↓ forced expiratory volume in 1 second (FEV1) on pulmonary function test Note: Forced Vital Capacity: the volume of air that can forcibly be blown out after full inspiration Forced Expiratory Volume in 1 second: the volume of air that can forcibly be blown out in first 1 second, after full inspiration Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 12, 2021 on www.thecalgaryguide.com

COVID-19 (Corona Virus Disease 2019): Pathophysiologie und Klinische Befund

COVID-19 (Corona Virus Disease 2019): Pathophysiologie und Klinische Befund Autoren:: Ryan Brenneis, Yan Yu* Rezensenten: Ciara Hanly, Yonglin Mai (麦泳琳)*, Stephen Vaughan* Übersetzerin: Sarah Schwarz Übersetzungsprüfer: Gesche Tallen* * MD zum Zeitpunkt der Veröffentlichung Produktion von respiratorischen Tröpfchen (husten, sprechen, niessen) durch Mensch oder Tier, welche mit SARS-CoV-2 infiziert sind Beachte: Schweres Akutes Respiratorisches Syndrom Coronavirus 2 (SARS- CoV-2) ist der Name des Betacoronavirus (mit positiver Einzelstrang RNA ). COVID-19 ist der Name der Krankheit die das Virus verursacht Kleine Tröpfchen (Durchmesser <5μm) werden aerosoliert & verteilen sich in der Luft Inhalation der Aerosole Exposition des Patienten gegenüber dem Virus (SARS-CoV-2) Kontakt der Tröpfchen mit Schleimhäuten (Augen, Nase, Mund) des Empfängers Kontaminierung eines unbelebten Gegenstandes (z.B. einer Türklinke) mit aktiven Viruspartikeln -Fieber -Husten -Gliederschmerzen -Schwäche -Übelkeit/Erbrechen -Durchfall -Geruchs-und Geschmacksverlust Mild Symptome nach Schweregrad -Dyspnoe: Atemfrequenz↑, Sauerstoffsättigung ↓, -Bilaterale interstitielle Infiltrationen im Röntgen -progrediente Verschlechterung -Respiratorische Insuffizienz -Septischer Schock -Multiorganversagen Kritisch Zelltot & vermehrte Zytokinausschüttung aktiviren die Immunantwort Zytokine stimulieren die hypothalamische Prostaglandinaussc hüttung Erhöhung der Körpertemperatur zur Bekämpfung der Infektion Empfänger berührt den infizierten Gegenstand & anschließend einen Schleimhautbereich Moderat Schwer Virusausbreitung im Körper 1) über die Schleimhäute in die Umgebung & 2) die Blutzirkulation Das Virus imitiert das Angiotensin-Converting-Enzyme 2 (ACE2), haftet an dessen Rezeptoren & kann so in verschiedene Körperzellen eindringen COVID-19 Symptomatische Infektion mit SARS-CoV-2 Virale Proliferation in Geweben mit vermehrter ACE2-Rezeptor Expression: in Lunge (Typ II Pneumozyten), Gefäßen (Endothelzellen), Niere (Zellen des Proximalen Tubulus), Herz (Myokardzellen), GIT (Enterozyten) Virusanteile setzen virale RNA frei, die die Ribosomen der infizierten Zelle nutzen, um Proteine wie die RNA- Polymerase zu synthetisieren Die neue Polymerase benutzt die Nukleotide der Zelle um neue Virus - RNA zu produzieren Bilaterale Milchglastrübung (CT Lunge) & interstitielle Infiltrate im Röntgen Luftnot Neutrophile setzen reaktive Sauerstoffspezies & Zytokine in der Lunge frei Alveolärer und kapillärer Schaden Flüssigkeitsansammlungen in Alveolaren und Interstitium Diffusionsstrecke für O2 zw. Alveole und Kapillare ↑, Sauerstoffsättigung↓ Irritation der Atemwege Husten Myokardschaden Troponin ↑ Aus viraler RNA und Proteinhülle entstehen neue Viruspartikel Die neuen Viren werden freigesetzt, die Zelle geht dabei unter, was zu den Symptomen der Krankheit beiträgt Die durchschnittliche Inkubationszeit (von Infektion bis zu ersten Symptomen) beträgt 4-5 Tage, kann aber bis zu 14 Tagen andauern Herz versucht, Hypoxie zu kompensieren, HZV ↑, erhöhte Herzbelastung Herzrythmusstörung Skelettmuskels chaden Fieber Myalgie Legende: Pathophysiologie Mechanismen Symptome/Klinische Befunde Komplikationen Veröffentlicht: 22. März, 2020, aktualisiert Aug 18, 2021 on www.thecalgaryguide.com

Pathogenese des Diabetes Mellitus (DM), Typ II

Pathogenese des Diabetes Mellitus (DM), Typ II Genetische Prädisposition: Poly- oder monogenetische Faktoren (z.B. „Maturity- onset diabetes of the young“ (MODY)) können eine Insulinresistenz prädispositionieren Altern: Betazellen verlieren im Rahmen des Alterungsprozesses an Masse, wodurch sich, bei bereits bestehender Pädisposition, im Alter ein DM Typ II entwickeln kann . Medikamente: z.B. Cortison, Psychopharmaka, hochaktive antiretrovirale Therapie(HAART), Minipille (nur auf Progesteron basierende Kontrazeptiva) Blutzucker bleibt im Normbereich Zuckervergiftung: Hyperglykämien wirken toxisch auf Betazellen Hyperglykämie Beachte: Es besteht eine beträchtliche genetische Komponente: bei familiärer Vorbelastung ist die Erkrankungswahrscheinlichkeit sehr hoch ( bei eineiigen Zwillingen bis zu 90%). Bei Verwandtschaftsgrad ersten Grades ist das Risiko einer Erkrankung 5-10 Mal höher Ungesunder Lebensstil (z.B. Übergewicht, Bewegungsmangel) Intraabdominell akkumuliert „Viszeralfett“ (Bauchfett) welches als endokrines Organ funktioniert: Beachte: „Adipokine“ sind von Fettgewebe produzierte Entzündungsmediatoren (z.B. TNFalpha). Je mehr Fettgewebe ein Mensch besitzt, desto mehr Adipokine werden produziert. Entzündungsm ediatoren Freie Fettsäuren Adipokine Komplexe, teils unklare Interaktionen mit dem Gewebe Insulinresistenz (Die Wirkung des Insulins auf Leber, Muskel und Fettgewebe ist vermindert, Glucose kann deshalb nicht als Energiequelle genutzt werden ) Zunächst kompensieren Betazellen des Pankreas die verminderte Insulinwirkung durch vermehrte Produktion Fettvergiftung: Längerfristig nimmt die Kompensationsfähigkeit der Betazellen ab, Insulinproduktion ↓ (relativer Insulinmangel) Nach Jahren nimmt die Leistungsfähigkeit der Betazellen soweit ab, dass kein Insulin mehr produziert wird (absoluter Insulinmangel) Diabetes Mellitus Typ II Freie Fettsäuren blockieren den GLUT2 der Betazellen, Glucoseimport ↓ Betazellen erkennen den erhöhten Blutzucker nicht, Insulinproduktion sinkt Da der Körper keine Glukose nutzen kann, werden Triglyceride zu freien Fettsäuren umgewandelt damit diese als Energiequelle dienen können Autor: Yan Yu Rezensenten: Peter Vetere Gillian Goobie Doreen Rabi* Übersetzerin: Sarah Schwarz Übersetzungsprüfer: Gesche Tallen* * MD zum Zeitpunkt der Veröffentlichung Legende: Pathophysiologie Mechanismen Symptome/Klinische Befunde Komplikationen Veröffentlicht 11. Juli 2013 auf www.thecalgaryguide.com

Pathogenese des Diabetes Mellitus (DM), Typ I

Pathogenese des Diabetes Mellitus (DM), Typ I Genetische Prädisposition IDDM1 (HLA) Mutation IDDM2 (Insulingene) Mutationen Diet (Kuhmilch, Nitrosamine) Viren (Röteln, Coxsackie-Virus, Masern) Drogen/Toxine (Pyrinuron,Alloxan, Streptozocin, Pentamidine) Direkter Schaden an Betazellen, sodass deren Antigene dem Immunsystem ausgesetzt werden Stress (häufige Infektionen, Operationen, Pupertät) Externe Risikofaktoren Reifende T-Zellen im Thymus sind nicht in der Lage, die Fähigkeit der Erkennung von Insulingenen zu entwickeln T-Zellen greifen Insulin produzierende Betazellen an Mutationen des HLA (MCH) Gens können die Bindung von T-Zellen an Betazellen fördern aber auch verhindern Körperfremde Antigene imitieren Betazellantigene (Molekulare Mimiky), sodass sich die Immunantwort gegen diese Antigene auch gegen Betazellen richtet Beeinträchtigung der Toleranz des Immunsystem gegen körpereigene pankreatische Betazellen Autoimmunreaktion gegen Betazellen (sowohl durch angeborenes, als auch durch erworbenes Immunsystem: Infiltration der Langerhans-Inseln durch Monozyten und Zerstörung durch T-Zellen, auch als Insulitis bezeichnet ) Atrophie der Langerhans-Inseln auf die Hälfte ihrer Ausgangsmasse Längerfristig sind nur noch <10% der Betazellen funktionstüchtig Beachte: Die Anzahl an Autoantikörpern im Körper korrelieren mit der Wahrscheinlichkeit einen DM Typ I zu entwickeln Autor: Yan Yu Rezensenten: Peter Vetere Gillian Goobie *Doreen Rabi Übersetzerin: Sarah Schwarz Übersetzungsprüfer: Gesche Tallen* * MD zum Zeitpunkt der Veröffentlichung Produktion von Autoantikörper gegen Betazellen “Prä-diabetes” Diabetes Mellitus Typ I Absoluter Insulinmangel Anti-Insulin & Anti-GAD65 nachweisbar im Serum Noch asymptomatisch Hoher postprandialer Blutzucker Abgeschwächte Insulinreaktion nach i.v. Glucosegabe Legende: Pathophysiologie Mechanismen Symptome/Klinische Befunde Komplikationen Veröffentlicht: 11. Juli 2013 auf www.thecalgaryguide.com

Primary-Adrenal-Insufficiency

Primary Adrenal Insufficiency: Clinical findings Infection (fungal or tuberculosis) Note: “Primary” refers to pathology in the gland that produces the functional hormone (in this case, the adrenal gland), as opposed to “secondary” or “tertiary” which refers to pathology in glands that indirectly control the primary gland. Bilateral adrenal Autoimmune damage (cancer, ↓ Androgen levels in women (in whom adrenal glands are the primary source) ↓ Libido ↓ Axillary and pubic hair Muscle/joint pain Anorexia, weight loss Abdominal pain, nausea, vomiting Diseases bleeding, etc) ↓ Androgen production from the zona reticularis ↓ Cortisol production from the zona fasciculata ↓ Serum cortisol Patients could present with many severe symptoms of adrenal insufficiency, e.g. low blood pressure refractory to fluid resuscitation Significant bilateral damage to the adrenal glands Entire adrenal cortex function impaired ↓ Serum levels of adrenal steroid hormones exert positive feedback effect on pituitary gland, ↑ pituitary gland’s production of adrenocorticotropic hormone (ACTH) ↑ Serum levels of ACTH The same gene that encodes ACTH also encodes melanocyte stimulating hormone (MSH) Coincidental ↑ in MSH production by the pituitary ↓ Serum DHEAS, testosterone and androstenedione Unknown mechanism(s) Malaise Adrenal Crisis ↓ Cortisol mediated gluconeogenesis and glycogenolysis ↑ Cortisol Releasing Hormone (CRH) from the hypothalamus Lack of cortisol-driven vasoconstriction of blood vesselsà↑ Vasodilation ↓ Blood pressure, postural dizziness Water follows sodiumà ↑ excretion of water ↓ Sodium resorbed from kidney tubulesà↑ Sodium excretion ↓ Potassium pumped into kidney tubules à↑ potassium retained in serum Hypoglycemia (↓ blood glucose) ↑↑ Antidiuretic hormone (ADH) release Kidneys reabsorb water à↑ total body water Hyponatremia (↓ serum sodium) ↑ Salt craving Hyperkalemia (high serum potassium level) ↓ Aldosterone production from the zona glomerulosa ↓ Serum aldosterone MSH triggers ↑ production of melanin by the melanocytes in skin ↓ Excretion of hydrogen ions from kidneys (See type IV RTA slide for full mechanism) Metabolic acidosis (low pH, low bicarbonate) ↓ Sodium channel and Na/K ATPase expression on principle cells of the kidney Hyperpigmentation of the skin and mucosal surfaces Authors: Jaye Platnich, Brooke Fallis, Yan Yu* Reviewers: Mark Elliott, Alexander Arnold, Hanan Bassyouni*, David Campbell* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 13, 2013, updated October 1, 2021 on www.thecalgaryguide.com

A-a Gradient: why it exists and why we care

The Alveolar-arterial pO2 gradient: Author: Yan Yu Reviewers: Steven Liu, Amogh K. Agrawal, Ciara Hanly, Xiumei Deng (邓秀梅), Zesheng Ye (叶泽生), Yonglin Mai (麦泳琳)*, Juri Janovcik* * MD at time of publication Why it exists, and why we care Key Abbreviations: • pO2: partial pressure of O2, aka. “O2 content”. • PaO2: partial pressure of O2 in the arteries. Measured directly via Arterial Blood Gas (ABGs). • PAO2: partial pressure of O2 in the Alveoli. (Can’t be measured directly, must be calculated). Theoretically, in lung capillaries adjacent to alveoli: O2 should diffuse from alveoli into lung capillaries, and no O2 should be lost from the blood until the blood reaches the systemic arteries – so the PaO2 should equal PAO2. But in reality... Blood in the lung capillaries are not fully oxygenated to begin with: Since gravity causes more blood to settle to the lung bases, there is too much blood there for it all to be fully oxygenated by the alveoli. Less well-oxygenated blood from lung bases reduces the blood’s overall pO2 Less oxygenated blood from systemic veins are mixed into oxygenated blood from the lungs (“Venous admixture”): Venous drainage from the bronchial artery directly mixes with the pulmonary veins (oxygenated blood) Some veins in the coronary circulation drain into the left ventricle, instead of into the coronary sinus/R atrium Thus, O2 content of blood when it finally reaches the systemic arteries (PaO2) is less than the O2 content in the alveoli (PAO2) PAO2 - PaO2 = the pO2 “gradient” between the alveoli and the systemic arteries Note: Abnormally high A- a gradients indicate issues with gas diffusion between alveoli & the pulmonary capillaries. Note: some respiratory pathologies can present with a normal A-a gradient as well (see relevant slides) Normal A-a Gradient: <15 mmHg High A-a Gradient (>15 mmHg) is always a sign of pathology (see relevant slides) Legend: Definitions Explanations Sign/Symptom/Lab Finding Complications Published September 4, 2013, updated October 5, 2021 on www.thecalgaryguide.com The Alveolar-arterial pO2 gradient: Explainingtheformula A-aGradient=PO –PO (The simplified explanation) A 2 a 2 For an explanation of the physiology behind why an A-a gradient exists, please consult: “The Alveolar-arterial pO2 gradient: Why it exists, and why we care” Fraction of inhaled air made up of O2 (21%, if atmospheric) Partial Pressure of O2 within the alveoli: Partial Pressure of O2 in systemic arteries Measured directly via Arterial Blood Gas (ABG) PAO2 = (Total pressure of O2 inhaled into alveoli) (Air pressure generated by CO2 – molecules that are produced by the consumption of O2 molecules PAO2 = FiO2(PB – PH2O) – (PaCO2/0.8) Barometric Pressure Total air pressure inhaled into lungs (760mmHg at sea level, and less at higher altitudes) Partial pressure of water (47 mmHg): Inspired air is humidified once inside airways. Water vapor adds to total inhaled air pressure, and must be accounted for Partial pressure of dissolved CO2 in arteries, directly measured by an ABG Respiratory quotient: conversion ratio reflecting how, for every 5 molecules of O2 the blood absorbs or consumes, it releases approximately 4 CO2 molecules into the alveoli Partial pressure of gaseous CO2 in alveoli (PACO2) CO2 produced by body metabolism, exhaled into alveoli Author: Yan Yu Reviewers: Steven Liu, Amogh K. Agrawal, Ciara Hanly, Xiumei Deng (邓秀梅), Zesheng Ye (叶泽生), Yonglin Mai (麦泳琳)*, Juri Janovcik* * MD at time of publication Legend: Definitions Explanations Sign/Symptom/Lab Finding Complications Published September 4, 2013, updated October 5, 2021 on www.thecalgaryguide.com The Alveolar-arterial pO2 gradient: Explaining the formula (The scientifically-correct explanation) For an explanation of the physiology behind why an A-a gradient exists, please consult: “The Alveolar-arterial pO2 gradient: Why it exists, and why we care” A-a Gradient = PAO2 – PaO2 Partial Pressure of O2 within the alveoli: Partial Pressure of O2 in systemic arteries Measured directly via Arterial Blood Gas (ABG) Rationale: While O2 is being absorbed from the alveoli into the capillary, CO2 is being released from the capillary into the alveoli. Normal body metabolism is such that the amount of CO2 released is directly proportional to the amount of O2 absorbed. PAO2 = (Total pO2 entering alveoli) Can be calculated easily – (total pO2 leaving alveoli and absorbed into blood) Cannot be directly measured; need to estimate it using the level of CO2 in the alveoli, which we can measure PAO2 = FiO2(PB – PH2O) – (PaCO2/0.8) Fraction of inhaled air made up of O2 (21%, if atmospheric) Barometric Pressure Total air pressure inhaled into lungs (760mmHg at sea level, and less at higher altitudes, ie: 660mmHg in Calgary) 47 mmHg: Inspired air is humidified once inside airways. Water vapor adds to total inhaled air pressure, and must be accounted for Partial pressure of dissolved CO2 in arteries, directly measured by an ABG Respiratory quotient (RQ): the ratio of the amount of CO2 released from the arterial blood to the amount of O2 absorbed or consumed by the blood. The value of the RQ can vary depending upon the diet consumed Note: The respiratory quotient (carbohydrates, fats, and proteins) (RQ) is always <1 because and the metabolic state. RQ is around 0.82 for the average human diet. Author: Yan Yu Reviewers: Steven Liu, Amogh K. Agrawal, Ciara Hanly, Xiumei Deng (邓秀梅), Zesheng Ye (叶泽生), Yonglin Mai (麦泳琳)*, Juri Janovcik* * MD at time of publication Legend: Definitions Explanations Sign/Symptom/Lab Finding Complications Published September 4, 2013, updated October 5, 2021 on www.thecalgaryguide.com

A-a Gradient: Explaining the formula simplified

The Alveolar-arterial pO2 gradient: Author: Yan Yu Reviewers: Steven Liu, Amogh K. Agrawal, Ciara Hanly, Xiumei Deng (邓秀梅), Zesheng Ye (叶泽生), Yonglin Mai (麦泳琳)*, Juri Janovcik* * MD at time of publication Why it exists, and why we care Key Abbreviations: • pO2: partial pressure of O2, aka. “O2 content”. • PaO2: partial pressure of O2 in the arteries. Measured directly via Arterial Blood Gas (ABGs). • PAO2: partial pressure of O2 in the Alveoli. (Can’t be measured directly, must be calculated). Theoretically, in lung capillaries adjacent to alveoli: O2 should diffuse from alveoli into lung capillaries, and no O2 should be lost from the blood until the blood reaches the systemic arteries – so the PaO2 should equal PAO2. But in reality... Blood in the lung capillaries are not fully oxygenated to begin with: Since gravity causes more blood to settle to the lung bases, there is too much blood there for it all to be fully oxygenated by the alveoli. Less well-oxygenated blood from lung bases reduces the blood’s overall pO2 Less oxygenated blood from systemic veins are mixed into oxygenated blood from the lungs (“Venous admixture”): Venous drainage from the bronchial artery directly mixes with the pulmonary veins (oxygenated blood) Some veins in the coronary circulation drain into the left ventricle, instead of into the coronary sinus/R atrium Thus, O2 content of blood when it finally reaches the systemic arteries (PaO2) is less than the O2 content in the alveoli (PAO2) PAO2 - PaO2 = the pO2 “gradient” between the alveoli and the systemic arteries Note: Abnormally high A- a gradients indicate issues with gas diffusion between alveoli & the pulmonary capillaries. Note: some respiratory pathologies can present with a normal A-a gradient as well (see relevant slides) Normal A-a Gradient: <15 mmHg High A-a Gradient (>15 mmHg) is always a sign of pathology (see relevant slides) Legend: Definitions Explanations Sign/Symptom/Lab Finding Complications Published September 4, 2013, updated October 5, 2021 on www.thecalgaryguide.com The Alveolar-arterial pO2 gradient: Explainingtheformula A-aGradient=PO –PO (The simplified explanation) A 2 a 2 For an explanation of the physiology behind why an A-a gradient exists, please consult: “The Alveolar-arterial pO2 gradient: Why it exists, and why we care” Fraction of inhaled air made up of O2 (21%, if atmospheric) Partial Pressure of O2 within the alveoli: Partial Pressure of O2 in systemic arteries Measured directly via Arterial Blood Gas (ABG) PAO2 = (Total pressure of O2 inhaled into alveoli) (Air pressure generated by CO2 – molecules that are produced by the consumption of O2 molecules PAO2 = FiO2(PB – PH2O) – (PaCO2/0.8) Barometric Pressure Total air pressure inhaled into lungs (760mmHg at sea level, and less at higher altitudes) Partial pressure of water (47 mmHg): Inspired air is humidified once inside airways. Water vapor adds to total inhaled air pressure, and must be accounted for Partial pressure of dissolved CO2 in arteries, directly measured by an ABG Respiratory quotient: conversion ratio reflecting how, for every 5 molecules of O2 the blood absorbs or consumes, it releases approximately 4 CO2 molecules into the alveoli Partial pressure of gaseous CO2 in alveoli (PACO2) CO2 produced by body metabolism, exhaled into alveoli Author: Yan Yu Reviewers: Steven Liu, Amogh K. Agrawal, Ciara Hanly, Xiumei Deng (邓秀梅), Zesheng Ye (叶泽生), Yonglin Mai (麦泳琳)*, Juri Janovcik* * MD at time of publication Legend: Definitions Explanations Sign/Symptom/Lab Finding Complications Published September 4, 2013, updated October 5, 2021 on www.thecalgaryguide.com The Alveolar-arterial pO2 gradient: Explaining the formula (The scientifically-correct explanation) For an explanation of the physiology behind why an A-a gradient exists, please consult: “The Alveolar-arterial pO2 gradient: Why it exists, and why we care” A-a Gradient = PAO2 – PaO2 Partial Pressure of O2 within the alveoli: Partial Pressure of O2 in systemic arteries Measured directly via Arterial Blood Gas (ABG) Rationale: While O2 is being absorbed from the alveoli into the capillary, CO2 is being released from the capillary into the alveoli. Normal body metabolism is such that the amount of CO2 released is directly proportional to the amount of O2 absorbed. PAO2 = (Total pO2 entering alveoli) Can be calculated easily – (total pO2 leaving alveoli and absorbed into blood) Cannot be directly measured; need to estimate it using the level of CO2 in the alveoli, which we can measure PAO2 = FiO2(PB – PH2O) – (PaCO2/0.8) Fraction of inhaled air made up of O2 (21%, if atmospheric) Barometric Pressure Total air pressure inhaled into lungs (760mmHg at sea level, and less at higher altitudes, ie: 660mmHg in Calgary) 47 mmHg: Inspired air is humidified once inside airways. Water vapor adds to total inhaled air pressure, and must be accounted for Partial pressure of dissolved CO2 in arteries, directly measured by an ABG Respiratory quotient (RQ): the ratio of the amount of CO2 released from the arterial blood to the amount of O2 absorbed or consumed by the blood. The value of the RQ can vary depending upon the diet consumed Note: The respiratory quotient (carbohydrates, fats, and proteins) (RQ) is always <1 because and the metabolic state. RQ is around 0.82 for the average human diet. Author: Yan Yu Reviewers: Steven Liu, Amogh K. Agrawal, Ciara Hanly, Xiumei Deng (邓秀梅), Zesheng Ye (叶泽生), Yonglin Mai (麦泳琳)*, Juri Janovcik* * MD at time of publication Legend: Definitions Explanations Sign/Symptom/Lab Finding Complications Published September 4, 2013, updated October 5, 2021 on www.thecalgaryguide.com

A-a Gradient: Explaining the formula scientific

The Alveolar-arterial pO2 gradient: Author: Yan Yu Reviewers: Steven Liu, Amogh K. Agrawal, Ciara Hanly, Xiumei Deng (邓秀梅), Zesheng Ye (叶泽生), Yonglin Mai (麦泳琳)*, Juri Janovcik* * MD at time of publication Why it exists, and why we care Key Abbreviations: • pO2: partial pressure of O2, aka. “O2 content”. • PaO2: partial pressure of O2 in the arteries. Measured directly via Arterial Blood Gas (ABGs). • PAO2: partial pressure of O2 in the Alveoli. (Can’t be measured directly, must be calculated). Theoretically, in lung capillaries adjacent to alveoli: O2 should diffuse from alveoli into lung capillaries, and no O2 should be lost from the blood until the blood reaches the systemic arteries – so the PaO2 should equal PAO2. But in reality... Blood in the lung capillaries are not fully oxygenated to begin with: Since gravity causes more blood to settle to the lung bases, there is too much blood there for it all to be fully oxygenated by the alveoli. Less well-oxygenated blood from lung bases reduces the blood’s overall pO2 Less oxygenated blood from systemic veins are mixed into oxygenated blood from the lungs (“Venous admixture”): Venous drainage from the bronchial artery directly mixes with the pulmonary veins (oxygenated blood) Some veins in the coronary circulation drain into the left ventricle, instead of into the coronary sinus/R atrium Thus, O2 content of blood when it finally reaches the systemic arteries (PaO2) is less than the O2 content in the alveoli (PAO2) PAO2 - PaO2 = the pO2 “gradient” between the alveoli and the systemic arteries Note: Abnormally high A- a gradients indicate issues with gas diffusion between alveoli & the pulmonary capillaries. Note: some respiratory pathologies can present with a normal A-a gradient as well (see relevant slides) Normal A-a Gradient: <15 mmHg High A-a Gradient (>15 mmHg) is always a sign of pathology (see relevant slides) Legend: Definitions Explanations Sign/Symptom/Lab Finding Complications Published September 4, 2013, updated October 5, 2021 on www.thecalgaryguide.com The Alveolar-arterial pO2 gradient: Explainingtheformula A-aGradient=PO –PO (The simplified explanation) A 2 a 2 For an explanation of the physiology behind why an A-a gradient exists, please consult: “The Alveolar-arterial pO2 gradient: Why it exists, and why we care” Fraction of inhaled air made up of O2 (21%, if atmospheric) Partial Pressure of O2 within the alveoli: Partial Pressure of O2 in systemic arteries Measured directly via Arterial Blood Gas (ABG) PAO2 = (Total pressure of O2 inhaled into alveoli) (Air pressure generated by CO2 – molecules that are produced by the consumption of O2 molecules PAO2 = FiO2(PB – PH2O) – (PaCO2/0.8) Barometric Pressure Total air pressure inhaled into lungs (760mmHg at sea level, and less at higher altitudes) Partial pressure of water (47 mmHg): Inspired air is humidified once inside airways. Water vapor adds to total inhaled air pressure, and must be accounted for Partial pressure of dissolved CO2 in arteries, directly measured by an ABG Respiratory quotient: conversion ratio reflecting how, for every 5 molecules of O2 the blood absorbs or consumes, it releases approximately 4 CO2 molecules into the alveoli Partial pressure of gaseous CO2 in alveoli (PACO2) CO2 produced by body metabolism, exhaled into alveoli Author: Yan Yu Reviewers: Steven Liu, Amogh K. Agrawal, Ciara Hanly, Xiumei Deng (邓秀梅), Zesheng Ye (叶泽生), Yonglin Mai (麦泳琳)*, Juri Janovcik* * MD at time of publication Legend: Definitions Explanations Sign/Symptom/Lab Finding Complications Published September 4, 2013, updated October 5, 2021 on www.thecalgaryguide.com The Alveolar-arterial pO2 gradient: Explaining the formula (The scientifically-correct explanation) For an explanation of the physiology behind why an A-a gradient exists, please consult: “The Alveolar-arterial pO2 gradient: Why it exists, and why we care” A-a Gradient = PAO2 – PaO2 Partial Pressure of O2 within the alveoli: Partial Pressure of O2 in systemic arteries Measured directly via Arterial Blood Gas (ABG) Rationale: While O2 is being absorbed from the alveoli into the capillary, CO2 is being released from the capillary into the alveoli. Normal body metabolism is such that the amount of CO2 released is directly proportional to the amount of O2 absorbed. PAO2 = (Total pO2 entering alveoli) Can be calculated easily – (total pO2 leaving alveoli and absorbed into blood) Cannot be directly measured; need to estimate it using the level of CO2 in the alveoli, which we can measure PAO2 = FiO2(PB – PH2O) – (PaCO2/0.8) Fraction of inhaled air made up of O2 (21%, if atmospheric) Barometric Pressure Total air pressure inhaled into lungs (760mmHg at sea level, and less at higher altitudes, ie: 660mmHg in Calgary) 47 mmHg: Inspired air is humidified once inside airways. Water vapor adds to total inhaled air pressure, and must be accounted for Partial pressure of dissolved CO2 in arteries, directly measured by an ABG Respiratory quotient (RQ): the ratio of the amount of CO2 released from the arterial blood to the amount of O2 absorbed or consumed by the blood. The value of the RQ can vary depending upon the diet consumed Note: The respiratory quotient (carbohydrates, fats, and proteins) (RQ) is always <1 because and the metabolic state. RQ is around 0.82 for the average human diet. Author: Yan Yu Reviewers: Steven Liu, Amogh K. Agrawal, Ciara Hanly, Xiumei Deng (邓秀梅), Zesheng Ye (叶泽生), Yonglin Mai (麦泳琳)*, Juri Janovcik* * MD at time of publication Legend: Definitions Explanations Sign/Symptom/Lab Finding Complications Published September 4, 2013, updated October 5, 2021 on www.thecalgaryguide.com

copd-overview-and-definitions

Defining “Chronic Obstructive Pulmonary Disease (COPD)” Author: Yan Yu Reviewers: Jason Baserman, Jennifer Au, Ciara Hanly, Zesheng Ye (叶泽生), Yonglin Mai (麦泳琳)*, Naushad Hirani*, Juri Janovcik* * MD at time of publication Cystic Fibrosis Multisystem disease due to CFTR gene mutation, that presents in the lungs as bronchiectasis Bronchiectasis, Cystic Fibrosis, etc COPD Systemic disease, largely manifesting as an airflow-obstructing respiratory disorder; can manifest in the form of any of the following disorders: Emphysema Lung tissue destruction & abnormal, permanent enlargement of lung acini: airspaces distal to terminal bronchioles Chronic Bronchitis Chronic, productive cough for a total duration of 3 months per year, over 2 continuous years Asthma Asthma that does not remit completely with treatment (thus, chronic airflow obstruction) is defined as asthma-COPD overlap syndrome (ACOS) Emphysema Bronchiectasis Destruction and widening of large airways, resulting in mucus hyper-secretion and recurrent infections Chronic Bronchitis Most common COPD manifestations (most patients suffer from a combination of emphysema and chronic bronchitis) Clinically, COPD is seen as: • Progressive, partially reversible airflow obstruction and lung hyperinflation (causing respiratory symptoms like cough, sputum production, and dyspnea) • Post-bronchodilator spirometry results: FEV1/FVC ratio <0.7 (FEV1 is not a defining feature of COPD, but a marker of severity) • ↑ frequency & severity of acute exacerbations • Systemic manifestations such as deconditioning and muscle weakness Chronic Obstructive Pulmonary Disease (COPD) Asthma Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013, updated October 5, 2021 on www.thecalgaryguide.com

Hypersensitivity-Pneumonitis

Hypersensitivity Pneumonitis: Pathogenesis and clinical findings Authors: Zarrukh Baig, Zaini Sarwar Reviewers: Natalie Morgunov, Sadie Kutz, Laura Byford-Richardson, Ciara Hanly, Yonglin Mai (麦泳琳)*, Kerri Johannson* * MD at time of publication Farming and Compost Farmer’s Lung (Common) Bird and Animal Proteins Bird Fancier’s Lung (Common) Water Contamination and Ventilation Organic antigen identified by dendritic cells Manufacturing and Chemical Workers Grain and Flour Processors Notes: Immune complex - Production of IgG antibodies (Type III hypersensitivity) Cell mediated - Sensitization of helper T cells (Type IV hypersensitivity) • Thereare3typesofhypersensitivity pneumonitis: acute, subacute, chronic • InacuteHP,removalofincitingantigen results in resolution of symptoms within days. *Lymphoplasmocytic interstitial infiltrate with bronchiolocentric distribution on pathology Epithelial injury (exact mechanism unknown) *Organizing pneumonia Dyspnea, tachypnea, and crackles Abbreviations: • HP – Hypersensitivity Pneumonitis • PFT – Pulmonary Function Test ↑ Neutrophils, mast cells, macrophages, CD8+ T cells, & inflammatory cytokines • *TriadofmainfindingsforsubacuteHP Systemic release of cytokines disrupts hypothalamic regulation Fever Macrophages ingest antigens *Poorly formed granulomas on pathology Tissue breakdown from neutrophils activates fibroblasts, which deposit collagen CT: Normal or diffuse ground- glass opacity (acute) Chronic deposition of collagen replaces normal lung parenchyma by scar tissues (Chronic Findings) Neutrophil elastase breaks down lung elastic fibers Tissue destruction of alveolar walls creates larger air spaces CT: Emphysema CT: Honeycombing (End stage Iung disease) Pathology: Advanced interstitial fibrosis PFT: Restrictive pattern ↓FEV1, ↓FVC, and ↓ DLCO Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 1, 2016, updated October 5, 2021 on www.thecalgaryguide.com

Tension Pneumothorax

Tension Pneumothorax: Pathogenesis, clinical findings and findings on X-Ray Authors: Mark Elliott, Davis Maclean, Evan Allarie, Shelly Spanner* Reviewers: Steven Liu, David Nicholl, Ciara Hanly, Zesheng Ye (叶泽生), Yonglin Mai (麦泳琳)*, Naushad Hirani*, Yan Yu* * MD at time of publication Contralateral Trachea Shift Contralateral Mediastinal Shift Absence of lung markings Collapsed lung (visceral pleural line) Rib splaying Depressed Hemidiaphragm Tachycardia Hypotension ↑ Jugular venous pressure ↓ blood oxygenation (partial pressure of O2) Tachypnea (↑ respiratory rate) Secondary Spontaneous Pneumothorax (underlying lung disease) Procedures (E.g. thoracentesis, central line insertion, lung nodule biopsy) Positive Pressure Ventilation Barotrauma Primary Spontaneous Pneumothorax (no underlying lung disease) Traumatic Pneumothorax E.g. penetrating wound, rib fracture Iatrogenic Pneumothorax Disruption of parietal or visceral pleura or the tracheobronchial tree Injured tissue forms a one- way valve into pleural space Air enters and fills pleural space (due to physiologic negative pleural pressure), but cannot leave ↑ Pressure in ipsilateral hemithorax ↑ Pressure collapses ipsilateral lung Irritation of highly sensitive parietal pleura Acute onset severe, stabbing, pleuritic chest pain (can radiate to shoulder) Contralateral cardiac silhouette shift Air between visceral & parietal pleura separates the two layers, allowing visualization of a pleural “line” Visible visceral pleural line Ipsilateral rib splaying (↑ space between ribs) Depressed hemidiaphragm Contralateral cardiac silhouette and tracheal Deviation Compresses superior vena cava and/or inferior vena cava ↑ sound resonance through air compared to lung tissue Tympany/ hyper-resonant (on manual percussion over affected area) Sound vibrations unable to travel from the larynx through lung tissue to chest wall as normal ↓ vocal fremitus (palpable vibration of chest wall during speech) No air entry in to affected lung ↓ chest wall expansion Lack of lung markings beyond the pleural line ↓ breath sounds Dyspnea Mediastinal shift away from the affected side ↓ cardiac output Blood backs up into venous system Potential contralateral lung impingement Impaired gas exchange in the affected alveoli ↓ blood return to right atrium Risk of ipsilateral lung collapse Ventilation/Perfusion mismatch and blood shunt Hypoxia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding X-Ray Findings Initially published December 11, 2013, reviewed & updated October 24, 2020 and October 5, 2021 on www.thecalgaryguide.com

COPD Acute Exacerbations

COPD Acute Exacerbations: Triggers and Signs/Symptoms Authors: Brianne McDonald, Yan Yu* Reviewers: Nilani Sritharan, Sean Doherty, Zihong Xie (谢梓泓), Zesheng Ye (叶泽生), Yonglin Mai (麦泳琳)*, Kerri Johannson* * MD at time of publication Notes: • The triggers for acute exacerbations of COPD are unknown in approximately 1/3 of cases • Changes in pulmonary function (e.g. FEV1) are poorly sensitive in the individual diagnosis of acute exacerbations of COPD due to individual variability Acute Bacterial Infection Activation of proinflammatory cytokines and recruitment of neutrophils Acute Viral Infection Epithelial cell secretion of cytokines and ↑ airway lymphocythemia Acute ↑ in airway inflammation (accumulation of inflammatory cells and release of harmful mediators, such as reactive oxygen species and proteases, into the lung tissue/airways) Air pollution (including cigarette smoke) ↑ reactive oxygen species in lungs Airway inflammation ↑ secretions that accumulate in the airway lumen Airway wall edema Limits outflow of air from lungs on expiration Airway bronchoconstriction in response to inflammation Constricted airways create audible turbulent airflow on expiration Systemic spread of inflammatory markers via the bloodstream cause inflammation throughout the body ↑ Cardiac Morbidity ↑ CRP Worsening of respiratory symptoms Irritation of cough reflexes in airways Cough ↑ Sputum production and sputum purulence ↑ Wheeze Unexpired air becomes trapped in the lungsàDynamic Hyperinflation Bloodflow to lungs continue to perfuse under- ventilated regions of lungs àV/Q Mismatch Lungs are larger àmore blood remains in lungs à↓ preload Acute Respiratory Failure Tachypnea ↑ Dyspnea Accessory Muscle Use Attempts to restore normal arterial CO2 and O2 levels Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 21, 2019, updated October 6, 2021 on www.thecalgaryguide.com

Hypercortisolemia

Hypercortisolemia (Cushing’s Syndrome): Clinical Findings Cortisol is a net catabolic hormone affecting many body systems, serving to release energy into the blood in response to stress. Excess cortisol also impacts circulation and impairs immune function. Excess Serum Cortisol affects: Authors: Samin Dolatabadi, Yan Yu* Reviewers: Meena Assad, Amanda Henderson, Brooke Fallis, David Campbell* * MD at time of publication Bone and Calcium Metabolism Kidney and vasculature Excess cortisol in the renal tubule saturates the enzyme 11β- HSD2, which converts cortisol to cortisone Capacity of body to convert cortisol to cortisone is exceeded Excess cortisol can mimic aldosterone and bind to mineralocorticoid receptors (cortisone can’t bind to these receptors) ↑ Aldosterone effect → ↑ Na+ reabsorption from the cortical collecting duct into blood vessels Liver and Peripheral Tissue Cortisol ↑ gluco- neogenesis in liver, and ↑ insulin resistance by body tissue (unclear mechanisms) Hyper- glycemia Reproductive System Cortisol exerts negative feedback on hypothalamus à↓ gonadotropin releasing hormone (GnRH) secretion ↓ GnRH → ↓ LH/FSH → ↓ estrogen and testosterone production (especially important in females) Infertility, ↓ Libido, Irregular Menses Adipose Tissue Cortisol ↑ fat breakdown (lipolysis) Selective expression of cortisol receptor on different adipose tissuesàcentral, facial, dorsal fat is less broken down than in other areas (mechanism unclear) Combined with cortisol ↑ appetite: Skin & Connective Tissue ↑ Serum cortisol à↓ Fibroblast proliferation → ↓ Collagen synthesis Skin atrophy with loss of connective tissue Muscle ↑ Proteolysis & ↓ Protein synthesisà↓ muscle growth and function Immune System Normal serum cortisol protects against damaging effects of uncontrolled inflammatory and immune responses ↑ Serum cortisolà over-suppression of inflammation and impaired cell- mediated immunity ↑ Serum cortisol leads to ↓ Intestinal Ca2+ absorption and ↓ renal Ca2+ reabsorption ↓ Serum Ca2+ ↑ PTH secretion ↑ Serum cortisolà↑ RANKL:OPG ratio ↓ Osteoblast activity & ↑ Osteoclast activity Cardiac muscle Cardio- myopathy, Heart Failure Skeletal muscle, especially upper arms & thighs (for unclear reasons) Proximal Muscle Weakness Easy Bruising ↑ abdominal size stretches the fragile skin to become thinneràvenous blood of the underlying dermis becomes visible Purple Striae If hypertension is chronic Ca2+ resorption from bone into the blood Osteoporosis Supraclavicular & Dorsal Fat Pads Central Obesity Poor Wound Healing Susceptibility to infection Round Face (Moon Face) Abbreviations: • RANKL – Receptor activator of nuclear factor kappa-Β ligand • OPG – Osteoprotegerin • 11β-HSD2 – 11β-hydroxysteroid dehydrogenase type 2 Water follows Na+ into blood vessels to balance the osmotic pressure between the blood and renal tubules Water reabsorption → Expansion of blood volume Hypertension Both primary Cushing’s (e.g. adenomas that extend into zona reticularis of the adrenal cortex) and central/secondary Cushing’s (e.g. ↑ ACTH stimulation of zona reticularis) are associated with ↑ adrenal androgen secretion Removal of positively charged Na+ from tubular lumen creates a negative luminal environment K+ follows the electrical gradient and is secreted into tubular lumen ↓ Serum K+ concentration Hypokalemia Arrhythmia, Paralysis, Cramps (see Hypokalemia: Clinical Findings slide) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 17, 2021 on www.thecalgaryguide.com Hirsutism, Acne

Twins Mechanisms and Complications

Twins: Mechanisms and Complications Single ovum ovulatedàOvum fertilized by single sperm Single zygote develops into a single embryo, but for unknown mechanisms, cells in this embryo can separate from one another, causing the embryo to “split” Risk factors for dizygotic twins: ↑ follicle-stimulating hormone (age >35, family history) Allows multiple follicles to mature IVF (multiple embryo transfer) Ovulation induction/ superovulation fertility medications Embryo splits during days 0-3 Embryo splits during days 4-8, after trophoblast cells (outer layer of blastocyst) have already invaded the endometrium and formed part of the placenta Each embryo forms its own amniotic sac, both fed by 1 placenta Monochorionic (1 placenta) Diamniotic (2 amniotic sacs) Monozygotic Twins Embryo splits during days 9-12, when both placental and amniotic sac development have started The embryos must now develop within a shared amniotic sac & placenta Monochorionic (1 placenta) Monoamniotic (1 amniotic sac) Monozygotic Twins Two ova ovulatedàEach ovum fertilized by a separate sperm Cells still undifferentiated at this stage, allows each embryo to develop it’s own placenta and amniotic sac Dichorionic (2 placentas) Diamniotic (2 amniotic sacs) Monozygotic Twins Two embryos develop that implant separately into the endometrium and develop their own placenta and amniotic sac Dizygotic Twins (Dichorionic, Diamniotic by default) Complications of all types of twins: Overdistention of the uterus Weakened uterine muscles leading to uterine atony Postpartum Hemorrhage (see relevant slide) Larger placental mass without ↑ placental blood flow Placental hypoperfusion (plus other complex mechanisms) Gestational Hypertension and Pre- Eclampsia ↑ plasma volumeà diluting red blood cells, plus ↑ fetal iron consumption from mother’s stores Anemia High β- HCG Mechanism unknown Hyperemesis Gravidarum Operative Delivery Preterm Birth Insufficient maternal nutritional supplies Abnormal placental vascular connections Fetal Death Interplacental vascular connections lead to uneven distribution of nutrients and blood flow Twin-Twin Transfusion Syndrome (growth discordance between twins, see relevant slide) Note: all complications are more likely in monozygotic twins Umbilical cords become entangled within shared amniotic sac Cord Entanglement Authors: Jemimah Raffé- Devine, Yan Yu* Reviewers: Brianna Ghali Jadine Paw* *MD at the time of publication Uterine crowding ↑ risk of fetal malpresentation Less space in uterus for continued growth Congenital Anomalies Intrauterine Growth Restriction Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 18, 2021 on www.thecalgaryguide.com

Ectopic Pregnancy

Ectopic Pregnancy: Pathogenesis and Clinical Findings In vitro fertilization Tubal disorders leading to infertility and unknown procedural causes Previous ectopic pregnancy Underlying tubal disorder leading to previous ectopic Pelvic inflammatory disease (PID) Endometriosis Tubal surgery or disorders Age >35 Risk factor accumulation over time Smoking Impairment in tubal motility; impaired immunity (risk factor for PID) Tubal scarring leading to adhesions, obstruction, and alteration of tubal function Ectopic Pregnancy: Implantation of developing blastocyst outside the uterine cavity, most commonly in fallopian tube (other locations: interstitial > cornual > cervical > ovarian > abdominal) Embryo releases human chorionic gonadotropin (β-hCG), which supports corpus luteum to continue producing progesterone On transvaginal ultrasound: Extrauterine gestational sac with a yolk sac or embryo Embryo & trophoblast deathàloss of hormone support for the decidua (modified endometrial lining) Progesterone maintains the endometrial lining, preventing it from shedding Missed period Penetration of ovum into muscular wall of fallopian tube Tubal distention àTubal rupture Intra-abdominal hemorrhage Pregnancy cannot survive without the uterine endometrium Maternal blood extrudes through fimbriae of fallopian tubes and into peritoneal cavity Lower abdominal pain (including peritonitis in cases of hemoperitoneum) Hemoperitoneum (blood in the peritoneal cavity) Sloughing of decidua out of the uterus through the vagina Vaginal bleeding (usually in first trimester) Cessation of human chorionic gonadotropin (β-hCG) release from embryo β-hCG plateaus or decreases Authors: Jemimah Raffé-Devine Tahsin Khan Yan Yu* Reviewers: Brianna Ghali Bishwas Paudel Mackenzie Grisdale Christina Schweitzer Ron Cusano* Jadine Paw* * MD at time of publication Syncope ↓ Level of consciousness Positive β-hCG, but rising <35% over 2 days Discriminatory zone: β-hCG >2000 + absence of intrauterine pregnancy Hypotension Shock Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Oct 1, 2017, updated Oct 19, 2021 on www.thecalgaryguide.com

Acne Vulgaris Complications

Acne vulgaris: Complications Acne vulgaris Cutaneous inflammation caused by acne lesions True Scars Authors: Stephen Williams Reviewers: Mehul Gupta, Lauren Lee, Yan Yu*, Laurie Parsons* * MD at time of publication Elevated Acne Scars ↑ collagen exceeds collagen degradation Prostaglandins (PGE2), leukotrienes (LTC4, LTD4), and thromboxane A2 are released in response to inflammation Atrophic Acne Scars Collagen degradation and disordered deposition during healing Formation of round- rectangular depressions with defined edges Box Car Scar True scars with textural change, very slow autoresolution over time The pigmentary changes and true scar formation resulting from acne may be more psychologically distressing than the original acne lesions Healing processes favoring deposition of Type 1 & Type 3 collagen Proliferation beyond the borders of original acne lesion Keloid Formation Healing processes favoring deposition of Type 4 collagen Growth remains within the margins of acne lesion Hypertrophic Scar Formation Dermal inflammation: Due to disruption of basal cell layer, melanin released and trapped by macrophages in the dermis. Epidermal inflammation: ↑ melanin production and transfer of melanin to keratinocytes Microvascular dilatation and ↑presence of erythrocytes Erythematous macules appear where acne was present Post- inflammatory Erythema (PIE). More common in Fitzpatrick Skin Types I-III Formation of V- shaped tracts with sharp margins Ice Pick Scar Formation of a shallow edged depression layer anchored to dermal layer and subcutis Rolling Scar Pigmented macules or patches appear where acne was present Post-inflammatory Hyperpigmentation (PIH). More common in Fitzpatrick Skin Types III-VI No textural change, slow autoresolution over time True scars with textural change, do not resolve over time Psychosocial Concerns (Depression, Anxiety, Social Isolation) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 19, 2021 on www.thecalgaryguide.com

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Authors: Lauren D. Lee, Harry C. Liu* Reviewers: Mehul Gupta, Brian Rankin, Julia Chai, Stephen Williams Yan Yu* Laurie Parsons* *MD at time of publication Pathogenesis and clinical findings Genetic susceptibility Certain HLAs (e.g., HLA-B*58:01, HLA-B*57:01, and HLA-A*31:01) HLA alleles encode for MHC structure and may influence how specific drugs/drug metabolites interact with T cell receptors and MHC proteins on antigen-presenting cells Exposure to offending drug E.g., Aromatic anticonvulsants (lamotrigine, carbamazepine, and phenytoin), allopurinol, and sulfonamides Drug-specific CD4+ and CD8+ T cells produce tumor necrosis factor-alpha and interferon gamma ↑ activated T-cells 2-6 weeks after drug exposure Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Latent Viral infection Latent viruses (HHV-6, HHV- 7, CMV, and EBV) concealed in regulatory T-cells Reactivation of latent viruses may be contributory or secondary to T cell activation by drugs Eosinophilia +/- atypical lymphocytes T helper type 2 cells recruit and activate eosinophils by releasing cytokines Activated leukocytes create a humoral immune and allergic response Dysfunction of regulatory T cells, resulting in failure to control unwanted immune responses against “self” Autoimmune processes with single- or multi-organ involvement CMV- Cytomegalovirus EBV- Epstein-Barr Virus HHV- Human Herpesvirus HLA- Human Leukocyte Antigens MHC – Major Histo- compatibility Complex Endocrine system mechanism of dysfunction unclear but may be linked to autoreactive T cells Autoimmune Type 1 thyroiditis diabetes Lymphadenopathy Fever Facial edema Liver lobular inflammation, dispersed foci of necrotic hepatocytes, granulomatous infiltrates consisting of eosinophils Hepatitis Kidney Interstitial edema and infiltrates of lymphocytes, histiocytes, eosinophils, and plasma cells Acute interstitial nephritis Lung increased pulmonary infiltrate and edema Morbilliform Skin Eruption Spongiosis Epidermal layer Dermal- Epidermal Junction Dermal layer Interface dermatitis Skin eruption (morbilliform to diffuse erythema with follicular accentuation) Interstitial pneumonitis Pleural effusion Eosinophilic infiltration Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 19, 2021 on www.thecalgaryguide.com

Vestibular Neuritis

Vestibular Neuritis: Pathogenesis and Clinical Findings Authors: Ryan Chan Jonathan Wong Reviewers: Mehul Gupta Davis Maclean Saud Sunba Yan Yu* Euna Hwang* * MD at time of publication Recent viral illness or upper respiratory tract infection Virus spreads along upper respiratory mucosa and into the inner ear structures Vestibular Neuritis Presumed idiopathic viral-induced inflammation of the vestibular nerve; typically unilateral Reactivation of Herpes Simplex Virus-1 in vestibular (Scarpa’s) ganglion Inflammatory cell infiltration leads to degeneration and atrophy of the vestibular nerve Superior Vestibular Neuritis (40-48%) Inflammatory cells traverse through only one long bony canal, easier for inflammatory cell infiltration Loss of afferent innervation from the superior and horizontal semicircular canal (SCC), utricle, and parts of the saccule Combined Superior Vestibular Neuritis and Inferior Vestibular Neuritis (34-56%) Inferior Vestibular Neuritis (1.3-18%) Inflammatory cells must pass through two separate bony canals, making inflammatory cell infiltration more difficult Loss of afferent innervation from the posterior semicircular canal (SCC) and saccule Utricular degeneration Displacement of otoliths/ otoconia (commonly into the posterior SCC) BPPV (can occur several months after onset of neuritis) Loss of horizontal SCC afferent neuron signaling to the brain Unilateral Loss or ↓ of normal nystagmus response to Caloric Testing (insertion of cold and warm water/air into the ear canal while supine) Loss of utricular afferent neuron signaling to the brain ↓ or absent Ocular Vestibular- Evoked Myogenic Potentials (VEMPs) and Normal Cervical VEMPs ↓ unilateral vestibular input to the brain leads to acute phase symptoms (over time, brain can compensate which allows for some symptom improvement) Loss of posterior SCC and saccular afferent neuron signaling to the brain ↓ or absent Cervical VEMPs, but Ocular VEMPs are normal ↓ or absent input to the ipsilateral vestibular nuclei elicits a vestibular nucleus response similar to contralateral SCC excitation Acute-Phase Spontaneous Nystagmus Fast phase beats away from the affected side (3- 10 days) And Loss of ocular fixation on Head Impulse Test ↓ or absent saccular input to the lateral vestibular nuclei (e.g., lateral vestibulospinal tract) results in the loss of lower limb postural adjustability Postural Instability (e.g., abnormal Romberg/sharpened Romberg, Fukuda step test) Bilateral mismatch of vestibular information to the brain Peripheral Vertigo (lasts several hours to days; rapid onset, severe, constant) Nausea and Vomiting Only the vestibular part of the vestibulo- cochlear nerve is affected, not the cochlear nerve No Hearing Loss or Tinnitus Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 19, 2021 on www.thecalgaryguide.com

Summary of Cyanotic Congenital Heart Diseases

Summary of Cyanotic Congenital Heart Diseases (CHD) Authors: Winnie Nagesh, Gaya Narendran, Deborah Fruitman* Reviewers: Austin Laing, Yan Yu* * MD at time of publication Right heart normally carries deoxygenated blood to the pulmonary circulation while the left heart carries oxygenated blood to the systemic circulation. Cyanosis can be due to varied pathophysiology, most involve a R-L shunt (described below) Typically presents in the newborn period but depends on the severity and the type of lesion Tetralogy Of Fallot (TOF) Main features: 1.VSD, 2. Overriding aorta, 3. RVH, 4. Pulmonary Valve stenosis 1. VSD causes equal systolic pressure in R and L ventricles 2. Pulmonary Valve stenosisàRight Ventricle Outflow Tract Obstructionà↓ pulmonary blood flow (degree depends on severity of obstruction) 3. RVàLV flow across VSD Presents in the 1st days to weeks, depending on severity of pulmonary valve stenosis On exam: LUSB SEM; loud S2; hypoxemia (degree depends on severity of Right Ventricle Outflow Tract Obstruction) CXR: “boot-shaped” heart, decreased pulmonary vasculature Presents at birth On exam: Often no murmur, no respiratory distress, severe cyanosis/hypoxemia CXR: “egg on a string”, normal pulmonary vasculature Presents in the 1st days to weeks as CHF symptoms develop On exam: Systolic ejection click, Single S2 , SEM, mild hypoxemia due to mixing of blood, +/- tachypnea, hepatomegaly (CHF symptoms) CXR: normal or ↑ pulmonary vasculature Presentation varies based on the degree of the outflow tract obstruction On exam: +/- Holosystolic murmur at LLSB (from VSD), or SEM if outflow tract obstruction, +/- severe cyanosis dependent on severity of pulmonary stenosis CXR: normal or ↓ pulmonary vasculature Presents in early infancy (earlier and more severe presentation if obstructed) On exam: +/-split S2, SEM LUSB, tachypnea, mild cyanosis CXR: cardiomegaly with ↑ pulmonary vasculature Note: see relevant Calgary Guide slides for each heart condition for full explanation of their pathophysiology. Figures are hand-drawn by the authors. Transposition of the Great Arteries (TGA) Aorta is the outflow for RV and pulmonary artery is the outflow for the LV (parallel circulation) Truncus Arteriosus 1. Single vessel (truncus) fails to divide into pulmonary artery and aorta, 2. Single outlet overriding VSD Tricuspid Atresia Tricuspid valve fails to develop normally with a hypoplastic right heart and VSD 1. Deoxygenated blood pumped from RVàaortaà systemic circulation, bypassing the lungs. 2. Oxygenated blood pumped from LVàPA 1. RV + LV pumped through VSDàoverriding truncal artery 2. Mixed deoxygenated and oxygenated blood enters systemic, pulmonary and coronary circulations 1. Blood cannot enter RV due to lack of tricuspid valve 2. Deoxygenated blood pumped from RAàASDàLA and mixes with oxygenated blood 3. Mixed blood enters systemic circulation Total Anomalous Pulmonary Venous Return (TAPVR) Pulmonary veins return blood to systemic venous circulation (most common type of supracardiac congential heart disease) 1. Oxygenated blood flows through pulmonary veinsàenters Superior or Inferior Vena CavaàRight atrium (all systemic & pulmonary venous blood returns to the RA, resulting in mixing of blood) 2. Blood follows pressure gradient, flows from RAàLA via ASD 3. Flow from LAàLVàAortaàSystemic Circulation Abbreviations: VSD: Ventral Septal Defect; RVH: Right Ventricular Hypertrophy; RV: Right Ventricle, LLSB: Left Lower Sternal Border, LUSB: Left Upper Sternal Border; SEM: Systolic ejection Murmur; RVOTO: Right Ventricle Outflow Tract Obstruction Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 21, 2021 on www.thecalgaryguide.com

Summary of Acyanotic Congenital Heart Diseases

Summary of Acyanotic Congenital Heart Diseases (Left-to-Right Shunts) Authors: Gaya Narendran, Winnie Nagesh Reviewers: Jack Fu, Usama Malik, Yan Yu*, Deborah Fruitman* * MD at time of publication Asymptomatic M, ↑ respiratory tract infections, rarely: failure to thrive Left to Right Shunt ↑ flow from left to right heart Dilation of chambers exposed to ↑ flow Atrial Septal Defect (ASD) Presents later in childhood – often asymptomatic Note: These conditions tend to be acyanotic in presentation. Clinical severity will depend on the defect’s size, anatomic location and the presence of other cardiac anomalies. Please see relevant Calgary Guide slides for each heart condition for full explanation of their pathophysiology. Figures are hand-drawn by the authors. L to R physical communication between atria 1. Pressure in LA > pressure in RA à blood shunts from LA to RA 2. Dilation of RAàdilation of RV 3. ↑ pulmonary blood flow On exam: Systolic Ejection Murmur at LUSB, fixed split S2, RV heave, tachypnea CXR: +/- ↑ pulmonary vasculature Ventricular Septal Defect (VSD) 1. Pressure in LV > pressure in RV (after 4-6wks old) On exam: harsh pansystolic M +/- diastolic rumble at LLSB, +/- hepatomegaly, WOB, tachypnea, +/- ↓ perfusion signs e.g. pallor CXR: ↑ vascular markings, cardiomegaly, pulmonary edema Feeding difficulties, failure to thrive, congestive heart failure (CHF) L to R physical communication between ventricles 2. This causes blood in LV to flow to RV in systole 3. ↑ flow to RVà↑ flow to pulmonary arteriesà ↑ pulmonary blood flow 4. ↑ blood returning to LA & LVàLA & LV dilation Presents usually at 4-6 weeks as PVR falls to normal (after birth) Patent Ductus Arteriosus (PDA) 1. Pressure in aorta > pressure in pulmonary arteries (PA) à continuous flow from aorta to PA 2. ↑ bloodflow load in the PA 3. ↑ flow in PA/lung vasculature à ↑ return to left Note: Adult presentation or unrepaired large VSD may cause pulmonary HTN, leading to Eisenmenger’s Syndrome (see relevant slide) Vessel linking descending aorta & pulmonary arteries remains after birth On exam: Continuous machine-like murmur in sub-clavicular region, wide pulse pressure, tachypnea CXR: ↑ pulmonary vasculature, LV enlargement, cardiomegaly, prominent PA Asymptomatic M , less commonly: failure to thrive, congestive heart failure heart à Dilation of the LA and LV Typically presents later in infancy – dependent on shunt size. Presentation and management may differ in preterm infants. Atrioventricular septal defects (AVSD) Defect in the crux/ center of heart involving both atria and ventricles, with AV abnormalities on a spectrum 1. Pressure in left heart > pressures in right heart 2. Thus blood shunts left à right at atrial and ventricular levels 3. As PVR falls (as part of normal newborn development) à ↑ pulmonary blood flow, +/- AV regurgitation 4. ↑ pulmonary flow à ↑ return to left heart à Cardiomegaly On exam: Systolic Ejection Murmur at LUSB, hepatomegaly, mild O2 desaturation in children CXR: ↑ pulmonary vasculature, cardiomegaly defect Similar to VSD – may present earlier, dependent on severity of defect – associated with Trisomy 21 Abbreviations: AV: Atrioventricular valve; CHF: Congestive Heart Failure; CXR: Chest X-ray; LA: Left Atrium; LV: Left Ventricle; LUSB: Left Upper Sternal Border; LLSB: Left Lower Sternal Border; M : Murmur; PA: Pulmonary Artery; PVR: Pulmonary Vascular Resistance; RA: Right Atrium; RV: Right Ventricle; WOB: Work of Breathing Same as VSD; dependent on severity of Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Nov 15, 2017, updated Oct 21, 2021 on www.thecalgaryguide.com

2-DM-II-pathogenesis-1

EPOC-Descripcion-general-y-definiciones

Enfermedad pulmonar obstructiva crónica (EPOC): Definiciones Autor: Yan Yu Revisores: Jason Baserman, Jennifer Au, Ciara Hanly, Zesheng Ye (叶泽生), Yonglin Mai (麦泳琳)*, Naushad Hirani*, Juri Janovcik* * MD at time of publication Traductor: Margith Izaguirre María Rosario Talavera* Fibrosis quística Enfermedad multisistémica debida a la mutación del gen CFTR, que se presenta en los pulmones como bronquiectasia Bronquiectasia, Fibrosis quística, etc EPOC Enfermedad sistémica, manifestado en gran parte como un trastorno en la obstrucción del flujo del aire, se puede manifestar como alguna de las siguientes enfermedades Ensifema Destrucción tisular anormal de pulmón, agrandamiento de los acinos pulmonares: espacios aéreos distales de los bronquios terminales Bronquitis crónica Tos productiva crónica por una duración total de 3 meses al año, por 2 años continuos. Asma Asma que no mejora completamente con tratamiento(por lo tanto, obstrucción aerea crónica) Definido como síndrome de solapamiento asma-EPOC Ensifema Bronquiectasia Destrucción y ensanchamiento de las vías aéreas mayores, resultando hipersecreción de moco e infecciones recurrentes Bronquitis crónica Manifestaciones más communes del EPOC (la mayoría de los pacientes sufren una combinación de enfisema y bronquitis crónica) Clínicamente, el EPOC es visto como: • Progresivo,reduccióndelflujoaéreo parcialmente reversible, e hiperinflación del pulmón (causando síntomas respiratorios como tos, producción de esputo y disnea) • Resultadodeespinometríapost broncodilatador: FEV1/FVC razón <0.7 (FEV1 no es una característica definida de EPOC, pero es un marcador de severidad) • Aumentalafrecuenciaeintensidadde exacerbaciones agudas • Manifestacionessistémicascomofaltade energía y debilidad muscular Enfermedad pulmonar obstructiva crónica (EPOC) Asma Legend: Fisiopatología Mecanismo Signos/Sintomas/Hallazgo de laboratorio Complicaciones Publicado 7 Enero, 2013, Actualizado 5 Octubre, 2021 en www.thecalgaryguide.com

Hypersensitivity-Definitions

Type-1-HS

Type-2-HS

Type-3-HS

Type-4-HS

Femoroacetabular Impingement (FAI)

Femoroacetabular Impingement (FAI): Pathogenesis and clinical findings Hip dysplasia Overcorrection of deformity during surgery Developmental abnormalities Malunion of femoral neck fracture Altered femoral head/neck shape Repetitive Leisure or Occupational Activity Repetitive movement of the legs beyond normal range of motion Altered hip joint structure Excess bone or abnormal orientation between the femoral head and acetabulum: Residual pediatric hip conditions (slipped capital femoral epiphysis, Perthe’s disease) Structurally abnormal hip joint prior to skeletal maturity Hip joint remodeling Femoroacetabular impingement (FAI) Pincer lesion: extra bone extending over rim of acetabulum Cam lesion: extra bone growth on femoral head Combined lesion: both pincer and cam lesions Decreased femoral anteversion: femoral neck rotated backwards in relation to the femoral shaft Abnormal contact between the femoral head and acetabulum with specific movements (sitting, leaning forward, walking, climbing stairs, squatting, pivoting) Repetitive bumping of bone against articular cartilage and the joint labrum Bones rubbing together activates nociceptors within the hip joint Bone on bone contact restrict movement of the hip joint, especially the movements that further narrow the joint space Cartilage degeneration tear Secondary hip osteoarthritis Authors: Alyssa Federico, Yan Yu* Reviewers: Mehul Gupta, Kelly Johnston* * MD at time of publication Labral Sensation of clicking, catching, or locking in the hip Hip and groin pain Patient restricts use of surrounding muscles to prevent further pain Weakness of hip flexor and abductor muscles Favouring the non- injured leg to avoid pain while walking Antalgic gait + FADIR test: pain with flexion, adduction, and internal rotation of the hip joint Restricted flexion and internal rotation Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 1, 2021 on www.thecalgaryguide.com

Sekundäre Hämostase: Koagulationskaskade

Sekundäre Hämostase: Koagulationskaskade Autor: Christina Schweitzer Rezensenten: David Lincoln Yan Yu* Lynn Savoie* Übersetzung: Sarah Schwarz, Gesche Tallen* * MD zum Zeitpunkt der Veröffentlicung Abkürzungen: • TPZ/PT – Thomboplastinzeit • INR - International Normalized Ratio • (a)PTT – Aktivierte Partielle Thromboplastinzeit • F – Koagulationsfaktor • a – Aktivierter Koagulationsfaktor • N – Normal • HMWK – Hochmolekulares Kininogen • * – Vitamin K abhängig (für weitere Erläuterung siehe Vitamin K-Mangel Folie) Eselsbrücken: • Faktoren der Endstrecke: 10/5=2, 2/2=1 (F10, 5, 2, 1) • Vitamin K abhängige Faktoren– 1972 F10, 9, 7, 2 Normales extrinsisches und, intrinsisches System, Normale Endstrecke N TPZ, N (a)PTT Intrinsischer Weg: Extrinsischer Weg: Gewebeschaden Durch vaskulären Endothelschaden wird der subendotheliale Gewebefaktor freigesetzt F12 F12a F9* Aktivierung durch Kontakt mit negativ geladenen Oberflächen (z.B. HMWK Kollagen, Krallikrein) Gewebefaktor (Thromboplastin) F7a* F11 F11a F10* F10a* F9a* F8a Ca2+ Ca2+ Gewebefaktor– F7a* Komplex Gemeinsame Endstrecke: F5a Prothrombin (F2*) Ca2+ Thrombin (F2a*) Ca2+ Gängige Gerinnungstest: • TPZ, Quick-Wert, PT – Zeit bis zur Bildung eines Thrombus bei Aktivierung des extrinsischen Weges • INR – Standardisierung der TPZ • (a)PTT – Zeit bis zur Bildung eines Thrombus bei Aktivierung des intrinsischen Weges Koagulation Bildung eines Fibrinthrombus Fibrinogen (F1) Störung des intrinsischen Systems N TPZ, ↑ (a)PTT Fibrin (F1a) Störung des extrinsischen Systems ↑TPZ, N (a)PTT Verlängerte Blutungszeit Störung der gemeinsamen Endstrecke ↑TPZ, ↑(a)PTT Legende: Pathophysiologie Mechanismen Symptome/Klinische Befunde Komplikationen Veröffentlicht: 12. Mai 2017 auf www.thecalgaryguide.com

Pneumonie: Pathogenese und klinische Befunde

Pneumonie: Pathogenese und klinische Befunde Autoren: Laura Byford-Richardson Rezensenten: *Yan Yu, Sadie Kutz, Natalie Morgunov, *Kerri Johannson Übersetzung: Sarah Schwarz Übersetungsprüfung: Gesche Tallen* *MD zum Zeitpunkt der Veröffentlichung Anmerkungen: • Pathogene können Bakterien, Viren, Pilze oder Parasiten sein • Die Pneumonie ist eine Entzündung der unteren Atemwege (im Gegensatz zur Entzündung der oberen Atemwege z.B. die Bronchitis) und kann unterteilt werden in: Ambulant erworbene, nosokomial (im Krankenhaus) erworbene Pneumonie Die Immunantwort variiert je nach eingedrungenem Erreger (z.B. Pneumokokken verursachen ein lobär betontes, H. influenzae ein interstitiell betontes Entzündungsbild) Rauchen unterdrückt die Funktionsfähigkeit der neutrophilen Granulozyten und schädigt das Lungenepithel Chronische Lungenerkrankungen z.B. COPD, Asthma oder Lungenkrebs zerstören das Lungengewebe und bieten Krankheitserregern mehr Angriffsfläche für Infektionen Durch Immunsuppression z.B. bei HIV, Sepsis, Glucocorticoid- oder Chemotherapie wird die Immunantwort eingeschränkt Systemisch kommt es zu einer inflammatorischen Immunantwort Durch systemische Zytokinfreisetzung wird die hypothalamische Thermoregulation beeinträchtigt Erregersexposition durch Inhalation, Aspiration, Kontakt- oder hämatologische Übertragung Anfällige Person und/oder virulenter Erreger Proliferation des Erregers in unteren Atemwegen und Alveolen Lokal reagiert das Alveolarepithel mit einer Chemokinausschüttung um neutrophile Granulozyten an den Entzündungsort zu mobilisieren LOBÄR betont: Lokal begrenzte Akkumulation von neutrophilen Granulozyten und Plasmaexudat in Alveolen INTERSTITIELL betont: Zelluläre Infiltrate (Immunzellen und Immunzellfragmente) in den Alveolarwänden (zwischen Alveolen und Kapillaren) Fieber Anmerkungen: Schüttelfrost Irritation der Atemwege mit Hustenreiz Flüssige Infiltrate in Alveolen führen zur Schleimbildung Produktiver Husten Das Exudat vermindert die Röntgenstrahlendur chlässigkeit, entzündete Areale erscheinen im Röntgenbild heller/weiß. Verschattung im Röntgen Alveolen sind durch Flüssigkeitsansamml ungen blockiert Verdickung der Alveolarwände, Diffusionsstrecke ↑ Irritation der Alveolarwände mit Hustenreiz Bei ausschließlich interstitieller Infiltration -> Husten ohne Schleimproduktion Trockener Husten • Andere Symptome der Pneumonie sind: Brustschmerzen, Nutzung der Atemhilfsmuskulatur, auskultatorisch Rasselgeräusche, Müdigkeit • Diese Symptome sind jedoch unspezifisch O2 und CO2- Austausch vermindert Hypoxie Periphere & zentrale Chemorezeptoren werden aktiviert, Atemfrequenz ↑ Luftnot Legende: Pathophysiologie Mechanismen Symptome/Klinische Befunde Komplikationen Veröffentlicht: 26. September 2016 auf www.thecalgaryguide.com

Diabetische Ketoazidose (DKA)

Diabetische Ketoazidose (DKA) Betrifft hauptsächlich Patienten mit Diabetes Mellitus Typ 1: Bestimmte Situationen (z.B. Infektionen) erhöhen den Insulinbedarf, welcher durch fehlende Produktion/unzureichende Substitution nicht gedeckt werden kann Autor: Yan Yu Rezensenten: Peter Vetere, Gill Goobie, Sean Spence, Hanan Bassyouni* Übersetzung: Sarah Schwarz Übersetzungsprüfung: Dr. Gesche Tallen * MD zum Zeitpunkt der Veröffentlichung Hyperglykämie (erhöhter Blutzucker) Bei >12mmol/L, Glukosefiltration > - resorption, Glukose verbleibt im Urin Glukosurie Glukose ist osmotisch wirksam und zieht große Mengen Wasser mit sich (Osmotische Diurese) Polyurie Schwere Dehydrierung(bis zu 4-5L) (ZVD↓, Orthostase: posturale Hypotension/ posturale Tachykardie, Ruhepuls ↑ ) Insulinmangel enthemmt die Lipolyse, sodass der Körper Energie aus Triglyceriden produziert Freisetzung von freien Fettsäuren aus Fettgewebe Absoluter Insulinmangel Hypothalamische Zellen induzieren bei geringem intrazellulären Glukosespiegel ein starkes Hungergefühl Glukose bleibt im Blut & kann nicht durch Muskel- /Fettgewebe verstoffwechselt werden “Ausgehungerte” Zellen triggern die Freisetzung kataboler Hormone: Glucagon, Katecholamine, Cortisol, Somatotropin Damit intrazellulärer Glukosespiegel ↑, erhöht der Körper den Blutzucker Hydrolyse von freien Fettsäure in der Leber (Ketogenese) Polyphagie ↓ Proteinsynthese, ↑ Proteolyse (in Muskelgewebe) ↑ Gluconeogenese, ↑ Glykogenolyse (in der Leber) Acetyl Co-A Energiequelle für “ausgehungerte” Zellen Beachte: Neben Glukose sind Ketonkörper die einzigen Energieträger die von Nervenzellen metabolisiert werden können. Deshalb werden sie vom Körper bei geringem Glukoseangebot produziert. Ketonkörper ( β-Hydroxybutyrat, Acetoacetat, Aceton, akkumulieren im Blut) Ketonurie Metabolische Azidose (↑Anionenlücke: Ketonkörper verbrauchen den HCO3--Puffer) Substrate der Gluconeogenese↑ Durch ↓ Extrazellulärflüssigkeit, werden Ketonkörper konzentriert → Azidose Stört das enterische Nervensystem, Magenentleerung ↓, Ileus Bauchschmerzen, Übelkeit, Erbrechen (Dehydration↑) Abatmen von CO2 um Azidose auszugleichen Kussmaul- Atmung (Tiefe, schnelle Züge) Abatmen von Keton- körpern Azeton- geruch der Atemluft Beeinträchtigung elektrischer Signale zum Gehirn, Rücken- mark und Nervenzellen Perfusion des Gehirns, Rückenmark, Nervenzellen↓ Verschiebung des Wasser- und Elektrolythaushalts Falls Trinkwasser vorhanden Polydipsie Beachte: Während der DKA verliert der Körper K+ durch Elektrolytstörung Schwäche, Delirium +/- Koma osmotische Diurese und Erbrechen. Da gleichzeitig allerdings K+ aus den Zellen diffundiert, kann das Serumkalium unauffällig/erhöht sein. Um Hypokaliämien zu verhindern sollte bei K+ <5.0mmol/L KCl zusammen mit Insulin i.v. verabreicht werden. Cave: gute Nierenfunktion des Patienten Therapie: 1) +++ Flüssigkeit. 2) Insulin + KCl. 3) Auffüllen der Anionenlücke. 4) Auslösende Faktoren identifizieren. 5) Wenig PO4 (typischerweise wenige Stunden bis einen Tag nach der Ketoazidose durch ↑ ATP-Produktion.) Legende: Pathophysiologie Mechanismen Symptome/Klinische Befunde Komplikationen Publikationsdatum: 17 Juni 2013 auf www.thecalgaryguide.com Hyperosmolares/ Hyperglykämisches Koma (HHS) Beachte: betrifft nur Patienten mit Diabetes mellitus Typ II Beachte: Es sollte stets nach auslösenden Faktoren z.B. einer Infektion gesucht werden Autor: Yan Yu Rezensenten: Peter Vetere Gill Goobie Hanan Bassyouni* Übersetzung: Sarah Schwarz Übersetzungsprüfung: Dr. Gesche Tallen * MD zum Zeitpunkt der Veröffentlichung Verschiebung des Wasser- und Elektrolythaushalts Elektrolytstörung Unzureichende Insulin- produktion, Insulinresistenz, Nichtansprechen auf Insulintherapie Relativer Insulinmangel Situationen mit ↑Insulinbedarf: Infekt, Pneumonie, Herzinfarkt, Pancreatitis, etc.) Hyperglykämie (Stark erhöhter Blutzucker, höher als bei der DKA) Bei >12mmol/L, Glukosefiltration > - resorption, Glukose verbleibt im Urin Glukosurie Glukose ist osmotisch wirksam und zieht große Mengen Wasser mit sich (Osmotische Diurese) Polyurie Dehydration (ZVD↓, Orthostase: posturale Hypotension/posturale Tachykardie, Ruhepuls ↑ ) Durch das wenige noch vorhandene Insulin, wird ein Teil der Glukose von Muskel- /Fettgewebe verstoffwechselt, ein Teil verbleibt im Blut Körperzellen brauchen eine weitere Energiequelle Freisetzung kataboler Hormone: Glucagon, Katecholamine, Cortisol, Somatrotropin Damit intrazellulärer Glukosespiegel ↑, erhöht der Körper den Blutzucker Hypothalamische Zellen induzieren bei geringem intrazellulären Glukosespiegel ein starkes Hungergefühl Polyphagie Beachte: Durch das wenige noch vorhandene Insulin wird die Lipolyse gehemmt und werden keine Ketonkörper produziert. Es kommt nicht zur Azidose und Ketonurie (Gegensatz zur DKA). Sollte es doch zur Ketourie kommen, ist das meist Folge von Hungerzuständen oder anderen Mechanismen Extrazellulärflüssigkeit ↓ mit erhöhter Osmolarität (z.B. Hypernatriämie) ↑ Gluconeogenese, ↑ Glykogenolyse (in der Leber) ↓ Proteinsynthese, ↑ Proteolyse (in Muskelgewebe) Substrate der Gluconeogenese ↑ Sollte der Patient nicht ausreichend trinken um das Volumendefizit auszugleichen Falls Trinkwasser vorhanden Polydipsie Wasser verlässt Zellen entlang des osmotischen Gradienten, Neuronen schrumpfen Neuronaler Schaden: Delirium, Krampfanfall, Benommenheit, Koma Renale Perfusion↓, GFR ↓ Nierenversagen (prä-renal, siehe entsprechende Folie) Beachte: Während der DKA verliert der Körper K+ durch osmotische Diurese. Da gleichzeitig allerdings K+ aus den Zellen diffundiert, kann das Serumkalium unauffällig/erhöht sein. Um Hypokaliämien zu verhindern sollte bei K+ <5.0mmol/L KCl zusammen mit Insulin i.v. verabreicht werden. Cave: gute Nierenfunktion des Patienten Beachte: Elektrolytstörungen (z.B. Hyperkaliämien, Hypernatriämien) verschlechtern sich bei akutem Nierenversagen, welches bei der DKA &HK häufig auftritt Legende: Pathophysiologie Mechanismen Symptome/Klinische Befunde Komplikationen Veröffentlicht: 3. November 2016 auf www.thecalgaryguide.com

Hyperosmolares/ Hyperglykämisches Koma (HHS)

Diabetische Ketoazidose (DKA) Betrifft hauptsächlich Patienten mit Diabetes Mellitus Typ 1: Bestimmte Situationen (z.B. Infektionen) erhöhen den Insulinbedarf, welcher durch fehlende Produktion/unzureichende Substitution nicht gedeckt werden kann Autor: Yan Yu Rezensenten: Peter Vetere, Gill Goobie, Sean Spence, Hanan Bassyouni* Übersetzung: Sarah Schwarz Übersetzungsprüfung: Dr. Gesche Tallen * MD zum Zeitpunkt der Veröffentlichung Hyperglykämie (erhöhter Blutzucker) Bei >12mmol/L, Glukosefiltration > - resorption, Glukose verbleibt im Urin Glukosurie Glukose ist osmotisch wirksam und zieht große Mengen Wasser mit sich (Osmotische Diurese) Polyurie Schwere Dehydrierung(bis zu 4-5L) (ZVD↓, Orthostase: posturale Hypotension/ posturale Tachykardie, Ruhepuls ↑ ) Insulinmangel enthemmt die Lipolyse, sodass der Körper Energie aus Triglyceriden produziert Freisetzung von freien Fettsäuren aus Fettgewebe Absoluter Insulinmangel Hypothalamische Zellen induzieren bei geringem intrazellulären Glukosespiegel ein starkes Hungergefühl Glukose bleibt im Blut & kann nicht durch Muskel- /Fettgewebe verstoffwechselt werden “Ausgehungerte” Zellen triggern die Freisetzung kataboler Hormone: Glucagon, Katecholamine, Cortisol, Somatotropin Damit intrazellulärer Glukosespiegel ↑, erhöht der Körper den Blutzucker Hydrolyse von freien Fettsäure in der Leber (Ketogenese) Polyphagie ↓ Proteinsynthese, ↑ Proteolyse (in Muskelgewebe) ↑ Gluconeogenese, ↑ Glykogenolyse (in der Leber) Acetyl Co-A Energiequelle für “ausgehungerte” Zellen Beachte: Neben Glukose sind Ketonkörper die einzigen Energieträger die von Nervenzellen metabolisiert werden können. Deshalb werden sie vom Körper bei geringem Glukoseangebot produziert. Ketonkörper ( β-Hydroxybutyrat, Acetoacetat, Aceton, akkumulieren im Blut) Ketonurie Metabolische Azidose (↑Anionenlücke: Ketonkörper verbrauchen den HCO3--Puffer) Substrate der Gluconeogenese↑ Durch ↓ Extrazellulärflüssigkeit, werden Ketonkörper konzentriert → Azidose Stört das enterische Nervensystem, Magenentleerung ↓, Ileus Bauchschmerzen, Übelkeit, Erbrechen (Dehydration↑) Abatmen von CO2 um Azidose auszugleichen Kussmaul- Atmung (Tiefe, schnelle Züge) Abatmen von Keton- körpern Azeton- geruch der Atemluft Beeinträchtigung elektrischer Signale zum Gehirn, Rücken- mark und Nervenzellen Perfusion des Gehirns, Rückenmark, Nervenzellen↓ Verschiebung des Wasser- und Elektrolythaushalts Falls Trinkwasser vorhanden Polydipsie Beachte: Während der DKA verliert der Körper K+ durch Elektrolytstörung Schwäche, Delirium +/- Koma osmotische Diurese und Erbrechen. Da gleichzeitig allerdings K+ aus den Zellen diffundiert, kann das Serumkalium unauffällig/erhöht sein. Um Hypokaliämien zu verhindern sollte bei K+ <5.0mmol/L KCl zusammen mit Insulin i.v. verabreicht werden. Cave: gute Nierenfunktion des Patienten Therapie: 1) +++ Flüssigkeit. 2) Insulin + KCl. 3) Auffüllen der Anionenlücke. 4) Auslösende Faktoren identifizieren. 5) Wenig PO4 (typischerweise wenige Stunden bis einen Tag nach der Ketoazidose durch ↑ ATP-Produktion.) Legende: Pathophysiologie Mechanismen Symptome/Klinische Befunde Komplikationen Publikationsdatum: 17 Juni 2013 auf www.thecalgaryguide.com Hyperosmolares/ Hyperglykämisches Koma (HHS) Beachte: betrifft nur Patienten mit Diabetes mellitus Typ II Beachte: Es sollte stets nach auslösenden Faktoren z.B. einer Infektion gesucht werden Autor: Yan Yu Rezensenten: Peter Vetere Gill Goobie Hanan Bassyouni* Übersetzung: Sarah Schwarz Übersetzungsprüfung: Dr. Gesche Tallen * MD zum Zeitpunkt der Veröffentlichung Verschiebung des Wasser- und Elektrolythaushalts Elektrolytstörung Unzureichende Insulin- produktion, Insulinresistenz, Nichtansprechen auf Insulintherapie Relativer Insulinmangel Situationen mit ↑Insulinbedarf: Infekt, Pneumonie, Herzinfarkt, Pancreatitis, etc.) Hyperglykämie (Stark erhöhter Blutzucker, höher als bei der DKA) Bei >12mmol/L, Glukosefiltration > - resorption, Glukose verbleibt im Urin Glukosurie Glukose ist osmotisch wirksam und zieht große Mengen Wasser mit sich (Osmotische Diurese) Polyurie Dehydration (ZVD↓, Orthostase: posturale Hypotension/posturale Tachykardie, Ruhepuls ↑ ) Durch das wenige noch vorhandene Insulin, wird ein Teil der Glukose von Muskel- /Fettgewebe verstoffwechselt, ein Teil verbleibt im Blut Körperzellen brauchen eine weitere Energiequelle Freisetzung kataboler Hormone: Glucagon, Katecholamine, Cortisol, Somatrotropin Damit intrazellulärer Glukosespiegel ↑, erhöht der Körper den Blutzucker Hypothalamische Zellen induzieren bei geringem intrazellulären Glukosespiegel ein starkes Hungergefühl Polyphagie Beachte: Durch das wenige noch vorhandene Insulin wird die Lipolyse gehemmt und werden keine Ketonkörper produziert. Es kommt nicht zur Azidose und Ketonurie (Gegensatz zur DKA). Sollte es doch zur Ketourie kommen, ist das meist Folge von Hungerzuständen oder anderen Mechanismen Extrazellulärflüssigkeit ↓ mit erhöhter Osmolarität (z.B. Hypernatriämie) ↑ Gluconeogenese, ↑ Glykogenolyse (in der Leber) ↓ Proteinsynthese, ↑ Proteolyse (in Muskelgewebe) Substrate der Gluconeogenese ↑ Sollte der Patient nicht ausreichend trinken um das Volumendefizit auszugleichen Falls Trinkwasser vorhanden Polydipsie Wasser verlässt Zellen entlang des osmotischen Gradienten, Neuronen schrumpfen Neuronaler Schaden: Delirium, Krampfanfall, Benommenheit, Koma Renale Perfusion↓, GFR ↓ Nierenversagen (prä-renal, siehe entsprechende Folie) Beachte: Während der DKA verliert der Körper K+ durch osmotische Diurese. Da gleichzeitig allerdings K+ aus den Zellen diffundiert, kann das Serumkalium unauffällig/erhöht sein. Um Hypokaliämien zu verhindern sollte bei K+ <5.0mmol/L KCl zusammen mit Insulin i.v. verabreicht werden. Cave: gute Nierenfunktion des Patienten Beachte: Elektrolytstörungen (z.B. Hyperkaliämien, Hypernatriämien) verschlechtern sich bei akutem Nierenversagen, welches bei der DKA &HK häufig auftritt Legende: Pathophysiologie Mechanismen Symptome/Klinische Befunde Komplikationen Veröffentlicht: 3. November 2016 auf www.thecalgaryguide.com

Asthma: Pathogenese

Asthma: Pathogenese Autor: Yan Yu Rezensenten: Jason Baserman Jennifer Au Ciara Hanly Yonglin Mai (麦泳琳) Naushad Hirani* Übersetzung: Sarah Schwarz Übersetzungsprüfung: Dr. Gesche Tallen * MD zum Zeitpunkt der Veröffentlichung Genetische Faktoren (z.B. Mutationen im HLA- Gen, Defekte im bronchialen Endothel) Umwelteinflüsse (z.B. übermäßige Hygiene, wenige Geschwister, Antibiotikaeinnahme in den ersten 2 Lj.) Asthma: Eine chronisch-entzündliche Erkrankung welche durch hyperreagible Atemwege zu variablen, reversiblen Obstruktionen führt Trigger für Hyperreagibilität der Atemwege: Atopie: Neigung zu allergischen Überempfindlichkeitsreaktionen der Atemwege Erstexposition gegenüber des Triggers Sensibilisierung der T-Helferzellen Stimulation der B-Zellen zur IgE Produktion, welche an Mastzellen binden und diese aktivieren Aktivierte T-Helferzellen und Mastzellen säumen die Atemwege Infektionen des oberen Respirationstrakts Allergene (Pollen, Haus- staub, Tierhaar etc.) Luftverschmutzung, Zigarettenrauch, Chemikalien Medikamente (ASS, NSAR, Beta-Blocker) kalte Luft Bewegung Mastzellen setzen Histamine, Leukotriene und andere Entzündungsmediatoren frei Induzieren Zellreifung eosinophiler Granulozyten Eosinophile migrieren in: Gefäßpermeabilität ↑, Schleimhautödem in Bronchien Becherzellhyperplasie, Schleimsekretion ↑ Kontraktion der Bronchialmuskulatur Zweitkontak t mit dem Trigger Frühe Reaktion (0-2 h) Verspätet e Reaktion (3-4 h) Allergene binden an IgEs auf Mastzellen Aktivierte T- Helferzellen & Mastzellen setzen Zytokine frei Obstruktion der Atemwege Asthma Bronchokonstriktion Konjunktivitis Beachte: Verspätete Reaktionen beginnen nach 3-4h, erreichen ihren Höhepunkt nach 6-8h und klingen nach 24h ab Atemwege Augen Nase Rhinitis Legende: Pathophysiologie Mechanismen Symptome/Klinische Befunde Komplikationen Veröffentlicht: 17. Dez. 2012, aktualisiert: 19. Aug. 2021 auf www.thecalgaryguide.com

Nephrotisches Syndrom: Pathogenese und klinische Befunde

Nephrotisches Syndrom: Pathogenese und klinische Befunde Membranoproliferative Glomerulonephritis (MPGN) Lupus-Nephritis Postinfektiöse Glomeruloneprhitis IgA Nephropathie Membranöse Glomerulonephritis Antikörper greifen Podozyten an, Verdickung der glomerulären Basalmembran Fokal-segmentale Glomerulosklerose (FSSGN) Schädigung des glomerulären Endo- und Epithels Minimal Change Glomerulo- nephritis (MCNG) Diabetes mellitus Autor: Yan Yu Rezensenten: Alexander Arnold David Waldner Sean Spence Stefan Mustata* Übersetzung: Sarah Schwarz Übersetzungsprüfung: Gesche Tallen* * MD zum Zeitpunkt der Veröffentlichung Podozyten-Schädigung auf der epithelialen Seite des Glomerulums (Abflachung der Podozytenfortsätze) Glomeruläre Immunkomplex- ablagerungen Chronische Hyperglykämien schädigen das Glomerulum Geschädigter Proteinfilter (v.a. für geladene Proteine) Ablagerungen von Immunglobulin-Leichtketten im Glomerulum Amyloidose Geschädigte Glomeruli --> gestörte Filterbarriere v.a. für Proteine --> übermäßige Filtration von Plasmaproteinen Vermehrte renale Ausscheidung von Immunglobulin-Leichtketten (Filtration>Resorption) Hypoalbuminämie* Übermäßiger Verlust an Albumin über den Urin Proteinurie >3.5g/Tag* Verlust an Antikoagulationsproteinen (Antithrombin, Plasminogen, Protein C & S) über den Urin Koagulations- /Gerinnungsfaktoren (z.B. 1,7,8, 10) sind in Überzahl Proteinurie >3.5g/Tag* Thrombophilie Anasarka (Generalisiertes Ödem) Lidödem (klassisches Frühzeichen) Lipidurie (zeigt unter gekreuztem polarisiertem Licht eine Malteserkreuz- form) 50% des Serumkalziums sind an Albumin gebunden, sodass Serumkalzium- spiegel ↓ Serum- Ca2+ repräsentiert nicht mehr das Gesamt-Ca2+ Beachte: • DerklassischeSymptomkomplex(*)desnephrotischen Syndroms besteht aus: Proteinurie (>3,5g/Tag), Ödemen, Hypoalbuminämie,Hyperlipidämie • Fürjede10g/LmitAlbumin<40: ➔ Addiere 2.5 zur errechneten Anionenlücke um dessen “wahren” Wert zu bekommen ➔ Addiere 0,2mmol/L zum Gesamt-Ca um den Wert des ionisierten Kalziums zu errechnen Blut neigt zur Bildung von Thromben Ödeme* ↑ Renale Filtrationder Lipide und Ausscheidung über den Urin Die Anionenlücke ergibt sich hauptsächlich aus negativ geladenem Serumalbumin Anionenlücke↓ Kolloid- osmotischer Druck ↓ Flüssigkeit kann nicht mehr in den Blutgefäßen gehalten werden und diffundiert ins Gewebe Signalisiert der Leber die Albuminproduktion zuerhöhen,Albumin wird aber weiterhin über die Nieren verloren Synthese- arbeit der Leber↑, auch ↑ Lipoprotein- synthese Hyperlipidämie*: (Serum-LDL, -VLDL, - TG ↑ ) Legende: Pathophysiologie Mechanismen Symptome/Klinische Befunde Komplikationen Veröffentlicht: 19. August 2013 auf www.thecalgaryguide.com

COPD-发病机制

COPD: 发病机制 作者: Yan Yu 审稿人:Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人:Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 /012 (如a1-抗胰蛋白酶缺乏) 阻止肺组织损伤的能力↓ +,-. (如长期吸烟、环境污染、感染) 肺内产生自由基 34*5 肺抗蛋白酶的失活 ↑氧化应激，炎性细胞因子，蛋白酶功能 支气管的持续、反复损伤 炎性细胞浸润， 杯状细胞增殖， 气道上皮纤毛 尤其中性粒细 黏液产生↑ 细胞死亡 气道弹性↓ (弹性回缩 肺实质的蛋白水解破坏↑ 维持气道开放 肺泡永久性异常 的结构支持↓ 扩张 胞 力) 肺气体潴留 气道狭窄与 肺过度 肺大泡 气道黏液潴留，成为感染 狭窄 病灶 塌陷 充气 肺气肿 (容易肺泡 破裂) 气道纤维化和 %&'()* 慢性阻塞性肺疾病(COPD) 临床表现 并发症 (参阅相关幻灯片) (参阅相关幻灯片) 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Clinical Findings Lung tissue Chronic Obstructive Pulmonary Disease (COPD) damage ↓ elastic recoil to push air out of lungs on expiration Lungs don’t fully empty, air is trapped in alveoli (lung hyperinflation) ↑ lung volume means diaphragm is tonically contracted (flatter) If occurring around airways Airflow obstruction ↑ mucus production ↓ number of epithelial ciliated cells to clear away the mucus (the cells have been killed by airway inflammation) Chronic cough with sputum Author: Yan Yu Reviewers: Jason Baserman Jennifer Au Naushad Hirani* Juri Janovcik* * MD at time of publication During expiration, positive pleural pressure squeezes on airwaysà↑ obstruction ↓ ventilation of alveoli ↓ oxygenation of blood (hypoxemia) ↓ perfusion of body tissues (i.e. brain, muscle) Fatigue; ↓ exercise tolerance Total expiration time takes longer than normal Prolonged expiration More effort needed to ventilate larger lungs Respiratory muscles must work harder to breathe Turbulent airflow in narrower airways is heard on auscultation Expiratory Wheeze Diaphragm can’t flatten much further to generate deep breaths To breathe, chest wall must expand out more Dyspnea Shortness of breath, especially on exertion Breathes are rapid & shallow If end-stage: Chronic fatigue causes deconditioning Muscle weakness & wasting Barrel chest If end-stage: diaphragm will be “flat”. Continued Patient tries to expire against higher mouth air pressure, forcing airways to open wider Pursed-lip breathing Patient breathes with accessory muscles as well as diaphragm to try to improve airflow inspiratory effort further contracts diaphragmà pull the lower chest wall inwards Hoover’s sign (paradoxical shrinking of lower chest during inspiration) Tripod sitting position (activates pectoral muscles) Neck (SCM, scalene) muscles contracted Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: ! 45 (on ABGs) Ventilation- perfusion mismatch High A-a gradient (calculated from ABGs) Low, flat diaphragm, >10 posterior ribs (on frontal CXR) High TLC and VC (on spirometry) • • PaO2: partial pressure of O2 in arterial blood PaCO2: partial pressure of CO2 in arterial blood • In the setting of fever and productive cough, especially if lung field opacifications are seen on CXR: consider sputum gram stain and culture to rule out pneumonia. Air does not block X-ray beams, will appear black on X-ray film Chronic hypercapnia makes breathing centers less sensitive to the high PaCO2 stimulus for breathing, & more reliant on the low PaO2 stimulus (“CO2 retention”) Give O2 carefully to these patients (high PaO2 may suppress patients’ hypoxic respiratory drive, ↓ their breathing, & ↑↑↑ PaCO2) ↑ retrosternal air space (on lateral CXR) Hyper-lucent (darker) lung fields, ↓ lung markings (on frontal CXR) • Arterial Blood Gasses (ABGs) • Chest X-Ray (CXR): frontal and lateral Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"#$ 气流阻塞 肺泡通气↓ 呼气时，胸膜腔正压挤压气 道à 阻塞↑ 作者: Yan Yu 审稿人: Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者:Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 慢性阻塞性肺疾病 (COPD) 肺组织损伤 没有弹性回缩力将 气体排出肺 肺实质与血管分布减少导 致气体交换面积↓ 弥散功能↓ (肺功能检查) 更多的CO2残留 并扩散到血液中 高碳酸血症: PaCO2 > 45 (动脉血气) 血流灌注通气不良的肺泡 时无法获得足够的氧气 总呼气时长较正常长 FEV1/FEV < 0.7 (肺功能检查) 肺无法完全排空 更多空气潴留在肺部 (肺过度充气) 低氧血症: PaO2 < 70mmHg (动脉血气) 通气-灌注不匹配 肺泡-动脉氧分压差↑ (可通过动脉血气分析计算得出) 横膈低平， 下移至第10肋后端 及以下部位 (胸部正位片) TLC与VC增大 (肺功能检查) 缩写: • • FEV1: 1秒用 • VC:肺活量 PaO2: 动脉血 力呼气量 氧分压 空气不会阻挡X射线， 在X光片上呈现为黑色 慢性高碳酸血症使呼吸中枢对PaCO2 刺激呼吸的敏感性下降 & 更依赖于低PaO2的刺激 (“二氧化碳潴留”) 给患者吸氧时需注意(高PaO2 可能会抑制患者低氧时对呼吸的 刺激，使呼吸驱动↓ & PaCO2↑↑↑ ) • FVC: 用力肺 • 活量 • TLC:肺总量 慢阻肺相关检查 : PaCO2: 动脉 血二氧化碳 分压 胸骨后间隙↑ (胸部侧位片) 肺纹理↓ • 肺功能检查 • 动脉血气分析(Arterial Blood Gasses, ABGs) • 胸部正侧位片 • 当患者发热和湿咳，特别是胸片上见肺野不清晰时: 肺透亮度↑, (胸部正位片) 考虑进行痰革兰氏染色及痰培养以排除肺炎可能 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Complications Lung inflammation Chronic Obstructive Pulmonary Disease (COPD) Airway obstruction ↓ inhaled air in alveoli and terminal bronchioles Rupture of emphasematous bullae on surface of lung Inhaled air leaks into pleural cavity and is trapped there Pneumothorax Feeling a loss of control over one’s life, and hopelessness for the future Goblet cell proliferation, ↑ mucus production Death of airway epithelium ciliated cells ↓ oxygenation of the blood passing through the lungs Chronic hypoxemia Kidneys compensate by ↑ erythropoietin (EPO) production ↑ Hemoglobin and red blood cell synthesis Polycythemia (secondary) Hypoxic alveoli cause the pulmonary arterioles perfusing them to reflexively vasoconstrict Since most alveoli in the lungs are hypoxic, hypoxic vasoconstriction occurs across entire lung Vasoconstriction ↑ blood pressure within lung vasculature Pulmonary hypertension ↑ workload of the right ventricle (to pump against higher pressures) To compensate, the right ventricle progressively hypertrophies and dilates, but over time its output ↓ Cor pulmonale (Right heart failure in isolation, not due to Left heart failure) Mucus trapped in airways, serve as nidus for infection Acute exacerbation of COPD (AECOPD) Pneumonia The chronic, systemic inflammation in COPD is a hyper-metabolic state that consumes calories Macro-nutrient deficiency Trouble with respiration lead to inactivity and deconditioning Wasting, muscle atrophy More inactivity and deconditioning perpetuates the cycle Depression Author: Yan Yu Reviewers: Jason Baserman Naushad Hirani* Juri Janovcik* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"# 肺部炎症 杯状细胞增殖， 气道上皮纤毛 粘液产生↑ 细胞死亡 黏液潴留呼吸道，成为感 染的病灶 慢性阻塞性肺疾病 (COPD) 气道阻塞à 吸入肺泡和终末细 肺大疱破裂 吸入的空气渗入 并潴留于胸腔 气胸 感觉生活失控，对未 来感到绝望 抑郁 作者: Yan Yu 审稿人: Jason Baserman, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 支气管的空气 ↓ 流经肺的血液进行气 缺氧的肺泡à灌注肺泡的肺小动 慢性阻塞性肺疾 病急性加重期 (AECOPD) 肺炎 体交换↓ 慢性低氧血症 肾脏合成促红细胞 生成素进行代偿↑ 血红蛋白与红 细胞合成↑ 红细胞增多症 (继发性) 脉发生反射性血管收缩 肺大部分肺泡缺氧à整个肺 都出现缺氧性血管收缩 肺血管收缩 à 肺血管压力↑ 肺动脉高压 ↑ 右心室负荷(泵血时对抗高压) 为了代偿，右心室逐渐肥大和扩张， 但随着病程进展，右心室输出量 ↓ 肺心病 (单独出现右心衰竭，非左心衰) COPD所致的慢性全身 呼吸困难导致活 性炎症会使机体处于高 动量减少和活动 代谢状态，消耗能量 耐量降低 宏量营养 素缺乏症 消瘦，肌肉萎缩 运动量下降和活动耐量 的降低造成恶性循环 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com " title="COPD: 发病机制 作者: Yan Yu 审稿人:Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人:Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 /012 (如a1-抗胰蛋白酶缺乏) 阻止肺组织损伤的能力↓ +,-. (如长期吸烟、环境污染、感染) 肺内产生自由基 34*5 肺抗蛋白酶的失活 ↑氧化应激，炎性细胞因子，蛋白酶功能 支气管的持续、反复损伤 炎性细胞浸润， 杯状细胞增殖， 气道上皮纤毛 尤其中性粒细 黏液产生↑ 细胞死亡 气道弹性↓ (弹性回缩 肺实质的蛋白水解破坏↑ 维持气道开放 肺泡永久性异常 的结构支持↓ 扩张 胞 力) 肺气体潴留 气道狭窄与 肺过度 肺大泡 气道黏液潴留，成为感染 狭窄 病灶 塌陷 充气 肺气肿 (容易肺泡 破裂) 气道纤维化和 %&'()* 慢性阻塞性肺疾病(COPD) 临床表现 并发症 (参阅相关幻灯片) (参阅相关幻灯片) 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Clinical Findings Lung tissue Chronic Obstructive Pulmonary Disease (COPD) damage ↓ elastic recoil to push air out of lungs on expiration Lungs don’t fully empty, air is trapped in alveoli (lung hyperinflation) ↑ lung volume means diaphragm is tonically contracted (flatter) If occurring around airways Airflow obstruction ↑ mucus production ↓ number of epithelial ciliated cells to clear away the mucus (the cells have been killed by airway inflammation) Chronic cough with sputum Author: Yan Yu Reviewers: Jason Baserman Jennifer Au Naushad Hirani* Juri Janovcik* * MD at time of publication During expiration, positive pleural pressure squeezes on airwaysà↑ obstruction ↓ ventilation of alveoli ↓ oxygenation of blood (hypoxemia) ↓ perfusion of body tissues (i.e. brain, muscle) Fatigue; ↓ exercise tolerance Total expiration time takes longer than normal Prolonged expiration More effort needed to ventilate larger lungs Respiratory muscles must work harder to breathe Turbulent airflow in narrower airways is heard on auscultation Expiratory Wheeze Diaphragm can’t flatten much further to generate deep breaths To breathe, chest wall must expand out more Dyspnea Shortness of breath, especially on exertion Breathes are rapid & shallow If end-stage: Chronic fatigue causes deconditioning Muscle weakness & wasting Barrel chest If end-stage: diaphragm will be “flat”. Continued Patient tries to expire against higher mouth air pressure, forcing airways to open wider Pursed-lip breathing Patient breathes with accessory muscles as well as diaphragm to try to improve airflow inspiratory effort further contracts diaphragmà pull the lower chest wall inwards Hoover’s sign (paradoxical shrinking of lower chest during inspiration) Tripod sitting position (activates pectoral muscles) Neck (SCM, scalene) muscles contracted Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"#$ 慢性阻塞性肺疾病 (COPD) 如果出现在气道周围 气流阻塞 肺不能完全排空 气体，气体潴留 于肺泡(肺过度 充气) 总呼气时长大于 正常时长 呼气相延长 肺组织损伤 呼气时，将空气排出肺外 的弹性回缩力↓ 肺不能完全排空气体， 气体潴留于肺泡内 (肺过度充气) 肺容积↑，膈肌紧张 性收缩(膈肌平坦) 呼气时，胸膜腔正压挤压气道 à 气道阻塞↑ 肺泡通气↓ 血液氧合↓ (低 氧血症) 身体组织灌注 量↓ (比如脑、 肌肉) 疲劳; 运动耐量↓ 黏液生成↑ 清除黏液的上皮纤 毛细胞数量↓ (受 气道炎症损伤) 慢性咳嗽伴咳 痰 作者: Yan Yu 审稿人: Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 容积较大 的肺需要 更加努力 才能通气 呼吸肌必须 更用力才能 呼吸 听诊闻及狭窄气 道中的湍流气流 呼气喘鸣音 呼吸困难 气促，尤其是劳累 膈肌无法进一步收缩以 产生深呼吸 呼吸浅快 为了呼吸， 胸壁必须延 展得更大 桶状胸 晚期病人: 患者试图在较高的口 慢性疲劳导致 患者动用辅助呼吸肌和膈肌呼吸， 腔内气压下进行呼气， 活动耐量下降 从而使气道更开放 以改善气流 晚期病人:膈肌 “平坦” ，持续吸气进一步压 缩膈肌à 向内拉季肋部胸壁 胡佛征 (吸气时，胸廓下侧季肋部内收) 缩唇呼吸 肌肉无力 & 消瘦 端坐呼吸 (调动胸肌) 颈部肌肉收 缩(胸锁乳 突肌、斜角 肌) 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Findings on Investigations Chronic Obstructive Pulmonary Disease (COPD) Author: Yan Yu Reviewers: Jason Baserman Jennifer Au Naushad Hirani* Juri Janovcik* * MD at time of publication Airflow obstruction Lung tissue damage ↓ ventilation of alveoli Blood perfusing ill- ventilated alveoli does not receive normal amounts of oxygen During expiration, positive pleural pressure squeezes on airwaysà↑ obstruction) No elastic recoil to push air out of lungs Loss of lung parenchyma and vasculature ↓ surface area for gas exchange ↓ diffusion capacity (on spirometry) Hypoxemia: PaO2 < 70mmHg (on ABGs) Abbreviations: • FEV1: Forced expiratory volume in 1 second • FVC: Forced vital capacity • TLC: Total lung capacity • VC: Vital Capacity Investigations for COPD : • Spirometry (Pulmonary function test) Total expiration time takes longer than normal FEV1/FEV < 0.7 (on spirometry) Lungs don’t fully empty More air trapped within lungs (hyperinflation) More CO2 remains and diffuses into the blood Hypercapnia: PaCO2 > 45 (on ABGs) Ventilation- perfusion mismatch High A-a gradient (calculated from ABGs) Low, flat diaphragm, >10 posterior ribs (on frontal CXR) High TLC and VC (on spirometry) • • PaO2: partial pressure of O2 in arterial blood PaCO2: partial pressure of CO2 in arterial blood • In the setting of fever and productive cough, especially if lung field opacifications are seen on CXR: consider sputum gram stain and culture to rule out pneumonia. Air does not block X-ray beams, will appear black on X-ray film Chronic hypercapnia makes breathing centers less sensitive to the high PaCO2 stimulus for breathing, & more reliant on the low PaO2 stimulus (“CO2 retention”) Give O2 carefully to these patients (high PaO2 may suppress patients’ hypoxic respiratory drive, ↓ their breathing, & ↑↑↑ PaCO2) ↑ retrosternal air space (on lateral CXR) Hyper-lucent (darker) lung fields, ↓ lung markings (on frontal CXR) • Arterial Blood Gasses (ABGs) • Chest X-Ray (CXR): frontal and lateral Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"#$ 气流阻塞 肺泡通气↓ 呼气时，胸膜腔正压挤压气 道à 阻塞↑ 作者: Yan Yu 审稿人: Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者:Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 慢性阻塞性肺疾病 (COPD) 肺组织损伤 没有弹性回缩力将 气体排出肺 肺实质与血管分布减少导 致气体交换面积↓ 弥散功能↓ (肺功能检查) 更多的CO2残留 并扩散到血液中 高碳酸血症: PaCO2 > 45 (动脉血气) 血流灌注通气不良的肺泡 时无法获得足够的氧气 总呼气时长较正常长 FEV1/FEV < 0.7 (肺功能检查) 肺无法完全排空 更多空气潴留在肺部 (肺过度充气) 低氧血症: PaO2 < 70mmHg (动脉血气) 通气-灌注不匹配 肺泡-动脉氧分压差↑ (可通过动脉血气分析计算得出) 横膈低平， 下移至第10肋后端 及以下部位 (胸部正位片) TLC与VC增大 (肺功能检查) 缩写: • • FEV1: 1秒用 • VC:肺活量 PaO2: 动脉血 力呼气量 氧分压 空气不会阻挡X射线， 在X光片上呈现为黑色 慢性高碳酸血症使呼吸中枢对PaCO2 刺激呼吸的敏感性下降 & 更依赖于低PaO2的刺激 (“二氧化碳潴留”) 给患者吸氧时需注意(高PaO2 可能会抑制患者低氧时对呼吸的 刺激，使呼吸驱动↓ & PaCO2↑↑↑ ) • FVC: 用力肺 • 活量 • TLC:肺总量 慢阻肺相关检查 : PaCO2: 动脉 血二氧化碳 分压 胸骨后间隙↑ (胸部侧位片) 肺纹理↓ • 肺功能检查 • 动脉血气分析(Arterial Blood Gasses, ABGs) • 胸部正侧位片 • 当患者发热和湿咳，特别是胸片上见肺野不清晰时: 肺透亮度↑, (胸部正位片) 考虑进行痰革兰氏染色及痰培养以排除肺炎可能 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Complications Lung inflammation Chronic Obstructive Pulmonary Disease (COPD) Airway obstruction ↓ inhaled air in alveoli and terminal bronchioles Rupture of emphasematous bullae on surface of lung Inhaled air leaks into pleural cavity and is trapped there Pneumothorax Feeling a loss of control over one’s life, and hopelessness for the future Goblet cell proliferation, ↑ mucus production Death of airway epithelium ciliated cells ↓ oxygenation of the blood passing through the lungs Chronic hypoxemia Kidneys compensate by ↑ erythropoietin (EPO) production ↑ Hemoglobin and red blood cell synthesis Polycythemia (secondary) Hypoxic alveoli cause the pulmonary arterioles perfusing them to reflexively vasoconstrict Since most alveoli in the lungs are hypoxic, hypoxic vasoconstriction occurs across entire lung Vasoconstriction ↑ blood pressure within lung vasculature Pulmonary hypertension ↑ workload of the right ventricle (to pump against higher pressures) To compensate, the right ventricle progressively hypertrophies and dilates, but over time its output ↓ Cor pulmonale (Right heart failure in isolation, not due to Left heart failure) Mucus trapped in airways, serve as nidus for infection Acute exacerbation of COPD (AECOPD) Pneumonia The chronic, systemic inflammation in COPD is a hyper-metabolic state that consumes calories Macro-nutrient deficiency Trouble with respiration lead to inactivity and deconditioning Wasting, muscle atrophy More inactivity and deconditioning perpetuates the cycle Depression Author: Yan Yu Reviewers: Jason Baserman Naushad Hirani* Juri Janovcik* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"# 肺部炎症 杯状细胞增殖， 气道上皮纤毛 粘液产生↑ 细胞死亡 黏液潴留呼吸道，成为感 染的病灶 慢性阻塞性肺疾病 (COPD) 气道阻塞à 吸入肺泡和终末细 肺大疱破裂 吸入的空气渗入 并潴留于胸腔 气胸 感觉生活失控，对未 来感到绝望 抑郁 作者: Yan Yu 审稿人: Jason Baserman, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 支气管的空气 ↓ 流经肺的血液进行气 缺氧的肺泡à灌注肺泡的肺小动 慢性阻塞性肺疾 病急性加重期 (AECOPD) 肺炎 体交换↓ 慢性低氧血症 肾脏合成促红细胞 生成素进行代偿↑ 血红蛋白与红 细胞合成↑ 红细胞增多症 (继发性) 脉发生反射性血管收缩 肺大部分肺泡缺氧à整个肺 都出现缺氧性血管收缩 肺血管收缩 à 肺血管压力↑ 肺动脉高压 ↑ 右心室负荷(泵血时对抗高压) 为了代偿，右心室逐渐肥大和扩张， 但随着病程进展，右心室输出量 ↓ 肺心病 (单独出现右心衰竭，非左心衰) COPD所致的慢性全身 呼吸困难导致活 性炎症会使机体处于高 动量减少和活动 代谢状态，消耗能量 耐量降低 宏量营养 素缺乏症 消瘦，肌肉萎缩 运动量下降和活动耐量 的降低造成恶性循环 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com " />

COPD-临床表现

COPD: 临床表现 作者: Yan Yu 审稿人:Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人:Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 /012 (如a1-抗胰蛋白酶缺乏) 阻止肺组织损伤的能力↓ +,-. (如长期吸烟、环境污染、感染) 肺内产生自由基 34*5 肺抗蛋白酶的失活 ↑氧化应激，炎性细胞因子，蛋白酶功能 支气管的持续、反复损伤 炎性细胞浸润， 杯状细胞增殖， 气道上皮纤毛 尤其中性粒细 黏液产生↑ 细胞死亡 气道弹性↓ (弹性回缩 肺实质的蛋白水解破坏↑ 维持气道开放 肺泡永久性异常 的结构支持↓ 扩张 胞 力) 肺气体潴留 气道狭窄与 肺过度 肺大泡 气道黏液潴留，成为感染 狭窄 病灶 塌陷 充气 肺气肿 (容易肺泡 破裂) 气道纤维化和 %&'()* 慢性阻塞性肺疾病(COPD) 临床表现 并发症 (参阅相关幻灯片) (参阅相关幻灯片) 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Clinical Findings Lung tissue Chronic Obstructive Pulmonary Disease (COPD) damage ↓ elastic recoil to push air out of lungs on expiration Lungs don’t fully empty, air is trapped in alveoli (lung hyperinflation) ↑ lung volume means diaphragm is tonically contracted (flatter) If occurring around airways Airflow obstruction ↑ mucus production ↓ number of epithelial ciliated cells to clear away the mucus (the cells have been killed by airway inflammation) Chronic cough with sputum Author: Yan Yu Reviewers: Jason Baserman Jennifer Au Naushad Hirani* Juri Janovcik* * MD at time of publication During expiration, positive pleural pressure squeezes on airwaysà↑ obstruction ↓ ventilation of alveoli ↓ oxygenation of blood (hypoxemia) ↓ perfusion of body tissues (i.e. brain, muscle) Fatigue; ↓ exercise tolerance Total expiration time takes longer than normal Prolonged expiration More effort needed to ventilate larger lungs Respiratory muscles must work harder to breathe Turbulent airflow in narrower airways is heard on auscultation Expiratory Wheeze Diaphragm can’t flatten much further to generate deep breaths To breathe, chest wall must expand out more Dyspnea Shortness of breath, especially on exertion Breathes are rapid & shallow If end-stage: Chronic fatigue causes deconditioning Muscle weakness & wasting Barrel chest If end-stage: diaphragm will be “flat”. Continued Patient tries to expire against higher mouth air pressure, forcing airways to open wider Pursed-lip breathing Patient breathes with accessory muscles as well as diaphragm to try to improve airflow inspiratory effort further contracts diaphragmà pull the lower chest wall inwards Hoover’s sign (paradoxical shrinking of lower chest during inspiration) Tripod sitting position (activates pectoral muscles) Neck (SCM, scalene) muscles contracted Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: ! 45 (on ABGs) Ventilation- perfusion mismatch High A-a gradient (calculated from ABGs) Low, flat diaphragm, >10 posterior ribs (on frontal CXR) High TLC and VC (on spirometry) • • PaO2: partial pressure of O2 in arterial blood PaCO2: partial pressure of CO2 in arterial blood • In the setting of fever and productive cough, especially if lung field opacifications are seen on CXR: consider sputum gram stain and culture to rule out pneumonia. Air does not block X-ray beams, will appear black on X-ray film Chronic hypercapnia makes breathing centers less sensitive to the high PaCO2 stimulus for breathing, & more reliant on the low PaO2 stimulus (“CO2 retention”) Give O2 carefully to these patients (high PaO2 may suppress patients’ hypoxic respiratory drive, ↓ their breathing, & ↑↑↑ PaCO2) ↑ retrosternal air space (on lateral CXR) Hyper-lucent (darker) lung fields, ↓ lung markings (on frontal CXR) • Arterial Blood Gasses (ABGs) • Chest X-Ray (CXR): frontal and lateral Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"#$ 气流阻塞 肺泡通气↓ 呼气时，胸膜腔正压挤压气 道à 阻塞↑ 作者: Yan Yu 审稿人: Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者:Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 慢性阻塞性肺疾病 (COPD) 肺组织损伤 没有弹性回缩力将 气体排出肺 肺实质与血管分布减少导 致气体交换面积↓ 弥散功能↓ (肺功能检查) 更多的CO2残留 并扩散到血液中 高碳酸血症: PaCO2 > 45 (动脉血气) 血流灌注通气不良的肺泡 时无法获得足够的氧气 总呼气时长较正常长 FEV1/FEV < 0.7 (肺功能检查) 肺无法完全排空 更多空气潴留在肺部 (肺过度充气) 低氧血症: PaO2 < 70mmHg (动脉血气) 通气-灌注不匹配 肺泡-动脉氧分压差↑ (可通过动脉血气分析计算得出) 横膈低平， 下移至第10肋后端 及以下部位 (胸部正位片) TLC与VC增大 (肺功能检查) 缩写: • • FEV1: 1秒用 • VC:肺活量 PaO2: 动脉血 力呼气量 氧分压 空气不会阻挡X射线， 在X光片上呈现为黑色 慢性高碳酸血症使呼吸中枢对PaCO2 刺激呼吸的敏感性下降 & 更依赖于低PaO2的刺激 (“二氧化碳潴留”) 给患者吸氧时需注意(高PaO2 可能会抑制患者低氧时对呼吸的 刺激，使呼吸驱动↓ & PaCO2↑↑↑ ) • FVC: 用力肺 • 活量 • TLC:肺总量 慢阻肺相关检查 : PaCO2: 动脉 血二氧化碳 分压 胸骨后间隙↑ (胸部侧位片) 肺纹理↓ • 肺功能检查 • 动脉血气分析(Arterial Blood Gasses, ABGs) • 胸部正侧位片 • 当患者发热和湿咳，特别是胸片上见肺野不清晰时: 肺透亮度↑, (胸部正位片) 考虑进行痰革兰氏染色及痰培养以排除肺炎可能 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Complications Lung inflammation Chronic Obstructive Pulmonary Disease (COPD) Airway obstruction ↓ inhaled air in alveoli and terminal bronchioles Rupture of emphasematous bullae on surface of lung Inhaled air leaks into pleural cavity and is trapped there Pneumothorax Feeling a loss of control over one’s life, and hopelessness for the future Goblet cell proliferation, ↑ mucus production Death of airway epithelium ciliated cells ↓ oxygenation of the blood passing through the lungs Chronic hypoxemia Kidneys compensate by ↑ erythropoietin (EPO) production ↑ Hemoglobin and red blood cell synthesis Polycythemia (secondary) Hypoxic alveoli cause the pulmonary arterioles perfusing them to reflexively vasoconstrict Since most alveoli in the lungs are hypoxic, hypoxic vasoconstriction occurs across entire lung Vasoconstriction ↑ blood pressure within lung vasculature Pulmonary hypertension ↑ workload of the right ventricle (to pump against higher pressures) To compensate, the right ventricle progressively hypertrophies and dilates, but over time its output ↓ Cor pulmonale (Right heart failure in isolation, not due to Left heart failure) Mucus trapped in airways, serve as nidus for infection Acute exacerbation of COPD (AECOPD) Pneumonia The chronic, systemic inflammation in COPD is a hyper-metabolic state that consumes calories Macro-nutrient deficiency Trouble with respiration lead to inactivity and deconditioning Wasting, muscle atrophy More inactivity and deconditioning perpetuates the cycle Depression Author: Yan Yu Reviewers: Jason Baserman Naushad Hirani* Juri Janovcik* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"# 肺部炎症 杯状细胞增殖， 气道上皮纤毛 粘液产生↑ 细胞死亡 黏液潴留呼吸道，成为感 染的病灶 慢性阻塞性肺疾病 (COPD) 气道阻塞à 吸入肺泡和终末细 肺大疱破裂 吸入的空气渗入 并潴留于胸腔 气胸 感觉生活失控，对未 来感到绝望 抑郁 作者: Yan Yu 审稿人: Jason Baserman, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 支气管的空气 ↓ 流经肺的血液进行气 缺氧的肺泡à灌注肺泡的肺小动 慢性阻塞性肺疾 病急性加重期 (AECOPD) 肺炎 体交换↓ 慢性低氧血症 肾脏合成促红细胞 生成素进行代偿↑ 血红蛋白与红 细胞合成↑ 红细胞增多症 (继发性) 脉发生反射性血管收缩 肺大部分肺泡缺氧à整个肺 都出现缺氧性血管收缩 肺血管收缩 à 肺血管压力↑ 肺动脉高压 ↑ 右心室负荷(泵血时对抗高压) 为了代偿，右心室逐渐肥大和扩张， 但随着病程进展，右心室输出量 ↓ 肺心病 (单独出现右心衰竭，非左心衰) COPD所致的慢性全身 呼吸困难导致活 性炎症会使机体处于高 动量减少和活动 代谢状态，消耗能量 耐量降低 宏量营养 素缺乏症 消瘦，肌肉萎缩 运动量下降和活动耐量 的降低造成恶性循环 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com " title="COPD: 临床表现 作者: Yan Yu 审稿人:Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人:Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 /012 (如a1-抗胰蛋白酶缺乏) 阻止肺组织损伤的能力↓ +,-. (如长期吸烟、环境污染、感染) 肺内产生自由基 34*5 肺抗蛋白酶的失活 ↑氧化应激，炎性细胞因子，蛋白酶功能 支气管的持续、反复损伤 炎性细胞浸润， 杯状细胞增殖， 气道上皮纤毛 尤其中性粒细 黏液产生↑ 细胞死亡 气道弹性↓ (弹性回缩 肺实质的蛋白水解破坏↑ 维持气道开放 肺泡永久性异常 的结构支持↓ 扩张 胞 力) 肺气体潴留 气道狭窄与 肺过度 肺大泡 气道黏液潴留，成为感染 狭窄 病灶 塌陷 充气 肺气肿 (容易肺泡 破裂) 气道纤维化和 %&'()* 慢性阻塞性肺疾病(COPD) 临床表现 并发症 (参阅相关幻灯片) (参阅相关幻灯片) 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Clinical Findings Lung tissue Chronic Obstructive Pulmonary Disease (COPD) damage ↓ elastic recoil to push air out of lungs on expiration Lungs don’t fully empty, air is trapped in alveoli (lung hyperinflation) ↑ lung volume means diaphragm is tonically contracted (flatter) If occurring around airways Airflow obstruction ↑ mucus production ↓ number of epithelial ciliated cells to clear away the mucus (the cells have been killed by airway inflammation) Chronic cough with sputum Author: Yan Yu Reviewers: Jason Baserman Jennifer Au Naushad Hirani* Juri Janovcik* * MD at time of publication During expiration, positive pleural pressure squeezes on airwaysà↑ obstruction ↓ ventilation of alveoli ↓ oxygenation of blood (hypoxemia) ↓ perfusion of body tissues (i.e. brain, muscle) Fatigue; ↓ exercise tolerance Total expiration time takes longer than normal Prolonged expiration More effort needed to ventilate larger lungs Respiratory muscles must work harder to breathe Turbulent airflow in narrower airways is heard on auscultation Expiratory Wheeze Diaphragm can’t flatten much further to generate deep breaths To breathe, chest wall must expand out more Dyspnea Shortness of breath, especially on exertion Breathes are rapid & shallow If end-stage: Chronic fatigue causes deconditioning Muscle weakness & wasting Barrel chest If end-stage: diaphragm will be “flat”. Continued Patient tries to expire against higher mouth air pressure, forcing airways to open wider Pursed-lip breathing Patient breathes with accessory muscles as well as diaphragm to try to improve airflow inspiratory effort further contracts diaphragmà pull the lower chest wall inwards Hoover’s sign (paradoxical shrinking of lower chest during inspiration) Tripod sitting position (activates pectoral muscles) Neck (SCM, scalene) muscles contracted Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"#$ 慢性阻塞性肺疾病 (COPD) 如果出现在气道周围 气流阻塞 肺不能完全排空 气体，气体潴留 于肺泡(肺过度 充气) 总呼气时长大于 正常时长 呼气相延长 肺组织损伤 呼气时，将空气排出肺外 的弹性回缩力↓ 肺不能完全排空气体， 气体潴留于肺泡内 (肺过度充气) 肺容积↑，膈肌紧张 性收缩(膈肌平坦) 呼气时，胸膜腔正压挤压气道 à 气道阻塞↑ 肺泡通气↓ 血液氧合↓ (低 氧血症) 身体组织灌注 量↓ (比如脑、 肌肉) 疲劳; 运动耐量↓ 黏液生成↑ 清除黏液的上皮纤 毛细胞数量↓ (受 气道炎症损伤) 慢性咳嗽伴咳 痰 作者: Yan Yu 审稿人: Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 容积较大 的肺需要 更加努力 才能通气 呼吸肌必须 更用力才能 呼吸 听诊闻及狭窄气 道中的湍流气流 呼气喘鸣音 呼吸困难 气促，尤其是劳累 膈肌无法进一步收缩以 产生深呼吸 呼吸浅快 为了呼吸， 胸壁必须延 展得更大 桶状胸 晚期病人: 患者试图在较高的口 慢性疲劳导致 患者动用辅助呼吸肌和膈肌呼吸， 腔内气压下进行呼气， 活动耐量下降 从而使气道更开放 以改善气流 晚期病人:膈肌 “平坦” ，持续吸气进一步压 缩膈肌à 向内拉季肋部胸壁 胡佛征 (吸气时，胸廓下侧季肋部内收) 缩唇呼吸 肌肉无力 & 消瘦 端坐呼吸 (调动胸肌) 颈部肌肉收 缩(胸锁乳 突肌、斜角 肌) 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Findings on Investigations Chronic Obstructive Pulmonary Disease (COPD) Author: Yan Yu Reviewers: Jason Baserman Jennifer Au Naushad Hirani* Juri Janovcik* * MD at time of publication Airflow obstruction Lung tissue damage ↓ ventilation of alveoli Blood perfusing ill- ventilated alveoli does not receive normal amounts of oxygen During expiration, positive pleural pressure squeezes on airwaysà↑ obstruction) No elastic recoil to push air out of lungs Loss of lung parenchyma and vasculature ↓ surface area for gas exchange ↓ diffusion capacity (on spirometry) Hypoxemia: PaO2 < 70mmHg (on ABGs) Abbreviations: • FEV1: Forced expiratory volume in 1 second • FVC: Forced vital capacity • TLC: Total lung capacity • VC: Vital Capacity Investigations for COPD : • Spirometry (Pulmonary function test) Total expiration time takes longer than normal FEV1/FEV < 0.7 (on spirometry) Lungs don’t fully empty More air trapped within lungs (hyperinflation) More CO2 remains and diffuses into the blood Hypercapnia: PaCO2 > 45 (on ABGs) Ventilation- perfusion mismatch High A-a gradient (calculated from ABGs) Low, flat diaphragm, >10 posterior ribs (on frontal CXR) High TLC and VC (on spirometry) • • PaO2: partial pressure of O2 in arterial blood PaCO2: partial pressure of CO2 in arterial blood • In the setting of fever and productive cough, especially if lung field opacifications are seen on CXR: consider sputum gram stain and culture to rule out pneumonia. Air does not block X-ray beams, will appear black on X-ray film Chronic hypercapnia makes breathing centers less sensitive to the high PaCO2 stimulus for breathing, & more reliant on the low PaO2 stimulus (“CO2 retention”) Give O2 carefully to these patients (high PaO2 may suppress patients’ hypoxic respiratory drive, ↓ their breathing, & ↑↑↑ PaCO2) ↑ retrosternal air space (on lateral CXR) Hyper-lucent (darker) lung fields, ↓ lung markings (on frontal CXR) • Arterial Blood Gasses (ABGs) • Chest X-Ray (CXR): frontal and lateral Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"#$ 气流阻塞 肺泡通气↓ 呼气时，胸膜腔正压挤压气 道à 阻塞↑ 作者: Yan Yu 审稿人: Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者:Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 慢性阻塞性肺疾病 (COPD) 肺组织损伤 没有弹性回缩力将 气体排出肺 肺实质与血管分布减少导 致气体交换面积↓ 弥散功能↓ (肺功能检查) 更多的CO2残留 并扩散到血液中 高碳酸血症: PaCO2 > 45 (动脉血气) 血流灌注通气不良的肺泡 时无法获得足够的氧气 总呼气时长较正常长 FEV1/FEV < 0.7 (肺功能检查) 肺无法完全排空 更多空气潴留在肺部 (肺过度充气) 低氧血症: PaO2 < 70mmHg (动脉血气) 通气-灌注不匹配 肺泡-动脉氧分压差↑ (可通过动脉血气分析计算得出) 横膈低平， 下移至第10肋后端 及以下部位 (胸部正位片) TLC与VC增大 (肺功能检查) 缩写: • • FEV1: 1秒用 • VC:肺活量 PaO2: 动脉血 力呼气量 氧分压 空气不会阻挡X射线， 在X光片上呈现为黑色 慢性高碳酸血症使呼吸中枢对PaCO2 刺激呼吸的敏感性下降 & 更依赖于低PaO2的刺激 (“二氧化碳潴留”) 给患者吸氧时需注意(高PaO2 可能会抑制患者低氧时对呼吸的 刺激，使呼吸驱动↓ & PaCO2↑↑↑ ) • FVC: 用力肺 • 活量 • TLC:肺总量 慢阻肺相关检查 : PaCO2: 动脉 血二氧化碳 分压 胸骨后间隙↑ (胸部侧位片) 肺纹理↓ • 肺功能检查 • 动脉血气分析(Arterial Blood Gasses, ABGs) • 胸部正侧位片 • 当患者发热和湿咳，特别是胸片上见肺野不清晰时: 肺透亮度↑, (胸部正位片) 考虑进行痰革兰氏染色及痰培养以排除肺炎可能 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Complications Lung inflammation Chronic Obstructive Pulmonary Disease (COPD) Airway obstruction ↓ inhaled air in alveoli and terminal bronchioles Rupture of emphasematous bullae on surface of lung Inhaled air leaks into pleural cavity and is trapped there Pneumothorax Feeling a loss of control over one’s life, and hopelessness for the future Goblet cell proliferation, ↑ mucus production Death of airway epithelium ciliated cells ↓ oxygenation of the blood passing through the lungs Chronic hypoxemia Kidneys compensate by ↑ erythropoietin (EPO) production ↑ Hemoglobin and red blood cell synthesis Polycythemia (secondary) Hypoxic alveoli cause the pulmonary arterioles perfusing them to reflexively vasoconstrict Since most alveoli in the lungs are hypoxic, hypoxic vasoconstriction occurs across entire lung Vasoconstriction ↑ blood pressure within lung vasculature Pulmonary hypertension ↑ workload of the right ventricle (to pump against higher pressures) To compensate, the right ventricle progressively hypertrophies and dilates, but over time its output ↓ Cor pulmonale (Right heart failure in isolation, not due to Left heart failure) Mucus trapped in airways, serve as nidus for infection Acute exacerbation of COPD (AECOPD) Pneumonia The chronic, systemic inflammation in COPD is a hyper-metabolic state that consumes calories Macro-nutrient deficiency Trouble with respiration lead to inactivity and deconditioning Wasting, muscle atrophy More inactivity and deconditioning perpetuates the cycle Depression Author: Yan Yu Reviewers: Jason Baserman Naushad Hirani* Juri Janovcik* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"# 肺部炎症 杯状细胞增殖， 气道上皮纤毛 粘液产生↑ 细胞死亡 黏液潴留呼吸道，成为感 染的病灶 慢性阻塞性肺疾病 (COPD) 气道阻塞à 吸入肺泡和终末细 肺大疱破裂 吸入的空气渗入 并潴留于胸腔 气胸 感觉生活失控，对未 来感到绝望 抑郁 作者: Yan Yu 审稿人: Jason Baserman, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 支气管的空气 ↓ 流经肺的血液进行气 缺氧的肺泡à灌注肺泡的肺小动 慢性阻塞性肺疾 病急性加重期 (AECOPD) 肺炎 体交换↓ 慢性低氧血症 肾脏合成促红细胞 生成素进行代偿↑ 血红蛋白与红 细胞合成↑ 红细胞增多症 (继发性) 脉发生反射性血管收缩 肺大部分肺泡缺氧à整个肺 都出现缺氧性血管收缩 肺血管收缩 à 肺血管压力↑ 肺动脉高压 ↑ 右心室负荷(泵血时对抗高压) 为了代偿，右心室逐渐肥大和扩张， 但随着病程进展，右心室输出量 ↓ 肺心病 (单独出现右心衰竭，非左心衰) COPD所致的慢性全身 呼吸困难导致活 性炎症会使机体处于高 动量减少和活动 代谢状态，消耗能量 耐量降低 宏量营养 素缺乏症 消瘦，肌肉萎缩 运动量下降和活动耐量 的降低造成恶性循环 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com " />

COPD-检查结果

COPD: 检查结果 气流阻塞 肺泡通气↓ 呼气时，胸膜腔正压挤压气 道à 阻塞↑ 作者: Yan Yu 审稿人: Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者:Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 慢性阻塞性肺疾病 (COPD) 肺组织损伤 没有弹性回缩力将 气体排出肺 肺实质与血管分布减少导 致气体交换面积↓ 弥散功能↓ (肺功能检查) 更多的CO2残留 并扩散到血液中 高碳酸血症: PaCO2 > 45 (动脉血气) 血流灌注通气不良的肺泡 时无法获得足够的氧气 总呼气时长较正常长 FEV1/FEV < 0.7 (肺功能检查) 肺无法完全排空 更多空气潴留在肺部 (肺过度充气) 低氧血症: PaO2 < 70mmHg (动脉血气) 通气-灌注不匹配 肺泡-动脉氧分压差↑ (可通过动脉血气分析计算得出) 横膈低平， 下移至第10肋后端 及以下部位 (胸部正位片) TLC与VC增大 (肺功能检查) 缩写: • • FEV1: 1秒用 • VC:肺活量 PaO2: 动脉血 力呼气量 氧分压 空气不会阻挡X射线， 在X光片上呈现为黑色 慢性高碳酸血症使呼吸中枢对PaCO2 刺激呼吸的敏感性下降 & 更依赖于低PaO2的刺激 (“二氧化碳潴留”) 给患者吸氧时需注意(高PaO2 可能会抑制患者低氧时对呼吸的 刺激，使呼吸驱动↓ & PaCO2↑↑↑ ) • FVC: 用力肺 • 活量 • TLC:肺总量 慢阻肺相关检查 : PaCO2: 动脉 血二氧化碳 分压 胸骨后间隙↑ (胸部侧位片) 肺纹理↓ • 肺功能检查 • 动脉血气分析(Arterial Blood Gasses, ABGs) • 胸部正侧位片 • 当患者发热和湿咳，特别是胸片上见肺野不清晰时: 肺透亮度↑, (胸部正位片) 考虑进行痰革兰氏染色及痰培养以排除肺炎可能 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com

COPD-并发症

COPD: 并发症 肺部炎症 杯状细胞增殖， 气道上皮纤毛 粘液产生↑ 细胞死亡 黏液潴留呼吸道，成为感 染的病灶 慢性阻塞性肺疾病 (COPD) 气道阻塞à 吸入肺泡和终末细 肺大疱破裂 吸入的空气渗入 并潴留于胸腔 气胸 感觉生活失控，对未 来感到绝望 抑郁 作者: Yan Yu 审稿人: Jason Baserman, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 支气管的空气 ↓ 流经肺的血液进行气 缺氧的肺泡à灌注肺泡的肺小动 慢性阻塞性肺疾 病急性加重期 (AECOPD) 肺炎 体交换↓ 慢性低氧血症 肾脏合成促红细胞 生成素进行代偿↑ 血红蛋白与红 细胞合成↑ 红细胞增多症 (继发性) 脉发生反射性血管收缩 肺大部分肺泡缺氧à整个肺 都出现缺氧性血管收缩 肺血管收缩 à 肺血管压力↑ 肺动脉高压 ↑ 右心室负荷(泵血时对抗高压) 为了代偿，右心室逐渐肥大和扩张， 但随着病程进展，右心室输出量 ↓ 肺心病 (单独出现右心衰竭，非左心衰) COPD所致的慢性全身 呼吸困难导致活 性炎症会使机体处于高 动量减少和活动 代谢状态，消耗能量 耐量降低 宏量营养 素缺乏症 消瘦，肌肉萎缩 运动量下降和活动耐量 的降低造成恶性循环 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症

毛细支气管炎-发病机制及临床表现

毛细支气管炎: 发病机制及临床表现 病毒病原体, 最常见的是呼吸道合胞病毒(RSV), 但也可以是其他病毒，如鼻病毒、腺病毒、 副流感病毒、流感病毒和冠状病毒，最初在鼻黏膜定植 病毒通过呼吸道上皮迁移至下呼吸道及终末细支气管(小气道) 毛细支气管炎 (细支气管炎症 ) 作者: Nick Baldwin,Rebecca Lindsay 审稿人: Kayla Nelson, Yan Yu，Timothy Fu, Danielle,Nelson* 译者: Yonglin Mai(麦泳琳) 翻译审稿人 : Zesheng Ye (叶泽生) *发表时担任临床医生 呼吸道合胞病毒融合蛋白促进病毒与宿 主细胞融合,直接介导病毒侵袭并感染邻 近正常组织细胞 合胞体形成 (多核巨细胞) 合胞体从支气管上 纤毛上皮细胞破坏 上呼吸道黏膜 炎症反应 细胞因子释 蛋白质和液 放到血液循 体渗漏至鼻 环系统 咽间质 下丘脑体温 间质水肿 调节点↑ 低烧 流鼻涕 鼻塞 ↑毛细血 管通透性 蛋白质和液 体渗漏至细 支气管及周 围间质，并 积聚在支气 管壁周围 气管管壁增厚，X 光征象更为明显 支气管周围袖口征 (X光征象正位可见支 气管壁增厚，如增厚 “袖口”) 炎症刺激使分泌黏液的 杯状细胞增多 ↑黏液分泌 肺泡中的黏液使得肺泡内表 面张力↑à肺泡壁塌陷 在吸气过程中， 如气道尚未阻塞， 空气可以进入塌 陷的肺泡当中 肺泡内压力↑使得塌陷 的肺泡骤然打开 听诊时可闻及吸气 性爆裂音(湿啰音) 呼吸暂停 (呼吸停止;具体机 制未明，可能触发呼 吸暂停反射 ) 皮脱落至气道 气道变窄及闭塞 (其功能是清除粘 液排出气道，将其 送入咽部被吞咽或 者被排出) ↓ 气道粘 液清除 过多气道粘液触 发咳嗽反射 咳嗽 堵塞支气管远端 的气体被吸收 ( 气体潴留) 气体被全部吸收后,肺 泡会塌陷 (吸收性肺不 张) 在剩余肺泡中,血气屏障 处气体交换↓ ↓ 血氧(O2 )饱和度 & ↑ 血二氧化碳(CO2)浓度 尤其在呼 气时，更 狭窄的气 道会产生 湍流气流 听诊可闻及呼 气相哮鸣音 图注: 病理生理 机制 体征/症状/实验室检查 并发症 2020年11月29日重新发布于 www.thecalgaryguide.com

支气管扩张-胸部 X线和 CT扫描的表现

支气管扩张: 胸部 X线和 CT扫描的表现 作者: Sean Kennedy 审稿人: Yan Yu,Matthew Harding,Amogh Agrawal,Naushad Hirani* 译者: Huiting Wang(王慧婷), Yang Xiang(向阳) 翻译审稿人:Ran Zhong(钟然), Yonglin Mai(麦泳琳), Zesheng Ye(叶泽生) * 出版时担任临床医生 支气管扩张: 支气管的 异常损伤和扩张 在一些炎症过程下，中性粒细胞、细胞因 子、一氧化氮和氧自由基积聚在肺内 支气管和支气管周围组织炎性破坏 支气管的弹性成分被破坏 弹性组织的丢失使得支气管壁的完整性受 损，使其结构更松散 当支气管向远端延伸时，支气管仍 扩张(但通常情况支气管是变细) 异常扩张的支气管比其 伴行的动脉更宽 (支气管:动脉直径比1.5) 支气管内的空气呈黑色 ，对比之下周围动脉内 的血液呈白色，形成环 状外观 CT下的印戒征 成像时显示支气 管扩张增厚轮廓 胸片下的轨道征 支气管扩张使远 端支气管在影像 学上更明显 CT可见距胸膜 1cm内的支气管 囊状支气管扩张可 能出现聚集成簇 横断面CT扫描显 示葡萄串征 图注: 病理生理 机制 体征/症状/实验室检查 并发症 2013年7月30日发布于 www.thecalgaryguide.com

哮喘急性发作-发病机制和治疗

哮喘急性发作: 发病机制和治疗 病毒性上呼吸道感染 接触变应原 环境污染 其他诱因 作者: Luke Gagnon 审稿人:Midas (Kening) Kang，Usama Malik，Lian Szabo* 译者:Yonglin Mai (麦泳琳) 翻译审核人:Zesheng Ye (叶泽生) * 发表时担任临床医生 下呼吸道炎症 免疫系统激活:气道上皮趋化因子、淋巴细胞和巨噬细胞激活, 白三烯产生↑ 炎症介质释放 哮喘轻中度急性发作: PEF ≥ 预计值50% 疗效良好: 症状缓 解, PEF ≥ 80% 患者日常在家 服用糖皮质激 素及必要时使 用SABA 支气管狭窄 残气量↑ 及PaCO2↑ 气体潴留↑，肺 泡内压力 ↑ 奇脉 气体通过 发炎的呼 吸道产生 的刺激↑ 咳嗽和喘息 Notes 呼吸 困难 黏膜水肿会导 致气流湍急 喘息 吸O2使SpO2 ≥ 92%, 给予SABA & 糖皮质激素 治疗 重度急性发作: PEF ≤预计值 50% 呼吸困难 呼吸急促 呼吸衰竭 意识丧失 ↓ 向肺泡传送 空气氧含量 血氧饱和度↓ • • Asthma哮喘: Airway hyper- responsiveness causing airflow obstructions气道高反应性引起气流受 限 Acute Exacerbation (Asthma)哮喘急性 发作: An episode of increased symptoms due to decreases in airflow气流减少而 引起一系列症状加重 Abbreviations • PaCO2动脉二氧化碳分压:Partial pressure of CO2 in arterial blood • PEF最大呼气流量/呼气流量峰值: Peak expiratory flow • SABA短效beta-2受体激动剂: Short- acting beta-2 agonists • SpO2血氧饱和度: Blood oxygen saturation level 昏睡 气胸 中枢性紫绀 心动过速 患者宣教: 正确服用药物，使用 药物吸入装置 &全科医生密切医学随 访 吸 O 使 SpO ≥ 2 2 症状恶化和/或呼吸衰竭 :及时气 管插管, 送往ICU, 给予SABA, 糖皮 质激素 & 硫酸镁 取决于气胸严 重程度: 密切观 察或者置入胸 腔引流管 93%, 给予 SABA, 糖皮质激素 & 硫 酸镁 图注: 病理生理 机制 体征/症状/实验室检查 并发症 2018年 2月6日发布于 www.thecalgaryguide.com

新冠肺炎腺病毒载体疫苗-制备及其作用机制

新冠肺炎腺病毒载体疫苗：制备及其作用机制 牛津/阿斯利康 56%&'H^89:;H^< 56%&'789:;7< 56CDD%&':EFGHHH9IJ:;KLGB9MNO 美国强生 康希诺生物 =>?@4A%&'B =>?@4A%&'B PQRS4TUVWA)XYZ[*]B2 *+4-. 利用逆转录聚合酶链反应(RT-PCR)和全基因组测序技术，将 SARS-CoV-2(导致COVID-19的病毒)的RNA合成DNA文库 从SARS-CoV-2基因组中提取出刺突蛋白的DNA序列 将启动子添加到刺突蛋白的DNA序列中，使该序列在导入细胞 后能被RNA聚合酶识别并转录 应用基因重组技术将修饰后的刺突蛋白DNA序列插入到质粒中。 质粒:一种环状DNA，能使新基因(如刺突蛋白基因)插入到 先前感染Ad5或Ad26可能导致机 腺病毒DNA可通过多种细胞裂解剂以及 黑猩猩病毒可免去先前对该病 体已对腺病毒载体产生免疫1 人腺病毒疫苗可能因曾感染Ad5或 Ad26而失效 ,因为免疫力并不是针 对刺突(Spike)蛋白而建立的 洗涤剂提取(可打破细胞膜并去除非核 酸细胞物质的化学试剂) 毒载体产生免疫的可能性1 黑猩猩病毒载体使机体更好地 使用全基因组测序对腺病毒DNA 进行测序，并进行以下修饰: 对刺突蛋白产生免疫反应 去除腺病毒基因组的E1区， 去除腺病毒基因组的E3区，为SARS-CoV-2 宿主基因组中(如腺病毒载体DNA基因组) 以阻断病毒复制3 刺突蛋白DNA的插入腾出空间3 修饰后的腺病毒DNA基因组将重新插入到腺病毒 将病毒载体与刺突蛋白质粒混合在一起，DNA重组技 颗粒中，形成“病毒载体” 术使质粒中的刺突蛋白基因插入到腺病毒DNA中2 作者: Ryan Brenneis, Yan Yu* 审稿人: Davis MacLean, Hannah Yaphe Stephen Vaughan* 译者: Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳) * 出版时担任临床医生 最终制备出的疫苗中的腺 病毒不能在人体细胞内复 制，也不会引起人类疾病 参考文献 1. ACS Nano 2020, 14, 10, 12522–12537, Publication Date: October 9, 2020, https://doi.org/10.1021/acsnano.0c07197 含有可转录SARS-CoV-2刺突蛋白DNA的腺病毒放置于 一种特殊的细胞培养环境中，该环境允许病毒DNA在修 饰后仍进行复制2, 3 2. Nature 2020, 586, 578–582, Publication Date: October 20, 2020, https://doi.org/10.1038/s41586- 020-2608-y 3. Frontiers in Immunology 2018, 9, 1963, Publication Date: September 19, 2018, doi: 10.3389/fimmu.2018.01963 4. NPJ Vaccines 2020, 5, 69, Publication Date: July 27, 2020, doi: 10.1038/s41541-020-00221-3 5. The Lancet 2020, Publication Date: Dec. 8, 2020, https://doi.org/10.1016/S0140-6736(20)32623-4 6. BMJ 2000, 321, 7271, 1237-1238, Publication Date: November 18, 2000, DOI: 10.1136.bmj.321.7271.1237 7. NEJM 2021, Publication Date: Jan. 13, 2021, DOI: 10.1056/NEJMoa2034201 提取含有可转录SARS-CoV-2刺突蛋 白DNA的腺病毒，并将其配置到疫 苗注射的浓度 腺病毒有一个外层蛋白质层(称为衣 壳)来保护它的DNA DNA比mRNA更稳定，因为DNA具有脱 氧核糖骨架以及双链间的分子键 与mRNA脂质纳米粒 疫苗相比，腺病毒疫 苗的稳定性更强 可在2-8°C 中保存长 达3-6个月 注射部位红、肿、痛 (一过性) 注意: 强生疫苗在单剂接种 后有效率可能为90%7 肌肉是首选的注射 部位，因为肌肉血 供比其他组织多 疫苗作用 细胞免疫 能使免疫细胞更快处 理外来抗原6 能让外来的疫苗物质更快 扩散，使局部反应最小化6 病毒载体疫苗通过肌肉注射到健康人体内 建议在28天后接种第二剂疫苗以增强免疫反应(超过COVID-19康复者 的免疫反应水平)，从而提高疫苗效力，特别是对老年人5 外来异物可引起局 部炎症反应 腺病毒表面抗原与人体细胞受体相互作用，使病毒通过内吞作用进入人体细胞3 腺病毒载体进入细胞核，与核被膜融合，并将其DNA(包括刺突蛋白DNA)注入细胞核 细胞核内的RNA聚合酶转录病毒的DNA，合成SARS-CoV-2刺突蛋白的信使RNA(mRNA) mRNA被运回胞浆，由细胞自身的核糖体进行翻 体液免疫 刺突蛋白被胞内酶降解为片段 刺突蛋白片段与MHC-I类分子结合 MHC-I类分子将刺突蛋白片段转移到人体细胞表面 MHC-I类分子将刺突蛋白片段呈递给幼稚CD8+ T细胞 与刺突蛋白-MHC-I类分子复合物结合后，幼稚CD8+ T细胞活化， 并转移到淋巴系统进一步成熟3 译合成全长SARS-CoV-2刺突蛋白 MHC = 主要组织相容性复合体(Major Histocompatability Complex);细胞表面蛋 白，对免疫功能至关重要 CD = 分化簇(Cluster of Differentiation); T细胞表面的糖蛋白，可作为辅助受体，促 进T细胞与抗原/MHC复合物的结合，同时 可用来区分T细胞类型 刺突蛋白的成分从细胞内释放到血液中 刺突蛋白被抗原提呈细胞 (树突状细胞、B细胞、巨噬 细胞)吞噬、碎裂，与特异的MHC-II类分子结合 MHC-II类分子将刺突蛋白片段转移到抗原提呈细胞表面， 将它们提呈给血循环里的幼稚CD4+ (辅助)T细胞 与复合物结合后，活化刺突蛋白特异性辅助T细胞 结合成刺突蛋白特异性辅助T细胞后被激活 部分T细胞成熟后成为细胞毒性T 细胞，可识别SARS-CoV-2刺突蛋白 细胞毒性T细胞与感染SARS-CoV-2并表达刺 突蛋白的人体细胞或刺突蛋白片段结合 细胞毒性T细胞释放酶，使感染 的细胞穿孔，导致细胞死亡 免疫系统可以更快地识 别和消灭受感染的细胞 部分T细胞成熟后成为记忆 性T细胞 (在辅助性T细胞 释放的细胞因子的刺激下) 记忆T细胞转移到淋巴组 织后进入待定状态，在下 一次接触刺突蛋白时活化 以后SARS-CoV-2 感染时 可介导更快的细胞免疫 (获得免疫力) 活化的刺突蛋白 特异性辅助T细胞 分泌细胞因子， 促进免疫活性 全身性细胞因子释放 可导致全身反应，如 发烧、寒战、疲劳以 及肌痛 (一过性) 注意: 细胞/体液免疫 持续的时间尚不清楚 部分B细胞成熟为浆细胞，产 生病毒刺突蛋白的IgG抗体 刺突蛋白抗体识别标记SARS- CoV-2，使免疫系统能消灭病毒 根除细胞外SARS-CoV-2 淋巴组织中，活化 的辅助性T细胞与幼 稚B细胞相互作用 部分B细胞成熟为 SARS-CoV-2刺突蛋 白特异性记忆B细胞 以后一旦接触刺突蛋白，就能再次活 化淋巴组织里的记忆B细胞，使其变成 浆细胞，更快地合成抗体 以后SARS-CoV-2 感染时可介导更快的体液免疫 (获得免疫力) 图注: 病理生理 机制 体征/临床表现/实验室检查 最终结果 2021年2月11日发布于www.thecalgaryguide.com

急性呼吸窘迫综合征: 发病机制及临床表现

急性呼吸窘迫综合征: 发病机制及临床表现 直接性肺损伤 病因包括肺炎、肺源性脓毒血症(社区获得性、医院获得性、吸入性、病 毒)、溺水及吸入化学物质(如胃内容物或直接吸入性肺损伤)。 作者 : David Olmstead 审稿 : Midas (Kening) Kang, Usama Malik, Kevin Solverson* 译者:Xiumei Deng(邓秀梅) 翻译审稿人: Yonglin Mai (麦泳琳)，Zesheng Ye(叶泽生) • 出版时担任临床医生 间接性肺损伤 病因包括非肺源性的脓毒血症、创伤、严重烧伤、输血相关 性肺损伤以及胰腺炎。 Note: 急性呼吸窘迫综合征是一种以急性肺损伤为 主要表现的临床综合征，表现为严重低氧血症及 双侧肺泡损伤，不伴左心压力增高。 肺组织炎症 渗出期: 由于炎症性刺激，中性 粒细胞迁移聚集至肺泡 Note: 虽然ARDS的三个病理阶段相 继发生，但是肺组织的每一个区 域并非同时处于相同的病理阶段， 因此三个病理阶段常重叠存在。 增生期: 机体试图修复肺损伤， 若修复失败，则进入纤维化期 以中性粒细胞为主的炎性渗出液 破坏肺泡表面活性物质的功能 中性粒细胞浸润及促炎细 胞因子导致肺水肿、肺功 能障碍及继发肺上皮损伤 缩略词表: PaO2: Partial pressure of oxygen in arterial blood(动脉氧分压) SpO2: Peripheral oxygen saturation(外周 血氧饱和度). CXR: Chest radiograph(肺部影像学). 由于缺乏肺泡表面活性物 质，导致肺泡塌陷 肺上皮损伤，气体交换障碍 肺毛细血管不能 完全吸收渗出液 机体尝试修复肺损伤，肺 透明膜形成 通气/血流 比值失调 肺水肿 气体扩散障碍 ↓ PaO2, ↓SpO2 呼吸急促 心动过速 呼吸困难 CXR:双肺 浸润影 ↓ PaO2, ↓SpO2 ↑ PaCO2 ↑ PaO2, ↓PaCO2 呼吸恢复正常 ↓需O 量 吞噬细胞清除肺泡腔里细胞碎片 肺泡上皮细胞修复 疾病迁延导致机体功能损伤 成纤维细胞的作用导 致胶原蛋白沉积于肺 泡腔及肺毛细血管内 气体交换的有效 肺泡表面积↑ 肺泡上皮的修复，有 助于渗出液的重吸收 2 CXR:肺浸润影消散 抑郁, 焦虑,创 伤后应激障碍 咳嗽/呼吸困难 神经源性肌无力 杵状指 纤维化期: 肺修复能力不足导 致长期的肺损伤(少见) 肺纤维化 肺动脉高压 疲劳 慢性呼吸功能障碍 图注: 病理生理学 机制 体征/症状/实验室检查 并发症 2018年2月6日发布于 www.thecalgaryguide.com

原发性自发性气胸-发病机制和临床发现

原发性自发性气胸:发病机制和临床发现 遗传因素(即: FLCN 突 胸部子宫内膜 高且瘦 变，高胱氨酸尿症,马凡 胸部子宫内 吸烟 缺血 膜异位症 炎症破坏了脏层胸膜 的间皮细胞层 突发的胸痛 心动过速 Abbreviations: • FLCN-卵巢滤泡激素基因 • HCY-高胱氨酸尿症 • MFS-马凡氏综合征 • CTD-结缔组织病 • PSP-原发性自发性气胸 • V/Q-通气与血流灌注比值 • SpO2-血氧饱和度 流向肺不张区域的血流不 变 ，但通气量↓ 通气/灌注比失衡 氧饱和度下降、突发性呼 吸困难、心动过速 异位症 男性 氏综合征,结缔组织病) 营养不良 呼吸过程中产生的机械力会引 起肺小疱和/或大疱产生 肺小疱或大疱自发破裂 原发性自发性气胸: 在没有确诊肺部疾病或临床表现患者的胸膜腔中存在或进入空气 肺泡和胸膜腔相通 肺泡内压力> 胸膜腔内压力 肺部空气进入胸膜腔 肺实质结构受损 注意: • PSPs通常在休息时发生。 • 呼吸系统症状的严重程度不 同。年轻女性在月经期间反 复出现PSP，应怀疑胸部子宫 内膜异位症 • *张力性气胸的病理生理学在 另一幻灯片中描述 空气渗入皮下组织 皮下气肿 作者: Lauren Hampton 审稿人: Kening (Midas) Kang, Natalie Morgunov, Sadie Kutz, Usama Malik, Leila Barss* 译者:Huiting Wang (王慧婷), Yang Xiang (向阳) 翻译审稿人:Ran Zhong (钟然), Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 空气将肺实质从胸部分离 患侧肺: 胸壁活动度↓ 叩诊音↑ 或语音震颤↓ 或消失呼吸音↓ 胸片出现气胸线 张力性气胸* 低血压, 颈静脉怒张, 奇脉 胸腔内压力↑ 在非抵抗性内源性弹性回缩力 作用下，小面积肺萎陷 肺顺应性↓ 呼吸做功↑ 辅助性肌肉使用，呼吸急促 图注: 病理生理 机制 体征/症状/实验室检查 并发症 2017年11月14日发布于 www.thecalgaryguide.com

支气管肺癌-肺尖部肺癌肺上沟瘤-pancoast-瘤-发病机制和

支气管肺癌- 肺尖部肺癌(肺上沟瘤/Pancoast 瘤): 发病机制和临床表现 Abbreviation: 作者: Bradley Stebner , Daniel Meyers, Midas (Kening) Kang 审稿人: Natalie Morgunov, Sadie Kutz, Usama Malik, Kerri Johannson* 译者: Ran Zhong (钟然) 翻译审稿人: Yonglin Mai (麦泳 琳), Zesheng Ye (叶泽生) *发表时担任临床医生 Note: • Pancoast 瘤: 在肺上沟 (肺尖)的恶性病灶 • 支气管源性癌:支气管 或细支气管上皮引起的 原发性恶性肿瘤 • Pancoast肿瘤可能是由 原发性或转移性肺肿瘤 (在此描述)以及感染 灶引起的 影响RLN 声音嘶哑 ↓上胸腔的静脉回流 上肢的液体潴留 • • • • • • NSCLC- 非小细胞肺癌 Non Small Cell Lung Cancer SCLC – 小细胞肺癌 Small Cell Lung Cancer RLN –喉返神经 Recurrent Laryngeal Nerve SVC –上腔静脉 Superior Vena Cava RA–右心房 Right Atrium STM –上睑板肌 Superior Tarsal Muscle 胸痛 胸内筋膜 胸膜摩擦 胸膜壁层 肩痛 上肋骨 压迫C8和T1神经 肩痛(尺神经) 大细胞癌 肺腺癌 非小细胞肺癌 (常见) 肺鳞癌 小细胞肺癌 (少见) 原发性支气管肺癌 Pancoast 瘤:位于同侧肺尖 部的肺癌/转移癌 压迫肺上沟部邻近结构 压迫破坏椎旁交感神经链 Horner综合征 ↓对瞳孔开大 肌的交感控制 侵犯气道并引起阻塞 (后期) 呼吸困难 咯血 咳嗽 手部肌肉无力 压迫SVC 上腔静脉阻塞综合征 ↓ 静脉回流到 RA ↓ 心脏到肺的血流 第4/5手指或者手 臂内侧/前臂 出现感觉异常 ↓ 对STM的交 感控制 ↓对外分泌汗 腺的交感控制 上眼睑下垂 瞳孔缩小 无汗 呼吸困难 面部和四肢水肿 图注: 病理生理 机制 体征/症状/实验室检查 并发症 2017年11月16日发布于 www.thecalgaryguide.com

新型冠状病毒肺炎(COVID-19)mRNA疫苗-制备及其作用机制

新型冠状病毒肺炎(COVID-19)mRNA疫苗: 制备及其作用机制 作者: Ryan Brenneis, Yan Yu* 审稿人: Davis MacLean, Hannah Yaphe, Timothy Fu, Stephen Vaughan* 译者: Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳) * 发表时担任临床医生 参考文献 1. ACS Nano 2020, 14, 10, 12522–12537, Publication Date: October 9, 2020, https://doi.org/10.1021/acsnano.0c07197 2. NEJM 2020, Publication Date: December 10, 2020, DOI: 10.1056/NEJMoa2034577 3. Expert Review of Vaccines 2017, 16, 9, 871-881, Publication Date: 2017, DOI: 10.1080/14760584.2017.1355245 4. NEJM 2020, 383, 2439-2450, Publication Date: December 17, 2020, DOI: 10.1056/NEJMoa2027906 5. NEJM 2020, 383, 2427-2438, Publication Date: December 17, 2020, DOI: 10.1056/NEJMoa2028436 6. BMJ 2000, 321, 7271, 1237-1238, Publication Date: November 18, 2000, DOI: 10.1136.bmj.321.7271.1237 注意: • 这两种疫苗的 modRNA所编码的 刺突蛋白是相似的 • 两种疫苗的主要区 别是各家专利的脂 质纳米粒配方(未 公开) 注射部位红、 肿、痛 (一过性) 疫苗制备 通过用鼻咽拭子等方法采集感染患者身上的SARS-CoV-2(引起COVID-19的RNA病毒) 将各种试剂加入到含有人体细胞和病毒成分的样本中 试剂使细胞/病毒膜溶解，释放出细胞内容物、病毒颗粒以及病毒RNA 用各种洗涤剂去除脂肪、蛋白质和碳水化合物，只留下核酸(比如RNA) 利用逆转录聚合酶链反应(RT-PCR)合成病毒RNA的互补DNA(cDNA) 通过其cDNA文库，利用全基因组测序技术绘制SARS-CoV-2的基因组图谱 找到SARS-CoV-2刺突蛋白的DNA序列，并作为模板构建合成病毒刺突蛋白的mRNA 将额外的RNA碱基添加到这条mRNA上以提高它的稳定性，由此产生的RNA链称为“核酸修饰的RNA”(“modRNA”) 用一系列沉淀、提取和层 析等方法分离出刺突蛋白 modRNA 最后，modRNA脂质纳米 粒疫苗研制完成，可用于 肌肉注射 modRNA疫苗通过肌肉注射到健康人体内 3-4周后需接种第二剂疫苗以增强免疫反应(超过COVID-19康复者 通过对其他冠状病 毒(如SARS-CoV-1和 MERS-CoV)的研究 可知，“刺突(Spike) 蛋白”是一种主要的 病毒表面抗原 辉瑞/BNT162b2疫苗成分: 莫德纳mRNA-1273疫苗: 注解: 脂质纳米粒 是一种空心“球”， 由外层脂膜加上其 他乳化剂和膜稳定 剂制成。 脂质纳米粒能够包 裹较小的分子(如 RNA)，并与正常 细胞膜结合。 肌肉是首选的注射 部位，因为肌肉血 供比其他组织多 疫苗作用 能使免疫细胞更快处理外 来抗原6 能让外来的疫苗物质更快扩 散，使局部反应最小化6 细胞免疫 的免疫反应水平)，从而提高疫苗效力，特别是对老年人 4,5 外来异物可引起局部 炎症反应 辉瑞/ BioNTech专 利脂质纳米 粒 modRNA可编码一个由 两个脯氨酸修饰的全 长刺突蛋白(为了稳 定性和免疫原性)2 modRNA可编码一个 由两个脯氨酸修饰的 全长刺突蛋白(为了 稳定性)1 莫德纳专利 脂质纳米粒 将这种modRNA封装在辉瑞/ BioNTech的脂质纳米颗粒中，得到 162b2疫苗 这种疫苗需要更低的储存温度((-700C) 将这种modRNA封装在莫德纳的脂 质纳米粒种，得到mRNA-1273疫苗 这种疫苗可以在稍微温暖的温 度下储存(-200C) 刺突蛋白被胞内酶降解为片段 刺突蛋白片段与MHC-I类分子结合 MHC = 主要组织相容性复合体(Major Histocompatability Complex);细胞表 面蛋白，对免疫功能至关重要 CD = 分化簇(Cluster of Differentiation); T细胞表面的糖蛋白，可作为辅助受体， 促进T细胞与抗原/MHC复合物的结合， 同时可用来区分T细胞类型 刺突蛋白的成分从细胞内释放到血液中 刺突蛋白被抗原提呈细胞 (树突状细胞、B细胞、巨噬细 胞)吞噬、碎裂，与特异的MHC-II类分子结合 MHC-II类分子将刺突蛋白片段转移到抗原提呈细胞表面， 将它们提呈给血循环里的幼稚CD4+ (辅助)T细胞 部分幼稚CD4+ 辅助T细胞能够与刺突蛋白-MHC-II类 分子复合物顺利结合 与复合物结合后，活化刺突蛋白特异性辅助T细胞 脂质纳米粒通过内吞作用与人体细胞的磷脂膜融合，将 modRNA释放到细胞的胞浆中 体液免疫 modRNA由人体细胞中自带的核糖体翻译，合成刺突蛋白 相关成分 MHC-I类分子将刺突蛋白片段转移到人体细胞表面 MHC-I类分子将刺突蛋白片段呈递给幼稚CD8+ T细胞 与刺突蛋白-MHC-I类分子复合物结合后，幼稚CD8+ T 细胞活化并转移到淋巴系统进一步成熟 部分T细胞成熟后成为细胞毒性T细 胞，可识别刺突蛋白 细胞毒性T细胞与感染SARS-CoV-2并表 达刺突蛋白的人体细胞或刺突蛋白片 段结合 细胞毒性T细胞释放酶，使感染的细 胞穿孔，导致细胞死亡 免疫系统可以更快地识别和消灭 SARS-CoV-2感染的人体细胞，使病 毒扩散速度减缓 部分T细胞可以成熟为记 忆性T细胞 (在辅助性T 细胞释放的细胞因子的 刺激下) 记忆T细胞转移到淋巴组 织后进入待定状态，在下 一次接触刺突蛋白时活化 以后SARS-CoV-2 感染时可 介导更快的细胞免疫 (获得免疫力) 活化的刺突蛋白 特异性辅助T细胞 分泌细胞因子， 促进免疫活性 全身性细胞因子释放 导致全身反应:如发 烧、寒战、疲劳以及 肌痛 (一过性) 部分B细胞成熟为浆细胞，产 生病毒刺突蛋白的IgG抗体 刺突蛋白抗体识别标记SARS- CoV-2，使免疫系统能消灭病 毒 根除细胞外的SARS-CoV-2 淋巴组织中，活 化的辅助性T细胞 与幼稚B细胞相 互作用 部分B细胞成熟为 SARS-CoV-2刺突蛋白 特异性记忆B细胞 以后一旦接触刺突蛋白，就能再次活化淋巴 组织里的记忆B细胞，使其变成浆细胞，更 快地合成抗体 以后SARS-CoV-2 感染时可介导更快的体 液免疫 (获得免疫力) 图注: 病理生理 机制 体征/临床表现/实验室检查 最终结果 2020年12月19日发布于 www.thecalgaryguide.com

肺癌：临床发现和副癌综合征

肺癌：临床发现和副癌综合征 作者: Yoyo Chan 审稿人: Midas (Kening) Kang Usama Malik, Leila Barss* 译者: Huiting Wang (王慧婷), Yang xiang (向阳) 翻译审稿人: Ran Zhong (钟然), Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 肿瘤分泌生物活性物质 副癌综合征à 与恶性疾病相关的症状 注意: 肺癌的大多数表现隐匿，具有非特异性的 症状和体征(即发烧、体重减轻、全身不适) 单侧或双侧肺部发生的不受控 异常细胞增生à肺癌 近端气道梗阻 无法清除吸入的 病原体 局部肿瘤生长 肿瘤向胸膜 气道侵袭 表面扩散 胸部不适 胸腔积液 咯血 肺癌梗阻性肺炎 局部阻塞 或 压迫 咳嗽、发热、呼 吸困难 肺通气做功↑ 喉神经压迫 ↑ ADH 合征 水重吸收↑ 低钠血症 血钠 <135mEq/L Lambert-Eaton 综合征 (肌无力样综合征) (产生针对钙通道的自身 抗体) 肌肉无力 上腔静脉 压迫 ↑ TGFβ1 细胞外基 质蛋白↑ 杵状指 ↑ PTHrP 骨骼钙 ↑释放 高钙血症 血钙 >2.6 mmol/L ↑ ACTH 皮质醇的产生 分泌异常综 和释放↑ 抗利尿激素 臂丛神经 压迫 库欣综合征 (长期皮质醇增 多所引起的症状 和体征) 肌肉无力、高血 糖、严重低钾血 症 呼吸困难 呼吸急促 支配声带的神经受损 声音嘶哑 手臂/肩膀/颈 面部/手臂 部疼痛 水肿 缩写: • ACTH:促肾上腺皮质激素 • ADH: 抗利尿激素 • PTHrP: 甲状旁腺激素相关肽 • SIADH:抗利尿激素分泌异常综合征 • TGFβ1: 转化生长因子β1 图注: 病理生理 机制 体征/症状/实验室检查 并发症 2018年2月6日发布于 www.thecalgaryguide.com

新生儿呼吸窘迫-临床表现

新生儿呼吸窘迫:临床表现 由于解剖与生理的差异，新生儿呼吸窘迫的表现与成人不同: 气道更细 气道更容易受阻 膈肌更低平 肋骨呈水平位 正常吸气过程中膈肌 新生儿的肋骨无法向 收缩下降的能力↓ 上及向外移动，胸腔 无法进一步扩大 潮气量受限 呼吸系统疾病引起的问题: 胸廓顺应性更好 胸廓向外扩的压力更 小，与此同时向内的 肺弹性回缩压却不变 静息时肺容积↓ (功能残气量) 新生儿用鼻孔呼吸(6个月前) 通过鼻腔时气流受阻(由 于上呼吸道感染，鼻胃导 管，后鼻孔闭锁等) 鼻翼煽动 喂食困难 ( (扩大鼻孔以 鼻腔受阻时， 下气道阻 塞(如: 细支气管) 喘息(通 常为呼气 相) 喉部以上部 位阻塞(如. 咽, 鼻等,) 鼾音 ↓ O2 储备, 氧 ↓ 气流阻力) 由于潮气量受 限，新生儿只 能通过↑ RR(呼吸频率) 增加通气量 新生儿在呼吸疾 病的早期即可表 现出呼吸急促 辅助呼吸肌收缩， 试图抬高肋骨 由于肋骨无法上抬， 因此肌肉将头拉低 点头呼吸 肺泡更容易塌 陷à肺不张 气饱和度下降 口腔进食与 鼻腔呼吸的 协调难度↑) 作者: Yan Yu 审稿人:Elizabeth de Klerk Hailey Barker Naminder Sandhu* 译者: Xiumei Deng (邓秀梅) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 喉、气管或支气管阻塞 喘鸣(通常为吸气性， 也可以是双相的) 为了防止肺不张 & 氧气饱和度下降， 新生儿通常不会完全呼气:肺内残留 气体可维持肺泡开放 新生儿发生呼吸窘迫时，呼吸动作异常明显 呼吸肌试图 ­ 潮气量, 但由于胸腔容积无 法进一步扩大，呼吸无效做功，长此以往 新生儿显得疲惫不堪 ̄ 呼吸频率(RR); 可能出现呼吸衰竭 用力呼气冲开声门， 肺泡内气体压力 ↑， 以维持肺泡开放 鼾音 深吸气使得胸腔 内压↓，以抵抗 胸廓的顺应性 胸廓凹陷 图注: 病理生理 机制 体征/症状/实验室检查 并发症 2013年1月15日发布于 www.thecalgaryguide.com

异物吸入: 发病机制和临床表现

异物吸入: 发病机制和临床表现 气球 不可食用物，如小玩 具、硬币、大头针 食物:最常见的异物吸入( 尤其是坚果类食物) 作者: Nick Baldwin 审稿人: Elizabeth de Klerk, Yan Yu, Naminder Sandhu* 译者: Huiting Wang (王慧婷), Yang Xiang (向阳) 翻译审稿人: Ran Zhong (钟然), Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) *发表时担任临床医生 气球易压缩及表面光 滑，容易通过气道 气球与气道贴合， 导致气道完全梗阻 口腔探索行为 口腔和吞咽运动 功能不协调 异物在后咽部引起不适，引起儿童猛然吸气 将异物吸入到气道中 异物(FB)吸入: 异物进入呼吸道 Note: Note: 临床实际中 气球误吸十分罕见 死亡率最高 上呼吸道阻塞:从咽部到喉部 • 窒息是一个重要的l体征，但并不易被人 察觉 • 最常见于3岁以下儿童 • 异物误吸最常发生于右肺，由于右主支气 管较左侧管径更粗、走向较垂直 下气道阻塞: 从气管到肺泡 部分性 完全性: 肺和外界没有气体交换 氧气和二氧化碳交换量↓ 缺氧:组织供氧不足 心肌供氧不足 心肌供氧不足 心脏停搏 空气通气量↓ 氧气和二氧化 碳交换量↓ 缺氧 氧气需求增多 呼吸中枢刺激的呼吸 驱动↑ 呼吸急促，用力呼 吸 气道狭窄 经过狭窄 处时，湍 流气流会 产生独特 的声音 吸气时气道变宽，空气 能通过异物与气道空隙, 但在呼气时气道狭窄引 起气体潴留 单向阀让空气只进不出 湍流气流通过 狭窄的上呼吸 喉刺激 声带振动受损 空气进入 道à刺耳， 量↓，肺 高调呼吸音 部无法充 分通气 吸气性喘 焦躁不安，用 声音嘶哑 鸣音 力呼吸 呼气相喘 呼气相X线提 呼吸音 息: 听诊可 示单侧肺过度 减弱 闻及 充气 图注: 病理生理 体制 体征/症状/实验室检查 并发症 2013年5月29日发布于 www.thecalgaryguide.com

囊性纤维化-发病机理临床表现及并发症

囊性纤维化: 发病机理, 临床表现及并发症 第7号染色体上的囊性纤维化跨膜传导调节因子(CFTR)基因突变à 囊性纤维化跨膜传导调节( CFTR )蛋白 (一种表达在外分泌组织中的氯离子通道蛋白)功能紊乱 作者: Spencer Montgomery 审稿人: Yan Yu, Kayla Nelson, Mark Montgomery* 译者: Huiting Wang (王慧婷), Yang Xiang (向阳) 翻译审稿人:Ran zhong (钟然), Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) *发表时担任临床医生 异常氯离子通道蛋白影响Cl-跨膜运输 注意: • CFTR突变呈常染色体隐性遗传 • 已知有> 1700种不同CFTR基因突变类型, ∆F508突变占了高加索人群发病总 数的67% • 囊性纤维化的诊断依据:汗液氯离子浓度↑, CFTR基因突变 & ≥1个相关内 在汗腺中， CFTR蛋白主要 功能为Cl-重吸收 重吸收↓ =汗 液中Cl- 浓度↑ 汗液中Cl- 浓度↑ 在母体 子宫内 输精管 中肾管、输精 管及相关结构 退行性变 男性不育 在身体其他部位的管道上皮组织中， CFTR蛋白促进 Cl- 扩散到分泌物中 外周纤毛液体层Cl- ↓ → 外周纤毛液 体层的含水量↓ 黏液-纤毛系统清除分泌物↓ 分泌物异常聚集并阻塞全身各处的 分泌管腔 下呼吸道 脏有器官系统的 临床症状 儿童/成人: 远端肠梗阻综合征(DIOS) 胃肠道 胆道系统 鼻息肉 胃肠道内容 物蠕动↓ 新生儿: 胎粪性 肠梗阻 胎粪潴留↑→ 肝硬化 & 门静脉高压 新生儿黄疸 胆红素重吸收↑ 时间延长 胆汁排出延迟 →肝炎症反应 上呼吸道 胰腺 淤积在胰腺内 的消化酶消化 胰腺自身 炎症 ;瘢痕增生 & 脂肪组织渗 透 ; 胰岛细胞 受损 II型糖尿病 慢性湿咳 诊断肺部阻塞标志: i.e. 肺过度充气(X线), 肺功能检测异常 鼻窦内分泌 胰腺分泌的消化酶无法进入 物潴留 → 细 胃肠道中 (胰液不足) 分泌物在气道内潴留→ 细菌增殖à 气道感染 & 炎症 持续呼吸道感染可进展为慢性支气管炎 ± 支气管扩张(囊性纤维化最主要的死亡原因) 菌增殖 慢性鼻窦炎 脂质和蛋白 脂溶性维生素吸收 质吸收不良 ↓ 发育不良 血清Vit. D ↓ 骨质疏松症 图注: 病理生理 机制 体征/症状/实验室检查 并发症 2013年1月21日发布于 www.thecalgaryguide.com

哮吼-发病机制和临床表现

哮吼:发病机制和临床表现 病原体最初定植在鼻咽 黏膜，最常见病原体为 副流感病毒 1 病原体向下迁移到咽 喉、气管，引起该处 呼吸道内皮炎症 儿童气管壁柔软， 因而更容易塌陷 Notes: 哮吼亦称为咽喉气管支气管炎 好发于3个月到3岁之间的儿童， 集中于秋冬季发生 炎症细胞因 子释放 鼻黏膜毛细血 管通透性↑ 蛋白质和液 鼻黏膜肿 体渗出到周 胀和易激 围组织 鼻炎样症状: 分泌鼻粘液 鼻塞 发热 声嘶 全身炎症细胞因子导致下丘脑体温调节紊乱 引起类似于鼻咽粘膜的 反应:蛋白质和液体渗 出到周围组织 气管周围组织肿胀 气管变窄 咽喉肿胀刺激声带 狭窄的管道(如气管 )导致管道内流速↑以 及压力↓ (Bernoulli's principle伯努利原理) 真空的产生， 使得狭窄处远 端气道塌陷 气流通过狭窄的气管 会产生湍流，从而发 出独特的声音 肺通气做功↑ 用力呼气: 吸气: “犬吠样”咳嗽 喘鸣: 刺耳、高音调 的声音 呼吸窘迫: (动用辅助呼吸肌, 鼻翼煽动, 胸壁凹陷), 呼吸急促 作者: Nick Baldwin 审稿人: Jody Platt, Elizabeth de Klerk, Yan Yu, Naminder Sandhu* 译者:Yonglin Mai (麦泳琳) 翻译审稿人:Zesheng Ye (叶泽生) *发表时担任临床医生 图注: 病理生理 机制 体征/症状/实验室结果 并发症 2013年5月28日发布于 www.thecalgaryguide.com

世界卫生组织对治疗covid-19新型冠状病毒肺炎的药物研

世界卫生组织对治疗COVID-19(新型冠状病毒肺炎)的药物研 作者: Hannah Yaphe 审稿人: Davis Maclean, Timothy Fu, Yan Yu*, Stephen Vaughan* 译者: Zesheng Ye (叶泽生) 翻译审稿人: Zihong Xie (谢梓泓) * 发表时担任临床医生 注:此幻灯片基于截至 2020年3月30日的文献。 此处展示的药物是世卫 组织联合试验中涉及到 的药物，这些药物是根 据体外工作和MERS和 SARS的临床数据选择的。 机制研究尚处于初步阶 段，现并无足够的数据 支持或驳斥这些药物对 COVID-19的作用。研究 目前仍在进行中。 病毒复制 被终止 更少细胞被感染 炎症反应及免疫 反应的激活↓ 感染的临床症 状得以改善* *See slide on pathophysiology and clinical findings of COVID19 究:假设作用机制 COVID-19 病毒复制途径 病毒与人体细胞表面的血管 紧张素转换酶2 (ACE-2)受体 结合 病毒被网格蛋白包被形成囊 泡，通过内吞作用进入细胞 囊泡通过内溶酶体途径成熟 病毒膜与成熟内溶酶体融合， 将病毒RNA释放到细胞质中 病毒RNA利用宿主细胞核糖 体合成新的病毒蛋白质，如 RNA聚合酶 病毒RNA聚合酶与宿主 细胞的核苷酸结合 新病毒RNA产生 氯喹或羟氯喹 (CQ, HCQ) 弱碱性导致内体及 溶酶体内的pH值↑ 高尔基体中 ACE-2的N端糖 基化受抑制 细胞表面表达的 ACE-2受体结构 异常 病毒膜无法与未 成熟内体结合 病毒和ACE-2受 体结合受影响， 阻断病毒进入人 体宿主细胞 病毒内含物 无法释放 内体成 熟障碍 干扰素-β (IFNβ) (联合洛匹那韦/ 利托那韦) 利托那韦 (RTV) (联合洛匹那韦) 抑制CYP450(一 种药物代谢酶) 激活 JAK/STA IFN-调控 与干扰素 受体结合 (机制尚未明确) 瑞德西韦 (RDV) 瑞德西韦磷酸化成 三磷酸-瑞德西韦 (RDV-TP) 洛匹那韦 (LPV) LPV在血浆中半衰 抑制病毒3-糜蛋白酶 熟的病毒蛋白 T通路 基因转录 可能使LPV/RTV的抗病毒作用↑ 抗病毒和免疫调节 蛋白的表达↑ 抑制病毒复制(多种机制) RDV-TP与ATP 竞争性结合 病毒的RNA聚 合酶 RDV-TP的掺 入终止了延 长中的RNA 洛匹那韦(LPV) 的降解速度↓ 病毒蛋白前体 无法切割为成 病毒RNA及蛋白质组装成新 新形成的 的病毒颗粒 病毒颗粒 无法感染 新的细胞 病毒颗粒从细胞中释放出来 期及作用时间↑ 样蛋白酶 图注: 病理生理 机制 体征/症状/实验室检查 并发症 2020年3月30日发布于 www.thecalgaryguide.com

肺高血压-病理生理特点和临床表现

肺高血压: 病理生理特点和临床表现 作者: Grant E. MacKinnon, Davis Maclean, Hannah Yaphe 审稿人: Yan Yu*, Jason Weatherald* 译者:Jieling Ma (马杰羚) 翻译审稿人: Yonglin Mai (麦泳琳) * 发表时担任临床医生 左心疾病(心力衰竭,心肌梗死) 心肌收缩能力 和/ 或舒张能力↓ 左心室心输出量 ↓ 左心(心室、心房)血液充盈，充盈压升高 肺血管血液充盈，压力升高 肺毛细血管楔压↑– 估测左心房压力 慢性贫血 血浆血红蛋白↓ 单位血液携氧能力 ↓ 心率代偿性 ↑， 以维持组织供氧 肺部疾病(慢性阻塞性肺疾病) 肺组织损失 ，肺弹性↓ 肺通气表面 积↓à气体 交换↓ 慢性血栓栓塞 肺血管疾病(肺动脉 高压, 硬皮病) 肺通气能 力↓ 血管阻塞/纤维化 慢性低氧血症 局部肺泡氧分压↓ 肺动脉血压力↑ 肺高血压 右心室后负荷↑ (心脏收缩射 血所承受的压力) 右室心输出量↓ 心脏收缩后右心剩余容积↑ 体循环淤血 静脉系统血容量↑ 毛细血管血容量↑及压力↑ 液体从血管进入组织间隙 血管顺应性↓ 肺血管发生局部反应性 血管收缩，将血液分配 到通气较好的区域 血管壁增厚， 气体交换受损 血氧分压↓， 二 氧化碳分压↑ 组织中氧气供应不足， 二氧化碳清除不足 心输出量↑ 慢性压力↑–血 管纤维化 左心循环血量↓， 左室充盈↓ 左心室输出量↓ 肺血管阻力↑ (PVR) 随病程进展，发生心肌 肥厚(向心性&偏心性) 心脏体积↑ 心肌需氧量↑ 心肌缺血(供/需不匹配) 当需氧量↑时， 胸痛风险↑ 外周水肿 心脏异常传导 通路和异位起 搏点形成 心律失常 心悸 组织灌注↓ 乏力 脑组织灌注↓ 晕厥 反射性触发代偿性深、 呼吸困难 快呼吸 t 图u : 注 : 病理生理学 发病机制 体征/症状/实验室检查 并发症 2020年9月8日发布于 www.thecalgaryguide.com

gastroenteritis-patogenesis-y-hallazgos-clinicos

Gastroenteritis: Patogénesis y hallazgos clínicos Autor: Nicholas Monfries Revisores: Charissa Chen Dr. Lindsay Long* Dr. Naminder Sandhu* * MD en el momento de la publicación Traducción: Anagabriela Duarte María Rosario Talavera* Virus (70%) Rotavirus, norovirus, adenovirus, astrovirus, enterovirus Bacterias (10-20%) Campylobacter jejuni, Salmonella spp, Escherichia coli, Shigella, Yersinia, Vibrio cholerae Infiltración patógena del tracto gastrointestinal Otros (<10%) Cryptosporidium, Giardia lamblia, Entamoeba histolytica, Strongyloides Notas: • La edad más frecuente para la gastroenteritis abarca de los 6 meses a los 2 años. • La diseminación de la infección se produce por las vías respiratoria y fecal-oral. Estímulos nocivos e inflamación del tracto gastrointestinal Estimulación de nervios viscerales aferentes Dolor abdominal Notas: • Diarrea = aumento de la frecuencia y disminución de la consistencia de las heces, típicamente evacuación de ≥3 heces blandas/acuosas por día. • Los mecanismos exactos para cada hallazgo clínico son probablemente multifactoriales y pueden variar según el patógeno involucrado. ** Las toxinas patógenas estimulan la secreción entérica de cloruro Interacción patogénica con el sistema nervioso entérico Alteración de la actividad y/o estructura del borde en cepillo Deterioro de la absorción de sustancias en el intestino delgado Sustancias osmóticamente activas ingresan al intestino grueso Capacidad de reabsorción de agua en el intestino grueso es sobrepasada Liberación de 5HT por las células enterocromafines Estimulación de la zona de activación de los quimiorreceptores (área postrema) Estimulación del centro del vómito (formación reticular lateral) Náuseas/Vómitos ↑ Secreción del líquido GI Diarrea *mecanismo propuesto, mecanismo exacto desconocido Leyenda: Patofisiología Mecanismo Signos/Síntomas/Hallazgos de Laboratorio Complicaciones Publicado el 28 Agosto, 2015 en www.thecalgaryguide.com

faringitis-por-estreptococo-del-grupo-a-patogenesis-y-hallazgos-clinicos

Faringitis por Estreptococo del Grupo A : Patogénesis y hallazgos clínicos Infección Estreptococo del Grupo A GAS libera exotoxinas tales como5: Autor: Jason An Revisores: Riley Hartmann Amanda Ang Haotian Wang Stephen Vaughan* * MD en el momento de la publicación Traducción: Anagabriela Duarte María Rosario Talavera* Estreptolisina-O Entra en la circulación sistémica Se une al colesterol en las membranas de las células epiteliales Forma agregados tóxicos Lisis celular osmótica y respuesta inflamatoria local Exantema escarlatiniforme4 Las adhesinas incluyendo el ácido lipoteicoico y la proteína M de la pared celular del GAS facilitan la adherencia regional a las células epiteliales faríngeas SPE A, B y C, y SSA Actúan como superantígenos y estimulan a las células T para que liberen citocinas (IL1 / 6, FNTα / β, IFN-γ) Lesión celular inadvertida y hemólisis Petequias palatinas + Eritema Abreviaciones: GAS – Estreptococo del Grupo A IL – Interleucina IFN – Interferón SPE –Exotoxina Pirogénica Estreptocócica SSA – Superantígeno estreptocócico FNT –Factor de Necrosis Tumoral GB – Glóbulos Blancos Estimulan a las células mononucleares1 Liberación de IL-1 Estimula el centro de control de temperatura hipotalámico Fiebre ↑ drenaje linfático a los ganglios regionales Ganglios cervicales anteriores sensibles y agrandados>1cm Liberación de FNTα Facilta la infiltración de GB en el sitio de infección Liberación de moduladores endoteliales2 ↑separación entre las células endoteliales Líquido y proteínas de los vasos se filtran al espacio intersticial Edema faríngeo Notas 1. También conocidos como agranulocitos, incluidos los leucocitos que comprenden linfocitos, macrófagos y monocitos. 2. Histamina, bradicinina, sustancia P, leucotrienos. 3. Proceso sofisticado y multifacético que involucra la fagocitosis de bacterias por macrófagos y la posterior destrucción por exposición a radicales libres, así como a compuestos bactericidas como lactoferrina, elastasa y lisozimas producidas dentro de los macrófagos. 4. Erupción papular fina descrita clásicamente como

hipersensibilidad-tipo-i-patogenesis-y-hallazgos-clinicos

Celulitis

Celulitis: Patogénesis, hallazgos clínicos y complicaciones Autores: Tegan Evans, Spencer Yakaback Revisores: Brian Rankin, Timothy Fu, Laurie Parsons*, Yan Yu* * MD en el momento de la publicación Traducción: Anagabriela Duarte María Rosario Talavera* Piel agrietada Cirugía Inoculación directa (e.j., trauma) Organismos penetran los vasos sanguíneos Bacteremia (presencia de bacterias en sangre) Piel normal Capa epidérmica Unión dérmica- epidérmica Capa dérmica Grasa subcutánea Flora cutánea residente: Staphylococcus coagulasa negativos* Flora cutánea transitoria: Staphylococcus aureus* Streptococcus pyogenes Bacterias gram negativas Hongos Patógeno en dermis profunda y grasa subcutánea *patógenos más comunes Rotura de la barrera cutánea (puede que no sea evidente) y entrada de patógenos Virulencia del organismo supera los mecanismos de defensa del huésped (asociado a los factores de riesgo) Celulitis: Una infección bacteriana en la que los patógenos penetran la dermis profunda y/o la grasa subcutánea Citocinas activan la respuesta inmune Acumulación de pus (bacterias, glóbulos blancos, piel muerta) Formación de abscesos Factores de riesgo: Huésped inmunodeprimido: -Diabetes mellitus+ -Linfedema -Desnutrición -Paciente adulto mayor+ -Obesidad+ -Enfermedad vascular periférica Riesgo de infección general: -Historia de celulitis+ +factores de riesgo mayores Factores de riesgo para celulitis por SARM: Mayor exposición a SARM: -Deportes de contacto -Hacinamiento -Trabajadores de la salud -Ascendencia indígena -Compartir toallas, equipos Mayor susceptibilidad: -Inmunodeficiencia -Edad temprana Infección se propaga a los ganglios linfáticos cercanos Linfadenitis infección se propaga a través de los vasos linfáticos Linfangitis ascendente Respuesta inflamatoria local en la piel Diseminación a distancia en endocardio (revestimiento interno de las cámaras y válvulas del corazón) Endocarditis SARM: Staphylococcus aureus resistente a meticilina Dolor Calor Fiebre Malestar Diseminación a distancia en el hueso Osteomielitis Escalofríos Inflamación sistémica Edema Eritema (enrojecimiento) con márgenes indefinidos Vesículas y ampollas (poco frecuente) Sepsis Abreviaturas: Leyenda: Patofisiología Mecanismo Signos/Síntomas/Hallazgos de Laboratorio Complicaciones Publicado el 27 Septiembre, 2020 en www.thecalgaryguide.com

Inmunidad Humoral

Inmunidad Humoral: Patogénesis y hallazgos clínicos Autor: Erin Stephenson Revisores: Jessica Tjong Crystal Liu Yan Yu* Nicola Wright* *MD en el momento de la publicación Traducción: Anagabriela Duarte María Rosario Talavera* Células B de memoria son detectores de larga duración Células B de memoria secuestradas en sitios de almacenamiento (e.j., ganglios linfáticos, bazo) o circulan en la sangre Células B de memoria proliferan y se diferencian en células plasmáticas en respuesta a la reexposición al antígeno. ↑ Tasa y amplitud de la respuesta inmune secundaria en exposiciones repetidas Antígenos (Ag) son producidos por los patógenos (bacterias, virus, hongos, parásitos) o el paciente (a través de traumatismos, tumores, metabolismo), y circulan en el plasma, linfa u otros tejidos Expansión clonal (proliferación de células B activadas) ↑ GB (linfocitosis) Enfermedad autoinmune si células B reconocen autoantígeno Diferenciación (en células B de memoria o células plasmáticas) Células plasmáticas producen anticuerpos, que contribuyen a la inmunidad de 3 formas: Opsonización: Los Acs recubren a los patógenos, ayudando al reconocimiento por los fagocitos Neutralización: Acs se unen a las moléculas de superficie de los patógenos que se necesitan para invadir las células del huésped, neutralizándolas Activación del complemento: Acs activan las proteínas del complemento a través de la vía clásica (consulte la diapositiva de Activación del complemento) Eliminación de patógeno por la respuesta inmune adaptativa Ag dependiente de células T: Las células presentadoras de Ag (como las células dendríticas o los macrófagos) presentan el Ag a las células T auxiliares CD4+ y las activan. Las células T colaboradoras activadas luego estimulan a las células B Ag independiente de células T: Ags como péptidos, carbohidratos y lípidos pueden ser reconocidos directamente por las células B, lo que desencadena su activación Complemento: Proteínas del complemento circulantes en el plasma detectan y se unen a Ag. Los Ags marcados con el fragmento C3 del complemento se unen al complejo correceptor de las células B y mejoran la activación de las células B. Abreviaturas: Ac – Anticuerpo Ag – Antígeno Ig – Inmunoglobulina GB – Glóbulos blancos Células B vírgenes Células plasmáticas producen primero IgM Citocinas y células T estimulan el cambio de clase de Ig de las células B (cambiando las regiones constantes de la cadena pesada de la molécula de Ig) La producción de Ig cambia de IgM a IgG, IgA, IgE o IgD IgG es la Ig más común en las reacciones inmunes. La IgA se concentra en la mucosa, la IgE desgranula a los mastocitos, la IgD ayuda a las células B maduras. Células B activadas (en órganos linfoides secundarios, como el bazo o los ganglios linfáticos) ↑ Ig plasmática Leyenda: Patofisiología Mecanismo Signos/Síntomas/Hallazgos de laboratorio Complicaciones Publicado el 2 Mayo, 2020 en www.thecalgaryguide.com

impetigo-patogenesis-y-hallazgos-clinicos

Impétigo: Patogénesis y hallazgos clínicos Infección de la epidermis superficial Autor: Taylor Woo Revisores: Gurleen Chahal Usama Malik Laurie M. Parsons* * MD en el momento de la publicación Traducción: Anagabriela Duarte María Rosario Talavera* Temprano: pequeñas vesículas que progresan hacia ampollas superficiales Tardío: ampollas flácidas grandes de base eritematosa con

cascada-inflamatoria-patogenesis-y-hallazgos-clinicos

Cascada inflamatoria: Patogénesis y hallazgos clínicos Autor: Heather Yong Revisores: MeghanJackson Sean Doherty Dr. Luis Murguia Favela* * MD en el momento de la publicación Traducción: Anagabriela Duarte María Rosario Talavera* Células endoteliales alteradas liberan factores inductores de leucocitosis ↑ GB circulantes Nota: La cascada inflamatoria es una respuesta inespecífica a todos los patógenos extraños y traumas. Abreviaturas: IL’s: Interleucinas GB: Glóbulos blancos FNT: Factor de necrosis tumoral Mastocitos en el sitio de la lesión liberan histamina Ruptura de la barrera física y celular (e.j. punción cutánea) Activación de la respuesta inmune en el sitio de la lesión Células endoteliales alteradas liberan citocinas proinflamatorias (e.j., IL’s, FNTα) y quimiocinas ↑ Permeabilidad vascular: extravasación de células inmunitarias/mediadores (e.j., GB, proteínas del complemento, plaquetas) Vasodilatación: ↑ flujo sanguíneo al sitio lesionado Quimiotaxis: células inmunes migran al sitio de la lesión Signos cardinales de la respuesta inflamatoria Enrojecimiento (rubor) ↑Temperatura local (calor) Continuación Inmunidad innata Dolor (dolor) Tumefacción (tumor) Activación de la inmunidad adquirida Fagocitosis: (*mecanismo principal) neutrófilos y macrófagos engullen patógenos extraños y tejido muerto Pus Sistema complemento: opsonización del patógeno (marcado para ser destruido), promueve inflamación Células Natural Killer: ruptura de la pared mediada por perforinas (orificios), destrucción mediada por enzimas Humoral: (Respuesta de células B) producción de anticuerpos, activación del sistema del complemento Mediada por células: (Respuesta de células T) ↑ actividad de células ayudadoras y células citotóxicas Nota: células dendríticas en el sitio de la lesión ayudan en la fagocitosis y la presentación de antígenos a las células T. Leyenda: Patofisiología Mecanismo Signos/Síntomas/Hallazgos de laboratorio Complicaciones Publicado el 14 Diciembre, 2018 en www.thecalgaryguide.com

respuesta-inmune-innata-patogenesis-y-hallazgos-clinicos

Respuesta inmune innata: Patogénesis y hallazgos clínicos Autor: Erin Stephenson Revisores: Jessica Tjong Crystal Liu Nicola Wright* * MD en el momento de la publicación Traducción: Anagabriela Duarte María Rosario Talavera* Patógenos superan las barreras químicas (e.j., lisozima, pH bajo) Patógenos superan las barreras físicas (e.j., epitelio, cilios) Patrones moleculares asociados a patógenos Trauma Patrones moleculares asociados a daños Ejemplos de macrófagos tisulares: • Macrófagos alveolares– Pulmón • Histiocitos – Tejido conectivo • Células de Kupffer – Hígado • Células mesangiales– Riñón • Células microgliales– Cerebro • Osteoclastos – Hueso Microbio es envuelto y expuesto al estallido respiratorio Microbios destruidos Pus Reconocimiento por receptores de reconocimiento de patrones (e.j., receptores tipo toll) Quimiocinas proinflamatorias Reclutamiento de granulocitos y monocitos circulantes Citoquinas proinflamatorias (e.j., IL- 1β, TNFα, IL-6) Activación de macrófagos tisulares Proteínas antimicrobianas Infección/inflamación no resuelta Antígeno es presentado a las células T Reclutamiento de la respuesta inmune adaptativa Respuestas immunes mejoradas Producción hepática de proteína de fase aguda (es decir, proteína C reactiva) Producción de prostaglandinas en el hipotálamo Fiebre Ruptura de las uniones estrechas de las células endolteliales de la vasculatura Fuga de líquido intravascular al espacio extravascular Edema Leyenda: Patofisiología Mecanismo Signos/Síntomas/Hallazgos de laboratorio Complicaciones Publicado el 19 Enero, 2020 en www.thecalgaryguide.com

serologia-vhb-principios-basicos-e-interpretacion-de-patrones

hepatitis-viral-patogenesis-y-hallazgos-clinicos

infeccion-por-hepatitis-a-vha-explicacion-de-los-patrones-serologicos

infeccion-por-hepatitis-c-vhc-explicacion-de-los-patrones-serologicos

fiebre-reumatica-aguda-patogenesis-y-hallazgos-clinicos

hemorroides-patogenesis-y-hallazgos-clinicos

sangrado-gi-bajo-patogenesis-y-hallazgos-clinicos

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gastro-duodenale-ulkuskrankheit-pathogenese-und-klinische-befunde

rechtsherzinsuffizienz-pathogenese-und-klinische-befunde

linksherzinsuffizienz-korperliche-untersuchungsbefunde

linksherzinsuffizienz-klinische-befunde

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copd-klinische-befunde

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leberzirrhose-pathogenese-und-komplikationen

local-anesthetics-lidocaine-bupivacaine-ropivacaine-procaine-cocaine-mechanism-of-action-and-pharmacodynamics

Local Anesthetics (Lidocaine, Bupivacaine, Ropivacaine, Procaine, Cocaine): Mechanism of Action and Pharmacodynamics Ester Class Cocaine Local Anesthetics Lidocaine Local infiltration of the drug in tissue Amide Class Ropivacaine Authors: Evan Allarie Yan Yu* Reviewers: Stephen Chrusch Wendy Yao Brooke Fallis Melinda Davis* * MD at time of publication These traits enable the anesthetic to be highly lipophilicà↑ anesthetic diffusion through nerve sheaths ↑ anesthetic potency Anesthetics’ effect differ based on neuronal features. For instance: comparing small diameter unmyelinated nociceptive neuron vs. larger diameter myelinated motor neurons: Procaine Bupivacaine Addition of a vasoconstrictor (e.g. epinephrine) to the anesthetic solution Local vasoconstriction at site of anesthetic infiltration Aliphatic side chains and lipophilic linkages High Molecular Weight ↓ systemic absorption of the anesthetic ↓ side effects Larger amounts of local anesthetic can be safely administered ↑ anesthesia duration ↓ bleeding at site of infiltration ↑ pH of injected solution (e.g. adding sodium bicarbonate) ↓ pKa of local anestheticà↑ in unprotonated form of local anesthetic ↑ uptake of anesthetic into neurons Short onset time When the molecule’s tertiary amine is in its unprotonated form, the anesthetic is lipophilic and is able to diffuse across nerve cell lipid membranes Anesthetic molecule becomes protonated within the neuron Protonated form of anesthetic binds to transmembrane sodium channel Sodium channels become impermeable to sodium ions, preventing sodium movement across the membrane ↓ nociceptive neuronal depolarization ↓ Pain sensation Small diameter = fewer sodium channels for anesthetic to inhibit Unmyelinated = anesthetic free to diffuse anywhere along neuron Differential nerve blockade Pain sensation is blocked much more quickly than motor function Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 4, 2021 on www.thecalgaryguide.com

local-anesthetics-lidocaine-bupivacaine-ropivacaine-procaine-cocaine-side-effects-and-complications

Local Anesthetics (Lidocaine, Bupivacaine, Ropivacaine, Procaine, Cocaine): Side Effects and Complications Cocaine Procaine Ropivacaine Bupivacaine Amide Class Lidocaine Authors: Evan Allarie Yan Yu* Reviewers: Stephen Chrusch Wendy Yao Brooke Fallis Melinda Davis* * MD at time of publication Ester Class Both classes share a similar molecular structure, containing a lipophilic (hydrophobic) aromatic ring and a hydrophilic tertiary amine, making them amphipathic molecules (possessing both hydrophobic and hydrophilic components) Local infiltration of the drug into tissue Ester local anesthetics have a carboxylic ester bond between the aromatic ring and tertiary amine Metabolized by plasma cholinesterases If the patient is afflicted with atypical pseudocholinesterase or pseudocholinesterase deficiency, this condition will impair breakdown of ester local anesthetics Amide local anesthetics have an amide bond between the aromatic ring and tertiary amine Metabolized in liver by hepatic enzymes If the patient is afflicted with liver disease, this condition will impair breakdown of amide local anesthetics Local anesthetic can diffuse into sympathetic nervesàblocks sodium channels on neuronal membranes, inhibiting sympathetic nerve function ↓ vasoconstrictive signals to vascular smooth muscle Vasodilation of systemic arteries Hypotension Some local anesthetic can enter systemic circulation and physically reach the heart Anesthetic molecule will block ion channels on cardiac myocytes If enough anesthetic reaches cardiac myocytes, their action will ↓ myocardial electrical signalling and thus ↓ cardiac rhythm and contractility Prolonged clearance and ↑ duration of anesthetic blockade Cardiac Arrest Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 4, 2021 on www.thecalgaryguide.com

Psuedocholinesterase Deficiency

Pseudocholinesterase Deficiency: Pathophysiology and Anesthetic Considerations Drugs (anticholinesterases) Break down or inhibit the pseudocholinesterase enzymeà↓ pseudo- cholinesterase activity Note: Pseudocholinesterase has many synonymous names including butyrylcholinesterase, BChE, BuChE, plasma esterase, plasma cholinesterase, and serum cholinesterase Malignancy Abnormal gene expressionà↓ protein synthesis Acquired Liver disease ↓ liver’s ability to synthesize proteins Malnutrition ↓ molecular precursors for protein production Renal Disease Mechanism unclear Fluid Overload Hemodilution of circulating proteins Hereditary BChE (Butyrylcholinesterase) gene mutation ↓ production or production of non-functional pseudo- cholinesterase by the liver ↓ synthesis of pseudocholinesterase by the liver Pseudocholinesterase Deficiency: reduced levels of functional pseudocholinesterase in plasma and tissues Impaired ability to hydrolyze ester linkages of substrates like neuromuscular blocking agents (e.g. succinylcholine, mivacurium, diamorphine, acetylsalicylic acid, methylprednisolone, cocaine, heroin ) Prolonged binding of neuromuscular blocking agent to nicotinic cholinergic receptors in neuromuscular junctions ↑ patient’s susceptibility to side effects from drugs with ester linkages Mivacurium administered to produce muscle paralysis Succinylcholine administered to produce muscle paralysis Competitively binds to acetylcholine nicotinic receptor Irreversibly binds to acetylcholine nicotinic receptor Active site of post-synaptic acetylcholine receptor is blocked Continuous depolarization of skeletal muscle Acetylcholine cannot act on receptor = skeletal muscle can’t depolarize Skeletal muscle unable to repolarize Skeletal muscle paralysis Acetylcholine released cannot trigger an action potential ↑ duration of muscle fiber paralysis Since respiratory muscles are affectedà Apnea requiring sedation and respiratory assistance for up to several hours Extended paralysis and/or anesthesia Authors: Evan Allarie Yan Yu* Reviewers: Stephen Chrusch Brooke Fallis Melinda Davis* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 4, 2021 on www.thecalgaryguide.com

chronic-hypertension-complications

Chronic Hypertension: Complications Chronic Hypertension Long term Blood Pressure (BP) ≥ 135/85 (on ambulatory or home blood pressure measurement) in patients without diabetes, or BP ≥ 130/80 in patients with diabetes Authors: Samin Dolatabadi, Yan Yu* Reviewers: Meena Assad, Jessica Krahn Juliya Hemmett* * MD at time of publication ↑ Afterloadà ↑ Resistance to left ventricle ejection To overcome resistance and preserve cardiac output, the myocardium undergoes structural and functional changes Left ventricular hypertrophy and fibrosis Stiff ventricle ↓ Contractility of the left ventricle Impaired forward flow of blood from heart Chronic stress on the endothelium of systemic blood vessels ↑ Blood pressure in retinal circulation Hypertensive Retinopathy (See slide on Chronic Hypertensive Retinopathy: Pathogenesis and Clinic Findings) Smooth muscle of kidney’s afferent arterioles constricts to prevent transmission of ↑ blood pressure to glomerulus Overtime, smooth muscles of afferent arterioles hypertrophy from prolonged vasoconstriction Chronic stress and trauma on endothelial and smooth muscle cells of kidney Injury leads to excretion of cytokines and extracellular matrix such as fibrin and collagen into subendothelial layer Endothelial dysfunction (See slide on Atherosclerosis: Pathogenesis) Atherosclerosis Loss of normal arterial architecture in the brain due to stress of ↑ blood pressure Weakening of cerebral arteries Formation and rupture of microaneurysms Intracerebral Hemorrhage Accumulation of plaques in the walls of cerebral arteries ↓ Cerebral blood flow Ischemic Stroke Accumulation of plaques in the walls of coronary arteries ↓ Myocardial blood flow Oxygen supply- demand mismatch Coronary Artery Disease Thickening of arteriolar wall and narrowing of afferent arterioles ↓ Glomerular blood flow Glomerular and tubular ischemia Glomerular sclerosis and tubular atrophy Blood backs up into lungs ↓ perfusion of blood throughout the bodyà inability of the heart to meet metabolic demands Congestive Heart Failure Hypertensive Nephrosclerosis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 4, 2021 on www.thecalgaryguide.com

Primary Aldosteronism Pathogenesis

Primary Aldosteronism: Pathogenesis and clinical findings Unilateral aldosterone producing adenoma Benign tumours of the adrenal glands develop ion channel mutations ↑ Na+ movement into adrenal gland cellsàcell depolarizationà↑ Ca+ entry into zona glomerulosa Bilateral adrenal hyperplasia Unknown mechanisms cause bilateral adrenal hyperplasia of the zona glomerulosa ↑ Ca+ leads to cellular replication and hyperplasia of the zona glomerulosaà ↑aldosterone release Adrenocortical carcinoma Abnormal and excessive growth of the zona glomerulosa (neoplasia)à↑ aldosterone Overproduction of aldosterone, independent from renin-angiotensin- aldosterone system (RAAS) Ectopic aldosterone secreting tumor adrenocortical tissue outside of the adrenal glands produce aldosterone Familial hyperaldosteronism (FH) Type I Rare mutation causing ACTH- sensitive aldosterone production in the zona fasciculata Aldosterone binds its receptor on the principal cells located in the collecting duct of the kidney ↑ Na+ and K+ channel insertion on luminal surface of the principal cell and ↑ Na/K ATPase activity on basolateral surface Na+ follows the concentration gradient and moves into the principal cell cytoplasmàK+ moves into the collecting duct to maintain electroneutrality Aldosterone binds its receptor on the alpha intercalated cells located in the late distal tubule and collecting duct of the kidney ↑ H+ ATPase and Na/H+ ATPase activity on the luminal surface of alpha intercalated cellsà↑ H+ excretion H+ loss permits HCO3- to move down the electrochemical gradient across the luminal surfaceà↑ HCO3- resorption into peritubular capillaries Metabolic alkalosis K+ efflux (or hypokalemia of any etiology) is counterbalanced by influx of H+ into tubular cells to maintain electroneutrality ↓ pH in tubular cells activates glutaminase (a pH dependent enzyme) generating glutamate from glutamine Glutamate within renal tubules dissociates into NH4+, HCO3- Intracellular acidosis within tubular cells Disrupted cellular signaling within the collecting duct results in reduced APQ2 translocation to luminal surface Authors: Kyle Moxham Reviewers: Emily Wildman Austin Laing Yan Yu* Matthew Harding* * MD at time of publication Hypertension ↑ Na+ reabsorption H2O follows active reabsorption of solute into circulationà ↑ effective arterial blood volume (EABV) Chronic EABV expansion resets hypothalamic osmotic sensitive ADH releaseàdecreased ADH production ↑ K+ excretion Hypokalemia (see our Hypokalemia: Clinical Findings Slide) ↓ Na+ delivery to macula densa in the distal convoluted tubule ↓Endogenous renin secretion by juxtaglomerular apparatus while aldosterone continues to be independently produced Polydipsia & Polyuria Mild hypernatremia ↓ Renin: Aldosterone ratio Nephrogenic diabetes insipidus: ↓ urinary concentrating ability Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 4, 2021 on www.thecalgaryguide.com

Asthma clinical findings

Asthma: Clinical Findings Asthma Episodic airway constriction and airflow obstruction, due to hyper- responsiveness to certain triggers (see slide on asthma pathogenesis) Author: Yan Yu Reviewers: Jason Baserman Jennifer Au Yonoglin Mai (麦泳琳) Naushad Hirani* * MD at time of publication Variable, sporadic airway obstruction in response to triggers Associated allergic eosinophil response Eosinophils infiltrate: Skin If severe: ↓ ventilation of alveoli ↓ oxygenation of blood (hypoxemia) During expiration, positive pleural pressure squeezes on airwaysà↑↑ airway obstruction Heart rate ­ to improve perfusion of tissue Tachycardia Respiratory centers ­ rate of breathing to compensate Tachypnea Gas is trapped within alveolià hyperinflates lungs Ventilating larger lungs needs more effort Patients need to voluntarily contract their expiratory muscles faster and more forcefully to effectively expire Narrower airways àturbulent airflow, heard on auscultation Expiratory Wheeze (high-pitched expiratory sound) Nose Rhinitis/ sinusitis Runny nose, sneezing, etc Atopic dermatitis Skin rash, hives Eyes Conjunctivitis Red itchy eyes, visual blurring Episodic dyspnea (shortness of breath) Chest tightness During severe attacks: Note: Asthma attacks often have two phases: • An immediate attack (within 0-2 hours of the trigger, due to acute release of histamine from mast cells) • A delayed attack (due to eosinophil infiltration of airways, presents within 3-4 hours after exposure to the trigger, peaks within 6-8 hours, and resolves within 24 hours). Keep the possibility of a delayed attack in mind when treating patients in Emergency! Note: Symptoms often worse at night or early in the morning. Note: Asthma should be suspected in children experiencing dyspnea with multiple episodes of Upper Respiratory Tract Infections or Croup. Patient compensates by activating accessory respiratory muscles to ↑ thoracic volume Visible contraction of neck muscles (Scalene, sternocleidomastoids) ↑↑↑ airway obstruction on expiration, lungs take more time to empty Prolonged expiratory phase of breathing Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Dec 17, 2012 and updated Dec 4, 2021 on www.thecalgaryguide.com

Chronic Cough Pathogenesis_2021

Chronic Cough: Pathogenesis ACE Inhibitors Protussive mediator accumulation (bradykinin, substance P) Infection IP; likely chronic ↑ cough receptors commonly pertussis- related or post-viral Asthma ↑ EDN ↑ MBP levels in RT Neoplasm Bronchiectasis COPD GERD Allergic Rhinitis ↑ sputum production and accumulation Damage from chronic inflammation causes poor mucus clearance Inhalants trigger ↑ cytokines ↑ mucus Aspiration of refluxed microdroplets Irritation by post- nasal drip ↑ inflammatory mediators in RT Mechanical obstructions (i.e. mediastinal masses, neoplasms) Foreign body Presence irritation of irritants Stimulation of sensory nerve receptors expressed on nerve endings penetrating the epithelia of the upper RT Abbreviations: • RT: respiratory tract • IP: indefinite pathophysiology • GERD: Gastro-esophageal reflux disease • EDN: Eosinophil-derived neurotoxin • MBP: Major basic protein • COPD: Chronic Obstructive Pulmonary Disease Complications: Syncope, insomnia, hemoptysis, rib fractures Slowly adapting receptors Respond to mechanical forces during breathing Stimulation of the vagus nerve Activation of nucleus tractus solitarius in central respiratory generator (brainstem) Generation of efferent cough signal Chronic cough: Cough of over 8 weeks duration with no dyspnea or fever C-fibre receptors Respond to chemical stimuli (bradykinin, capsaicin, acid/alkaline solutions, mannitol, hypertonic saline, and other inhaled irritants) Authors: Arsalan Ahmad Lance Bartel Reviewers: Midas (Kening) Kang Usama Malik Ciara Hanly Yonglin Mai (麦泳琳) Yan Yu*, Eric Leung* * MD at time of publication Rapidly adapting receptors Responds to mechanical stimuli, such as physical obstruction of the airways Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Feb 06, 2018, updated Dec 4, 2021 on www.thecalgaryguide.com

慢性咳嗽-发病机制

慢性咳嗽-发病机制

哮喘-发病机制

哮喘-发病机制

哮喘-临床表现

哮喘-临床表现

哮喘-检查结果

哮喘-检查结果

过敏反应-发病机制

过敏反应-发病机制

肺栓塞并发症

肺栓塞并发症

慢性阻塞性肺疾病简称copd定义

慢性阻塞性肺疾病简称copd定义

copd-诱发因素和体征-急性加重的症状

copd-诱发因素和体征-急性加重的症状

咳嗽生理机制

咳嗽生理机制

应对covid-19公共卫生作用

应对covid-19公共卫生作用

肺栓塞-发病机制-及实验室检查

肺栓塞-发病机制-及实验室检查

Mycobacterium-Tuberculosis

Mycobacterium Tuberculosis: Pathogenesis and clinical findings Airborne droplets containing Mycobacterium tuberculosis bacilli enter the airway Authors: Michael Moroz Teagan King* Reviewers: Rachel Fung Austin Laing Yan Yu* Brett Edwards* * MD at time of publication Airflow and lung anatomy favors deposition of bacilli in the midlung zone Alveolar macrophages engulf inhaled bacilli via the process of phagocytosis Bacilli evade intracellular destruction via complex mechanisms Macrophages infected with bacilli are activated and release inflammatory cytokines (TNF-a, IL-1B, IL-6/8) Pro-inflammatory cytokines further activate and recruit neutrophils, T- lymphocytes and monocytes to the site of respiratory infection Intracellular lysosomal enzymes are released into the vesicle containing the bacilli Lysosomal enzymes digest and destroy the bacilli M. tuberculosis infection is cleared from the body Sputum culture and smear microscopy –ve for M. tuberculosis Infected macrophages travel to thoracic lymph nodes via the lymphatic systemàimmune cell proliferation within thoracic nodes Bacilli activate macrophage cell death programsàbacilli are released and enter the lymphatic and circulatory system Bacilli spread to other regions of the body Extrapulmonary tuberculosis Abbreviations TNF-a: tumor necrosis factor alpha IL-1B: interleukin 1B IL-6, IL-8: interleukin 6 & 8 MHC: Major histocompatibility complex IFN-y: Interferon gamma Hilar + paratracheal lymphadenopathy Recruited macrophages phagocytose extracellular bacilli and become infected Macrophages form a granuloma to isolate and contain the bacilli to that area of the lung Recruited dendritic cells phagocytose M. tuberculosis and present antigens to T-cells via MHC class II receptors CD4+ T-cells are sensitized to M. tuberculosis antigens and release IFN-y IFN-y activates infected macrophages within granuloma to more effectively destroy intracellular bacilli via lysosomal enzymes Sputum culture and smear microscopy +ve for M. tuberculosis Ghon focus visible on Chest X-Ray +ve tuberculin skin test and +ve IFN-y Release Assay Resilient bacilli within granuloma survive lysosomal enzymes and become dormant Latent M. tuberculosis; +/- reactivation due to immune suppression (ie: TNF-a inhibitors) T-cell response is delayed in an immunocompromised hostà prolonging infection Center of the granuloma necroses and liquifies allowing the bacilli to escape back into the airways Bacilli re-enter host’s airway, allowing droplet transmission to other hosts Accumulation of inflammatory mediators and necrotic tissue in lung, irritating airways Chronic cough Active M. tuberculosis Multifactorial response, most with unclear mechanisms Fevers, night sweats, weight loss Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 6, 2021 on www.thecalgaryguide.com

brulures-non-accidentelles-chez-les-enfants-resultats-de-lexamen-physique

brulures-non-accidentelles-chez-les-enfants-resultats-de-lexamen-physique

psychodynamic-psychotherapy-principles-and-reasoning

Psychodynamic Psychotherapy: Principles and Reasoning Authors: Ryan Widmer Erik Fraunberger Reviewers: Brooke Fallis Yan Yu* Dr. Margaret Oakander* * MD at time of publication Childhood Experiences Early life experiences, positive or negative, reinforce personality traits and relational patterns Patterns and traits solidify as unconscious attitudes, thoughts, and emotions that drive behaviour Conflict between egocentric, immediate gratification and societal expectations or moral standards produces psychological tension, creating maladaptive thoughts, emotions, and behaviors toward external stressors Defense Mechanisms Psychological coping strategies that attempt to rectify anxiety between internal conflict and external stressors Regression: Returning to an earlier stage of development (ie. Adopting child-like behaviours) Projection: Qualities felt about one person are directed towards another Denial: Refusing to admit unpleasant emotion/experience Repression: Blocking a threatening memory from entering consciousness Maladaptive thoughts include worthlessness, hopelessness or grandiosity Maladaptive emotions include explosive anger or extreme self-loathing Maladaptive behaviours include passive aggressiveness or withdrawal from others Recognition of maladaptation to external stressors motivates patient to engage in therapeutic process Patient and therapist attempt co-construction of connections between maladaptive behaviours and past experiences Initiation of therapy challenges patient’s unconscious psychic equilibrium Transference Patient’s transfers thoughts on therapist rooted in emotions from previously important individuals Counter-transference Therapist’s thoughts and feelings about the patient hinders co-constructive therapeutic process Resistance Interferes with therapy due to subjective sense of shame and judgement Patient and Therapist work through therapeutic barriers Supportive interventions include advice and praise, psychoeducation, and empathic validation Expressive interventions include clarification, confrontation, and interpretation Patient accepts therapist’s connection Patient gains insight into how they feel and think and can then make better choices about their lives Patient continues to engage in therapeutic processes, utilizing strategies to reduce maladaptive responses Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 9, 2021 on www.thecalgaryguide.com

mechanical-bowel-obstruction-and-ileus-pathogenesis-and-clinical-findings

Mechanical Bowel Obstruction and Ileus: Pathogenesis and clinical findings Anti-motility Diabetic Sepsis drugs gastroparesis Nerves coordinating bowel peristalsis are disrupted Ileus: functional bowel ‘blockage’, no peristalsis Post- operation Hernia (no past surgery) Post-abdominal surgery Authors: Yan Yu, Wayne Rosen* Reviewers: Nicole Burma, Jason Baserman, Jennifer Au, Maitreyi Raman* * MD at time of publication Adhesions Note: • Complete obstruction typically presents with acute abdominal pain and related symptoms • Incomplete obstructions can present with either acute or Congenital abnormality GI neoplasms If partial obstruction: ↓ frequency of bowel movements Since gas/air sounds hollow to percussion Abdomen tympanic to percussion Mechanical obstruction: physical blockage of bowel lumen Inflammatory bowel disease (IBD) Gas (from swallowed air, bacterial fermentation, & CO2 made via HCO3- neutralization) & ingested gastro- intestinal (GI) contents accumulate before obstruction Accumulated GI contents contain salts and other osmotically active solutes that osmotically draw water into the GI tract Continued ↑ bowel distention & ↑ luminal pressure over time ↑ pressure squeezes shut intestinal blood vesselsà↓ bowel perfusion chronic abdominal pain If complete obstruction: Obstipation (no flatus) & absent bowel movements Irritation of autonomic nerves in visceral peritoneum Lower effective arterial blood volumeàdehydration Continued peristalsis proximal to obstruction continues to push GI contents against the obstruction If obstruction is proximal (closer to mouth), higher luminal pressure may force regurgitation of GI contents Bloating, cramping, anorexia Diffuse visceral abdominal pain Flat/low jugular venous pressure (JVP), resting tachycardia, orthostatic hypotension Severe abdominal pain (may come in waves), peritonitis, guarding, rigidity Hyperactive bowel sounds (proximal to obstruction) or absent bowel sounds (ileus) Nausea/vomiting Bowel ischemia and infarction, tissue necrosis, possible perforation +/- bacterial invasion (see relevant slides) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published December 15, 2021 on thecalgaryguide.com

hernias-inguinales-adquiridas-indirecta-directa

hernias-inguinales-adquiridas-indirecta-directa

dolor-abdominal-agudo-relacionado-con-el-tracto-gi-patogenesis-y-caracteristicas

dolor-abdominal-agudo-relacionado-con-el-tracto-gi-patogenesis-y-caracteristicas

pancreatitis-aguda-patogenesis-y-hallazgos-clinicos

pancreatitis-aguda-patogenesis-y-hallazgos-clinicos

apendicitis-patogenesis-y-hallazgos-clinicos

apendicitis-patogenesis-y-hallazgos-clinicos

culebrilla-herpes-zoster-patogenesis-y-hallazgos-clinicos

culebrilla-herpes-zoster-patogenesis-y-hallazgos-clinicos

infeccion-por-herpes-simple-patogenesis-y-hallazgos-clinicos

infeccion-por-herpes-simple-patogenesis-y-hallazgos-clinicos

enfermedad-de-huntington-patogenesis-y-hallazgos-clinicos

enfermedad-de-huntington-patogenesis-y-hallazgos-clinicos

escabiosis-patogenesis-y-hallazgos-clinicos

escabiosis-patogenesis-y-hallazgos-clinicos

sifilis-1ria-y-2ria-patogenesis-y-hallazgos-clinicos

sifilis-1ria-y-2ria-patogenesis-y-hallazgos-clinicos

necrotizing fasciitis

Necrotizing Fasciitis: Pathogenesis and Clinical Findings Authors: Alyssa Federico, Amanda Eslinger, Matthew Harding, Mehul Gupta Reviewers: Heena Singh, Yan Yu*, Donald Graham*, Duncan Nickerson* * MD at time of publication Diabetes Loss of protective sensation in lower extremities Peripheral vascular disease Poor arterial perfusion causes necrosis of tissue Immune compromised host Increased susceptibility to infection Bacteria introduced to tissue Pharyngitis Blood carries bacteria from throat to other tissue (hematogenous spread) Laceration Recent surgery Injection Burn Blunt force trauma Childbirth Lower extremity wounds Bacteria enters tissue through open wound Infection of muscle fascia Local immune response Production of exotoxins by bacteria Disruptions of protective skin barrier Bacteria introduced into tissue during injury Necrotizing Fasciitis Type I infection: mixed aerobic and anaerobic bacteria Type II infection: group A streptococcus Type III infection: marine organisms, clostridial infections Type IV infection: fungal organisms Poor blood supply of muscle fascia allows for progressive spread of infection Systemic immune response Pyrogens produced by immune system Pyrogens travel through the bloodstream to the hypothalamus and alters the body’s thermal setpoint Transmission of bacteria from infected tissue to blood Sepsis Streptolysin (exotoxin) causes blood clot formation Blood clots in vessels Tissue ischemia in epidermis, dermis, subcutaneous fat, muscle fascia, and/or muscle Stimulation of programmed cell death Tissue destruction Pain more severe than clinical findings ↓ blood flow fails to meet tissue’s needs Tissue death Build up of gas in subcutaneous tissue from bacteria metabolism Crepitus ↑ serum creatinine kinase from protein breakdown ↑ blood flow to infected tissue Warmth Erythema Immune cells release vasoactive cytokines into the blood Capillary vasodilation Fluid and proteins shift from cells and capillaries to interstitial space Blood vessel dilation ↓ perfusion of vital organs Organ failure Hypotension ↑ heart rate to perfuse vital organs Tachycardia Bacteria releases toxins which are taken up into the bloodstream Immune cells produce inflammatory cytokines Circulating toxins activate T cells, over- activating the systemic immune response Toxic Shock syndrome Infection ↑ white blood cell production in bone marrow ↑ white blood cells Destructionof peripheral nerve endings Insensitivity to pain Tissue hypoxia à anaerobic metabolism Poor perfusion of lungs impairs gas exchange Tachypnea Cytokines affect dopamine production in the basal ganglia Acute malaise Production of non-specific acute phase reactants ↑ C reactive protein and erythrocyte sedimentation rate Fluid-filled blisters Edema Fever Compartment syndrome (see relevant Calgary Guide slide) Amputation ↑ serum lactate Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications First published Nov 20, 2013, updated Dec 19, 2021 on www.thecalgaryguide.com

generalized-seizures-pathogenesis-clinical-findings-and-complications

Generalized Seizures: Pathogenesis, Clinical Findings, and Complications Infection Invasion of central nervous system by pathogen Immune response ↑ cytokine production and produces edema Direct stimulation of neural receptors & altered expression of ion channels Neoplastic Mass effect Paraneoplastic reaction Structural, biochemical, and electrical alterations to nearby neurons Cerebrovascular & Trauma Hypoxia/ischemia due to interrupted oxygenated blood flow ↑ extracellular glutamate released from injured cells Glutamate receptor activationàNa+/Ca2+ influx into neurons Metabolic Toxic/Other Disinhibition of excitatory neurons or direct activation of sodium channels ↑ intracellular Na+ Electrolyte abnormalities (ex. ↑ or ↓ Ca2+/Na+/Mg2+) ↑ CNS neuronal irritability or encephalopathy Glycemic dysregulation ↓ ATP production Impaired Na+/K+ ATPase function Author: Erik Fraunberger Yan Yu* Reviewers: Davis Maclean Ephrem Zewdie Negar Tehrani Mehul Gupta Carlos Camara-Lemarroy* * MD at time of publication Overall ↑ in excitatory tone producing aberrant cortical electrical activity Cerebral hemispheres synchronously and spontaneously depolarize as electrical signals spread diffusely through brain tissue Resting membrane potential maintained above threshold Altered neuronal excitability Altered communication between cortex and subcortical structures See “Focal Seizures in the Adult” slide Motor (tonic-clonic, tonic, clonic, other) Generalized Seizures Failure of seizure termination mechanisms and/or ↑ propensity for abnormally prolonged seizures Physical injury, rhabdomyolysis, aspiration, fractures (See “Status Epilepticus” slide) Nonmotor (absence) ↑ corticothalamic signaling and inhibition of the default mode network Impairment of consciousness Abrupt cessation or impairment of activities Learning difficulties, behavioural issues, progression to generalized tonic-clonic seizures Dysregulation of autonomic control Post-ictal cardiac dysrhythmias and respiratory dysfunction ↓ cerebral blood flow & oxygenation Post-ictal Sudden Unexpected Death Confusion In Epilepsy (SUDEP) Loss of consciousness & synchronized muscular contractions Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 19, 2021 on www.thecalgaryguide.com

obstruccion-del-intestino-delgado-hallazgos-en-los-rayos-x

obstruccion-del-intestino-delgado-hallazgos-en-los-rayos-x

bronquiolitis-patogenesis-y-hallazgos-clinicos

bronquiolitis-patogenesis-y-hallazgos-clinicos

asma-patogenesis

asma-patogenesis

otitis-media-aguda-complicaciones

otitis-media-aguda-complicaciones

otitis-media-aguda-oma-patogenesis-y-hallazgos-clinicos-en-ninos

otitis-media-aguda-oma-patogenesis-y-hallazgos-clinicos-en-ninos

diverticulitis-aguda-patogenesis-y-hallazgos-clinicos

diverticulitis-aguda-patogenesis-y-hallazgos-clinicos

meningitis-bacteriana-patogenesis

meningitis-bacteriana-patogenesis

meningitis-bacteriana-hallazgos-clinicos

meningitis-bacteriana-hallazgos-clinicos

meningitis-bacteriana-complicaciones

meningitis-bacteriana-complicaciones

carcinoma-colorectal-patogenesis-y-hallazgos-clinicos

carcinoma-colorectal-patogenesis-y-hallazgos-clinicos

crup-patogenesis-y-hallazgos-clinicos

crup-patogenesis-y-hallazgos-clinicos

trastornos-de-la-vesicula-biliar

trastornos-de-la-vesicula-biliar

enfermedad-por-reflujo-gastroesofagico-erge-complicaciones

enfermedad-por-reflujo-gastroesofagico-erge-complicaciones

hernia-incisional-patogenesis-y-hallazgos-clinicos

hernia-incisional-patogenesis-y-hallazgos-clinicos

colitis-isquemica-patogenesis-y-hallazgos-clinicos

colitis-isquemica-patogenesis-y-hallazgos-clinicos

obstruccion-intestinal-mecanica-e-ileo-patogenesis-y-hallazgos-clinicos

obstruccion-intestinal-mecanica-e-ileo-patogenesis-y-hallazgos-clinicos

sepsis-y-shock-septico-patogenesis-y-hallazgos-clinicos

sepsis-y-shock-septico-patogenesis-y-hallazgos-clinicos

prolapso-del-cordon-umbilical-patogenesis-y-hallazgos-clinicos

prolapso-del-cordon-umbilical-patogenesis-y-hallazgos-clinicos

Normal anion gap metabolic acidosis

Normal Anion Gap Metabolic Acidosis: Pathogenesis and Laboratory Findings Authors: Wazaira Khan Reviewers: Jessica Krahn, Timothy Fu, Emily Wildman, Austin Laing, Yan Yu*, Juliya Hemmett* * MD at time of publication GI Loss ↑ gut motility and secretion ↑ HCO3- loss through stool Distal nephron is unaffected and continues to secrete excess acid into the urine in the form of NH4+ For every major urine cation (Na+, K+, NH4+), the distal nephron secretes one corresponding urine Cl- anion Urine NH4+ cannot be measured, so measured urine Cl- exceeds measured urine (Na+ + K+) Negative urine net charge (Urine (Na+ + K+) - Urine Cl-) Type II RTA RTA: renal tubular acidosis ↓ activity of proximal Type I RTA ↓ activity of H+ ATPase on luminal surface of ⍺- intercalated cell in the collecting duct Impaired ⍺-intercalated cell function ↓ H+ secretion into urine by ⍺- intercalated cell ↑ H+ concentration in plasmaà↓ in blood pH Activation of blood bicarbonate buffer system Compensatory ↓ in plasma HCO3- (in response to ↑ in plasma H+) Type IV RTA ↓ aldosterone production or aldosterone resistant state ↓ Na+ channels on luminal surface of principal cell in the collecting duct Impaired principal cell function ↓ Na+ reabsorption by principal cell ↑ Na+ remains in collecting duct lumen ↓ negative charge in collecting duct lumen ↓ K+ secretion into urine by principal cell ↑ K+ in plasma Hyperkalemia Normal anion gap tubule transporters, pumps or enzymes Impaired proximal tubule cell function reabsorption Complex and Incompletely understood mechanisms Hypokalemia Distal nephron function is impairedàdistal nephron is unable to secrete excess acid into the urine in the form of NH4+ ↓ in urinary NH + 4 secretion is accompanied by corresponding ↓ in urinary Cl- secretion Measured urine (Na+ + K+) exceeds measured urine Cl- Positive urine net charge (Urine (Na+ + K+) - Urine Cl-) ↓ HCO3 - in proximal tubule ↑ HCO3- loss through urine ↓ HCO3- concentration in plasma Relative ↑ in plasma H+ compared to plasma HCO3- Compensatory ↑ in CO2 exhalation by lungs (since CO2 is acidic once metabolized in the blood) Since Anion gap = Na+ - Cl- - HCO3-, 1 to 1 replacement of Cl- for HCO - in the 3 plasma results in anion gap unchanged ↓ ability to buffer excess acid Activation of the membrane Cl-/HCO3- exchanger in the collecting duct Exchanger works to ↑ Cl- levels in the plasma by one Cl- for each ↓ of one HCO3- in the plasma Metabolic Acidosis ↓ Plasma partial pressure of CO2 Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 21, 2021 on www.thecalgaryguide.com

SIADH

Syndrome of Inappropriate Anti-Diuretic Hormone (SIADH): Pathogenesis and clinical Malignancy (e.g. Small cell lung cancer, head and neck cancer) Tumor originates from neuroendocrine cells Tumor acts as an ectopic site of ADH production ADH binds receptors on basolateral side (facing peritubular capillary) of principal cells in nephron ADH ↑ principal cells’ production of Aquaporin type II channels on their apical surface (side facing tubule lumen) ↑ Reabsorption of water from the collecting ducts back into circulation ↑ Blood Volume (↑ extracellular fluid volume) Blood Na+ levels diluted Hyponatremia (blood Na+ <135 mEq/L) Brain injury (e.g. Stroke, encephalitis hemorrhage, trauma) ↑ hypothalamic ADH production, storage in posterior pituitary, & pituitary secretion of ADH ↑ Uncontrolled ADH secretion SIADH (Syndrome of Inappropriate Anti-Diuretic Hormone) Drugs (e.g. Cyclophosphamide, SSRIs, vincristine) Break down into active metabolites Metabolites mimic ADH activity findings Authors: Krusang Patel Yan Yu* Reviewers: Davis Maclean Brooke Fallis Juliya Hemmett* * MD at time of publication Atria and Ventricles of the heart stretch Heart secretes ↑ atrial natriuretic and B-type natriuretic peptides (ANP/BNP) Peptides promotes natriuresis (excretion of Na+ into urine) Loss of Na+ in serumàalters charge balance across neuron membranesàImproper action potential firing: ↓ Renin secretion ↓ Release of Angiotensin II & Aldosterone ↓Reabsorption of Na+ into circulation in area postrema of medulla in hypothalamus in motor neurons Extracellular fluid volume becomes hypotonic relative to intracellular fluid volume Water moves from circulation into cells Extracellular fluid volume normalizes Euvolemia Nausea Headaches Muscle Cramps ↓ Urine volume Cells, particularly neurons, swell up Cerebral edema Neurons burst and die Severe Neurocognitive Effects (confusion, mood swings, hallucinations, seizure, coma) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Dec 30, 2021 on www.thecalgaryguide.com

Renal Artery Stenosis

Renal Artery Stenosis: Pathogenesis and clinical findings Atherosclerosis: A collection of inflammatory cells, lipids, & Fibromuscular Dysplasia: A rare vascular condition characterized by fibrous connective tissue deposits on the renal artery wall abnormal cellular growth in arterial walls, especially renal & carotid arteries Narrowing (stenosis) of the renal artery Renal Artery Stenosis can be unilateral or bilateral Authors: Samin Dolatabadi, Yan Yu* Reviewers: Meena Assad, Jessica Krahn Timothy Fu, Brooke Fallis, Juliya Hemmett* * MD at time of publication ↓ Pressure perfusing the kidney ↑ RAAS (renin-angiotensin- aldosterone system) activation ↓ pressure gradient in glomerulus ↓ Glomerular filtration rate (GFR) ↑ Secretion of aldosterone Turbulent blood flow through area of stenosis Abdominal bruit on side of affected kidney(s) ↑ Secretion of Angiotensin IIà ↑ Systemic vasoconstriction Hypertension ↑ Expression of epithelial sodium channels in cortical collecting duct ↑ Blood volume within volume- constrained space of blood vessels ↓ Renal blood flowà ischemic renal injury Atrophy and fibrosis of affected kidney(s) Unilateral stenosis à Kidney size asymmetry (≥1.5cm difference) ↓ Positively charged Na+ in lumen à Electronegative lumen compared to the interstitial/tubular epithelial cells K+ follows the electrical gradient and is secreted into the electronegative tubular lumen ↓ Serum K+ concentration Hypokalemia *Note: In unilateral renal artery stenosis, the contralateral (normal) kidney can compensate for the increase in renal perfusion pressure caused by hypertension by increasing sodium excretion (pressure natriuresis), preventing flash pulmonary edema. ↑ NHE3 (Sodium Hydrogen Exchanger 3) activity in proximal collecting tubule ↑ Na+ and water reabsorption from renal tubular lumen into blood vessels Chronic left ventricle pressure overload àLeft ventricle hypertrophy (see Left Heart Failure: Pathogenesis Slide) Systolic dysfunction → ↓ left ventricle stroke volume Normally, ↑ in renal perfusion pressureà↑ Na+ excretion and water loss (pressure natriuresis) In bilateral renal artery stenosis*, ↓ GFRàinability for kidney to ↑ renal Na+ & water excretion à volume overload Acute increase in afterload or preload → sudden ↑ in left ventricular filling pressures → blood backup into lungs Pulmonary vasculature hypertension → ↑ fluid filtration across the pulmonary endothelium into interstitium and alveolar spaces Flash (rapid onset) pulmonary edema Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 30, 2021 on www.thecalgaryguide.com

Membranous Nephropathy

Authors: Jessica Krahn Membranous Nephropathy: Pathogenesis and clinical findings Reviewers: Brooke Fallis, Yan Yu*, Juliya Hemmet* * MD at time of publication Primary (Idiopathic) Membranous Nephropathy Secondary Membranous Nephropathy Drugs, infections, auto-immune diseases, and malignancies make antigens Blood tests for Anti- PLA2R antibodies are positive in ~70% of cases Autoantibodies are made to antigens expressed near or on podocyte surfaces or planted in the glomerular capillary wall (ie. PLA2R; THSD7A; NELL-1) IgG antibodies filter through the glomerulus Autoimmune: (e.g. Systemic Lupus Erythematous, thyroiditis) Drugs: (e.g. NSAIDs, gold, penicillamine, captopril) Malignancies: (ie. Prostate, Colon) Infections: (e.g. Hepatitis B, Syphilis) Circulating antigens filter through the glomerulus and between the GBM and podocytes Antibodies & antigens form immunocomplexes, which lodge Immunofluorescence shows diffuse “granular” between the glomerular basement membrane & podocytes deposits of immunocomplexes throughout GBM Basement membrane is formed between and around immunocomplex deposits Immunocomplexes activate complement and the assembly of the Membrane attack complex (MAC) MAC creates holes in podocyte plasma membranes Stimulates the release/activation of proteases and oxidases from glomerular podocytes and mesangial cells GBM appears thick on light microscopy “Spike and dome” pattern appears with silver stain Podocyte effacement Damage to negatively charged foot processes damages the charge barrier of the glomerulus that repels negatively charged molecules Increased filtration of large negatively charged molecules, especially albumin Induces ↑ hepatic lipoprotein synthesis and ↓ lipoprotein catabolism Hyperlipidemia (↑ serum LDL, VLDL, and triglycerides) ↑ lipid filtration through glomerulus Lipiduria (fatty casts) *Hypo-albuminemia ↓ oncotic pressure in capillaries Fluid leaks into interstitial space ↑ Filtration of Proteins C and S and antithrombin Hypercoagulable state Thrombosis *Edema (especially *Proteinuria ↑ Filtration of immunoglobulins Immunosuppression Infections ↑ Filtration of Plasminogen Plasminogen converted to plasmin in the cortical collecting duct via urokinase- type plasminogen activator Plasmin activates the epithelial sodium channel ↓ intravascular volume Hypotension Pre-Renal Acute Kidney Injury Underfill edema (see slide) peri-orbital, scrotal, labial, and extremities) Overfill edema (see slide) ↑ Na+ and water reabsorption Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published MONTH, DAY, YEAR on www.thecalgaryguide.com

Overview of Calcium Phosphate Vitamin D Physiology

Overview of Calcium, Phosphate, and Vitamin D Physiology Note: In circulation, 40% of Ca2+ is bound to plasma proteins, mainly albumin, 10% is complexed with citrate, and 50% is unbound and biologically active. Bone PTH binds to osteoblasts ↑ Osteoblast production of receptor activator of nuclear factor kappa-B ligand (RANKL) and ↓ expression of osteoprotegerin (OPG), a decoy receptor for RANKL RANKL binds to receptor activator of nuclear factor kappa-B (RANK) on osteoclasts ↑ Osteoclast differentiation and activity ↑ Ca2+ resorption from bone into blood Sensed by Calcium-Sensing Receptor on Chief Cells of the Parathyroid Gland − − ↑ Serum phosphate (PO4) ↓ Serum calcium (Ca2+) Parathyroid Gland releases Parathyroid Hormone (PTH) into the blood, which acts on the kidneys and the bones Kidney ↑ Activation of Transient Receptor Potential Vanilloid subfamily member 5 (Ca2+ channel) in the distal convoluted tubule ↓ Expression of 24-hydroxylase enzyme (which functions to catabolize calcitriol) ↑ Expression of 1α- hydroxylase enzyme ↑ Conversion of 25-hydroxy vitamin D (Calcidiol) to the active form, 1,25-dihydroxy vitamin D (Calcitriol) ↑ Calcitriol Small Intestine ↑ Endocytosis of sodium phosphate co-transporters NaPi-2a and NaPi-2c, which reabsorb PO4 from ultrafiltrate in the renal tubules ↓ Reabsorption of PO 4 ↓ Serum PO Calcitriol negatively feeds back on parathyroid gland to inhibit PTH production ↑ Expression of sodium phosphate co- transporters NaPi-2a and NaPi-2b that absorb PO4 from intestinal lumen 4 ↑ Expression of apical epithelial Ca2+ channels (Transient Receptor Potential Vanilloid subfamily member 6) ↑ Entry of Ca2+ on apical side of enterocytes ↑ Reabsorption of Ca2+ in the distal convoluted tubule through Ca2+ channels ↑ Reabsorption of PO ↑ Expression of cytoplasmic Calbindin-D ↑ Transport of Ca2+ across enterocytes ↑ Absorption of Ca2+ in small intestine ↑ Serum Ca+2 ↑ Expression of basolateral plasma membrane calcium ATPase ↑ Extrusion of Ca2+ from enterocytes into bloodstream 4 Authors: Samin Dolatabadi, Hannah Yaphe Reviewers: Amanda Henderson, Meena Assad, Brooke Fallis, Yan Yu*, Hanan Bassyouni* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications First published Oct 15, 2017, updated Nov 11, 2021 on www.thecalgaryguide.com

Minimal Change Disease

Minimal Change Disease: Pathogenesis and clinical findings Authors: Jessica Krahn Reviewers: Timothy Fu Brooke Fallis Yan Yu* Juliya Hemmet* * MD at time of publication Damage induced by cytokines, not immunocomplexes Lack of abnormal immunocomplexes (antibody-antigen complexes) present in serum Immunofluorescence test negative Idiopathic/Primary Minimal Change Disease No identifiable extraglomerular disease process causes this condition Secondary Minimal Change Disease Infections, NSAIDS, neoplasms via unclear mechanisms Minimal change to glomerulus seen on light microscopy Podocyte effacement seen on electron microscopy Abnormal T Cell activation and release of cytokines (sometimes called permeability factors) that are toxic to podocytes Podocyte foot processes efface (become flattened) or fuse together Damage to negatively charged foot processes damages the charge barrier of the glomerulus that repels negatively charged molecules ↑ filtration of larger negatively charged molecules, such as low-molecular weight proteins like albumin, from the blood into the renal tubular filtrate Induces ↑ hepatic lipoprotein synthesis and ↓ lipoprotein catabolism Hyperlipidemia (↑ serum LDL, VLDL, and triglycerides) ↑ lipid filtration through glomerulus Lipiduria (fatty casts) Hypo-albuminemia ↓ oncotic pressure in capillaries Fluid leaks into interstitial space ↑ Filtration of Proteins C and S and antithrombin Hypercoagulable state Proteinuria ↑ Filtration of immunoglobulins Immunosuppression Infections ↑ Filtration of Plasminogen Plasminogen converted to plasmin in the cortical collecting duct via urokinase- type plasminogen activator Plasmin activates the epithelial sodium channel ↓ intravascular volume Hypotension Pre-Renal Acute Kidney Injury Underfill edema (see slide) Thrombosis Edema (especially peri- orbital, scrotal, labial, and extremities) Overfill edema (see slide) ↑ Na+ and water reabsorption Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 30, 2021 on www.thecalgaryguide.com

Cerebral Edema

Cerebral Edema: Signs and Symptoms Monro-Kellie Doctrine: The skull has a fixed volume made up of cerebral spinal fluid, blood, and brain matter. An increase in one of these components must result in equal displacement of the other two. Cerebral Edema (swelling of the brain tissue) ↑ Intra-Cranial Pressure (ICP) Cerebral vasculature compressed ↓ Cerebral Perfusion Pressure (CPP; CPP = Mean Arterial Pressure – Intracranial Pressure) Cerebral hypoxia ↓ O2 detection in vasomotor center within medulla ↑ Sympathetic nervous system activity in attempt restore cerebral perfusion Release of adrenergic and noradrenergic neurotransmitters from nerve terminals Stimulation of α1, α2, β1, and β2 receptors located on the cell surface of target organ tissue ↑ Peripheral arteriole constriction Optic Nerve swelling Distortion of brainstem Compression of the medulla Nerve fibre dysfunction Axoplasmic stasis within optic nerve fibers Oculomotor nerves compressed Vision loss Papilledema Dilation and fixation of ipsilateral pupil Distortion of cortex Brain Herniation (e.g. Subfalcine, Uncal, Tonsillar) Massive cerebral malperfusion Neuronal cell injury and death Hypoxic Brain Injury and Brain Death Compression of frontal cortex Neuron dysfunction Frontal cortex behaviour changes (lethargy, irritability, anxiety, seizures) Meninges compressed between brain and skull Meningeal pain receptors activated Headache Compression of the diencephalon and midbrain Dysfunction of respiratory control center Slow and irregular respirations Area postrema (nausea control center) compressed Nausea & Vomiting Descending corticospinal tract compressed against tentorium Upper Motor Neuron (UMN) dysfunction Impaired function of the Reticular Activating System Depressed level of consciousness Cushing’s Triad UMN disease (see relevant slide for full mechanisms) Signs of increased ICP associated with impending herniation of the brain: 1. Irregular, slow respirations 2. Bradycardia 3. Systolic Hypertension Author: Stephen Chrusch Reviewers: Emily Wildman Austin Laing *Scott Jarvis *Yan Yu * MD at time of publication Muscle weakness Hyperreflexia Spasticity (Hypertonicity) Extensor Plantar Response Systolic Hypertension ↑ Heart rate and cardiomyocyte contractility Carotid and aortic baroreceptors detect ↑ BP Tachycardia (early) Vagus nerve stimulation Parasympathetic response triggered Reflex bradycardia (late) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Jan 5, 2022 on www.thecalgaryguide.com

BPPV

Benign Paroxysmal Positional Vertigo (BPPV): Pathogenesis and Clinical Findings Authors: Ryan Chan, Jonathan Wong, Mehul Gupta, Yan Yu* Reviewers: Davis Maclean, Saud Sunba, Euna Hwang* * MD at time of publication Up-beating, torsional geotropic (towards the ground) fast-phase nystagmus (towards affected side) Down-beating +/-torsional fast-phase nystagmus (towards opposite side) Idiopathic Older Age Head trauma Recent Ear Surgery Underlying Vestibular Disorders/Infections: Meniere’s Disease, Vestibular Neuritis, Labyrinthitis Risk Factors of Labyrinth Ischemia: Hypertension, Hyperlipidemia, Migraines Dislodged otoliths/otoconia from the macula of the utricle Posterior Canal BPPV (~95-99%) Superior Canal BPPV (~1%) Horizontal Canal BPPV (~5-20%) Ocular muscles are stimulated to generate a downward, torsional slow-phase movement Ocular muscles are stimulated to generate an upward, torsional slow-phase movement Cupulolithiasis Theory: Otolith adheres to cupula of the semicircular canal (SCC) Otolith displaces the cupula during head position changes resulting in prolonged sense of head rotation along the semicircular canal axis OR Canalithiasis Theory: Free-floating otolith in the semicircular canal (SCC) Otolith induces inertial drag of the endolymph fluid during motion, displacing the cupula, resulting in prolonged sense of head rotation Dix-Hallpike Maneuver: Sitting with head rotated laterally (45°), moving quickly to supine with head extended 30° off table. Observe for any nystagmus. Direction of nystagmus indicates which of the three semicircular canals is affected. Ocular muscles are stimulated to generate a horizontal slow-phase movement away from affected side Horizontal Nystagmus: Fast phase beats toward the affected side Supine Head Roll Test: lying supine, roll head laterally to each side to move otoliths along horizontal SCC axis BPPV: Episodic, positional bouts of vertigo and nystagmus not due to an underlying neurological or insidious reason If the otolith is free-floating in the SCC, movement of the affected ear towards the table generates a net stimulatory endolymph flow in the affected horizontal SCC The stimulatory signal is carried to brainstem nuclei, generating a reflexive slow movement of the eyes away from the affected ear, and quick horizontal movements back towards the affected ear Geotrophic Horizontal Nystagmus: fast-phase nystagmus beats horizontally towards the table If the otolith is adherent to the SCC cupula, movement of the affected ear towards the table generates a net inhibitory deflection of the horizontal SCC cupula The inhibitory signal is carried to brainstem nuclei, generating a reflexive slow movement of the eyes towards the affected ear, and quick horizontal movements away from the affected ear Apogeotropic Horizontal Nystagmus: fast-phase nystagmus beats horizontally towards the ceiling Otoconia & otoliths only affect the semicircular canal (SCC), not the cochlea No tinnitus or hearing loss Otoconia tend to settle quite quickly (<1 min) when body is still, resolving the mismatch of body movement & semicircular canal (SCC) excitation Vertigo and nystagmus is transient (lasting ~1min or less) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 9, 2022 on www.thecalgaryguide.com

ACE inhibitors

Angiotensin Converting Enzyme (ACE) inhibitors: Mechanism of Action and Clinical Findings Angiotensin Converting Enzyme (ACE) Inhibitors Inhibits the conversion of angiotensin I to angiotensin IIà↓ serum angiotensin II levels Inhibits breakdown of bradykinin ↓ Activation of zona glomerulosa region of the adrenal cortex ↓ Aldosterone secretion from the adrenal cortex ↓ Expression of basolateral Na+/K+ pump and ↓ insertion of luminal Na+ channels in principal cells of the cortical collecting duct in kidney ↓ K+ secretion into urine ↑ Serum K+ concentration Hyperkalemia ↓ Activation of Na+/H+ exchanger in proximal convoluted tubule (PCT) of the kidney ↓ Na+ absorption into PCT and ↓ H+ excretion into lumen ↓ Na+ absorption into the blood ↓ Renal H2O reabsorption via osmosis ↓ Activation of paraventricular nuclei located in the hypothalamus ↓ Secretion of anti- diuretic hormone (ADH) into the capillaries of the posterior pituitary gland ↓ Aquaporin channel insertion at cortical collecting duct in kidney ↓ Renal H2O reabsorption à↑ serum bradykinin levels Vasodilation of efferent arteriole in kidneys ↓ Hydrostatic pressure within the glomerular capillaries ↑ Activation of cyclooxygenase-2 pathway ↑ Prostaglandin production ↓ Activation of angiotensin II type 1 receptors on surface of arteriolar smooth muscle ↓ Activity of G protein-coupled receptor intracellular secondary messenger cascade ↓ Systemic arteriolar vasoconstriction ↓ Total peripheral resistance (resistance to blood flow by systemic vasculature) ↓ Blood Pressure ↓ total blood flow perfusing kidneys Renal hypoxia ↑ Systemic arteriolar vasodilation ↓ Total peripheral resistance ↓ Blood Pressure ↓ Concentration of protein travelling through tubules for excretion ↓ Fraction of H2O filtered from glomerular capillaries into bowman’s capsule (start of the renal tubule) ↓ Filtration of blood contents through glomerular membranes Sensitization of airway vagal afferent receptors Stimulation of the cough center located in the medulla oblongata Cough ↓ Protein in urine High K+ levels surrounding the heart muscle cellsàchronic depolarization of the cardiomyocyte cell membrane àalters cardiomyocyte conduction (complex mechanisms) Cardiac Arrythmias (see relevant slide on Hyperkalemia: Clinical Findings) ↓ Effective arterial blood volume Authors: Nicole Brockman Reviewers: Emily Wildman, Austin Laing Adam Bass*, Yan Yu* * MD at time of publication Renal tubules have relatively less water compared with the peritubular capillaries ↓ H2O reabsorption from the renal tubule back into the blood ↑ Serum creatinine, ↓ estimated glomerular filtration rate Renal nephron injury and dysfunction Acute Kidney Injury (rise in creatinine >26.5umol/L in <7 days) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 10, 2022 on www.thecalgaryguide.com

complications-of-chronic-kidney-disease-ckd

Complications of Chronic Kidney Disease Chronic Kidney Disease (CKD) Authors: Samin Dolatabadi, Brooke Fallis Reviewers: Jessica Krahn, Meena Assad, Yan Yu* Juliya Hemmett* * MD at time of publication Abnormalities of kidney structure or function that is present for 3 or more months Kidney tubules atrophy & kidney interstitial tissue undergo fibrosis Kidney damage ↓ erythropoietin production (normally a kidney function) ↓stimulation of bone marrow → ↓ red blood cell production Build up of toxic substances (e.g. urea, guanidine, and indoxyl sulfate) ↓ Conversion of calcidiol to calcitriol in by kidney ↓ Calcitriol levels in blood ↓ Ca+2 absorption from small intestine Hypocalcemia ↓ Glomerular Filtration Rate ↑ Vascular calcification and endothelial dysfunction (e.g. changes in permeability, clotting response to inflammation, amongst other mechanisms) Atherosclerotic disease (see “Complications of Atherosclerosis” slide) ↓ Lipoprotein lipase, apoA-1, and Lecithin-cholesterol acyltransferase activity acting on serum lipoproteins (complex mechanisms) ↓ Lipoprotein clearance from blood Dyslipidemia (↑ LDL, ↑ triglycerides, ↓ HDL) Toxic damage ↓ red blood cell survival Anemia Uremic Syndrome ↓ Renal excretion of phosphate ↑ phosphate remaining in bloodstream Hyperphosphatemia ↑ serum phosphate binds with ionized calcium ↓ Renal excretion of K+ ↑ K+ remaining in bloodstream Hyperkalemia Edema ↓ Renal excretion of ammonium Reduced filtration capability ↑ organic anions remaining in blood→ ↑ anion gap ↓ Renal excretion of salt and water ↑ in extracellular fluid → systemic volume overload ↓ calcium in blood ↓ inhibition of Parathyroid Hormone (PTH) release ↑ PTH in blood Secondary hyperparathyroidism Metabolic Acidosis Hypertension Pitting Chronic kidney disease – mineral and bone disorder (CKD-MBD) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Jan 4, 2022 on www.thecalgaryguide.com

NSAIDs and the Kidney Nephrotoxicity

NSAIDs and the Kidney: NSAID induced Nephrotoxicity Non-steroidal anti-inflammatory drugs (NSAID) Authors: Kyle Moxham Mehul Gupta Reviewers: Emily Wildman Yan Yu* Adam Bass* * MD at time of publication Inhibition of Cyclooxygenase COX-1 (expressed in kidney) and COX-2 (expressed in kidney and sites of inflammation) NSAID induced nephrotoxicity: associated with chronic NSAID usage independent of dosage COX inhibition ↑ conversion of arachidonic acid (AA) to leukotrienes, causing systemic T-cell dysfunction (unknown mechanism) Type IV systemic hypersensitivity (delayed T helper cell mediated) reaction to drug exposure T cells release inflammatory cytokines into the bloodstream (see Calgary Guide slide on NSAIDs and the Kidney: Mechanism of Action and Side Effects) T cells infiltrate the renal interstitium, sparing the glomeruli and blood vessels Overproduction of cytokines by T cells causing inflammation, tissue damage, and cell death, of the renal intersitium Drug Induced Acute interstitial nephritis (AIN): a type of immune-mediated tubulointerstitial injury Activated T-cells infiltrate the glomerulus and cause podocyte injury (epithelial cells attached to the glomerular basement membrane) Membranous nephropathy: nephrotic syndrome involving autoimmune glomerular basement membrane thickening & complete podocyte effacement (seen on kidney biopsy) Minimal change disease: nephrotic syndrome caused by autoimmune podocyte effacement (seen on kidney biopsy) Cytokine mediated activation and proliferation of immune cells like macrophages and eosinophils Cytokines travel to hypothalamus, causing change in the body’s thermal set point Fever Podocyte effacement allows for serum proteins to across the glomerulus into the tubular lumen (see Calgary Guide slide on Nephrotic Syndrome for full mechanisms) Repeated NSAID exposure causing recurrent unrecognized AIN and damage of the kidney Chronic interstitial nephritis /analgesic nephropathy Infiltrating immune cells (predominantly neutrophils) are filtered into/enter the renal tubules, and form clumps (“casts”) within the tubulesà casts are then released into urine WBC cast on urinalysis ↑ Blood eosinophils Immune cells infiltrate the dermis and epidermis of the skin Rash Abnormal quantities of protein present in urine Protein present in the blood is improperly filtered into the filtrate at the glomerulus Protein- Creatinine Ratio >3.5mg/mg Proteinuria >3.5g/d Hypo- albuminemia ↓ plasma oncotic pressure resulting in fluid extravasation into the interstitium (see Calgary guide slide on Edema for full mechanisms) Pitting Edema Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 13, 2022 on www.thecalgaryguide.com

Langerhans Cell Histiocytosis

Langerhans Cell Histiocytosis: Pathogenesis and clinical findings Precursor cells differentiateàClonal expansion of abnormal (constitutive MAPK activation) CD1a+/CD207+ (Langerhans cell phenotype surface receptors) dendritic cells in tissue(s) Somatic BRAFV600E mutation: BRAF is a kinase in the MAPK pathway Other somatic (non- reproductive cell) mutations Idiopathic (unknown cause) Mutation(s) can occur in one of these precursor cell types* Hematopoietic stem cell (earliest cell of blood cell differentiation) in bone marrow Committed dendritic cell (type of myeloid antigen-presenting cell) precursor in bone marrow or blood Committed dendritic cell precursor in tissue Constitutive activation of the MAPK pathway (signalling pathway that regulates variety of cellular processes) in one of these precursor cell types *Note: Based on the “misguided myeloid differentiation” modelàthe earlier the mutation(s) occur in the myeloid cell differentiation pathway, the more severe the disease. Langerhans Cell Histiocytosis Accumulation of abnormal CD1a+/CD207+ dendritic cells (Langerhans Cell Histiocytosis cells or LCH cells) with an inflammatory background in one or more organs Authors: Ran (Marissa) Zhang Reviewers: Mehul Gupta Kiera Pajunen Yan Yu* Lynn Savoie* * MD at time of publication ↑ recruitment & activation of T cells, macrophages, eosinophils in tissue(s) around the body ↓ CCR7 & CXCR4 (chemokine receptors) expression on LCH cellsàinhibits migration of LCH cells to lymph nodes ↑ BCLXL (an apoptosis regulator protein) expression on LCH cellsà inhibits apoptosis of LCH cells Immune cell infiltration & ↑ pro-inflammatory chemokine/cytokine release à dysregulated local & systemic inflammation Accumulation of LCH cells in tissue(s) around the body Inflammatory lesion (an area of abnormal tissue) formation in one or more organs: In pituitary stalk Mass effectà obstruction of antidiuretic hormone (complex mechanisms) In liver Invasion & accumulation of cells foreign to liverà expands liver Chronic local inflammation Scarring of bile ducts ↓ bilirubin clearance from liveràbuildup into serum ↑ serum bilirubin Jaundice In cortical bone Cytokine production à↑ osteoclast (cells that break down bone) activity ↑ rate of bone loss Osteolytic bone lesions In bone marrow Unclear mechanism but likely due to macrophage activation ↑ phagocytosis (ingestion & destruction) of blood cells In spleen Invasion & accumulation of cells foreign to spleen Forms aggregates that expand the red pulp (functions as the blood filter in spleen) Splenomegaly In skin Unclear mechanisms Variable presentations: most commonly pinpoint erythematous (red) papules or erythematous plaques with crusting & scaling Hepatomegaly • BRAF- B-Raf proto-oncogene, serine/threonine kinase • CCR7- C-C motif chemokine receptor type 7 • CD1a- Cluster of differentiation 1A • CD207- C-type lectin domain family 4 member k • CXCR4- C-X-C chemokine receptor type 4 • LCH- Langerhans Cell Histiocytosis • MAPK- Mitogen-activated protein kinase Diabetes Insipidus Abbreviations: • BCLXL- B-cell lymphoma-extra large Anemia, thrombocytopenia &/or neutropenia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 13, 2022 on www.thecalgaryguide.com

Overfill Edema Pathogenesis

Overfill Edema: Pathogenesis Nephrotic Syndrome Damage to the glomeruli of the kidneys (See Nephrotic Syndrome: Pathogenesis and Clinical Findings Slide) Aberrant filtration of proteins including plasminogen (glycoprotein in the systemic circulation involved in the dissolution of fibrin blood clots) ↑ Plasminogen concentration in tubular fluid Conversion of plasminogenà plasmin by urokinase-type plasminogen activator in the cortical collecting tubule Plasmin activates epithelium sodium channels (involved in Na+ reabsorption) in principal cells of the cortical collecting duct Nonsteroidal Anti-inflammatory Drugs Inhibition of cyclooxygenase throughout body (enzyme that converts arachidonic acidàprostaglandins) ↓ Prostaglandins throughout body Thiazolidines ↓ Prostaglandin- mediated inhibition of Na+ and Cl- transport in ascending loop of Henle and collecting ducts ↑ Na+ reabsorption from kidney tubules back into blood ↓ Prostaglandin-mediated vasodilation in kidneys ↓ Pressure of blood perfusing kidneys → ↓ pressure gradient between glomerulus and bowman’s capsule ↓ Glomerular filtration rate ↓ Renal excretion of salt & water ↑ Salt and water retention ↑ Effective arterial blood volume ↑ blood pressure in veins Unclear mechanism but possible theories include upregulation of epithelium sodium channels in the cortical collecting tubule and involvement of other transporters in the proximal tubule and cortical collecting tubule Acute Renal Failure Chronic Renal Failure ↑ Hydrostatic pressure within capillariesàexceeds hydrostatic pressure within interstitial spaceàfluid moves from capillaries into interstitial space Overfill Edema Abnormal accumulation of fluid in the interstitial space where urine Na+ >40meq/L Authors: Samin Dolatabadi Reviewers: Meena Assad, Jessica Krahn, Brooke Fallis, Ran (Marissa) Zhang, Yan Yu*, Juliya Hemmett* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 23, 2022 on www.thecalgaryguide.com

telangiectasie-hemorragique-hereditaire-maladie-rendu-osler-pathogenie-et-resultats-cliniques

Télangiectasie hémorragique héréditaire (Maladie Rendu-Osler): Pathogénie et résultats cliniques

rosacee-pathogenie-et-resultats-cliniques

Rosacée: Pathogénie et résultats cliniques

molluscum-contagiosum-pathogenie-et-resultats-cliniques

Molluscum Contagiosum: Pathogénie et résultats cliniques

NSAIDs and the Kidney mechanism of action and side effects

NSAIDs and the Kidney: Mechanism of Action and Side Effects Authors: Kyle Moxham Mehul Gupta Reviewers: Emily Wildman Yan Yu* Adam Bass* *MD at time of publication Concurrent use of angiotensin- converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) AECi and ARBs act to ↓ renin- angiotensin-aldosterone system (RAAS) activation Reduced angiotensin (AT) 2 activity at its receptors on efferent arteriole of the nephron Net vasodilation of efferent arterioles ↓ in glomerular pressure ↓ blood perfusing kidney tissueà↑ hypoxemia & renal ischemia Pre-existing ↓effective arterial blood volume (EABV) from dehydration, GI loss, diuretics, CKD, CHF, cirrhosis, etc. Decreased EABV triggers endogenous renal autoregulation, resulting in norepinephrine (NE) mediated vasoconstriction of afferent arteriole of the nephron Net ↓ in renal blood flow and ↓ in glomerular pressure ↓ volume of blood filtered by the glomeruli per unit time Non-steroidal anti-inflammatory drugs (NSAIDs) Inhibition of Cyclooxygenase COX-1 (expressed in kidney) and COX-2 (expressed in kidney and sites of inflammation) ↓ Renal prostaglandin (PG) synthesis: local hormones involved in renal homeostasis NSAID induced nephrotoxicity: associated with chronic usage independent of dosage (see Calgary Guide slide on NSAIDs and the Kidney: NSAID induced nephrotoxicity) ↓ intrarenal PG reduces inhibitory effects of PG over ADH in cortical colleting duct (CCD) of the kidneyà↓ antagonism on ADH activity ↑ ADH activity causes insertion of more aquaporins (water channels) in the collecting duct of renal tubules Net ↑ in volume of water reabsorbed into the blood ↓ vasodilatory effect of PG at the afferent arteriole of the nephron ↓ Glomerular filtration rate (GFR) ↓ PG signalling results in ↓ renin secretion at juxtaglomerular apparatus Low renin levelsà↓ conversion of angiotensinogen into its AT1 form and, by extension, ACE mediated conversion of AT1 to AT2 ↓ ACE 2 signalling leads to ↓ levels of aldosterone in the serum ↓ Na+ and K+ channel insertion on apical surface and ↓ Na/K ATPase activity on basolateral surface of principal cells ↓ K+ excretion into urine, and ↓ Na+ reabsorption back into the blood, at the late DCT and collecting duct of the kidney Pre-renal Acute Kidney Injury (AKI): kidney injury due to renal hypoperfusion Prolonged and/or severe ischemia causes cell death and aggregation of tubular epithelial cells of the kidney with subsequent inability to reabsorb luminal Na+ Renal dehydration predisposes precipitation of uromodulin protein Renal tubules mold uromodulin into cylindrical structures known as “casts”. Casts that contain only uromodulin protein are known as “hyaline casts” Hyaline cast seen on urinalysis Hypoperfusion of the kidney activates the renin- angiotensin- aldosterone system (RAAS) ↑ amount of sodium (Na) reabsorbed from the filtrate (less Na excreted) Fractional excretion of Na <1% Papillary necrosis: ureteral passage of sloughed ischemic tissue causing ureteral obstruction Acute tubular necrosis: a type of kidney injury causing damage to the tubules Hypertension Post-renal AKI: a type of kidney injury due to obstruction of the urinary tract Distal distal obstruction of the urinary tract causes fluid to accumulate within the kidneysàenlarging the kidneys Renal Ultrasound shows hydronephrosis (enlarged kidneys) Damaged tubule epithelial cells slough into the tubular lumen Epithelial cell breakdown in the tubular lumen releases uromodulin & other proteins, which aggregate into “casts” (cylindrical imprints of the renal tubule). The varied protein content of these casts result in them having a coarse, granular appearance Damaged tubular epithelial cells are unable to properly reabsorb sodium ↓ amount of sodium (Na) reabsorbed from filtrate into the blood (more Na excreted) Fractional excretion of Na >2% True excess of free water relative to Na+ in the blood Excess free water ↑ venous hydrostatic pressure (see Calgary Guide slide on edema for full mechanisms) Pitting Edema Hyperkalemia Hyponatremia Coarse granular casts seen on urinalysis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 29, 2022 on www.thecalgaryguide.com

adult-pneumonia-pathogenesis-and-clinical-findings

Adult Pneumonia: Pathogenesis and clinical findings Author: Laura Byford-Richardson Reviewers: Tara Shannon, *Yan Yu, Sadie Kutz , Natalie Morgunov, *Kerri Johannson, *Julie Carson *MD at time of publication Smoking à suppressed neutrophil function and damaged lung epithelium Chronic lung conditions e.g. COPD, asthma, lung canceràdestroys lung tissue and offers pathogen more niduses for infection Immune suppression e.g. HIV, sepsis, glucocorticoids, chemotherapyà suppression of immune response Systemic inflammatory response towards invading microbe Systemic cytokine release leads to a disruption in hypothalamic thermoregulation Exposure to a pathogen via inhalation, aspiration, contiguous Notes: or hematological mechanism Susceptible host and/or virulent pathogen Proliferation of microbe in lower airways and alveoli Local response by alveolar epithelial cells release chemokines into surrounding tissue to recruit neutrophils to the site of inflammation • Pathogens can be bacteria, viruses, fungi and parasites • Pneumonia is a lower respiratory tract infection (in contrast to upper respiratory tract infections such as bronchitis) and can be further classified by location of exposure: community, health- care, hospital acquired Inflammatory response varies depending on type of invading pathogen (i.e. S. Pneumonia causes a lobar pattern and Influenza A & B cause an interstitial pattern) LOBAR: Accumulation of neutrophils and plasma exudate from capillaries into alveoli specific to a lung area/lobe INTERSTITIAL: Accumulation of infiltrates (i.e. inflamed cellular debris) in the alveolar walls (i.e. space between the alveolar spaces and bloodstream) Fever Notes: • Other signs and symptoms of pneumonia exist such as chest pain, accessory muscle use, crackles on auscultation and fatigue • These signs and symptoms are less specific to the ones outlined on this slide Irritation and attempted clearance of airways Fluid infiltrates are inside alveoli, airway clearance leads to phlegm production Productive Cough Fluid build up does not allow X-rays to pass through à white opacity on plain film at site of fluid buildup Consolidation on CXR Alveolar sacs blocked by fluid accumulation Thickening of alveolar walls ↑ diffusion distance between alveoli & capillaries Irritated alveolar walls trigger cough reflex Since fluid infiltrates are NOT in the alveoli, attempts to empty the alveoli through coughing doesn’t lead to production of fluid Dry Cough Chills/Rigors ↓ Exchange of CO2 and O2 Hypoxemia Triggers peripheral and central chemoreceptors to ↑ respiratory drive Dyspnea Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Sept 26 2016, updated Feb 9, 2022 on www.thecalgaryguide.com

greffes-de-peau-physiologie-de-la-greffe-et-resultats-cliniques

Greffes de peau : physiologie de la greffe et résultats cliniques Greffe de peau à épaisseur fractionnée (STSG) Épiderme Derme Follicule pileux Glande sudoripare Chronologie 1. Adhésion initiale (8 heures) 2. Imbibition plasmatique (24-48 heures) 3. Inoculation (2-4 jours) 4. Croissance néovasculaire (5-7 jours) 5. Épithélialisation (4 jours – 4 semaines) 6. Contraction de la plaie (6-18 mois) 7. Régénération & Ré- innervation (mois- années) Méchanisme Un réseau de fibrine se forme pour permettre l'adhérence du greffon Le greffon absorbe les nutriments et l'oxygène dissous de l'exsudat dans le lit tissulaire Les bourgeons capillaires du site receveur poussent vers les vaisseaux ouverts sous la greffe Les facteurs angiogéniques permettent la revascularisation ce qui permet un écoulement rapide et à volume élevé à travers les gros vaisseaux. Un drainage lymphatique est également mis en place Dans les greffes de peau maillées, les kératinocytes basaux au bord de la plaie facilitent la prolifération et la migration des cellules épithéliales L'actine dans les myofibroblastes se contracte et rapproche les bords de la plaie. La couche dermique profonde dans les greffes de pleine épaisseur peut mieux inhiber les myofibroblastes et réduire la contraction versus les greffes à épresseur fractionnée. Les follicules pileux, les glandes sudoripares et sébacées se régénèrent dans les greffes plus épaise. L'innervation commence à la périphérie et se développe au centre

Vitiligo Pathogenesis and Clinical Findings

Vitiligo: Pathogenesis and clinical findings Authors: Wisoo Shin Reviewers: Lauren Lee Stephen Williams Ben Campbell Laurie Parsons* Yan Yu* * MD at time of publication Genetic predisposition Variants in over 30 susceptibility loci Environmental exposure UV light, monobenzone, phenol, catechol Production of IgG auto- antibodies to melanocyte-specific proteins Auto-antibodies bind to melanocytes and trigger antibody-dependent cellular cytotoxicity: marking melanocytes for destruction by Fc- receptor bearing immune cells such as neutrophils Impaired mitochondrial function in melanocytes ↑ Susceptibility of melanocytes to oxidative stress ↓ E-cadherin or ↑ anti- adhesion molecule expression in melanocytes ↓ Adhesion of melanocytes to keratinocytes ↑ Clearance of melanocytes from epidermis ↑ Reactive oxygen species production within melanocytes Activation of apoptosis and senescence signaling pathways Pressure or friction Melanocytes excrete exosomes (melanocyte- specific antigens, microRNA, heat shock proteins) that, through complex mechanisms, stimulate the immune system’s CD8+ T-cells to destroy melanocytes Melanocytes enter apoptotic or senescent state ↓ Functional melanocytes ↓ Melanin production Overall loss of functional melanocytes Vitiligo Normal Skin Pigmented Epidermis Dermal- Epidermal Junction Dermis Autoimmune destruction of melanocytes Depigmented Epidermis Melanocytes Immune-mediated destruction of melanocytes (by both neutrophils and CD8+ T cells) A depigmenting skin disorder characterized by selective loss of melanocytes Depigmentation in areas of ↑ pressure, friction and/or trauma Nonsegmental vitiligo Smooth unpigmented macules or patches in bilateral, often symmetric pattern Somatic mosaicism (mutation limited to a subset of cells) in zygote during development Segmental vitiligo Smooth unpigmented macules or patches in unilateral pattern not crossing midline Vitiligo Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 15, 2022 on www.thecalgaryguide.com

angor-instable-angine-de-poitrine-pathogenese-et-observations-cliniques

angor-instable-angine-de-poitrine-pathogenese-et-observations-cliniques

Hypokalemia Physiology

Hypokalemia: Physiology Authors: Samin Dolatabadi, Ran (Marissa) Zhang, Mannat Dhillon Reviewers: Meena Assad, Yan Yu*, Juliya Hemmett* Beta-2 receptor stimulation (e.g. Salbutamol) ↑ Red blood cell production ↑ Na+/K+ ATPase activity in skeletal muscle cells (moves K+ into the cell & Na+ out of cell) ↑ K+ entry into skeletal muscle cells * MD at time of publication Abbreviations: • EABV – Effective Arterial Blood Volume • ENaC – Epithelial Sodium Channel • HCL – Hydrochloric acid • HCO3- –Bicarbonate ion ↑ K+ uptake by new red blood cells ↑ Intracellular shift of K+ into cells Refeeding Syndrome Exogenous insulin ↓ K+ dietary intake (rare cause in isolation) ↑ Insulin in response to carbohydrate load ↑ Na+/K+ ATPase activity in skeletal muscle & hepatic cells ↑ K+ entry into skeletal muscle & hepatic cells ↓ K+ availability for gastrointestinal absorption Hypokalemia (Serum [K+] < 3.5 mmol/L) ↑ Renal K+ secretion K+ follows the electrical gradient into tubular lumen ↑ Electronegativity of tubular lumen ↑ Na+ reabsorptionin principal cellsà Cl- left behind in tubular lumen of kidneys Gastric acid depletionà ↓HCl Loss of H+àShift in bicarbonate buffer system to ↑ plasma HCO3- Plasma HCO3- above reabsorptive capacity of the proximal tubule ↑ HCO3- in the distal tubular lumen of kidneys Vomiting Diarrhea Laxatives Renin secreting tumour Hyperaldosteronism Renal artery stenosis Loop and Thiazide diuretics Bartter’s and Gittelman’s syndrome Liddle syndrome Extracellular fluid volume depletion ↓ EABV ↑ Renin secretion ↓ Afferent arteriole pressure perfusing kidneys Renin-Angiotensin- Aldosterone System (RAAS) activationà ↑ Aldosterone release from the adrenal cortex ↑ Expression of ENaC (Na+ reabsorption) in principal cells of the cortical collectingduct) + ↑Na & water excretion in kidneys ↓ EABV Genetic condition leading to inability to degrade ENaC channels in principal cells of the cortical collecting duct Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 6, 2019, updated Jan 23, 2022 on www.thecalgaryguide.com Hypokalemia: Physiology Authors: Samin Dolatabadi Reviewers: Meena Assad Dr. Juliya Hemmett* * MD at time of publication TTKG > 4 with N/↑ EABV in hypokalemia is inappropriate and a principal cell problem. β2 Stimulation (e.g., Salbutamol) ↑ Na+/K+ ATPase activity ↑ K+ entry into cell ↑ RBC Production ↑ Cell production ↑ K+ uptake by new cells ↓ Extracellular ↑ Insulin in response to H+ carbohydrate load ↑ Na+/H+ antiporter activity (movement of H+ out of cell and Na+ into cell) ↑ Intracellular Na+ ↑ Na+/K+ ATPase activity ↑ K+ entry into cell ↑ Intracellular Shift of K+ Notes: Refeeding Syndrome Insulin Alkalemia • Abbreviations: • CCD – Cortical Collecting Duct • EABV – Effective Arterial Blood Volume • RAAS – Renin-Angiotensin-Aldosterone System • TTKG – Trans-tubular Potassium Gradient • ENaC – Epithelial Sodium Channel ↓ K+ Intake (Rare cause in isolation) ↓ K+ availability Diarrhea, Vomiting, Laxatives ↑ Gastrointestinal loss of K+ Polyuria ↑ Renal loss of K+ (TTKG < 4 as principal cell is working appropriately but small amount of K+ is lost per urination) Hypokalemia (Serum [K+] < 3.5 mmol/L) Liddle Syndrome Hyperaldosteronism Renin Secreting Tumour Renal artery stenosis Loop and Thiazide Diuretics Bartter’s and Gittelman’s Syndrome Genetic condition leading to inability to degrade ENaC channels ↑ Renin ↑ Renal K+ secretion K+ follows the electrical gradient Electronegative lumen ↓ Pressure perfusing the kidney RAAS activation RAAS activation ↑ Aldosterone ↑ Na+ and water excretion ↓ EABV ↑ Expression of ENaC in principal cells of CCD ↑ Na+ reabsorption Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 6, 2019 on www.thecalgaryguide.com

Hypokalemia Physiology

angine-de-poitrine-angor-stable-pathogenese-et-decouvertes-cliniques

Angine de Poitrine/Angor Stable: Pathogénèse et Découvertes Cliniques

hip-osteoarthritis-pathogenesis-and-clinical-findings

Hip Osteoarthritis: Pathogenesis and clinical findings Authors: Ebrahim Alawadhi, Alyssa Federico Reviewers: Mehul Gupta, Tara Shannon, Yan Yu*, Richard Ng* * MD at time of publication Primary causes Aging ↓ Synovial fluid in the hip joint Secondary causes Gender Females > males Genetics Family history of osteoarthritis High-impact sports, activities, and occupations Repetitive stress on the hip joints Obesity ↑ Loading on hip joints Inflammatory disease (e.g. Rheumatoid arthritis ) Trauma Infection (e.g. septic arthritis) Anatomical abnormality (e.g. developmental hip dysplasia) ↑ Cartilage stiffness and degeneration ↑ Friction in the hip joint with movement Changes in normal hip architecture Abnormal load on the hip joint Radiographic changes See Osteoarthritis (OA): X-Ray Features slide Repeated attempts to repair cartilage damage and bone Bone spur (bony growth) formation in joint Joint fluid accumulation from mild inflammation of the joint Stiffness Limited joint movement Hip Osteoarthritis Multifactorial condition that manifests as degeneration of cartilage, bone, and synovium in the hip joint ↓ Cartilage between femoral head and acetabulum ↑ Bone on bone contact Mechanical symptoms (crepitus, locking, clicking, catching) Bones rubbing together activates nociceptors within the hip joint Nociceptors further aggravated by actions that ↑ bone on bone contact (e.g. prolonged loading, movements that ↓ joint space) Worsening pain in the groin region Favour the affected leg to avoid pain while walking ↓ Space for the femoral head to move ↓ Range of motion of affected hip joint Limited range of motion when walking Antalgic gait ↓ Use of muscles around the affected hip Muscular atrophy around the hip C Sign: patient identifies location of pain by cupping lateral hip with one hand, which creates a “C” shape with that hand Pain in groin region ↑ Sensitivity of surrounding nerves Radiating pain to buttocks and knee Inactivity Hip instability when walking Muscle contractures ↑ Falls Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 6, 2022 on www.thecalgaryguide.com

topical-retinoids-mechanisms-and-side-effects

Topical Retinoids: Mechanisms and Side Effects Topical retinoids Authors: Ayaa Alkhaleefa Reviewers: Mehul Gupta, Ben Campbell Lauren Lee, Stephen Williams, Yan Yu*, Laurie Parsons* * MD at time of publication Gene products inhibit tyrosinase, an enzyme that controls the production of melanin in melanocytes No melanosome present to transfer to keratinocytes Melanogenesis is inhibited ↓ Epidermal pigmentation Lightens post- inflammatory hyperpigmented lesions Excessive pigment reduction Hypopigmentation of treated skin Gene products inhibit hyperproliferation of keratinocytes in pilosebaceous follicles Disrupts cohesion of overlying layer of dead keratinocytes (known as corneocytes) ↑ Corneocyte shedding Excessive corneocyte sheddingà desquamation of the skin Skin peeling Moisture loss and irritation Xerosis, pruritis, erythema (dryness, itchiness, redness) Retinoid molecules bind nuclear receptors in epidermal keratinocytes Bound nuclear receptors form heterodimers Heterodimers bind retinoic acid response elements, which transcribe retinoic acid-responsive genes Gene products inhibit leukocyte migration, toll-like receptors on monocytes, and transcription factor activator protein-1 Inhibits release of pro- inflammatory cytokines (IL-6, IL-12, TNF-α and IFN-γ) Shed corneocytes expel comedonal contents (open and closed types) Open comedone Inhibits C. acnes induced pro- inflammatory pathways Inhibits microcomedone formation (acne lesion precursor) ↑ Phagocytosis of vascular cell adhesion molecule 1 (mediates cytokine response) Anti-inflammatory Reduction of number and size of acne lesions Comedolytic Closed comedone Epidermal layer C. acnes Normal Skin Dermal-Epidermal Junction Dermal layer Pilosebaceous follicle Healthy hair follicle Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 13, 2022 on www.thecalgaryguide.com

cough-physiology

Cough: Physiology Mass or particulate matter in the throat & airways ↑ pressure on mucosa Pressure on rapidly and slowly adapting mechanoreceptors Mechanoreceptor activation opens ion channels on vagus neurons Authors: Calvin Howard Reviewers: Nilani Sritharan Ciara Hanly Yonglin Mai (麦泳琳)* Yan Yu* Stephen Field* * MD at time of publication Systemic immune reaction Inflammation of alveoli Cytokine release Cytokines bind to sensory neurons Neurons ↑ receptor sensitivity and number ↑ sensation of stimuli Ionic flux across neuronal membrane Vagus neurons depolarize Thinly myelinated axons (Aδ fibers) General chemicals, heat, cold, and hydrogen ions Transient receptor potential vanilloid (TRPV)/Transient receptor potential ankyrin (TRPA) receptors activate TRPV/TRPA activation opens ion channels on vagus neurons Unmyelinated axons (C fibers) carry depolarization Vagus nerves conduct depolarization to carry depolarization SUMMARY Afferent pathways activated Cough center (medulla) Efferent pathways Respiratory muscles nucleus of the solitary tract Medullary nuclei activated, stimulates: Phrenic nerves Diaphragm contraction Spinal nerves External intercostal contraction Vagal nerves Glottis closure Spinal nerves Thoracic, abdominal, and pelvic muscle contraction Vagal nerves Glottis opens, allowing forceful expiration Intrathoracic pressure and volume decrease Volume in lungs increases Intrathoracic pressure increases Mechanical Cough Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Sept 1, 2019, updated Dec 5, 2021 on www.thecalgaryguide.com

pancreatite-aigue-pathogenese-et-signes-cliniques

Pancréatite Aiguë: Pathogénèse et Signes Cliniques

pression-veineuse-jugulaire-pvj-signe-de-kussmaul-explique

Pression veineuse jugulaire (PVJ): signe de Kussmaul expliqué

isotretinoin-systemic-retinoid-mechanisms-and-side-effects

Isotretinoin (Systemic Retinoid): Mechanisms and Side Effects Isotretinoin Authors: Ayaa Alkhaleefa Reviewers: Mehul Gupta, Ben Campbell Stephen Williams, Lauren Lee, Yan Yu*, Laurie Parsons* * MD at time of publication ↑ Apoptotic signaling in sebocytes Inhibits androgen nuclear receptors responsible for sebum secretion ↓ Sebaceous lipogenesis ↑ Apoptotic signaling in neural crest cells during embryonic development Alterations in hindbrain, neural crest, otic anlage, and reduced pharyngeal arch in embryo Craniofacial, cardiac, thymic, and central nervous system malformations in fetus Isotretinoin isomerizes to all-trans retinoic acid (ATRA) ATRA enters cell nucleus and binds retinoic acid receptors and retinoic X receptors ATRA induces tumour necrosis factor-related apoptosis-inducing ligand ↑ Apoptotic signaling in epidermal keratinocytes ↑ Expression of FoxO1 ↑ Expression of p53 (tumour suppressor) Release of caspases 3, 6, 7, and 9 ↑ Cell cycle inhibitors p21 and p27 ↓ Pro-survival proteins (Survivin) Sebaceous gland involution Sebum suppression C. acnes unable to break down sebum into pro- inflammatory lipids ↓ Colonization with C. acnes Teratogenicity ↑ Cornification (death) of epidermal keratinocytes ↓ Corneodesmosomes (main adhesive structures of the stratum corneum) ↓ Cohesion of corneocytes (dead keratinocytes) ↓ Corneocyte buildup in pilosebaceous follicles C. acnes unable to populate and release cytokines in corneocytes Epidermis Dermis Pilosebaceous follicle ↓ Stratum corneum thickness ↑ Trans-epidermal water loss Dryness, peeling & inflammation of lips (cheilitis), skin (dermatitis) & mucosa (mucositis) ↓ Comedogenesis Sebum Hair follicle Dermal- Epidermal Junction Sebaceous gland (sebocytes) Death of sebocytes in pilosebaceous follicles Reduction of number and size of acne lesions Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 20, 2022 on www.thecalgaryguide.com

Diabetische Nephropathie: Pathogenese

Diabetische Nephropathie: Pathogenese

Verdachtsdiagnose tiefe Beinvenenthrombose (TVT): Pathogenese und Komplikationen

Verdachtsdiagnose tiefe Beinvenenthrombose (TVT): Pathogenese und Komplikationen

Hypovolämischer Schock: Pathogenese, Komplikationen und klinische Befunde

Hypovolämischer Schock: Pathogenese, Komplikationen und klinische Befunde

Akute Pankreatitis: Pathogenese und klinische Befunde

Akute Pankreatitis: Pathogenese und klinische Befunde

Akute Pankreatitis: Komplikationen

Akute Pankreatitis: Komplikationen

complications-of-pulmonary-embolism

Complications of Pulmonary Embolism Authors: Sravya Kakumanu, Dean Percy, Yan Yu Reviewers: Tristan Jones, Ciara Hanly, Jieling Ma (马杰羚), Ben Campbell, Dr. Man-Chiu Poon*, Dr. Lynn Savoie*, Dr. Tara Lohmann * * MD at time of publication IF CHRONIC: Unresolved clot after 2 years leading to fibrosis of pulmonary vasculature Chronic Thromboembolic Pulmonary Hypertension (CTEPH) (<5% of PE cases) Venous Stasis Hypercoagulable state Vessel Injury Virchow’s Triad (*See Suspected Deep Vein Thrombosis slide) Deep Vein Thrombosis Clot migrates from deep limb veins à femoral àiliac veins ACUTE/MASSIVE PE: Clot obstructs pulmonary arterial or arteriolar flow Lung infarction (tissue death) from ischemia Inflammatory cells migrate to site and release cytokines ↑ Permeability of blood vessels Permeability-driven (exudate) fluid leakage into pleural space Pleural Effusion Clot migratesàinferior vena cava àright atrium (RA) of heartà right ventricle (RV) à gets lodged in pulmonary arteries/arterioles Pulmonary Embolism (PE) ↑ RV afterload ↑ RV pressure and expansion Well-ventilated (V) areas of lung do not receive adequate blood supply (Q) V/Q Mismatch Leftward shift of ventricular septum ↓ Left ventricle filling in diastole ↓ Cardiac output Obstructive Shock Impaired heart filling Pulseless Electrical Activity (ECG activity in absence of palpable pulse) Back up of pressure in systemic venous system ↑ Pressure in capillaries draining parietal pleura Pressure-driven (transudate) fluid leakage into pleural space For signs and symptoms, see the Obstructive Shock slide For signs and symptoms refer to CTEPH slide Chronic ↑ RV afterload ↑ Stretching of myocytes causing RV hypertrophy and dilation ↓ RV ejection fraction Right Heart Failure “Cor Pulmonale” For signs and symptoms, see the Right Heart Failure slide Failure to oxygenate blood Type I Respiratory Failure Hypoxemic: patient has ↓ blood [O2] IF MASSIVE PE (less common): ↑ Alveolar dead space Failure to ventilate Type II Respiratory Failure Hypercapnic: patient has ↑ blood [CO2] Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 7, 2012, updated Mar 31, 2022 on www.thecalgaryguide.com

proximal-biceps-tendon-rupture

Proximal Biceps Tendon Rupture: Pathogenesis and clinical findings Author: Alyssa Federico Reviewers: Tara Shannon, Mehul Gupta, Yan Yu*, Gareth Ryan* * MD at time of publication Aging Decreased tendon strength from age- related changes in extracellular matrix Male gender Smoking Corticosteroid and fluoroquinolone use Shoulder Overuse Repetitive overhead sports like swimming & tennis Shoulder overuse injuries (rotator cuff tears, shoulder impingement, & tendonitis) place more stress on the proximal biceps tendon Repetitive microtrauma and inflammation of biceps tendon Compromised biceps tendon integrity from intra-tendinous collagen degeneration, disorientation, and thinning Increased involvement in physical labour and hobbies Impaired cell proliferation and healing after injury Exact mechanisms remain unclear Bicep tendon involved in shoulder stabilization, elbow flexion, and forearm supination Biceps muscle cannot contract with as much force when one head is detached Heavy lifting or fall on outstretched handà sudden tension in the proximal biceps tendon Proximal biceps tendon rupture Long head of proximal biceps tendon detaches from bony attachment on supraglenoid tubercle Audible “pop” at time of injury No tension to hold proximal bicep tendon head in place Proximal bicep tendon head retracts distally Biceps muscle fatigue and cramping Weakness in shoulder flexion, elbow flexion & supination Nerve damage (musculocutaneous nerve) during injury Local inflammatory response at site of injury Surrounding blood vessels damaged during injury Blood collection under skin surface Immediate bruising over rupture site Sudden and sharp pain at shoulder with initial injury Inflammatory response aggravates musculocutaneous nerve Swelling over rupture site + Speed test: affected elbow extended and forearm supinated. Shoulder flexed against resistanceàpain at bicipital groove + Neer test: on affected side, scapula stabilized while arm passively flexed and internally rotatedàpain at bicipital groove + Yergeson test: affected elbow flexed at 90° and forearm pronated. Forearm supinated against resistance àpain at bicipital groove “Popeye” deformity: mass in distal upper arm due to excessive retraction of biceps muscle distally, away from its origin Palpable gap between proximal biceps tendon and bicipital groove Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 20, 2022 on www.thecalgaryguide.com

distal-biceps-tendon-rupture

Distal Biceps Tendon Rupture: Pathogenesis and clinical findings Authors: Alyssa Federico Reviewers: Tara Shannon, Mehul Gupta, Yan Yu*, Gareth Ryan* * MD at time of publication Aging ↓ Tendon strength from age-related changes in extracellular matrix Male gender Overuse Common in throwing and racquet sports Repetitive microtrauma and inflammation of biceps tendon Corticosteroid and fluoroquinolone use Smoking Hypovascularity Area of hypovascularity between regions supplied by the brachial artery and posterior radial recurrent artery Impaired ability to heal from microtrauma Mechanical impingement Compression of distal biceps tendon by surrounding bone (radial tuberosity, proximal ulna) during forearm pronation Repetitive compressionà tendon degeneration ↑ Involvement in physical labour and hobbies Exact mechanisms remain unclear Impaired cell proliferation Biceps tendon inserts at the radial tuberosity to control forearm supination and flexion Compromised biceps tendon integrity from intra-tendinous collagen degeneration, disorientation, and thinning Sudden eccentric force to flexed elbow (forced lengthening of a contracted bicep muscle)àtension in the distal biceps tendon Biceps muscle cannot contract when distal tendon is detached from insertion site Distal biceps tendon rupture Complete detachment of distal biceps tendon at the attachment site on the radial tuberosity Audible “pop” at time of injury Weak forearm supination and flexion + Ruland biceps squeeze test: Affected elbow held in 60-80° of flexion, with forearm slightly pronated. Distal biceps muscle squeezed by practitioner à forearm does not supinate Local inflammatory response at site of injury Inflammatory response aggravates musculo- cutaneous nerve Pain over rupture site after initial injury Swelling over rupture site Nerve damage (musculocut aneous nerve) during injury Sudden and sharp pain at elbow at initial injury Surrounding blood vessels damaged during injury Blood collects under skin surface Immediate bruising over rupture site Biceps tendon retracts proximally High tension during tendon retraction Fragment of bone torn off from tendon insertion site on radial tuberosity Avulsion fracture of radial tuberosity Connective tissue attachment (aponeurosis) torn during injury Palpable gap between distal end of biceps tendon & radial tuberosity + Hook test: Elbow actively flexed to 90° and forearm supinated. Index finger of examiner cannot be placed beneath distal aspect of biceps tendon (>1 cm deep) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 20, 2022 on www.thecalgaryguide.com

肺泡-动脉氧分压差-为何它会存在，为什么我们要

肺泡-动脉氧分压差-为何它会存在，为什么我们要

肺泡-动脉氧分压差-关于公式的说明-科学正确的解

肺泡-动脉氧分压差-关于公式的说明-科学正确的解

肺泡-动脉氧分压差-关于公式的说明简易说明

肺泡-动脉氧分压差-关于公式的说明简易说明

cognitive-behavioural-therapy-cbt-principles-and-reasoning

Cognitive Behavioural Therapy (CBT): Principles and Reasoning A stressor, e.g., failing a test, activates underlying maladaptive core beliefs and personal rules (ie. schema) based in Beck’s cognitive triad: 1. Negative Views about the World 2. Negative Views about Oneself e.g., “Everyone is against me because I am e.g., “I’m worthless and inadequate.” worthless.” Authors: Erik Fraunberger, Alison Darnley Reviewers: Allen Vorobeichik, Brooke Fallis, Ran (Marissa) Zhang, Margaret Oakander* * MD at time of publication 3. Negative Views about the Future e.g., “I’ll never be good at anything.” Negative bias in thought patterns, attention, memory, and interpretation of events/stimuli Negative automatic thoughts activated in certain situations e.g., ”I will never succeed in anything I do” Emotional & behavioural reactions e.g., Feeling hopeless (emotional reaction) and unmotivated in school (behavioural reaction) Patient engages with the therapist to identify cognitive distortions about self, others, and the world (not an exhaustive list) Therapist and patient problem solve together and challenge existing cognitive distortions using these techniques (not exhaustive list) Therapist works with patient to improve awareness of cognitive distortions and employ techniques in daily life Over time with continued support and practice, the patient’s negative schemas are addressed, emotional and behavioral symptoms improve Personalization: assigning disproportionate personal blame Disattribution of bad events to the individual and recognizing role of environmental factors Catastrophizing: dwelling on the worst possible outcome Estimate actual probabilities, clearly state facts of situation & emphasize worst case scenario did not occur Dichotomous thinking: absolute thinking in the form of two extremes Demonstrate that a continuum of outcomes is possible Overgeneralization: making conclusions based on one event/situation Expose faulty logic and discuss similarities and differences in closely related events Improved function and ability to adapt to life stressors Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 26, 2022 on www.thecalgaryguide.com

irritable-bowel-syndrome-ibs-pathogenesis-and-clinical-findings

Irritable Bowel Syndrome (IBS): Pathogenesis and clinical findings Authors: Ben Campbell Reviewers: Mehul Gupta Kiana Hampton Yan Yu* Edwin Cheng* * MD at time of publication Note: *Several signaling pathways in the gut are believed to play a role in IBS. The serotonin pathway is represented here for illustrative purposes, and it is a common target of therapy. Pathogenesis is multifactorial, not fully understood, and may arise from any one or a combination of these factors Genetic factors are believed to influence many of these pathways Environmental factors Gut infection, ischemia, injury, chronic low-level inflammation, altered microbiome Abnormal gut chemical milieu (cytokines, lymphocytes, mast cells, hormones) One common pathway: altered quantity or activity of serotonin-releasing enterochromaffin * cells and serotonin reuptake transporters in gut Serotonin is a key stimulator of gut muscle contraction and sensory signaling Altered bowel motility Bowel motility can ↑, ↓ or alternate ↑/↓ Psychosocial factors Anxiety, depression, adverse experiences, dysregulated stress response Brain can alter normal reflexes of enteric nervous system (e.g. via hypothalamic stress hormone release) ↑ Activity of sensory receptors in gut + recruitment of formerly ”silent” receptors Altered visceral bowel sensation Visceral hypersensitivity Complex mechanisms ↓ Brain’s ability to modulate pain signals from gut; ↑ vigilance to pain Irritable Bowel Syndrome Disorder of brain-gut interaction with gastrointestinal manifestations Not a predominantly inflammatory condition During times of ↑ bowel motility: No lesions in gut mucosa (Absence of ”red flags” for organic disease) ↑ Impacts of other factors that precipitate diarrhea Dietary sensitivity (e.g. to intake of fermentable oligo/di/ monosaccharides and polyols— FODMAPs—which draw water into gut lumen by osmosis) ↑ Impacts of other factors that precipitate constipation Dietary sensitivity (e.g. to inadequate intake of motility- promoting fibre) During times of ↓ bowel motility: ↑ Time for water absorption from feces and bacterial fermentation ↑ Hard stool and trapped gas in bowel ↑ Number and sensitivity of active pain receptors (nociceptors) in gut Hyperalgesia ↑ Response to painful stimulus Stretch receptors in gut stimulate pain in normally unconscious neural pathways Allodynia Pain in response to normal stimulus ↑ Peristalsis ↓ Time for water absorption from feces ↑ Water volume in gut lumen ↑ Stretch / stimulation of visceral afferent nerves in gut Absence of bloody stool and anemia Absence of nocturnal symptoms and inflammatory markers Constipation Bloating Diffuse abdominal pain All symptoms may exacerbate psychosocial factors Bowel distension Diarrhea Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 30, 2022 on www.thecalgaryguide.com

成人肺炎发病机制和临床表现

成人肺炎:发病机制和临床表现

过敏性肺炎-发病机制和临床发现

过敏性肺炎: 发病机制和临床发现

肺栓塞症状和体征

肺栓塞症状和体征 Notes • 诊断率最低的疾病之一，通常无症状 ，心动过速通常是唯一的征兆 • 将 DVT 和 PE 视为一种疾病:如果 怀疑 PE，需寻找 DVT 的体征和症状 • 没有 DVT 不能排除 PE Virchow 三联征:高凝状态、静脉淤滞、血管 损伤(*见疑似 DVT此章节) 深静脉血栓形成——腘静脉、股静脉、髂静脉 栓子脱落移动à下腔静脉 IVC à右心房 à 右心室à 肺血管系统 大血块(鞍状栓塞)滞留在肺动脉中 小血块滞留在肺小动脉中 鞍状栓子(肺动脉阻塞) 血液回流至右心 右心组织受到牵拉 作者: Dean Percy Yan Yu 审稿人: Tristan Jones Julia Heighton Man-Chiu Poon* Lynn Savoie* 译者:Jieling Ma(马杰羚) 翻译审稿人: Ying Li(李颖), Yonglin Mai(麦泳琳) * 发表时担任临床医生 若肺外周循环阻断，可致胸膜 下肺组织缺血和梗塞 栓子导致肺动脉/小动脉血流↓ 输送到肺部，呼 输送至肺泡进行氧 肺通气良好 (V) 区域没有获得足 够的血流供应 (Q); 反之亦然 肺V/Q扫描提示: V/Q 异常 信号传导至中枢 使心率↑ 刺激壁层胸膜上躯体感觉 神经末梢 缺血组织发生炎症反 应，粘附胸膜 胸膜摩擦音 听诊时听到类似砂纸 的声音 出的CO2↓ 合的低氧血液↓ 主动脉/颈动脉化 学感受器检测到血 液低O2浓度(O2 饱和度↓) 信号传导至中枢 呼 吸频率↑ 呼出二氧化碳减 少，血液中二氧 化碳潴留，刺激 延髓化学感受器， 呼吸频率↑ 疼痛刺激肾上腺素系统反应 心动过速 胸膜炎性胸痛 呼吸困难/气短 (SOB) PE最敏感指标，但特异性不高 伴随每次呼吸出现的局部胸痛 图注: 病理生理学 机制 体征/症状/实验室检查 并发症 2019年6月15日重新发布于 www.thecalgaryguide.com

疑似深静脉血栓形成-dvt-发病机制和并发症

疑似深静脉血栓形成 (DVT): 发病机制和并发症 作者: Dean Percy Yan Yu 审稿人: Tristan Jones Ryan Brenneis Man-Chiu Poon* Maitreyi Raman* 译者:Jieling Ma(马杰羚) 翻译审稿人: Ying Li(李颖), Yonglin Mai(麦泳琳) * 发表时担任临床医生 Notes: 恶性肿瘤 血小板活化 遗传性疾病 遗传性易栓症(如:PC、PS、抗 凝血酶III、因子V Leiden突变)血 液易凝性↑ 雌激素促进血液高凝 ，尤其是存在其他危 险因素的情况下 • • 静脉血栓引起肺栓塞， 动脉血栓可引起中风; 既往 DVT 病史是当前 DVT复发 的危险因素 创伤/手术 促凝细胞因子异常释放 血栓形成增加 全身性损伤 高凝状态 凝血级联反应激活 血液在外界刺激下， 凝固能力↑ 血管损伤 Virchow 受损细胞和内皮组织 三要素 释放组织因子入血， 与vWF结合 脂肪含有大量芳香 酶，将更多的雄激 素转化为雌激素 久坐不动生活方式， 静脉回流不良 高血压 细菌 人工瓣膜 血管壁机械损伤 粘附/侵袭血管壁 瓣膜表面异常 静脉血淤滞 血管损伤部位血流慢， 凝血因子在该部位聚集 肥胖 1.血液回流至深静脉(血液淤滞，处于高 栓子导致静脉瓣膜功能受损 凝状态) 血栓形成通常发生在下肢静脉 肌肉运动↓ 静脉血流量↓ 骨折、固定、卧床休息、 长时间乘坐汽车/飞机 肺部血栓栓塞 血栓栓塞 2.下肢静脉回流需对抗重力(血液淤滞) 3.下肢静脉瓣膜易发生返流(血液淤滞) 怀孕，口服避孕药 (OCP) 静脉功能不全 凝块阻碍血液回流至心脏。 腿部血液淤 积，导致不对称性腿部水肿和静脉炎症 (发红、发热、压痛) -*肺栓塞(急性危及生命的并发症) -慢性血栓栓塞性肺动脉高压 图注: 病理生理 机制 体征/症状/实验室检查 并发症 2019年9月1日重新发表于 www.thecalgaryguide.com

张力性气胸发病机制，临床表现和x线表现

张力性气胸:发病机制，临床表现和X线表现 作者: Mark Elliott, Davis Maclean, Evan Allarie, Shelly Spanner* 审稿人: Steven Liu, David Nicholl, Ciara Hanly, Zesheng Ye (叶泽 生), Yonglin Mai (麦泳琳)*, Naushad Hirani*, Yan Yu* 译者: Huiting Wang(王慧婷), Yang Xiang (向杨) 翻译审稿人: Ran Zhong(钟然), Yonglin Mai (麦泳琳), Zesheng Ye(叶泽生) * 发表时担任临床医生 继发性气胸 (有基础性肺疾病) 手术 (如: 胸腔穿刺术，中心导管 正压通气 置入，肺结节活检) 原发性气胸 (无基础性肺疾病) 气压性创伤 医源性气胸 刺激高敏感性 起病急骤，突发刀割样胸痛 壁层胸膜 (可放射至肩部) 对侧气管移位 对侧纵膈移位 肺纹理 缺失 肺萎陷(脏层胸膜线 肋间隙增大 膈肌变平 创伤性气胸 如穿通性损伤，肋骨骨折 壁层胸膜/脏层胸膜/支气管树的破坏 胸膜裂口形成气体进入胸膜 腔的单向阀/单向活瓣 (由于生理性胸膜负压的存在) 空气进入、填充并潴留于胸膜腔 患侧胸腔内气压↑ 患侧肺因气压↑塌陷 较于萎陷的 肺实质，积 气部位叩诊 时发出叩诊 音音响↑ 叩诊呈鼓音, 取决于病情 轻重程度 (用手在患侧 叩击) 对侧心影移位 可见脏层 胸膜线 (气胸线) 患侧横膈膜变平 空气无法进入 纵膈偏离患 健侧在影像学上 进入胸腔的气体将内脏和壁层胸膜 两层胸膜隔开，可见脏层胸膜线 患侧肋骨张开 (肋间隙↑) 患侧肺 侧 挤压健侧肺 可见心影和肺门 压迫上腔静脉和(或)下腔静脉 右心房血液回流受阻 声音震动无法像 胸壁扩张度 正常那样从喉部 ↓ 发出，沿着肺部 组织传至胸壁引 心输出量↓ 血液倒流回静脉系统 心动过速 低血压 颈静脉压↑ 血液氧合 ↓(血氧分压) 呼吸急促 ( 呼吸频率 ↑) 起共鸣 X光可见,脏 胸膜和边缘 肺纹理缺失 语音震颤↓ 呼吸音↓ (发声时胸壁可 触及的震颤) 呼吸困难 患侧肺塌陷 患侧肺泡内的 气体交换受损 通气/灌注失调、 及出现血液分流 低氧 图注: 病理生理 机制 体征/症状/实验室检查 X-光检查结果 2013年12月11日首次发表，2020年10月24日更新www.thecalgaryguide.com )

abnormal-uterine-bleeding-aub-pathogenesis-and-clinical-findings

Abnormal Uterine Bleeding: Pathogenesis and clinical findings Authors: Joshua Yu, Karen Paik Reviewers: Ayaa Alkhaleefa, Parker Lieb, Hypothyroidism Hypothalamus senses ↓ serum thyroxine ↑Thyrotropin releasing hormone (TRH) release from hypothalamus ↑Prolactin (see Feedback Loop: Prolactin) Exogenous estrogen (e.g. estrogen-only birth control) ↑ Peripheral adipose tissue ↑ Aromatase (enzyme present in adipose tissue) ↑ Conversion of androgens to estrogens (aromatization) Excessive stress, exercise, low body mass (mechanism unclear) ↓ Hypothalamic gonadotropin releasing hormone secretion ↓Luteinizing hormone and follicle stimulating hormone release from pituitary ↑ Estrogen Heavier bleeding Angiogenesis in tumour tissue Polycystic ovarian syndrome (see slide) Pelvic inflammatory disease Immature hypothalamic- pituitary-ovarian axis (an immature axis is transient in most females) ↓ Positive feedback of estrogen in late follicular stage No LH surge Adenomyosis (endometrial tissue grows into uterus muscular wall) Endometrial polyps Retained products of contraception Infection Inflammation of endometrium Endometrium is more fragile Anovulatory Bleeding Leiomyoma (benign tumour in myometrium) Tara Shannon, Hannah Yaphe, Dr. Sarah Glaze* * MD at time of publication Ovarian Scarring Foreign bodies Intrauterine device perforation Physical trauma Impaired follicle maturation Anovulation Corpus luteum does not form No ovarian progesterone production ↑ Estrogen to progesterone ratio Proliferative effect of estrogen unopposed Endometrial proliferation No progesterone to organize growing endometrium Disorganized endometrium overgrows and sloughs off Irregular bleeding Menopause Premature ovarian insufficiency Intermittent congestion of polyp blood supply Transient ischemia and slight polyp necrosis Altered growth factor production Vascular dysregulation and leakier vessels Coagulopathies (e.g. von Willebrand disease) Impaired hemostasis Invasion of normal tissue ↓ Estrogen (hypoestrogenism) Atrophy of endometrium and vulvovaginal tissue Dry endometrial surfaces (↓ fluid to prevent friction) Endometrial carcinoma Micro- erosions of epithelium Inflammation Evidence unclear Heavier and more irregular bleeding Spotting Heavier and more irregular bleeding Light bleeding and spotting Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 2, 2022 on www.thecalgaryguide.com

rhumatisme-psoriasique-pathogenese-et-resultats-cliniques

rhumatisme-psoriasique-pathogenese-et-resultats-cliniques Psoriatic Arthritis: Pathogenesis and clinical findings Auteur: Payam Pournazari Rédacteurs: Yan Yu Scott Rapske Liam Martin* Traducteurs: Dianne Ganeswaran Stephen Williams Sylvain Coderre* * MD au moment de publication Note: L’arthrite rhumatoïde peut survenir avant ou après le psoriasis (la pathogenèse est la même). Augmentation de l’activité ostéoclastique Érosion de l’os sous- chondral mais formation de nouvelle osseuse ailleurs dans l’articulation Radiographie: la périostite; les syndesmophytes, érosions, déformation du crayon en godets (les articulations IP), ankylose des articulations IP HLA B27, Cw6 et d’autres sous- types Antécédents familiaux positifs Activation des cellules T (mécanisme inconnu) Infiltration du tissu synovial de l’articulation par les cellules T et B, cellules tueuses naturelles et les macrophages Production augmentée des molécules inflammatoires (les facteurs de nécrose tumorale [TNFs], les interleukines, etc.) qui agissent de façon systémique (dans tout le corps) Dans les tendons et le tissu conjonctif Inflammation des enthèses et du tissu conjonctif provoque le gonflement Dans la peau Réaction immunitaire détruisant les structures de la peau et des ongles (Voir diapositive Psoriasis) Le psoriasis en plaques sur la peau, dépressions punctiformes, onychorrhexie, taches d’huile, onycholyse, décoloration et hyperkératose Angiogenèse et vascularite dans les vaisseaux sanguins de la membrane synoviale Dans les articulations Les cytokines inflammatoires stimulent les nocicepteurs locaux 1. Oligoarthrites - asymétriques 2. Arthrite des articulations IPD 3. Polyarthrite rhumatoïde - symétrique 4. Atteinte axiale (raison inconnue, probablement en raison de « biomécanique », « innervation », et « vascularisation ». 5. Arthrite mutilante (grave et destructrice) L’enthésite (Douleur/sensibilité à l’insertion du ligament dans l’os) La dactylite (Inflammation de tout le doigt – les tissus mous et les articulations sont enflammés Légende: Physiopathologie Mécanisme Signe/Symptôme/Résultats de Laboratoire Complications Publié 10 November 2012 sur www.thecalgaryguide.com

tinea-capitis-tinea-corpora-and-tinea-pedis-pathogenese-et-resultats-cliniques

tinea-capitis-tinea-corpora-and-tinea-pedis-pathogenese-et-resultats-cliniques Tinea capitis, tinea corpora, and tinea pedis: Pathogenèse et résultats cliniques Auteurs: Kara Hawker Rédacteurs: Crystal Liu Yan Yu* Laurie Parsons* Traducteurs: Dianne Ganeswaran Stephen Williams Sylvain Coderre* * MD au moment de publication Peau lésée Facteurs prédisposant la peau de l’hôte à l’infection ↑ humidité ambiante Facteurs favorisant l’invasion fongique Cicatrice Brûlure ↑ CO2 Note: Infections causées par les dermatophytes sont appelées infections « tinea » ou « teigne du corps » en raison de leurs lésions annulaires Les plus courants champignons causant des infections dermatophytiques (par ordre): Contact direct avec des êtres humains, des animaux ou des objets inanimés qui sont infectés Le dermatophyte envahit la couche superficielle de la peau (non vivante et kératinisée), la couche cornée Le dermatophyte produit l’enzyme kératinase La kératinase catalyse la dégradation de kératine (une protéine) dans la peau Le dermatophyte s’infiltre dans les couches les plus profondes de la peau Les kératinocytes libèrent des cytokines inflammatoires en réaction aux antigènes dermatophytes Le dermatophyte peut se propager du site principal de l’infection aux sites avoisinants Taches rondes roses à rouges, avec guérison au centre Desquamation de la peau (écailles dans les espaces palmés entre les orteils: macération) 1. Trichophyton 2. Epidermophyton 3. Microsporum Invasion du follicule pileux La cassure de tige du cheveux Alopécie (perte de cheveux) Prurit (démangeaison) Érythème (rougeur) Induration (gonflement) Chaleur Réponse inflammatoire locale dans la peau Tinea capitis Tinea corporis Tinea pedis Mycose du pied (pied d’athlète) Infection du cuir chevelu Infection du tronc et des extrémités de corps Légende: Physiopathologie Mécanisme Signe/Symptôme/Résultats de Laboratoire Complications Publié 17 février 2020 sur www.thecalgaryguide.com

acute-cholecystitis

Acute Cholecystitis: Pathogenesis and clinical findings Gallstone blocks the cystic duct, backing up bile into the gallbladder Gallstones causing physical trauma to gallbladder wall Irritation of adjacent diaphragm, stimulates phrenic nerve (C3-C5) Activates stretch receptors of visceral peritoneum, stimulates foregut autonomic nerves (T5-T8) Inflammatory mediator (i.e. prostaglandin) release by gallbladder and systemic inflammatory response Thickened gallbladder wall on ultrasound (gold standard test) On inspiration, the diaphragm pushes the gallbladder downward Irritation of parietal peritoneum, stimulates somatic nerves ↑ Permeability of vessels with systemic inflammation, which leak fluid from the blood into the interstitial space Radiating pain to the back and right shoulder Dull, diffuse abdominal pain referred to the epigastric region Fever, nausea/vomiting, tachycardia Positive Murphy’s sign (pain upon palpation of right upper quadrant [RUQ] on inspiration) Persistent RUQ pain, abdominal guarding and peritoneal signs Dehydration Authors: Yan Yu, Vina Fan Reviewers: Dean Percy, Mirna Matta, Crystal Liu, Ben Campbell Maitreyi Raman* * MD at time of publication Inflammation self-perpetuates Irritation of inner gallbladder wall/mucosa ↑ Gallbladder lumen pressure Intraluminal pressure exceeds arterial pressure ↓ Blood flow to gallbladder Gallbladder ischemia Local inflammation, loss of gallbladder mucosal integrity Bacterial invasionàtransmural inflammation of gallbladder Without treatment, prolonged ischemia and inflammation of the gallbladder Gallbladder gangrene (20%) Gallbladder perforation (20%) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 4 2019, updated May 16 2022 on www.thecalgaryguide.com

clostridium-difficile-infection-pathogenesis-and-clinical-findings

Clostridium difficile (C. diff) Infection Authors: Ryan Brenneis, Sravya Kakumanu Reviewers: Yoyo Chan, Sean Doherty, Vina Fan, Ben Campbell, Dr. Steve Vaughan*, Dr. Sylvain Coderre* * MD at time of publication Community exposure Infected close contacts Nosocomial exposure (most common) Poor hand hygiene and sanitization of surfaces and medical equipment Nosocomial risk factors Any antibiotic use (Especially clindamycin, fluoroquinolones, penicillins, cephalosporins) ↑ Antibiotic resistant strains Presence of pre-disposing risk factors (Note: do not need to be present for infection) Recent GI surgery Chemotherapy that has antimicrobial and immunosuppressive effects Usage of medications that reduce stomach acid (↑ pH) ↑ C. diff spores on surfaces and personnel Contact exposure Environmental exposure to C. diff carriers Inoculation of GI tract Disruption of normal gut microbiome allowing C. diff overgrowth Comorbidities (>65 years old, cirrhosis, inflammatory bowel disease, enteral feeding, obesity) via fecal-oral route Clostridium difficile Infection of GI Tract Spores unaffected by antibiotics germinate post-antibiotic treatment Infection recurrence Pseudomembranous colitis on endoscopy (colonic ulcerations potentially seen with severe infection) Hypotension Acute kidney injury Release of C. diff toxin A and B inactivates Rho and Ras GTPases in colonic epithelial cells (colonocytes) (Rho and Ras GTPases control cytoskeletal dynamics and gene expression) Cytoskeletal disorganization and arrest of RNA synthesis causes necrosis of colonocytes and triggers host immune response Neutrophil chemotaxis and activation ↑ Inflammation of colon Disruption of tight junctions between colonocytes Release of fluid into intestinal lumen and inability of colon to reabsorb it Toxic megacolon Bowel perforation Bloody stool (<10% of patients) Abdominal cramps Large bowel dilation from muscle paralysis Inflammation and destruction of underlying smooth muscle Breakdown of colonocyte cell membranes Inflammation of visceral peritoneum Volume depletion Watery diarrhea: ↑ frequency, small volume Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 30, 2019, updated May 16, 2022 on www.thecalgaryguide.com

Osteoporosis Pathogenesis and risk factors

Osteoporosis: Pathogenesis and risk factors Primary Osteoporosis Bone loss that occurs during normal human aging (e.g. Age > 30, post-menopausal women, and genetics). Secondary Osteoporosis Smoking, alcohol, ↓ exercise, chronic malnutrition, hyperthyroidism, hyperparathyroidism, corticosteroid use, ↓ vitamin D, bone malignancies, chronic kidney or liver disease, and malabsorption. Reduced peak bone mass achieved during skeletal growth and/or an imbalance in the factors favoring bone resorption compared to bone formation in adult bone ↓ Serum vitamin D from malabsorption, poor nutrition, or chronic liver/ kidney disease ↓ Serum activated vitamin D (precursor for Ca2+ transporters in the gut) ↓ Ca2+ absorption from gut ↓ Ca2+ available for mineralization of bone matrix Age related bone degeneration and ↓ exercise ↑ Reactive oxygen species (ROS) systemically due to aging ↑ Oxidative stress on bone ↑ Osteocyte death in cortical bones ↓ Bone Formation ↓ Estrogen in post-menopausal women Hyperparathyroidism/ bone malignanciesà ↑ parathyroid hormone (PTH) or parathyroid hormone-related (PTHR) protein released ↑ PTH and PTHR peptide receptor signaling in osteocytes results in ↓ osteoprotegerin (OPG) expression ↓ OPG secretion Hyperthyroidism à↑ T3 and T4 ↑ Thyroid receptor- alpha-1 activation (located in bones) ↑ Osteoclasts (cells that break down bone) ↑ Bone Resorption Corticosteroid use ↑ Corticosteroid binding to glucocorticoid receptors on bone suppresses OPG expression in bone Smoking Multiple mechanisms (e.g. ↓ blood supply to bone, ↑ free radicals, direct effects on RANKL/RANK/ OPG bone remodeling axis leading to alterations in osteogenesis ↑ Bone Resorption and ↓ Bone Formation Abbreviations: • T3 - Triiodothronine • T4 - Thyroxine ↓ Stimulation of OPG transcription in osteoblasts Authors: Ben Wajda, Arsalan Ahmad, Lance Bartel Reviewers: Alyssa Federico, Mehul Gupta, Tara Shannon, Reza Ojaghi, Usama Malik, Carol Hutchinson*, David Hogan* * MD at time of publication ↓ Inhibition of receptor activator of nuclear factor kappa-B ligand (RANKL) (receptor that stimulates osteoclast growth) Osteoporosis: Imbalance of bone formation and resorption leading to decreased bone mineral density and bone mass, or quality changes that lead to a decrease in bone strength and an increase risk of fractures Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 20, 2022 on www.thecalgaryguide.com

constatations-classiques-de-sclerose-en-plaques-sep-sur-irm-cerebrale

Constatations classiques de sclérose en plaques (SEP) sur IRM cérébrale Auteurs: Evan Allarie Davis Maclean Viesha Ciura* Rédacteurs: Yan Yu* Traducteurs: Liana Martel Eddy Lang* * MD au moment de la publication Infiltrations dans la région infratentorielle Perte de la densité neuronale/axonale dans la région affectée, remplacée par une gliose au fil du temps Remarque : les constatations peuvent varier. Les constatations présentées ici ne sont pas exhaustives, mais constituent certaines des zones les plus fréquemment mises en évidence par l'IRM du cerveau dans la SEP. Les sites les plus communément observés sont : les régions juxtacorticales, périventriculaires, infratentorielles, la moelle épinière et le nerf optique. Cependant, les lésions peuvent apparaître partout où il y a de la myéline dans le SNC. L'inflammation et la destruction actives permettent au contraste de gadolinium de traverser la barrière hémato-encéphalique, ce qui peut être visualisé comme un marqueur de l'inflammation active dans la SEP Lésion classique du nerf optique (CN II) en cas de névrite optique. Rehaussement par Gadolinium (↑ intensité du signal de la lésion après l’injection de gadolinium) sur cette image en T1 démontre une inflammation active Image Credits: Dr. Viesha Ciura Pour plus de détails sur la pathogenèse, voir la diapositive du Guide de Calgary: Multiple Sclerosis (MS): Pathogenesis and Clinical Findings Inflammation dans le système nerveux central (SNC) Les cellules T, les cellules B et les macrophages infiltrent le SNC Infiltration se produit autour des veinsàinflammation locale Infiltrats périveineux autour des veines médullaires (perpendiculaires aux ventricules) Inflammation et destruction de la barrière hémato-encéphalique ↑ liquide inflammatoire extravasculaire autour des lésions, qui apparaît hyperintense/brillant Lésions s’étendent autour des veines, créant les lésions ovoïdes charactéristiques Plaques hyperintenses perpendiculaires périventriculaires classiques en T2/FLAIR suivant les veins médullaires – ‘Doigts de Dawson’ Lésion hyperintense du pédoncle cérebelleux moyen en T2/FLAIR dans une localisation classique de la SEP Légende: Physiopathologie Mécanisme Signe/Symptôme/Résultats de Laboratoire Complications Publié 25 octobre 2020 sur www.thecalgaryguide.com

syndrome-de-guillain-barre

Syndrome de Guillain-Barré Infection GI/respiratoire Campylobacter jejuni, CMV, VIH , VEB (1-3 semaines auparavant) Mimétisme moléculaire : antigènes gangliosidiques partagés entre le nerf périphérique et les protéines d'enveloppe des agents pathogènes Auteurs: Nissi Wei Rédacteurs: Owen Stechishin, Matthew Harding, Cory Toth* Traducteurs: Liana Martel, Eddy Lang* * MD au moment de la publication ↑ protéines dans le LCR Déclencheurs mineurs (chirurgie, trauma, greffe de moelle osseuse) Anticorps IgG contre les gangliosides dans le sérum ECN: ↓ vitesse de conduction, bloc de conduction Polyneuropathie inflammatoire démylisante aiguë (PIDA) (80-90%) Initiation de la réponse immunitaire (mécanisme inconnu) La réponse immunitaire déclenchée réagit de manière croisée avec les nerfs périphériques, en commençant par les racines nerveuses ↑ perméabilité de la barrière hémato-nerveuse au niveau des racines nerveuses proximales Démyélinisation: les anticorps attaquent les cellules de Schwann dommage secondaire Lésion axonale: les anticorps attaquent les noeuds de Ranvier ECN: ↓ PAMC amplitude, vitesse de conduction normale Anomalies des mouvements extraoculaires (Syndrome de Miller Fisher – forme rare de PIDA à restriction régionale) Neuropathie axonale motrice aiguë (NAMA) Neuropathie axonale sensorielle motrice aiguë (NASMA) Faiblesse oculomotrice (NC III, IV, VI) Paralysie bulbaire (NC IX, X, XI,XII) Atteinte du nerf phrénique Polyneuropathie aiguë à médiation immunitaire Atteinte des nerfs crâniens Dysautonomie Rétention urinaire (transitoire, en fin de parcours) ↓ capacité à évacuer les sécrétions des voies respiratoires Troubles de dégluttitionà pneumonie par aspiration Paralysie du diaphragme Insuffisance respiratoire (Menace la vie: besoin d’une surveillance respiatoire et possiblement une assistance respiratoire) Abbreviations: • ECN - examen de Déficits moteurs Faiblesse des membres (les jambes sont généralement touchées en premier) Aréflexie universelle Déficits sensoriels Douleur & paresthésies au dos et dans les extrémités Tachycardie, Dysrhythmies (besoin d’une surveillance cardiaque) Fluctuation de la TA, hypotension • orthostatique conduction nerveuse PAMC – potentiel d’action musculaire composé Remarque : les fibres nerveuses périphériques Aα, Aβ (grands axones à conduction rapide et fortement myélinisés pour l'étirement des muscles, le toucher léger et la proprioception) sont plus touchées que les fibres Aδ et C (petites fibres moins myélinisées et à conduction lente pour la douleur et la température). CMV - Cytomégalovirus • NC - Nerf cranien • VEB - Virus Epstein-Barr Mort soudaine • Légende: Physiopathologie Mécanisme Signe/Symptôme/Résultats de Laboratoire Complications Publié 1 novembre 2013 sur www.thecalgaryguide.com

pleural-effusions-pathogenesis-and-anterior-posterior-chest-x-ray-findings

Pleural Effusions: Pathogenesis and Anterior-Posterior Chest X-Ray Findings Decubitus chest x-ray view causes fluid to accumulate on ipsilateral side. (Most sensitive view for small effusions) Excess fluid accumulation within pleural space that is gravity- dependent/free- flowing Large accumulation of fluid pressing against lung tissue and mediastinum Fluid layering (i.e. opacification) between lung and chest wall Author: Sravya Kakumanu Reviewers: Reshma Sirajee, Tara Shannon *Stephanie Nguyen, *Shelley Spaner * MD at time of publication Transudative pleural effusion *See Pathogenesis and Clinical Findings of Transudative Pleural Effusions slide Exudative pleural effusion *See Pathogenesis and Clinical Findings of Exudative Pleural Effusions slide Fluid accumulation at bottom of pleural space in anterior- posterior chest x- ray Lung atelectasis (lung collapse) Fluid is denser than air and appears white on x-ray ↓ Pressure and occupied space in thoracic cavity Meniscus sign (concave line above opacification) Opacification of affected pleural space Blunting of costophrenic angles Diaphragmatic silhouette sign (sharp diaphragm edge obscured by fluid) Mediastinal shift towards atelectic lung Contralateral mediastinal shift (when no lung atelectasis) Contralateral tracheal deviation Pleural infections ↑ Inflammation at infection site à↑ permeability of parietal pleura endothelium Bacterial invasion into pleural space from pulmonary parenchyma ↑ Migration of neutrophils and release of inflammatory cytokines in pleural space Inflammation ↑ activation of coagulation cascade and ↓ fibrinolytic activity ↑ Deposition of fibrin clots/membranes within pleural space creating septations Loculated pleural effusion/empyema (fluid stuck within septations within the pleural space) Opacification does not follow gravity Effusion does not move in decubitus view Pleural thickening (whitening of lung perimeter from fibrin deposition - more visible on CT scan) More rounded margins with chest wall/fissures Note: ~175-500mL of fluid may need to accumulate before being visible on an Anterior-Posterior Chest X-Ray Image credit: https://radiopaedia.org/cases/pleural-effusion-7 Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 22, 2022 on www.thecalgaryguide.com

iliotibial-band-itb-syndrome-pathogenesis-and-clinical-findings

Iliotibial Band (ITB) Syndrome: Pathogenesis and clinical findings Authors: Ciara Hanly, Alyssa Federico Reviewers: Tara Shannon, Hannah Koury, Mehul Gupta Extrinsic Risk Factors Intrinsic Risk Factors Genu varum or valgum (deformity causing outward or inward bowing of knees, respectively) ↑ Lengthening of ITB at lateral femoral epicondyle Ryan Shields* * MD at time of publication Leg length discrepancy Compensatory unilateral foot pronation and hip drop of shorter leg ↑ Stretch of ITB on longer leg Sudden ↑ in training volume and overtraining Repetitive flexion and extension of lower limb (i.e. running, cycling) Running surface with horizontal or vertical gradient ↑ Knee flexion at foot strike Excessively long strides ↑ Hip flexion Hip abductor weakness (gluteus medius, gluteus minimus, tensor fascia latae) ↑ Hip adductionà internal rotation at the knee Excessive foot pronation ↑ Stretch of ITB ITB originates from the iliac crest, runs past the lateral femoral epicondyle, and inserts into the lateral aspect of the proximal tibia Lower limb flexion and extension displaces the ITB over the lateral femoral condyle in an anterior-posterior direction ↑ Friction between ITB and lateral femoral condyle Blood vessels, nerves, Pacinian corpuscles (pressure and vibration receptors), and vascularized fat pad are compressed in sub-ITB space Activation of nociceptors (pain receptors) in femur Micro-trauma to ITB Inflammatory response and scar tissue formation Fluid ITB + Noble’s compression test: Patient supine with hip and knee flexed to 90o, pressure is applied to distal ITB while patient extends hip and knee àpain over distal ITB at 30o flexion + Ober test: Patient lays on unaffected side with knee flexed to 90o, hip abducted and extended, and patient asked to adduct hip as far as possibleà ↓ hip adduction on affected side Tenderness to palpation over lateral femoral epicondyle (2- 3cm above lateral joint line) Radiating pain to lateral thigh and calf Pain over lateral femoral epicondyle during maximal point of ITB tension, just prior to or during foot strike (i.e. during downhill walking or running) collection deep to ITB thickens Persistent pain throughout exercise Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 27, 2022 on www.thecalgaryguide.com

metabolic-alkalosis-pathogenesis

Metabolic Alkalosis: Pathogenesis Authors: Wazaira Khan Reviewers: Jessica Krahn, Emily Wildman, Austin Laing, Huneza Nadeem, Ran (Marissa) Zhang, Adam Bass* * MD at time of publication Primary hyperaldosteronism E.g., aldosterone- secreting mass, adrenal hyperplasia Secondary hyperaldosteronism E.g., renin-secreting mass, renal artery stenosis Pseudo- hypoaldosteronism E.g., Liddle’s Syndrome Unregulated aldosterone production in adrenal cortex Excess aldosterone suppresses renin production Unregulated renin production by juxtaglomerular cells Sustained ↑ in mineralocorticoid (aldosterone) activity Insertion of epithelial sodium channels on principal cells in collecting duct ↑ Water retention by the kidney ↑ Na+ reabsorption by principal cells ↑ EABV • ↑ Jugular venous pressure • Hypertension • Urine Na+ > 40 mEq/L Low renin, high aldosterone state Activation of renin- angiotensin-aldosterone system (RAAS) Release of aldosterone from adrenal cortex High renin, high aldosterone state ↑ Negative charge in collecting duct lumen K+ leaks into collecting duct lumen by principal cell to maintain electroneutrality Hypokalemia Intracellular K+ leaks out of any cell in the body to compensate for low serum K+ levels Extracellular H+ enters cell to maintain electroneutrality Intracellular acidosis Activation of compensatory acid secreting mechanisms in kidney Impaired tubular function E.g., loop/thiazide diuretics, Bartter’s/ Gitelman’s Syndrome Upper GI Loss E.g., vomiting, nasogastric suction Unregulated epithelial sodium channel activity in collecting duct mimicking aldosterone function ↑ in Na+ and water retention à RAAS inhibition ↓ Na+ and Cl- reabsorption in thick ascending limb or distal convoluted tubule Low renin, low aldosterone state ↑ Na+, Cl- and water secretion through kidney RAAS activation See “Physiology of RAAS” slide ↓ EABV • • • Temporary ↑ in mineralocorticoid (aldosterone) activity ↓ Jugular venous pressure Orthostatic hypotension Dry mucous membranes Urine Na+ < 20 mEq/L • Loss of fluid through GI tract ↓ HCl delivery to small intestine ↑ NH + secretion and 4 ↑ HCO3- reabsorption in proximal tubule ↑ H+ secretion in cortical collecting duct Loss of gastric contents, including HCl ↓ HCO3- secretion by pancreas, liver and intestines to neutralize HCl Loss of intrinsic acid to neutralize HCO3- ↑ Plasma [HCO3-] Metabolic Alkalosis Arterial blood gas pH > 7.40 Plasma [HCO3-] > 24 mEq/L Effective Arterial Blood Volume (EABV): component of arterial blood volume that is effectively perfusing organs Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 31, 2022 on www.thecalgaryguide.com

obstructive-sleep-apnea-pathogenesis-and-clinical-findings

Obstructive Sleep Apnea: Pathogenesis and clinical findings Vascular Factors: During recumbent sleep, more bodily fluids enter the head and neck area (compared to when the patient is standing/sitting) ↑ volume of head/neck tissue surrounding the upper airwayà possible airway obstruction Authors: Ciara Hanly Austin Laing Alexander Arnold Reviewers: Steven Liu Amogh Agrawal Yonglin Mai (麦泳琳) Naushad Hirani* Yan Yu* *MD at time of publication Neuromuscular Factors: Sleep onset and/or the sleeping state reduces the drive of respiratory muscles to breathe ↓ Upper airway neuromuscular activityà↓ upper airway caliber, ↑ upper airway resistance, ↑ upper airway collapsibility during sleep Structural Factors: Obesity, tonsillar or adenoid hypertrophy, macroglossia, ↑ neck circumference, craniofacial abnormalities Excess pressure on upper airway, or deformity to that area, ↑ risk of upper airway collapse Polysomnography Absence of airflow but persistent ventilatory effort Hypopnea or Apnea Paradoxical breathing Chest wall draws in and abdomen expands during inspiration Ventilatory effort persists against closed airway No air entry due to collapsed upper airway ↑ Negative intrathoracic pressure ↑ Venous return to right atrium Stretching of right atrial myocardium à secretion of atrial natriuretic peptide (ANP) ANP inhibits epithelial Na+ channels (ENaC) in the collecting ducts of the kidney from reabsorbing Na+ à Na+ excretion ↑ Na+ excretionà↑ water excretion Nocturia Complete or partial upper airway obstruction during sleep ↑ PCO2 & ̄ PO2 in the lungsà ̄ diffusion gradient of CO2 & O2 between lungs & arteries ↑ PaCO2,, ̄ PaO2 Respiratory acidosis (↑ [H+] in blood)àactivation of vascular endothelial voltage gated K+ channels Cerebral blood vessel dilation to provide adequate O2 to brain Morning Headaches Activation of central (medulla oblongata) & peripheral (carotid body) chemoreceptors ↑ Respiratory drive à ↑ activation of respiratory muscles (ventilatory effort ) Transient arousal from sleep ↑ sympathetic nervous system activityà arterial vasoconstriction ↑ systemic vascular resistance Systemic Hypertension ↑ intraluminal pressure within blood vesselsàadaptive vascular endothelial and smooth muscle changes Artery walls thicken, harden and lose elasticityà ̄ perfusion to end organs (such as the brain) Ischemic stroke Hypoxia during the day and night ↑ pulmonary vascular resistance Pulmonary Hypertension Right heart pumps against higher pulmonary pressure àcardiomyocytes undergo concentric hypertrophy over time Cor Pulmonale (Right heart failure due to pulmonary hypertension, separate from left heart failure) Respiratory muscles overcome upper airway obstructionà airway patency restored Sleep fragmentation ̄ Daytime cognitive performance and attentiveness ↑ Risk of motor vehicle accidents Daytime Sleepiness Eg. Epworth Sleepiness Scale >10 Abbreviations: PCO2: partial pressure of carbon dioxide PO2: partial pressure of oxygen PaCO2: partial pressure of carbon dioxide in arteries PaO2: partial pressure of oxygen in arteries Ventilatory response overcompensatesà breathe out more CO2 than is required for homeostasisà ̄ PaCO2 ̄ respiratory driveà ̄ ventilatory effort Resuscitative Gasping Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 19, 2013, updated May 31, 2022 on www.thecalgaryguide.com 阻塞性睡眠呼吸暂停:发病机制及临床表现 作者:Ciara Hanly, Austin Laing, Alexander Arnold 审稿人: Steven Liu, Amogh Agrawal, Naushad Hirani*,Yan Yu* 译者: Zesheng Ye(叶泽生) 翻译审稿人: Yonglin Mai(麦泳琳) *发表时担任临床医生 神经肌肉因素: 睡眠状态下, 患者无法通过 适当增加上气道肌张力来维持气道通畅 上气道神经肌肉活动 ̄à上气道直径 ̄, 上气道 阻力↑, 睡眠时上气道塌陷 结构(解剖)因素: 肥胖、扁桃体或腺样体 肥大, 舌体肥大, 颈围增大, 颅面部畸形 上气道压力过大或上气道畸形, 上气道塌陷 的风险 ↑ 血管因素: 仰卧位睡觉引起 夜间嘴侧液体移位 周围组织与压力 ↑à上气道阻塞 多导睡眠描记术 没有气流，但持 续通气 呼吸浅慢或 呼吸暂停 反常呼吸 吸气时胸壁凹陷, 腹部膨隆 持续通气以抵抗气道 闭合 上气道塌陷导致空气进 入气道受阻 腹膜腔负压↑ 静脉血回流右心室阻力↑ 右心房心肌细胞拉伸 à心房利钠肽分泌 (ANP) ANP抑制肾集合管的上 皮Na+通道(ENaC)对 Na+重吸收à Na+排出 Na+排出量↑ à 水排出量 ↑ 睡眠时全部 或部分上呼 吸道阻塞 肺内PO2 ̄ 且 PCO2↑ à CO2 及 O2在肺和动脉 间的扩散梯度 ̄ ↑ PaCO2, ̄ PaO2 呼吸性酸中毒 (血液中 [H+] ↑) à激活血管内皮电压 门控 K+ 脑血管扩张为大 晨间头痛 脑提供足够的 O2 激活中央(延髓)和外周(颈动脉体)的化学感受器 呼吸驱动↑à呼吸肌活动 (呼吸做功 )↑ 短暂的睡眠唤醒 通道 交感神经系统活动↑ 全天缺氧 肺血管阻力↑ 肺动脉高压 右心泵血以抵抗肺 动脉高压à 随着时 间推移，心肌向心 性肥大 肺心病(区别于左 心衰，右心衰是肺 动脉高压所致) 呼吸肌克服上气道阻力à 气道 明显恢复 睡眠过程不连续 白天的认知功能 及注意力 ̄ 机动车辆事故风险↑ 白天嗜睡 à 动脉收缩 全身血管阻力↑ 高血压 血管内压力↑ à 血 管内皮和平滑肌发生 适应性改变 动脉壁增厚、硬化、失 去弹性à器官血液灌 注量 ̄ (如脑部) 缩写: PCO2:二氧化碳分压 PO2:氧分压 PaCO2:动脉二氧化 碳分压 PaO2:动脉血氧分压 通气过度 à呼出CO2 ↑ à PaCO2 ̄ 呼吸驱动 ̄à 呼吸做功 ̄ 复苏性鼾音 夜尿症 如:伊普沃斯嗜睡评分 >10 缺血性卒中 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年8月19日发表 www.thecalgaryguide.com, 2022年5月31日更新

阻塞性睡眠呼吸暂停-发病机制及临床表现

阻塞性睡眠呼吸暂停-发病机制及临床表现

囊性纤维化-胸部-x-线和肺窗-ct-扫描结果

囊性纤维化-胸部-x-线和肺窗-ct-扫描结果

gout-pathogenesis-of-x-ray-findings

Gout: Pathogenesis of X-Ray findings Authors: Omer Mansoor, Nameerah Wajahat Reviewers: Reshma Sirajee, Tara Shannon *Stephanie Nguyen, *Shelley Spaner *MD at time of publication Hyperuricemia See hyperuricemia slide for mechanism ↑ Uric acid concentration in blood leaks into joints as monosodium urate (MSU) crystals Uric acid crystallizes due to lower temperature, change in pH, mechanical stress and other synovial factors Crystals found more commonly in 1st MTP joint > ankle > wrist MSU deposits within the bone producing intra-osseus tophi (stone-like deposits of crystals) MSU deposits in soft tissue and bone ↑ Inflammatory marker recruitment causes granulomatous inflammation Osteoclasts (↑ bone resorption) are activated, and osteoblasts (↑ bone formation) are inhibited at site of inflammation Marked localized bone loss ‘Rat Bite’ erosions Intra-osseus bone lesion (rare and non-specific for gout) Joint effusions may be seen on x-ray as an early finding in the acute phase of gout Soft Tissue Tophi (appear cloudy and can hide other x-ray findings) Normal bone density and preserved joint space (until late in the disease) Overhanging sclerotic margins Bone remodelled in an outward fashion to create the edge Punched out lytic bone lesions Appear as circular ‘hole punches’ in bone Note: Repeated episodes of gout must occur for 5 to 10 years before most joint changes may be seen on x-ray Image credit: Radiopaedia Legend: Pathophysiology Mechanism Sign/Radiographic Findings Complications Published June 7, 2022 on www.thecalgaryguide.com

beta-thalassemia-minor

Beta Thalassemia Minor: Pathogenesis and clinical findings Authors: Andrew Brack Yan Yu Huneza Nadeem Reviewers: Wendy Yao Katie Lin Liana Martel Ran (Marissa) Zhang Man-Chiu Poon* Lynn Savoie* * MD at time of publication Composition of normal adult hemoglobin (Hb): Ineffective erythropoiesis Excessive free α-chains accumulate, and α-chains precipitate in RBC precursors and RBCs These precipitants (inclusion bodies) give RBCs an abnormal shape Spleen destroys abnormally shaped RBCs Spleen accumulates destroyed red blood cells and enlarges to an abnormal size Splenomegaly (*See Splenomegaly slide for clinical findings) Mild microcytic anemia Hb: ↓ MCV: ↓ • • • 96% HbA (ααββ=2 α chains + 2 β chains) 2% HbA2 (ααẟẟ) 2% HbF (αα!!; fetal hemoglobin) Genetic point mutation on a single allele of the β globin gene on chromosome 11 (heterozygous with one normal alleleà HbA ααββ0 or ααββ+) Mild ↓ of β-chain production relative to ⍺- chain ↓ β-chain available for HbA synthesis Body compensates by ↑ production of non-affected globins (HbA , HbF) 2 ↑ HbF (nonspecific), ↑ HbA2 (hallmark sign specific to Beta Thalassemia Minor) on electrophoresis • • α-chain precipitates form structures visible under the microscope Inclusion bodies Heme from the destroyed RBCs is degraded into bilirubin and iron Excess unconjugated bilirubin is released into the blood Excess bilirubin is deposited in the skin Jaundice Excess iron is stored as ferritin ↑ or normal ferritin Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published June 8, 2022 on www.thecalgaryguide.com

gastroenteritis-pathogenese-und-klinische-befunde

Gastroenteritis: Pathogenese und klinische Befunde

negativdruck-lungenodem-pathophysiologie

Negativdruck-Lungenödem: Pathophysiologie

benzodiazepine-wirkmechanismus

Benzodiazepine: Wirkmechanismus

succinylcholin-depolarisierende-muskelrelaxanzien

Succinylcholin (Depolarisierende Muskelrelaxanzien)

Status-Epilepticus

Status Epilepticus: Pathogenesis and clinical findings Authors: Katherine Liu Reviewers: Negar Tehrani Ephrem Zewdie Ran (Marissa) Zhang Carlos Camara-Lemarroy* * MD at time of publication Structural brain injury (stroke, trauma, hypoxia) Drugs that lower seizure threshold Antiseizure drug discontinuation Alcohol, barbiturate, benzodiazepine withdrawal Metabolic disturbance Infection See “Generalized Seizures” Altered excitability and communication between neuronal structures Isolated generalized seizures Ongoing seizure activity and repetitive neuronal firing Changes in receptor trafficking (seconds to minutes) Changes in neuromodulator expression in hippocampus (minutes to hours) Endocytosis of synaptic GABAA inhibitory receptors ↓ Number of inhibitory GABAA receptors Progressive resistance to benzodiazepines (drugs that upregulate GABA receptors) as seizure continues ↑ Expression of excitatory peptides (substance P, neurokinin B) Abbreviations: • GABA- γ-aminobutyric acid • NMDA- N-methyl-D-aspartic acid • AMPA- α-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid NMDA and AMPA excitatory receptors mobilize to synaptic membrane ↑ Number of excitatory NMDA and AMPA receptors ↓ Expression of inhibitory peptide (dynorphin, galanin, somatostatin, neuropeptide Y) Seizure-induced failure of inhibitory mechanisms involved in seizure termination and increased neuronal excitability Status Epilepticus (SE) An abnormally prolonged seizure ≥ 5 minutes or 2+ sequential seizures without full recovery in between ↑↑ Glutamate release and activation of NMDA excitatory receptors ↑ Ca2+ entry into neurons Mitochondrial dysfunction ↑ Reactive oxygen species (nitric oxide) production Neuronal injury/death (↑ risk of developing chronic epilepsy) ↑ Autonomic activity Intense, sustained muscle contractions Persistent stimulus OR altered neuronal landscape (i.e., Immune mediated) Refractory SE: SE that does not respond to 1st or 2nd line therapy Prolonged seizures (≥30 mins) lead to failure of compensatory mechanisms Circulatory collapse ↓ Cerebral blood flow • Hypertension • Hyperglycemia • ↑ Cardiac output • ↑ Secretions • Hypotension • Hypoventilation Energy demands > ATP produced through oxidative phosphorylation Myocytes start utilizing anerobic glycolysis ↑ Lactic acid production ↑ Serum lactate Sustained muscle activity produces body heat Hyperpyrexia (axillary temperature ≥ 40° C) Myocyte injury Leakage of muscle contents into the circulation (Rhabdomyolysis) ↑ Serum creatine kinase Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published June 27, 2022 on www.thecalgaryguide.com

pheochromocytoma-pathogenesis-and-clinical-findings

Pheochromocytoma: Pathogenesis and clinical findings Author: Jaye Platnich Huneza Nadeem Reviewers: Mark Elliott Alexander Arnold Ran (Marissa) Zhang Hanan Bassyouni* * MD at time of publication ↑ Blood pressure results in the activation of neural pain receptors Sustained or paroxysmal 2o hypertension (↑ blood pressure) Pallor Tachycardia (↑ heart rate), palpitations Diaphoresis (excessive sweating) Hyperglycemia Weight loss, fatigue Familial Disorders (10%) E.g., Multiple Endocrine Neoplasm 2 Syndrome (MEN2) types A and B, Neurofibromatosis 1 (NF-1), Von Hippel Lindau Syndrome (VHL), familial pheochromocytoma Dysfunction of various tumor suppressor and/or oncogene proteins Uncontrolled proliferation of the chromaffin cells in the medulla of the adrenal gland(s) Adenoma formation (10% bilateral) Over-production of epinephrine and norepinephrine from the adrenal adenoma(s) or extra- adrenal tumour (10%) Detectable metanephrines (epinephrine/norepinephrine breakdown products) in both plasma and urine Sporadic DNA mutations arising from DNA damage from exposure to mutagens, malignancy (10%), or during DNA replication Detectable mutations on the Von Hippel Linda (VHL), (Rearranged During Transcription) RET, (Succinate Dehydrogenase) SDH, and/or other tumour suppressor or oncogenes Visible adrenal mass on CT scan Heart attack, stroke, or death (Note: These tumors can be fatal therefore screening is essential in patients with adrenal masses or 2o hypertension) Episodic hyper-activity of the sympathetic nervous system Hyper-stimulation of G protein-coupled receptors involved in catabolic metabolic processes Headaches ↑ Vasoconstriction of peripheral blood vessels Hyper-stimulation of adrenergic receptors on cardiac myocytes ↑ Secretion from the eccrine sweat glands Panic, tremor, anxiety ↑ Ability to mobilize glucose into the bloodstream through enhanced lipolysis, glycogenolysis and gluconeogenesis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 20, 2014, updated June 27, 2022 on www.thecalgaryguide.com

overdiagnosis-in-medicine-causes-and-complications

Overdiagnosis in Medicine: Causes and Complications Expectation that negative experiences represent a symptom of pathology rather than a part normal human experience Profit-motivated industries (e.g pharmaceutical companies) ↑ The number of diagnosed individuals serves to ↑ profits by expanding consumer base for treatments Authors: Davis Maclean Reviewers: Ben Campbell Eddy Lang* *MD at time of publication Unintended consequences of disease screening programs Direct to consumer testing (e.g home medical genetics testing kits) Note: Misdiagnosis ≠ Overdiagnosis Misdiagnosis refers to making an incorrect diagnosis in a symptomatic patient. Defensive medical practices Increased testing to ‘rule out’ pathology and reduce legal liability ↑ Availability of diagnostic tests Technological advancements leading to ↑ sensitivity of diagnostic tests Common public perceptions of health and healthcare Public overestimation of benefit and underestimation of risk modern medical interventions Assumption that more medical information (e.g testing) results in better health ↑ Number of findings on diagnostic tests (e.g Imaging and lab work) Medicalization of normal life experiences Overdetection: Identification of an abnormality that would not have caused any symptoms or harm in the patient’s lifetime if left undiscovered (e.g detection of subsegmental pulmonary embolism) Overdefinition: Lowering thresholds for classification of diseases and what is considered abnormal without net benefit for those diagnosed (this includes people with symptoms but who are more likely to be harmed than benefit from a diagnosis) Overdiagnosis: making an accurate diagnosis in an patient where making the diagnosis does not produce a net benefit for the patient Overtreatment: treatment that occurs in absence of evidence for net benefit to the patient Treatment side effects ↓ Quality of life (e.g nausea and fatigue secondary to chemotherapy) Overtreatment and overutilization are common consequences of overdiagnosis, but can happen in the absence of overdiagnosis Overutilization: ↑ Use of health services and systems without evidence of net benefit ↑ Health system spending Unnecessary testing Testing-related complications (e.g infection of surgical biopsy site) ↑ Risk for other Illness (e.g ↑ risk of infection in the setting of immunotherapy) Indirect costs: (e.g time off work for medical appointment, travel costs) ↑ Individual costs Direct costs: paying for additional tests and treatment (e.g medications) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published June 30, 2022 on www.thecalgaryguide.com

kolorektales-karzinom-pathogenese-und-klinische-befunde

kolorektales-karzinom-pathogenese-und-klinische-befunde

epidurales-hamatom-pathogenese-und-klinische-befunde

epidurales-hamatom-pathogenese-und-klinische-befunde

nicht-depolarisierende-muskelrelaxanzien

Nicht-Depolarisierende Muskelrelaxanzien Z.B. Pancuronium, Rocuronium, Atracurium, Vecuronium

arteriosklerose-komplikationen

arteriosklerose-komplikationen

arteriosklerose-pathogenese

arteriosklerose-pathogenese

koronare-herzkrankheit-khk-pathogenese-verschiedener-formen-der-khk

koronare-herzkrankheit-khk-pathogenese-verschiedener-formen-der-khk

orthostatische-hypotonie-pathogenese-und-klinische-befunde

orthostatische-hypotonie-pathogenese-und-klinische-befunde

perikarderguss-tamponade-pathogenese-und-klinische-befunde

perikarderguss-tamponade-pathogenese-und-klinische-befunde

induction-of-labour-ripening-of-the-cervix-mechanisms-and-methods

Induction of Labour & Ripening of the Cervix: Mechanisms and methods Bishop Score – based on: • Cervical dilation • Cervical effacement • Cervical consistency • Cervical position • Station Amniotic membranes ruptured IV artificial oxytocin administration Stimulates Ca2+ release from intracellular stores in myometrium smooth muscle Selected Indications for Induction of Labour (Risk of continuing pregnancy > delivering) Please refer to “Induction of labour: Indications and contraindications” slide Bishop Score > 6 Cervix favorable ↑ Natural release of prostaglandins from uterine wall Bishop Score 4-5 Proceed based on clinical picture Amniotic membranes intact Amniotomy to artificially rupture amniotic membranes Rush of amniotic fluid Bishop Score < 3 Cervix unfavorable and requires ripening Artificial prostaglandin into vagina (gel or vaginal insert) Ripening options Ripening balloon in cervix Pressure applied to internal and external cervical os Foley catheter in cervix Pressure applied to internal cervical os Act as calcium ionophores to áintracellular Ca2+ Activate EP1 and EP3 receptors on myometrial cells Lack of fluid cushion causes more fetal head engagement Fluid flow may carry umbilical cord with it Cord prolapse (if fetal head not engaged/ low enough in pelvis to block exit of cord) Degradation of collagen in the connective tissue stroma of cervix Cervix softens Cervical dilation Cervix stretches (until balloon falls out) Author: Lindey Felske Reviewers: Ran (Marissa) Zhang Brianna Ghali Ingrid Kristensen* * MD at time of publication Risk of uterine rupture (if prostaglandins used as a ripening method after previous C- section) Uterine contractions ↑ Myometrial contractility ↑ Pressure on cervix Labour If needed, proceed to amniotomy and/or oxytocin once cervix is favorable Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 4, 2022 on www.thecalgaryguide.com

postpartum-puerperal-fever-pathogenesis-and-complications

Postpartum (Puerperal) Fever: Pathogenesis and complications Author: Lindey Felske Reviewers: Brianna Ghali Ran (Marissa) Zhang Ingrid Kristensen* * MD at time of publication Breast Feeding Delayed gastric emptying in pregnancy ↑ Risk of aspiration during delivery Inhalation of gastric contents Chemical burn of the airways from gastric acid Tissue injury Chemokines released by alveolar cells recruit neutrophils Accumulation of neutrophils and plasma exudate in alveoli Aspiration Pneumonia Delivery (Vaginal or Cesarean Section) Tissue damage: Urinary tract catheterization Foreign body can: Introduce bacteria into bladder Provide a biofilm surface for bacterial adhesion Cause mucosal irritation Invasion of bacteria into urinary tract mucosa • • • • Perineal tear/episiotomy (perineal incision) Abdominal incision site Uterine damage Retained products of conception (RPOC) Bacteria enter open tissue Production of antimicrobial peptides and proinflammatory mediators in epidermis Cellulitis Necrosis of RPOC (good medium for bacterial growth) Post-operative pain Hypoventilation from shallow breathing Low volume in alveoli Alveolar collapse Endogenous cervicovaginal flora migrate into the uterine cavity Infiltration of bacteria into endometrium Endometrial TLR4 receptors recognize the endotoxin of Gram-negative bacteria Secretion of proinflammatory cytokines (IL-6, IL-8) and prostaglandin E(2) Activation of coagulation cascade Coagulation in areas of hemostasis (e.g., deep veins) Deep vein thrombosis Dislodged DVT travels to pulmonary arteries Pulmonary embolism • • • Skin openings in breasts (milk ducts +/- cracks) Bacteria from skin and/or saliva enter body Milk backup from blocked duct or poor breastfeeding technique Milk stasis provides environment for bacterial growth Upregulation of IFN- γ, and IL-12A cytokines in milk ducts Mastitis Collection of inflammatory exudate Breast abscess Cytokine expression and inflammatory cell infiltration Sloughing of urinary tract lining to reduce bacterial load Atelectasis Maternal fever (> 38.0°C) within 6 weeks of delivery Urinary tract infection Endometritis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 4, 2022 on www.thecalgaryguide.com The image part with relationship ID rId4 was not found in the file.

Trendelenburg Gait: Pathogenesis and clinical findings

Trendelenburg Gait: Pathogenesis and clinical findings Authors: Cierra Stiegelmar, Meaghan MacKenzie Reviewers: Mehul Gupta, Alyssa Federico, Tara Shannon, Kristi Billard, Ranita Manocha*, Gentson Leung* * MD at time of publication Uncompensated Trendelenburg gait Compensated Trendelenburg gait Iatrogenic Muscle pathology Skeletal Pathology Neurological Pathology Congenital hip deformity (e.g., developmental dysplasia) Degradation or damage to hip bones (e.g., acetabular or femur fracture) Hip replacement surgery Strain or trauma to hip abductors (gluteus medius and minimus) Hip abductors detach from greater trochanter ↓ Structural integrity in bones that hip abductors use for leverage Hip abductors fail to maintain a level pelvis during stance phase of gait cycle Trendelenburg Gait Failure to keep the pelvis level when the contralateral leg is raised during walking (contralateral hemi-pelvis drops) Lesion at or above the superior gluteal nerve (innervates hip abductors) Paralysis or paresis of hip abductors Thorax doesn’t lean toward the affected hip to correct balance Thorax leans toward the affected hip to correct balance Trendelenburg sign Unable to maintain a horizontal pelvis during 30 seconds of standing on affected leg Can manifest as bilateral abductor dysfunction (same mechanisms as unilateral dysfunction) Knee valgus Accentuated side-to- side trunk movement Force of gait impact is directed to lateral knee joint Stimulation of pain receptors in bone Lateral Sacroiliac knee pain joint pain Abnormal biomechanical forces are applied to the affected hip and adjacent joints when walking Hip joint is subjected to abnormal wear and tear Degeneration of affected hip joint Suprapelvic muscles and hip flexors (psoas and rectus femoris) engage in an attempt to correct pelvis alignment Prolonged abnormal force and function of suprapelvic and hip flexor muscles Strain in suprapelvic, psoas and rectus femoris muscles ↓ Hip abductor activation in affected hip Abductor muscle atrophy in affected hip ↓ Range of motion in hip abduction and internal rotation Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Feb 15, 2016, updated July 5, 2022 on www.thecalgaryguide.com

Epilepsy Pathogenesis

Epilepsy: Pathogenesis Genetic susceptibility Angelman syndrome, Fragile X syndrome, Tuberous sclerosis, neurofibromatosis Chromosomal abnormalities cause abnormal neural patterns Neural Cerebral palsy, focal cortical dysplasia Malformation of cortical development Cerebrovascular Intracranial hemorrhage, ischemic stroke Other Acquired Head trauma, cerebral infection (i.e., HSV1, VZV, cysticercosis) Neoplasm Metabolic Inborn errors of metabolism Inherited enzyme deficiencies Neurodegenerative Alzheimer’s Disease Protein-rich plaque build-up and brain atrophy Inflammation and formation of scar tissue irritates neural tissue Infiltration of mass, grey matter irritation Damage to the brain and subsequent alteration of neuronal circuitry Neurotransmitter imbalances (i.e. ↑ glutamate, ↓ GABA, ↓ serotonin, ↓ dopamine, ↓ noradrenaline) Abbreviations: • HSV1 – Herpes Simplex Virus 1 • VZV – Varicella Zoster Virus ↑ Inflammatory cytokines (e.g. interleukin-6, tumor necrosis factor-α) Altered neurogenesis and gliosis Ion channel and receptor dysfunction causes imbalance of ion channel charges Authors: Keerthana Pasumarthi Christopher Li Reviewers: Negar Tehrani, Ephrem Zewdie, Ran (Marissa) Zhang, Carlos R. Camara-Lemarroy* * MD at time of publication Neurons fire in burst activity (referred to as paroxysmal depolarization shift) and often in groups (hypersynchrony) Abnormal neural activities eventually create self-reinforcing circuits and transform neural network over time Injuries from falls, bumps, operating heavy machinery Involuntary contractions Loss of consciousness Post-ictal confusion Recurrent seizures Sudden Unexplained Death of Epilepsy Patient (SUDEP) Loss of airway reflexes Aspiration of saliva or food contents Aspiration Pneumonia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 5, 2022 on www.thecalgaryguide.com

Cervical Insufficiency

Cervical Insufficiency: Pathogenesis and clinical findings Cervical lacerations Cervical loop Cone biopsy electrosurgical procedure excision procedure Cervical procedures Post-procedure cervical re-modelling ↓ Structural collagen in extracellular matrix Opened cervix allows for ↑ voiding of vaginal skin cells, bacteria, mucous and fluid Fetal head moves lower into pelvis, exerting pressure on pelvic ligaments Hysteroscopy dilatation and curettage Antepartum Sterile intra-amniotic infection inflammation Inflammatory cascade within cervix ↑ Local myometrial and cervical prostaglandins/ cytokines ↑ Collagenase and leukocyte elastase increases break down of collagen Congenital abnormality of collagen synthesis Ex. Ehler-Danlos syndrome ↑ Vaginal discharge Change in color of vaginal discharge Braxton-Hicks-like contractions Menstrual-like cramps Back ache ↓ Cervical tensile strength and rigidity Cervical Insufficiency Spontaneous dilation and thinning of cervix Unknown cause Prolapsed fetal membranes Second trimester loss or preterm birth Risk of recurrent second trimester loss or preterm birth Authors: Kiera Pajunen Reviewers: Ran (Marissa) Zhang Brianna Ghali Ingrid Kristensen* * MD at time of publication Debris seen in amniotic fluid on U/S Short cervix (<2.5cm on trans-vaginal ultrasound) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 5, 2022 on www.thecalgaryguide.com

Mastitis

etomidate

Etomidate Ultrashort-acting carboxylated imidazole anesthetic administered intravenously to induce unconsciousness, usual dose 0.3 mg/kg IV Directly inhibits adrenal 11-beta- hydroxylase (enzyme responsible for cortisol biosynthesis) ↓ Adrenal cortisol production ↓ Serum cortisol available for stress response Transient adrenal steroid insufficiency ↑ Morbidity & mortality in trauma/critically ill patients (Contraindicated in sepsis) Inhibits nitric oxide signaling Transient cerebral vasoconstriction ↓ Cerebral blood flow ↓ Oxygen delivery to brain ↓ Cerebral metabolic rate Suppression of electrical activity in brain Flat electroencephalogram Binds to GABAA (inhibitory CNS neurotransmitter) receptor Authors: Cindy Chang Ran (Marissa) Zhang Reviewers: Melissa King Brooke Fallis Julia Haber* * MD at time of publication Abbreviations: • CNS - Central Nervous System • GABAA- Gamma- aminobutyric acid type A • TRPA1- Transient receptor potential type A1 Higher selectivity for specific GABAA receptor subtypes compared to other induction agents Positively modulates GABAA receptor (GABAA receptor activated at lower concentrations of GABA ) ↓ Cerebral blood volume Activation of fewer GABAA receptor subtypes in neurons and cardiovascular structures compared to other induction agents ↓ Intracranial pressure ↑ Hemodynamic stability (minimal changes in blood pressure or heart rate) Myoclonus (brief, involuntary, irregular muscle twitch) ↑ Spontaneous CNS neuron firing to skeletal muscle Prolonged opening of GABAA receptors (acts as ion channel for chloride) Inhibits activity of nerve cells in the reticular activating system Activation of peripheral nociceptor receptors ↑ Involuntary muscle contractions Influx of chlorideàHyperpolarization of nerve membranes in reticular activating system (brainstem neuronal network that regulates arousal and sleep- wake transitions) Depression of arousal & loss of consciousness Induction of general anesthesia (no analgesic effect) Direct activation of TRPA1 cation channels (key receptor in pain pathway) Stinging pain with injection (Treat with co-administration of local anesthetic) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 9, 2022 on www.thecalgaryguide.com

hyperkalemia-pathophysiology-intracellular-shift-and-intake

Hyperkalemia (intracellular shift and ↑ intake): Pathophysiology ↑ K+ dietary intake (rarely causative) β2 receptor inhibition (i.e. beta blockers) Digoxin α1 receptor stimulation (i.e. epinephrine, norepinephrine) Insulin deficiency or resistance (i.e. diabetes mellitus) ↓ Stimulation of NHE1 (moves 1 Na+ into cell, 1 H+ out of cell) throughout body Normal Anion- Gap Metabolic Acidosis (NAGMA) Excess serum H+ results in ↓ NHE1 activity (See NAGMA: Pathogenesis and Laboratory Findings slide) ↑ Serum osmolarity (i.e. hyperglycemia) Osmotic movement of water from cells to serum Cell lysis (i.e. tumour lysis syndrome, rhabdomyolysis, hemolytic anemia) ↑ K+ release from lysed cells into the serum Na+/K+ ATPase (moves 3K+ into cell, 2 Na+ out) activity inhibited on cells throughout body ↓ Activity of Na+/K+ ATPase on cells throughout the body ↓ Amount of K+ entering cells ↓ NHE1 activity prevents Na+ from entering the cell Lack of high intracellular [Na+] needed to drive the Na+/K+ ATPase on cells Loss of water from cells ↑ intracellular [K+] K+ moves down concentration gradient from cell into serum ↑ K+ available for absorption Since K+ is dissolved in water, some K+ is carried by water as water osmotically moves through water channels into the serum (phenomenon known as “solvent drag”) See Hyperkalemia: Clinical Findings slide Authors: Mannat Dhillon, Joshua Low, Emily Wildman Reviewers: Huneza Nadeem, Marissa (Ran) Zhang, Andrea Kuczynski, Yan Yu*, Kevin McLaughlin*, Adam Bass* * MD at time of publication ↑ K+ in serum Hyperkalemia Serum [K+] > 5.1 mmol/L Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 17, 2022 on www.thecalgaryguide.com

complicaciones-de-la-enfermedad-renal-cronica

complicaciones-de-la-enfermedad-renal-cronica

fisiologia-del-sistema-renina-angiotensina-aldosterona-sraa

fisiologia-del-sistema-renina-angiotensina-aldosterona-sraa

covid-19-新型冠状病毒肺炎-病理生理学和临床表现

covid-19-新型冠状病毒肺炎-病理生理学和临床表现

hyperkalemia-↓-renal-excretion-pathophysiology

Hyperkalemia (↓ Renal Excretion): Pathophysiology Non-steroidal anti- inflammatory drugs (NSAIDs) Inhibition of prostaglandins which promote renin secretion (see NSAIDs and the Kidney: Mechanism of Action and Side Effects slide) Diabetic Nephropathy Acute (AIN)and chronic (CIN) interstitial nephritis Immune-mediated damage of the kidney tubule and interstitium Damage to distal tubule leads to aldosterone resistance at principal cell Aldosterone cannot ↑ EnaC insertion on principal cell of CCD Epithelial sodium channel (ENaC) blockers Acute kidney injury and chronic kidney disease ↓ Effective arterial blood volume (volume of blood effectively perfusing tissue) ↓ Oxygen perfusion to renal tissue causing renal ischemia Autonomic neuropathy ↓ sympathetic drive to produce renin Chronic juxtaglomerular cell damage ↓ synthesis of renin Blockage of ENaC on the principal cells of the CCD Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) Angiotensin II is either not formed (ACEi), or blocked at its receptor (ARBs) Angiotensin II cannot stimulate the release of aldosterone from the adrenal cortex Adrenal Insufficiency Adrenal gland cannot produce sufficient amounts of aldosterone ↓ Renin secretion by the afferent arteriole prevents RAAS activation ↓ Aldosterone release from adrenal cortex ↓ ENaC (Na+ reabsorption channel) expression on principal cells of the cortical collecting duct (CCD) Damage to kidney causes renal impairment and ↓ glomerular filtration rate ↓ Glomerular filtrate production means ↓ tubular flow rate ↓ Na+ delivery to the distal tubule ↓ Na+ reabsorption by ENaCs at the principal cell in CCD ↓ Na+ and water reabsorption by ENaCs in CCD ↓ Effective arterial blood volume (EABV) Activates renin-angiotensin-aldosterone system (RAAS) leads to ↑ renin secretion in the afferent arteriole (see Physiology of the renin-angiotensin-aldosterone system (RAAS) slide) ↑ Na+ and water loss in tubular lumen ↑ Positive charge in tubular lumen ↓ Electronegativity gradient in tubular lumen of CCD ↓ K+ excretion by the principal cell in the CCD as there is less of a electronegative gradient ↑ Accumulation of K+ in blood Hyperkalemia Serum [K+] > 5.1 mmol/L See Hyperkalemia: Clinical Findings slide In the case of diabetic nephropathy and NSAIDS ↓ EABV does not stimulate RAAS and therefore aldosterone production ↓ Renin ↓ Aldosterone ↑ Renin secretion activates an ↑ in aldosterone production but aldosterone action at the principal cell is blocked because of ENaCs or resistance in AIN and CIN ↑ Renin ↑ Aldosterone In the case of ACEi, ARBs, or adrenal insufficiency ↑ renin secretion does not lead to ↑ aldosterone ↑ Renin ↓ Aldosterone Note: as described in the above flow chart, measuring serum renin and aldosterone levels can be used to help diagnose the cause of hyperkalemia. Authors: Mannat Dhillon, Joshua Low, Emily Wildman, Huneza Nadeem Reviewers: Andrea Kuczynski, Marissa (Ran) Zhang, Adam Bass*, Kevin McLaughlin* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Aug 2, 2022 on www.thecalgaryguide.com

exudative-pleural-effusions-pathogenesis-and-lab-findings

Exudative Pleural Effusions: Pathogenesis and Lab Findings Authors: Sravya Kakumanu Reviewers: Ben Campbell *Tara Lohmann * MD at time of publication Chylothorax Damage to thoracic duct Leakage of lymphatic fluid into pleural space Pulmonary embolism Clot obstructs blood flow to lung Infarcted lung tissue Lung infection (e.g. pneumonia, tuberculosis) Lung infection signals inflammatory response Systemic Lupus Rheumatoid Erythematosus (SLE) arthritis (RA) Autoimmune antibodies localize to pleura Pleural tumors (primary or secondary from metastatic cancer) Inflammatory cells migrate to affected site and release cytokines ↑ Permeability of pleural capillaries ↑ Fluid leakage across capillaries Exudative Pleural Effusion Cancer invades lymphatic drainage of pleural space (PS) ↓ Drainage of pleural fluid (PF) from pleural space If infectious etiology Tumor invasion = inflammatory response See Pleural Effusions: X-ray Findings and Physical Exam Findings of Lung Diseases slides ↑ Permeable pleural capillaries allow ↑ protein and cell leakage into pleural space If pleural tumour: Release of cancer cells into pleural space Cancer cells on PF cytology 60-75% sensitive for malignancy If rheumatoid arthritis: Release of auto-antibodies into pleural space Auto-antibodies initiate inflammatory response in pleural space ↑ Inflammatory cells have ↑ glucose metabolism in pleural space Sterile PF with mildly elevated white blood cells, normal pH, normal glucose ↑ Inflammation at infection site damages endothelium of pleura Pleural Infection Stage I: Simple Parapneumonic Effusion ↑ Inflammatory cells and bacterial cells in pleural space have ↑ glucose metabolism in pleural space Bacterial invasion from infected parenchymaà pleural space < 40mg/dL glucose in PF ↑ Activation of coagulation cascade and ↓ fibrinolytic activity ↑ Deposition of fibrin clots/membranes within pleural space creates loculated effusion (compartmentalized effusion due to septations in pleural space) ↑ Production of lactate dehydrogenase (LDH) (LDH maintains NAD+ supply during ↑ glucose metabolism) ↑ CO2 production pH of PF < 7.20 ↑ CO2 production pH of PF < 7.20 < 3.3mmol/L glucose in PF Pleural Infection Stage II: Complicated Parapneumonic Effusion Loculated effusion OR bacteria present OR ↓ pH + ↓ glucose ↑ Fibroblast proliferation creates thickened pleura ↑ Pus in pleural space Pleural Infection Stage III/Empyema: Loculated effusion and pus in pleural space PF/serum protein ratio ≥ 0.5 PF/serum LDH ratio ≥ 0.6 Light’s Criteria: Any criteria can be met to be an exudative pleural effusion PF LDH ≥ 2/3 upper limit of normal Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 9, 2022 on www.thecalgaryguide.com

transudative-pleural-effusions-pathogenesis-and-lab-findings

Transudative Pleural Effusions: Pathogenesis and Lab Findings Authors: Sravya Kakumanu Reviewers: Ben Campbell, *Yan Yu, *Tara Lohmann * MD at time of publication Cirrhosis Cirrhotic liver ↑ pressure in hepatic veins Ascites: Leakage of fluid from hepatic capillariesàperitoneal cavity Negative intrathoracic pressure on inspiration and ↑ intra-abdominal pressureàfluid leakage from abdominal space into pleural space across diaphragmatic defects L heart failure (most common) Left ventricle unable to pump sufficient blood into systemic circulation Backup of blood in pulmonary veins ↑ Hydrostatic pressure in pulmonary veins Pulmonary embolism R ventricle unable to pump blood due to clot in pulmonary artery Backup of blood in systemic veins ↑ Hydrostatic pressure in veins draining parietal pleura Nephrotic syndrome Damaged glomerulus has ↑ permeability to plasma proteins in blood ↑ Loss of proteins through urine ↓ Oncotic pressure in systemic capillaries (including within parietal pleura) Normally, permeable pleural capillaries do not allow protein leakage into the pleural space ↑ Interstitial fluid leakage across intact pulmonary or pleural capillaries into pleural space Transudative Pleural Effusion Absence of bacteria and inflammatory cells in pleural space No increase in cellular activity in pleural space Normal levels of glucose metabolism in pleural space = low lactate dehydrogenase (LDH) (LDH increases when glucose metabolism, particularly glycolysis, increases to maintain supply of NAD+) Large accumulation of pleural fluid (PF) pressing against lung tissue and mediastinum Lung atelectasis (lung collapse) See Pleural Effusions: X- ray Findings and Physical Exam Findings of Lung Diseases slides PF/serum protein ratio < 0.5 PF LDH < 2/3 upper limit of normal Light’s Criteria: All three criteria must be met to be a transudative pleural effusion PF/serum LDH ratio < 0.6 See Hypoxemia: Pathogenesis and Clinical Findings slide for pathophysiology and signs of hypoxemia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 9, 2022 on www.thecalgaryguide.com

presentation-of-sah

Subarachnoid Hemorrhage: Clinical Findings Sudden bleeding into space surrounding the brain (for pathogenesis, see Subarachnoid Hemorrhage: Pathogenesis) Authors: Jason An, M. Patrick Pankow Reviewers: Owen Stechishin, Dave Nicholl, Haotian Wang, Hannah Mathew, Ran (Marissa) Zhang, Yan Yu*, Cory Toth* * MD at time of publication Bleed into subarachnoid space Subarachnoid Hemorrhage (SAH) Posterior hypothalamus ischemia (↓ Blood flow and oxygen) Red blood cell lysis from energy depletion or complement activation Release of spasmogens (spasm inducing agents) Cerebral vasospasm (narrowing of arteries from persistent contraction) ↓ blood flow Cerebral ischemia Release catecholamines (hormones from the adrenal gland; e.g., epinephrine, norepinephrine) ↑ Intracellular calcium Release of antidiuretic hormone Antidiuretic hormone acts on the distal convoluted tubule and collecting duct in kidney to reabsorb water Dilution of serum sodium Hyponatremia (low blood sodium levels) Release of epileptogenic (potential seizure causing agents) into cerebral circulation Seizure Products from blood breakdown in cerebral spinal fluid Irritation of meninges (membranes surrounding the brain) Aseptic meningitis (non-infectious inflammation) Meningismus (neck pain + rigidity) Cerebral infarction (death of tissue) Obstructs cerebral spinal fluid flow and absorption at subarachnoid granulations Hydrocephalus (fluid build up in ventricles) ↓ Level of consciousness Reduced cerebral blood flow Dilation of cranial vessels to ↑ blood flow Rapid ↑ internal carotid artery intracranial pressure Refer to Increased Intracranial Pressure: Clinical Findings slide Internal carotid artery Pituitary ischemia Hypopituitarism [underactive pituitary gland, failing to produce 1+ pituitary hormone(s)] Refer to hypopituitarism slides Myocardial disruption Left ventricle dysfunction ↑ Pressure in left heart Blood forced backwards into pulmonary veins ↑ Pulmonary blood pressure Fluid from blood vessels leaks into lungs Dysrhythmias (disturbance in rate/rhythm of heart) causing ↓ cardiac output Syncope (loss of consciousness due to ↓ blood flow to the brain) Pulmonary edema (excess accumulation of fluid in lung) Cerebral hypoperfusion Sudden ↑in blood volume Vessels and meninges suddenly stretch Thunderclap Headache (worst headache of patient's life) Shortness of breath Reactive cerebral hyperemia (excess blood in vessels supplying the brain) Artery specific findings: Rapid ↑ internal carotid artery intracranial pressure Middle cerebral artery Posterior communicating artery Compression of outer CN3 Compression of inner CN3 Anterior communicating artery Nonreactive pupil Gaze palsy (eye deviates down and out) Diplopia (double vision) Ptosis (drooping of upper eyelid) Frontal lobe ischemia Avolition (complete lack of motivation) Ischemia of motor strip pertaining to the legs Bilateral leg weakness Motor strip ischemia Hemiparesis (weakness/ inability to move one side of the body) Ischemia of parietal association areas (brain regions integral for motor control of the eyes, the extremities and spatial cognition) Aphasia (impaired ability to speak and/or understand language)/ neglect Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 1, 2014, updated August 10, 2022 on www.thecalgaryguide.com

hypercalcemia-pathogenesis

Hypercalcemia: Pathogenesis Malignancy Thiazide Diuretics Immobilization Granulomatous Diseases (e.g., sarcoidosis, tuberculosis, fungal infections) Ectopic (outside of kidney) production of 1-α-hydroxylase 1-α-hydroxylase converts calcidiol to calcitriol (aka 1,25-OH Vitamin D or active Vitamin D) ↑ 1-25 OH Vitamin D ↑ Absorption of Ca2+ in the small intestine ↑ Vitamin D Intake Dietary Vitamin D is converted to calcidiol (aka 25- OH Vitamin D or inactive Vitamin D) in the liver Primary Hyperparathyroidism ↑ or normal* serum parathyroid hormone (PTH) level Tumour released Parathyroid Hormone related Peptide (PTHrP) mimics natural PTH (PTH level itself is low) Tumour produces bone- reabsorbing substances (IL-6, IL-1, RANKL) Paget’s Disease Osteoblasts produce abnormally high levels of RANKL Block Na+/Cl- cotransporter (NCC) on distal convoluted tubule (DCT) cells of the nephron ↓ Na+ and Cl- transport from lumen into DCT cells ↓ Intracellular Na+ in DCT cells + To compensate Na , ↑ Ca-ATPase and 3:Na:Ca exchanger activity on DCT cells (moves 3 Na+ into cell, 1 Ca+ out into peritubular capillary) ↑ Ca+ moving into bloodstream ↓ Mechanical stimulation of osteocytes ↓ Signaling of osteoblasts (cells that form bone) ↓ New bone formation ↓ Ca2+ incorporation into bone ↑ Ca2+ in plasma ↑ reabsorption of Ca2+ from the distal portion of nephron back into the blood ↑ 1-α-hydroxylase production in the proximal convoluted tubule Milk Alkali Syndrome Ca2+ intake exceeding 2000 mg per day leads to unregulated gut Ca2+ absorption into the blood PTH binds to osteoblasts on the surface of bone Osteoblasts produce RANKL to stimulate osteoclast function ↑ Osteoclast (cells that breakdown bone) activity ↑ Bone breakdown Ca2+ within bone is released into the bloodstream Osteolytic bone metastases Hyperthyroidism ↑ Catabolic thyroid hormones ↑ RANKL: OP ratio, RANKL promotes bone breakdown by stimulating osteoclast growth while OP (osteogenic protein) promotes bone formation Hypercalcemia Hypercalcemia Authors: Alexander Arnold, Peter Vetere, Huneza Nadeem Reviewers: Mark Elliott, Ran (Marissa) Zhang, Yan Yu*, Hanan Bassyouni* * MD at time of publication See Hypercalcemia: Clinical Findings slide *Note: A normal PTH value is abnormal in the context of hypercalcemia, since hypercalcemia would normally negatively feed back to suppress PTH production. Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 11, 2014, updated Aug 11, 2022 on www.thecalgaryguide.com

lower-gi-bleed-risk-factors

Lower GI Bleeds: Risk factors Portal Esophageal varices (large veins in the esophagus that are at risk for bleeding) Rectal varices (large veins in the rectum that are at risk for bleeding) Splenomegaly (enlargement of the spleen) Large spleen sequesters (traps) platelets, reducing blood platelet counts ↓ Clotting ability of the blood ↓ Epithelial protection along entire GI tract Pre-existing damage to the lower GI tract epithelium Malignant tissue invades the colon wall and disrupts colonic blood vessels New, extremely friable blood vessels develop within the tumor Venous blood pressure exceeds vessel wall strength, and the vessel ruptures and bleeds Blood moves rapidly through the GI tract (this is an upper GI bleed that can produce lower GI bleed symptoms) Hematochezia (bright red blood per rectum) Damaged liver tissue restricts blood flow through liver hypertension (high blood pressure in the veins running from the GI tract to the liver) Blood backs up in the splenic vein Venous blood pressure exceeds vessel wall strength, and the vessel ruptures and bleeds Liver cirrhosis Authors: Yan Yu, Miranda Schmidt Illustrator: Mizuki Lopez Reviewers: Michael Blomfield, Tony Gu, Jason Baserman, Jennifer Au, Vina Fan, Ben Campbell, Kerri Novak* * MD at initial time of publication ↓ Synthesis of blood clotting factors that are normally produced in the liver (i.e. fibrinogen) Bleeding of capillaries under the skin Petechiae (small red dots on skin) Inferior Vena Cava Blood clotting defect (genetic disorder, Acetylsalicylic Acid use) Non-Steroidal Anti- Inflammatory Drug (NSAID) Use Prior lower GI bleeds Family history of colorectal cancer Diaphragm Esophagus ↓ Systemic prostaglandin synthesis ↑ Risk for lower GI bleed ↑ Risk for colorectal cancer Development of colorectal cancer Duodenum Ligament of Treitz Lower GI Bleeds are intra-luminal GI tract bleeds that occur anywhere distal to the ligament of Treitz (transition between duodenum and jejunum) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published June 30, 2019, updated August 15, 2022 on www.thecalgaryguide.com

burn-shock-pathogenesis-complications-and-clinical-findings

Burn Shock: Pathogenesis, Complications, and Clinical Findings Thermal burn injury > 20% Total Body Surface Area Authors: Shayan Hemmati Reviewers: Christy Chong Ben Campbell Donald McPhalen* * MD at time of publication ↑ Production of local inflammatory markers (ex. histamine, bradykinin, and prostaglandins) Endothelial cell lining in blood vessel walls is compromised ↑ Local vessel permeability Shift of plasma + proteins from vessel into interstitial space Direct vascular thermal injury (within burn wound) ↑ Production of circulating inflammatory mediators (ex. IL-1, IL-6, TNF-!) ↑ Systemic vessel permeability ↑ Circulating reactive oxygen species Damage to DNA, proteins, and lipids throughout body, including myocardium (muscle cells of the heart) ↑ Myocardial stress Myocardial dysfunction ↓ Cardiac contractility ↓ Stroke volume ↓ Cardiac output Cardiogenic Shock Refer to Cardiogenic Shock: Pathogenesis, Complications and Clinical Findings ↓ Protein concentration in vessels causes ↓ intravascular oncotic pressure Further shift of plasma from vessel into interstitial space (↑ interstitial proteins pull plasma into interstitium) ↓ Intravascular plasma ↑ RBCs per unit volume of plasma ↑ Systemic vasoconstriction to maintain blood pressure (↑ Afterload) ↓ Circulating blood volume leads to less venous return (↓ Preload) ↑ Hematocrit Pitting edema (burned & unburned tissue) ↓ Circulating blood volume Hypovolemic Shock Refer to Hypovolemic Shock: Pathogenesis, Complications and Clinical Findings Burn Shock: A complication of large burns causing end-organ hypoperfusion with resultant organ dysfunction Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 15, 2022 on www.thecalgaryguide.com

thrombose-veineuse-profonde-soupconne-tvp-pathogenese-et-complications

Thrombose veineuse profonde soupçonné (TVP) Auteurs: Dean Percy Yan Yu Rédacteur: Tristan Jones Julia Heighton Man-Chiu Poon* Lynn Savoie* Traducteurs: Sophia Shah Sylvain Coderre* *MD à la publication La grossesse, contraceptifs oraux Pathogénèse et complications Activation plaquettaire ↑ formation de caillots Maladies héréditaires Anomalie congénitale de la coagulation (p.e. facteur V Leiden, facteur II muté, déficit en protéine S/C) ↑ capacité de coagulation Notes: • TVP provoque une embolie pulmonaire, le thrombus artériel provoque un accident vasculaire cérébral • TVP précédente est un facteur de risque de TVP courante Malignité Libération anormale de cytokines favorisant la coagulation Traumatisme/opération Blessure systémiqueà activation de la cascade de coagulation État d'hypercoagulabilité↑ capacité du sang à coaguler lors de la stimulation Oestrogène favorise l'hypercoagulabilité, surtout en présence d'autres risques Hypertension Bactéries Valve artificielle Endommage les parois des vaisseaux Adhèrent/ envahissent / vaisseaux Surface anormale Blessure de vaisseau Expose le facteur tissulaire sur les cellules endommagées /sous-endothélium pour la liaison au FvW Triade de Virchow Stase veineuse ↓ débit sanguins au site de la lésion vasculaireà concentration des facteurs de coagulation sanguine sur ce site La graisse contient plus d'aromatase: ↑ d'androgènesà œstrogènes mode de vie sédentaire, mauvais retour veineux Obésité Les caillots se produisent généralement dans les veines des jambes 1. Les veines larges et profondes permettent l'accumulation de sang 2. Retour veineux des jambes est contre la gravité 3. Valves dans les veines des jambes enclins au refoulement ↓ mouvement musculaire = ↓ débit sanguin Fracture, immobilisation, alitement, long tour d’avion/ de véhicule Destruction de la valve veineuse par un caillot Insuffisance veineuse Les caillots empêchent le sang à retourner au cœur. L'accumulation de sang dans une jambe entraîne l’œdème unilatéral et l’inflammation veineuse (rougeur, chaleur, sensibilité) Le caillot s'embolie dans les poumons Thromboembole -*Embolie pulmonaire (complication aiguë mortelle) - Hypertension pulmonaire thromboembolique chronique Légende: Physiopathologie Mécanisme Signe/Symptôme/Résultats de Laboratoire Complications Publié 15 juin 2019 sur www.thecalgaryguide.com

anaphylaxie-traitements-aigu

anaphylaxie-traitements-aigu

alcoholic-fatty-liver-disease-pathogenesis-and-clinical-findings

Alcoholic Fatty Liver Disease: Pathogenesis and clinical findings Authors: Tara Shannon Reviewers: Ben Campbell, Yan Yu*, Samuel Lee* * MD at time of publication ↑NADH:NAD+ ratio in hepatic cells, a “high energy state” marker in the cell When a cell is in a high energy state, metabolic processes that provide energy are inhibited ↓ β-oxidation (break down) of triglycerides in the liver Abbreviations: • CYP2E1 – Cytochrome P450, subtype 2E1 • NADH/NAD+ – Nicotinamide Adenine Dinucleotide (in reduced and oxidized form respectively) Ethanol upregulates hepatic cell fatty acid transporters such as fatty acid transport protein 1 and 5 (FATP1,5) ↑ Fatty acid transporters in hepatic cells ↑ Uptake of free fatty acids from circulation into hepatic cells Alcohol (ethanol) consumption Ethanol is primarily metabolized in the liver by enzymes alcohol dehydrogenase (ADH) and CYP2E1 ADH converts ethanol into acetaldehyde & NADH CYP2E1 converts ethanol into acetaldehyde Excessive alcohol consumedàthe liver cannot process ethanol and its metabolites quickly enoughà ethanol, acetaldehyde, and NADH accumulate in the liver and may enter the bloodstream Acetaldehyde is a highly reactive and unstable molecule that can damage proteins, enzymes, and DNA (Hepatic stellate cells (HSC) are sensitive to liver damage and release cytokines when activated) Acetaldehyde activates HSCàHSC release tumor necrosis factor alpha (TNF-!), an inflammatory markerà↑ liver inflammation Acetaldehyde upregulates the production of enzymes required for fatty acid synthesis TNF-! stimulates fat production in liver cells TNF-! enters circulation and stimulates adipose cells to break down, releasing triglyceride stores as free fatty acids ↑ Free fatty acids released into circulation Liver biopsy shows liver inflammation TNF-! causes the production of reactive oxygen species (unstable, highly reactive molecules) Reactive oxygen species cause oxidative damage to hepatic cells’ mitochondria Damaged mitochondria can no longer efficiently perform metabolic tasks ↑ Building blocks, catalysts, and direct stimulating factorsàliver cells ↑ fat production ↑ Lipogenesis in the liver (triglyceride production) ↑ Triglyceride accumulation in liver cells Triglyceride-rich droplets in hepatic cells change the cells’ physical properties compared to normal liver cells, allowing imaging modalities to exploit these differences to detect lipid infiltration Fatty livers appear darker on CT scans Liver biopsy shows triglyceride- rich droplets inside liver cells Fatty livers appear brighter and with poorer visualization of structures (like bile ducts and vessels) on ultrasounds Imaging such as ultrasound, CT, and MRI can visualize and quantify liver fat Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 21, 2022 on www.thecalgaryguide.com

tetanos-patogenesis-y-hallazgos-clinicos

Tétanos: Patogénesis y hallazgos clínicos tetanos-patogenesis-y-hallazgos-clinicos

neumonia-del-adulto-patogenesis-y-hallazgos-clinicos

Neumonía del adulto: Patogénesis y hallazgos clínicos neumonia-del-adulto-patogenesis-y-hallazgos-clinicos

infeccion-por-clostridium-difficile-c-diff

Infección por Clostridium difficile (C. diff) infeccion-por-clostridium-difficile-c-diff

patellar-tendon-rupture-pathogenesis-and-clinical-findings

Patellar Tendon Rupture: Pathogenesis and clinical findings Author: Molly Joffe Reviewers: Liam Thompson, Alyssa Federico, Tara Shannon, Gentson Leung* *MD at time of publication Chronic disease (e.g. renal failure, gout, rheumatoid arthritis, and diabetes) Repetitive activities involving rapid knee flexion and extension Tendon inflammation and micro-tearing Fluoroquinolone (antibiotic class) use Smoking Immobilization of knee ↓ Muscle and tendon flexibility and strength Steroid use (including intraarticular injections) Changes in collagen fibrils composing tendon (exact mechanism unknown) Disrupted blood supply to tendon and poor healing Compromised integrity and strength of the tendon Sudden heavy load on flexed knee while foot is planted Quadriceps muscles contract while lengthening (eccentric contraction)àforce exceeds tendon strength Patellar tendon innervated by common peroneal (fibular) nerve Nociceptors (pain receptors) within tendon activated by tendon rupture Pain and tenderness below the patella Collagen fibres in tendon tear Tearing or popping sensation at time of injury Patellar Tendon Rupture Tendon/Ligament detaches from bony attachment on patella or tibial tubercle No connection of quadriceps to tibia via patellar tendon ↑ Force on tibial tubercle during tendon detachment Avulsion fracture of tibial tubercle Trauma to tendon ruptures surrounding blood vessels Coagulation cascade and inflammatory mediators released at rupture site Quadriceps muscles unable to stabilize patellar tracking Instability of knee joint Quadriceps muscle tension pulls patella upwards with no resistance from patellar tendon Patellar tendon cannot use distal attachment site for leverage Knee extensor muscles unable to effectively contract Knee buckling Abnormal gait Patella alta (high sitting patella) on X-ray Palpable gap below the patella Bruising below the patella Swelling below the patella ↑ Risk of falls Loss of patellar reflex Inability to perform a straight leg raise (hip flexes and knee cannot remain straight) Hematoma (blood collection under the skin) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 28, 2022 on www.thecalgaryguide.com

medial-epicondylitis-golfers-elbow-pathogenesis-and-clinical-findings

Medial Epicondylitis (Golfer’s Elbow): Pathogenesis and clinical findings Intrinsic Factors: age, body weight, nutrition, gender, anatomical variations, joint laxity, systemic disease, muscle weakness / imbalance, vascular perfusion Micro-tears within flexor-pronator tendons initiating healing process: inflammation, proliferation, and remodeling (see acute wound healing slide) Continued repetitive strains with inadequate recovery time between activitiesàhealing unable to meet tissue damage Authors: Brett Lavender Reviewers: Alyssa Federico, Liam Thompson, Tara Shannon, *Gerhard Nikolaus Kiefer * MD at time of publication Extrinsic Factors: activities involving repeated forceful use of the flexor-pronator muscle groups (sports including golf and baseball, activities such as shoveling, gardening or hammering nails) Ineffective revascularization of damaged tissue MRI or Ultrasound Findings: Tendon thickening, partial tears, disrupted vascular distribution +/- edema of surrounding tissues Disorganized collagen formation and scarring à↑ type III collagen (most common collagen involved with wound healing) ↑ Tendon thickening Decreased tensile strength of tendon Weakness of the flexor-pronator muscle groups ↑ Nerve growth within damaged tissue (consequence of healing response) Local nerves are compressed by thickened tendonànociceptors within tendon are activated (Ulnar nerve passes through cubital tunnel adjacent to medial epicondyle) Ulnar paresthesias may result to structures innervated distal to the cubital tunnel Medial Epicondylitis Tendinosis at the common flexor-pronator origin at the medial epicondyle of the humerus Pain with passive wrist extension or resisted flexion Tenderness over the proximal wrist flexor-pronator muscles Pain localized to medial epicondyle Severity ranges from mild to severe based on the effect on patient activities Mild tendinopathy: patient continues most activities with minor pain Moderate tendinopathy: patient continues some activities with modifications Severe tendinopathy: patient’s daily activities are impacted by severe pain Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 30, 2022 on www.thecalgaryguide.com

epithelial-ovarian-cancer-subtypes-molecular-alterations-risk-factors

Epithelial Ovarian Cancer: Subtypes, Molecular Alterations & Risk Factors Risk factors associated with developing specific subtypes of epithelial ovarian cancer Authors: Brian Yu Chieh Cheng Reviewers: Ayaa Alkhaleefa, Parker Lieb, Tara Shannon, Sarah Glaze* * MD at time of publication No known subtype specific risk factors Smoking Introduction of carcinogenic material ↑Rate of cancer causing genetic mutations 2) Mucinous carcinoma Ovarian endometriosis (implantation of endometrial tissue on the ovaries) ↑ Chance of endometrioma (cyst comprised of endometrial tissue) formation in ovaries See Endometriosis Slide Familial BRCA1 or BRCA2 mutation Impaired double strand DNA repair mechanism results in accumulation of DNA damage 5) High grade serous carcinoma Lynch syndrome (autosomal dominant mutations in DNA repair genes) Impaired DNA mismatch repair mechanismà accumulation of DNA damage 1) Low grade serous carcinoma 3) Clear cell carcinoma 4) Endometrioid carcinoma Either clear cell, endometrioid carcinomas, or a mix of both subtypes General risk factors for developing all epithelial ovarian cancer (unknown pathogenesis) 1. Old age 2. Family history of breast or ovarian cancer 3. Post-menopausal hormone replacement therapy 4. Irregular age of menarche & menopause 5. High number of lifetime ovulation events / nulliparity Alteration in genes like KRAS, NRAS, BRAF, ERBB2 & CDKN2A Alteration in genes like ARID1A, PIK3CA & ERBB2 Alteration in genes like POLE & TP53 Molecular alterations in genes like TP53 and/or CCNE1 Molecular alterations commonly associated with specific epithelial ovarian cancer subtypes Legend: Pathophysiology Mechanism Sign/Symptom/Lab Findings Complications Published August 30, 2022 on www.thecalgaryguide.com

epoc-patogenesis

EPOC: Patogénesis Susceptibilidad genética (deficiencia de a1-AT) ↓ Capacidad del pulmón para prevenir daños en el tejido Contaminantes ambientales (consumo de tabaco a largo plazo, contaminación, infecciones) Autores: Yan Yu Revisado por: Jason Baserman Jennifer Au Naushad Hirani* Juri Janovcik* Traductores Gloria Talavera Sandino María Rosario Talavera* * MD al momento de la publicación Radicales libres producidos en los pulmones Inflamación pulmonar Inactivación de las anti proteasas del pulmón ↑ estrés oxidativo, citoquinas inflamatorias, y función de las proteasas Daño continuo al árbol bronquial ↑ destrucción proteolítica del parénquima pulmonar ↓ Soporte estructural para la permeabilidad de la vía aérea Estrechamiento y colapso de la vía aérea Infiltración de células inflamatorias, especialmente de neutrófilos Estrechamiento y fibrosis de la vía aérea Proliferación de cel. caliciformes,↑ producción de moco Muerte de las células ciliadas de la vía aérea ↓ elasticidad de la vía aérea (Presión elástica de retroceso pulmonar) Atrapamiento de aire en los pulmones Agrandamiento permanente del alvéolo El moco atrapado en la vía aérea provoca el desarrollo de infecciones Pulmones hiper- insuflados Ampollas en la superficie pulmonar Bronquitis crónica Enfermedad pulmonar obstructiva crónica (EPOC) Enfisema Hallazgos clínicos (ver diapositiva correspondiente) Complicaciones (ver diapositiva correspondiente) Leyenda: Patofisiología Mecanismo Signos/Síntomas/Hallazgos de laboratorio Complicaciones Publicado el 7 de enero, 2013 en www.thecalgaryguide.com

gonorrea-patogenesis

Gonorrea: Patogénesis Transmisión Neonatal Contacto directo de la mucosa del paciente con la mucosa infectada de la madre mientras pasa por el canal de parto Transmisión Sexual Contacto directo de la mucosa del paciente con la mucosa infectada Autores: Ryan Iwasiw Revisado por: Riley Hartmann Haotian Wang Steve Vaughan* Traducción: Fernanda Vigil Contreras María Rosario Talavera* *MD al momento de la publicación Unión a la superficie celular de la mucosa Las porinas bacterianas y proteínas forman poros en la membrana de la célula huesped, induciendo la endocitosis por las células epiteliales del huésped Abreviaciones: PMN – Leucocitos polimorfonucleares LPS – Lipopolisacárido Bloqueo de antígeno mediante la unión de anticuerpos del huésped a una proteína modificable por reducción bacteriana (Rmp) Autoinoculación Transferencia inmediata de bacterias a la mucosa del paciente por medio del contacto indirecto con la mucosa infectada Los componentes bacterianos incluyen: pili y otras proteínas permiten la adherencia a las células de la mucosa del huésped Erradicación exitosa del patógeno. Patógeno eliminado del huésped Supervivencia y replicación dentro de los fagolisosomas de los leucocitos Diseminación del patógeno La bacteria invade y se replica dentro de las células epiteliales columnares Respuesta Imnune del Huésped Fagocitosis bacteriana por los monocitos circulantes Erradicación ineficaz del patógeno. La proteínas bacterianas bloquean la fusion fagolisosomal y el estallido oxidativo de los PMN Variación antigénica de proteínas y LPS en la bacteria El enmascaramiento del antígeno gonocócico por los LPS evita la unión de anticuerpos bactericidas y provoca una activación incompleta del sistema del complemento Inmunidad del huésped evitada Proceso multifactorial que conduce a la capacidad de evitar la respuesta inmune del huésped Mimetismo molecular (ejemplo, azúcares LPS terminales similares a los glicolípidos del huésped) Secreción de IgA proteasas Signos y síntomas de la infección por Gonorrea (ver diapositivas de hallazgos clínicos) Leyenda: Patofisiología Mecanismo Signos/Síntomas/Hallazgos de laboratorio Complicaciones Publicado el 15 marzo, 2015 en www.thecalgaryguide.com

Síndrome estafilocócico de piel escaldada

ascending-cholangitis-pathogenesis-clinical-findings

Ascending Cholangitis: Pathogenesis and clinical findings Authors: Brandon Hisey, Neel Mistry Reviewers: Alec Campbell, Vina Fan, Ben Campbell, Kelly Burak*, Eldon Shaffer* * MD at time of publication Reflux of biliary contents into the vascular system (cholangiovenous reflux) Bacteria ascends into biliary tract from duodenum via Sphincter of Oddi Gallstone in the common bile duct Stricture of biliary/hepatic ducts Biliary / pancreatic duct malignancy Biliary obstruction (partial bile duct obstruction) ↓ Excretion of bilirubin into bileà ↑ bilirubin in blood ↑ Serum bilirubin Deposition of bilirubin in the skin and mucous membranes Jaundice*† Parasites in bile duct (E.g. Clonorchis) Complication of endoscopic retrograde cholangiopancreatography (ERCP) Bile accumulates in biliary tract Bile duct dilation on ultrasound Sludge (bile precipitants) impact bile ducts worsening obstruction Obstruction & detergents in bile inflame ductal mucosa. Inflammation then spreads to adjacent structures Stimulates phrenic (C3-C5) and foregut autonomic nerves (T5-T8) Dull right upper quadrant pain*† radiating to back and right shoulder ↑ Intra-biliary pressure Impaired forward flowà ↑ backflow of bile Impaired bile secretion damages ductal epithelium of the biliary tract Damaged ductal epithelium leaks ALP and GGT (enzymes) into blood ↑ Serum ALP and GGT ↑ Permeability of bile ductules Reduced flushing of bile out to duodenum Inflammatory response triggered Fever*† ↑ WBCs Tachycardia Hypotension† Confusion† Oliguria Bacterial translocation from biliary tract into blood Bacteremia Massive systemic inflammatory response Septic Shock (see Distributive Shock slide) * Charcot’s triad ~20% of cases | † Reynolds’ pentad ~7% of cases Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications First published November 18, 2015; Updated August 31, 2022 on www.thecalgaryguide.com

acute-lower-gi-bleeds-pathogenesis-and-clinical-findings

Acute Lower GI Bleeds: Pathogenesis and Clinical Findings Diverticulosis Formation of diverticula (outpouchings of the bowel wall) Intestinal vessels are stretched over the domes of the diverticula Angiodysplasia Formation of dilated, thin- walled vessels in GI tract mucosa/ submucosa Colorectal Cancer Infectious Colitis Invasion of bacteria and/or bacterial toxins into intestinal wall Cell damage and cell death Sloughing off of intestinal epithelial cells Ischemic Colitis ↓ Blood flow to a portion of the colon Lack of oxygen delivery to colon wall Necrosis (cell death) in the colon wall Inflammatory Bowel Diseases (Note: these are chronic diseases and rarely present with acute lower GI bleed) New, extremely friable blood vessels develop within the tumor Malignant tissue invades the colon wall and disrupts colonic blood vessels Crohn Disease Immune- mediated full thickness inflammation of bowel wall Ulcer formation and disruption of intestinal vessels Ulcerative Colitis Recurrent immune- mediated inflammation of colon mucosa Authors: Miranda Schmidt Illustrator: Mizuki Lopez Reviewers: Vina Fan, Ben Campbell, Kerri Novak* * MD at initial time of publication Acute Lower GI Bleed ↑ Risk for vessel damage and rupture Blood travels rapidly through GI tract Hematochezia (bright red blood per rectum) May result in significant blood loss Blood from the small intestine or right colon travels a longer distance through the GI tract Bacteria in the GI tract has time to oxidize hemoglobin in the blood Oxidization makes blood a darker color Melena (rare in a lower GI bleed) (tarry black stool) Inferior Vena Cava Diaphragm Esophagus Loss of red blood cells results in a loss of hemoglobin (a component of red blood cells) Fluid from the extravascular space moves into the blood vessels to maintain vascular volume Fluid is administered in a healthcare setting to compensate for blood loss Hypovolemic Shock (rare in a lower GI bleed) (↓ Oxygen delivery to tissues due to low blood volume) See “Hypovolemic Shock” slide for signs and symptoms Lower GI Bleeds are intra-luminal GI tract bleeds that occur anywhere distal to the ligament of Treitz (transition between duodenum and jejunum) After 24 hours, the addition of fluid to the intravascular space dilutes hemoglobin in the blood Normocytic Anemia Duodenum Ligament of Treitz Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 31, 2022 on www.thecalgaryguide.com

melanoma-pathogenesis-and-clinical-findings

Melanoma: Risk factors, pathogenesis, and clinical findings Authors: Ayaa Alkhaleefa, Ryan T. Lewinson Reviewers: Tara Shannon, Harjot Atwal, Gurleen Chahal, Usama Malik, Laurie Parsons*, Habib A Kurwa* * MD at time of publication Oral methoxsalen (psoralen) and ultraviolet A radiation therapy used for psoriasis, vitiligo Genetic risk factors like fair skin, multiple nevi on skin surface, extreme sun hypersensitivity Intermittent intense sun exposure and sunburn in childhood No/minimal sunscreen use (broad spectrum SPF 30+) Minimal protective clothing e.g., sunglasses, hats Geographic location e.g., equatorial regions Tanning beds Pyrimidine Dimer Normal DNA ↑ Ultraviolet A and B exposure (UVA/B) Formation of cyclobutene pyrimidine dimers in melanocytes (see illustration) Radiant energy in UVA/B emits electromagnetic radiation Melanin and reactive oxygen species activation in melanocytes Oxidative DNA damage in melanocytes Mutation in tumour protein 53 (a tumor suppressor gene) in melanocytes ↑ Cell division of mutated melanocytes Melanoma Asymmetry: One half of lesion does not look like the other Borders: Irregular, poorly defined, or scalloped appearance Accelerated proto-oncogene serine/threonine kinase (BRAF) Rapid proliferation of abnormal melanocytes at different stages of growth Growth of mutated melanocytes at irregular and uncontrolled rates Unregulated production of melanin by each melanocyte Color: Varied throughout lesion e.g., black, blue, or red Plaque with prolonged horizontal growth phase occurring anywhere on the body Rapidly growing nodule occurring anywhere on the body Evolving solar freckle in sun exposed areas (head, neck) found in older adults Found in palms of hands and soles of feet Superficial spreading melanoma Nodular melanoma Lentigo maligna melanoma Acral lentiginous melanoma Diameter: Usually greater than 5 mm Evolving: Rapid change (few months) in shape, size, and color Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications First published August 14, 2017, updated September 3, 2022 on www.thecalgaryguide.com

croup

Croup: Pathogenesis and clinical findings Viral pathogen (parainfluenza, respiratory syncytial virus, influenza virus, Authors: Christy Chong, Nick Baldwin Reviewers: Tara Shannon, Jody Platt, Elizabeth de Klerk, Yan Yu*, Naminder Sandhu*, Danielle Nelson* *MD at time of publication measles morbillivirus, or adenovirus) colonizes the nasopharyngeal mucosa Virus migrates along epithelium and invades the upper airways in the larynx and trachea Croup (laryngotracheobronchitis) Cytokines disrupt hypothalamic thermoregulation Fever Refer to Fever: Pathogenesis slide Laryngeal swelling compresses vocal cords Hoarseness of voice Infection of the larynx, trachea, and bronchi – typically in children 6 years or younger in the Fall and Winter Host immune response to virus ↑ inflammatory cytokine release into circulation à Immune cells migrate to sites of infection and produce free radicals to fight off virus Damage to healthy cells within the upper airways ↑ Permeability of blood vessels within the upper airways Protein and fluid leak into nasopharyngeal, laryngopharyngeal, and/or tracheal interstitiums ↓ Ciliary cells (responsible for clearing mucous and dirt from the respiratory tract) ↓ Mucous movement across airway Nasal mucous discharge Nasal edema and swelling Nasal congestion ↑ Tracheal mucous Trachea is narrowed and clogged ↓ Diameter of trachea ↓ Air pressure inside the tracheaàtracheal wall collapses (Bernoulli's principle) ↑ Nasal mucous Immature/less rigid tracheal walls in young children susceptible to further structural narrowing Breathing across a narrowed trachea à turbulent airstreams ↑ Work of breathing to adequately ventilate lungs with O2 Inspiratory stridor Expiratory Children rely on compensatory respiratory mechanisms as they fatigue overtime (harsh, high- “barking” cough pitched sound) Respiratory distress Nasal flaring Chest-wall in-drawing Tachypnea Accessory respiratory muscle use Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications First published May 28, 2013, Updated September 3, 2022 on www.thecalgaryguide.com

ventilator-associated-pneumonia-pathogenesis-and-clinical-findings

Ventilator-Associated Pneumonia: Pathogenesis and Clinical Findings Respiratory failure or inability Risk factors: e.g. immunocompromised, poor swallowing to maintain airway ability, weakened respiratory muscles, chronic disease Insertion of endotracheal tube (ETT) for invasive mechanical ventilation to maintain respiration Paralytics and sedatives lead to inhibition of cough reflex Damage to cilia on epithelial cells of trachea during insertion of ETT ↓ Mucociliary clearance Insertion of nasogastric (NG) tube for feeding Constant opening by NG tube ↓ esophageal sphincter function Introduction of oropharyngeal microbes during intubation Severe acute illness impairs phagocytosis and dysregulates T- cells (mechanism unclear) Medications, chronic disease, or severe acute illness can weaken immune system Desensitization of pharyngoglottal adduction reflex (PAR) (PAR normally induces closure of epiglottis to protect the airway when swallowing) ↑ Reflux of gastric contents Accumulation of subglottic secretions containing microbes Microbial colonization on inside of ETT Development of biofilm on inside of ETT Dislodgement of biofilm into lower airway ↑ Age or chronic disease can weaken respiratory function Micro aspirations of subglottic and gastric contents Impaired mechanisms to remove microbes from airway Positive pressure pushes microbes down Fever/rigors ↑ White blood cell count Introduction of pathogenic microbes to airway Susceptible patient (not required for infection) Septic shock See Distributive Shock slide Sepsis Microbes descend airway and infect lungs Ventilator-Associated Pneumonia (VAP) Occurs > 48-72 hours after intubation ↑ Inflammatory response at infection site promoting immune cell extravasation and cytokine release Cytokine signalling ↑ permeability of capillaries leading to ↑ fluid leakage into interstitium and alveoli Authors: Sravya Kakumanu Reviewers: Ben Campbell *Tara Lohmann *Bryan Yipp * MD at time of publication Acute respiratory distress syndrome See ARDS pathogenesis slide Pleural effusion Lung consolidation on chest x-ray (CXR) ↑ Sputum production to clear fluid on CXR (Note: In patients with Acute Respiratory Distress Syndrome (ARDS), look for VAP consolidation in non- within alveoli/airways (may be Positive microbial culture from sputum dependent/upper regions of the lung where ARDS consolidation would be unexpected to extend to) purulent in worse infections) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 2, 2022 on www.thecalgaryguide.com

syndrome-du-compartiment-deffort-chronique-scec

syndrome-du-compartiment-deffort-chronique-scec

syndrome-du-compartiment-aigu-sca

syndrome-du-compartiment-aigu-sca

pyoderma-gangrenosum-type-classique-pathogenese-et-resultats-cliniques

pyoderma-gangrenosum-type-classique-pathogenese-et-resultats-cliniques

physiology-of-gene-transcription-translation

Physiology of Gene Transcription & Translation Authors: Sravya Kakumanu Reviewers: Parker Lieb, Ran Illustrator: Sravya Kakumanu (Marissa) Zhang, Yan Yu* Translation: RNAàProtein * MD at time of publication Each 3-nucleotide sequence in the mRNA is a codon. Each codon is recognized by a specific transfer RNA (tRNA) molecule through its complementary anticodon sequence (E.g. mRNA codon= AUG, tRNA anticodon= UAC) Transcription: DNAàRNA Ribosome attaches to mRNA (Ribosome= Cellular apparatus for translation made up of RNA and protein molecules) Basal levels of cellular activity/gene expression to maintain basic cellular functions (e.g. structural proteins, enzymes of glycolysis and metabolism) Changes to extracellular or intracellular environment (E.g. ↑ Blood glucose levels) Cell needs to respond to stimulus Stimulus produces a signal molecule (e.g. cytokines, hormones, other small molecules) Each tRNA molecule has a specific nucleotide sequence to bind to a singular amino acid. Therefore, each mRNA codon codes for a specific amino acid (Amino acids= Building blocks of proteins) The first transfer RNA (tRNA) enters the ribosome, carrying a specific amino acid, and binds to the first codon in the mRNA to initiate translation Subsequent tRNAs carrying amino acids corresponding to the next codons enter the ribosome and attach their amino acid to previous amino acids to create a polypeptide chain Ribosome reaches the last codon (translation ends). The polypeptide chain is released into cytosol or into other organelles (e.g. endoplasmic reticulum) for further processing The polypeptide chain folds together based on biochemical interactions between the individual amino acids Specific amino acid sequences within the nascent protein signal for further biochemical modifications (e.g. addition of phosphate, ions, sugar groups, other polypeptide chain) to make the protein functional Functional protein can stay intracellularly or get transported to cell membrane or extracellularly based on its function Amino Amino-acid acid Cells surface receptor detects signal molecule and activates an intracellular cascade of signalling proteins Signal molecule diffuses directly into cell nucleus binding site Anti-codon Ribosome Growing polypeptide chain tRNA Signal proteins/molecules activate transcription-promoting proteins in nucleus Transcription-promoting proteins help RNA polymerase (RNA building protein) bind to the appropriate gene sequence in DNA (complex mechanisms, simplified here) RNA polymerase transcribes gene sequence and creates complementary messenger RNA (mRNA) strand (Complementary strand= If the DNA sequence is TTGC the complementary mRNA sequence would be AACG) RNA polymerase releases mRNA once entire gene sequence has been transcribed mRNA gets transported from nucleus into the cell’s cytosol RNA Polymerase mRNA Nucleus Cytoplasm Legend: Pathophysiology Mechanism Published September 25, 2022 on www.thecalgaryguide.com

lateral-epicondylitis-tennis-elbow-pathogenesis-and-clinical-findings

Lateral Epicondylitis (Tennis Elbow): Pathogenesis and clinical findings Authors: Brett Lavender Reviewers: Alyssa Federico, Liam Thompson, Tara Shannon Gerhard Nikolaus Kiefe* * MD at time of publication Extrinsic Factors: activities involving repeated forceful use of the extensor-supinator muscle groups (sports including tennis and squash, activities such as painting, carpentry or using certain hand tools) Intrinsic Factors: age, body weight, nutrition, gender, anatomical variations, joint laxity, systemic disease, muscle weakness / imbalance, vascular perfusion Micro-tears within extensor-supinator tendons initiating healing process: inflammation, proliferation, and remodeling (see acute wound healing slide) Continued repetitive strains with inadequate recovery time between activitiesàhealing unable to meet tissue damage Ineffective revascularization of damaged tissue MRI or Ultrasound Findings: Tendon thickening, partial tears, disrupted vascular distribution +/- edema of surrounding tissues Disorganized collagen formation and scarringà↑ type III ↑ Nerve growth within damaged tissue collagen (most common collagen involved with wound healing) (consequence of healing response) ↑ Tendon thickening Decreased tensile strength of tendon Weakness of the extensor- supinator muscle groups Lateral Epicondylitis Tendinosis at the common extensor-supinator origin at the lateral epicondyle of the humerus Local nerves are compressed by thickened tendon ànociceptors within tendon are activated Pain with passive wrist Pain localized to flexion or resisted extension lateral epicondyle Tenderness over the proximal wrist extensor-supinator muscles Severity ranges from mild to severe based on the effect on patient activities Mild tendinopathy: patient continues Moderate tendinopathy: patient continues Severe tendinopathy: patient’s daily most activities with minor pain some activities with modifications activities are impacted by severe pain Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 25, 2022 on www.thecalgaryguide.com

diabetes-insipidus-pathogenesis-and-clinical-findings

Diabetes Insipidus: Pathogenesis and clinical findings Hereditary Autoimmune/ Idiopathic Auto-antibodies destroy neurons that release antidiuretic hormone (ADH) Mass Effect/ Tumor Invasion Mass pressing on hypothalamus or pituitary Electrolyte Imbalance (mechanism unclear) Hereditary Lithium (Li) (mechanism unclear) Li enters principal cells of collecting ducts via ENaCs Li inhibits GSK3β, reducing adenylyl cyclase activity ↓ cAMP- dependent phosphorylation of aquaporin-2 ↑ Serum [Ca2+] Activation of CaSR in thick ascending limb of Loop of Henle ↓ NaCl reabsorption in thick ascending limb ↓ Generation of medullary osmotic gradient ↓ Serum [K+] ↑ Degradation of aquaporin-2 channels in collecting duct ↓ Aquaporin- 2 channels transporting water across apical membrane of collecting duct Mutation of AVPR2 gene on X chromosome Antidiuretic hormone (ADH) receptor cannot reach basolateral surface of principal cells of collecting duct Mutation of aquaporin-2 gene on chromosome 12 ↓ Fusion of aquaporins with apical membrane of collecting duct Mutation of WFS1 gene on chromosome 4 (Wolfram syndrome) ↓ Processing of antidiuretic hormone (ADH) precursors and ↓ADH-releasing neurons Surgery/ Trauma Injury to hypothalamus or pituitary stalk Mutation of PCSK1 gene on chromosome 5 Deficiency in PC1/3 (encoded by PCSK1) ↓ Processing of ADH by PC1/3 Aquaporin dysfunction ↓ Kidney response to ADH, which mediates reabsorption of water down its osmotic gradient through aquaporins ↓ Production of ADH by hypothalamus or ↓ secretion from ADH-releasing neurons in posterior pituitary (depending on location of lesion) Central Diabetes Insipidus Nephrogenic Diabetes Insipidus Abbreviations: AVPR2: arginine vasopressin receptor 2 CaSR: calcium-sensing receptor ENaC: epithelial sodium channel GSK3β: glycogen synthase kinase type 3 beta PC1/3: proprotein convertase Diabetes Insipidus Decreased ability of kidneys to concentrate urine ↓ Reabsorption of water from collecting duct into vasculature Author: Oswald Chen Reviewers: Huneza Nadeem, Ran (Marissa) Zhang, Yan Yu* Sam Fineblit* * MD at time of publication Urine becomes more dilute ↓ Urine osmolality ↑ Urine output ↓ Blood volume Blood becomes more concentrated Occurs during late sleep period Nocturia Polyuria (>3 L/day) ↑ Serum osmolality Activation of hypothalamic osmoreceptors Hypernatremia (Serum [Na+] >145 mEq/L) Polydipsia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 25, 2022 on www.thecalgaryguide.com

quadriceps-tendon-rupture-pathogenesis-and-clinical-findings

Quadriceps Tendon Rupture: Pathogenesis and clinical findings Author: Molly Joffe Reviewers: Liam Thompson, Alyssa Federico, Tara Shannon, Gentson Leung* *MD at time of publication Repetitive activities involving, rapid, active flexion and extension of the knee Quadriceps tendon inflammation and micro-tearing Immobilization of leg/knee Steroid use (including intraarticular injections) Quadricep muscles atrophy ↓ Quadricep muscle strength Smoking Chronic disease (e.g. renal failure, gout, rheumatoid arthritis, and diabetes) Fluoroquinolone (antibiotic class) use Changes in collagen fibrils composing tendonàimpaired tendon strength (exact mechanism unknown) Quadriceps tendon shortens ↓ Quadricep tendon flexibility Disrupted blood supply to quadriceps tendon and poor healing Compromised integrity of the quadriceps tendon and ↓ strength Sudden heavy load on flexed knee while foot is plantedàquadriceps muscles contract while lengthening (eccentric contraction) Force on quadriceps tendon exceeds its strength Quadriceps Tendon Rupture Tendon detaches from bony attachment on patella ↑ Force on patella during quadriceps tendon detachment Collagen fibres in quadriceps tendon tear No connection of quadriceps to tibia via quadriceps tendon Patellar tendon tension pulls patella downwards with no resistance from quadriceps muscles Quadriceps tendon innervated by common peroneal (fibular) nerve Nociceptors (pain receptors) within tendon activated by tendon rupture Pain and tenderness above the patella Trauma to tendon ruptures blood vessels Coagulation cascade and inflammatory mediators released at rupture site Quadriceps muscles unable to stabilize patellar tracking Knee joint instability Patella baja (low sitting patella) on X-ray Palpable gap above the patella Loss of patellar reflex Patellar tendon cannot use proximal attachment site for leverage Knee extensor muscles unable to effectively contract Inability to perform a straight leg raise (hip flexes while knee cannot remain straight) Bruising above the patella Swelling above the patella Avulsion fracture of patella Tearing or popping sensation at time of injury Knee buckling Abnormal gait ↑ Risk of falls Hematoma (blood collection under the skin) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 2, 2022 on www.thecalgaryguide.com

unstable-angina-pathogenesis-and-clinical-findings

Unstable Angina/Unstable Angina Pectoris: Pathogenesis and clinical findings Primary cause: Secondary causes: Coronary artery vasospasm - primary or drug induced (Ex: cocaine, triptans) Coagulopathy (Ex: antiphospholipid antibody syndrome) Vasculitic syndromes (Ex: Takayasu arteritis) Authors: Marisa Vigna Ryan Wilkie Yan Yu* Reviewers: Julena Foglia Davis Maclean Mehul Gupta Andrew Grant* * MD at time of publication Atherosclerosis Fatty plaque accumulates inside the intimal walls of arteries Coronary arterial atherosclerotic plaque rupture or erosion Plaque disruption exposes subendothelial components of damaged vessel wall to platelets, initiating the coagulation cascade and platelet adhesion Aggregation of platelets results in the formation of a thrombus Thrombus partially occludes blood flow through a coronary artery âmyocardial blood supply Congenital anomalies (Ex: myocardial bridge, anomalous coronary) Spontaneous coronary artery dissection Increased blood viscosity (Ex: polycythemia, thrombocytopenia) Factors thatámyocardial (cardiac muscle) oxygen demand (Ex: tachycardia, hypotension, hypertension, anemia, exertion, stress) Coronary embolism (Ex: A. Fib, endocarditis, prosthetic valve thrombus) áheart rate, contractility, and/or wall tension ámyocardial oxygen demand Myocardial ischemia due to imbalance between blood supply and oxygen demand (insufficient blood/oxygen supply) Unstable Angina/Unstable Angina Pectoris Can be new onset angina; typically progressive in frequency, severity, or duration; can occur at rest Subtotal occlusion of a coronary arteryà reduced, but continued, myocardial blood supply Maintained perfusion means cardiomyocytes are still alive and thus do not leak troponin into bloodstream Normal serum troponin Diaphoresis (sweating) Since bloodflow occurs from epicardium to endocardium, myocardial ischemia is more pronounced in the subendocardium (region furthest away from heart’s external surface) Sufficient blood flow is maintained in regions superficial to the subendocardium, resulting in non-transmural (partial thickness) heart wall ischemia Non-inferior wall ischemia triggers a predominantáin sympathetic nervous system activity, given the proximity of cardiac sympathetic nerve innervation Ischemiaâ cardiomyocyte resting membrane potential andâ action potential duration Voltage gradient between normal and subendocardial ischemic zones creates injury currents, shifting the ST- vector on ECG ECG: ST depression and/or T wave inversion Cardiac sensory nerve fibres mix with somatic sensory nerve fibres and enter the spinal cord via the T1-T4 nerve roots Brain perceives increased cardiac sensory nerve signaling as nerve pain coming from the skin of T1-T4 dermatomes (“Referred Pain”) Myocardial ischemia causes hypoxic stress on cardiomyocytesàâaerobic (requiring oxygen) metabolism,áanaerobic (not requiring oxygen) metabolism áanerobic respirationálactic acid production,á[H+], andâcellular pH which impairs cardiomyocyte function Cardiomyocyte dysfunction impairs myocardial relaxation in diastole and/orâ left ventricular contractility in systole âleft ventricular cardiac output àbackup of blood in the left ventricle, atrium, and pulmonary vasculature ápulmonary capillary pressures pushes fluid out of the capillaries into the alveoli in the lungs Fluid filled alveoliâgas exchange andâ oxygenation, triggering harder and faster breathing in order to compensate Dyspnea Activation of sweat glands via acetylcholine release Hormones bind to cardiac β1 receptors Tachycardia (áheart rate) Epinephrine/ Norepinephrine hormone release from the adrenal medulla Hormones bind to arterial smooth muscle α1 receptors ávascular tone (vasoconstriction) Hypertension The Vagus nerve sits in close physical proximity to the inferior wall of the heart àinferior wall ischemia triggers involuntary Vagus nerve activation Since the Vagus nerve coordinates parasympathetic activity,áVagus nerve activity leads to a variety of parasympathetic nervous system responses: Retrosternal discomfort: May present as pain, heaviness, tightness, aching, pressure, burning or squeezing Pain radiation to T1-T4 dermatomes: Left shoulder and arm, lower jaw, neck, abdomen, upper back Syncope (fainting) Bradycardia Nausea Hypotension (âheart rate) (âblood pressure) (áblood pressure) (shortness of breath) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Findings Complications Published Oct 18, 2015, updated Aug 29, 2021 on www.thecalgaryguide.com

chest-exam-findings-of-lung-pleural-diseases

Chest Exam Findings of Lung & Pleural Diseases Note: Please see slides on pathogenesis of Transudative and Exudative Pleural Effusions, Primary and Tension Pneumothorax, Adult Pneumonia, Acute Respiratory Distress Syndrome (ARDS), Chronic Obstructive Pulmonary Disease (COPD), Heart Failure, and Kidney Disease Authors: Sravya Kakumanu Reviewers: Ben Campbell, *Tara Lohmann, *Yan Yu * MD at time of publication Interstitial Lung Disease Pneumothorax Rupture of visceral pleura Build-up of air within pleural space Pleural Effusion Atelectasis Consolidation ↑ Hydrostatic pressure pushes fluid into pleural space ↑ Capillary permeability = fluid leaks into pleural space ↓ Oncotic pressure = fluid moves into pleural space Bronchus obstructed Scarring/infiltration of lung tissue Surfactant dysfunction (ex. ARDS) Loss of contact between visceral and parietal pleura (ex. effusion, pneumothorax) Parenchymal compression (ex. loculated effusion, mass) ↑ Hydrostatic pressure pushing fluid into alveoli (ex. cardiogenic pulmonary edema) ↑ Capillary permeability allowing fluid to move into alveoli (ex. pneumonia) Idiopathic Connective tissue diseases Sarcoidosis, Amyloidosis Chronic medical diseases (ex. COPD, heart failure, kidney disease, etc) Occupational or environmental exposures (ex. silicosis, organic dusts, metals, gases, aerosols, etc) Accumulation of fluid in pleural space Collapse of alveoli Accumulation of fluid within alveoli Pulmonary fibrosis (scarring of alveoli bilaterally) Breath Sounds Lung unable to inflate fully Fluid in pleural space Collapsed lung unable to inflate Airspace filled with fluid and unable to fill with air dampens sound ↓ Breath sounds ipsilaterally Scarred alveoli unable to expand to fill with air ↓ Breath sounds bilaterally (may not be noticeable) Chest Rising on Inspiration Chest cavity filled with air, but lung Lung unable to inflate fully Scarred alveoli unable to expand to fill with air unable to inflate fully ↑ Chest size, ↓ Rising ipsilaterally ↓ Chest rising ipsilaterally ↓ Chest rising bilaterally (may not be noticeable) Percussion Sound resonates through air in pleural space Ipsilateral hyperresonance on percussion Sound unable to resonate through pleural fluid Sound unable to resonate through compacted lung tissue Ipsilateral dullness on percussion Sound unable to resonate through fluid-filled alveoli Diffuse scarring of alveoli No notable changes on percussion Tracheal Deviation Air pushes trachea Fluid pushes trachea ↓ Pressure within chest wall pulls trachea No pushing or pulling of trachea Contralateral tracheal deviation Ipsilateral tracheal deviation No tracheal deviation Adventitious Lung Sounds Alveoli not impacted (i.e. not collapsed or fluid-filled) Sudden opening of collapsed alveoli filling with air Fine inspiratory crackles Air movement through fluid-filled alveoli Coarse inspiratory crackles Fluid-filled alveoli can’t dampen breath sounds from larger central airways Bronchial breath sounds all over consolidated area (harsh, ↑ pitch with expiratory phase > inspiratory; only normal when heard centrally over trachea + bronchi) Scarred inelastic alveoli suddenly open on inspiration Fine inspiratory crackles No crackles No abnormal breath sounds Severe pneumothorax or effusion pushing against lung parenchyma Other sounds Amplification of patient voice through fluid-filled alveoli Tactile fremitus (↑ vibrations felt by hand placed on chest wall when patient speaks) *Whispers also sound louder on auscultation Fluid-filled alveoli only allow certain sound frequencies to be audible Egophony (“E” sounds like “A” on auscultation) Legend: Pathophysiology Mechanism Physical Exam Findings Complications Published October 9, 2022 on www.thecalgaryguide.com

isolated-anterior-cruciate-ligament-acl-injury-pathogenesis-and-clinical-findings

Isolated Anterior Cruciate Ligament (ACL): Pathogenesis and clinical findings Authors: Colleen Nesbitt, Amy Rudkoski Reviewers: M. Patrick Pankow, Tara Shannon, Reza Ojaghi, Usama Malik, Dr. Ryan Shields*, Dr. R. Buckley* * MD at time of publication Female Gender Extrinsic Risk Factors High traction playing surface and/or footwear ↑ Torque on knee during change of direction/deceleration Previous anterior cruciate ligament (ACL) injury Intrinsic Risk Factors Physical Fatigue Unknown mechanism – likely related to altered patterns in lower limb muscle activation Incomplete healing due to poor ligament blood supply Inadequate landing force attenuation after reconstruction/healing Hamstring weakness and under recruitment ↑ Quadriceps (Q) angle (angle formed between quad muscle and patella tendon) à↑ lateral pull of quadriceps + Lachman Test: Knee is placed in 30-degree flexion and an anterior force is applied to tibia. Excessive anterior translation of tibia relative to contralateral side is a positive result + Anterior Drawer Test: Knee is placed in 90-degree flexion and an anterior force is applied to tibia. Excessive anterior translation of tibia relative to contralateral side is a positive result + Pivot Test: Knee is internally rotated and a valgus stress applied. Reduction of tibia as it externally rotates from a subluxated position on the femoral condyles is a positive result MRI can confirm the grade of tear. Knee arthroscopy is gold standard to diagnose an ACL tear and grade the injury ↑ ACL vulnerability to injury Contact event (Ex: impact to lateral aspect of leg, motor vehicle accident) Anterior translation of tibia on femur +/- valgus deformation +/- hyperextension of the knee +/- internal rotation of tibia ↑ Forces on structures surrounding ACL Non-contact event (Ex: sudden deceleration and/or direction change) ACL stretches beyond capacity of collagen fibers in ligament ACL Injury Stretch of ligament, no tear Incomplete tear Complete tear Grade 1 Grade 2 Grade 3 Torn vessel inside the ACL bleeds into the joint capsule Meniscus injury Joint capsule Injury Femoral subchondral bone injury Antalgic gait Acute hemarthrosis Acute swollen knee Audible “pop” at time of injury Knee instability when full weight bearing Development of abnormal knee biomechanics ↑ Risk of developing osteoarthritis If all 3 findings presentàassociated with a likelihood ratio of 17.7 and positive predictive value of 81%* * Wagemakers HP, et al. Diagnostic accuracy of history taking and physical examination for assessing anterior cruciate ligament lesions of the knee in primary care. Arch Phys Med Rehabil. 2010. Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications First published Sept 28, 2018, updated Oct 9, 2022 on www.thecalgaryguide.com

asthma-how-treatments-work-and-common-side-effects

Asthma: How Treatments Work and Common Side Effects • Relievers: Used as needed to ↓ symptoms during attacks • Controllers: Used daily to ↓ frequency and severity of attacks Note: Please see slide on Asthma: Pathogenesis • Exacerbation: Used emergently in acute exacerbation Short-acting Beta Agonists (Reliever) Long-acting Beta Agonists (Controller) Short-acting Muscarinic Antagonists (Exacerbation) Long-acting Muscarinic Antagonists (Controller) Magnesium Sulfate (Exacerbation) Monoclonal Antibodies (Controller) Leukotriene Receptor Antagonists (Controller) Inhaled Corticosteroids (ICS) (Controller) Systemic Corticosteroids (Exacerbation) Binding to beta-2 adrenergic receptors and subsequent intracellular signal cascade in bronchial smooth muscle Off-target binding occurs in other systemic cells Inhibition of muscarinic acetylcholine receptors in airway muscle cells ↓ Activation of the inositol triphosphate (IP3) intracellular pathway (IP3 pathway normally functions to mobilize intracellular Ca2+ stores) Inhibition of Ca2+ channels on airway smooth muscle surface ↓ Influx of Ca2+ Binding and inactivation of inflammatory signal molecules (IgE, IL-5) Inhibition of leukotriene receptors in lung and immune cells Steroid binds to nuclear receptors within cells ↓ Gene expression/synthesis of immune mediators (ex. cytokines) Stimulation of Na/K ATPase (which transports K into cells) Hypokalemia Palpitations Tachycardia Muscle cramps Tremor Authors: Chunpeng Nie Reviewers: Sravya Kakumanu, Ben Campbell, *Tara Lohmann * MD at time of publication ↓ Activation of mast cells (by ↓ IgE) and eosinophils (by ↓ IL-5/leukotrienes) ↓ Release of inflammatory cytokines by these cells (↓ Type 2 inflammatory response in airways) ↓ Permeability of airway vasculature ↓ Microvascular leakage into airway Inadvertent sympathetic nervous system activation Bronchial smooth muscle cells have ↓ Ca2+ release from intracellular stores (i.e. from sarcoplasmic reticulum) ↓↓ Cytoplasmic Ca2+ Myosin (muscle protein) unable to be activated for muscle contraction ↓ Smooth muscle contraction in bronchioles Bronchodilation ICS cause ↓ immune cell activity in the oropharynx Susceptibility to infection and irritation of the oropharynx from inhaled particles and pathogens Hoarseness Thrush Systemic corticosteroids cause ↓ immune cell activity in whole body ↑ Susceptibility to any infection Many other side effects Similar effects on other muscles in the body outside bronchi Dry mouth Urinary retention Constipation ↓ Mucosal edema ↓ Airway Mucus Airflow improvement ↑ Peak flow, ↑ Oxygenation, ↓ Dyspnea Legend: Pathophysiology Mechanism Treatment Effect Complications Published October 9, 2022 on www.thecalgaryguide.com

beta-bloker-mekanisme-kerja-dan-efek-samping

beta-bloker-mekanisme-kerja-dan-efek-samping

farmakokinetik-prinsip-dasar

farmakokinetik-prinsip-dasar

syok-luka-bakar-patogenesis-komplikasi-dan-temuan-klinis

syok-luka-bakar-patogenesis-komplikasi-dan-temuan-klinis

syok-hipovolemik-patogenesis-komplikasi-dan-temuan-klinis

syok-hipovolemik-patogenesis-komplikasi-dan-temuan-klinis

chronic-pancreatitis-complications

Chronic pancreatitis: Complications Hypothesis: Cytokines stimulate hypersecretion of secretory proteins (lithostathine, GP2) from acinar cells in exocrine pancreas (early in disease course) Proteins precipitate and form aggregates within pancreatic ducts Accumulation of protein aggregates and localized fibrosis block pancreatic ducts Rupture of acinar cells near blocked ducts → release of intracellular enzymes and fluid Accumulation of enzyme- rich fluid within pancreas Intra-pancreatic pseudocysts (differ from pseudocysts in acute pancreatitis, which are primarily extra-pancreatic) Chronic Pancreatitis Recurrent episodes of acute pancreatitis leading to irreversible fibroinflammatory pancreatic damage Inflammatory cytokines are continuously released from damaged pancreas over years Cytokines damage endothelium of intra- and peri-pancreatic blood vessels (including splenic vein, which runs posteriorly behind pancreas and allows for its venous drainage) Thin and weakened vessel walls balloon outwards from pressure of blood flow Pseudoaneurysms Venous stasis (low blood flow) → ↑ concentration of clotting factors Obstruction of peripancreatic ducts Author: Ashar Memon Reviewers: Yan Yu*, Kiana Hampton, Sylvain Coderre* * MD at time of publication Exocrine insufficiency (↓ secretion of digestive enzymes, e.g., Lipase, into gastro-intestinal tract) ↓ digestion of foods and absorption of nutrients (including fats) ↓ absorption of fat-soluble vitamin D Metabolic bone disease (a group of disorders of decreased bone mineralization) Blood vessels dilate and swell from increased blood flow Gastric varices Cytokines perpetually activate pancreatic stellate cells (stellate cells produce proteins that remodel extra- cellular matrix) Pancreatic stellate cells increase amounts of collagen and other extra- cellular matrix molecules in pancreas → Fibrosis Pancreatic proteolytic enzymes (e.g., trypsin) in fluid-filled pseudocysts digest walls of adjacent blood vessels Fibrotic tissue and pseudocysts compress peripancreatic structures (including splenic vein) Cytokines stimulate apoptosis of hormone- producing pancreatic Islet cells (e.g., beta cells) Endocrine insufficiency (↓ production and secretion of pancreatic hormones) Damaged endothelial cells of splenic vein trigger coagulation cascade (See Calgary Guide slide on Coagulation Cascade) Splenic vein thrombosis ↑ resistance to blood flow through splenic vein Cytokines stimulate apoptosis of acinar cells in exocrine pancreas Malnutrition ↓ secretion of insulin ↓ cellular uptake and metabolism of glucose → hyperglycemia Diabetes mellitus Collateral blood vessels develop around stomach so blood can circumvent splenic vein and relieve splenic vein hypertension Duodenal obstruction Biliary obstruction Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 18, 2022 on www.thecalgaryguide.com

felty-syndrome

Felty Syndrome: Pathogenesis and clinical findings Authors: Anjali Arora Reviewers: Ben Campbell, Liam Martin*, Yan Yu* * MD at time of publication Longstanding chronic Rheumatoid Arthritis Rheumatoid Arthritis (RA): a disease of systemic autoimmunity – refer to Rheumatoid Arthritis slides for detailed pathogenesis Genetic susceptibility Presence of a specific type of Human Leukocyte Antigen (HLA-DR4), a surface protein on immune cells that is known to be associated with or worsen autoimmune activity Idiopathic autoimmunity Neutrophil activation, apoptosis and adherence to endothelial cells in the spleen Felty Syndrome An uncommon extraarticular manifestation of seropositive Rheumatoid Arthritis characterized by the triad of splenomegaly, neutropenia and arthritis Immunologic stress leads to proliferation of white pulp in spleen (responsible for initiating immune responses to foreign antigens) Splenomegaly ↑ RBC and platelet sequestration within the spleen leading to a quantitative shortage of these cells in circulation Enlarged spleen compresses stomach Loss of appetite Complex autoimmune phenomena lead to ↓ neutrophil production and ↑ removal from the circulating pool Neutropenia For a detailed mechanism, refer to Neutropenia slides ↓ Circulating neutrophils leads to ↑ susceptibility to infections Severe, untreated Rheumatoid Arthritis will lead to systemic inflammation See Rheumatoid Arthritis slides for detailed mechanism Chronic erosion of synovial membranes in joints commonly affecting the hands, wrists and knees Arthralgia (symmetric polyarthritis, usually with small joint distribution) Thrombocytopenia Refer to Thrombocytopenia slides for signs and symptoms Normocytic Anemia Refer to Normocytic Anemia slide for signs and symptoms Host becomes infected Fever Recurrent infections Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 18, 2022 on www.thecalgaryguide.com

microscopic-colitis-pathogenesis-and-clinical-findings

Microscopic Colitis: Pathogenesis and clinical findings Genetic Author: Tony Gu, Kayleigh Yang Reviewers: Yoyo Chan, Vina Fan, Ben Campbell, Dr. Edwin Cheng* * MD at time of publication Release of cytokines (e.g. interferon gamma (IFNγ)) Downregulation of intestinal tight junction proteins ↓ Epithelial barrier function ↑ Transmucosal permeability Infiltration of bacteria or antigens ↑ Expression of nuclear factor kappa B (NF-kB) in colonic epithelial cells NF-kB increases transcriptional activity in specific genes ↑ Inflammatory molecules (histamine, prostaglandins, and nitric oxide) in epithelium predisposition Unknown trigger ↑ Transforming growth factor beta 1 (TGF- β1) and vascular endothelial growth factor (VEGF) expression in colonic epithelial cells Equilibrium shift to more production of collagen (fibrinogenesis) than breakdown (fibrinolysis) Drug exposure (e.g., non- steroidal anti- (+) inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs)) Inflammation and accumulation of immature subepithelial collagen matrix Subtype: Collagenous Colitis Intestinal mucosal inflammation Subtype: Lymphocytic Colitis characterized by a colonic subepithelial characterized by intraepithelial collagen band on histology lymphocytic infiltrates on histology Microscopic Colitis Intestinal epithelial damage Malabsorption of nutrients (including bile acids) Weight loss ↑ Intestinal transmucosal permeability Water drawn into lumen through osmosis Ions and water back leak into intestinal lumen Non-bloody watery diarrhea Dehydration and electrolyte disturbances Continuous release of inflammatory mediators Peripheral afferent nerve sensitization Visceral hypersensitivity Abdominal pain Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 8, 2018, Updated October 18, 2022 on www.thecalgaryguide.com

thiazide-diuretics-mechanism-of-action-and-adverse-side-effects

Thiazide Diuretics: Mechanism of Action and Adverse Side Effects Thiazide diuretics Authors: Huneza Nadeem Reviewers: Ran (Marissa) Zhang, Julian Midgley* * MD at time of publication Thiazides in circulation enter the proximal convoluted tubule (PCT) cells by basolateral Organic Acid Transporter 1 (OAT1) ↑ Intracellular thiazide availability for apical OAT4 exchangers OAT4 reabsorb urate in lumen in exchange for thiazide that is excreted ↑ Urate in serum Hyperuricemia Uric acid build up in joints Gout Block the Na-Cl cotransporter (NCC) in the distal convoluted tubule (DCT) of the nephron Impaired water excretion, vasopressin release, and ↑ water intake (mechanisms unclear) Hyponatremia Lack of intracellular Na+ needed to drive the Na+/K+ ATPase (moves 2 K+ into cell, 3 Na+ out into peritubular capillary) ↓ Intracellular Na+ drives Ca-ATPase and 3:Na:Ca exchanger activity (moves 3 Na+ into cell, 1 Ca+2 out into peritubular capillary) ↑ Ca+2 in serum Hypercalcemia See Hypercalcemia: Clinical Findings slide ↓ Na+ and Cl- reabsorption into proximal DCT cells ↑ Na+ in DCT filtrate by ∼3-5% Water follows Na+ to maintain balanced osmotic pressure ↑ Water available for excretion Mild Diuresis ↓ Blood volume Hypotension ↑ Na+ filtrate delivery to cortical collecting duct (CCD) Epithelial sodium channels (ENaC)s on principal cells of the CCD transport Na+ from filtrate into the principal cells ↑ Intracellular Na+ drives Na/K+ ATPase activity on principal cells (moves 2 K+ into cell, 3 Na+ out into peritubular capillary) ↑ Intracellular K+ drives H/K+ ATPase activity on intercalated cells (moves 1 H+ into cell, 1 K+ out into tubular filtrate) ↓ K+ in serum Hypokalemia See Hypokalemia: Clinical Findings slide Acute response to high dose thiazide diuretics (mechanism unclear) Hyperlipidemia Hypokalemia induces hyperpolarization of pancreatic beta cells ↓ Number of voltage gated Ca+2 channels open given intracellular charge ↓ Ca+2 influx prevents exocytosis mediated insulin release ↓ Glucose uptake in the body Hyperglycemia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 18, 2022 on www.thecalgaryguide.com

les-signes-et-symptomes-de-lembolie-pulmonaire-ep

Les signes et symptômes de l'embolie pulmonaire (EP) les-signes-et-symptomes-de-lembolie-pulmonaire-ep

infarctus-du-myocarde-signes-sur-examen-physique

Infarctus du myocarde: Signes sur examen physique

bloc-de-branche-gauche-pathogenese-et-signes-cliniques

Bloc de branche gauche: Pathogénèse et signes cliniques

diverticulite-aigue-pathogenese-et-signes-cliniques

Diverticulite Aigüe: Pathogenèse et Signes Cliniques diverticulite-aigue-pathogenese-et-signes-cliniques

hernies-inguinales-acquises-indirect-directe

hernies-inguinales-acquises-indirect-directe

le-travail-comme-determinant-social-de-la-sante

le-travail-comme-determinant-social-de-la-sante

type-ii-proximal-renal-tubular-acidosis-pathogenesis-and-laboratory-findings

Type II/Proximal Renal Tubular Acidosis: Pathogenesis and Laboratory Findings Authors: Wazaira Khan* Reviewers: Huneza Nadeem, Ran (Marissa) Zhang, Julian Midgley* * MD at time of publication Overview of bicarbonate reabsorption in the proximal tubule (PT): Serum bicarbonate (HCO3-) is filtered by the glomerulus and enters PT lumen H+ ATPase and sodium- hydrogen exchanger 3 (NHE3) on luminal surface of PT cell secrete H+ into PT lumen H+ combines with HCO3- in PT lumen to form carbonic acid (H2CO3) H2CO3 is broken down to H2O and CO2 by luminal membrane carbonic anhydrase 4 CO2 diffuses into PT cell CO2 reacts with H2O to form H2CO3 in PT cell, catalyzed by cytosolic carbonic anhydrase 2 H2CO3 rapidly breaks down intracellularly to form HCO3- and H+ HCO3- is reabsorbed into plasma by sodium bicarbonate transporter (NBCE1) on basolateral surface of PT cell HCO3- is available for use to buffer plasma H+ H+ is available intracellularly for use by H+ ATPase and NHE3 exchanger Mutation encoding NHE3 exchanger ↓ H+ secretion into PT lumen Galactosemia, Wilson disease, cystinosis, tyrosinemia, glycogen storage disorders Dent disease, Lowe syndrome Infiltrative disorders e.g., amyloidosis, multiple myeloma, monoclonal gammopathies Drugs e.g., tenofivir, ifosfamide, cisplatin Carbonic anhydrase inhibitors ↓ H2CO3 breakdown to H2O and CO2 Mutation encoding CAII enzyme, carbonic anhydrase inhibitors ↓ H2CO3 production in PT lumen ↓ CO2 diffusion into PT cell ↓ H2CO3 production in PT cell ↓ HCO3- production in PT cell ↓ HCO3- reabsorption by PT cell into plasma Type II/Proximal Renal Tubular Acidosis (RTA) Defective HCO3- reabsorption in proximal tubule Normal anion gap metabolic acidosis (NAGMA) See NAGMA slide Accumulation of toxic metabolites systemically, including in the PT Disruption of endocytosis and intracellular transport systemically, including in the PT Accumulation of light chain/amyloid deposits in PT Interfere with PT’s ability to reabsorb ions/molecules • • • • Fanconi Syndrome: generalized PT dysfunction Defective tubular reabsorption of other ions/molecules to varying degrees, including phosphate, glucose, sodium and amino acids Tubular proteinuria Phosphaturia Glucosuria ↑ Na+ secretionàhypovolemia Mutation encoding NBCE1 transporter ↑ HCO3- delivery to distal nephron K+ in distal nephron lumen binds to HCO3- K+ is lost through osmotic diuresis Hypokalemia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 24, 2022 on www.thecalgaryguide.com

copd-findings-on-posterior-anterior-and-lateral-chest-x-ray-findings

Authors: Shayan Hemmati COPD: Findings on Posterior-Anterior and Lateral Chest X-ray Findings Reviewers: Reshma Sirajee, Sravya Kakumanu, Tara Shannon, *Stephanie Nguyen, *MD at time of publication Chronic Obstructive Pulmonary Disease (COPD) See Pathogenesis of COPD Slides Findings of COPD may not be apparent on chest X-ray early within the disease Lung inflammation causes proteolytic destruction of lung parenchyma (part of lungs involved in gas exchange) Alveolar walls are damagedàformation of fragile enlarged sacs of air called bullae Rupture of bullae due to weak alveolar walls Air leaves alveola and enters pleural space Pneumothorax See Primary Spontaneous Pneumothorax slide Vasoconstriction of pulmonary arteries to shunt blood to better ventilated areas Pulmonary hypertension See Pathogenesis of Pulmonary Hypertension slide ↑ Pressure within pulmonary arteries Enlargement of pulmonary arteries Hilar enlargement Lung hyperinflation (defined as 10 posterior ribs above the diaphragm level on the midclavicular line) ↑ Lucency of the lung field, ↓ lung markings (unless COPD is of chronic bronchitis phenotype) ↑ Size of retrosternal airspace ↑ Anterior – posterior (AP) diameter (“Barrel Chest”) Flattening of hemidiaphragms 12 3 4 5 6 7 8 9 10 Poorly ventilated areas of lung Hyperinflation as air becomes trapped in damaged lungs ↑ Total volume of air within the chest Airway fibrosisà bronchial wall thickening (yellow arrow heads) Air is less dense than soft tissue and vessels so it appears black ↑ Pressure anteriorly on sternum ↑ Pressure posteriorly on thoracic wall ↑ Pressure posteriorly on diaphragms PA Bullae sometimes visible on X-ray (focal areas of lucency with spread out vascular markings) Image credit: Bronchial wall thickening image courtesy of Dr. Ashley Davidoff Image credit: Radiopaedia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 26, 2022 on www.thecalgaryguide.com

Syok Obstruktif: Patogenesis, komplikasi, dan temuan klinis

Syok Obstruktif: Patogenesis, komplikasi, dan temuan klinis

Syok Kardiogenik: Patogenesis, komplikasi, dan temuan klinis

Syok Kardiogenik: Patogenesis, komplikasi, dan temuan klinis

Syok Distributif: Patogenesis, komplikasi, dan temuan klinis

Syok Distributif: Patogenesis, komplikasi, dan temuan klinis

Hidrosefalus: Temuan Klinis pada Pediatri

Hidrosefalus: Temuan Klinis pada Pediatri

Perubahan Normal pada Neonatus: Patogenesis dan temuan klinis

Perubahan Normal pada Neonatus: Patogenesis dan temuan klinis

Granulomatosis with Polyangiitis Pathogenesis

Granulomatosis with polyangiitis: Pathogenesis Author: Oswald Chen Reviewers: Ben Campbell *Liam Martin * MD at time of publication Drugs Thiol- and hydrazine-containing medications (e.g., hydralazine, propylthiouracil, allopurinol) Environmental exposures Silica dust, cigarette smoke, infections (Staphylococcus aureus) Genetic factors Alpha-1 antitrypsin deficiency, proteinase 3 gene mutation ↑ Production of cytokines and antineutrophil cytoplasmic antibodies (ANCAs) (mechanism unknown) Cytokines bind to endothelial cells (that line blood vessels) and neutrophils, priming them Proteinase 3 (PR3), an enzyme that degrades extracellular matrix proteins, migrates from neutrophil granules to neutrophil cell surface Circulating ANCAs bind to PR3 on neutrophils PR3 stimulates maturation of dendritic cells in lungs Dendritic cells present antigen (PR3) to naïve CD4+ T cells in peripheral lymph nodes T cells differentiate into type 1 and type 17 helper T cells (Th1 and Th17 cells) Th1 and Th17 cells secrete cytokines (interferon γ (INF-γ) and tumor necrosis factor α (TNF-α)) in lungs Secreted cytokines trigger macrophage maturation Formation of granulomas (giant cells with central necrosis surrounded by plasma cells, lymphocytes, and dendritic cells) primarily in lungs and upper airways ANCA-activated neutrophils release proinflammatory cytokines, attracting more neutrophils to endothelium (blood vessel wall) ANCA-activated neutrophils undergo firm adhesion to endothelium ANCAs stimulate ↑ secretion of proteolytic enzymes and reactive oxygen species from neutrophils Endothelial damage and tissue injury Granulomatosis with polyangiitis (GPA) ANCA-associated vasculitis affecting medium and small-sized arteries, associated with necrotizing granulomas Constitutional symptoms with involvement of multiple organ systems (see slide on clinical findings) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 4, 2022 on www.thecalgaryguide.com Granulomatosis with polyangiitis: Clinical findings Inflammation-mediated endothelial damage and granuloma formation (see slide on pathogenesis) Granulomatosis with polyangiitis (GPA) Author: Oswald Chen Reviewers: Ben Campbell *Liam Martin * MD at time of publication ANCA-associated vasculitis affecting medium and small-sized arteries, associated with necrotizing granulomas Constitutional symptoms Fever, unintentional weight loss, night sweats, arthralgias Skin involvement Inflammation of cutaneous vessels Systemic inflammation obstructing blood flow, with granulomatous lesions primarily in upper airways and lungs Ear, nose, and throat involvement ↑ C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) (markers of inflammation) Necrotizing granulomas on biopsy of affected tissue Positive PR3-ANCA/c-ANCA blood test (antibodies present in ~90% of patients, described in GPA Pathogenesis slide) Renal involvement Inflammation of renal vessels Rupture of basement membrane (layer that filters blood from glomerular capillaries into Bowman’s capsule) Pauci-immune glomerulonephritis (see Nephritic Syndrome slide) Rapidly progressive glomerulonephritis Eye involvement Inflammation of ocular tissue Conjunctivitis Scleritis/ episcleritis (painful red eye) Lower respiratory tract involvement Inflammation of pulmonary vessels Vessel occlusion and ischemia Skin necrosis Vessels burst and blood pools under skin Round and retiform (net- like) palpable purpura of lower extremities Granulomatous destruction of nasal cartilage Collapse of nasal bridge Saddle nose deformity Inflammation of paranasal sinus and nasal cavity vessels ↓ Perfusion of lungs Dyspnea Damage to interstitial capillaries Hemoptysis Diffuse alveolar hemorrhage Rhinitis/ sinusitis Granulomatous obstruction of eustachian tube Otitis media (see Otitis Media slide) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 4, 2022 on www.thecalgaryguide.com

Granulomatosis with polyangiitis: Clinical findings

Granulomatosis with polyangiitis: Clinical findings Inflammation-mediated endothelial damage and granuloma formation (see slide on pathogenesis) Granulomatosis with polyangiitis (GPA) Author: Oswald Chen Reviewers: Ben Campbell *Liam Martin * MD at time of publication ANCA-associated vasculitis affecting medium and small-sized arteries, associated with necrotizing granulomas Constitutional symptoms Fever, unintentional weight loss, night sweats, arthralgias Skin involvement Inflammation of cutaneous vessels Systemic inflammation obstructing blood flow, with granulomatous lesions primarily in upper airways and lungs Ear, nose, and throat involvement ↑ C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) (markers of inflammation) Necrotizing granulomas on biopsy of affected tissue Positive PR3-ANCA/c-ANCA blood test (antibodies present in ~90% of patients, described in GPA Pathogenesis slide) Renal involvement Inflammation of renal vessels Rupture of basement membrane (layer that filters blood from glomerular capillaries into Bowman’s capsule) Pauci-immune glomerulonephritis (see Nephritic Syndrome slide) Rapidly progressive glomerulonephritis Eye involvement Inflammation of ocular tissue Conjunctivitis Scleritis/ episcleritis (painful red eye) Lower respiratory tract involvement Inflammation of pulmonary vessels Vessel occlusion and ischemia Skin necrosis Vessels burst and blood pools under skin Round and retiform (net- like) palpable purpura of lower extremities Granulomatous destruction of nasal cartilage Collapse of nasal bridge Saddle nose deformity Inflammation of paranasal sinus and nasal cavity vessels ↓ Perfusion of lungs Dyspnea Damage to interstitial capillaries Hemoptysis Diffuse alveolar hemorrhage Rhinitis/ sinusitis Granulomatous obstruction of eustachian tube Otitis media (see Otitis Media slide) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 4, 2022 on www.thecalgaryguide.com

Erythema multiforme (EM): Pathophysiology and clinical findings

Erythema multiforme (EM): Pathophysiology and clinical findings Infectious agents (cause >90% of EM) Herpes simplex virus types 1 and 2 Mononuclear cells transport herpes simplex virus DNA fragments to keratinocytes in epidermis Herpes simplex virus-specific CD4 T-cells of the immune system are recruited to the epidermis CD4 T-cells release interferon-gamma (a pro-inflammatory cytokine) in response to viral antigens in keratinocytes in the epidermis Lymphocytes infiltrate along the dermal-epidermal junction of the skin Lymphocytes create an inflammatory and edematous environment Keratinocytes irreversibly degenerate and undergo apoptosis and necrosis Formation of inflammatory epidermal lesions Authors: Ayaa Alkhaleefa Reviewers: Ben Campbell Damilola Omotajo Jori Hardin* *MD at time of publication Drugs (a rare cause of EM) Non-steroidal anti- inflammatory drugs i.e. diclofenac sodium Antibiotics i.e. TMP- SMX Topical 5% Imiquimod, used to treat actinic keratoses Activate tumour-necrosis-factor- alpha, an inflammatory cytokine Skin Epidermal layer Dermal-Epidermal Junction Dermal layer Triggering agent (infection, drugs) Immune-mediated inflammation and epidermal tissue damage Erythema multiforme Inflammation ↑ capillary blood flow in dermis Red colouring of skin in the area Centre of lesions contain a necrotic core Inflammatory edema causes margins around necrosis to form a raised and pale ring Inflammation stimulates cutaneous itch receptors Erythematous, papular, target-shaped, pruritic lesions on mucosal and acral (palms of hands, soles of feet) sites and face Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 29, 2022 on www.thecalgaryguide.com

rheumatoid-pneumoconiosis-caplans-syndrome-pathogenesis-and-clinical-findings

Rheumatoid Pneumoconiosis (Caplan’s Syndrome): Pathogenesis and clinical findings Authors: Christopher Li Keerthana Pasumarthi Reviewers: Daniela Urrego, Ben Campbell, Liam Martin* * MD at time of publication Dust-exposed occupation (e.g. coal, asbestos, silica) ↑ Accumulation of dust particles in lungs Dust (e.g. silica) mobilizes from the lungs to other organs such as the kidneys, lymph nodes, and spleen Accumulation of silica in other organs which activate the immune system to secrete cytokines, chemokines, and lysosomal enzymes Activation of antigen- presenting and antibody- producing cells Increased risk to produce autoantibodies Increased risk for autoimmune conditions such as rheumatoid arthritis See slide: Rheumatoid Arthritis (RA): Extra- articular manifestations for mechanism of systemic inflammation See slide Pneumoconioses: Pathogenesis and clinical findings for mechanism Note: Rheumatoid arthritis may precede lung nodules or develop later in the course Rheumatoid arthritis Systemic autoimmune inflammatory disease that mainly involves synovial joints (+) Alveolar macrophages and neutrophils ingest dust particles ↑ Inflammation and cytokine production in pulmonary parenchyma (e.g. interleukin-1, tumor necrosis factor-α) Rheumatoid pneumoconiosis Interstitial lung disease, with characteristic nodules, resulting from the interaction between dust inhalation and rheumatoid arthritis inflammation Cytokines recruit histiocytes, neutrophils, lymphocytes, and fibroblasts to the area to produce a zone of inflammation around the dust-containing cell Necrosis and apoptosis of dust-containing cells, macrophages, and surrounding collagen Necrotic cells are digested by new macrophages to restart the process Production of nodules that contain a central necrotic area surrounded by alternate layers of dust and necrotic tissue (Caplan nodules) Hyperactive immune response to foreign materials in lungs Multiple concentric rings of dust seen histologically on light microscopy 0.5-5 cm rounded opacities on chest X-ray in periphery of lungs See slide on Pneumoconioses for symptoms and pulmonary function test results Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 17, 2022 on www.thecalgaryguide.com

Acute Liver Failure: Pathogenesis and clinical findings

Acute Liver Failure: Pathogenesis and clinical findings Authors: Juliette Hall Reviewers: Vina Fan, Ben Campbell, Mayur Brahmania* * MD at time of publication Acetaminophen Overdose Accumulation of toxic NAPQI (a metabolite of acetaminophen) NAPQI binds hepatocellular proteins (see Acetaminophen Overdose: pathogenesis and clinical findings slide) Drug-induced liver injury Metabolism of drugs by the liver can produce reactive drug metabolites Intracellular stress, mitochondrial injury, or immune response Viral Hepatitis (i.e. HAV, HBV, HEV, HSV) Acute infection or infection flare provokes an immune response against infected hepatocytes Autoimmune Hepatitis Autoimmune antibodies attack hepatocytes (see Auto-immune Hepatitis (AIH) slide) Ischemia (i.e. from shock) ↓ O2 delivery to the liver Hepatocellular hypoxia Wilson’s Disease Heritable mutation in the ATP7B gene ↓ Biliary excretion of copper Hepatic copper accumulation injures hepatocytes (see Wilson’s Disease slide) Accelerated rate of hepatocellular necrosis or apoptosis Hepatocyte death exceeds regeneration such that liver function is compromised within a short amount of time Acute Liver Failure An illness of <26 weeks duration in the absence of pre-existing cirrhosis, characterized by INR ≥1.5 and evidence of altered mentation (hepatic encephalopathy) Injured hepatocytes leak hepatic enzymes (AST, ALT, GGT) into circulation ↑ Liver enzymes Hepatocellular inflammation Stimulation of foregut autonomic nerves Right upper quadrant pain ↓ Toxin metabolism Toxins build up and activate microglial cells (brain macrophage) Oxidative stress and cerebral edema Hepatic encephalopathy Characteristic set of neuropsychiatric symptoms (see Hepatic Encephalopathy slide) ↓ Hepatocellular function and number ↓ Complement protein synthesis ↓ Ability to clear immune complexes and activate B cells Accumulation of pigmented bilirubin ↓ Synthesis of coagulation factors ↑ INR ↓ Conjugation of bilirubin by the liver and ↓ transport into bile for excretion ↑ Serum bilirubin Jaundice Infection Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 15, 2022 on www.thecalgaryguide.com

Acute and Chronic Gastritis: Pathogenesis and clinical findings

Acute and Chronic Gastritis: Pathogenesis and clinical findings Author: Oswald Chen Reviewers: Vina Fan, Ben Campbell, Eldon Shaffer* * MD at time of publication Infectious Helicobacter pylori (most common) Noninfectious NSAIDs, alcohol, gastric reflux Stress Critical illness, trauma Gastric ulceration (see Peptic Ulcer Disease slide) ↓ Gastric mucosal defense (↓ secretion of prostaglandins and mucus) Acid erodes gastric mucosa Inflammatory cells (primarily neutrophils) infiltrate site of injury Acute Gastritis Acute inflammation of gastric mucosa Inflammatory cells (primarily lymphocytes and plasma cells) accumulate in gastric mucosa Autoimmune Metaplastic Environmental Metaplastic Atrophic Gastritis (AMAG) Atrophic Gastritis (EMAG) Atrophic Gastritis Chronic inflammation of gastric mucosa Inflammatory cells destroy gastric glandular epithelial cells Gastric mucosal atrophy and metaplasia (replacement of gastric mucosal cells with intestinal epithelial cells, commonly goblet cells) Hypochlorhydria (parietal cell loss → ↓ hydrochloric acid secretion) ↓ Iron absorption Iron deficiency anemia (see Iron Deficiency Anemia slide) Activation of chemoreceptors and mechanoreceptors Activation of visceral nociceptors Visceral afferents stimulate chemoreceptor trigger zone of medulla Nausea/ vomiting Autoimmune Associated with human leukocyte antigens HLA-B8 and HLA-DR3, which are proteins expressed on immune cell surface Antibodies destroy parietal cells and intrinsic factor in gastric body and fundus Epigastric pain (typically burning or gnawing) Dyspepsia (abdominal discomfort after eating, often with early satiety and bloating) Parietal cell loss → ↓ intrinsic factor → ↓ vitamin B12 absorption Vitamin B12 deficiency (see Vitamin B12 Deficiency slide) Macrocytic Peripheral anemia neuropathy ↓ Gastric acidity leads to ↓ inhibition of G cells in antrum Hypergastrinemia (↑ gastrin release from G cells) Gastrin binds to cholecystokinin-B (CCK-B) receptors on parietal and enterochromaffin-like (ECL) cells of gastric body ↑ CCK-B signaling leads to ↑ cell proliferation and ↓ cell death (↓ apoptotic activity) Hyperplasia (↑ number of cells) Low-grade dysplasia (disordered growth of epithelium) High-grade dysplasia Carcinoid tumor (0.7% of cases) Malignancy arising from ECL cells Gastric adenocarcinoma (0.3% of cases) Malignancy arising from gastric epithelial cells Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 15, 2022 on www.thecalgaryguide.com

Pubic Rami Fracture: Pathogenesis and clinical findings

Pubic Rami Fracture: Pathogenesis and clinical findings Authors: Kaela Schill Reviewers: M. Patrick Pankow, Tara Shannon, Alyssa Federico, Dr. Linda Mrkonjic* * MD at time of publication High energy impact Osteoporosis (most common) Bone loses calcium, becoming less dense weaker and more susceptible to fracture (See Osteoporosis: pathogenesis and clinical findings slide) Athletic injury in skeletally immature athletes (e.g., soccer, gymnastics) Open growth plates are weak and more susceptible to injury Lateral compression or vertical shear fracture Mild to moderate osteoporosis Fragility pubic rami fracture from low-energy impact (e.g., falls from standing, falls in the bathtub) Severe osteoporosis Spontaneous pubic rami fracture Sudden, forceful contraction of the hamstring muscles (e.g. sudden change of direction, sudden stop) Hamstring pulls a piece of the ischial tuberosity from the pelvis boneàpubic rami avulsion fracture (Posterior pelvic rim fracture requires CT to diagnose and is often missed) Missed or delayed diagnosis due to incomplete workup Pubic Rami Fracture Fracture of the anterior pelvic ring, can be the superior and/or inferior pubic rami Co-existing posterior pelvic ring fracture (e.g. acetabulum, sacrum) Fracture on both sides of pelvis Unstable pelvis Blood vessels in and surrounding the bone rupture during injury Blood accumulates under the skin Bruising around fracture site Inflammatory response to injury Recruitment of white blood cells and fluid to the area Swelling around fracture site Irritation at superior/inferior pubic rami muscle attachment sites (groin and hip abductor muscles) Pain in groin near fracture site ↑ Displacement and incomplete healing of the posterior and anterior pelvic ring fracture ↑ Morbidity and mortality ↑ Disuse osteoporosis ex: lower limbs, pelvis, and back ↑ Muscle stiffness ex: lower limbs, pelvis, and back ↑ Joint stiffness ex: lower limbs, pelvis, and back Fracture hematoma in pubic rami Hematoma distends the periosteum, irritating nerves in the area Moving/walking further irritates nerves in the area Moving and walking ↑ pain àinadequate movement ↓ Mobility (to avoid pain) Antalgic gait (stance phase of walking is shortened relative to swing phase) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 4, 2022 on www.thecalgaryguide.com

COPD: Treatments and Common Side Effects

COPD: Treatments and Common Side Effects Note: Please see various slides on COPD related to pathogenesis and findings • Relievers: Used as needed to ↓ symptoms during attacks • Controllers: Used daily to ↓ frequency and severity of attacks • Exacerbation: Used emergently in acute exacerbation (relievers also often used) Short-acting Beta Agonists (SABA) Reliever Long-acting Beta Agonists (LABA) Controller Long-acting Muscarinic Antagonists Controller Inhaled Corticosteroids (ICS) Controller Phosphodiesterase Inhibitors (PDE4i) Controller Short-acting Muscarinic Antagonists Reliever Systemic Corticosteroids Exacerbation Antibiotic therapy Exacerbation + Controller Binds to beta-2 adrenergic receptors in bronchial smooth muscle cells Activation of intracellular signal cascade in bronchial smooth muscle Off-target binding occurs in other systemic cells Prevent phosphodiesterase enzymes from breaking down secondary messenger molecules such as cyclic adenosine monophosphate (cAMP) cAMP binds to other cell signaling proteins Bronchial smooth muscle cells have ↓ Ca2+ release from intracellular stores (i.e. from sarcoplasmic reticulum) Inhibition of muscarinic acetylcholine receptors in airway muscle cells ↓ Activation of the inositol triphosphate (IP3) intracellular pathway (IP3 pathway normally functions to mobilize intracellular Ca2+ stores) Steroid binds to nuclear receptors within cells ↓ Gene expression/ synthesis of immune mediators (ex. cytokines) Frequent moderate-severe exacerbations despite maximal therapy Prophylactic macrolide treatment in outpatients Certain macrolides have anti- inflammatory properties ↓ Infection risk = ↓ exacerbation risk COPD exacerbations often triggered by respiratory infections Empiric antibiotic therapy in hospitalized patients with acute exacerbations ↓ Infection in lungs ↓ Sputum production ↓ Respiratory distress Stimulation of Na/K ATPase (which transports K into cells) Hypokalemia Palpitations Tachycardia Muscle cramps Tremor Inadvertent sympathetic nervous system activation ↓↓ Cytoplasmic Ca2+ Myosin (muscle protein) unable to be activated for muscle contraction ↓ Smooth muscle contraction in bronchioles Bronchodilation ICS ↓ immune cell activity in the oropharynx Susceptibility to infection and irritation of the oropharynx due to inhaled particles and pathogens Hoarseness Thrush Systemic steroids cause ↓ immune cell activity in whole body ↑ Susceptibility to any infection (and many other side effects) ↓ Release of inflammatory cytokines (↓ Type 2 inflammatory response in airways) ↓ Permeability of airway vasculature ↓ Microvascular leakage into airway Authors: Reshma Sirajee, Chunpeng Nie Reviewers: Sravya Kakumanu, Ben Campbell, Tara Lohmann* * MD at time of publication Similar effects on other muscles in the body outside bronchi Dry mouth Urinary retention Constipation ↓ Airway mucus ↓ Mucosal edema Legend: Pathophysiology Mechanism Treatment Effect Side Effects Published November 15, 2022 on www.thecalgaryguide.com

Achalasia: Findings on Fluoroscopy with Barium Swallow

Achalasia: Findings on Fluoroscopy with Barium Swallow Authors: Nameerah Wajahat, Omer Mansoor, Aly Valji Reviewers: Tara Shannon, Reshma Sirajee, Stephanie Nguyen* *MD at time of publication Barium swallow performed (patient swallows barium contrast, a radiopaque agent, which outlines the gastro-intestinal (GI) tract during fluoroscopy) Primary Achalasia (idiopathic) Secondary (Pseudo) Achalasia (due to another disease process such as tumor, Chaga’s disease, diabetes mellitus) Achalasia Secondary disease processes can cause denervation or nerve dysfunction of esophageal myenteric plexus (EMP). Tumors can obstruct the lumen and infiltrate the EMP. Visual differences from primary achalasia Look for fixed abnormalities and/or mucosal irregularities and shouldering in the setting of a tumor Nerves controlling the lower esophagus are damaged, making it difficult for food and liquids to pass the esophagus See “Achalasia: Pathogenesis and Clinical Findings” for full pathogenesis of primary and secondary achalasia Inflammation and degeneration of nerves in the wall of esophagus Dysfunction of the esophageal myenteric plexus (network of nerves in the GI tract responsible for peristalsis and sphincter relaxation) Incomplete relaxation of the Loss of peristalsis in distal lower esophageal sphincter (LES) esophagus Barium has difficulty passing through the LES to the stomach Barium outlines the GI tract, following esophageal abnormalities Normal findings Esophageal Dilatation Occurs upstream of narrow LES Bird Beak Sign / Rat Tail Sign Smooth narrowing of the distal esophagus Incomplete LES relaxation Barium Swallow may be normal in some patients with achalasia. Esophageal manometry (gold standard for diagnosis) or upper endoscopy can be considered instead. Image Source: Radiopaedia Legend: Pathophysiology Mechanism Radiographic Findings Complications Published November 9, 2022 on www.thecalgaryguide.com

popliteal-bakers-cyst-pathogenesis-and-clinical-findings

Popliteal (Baker’s) Cyst: Pathogenesis and clinical findings Authors: Liam Thompson, Megan Ure Reviewers: M. Patrick Pankow, Tara Shannon, Reza Ojaghi, Usama Malik, Dr. Gerhard Kiefer* * MD at time of publication Repeated contraction of muscles surrounding the bursaàmicro trauma to bursa Inflammatory response Idiopathic (common: kids 4-7 years old) Bursa located between medial head of gastrocnemius and semimembranosus tendon Accumulation of inflammatory fluid into the bursa forming a cyst Meniscal Tear Tear creates a channel between joint capsule and bursa posterior to the knee joint Rheumatoid Arthritis Auto-immune mediated inflammation of knee joint Osteoarthritis Destruction of articular cartilageà inflammation within knee joint See Osteoarthritis: Pathogenesis slide Damage to joint capsule and accumulation of inflammatory fluid Proteolytic enzyme dysregulation Local muscle action influences fluid flow and pressure changes Extra- articular Popliteal Cyst Fluid filled sac behind knee Usually asymptomatic (resolves spontaneously) Synovial joint herniates into popliteal fossa (most commonly medially)àaccumulation of fluid (synovial + inflammatory) into synovial herniation, forming a cyst Knee flexion Intra-articular Popliteal Cyst Known as “Baker’s cyst” Knee extension ↑ Muscle tension around cyst Channel between knee joint and cyst gradually closes with ↑ tensionàat full extension, no fluid flow between the joint and cyst (trapping the fluid in the cyst) ↓ Muscle tension around cyst Channel between knee joint and cyst opens Knee joint pressure becomes negative ↑ Fluid flow from cyst into knee joint ↓ Fluid in popliteal cyst Knee joint pressure becomes positiveà ↑ Fluid flow from knee joint into cyst (Posterior tibial nerve located lateral to the popliteal cyst and enervates posterior knee, calf, and bottom of foot) Posterior tibial nerve becomes entrapped by mass (cyst) Enlarging mass in posterior knee Cyst reaches maximum volume Pressure within cyst exceeds tensile strength of surrounding sac Fluid drains distally into calf Popliteal vein located lateral to cyst ↑ Venous pressure distal to cyst Popliteal vein occluded by mass Venous pooling distal to site of occlusion ↓ Space in posterior calf compartmentàcompression of calf muscles and posterior tibial nerve Ankle dorsiflexion ↑ pressure in compartment Positive Homan’s sign (discomfort with passive ankle dorsiflexion) Posterior plantar numbness Pain receptors (nociceptors) activated Posterior knee pain/pressure Cyst Rupture Abrupt and intense pain Stimulates inflammatory response Fluid pushed from veins into interstitial space Swelling and erythema (redness) in distal calf and foot Pseudo-Thrombophlebitis worse with extension or physical activity (shares symptoms with deep vein thrombosis but no associated clot) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Feb 10, 2018, updated Nov 19, 2022 on www.thecalgaryguide.com

hypovolemic-shock

Hypovolemic Shock: Pathogenesis, Complications, and Clinical Findings Authors: Dean Percy Miranda Schmidt Reviewers: Yan Yu Tristan Jones Frank Spence* Ben Campbell Ayaaz Sachedina* * MD at time of publication Progressive ↓ in level of consciousness Pulseless Electrical Activity Acute Kidney Injury ↑ Reabsorption of salt and water in the kidney Oliguria (↓ urine output) Inflammation (pancreatitis, cirrhosis, post-operative, etc.) Inflammatory mediators ­ vessel permeability and fluid leaks out Trauma Ruptured vessels leak fluid into potential spaces Hemorrhagic losses (GI bleed, postpartum hemorrhage, etc.) ↓ Intravascular volume ↓ Venous return to the heart ↓ Cardiac output (blood pumped from the heart) Hypovolemic Shock ↓ Oxygen delivery to tissues due to low blood volume Insufficient organ perfusion Non-Hemorrhagic losses (dehydration, GI losses, skin losses / burns, renal losses, etc.) ‘Third Spacing’ of fluid (fluid located outside the intravascular or intracellular space; large collections can occur in the pelvis, thorax, GI tract, long bones of children, intra-abdominally, retroperitoneally) P = Q x R; less ‘flow’ in the vessels (Q), with vessels not constricting enough to maintain resistance (R)à pressure (P) will drop ↓ Blood Pressure Caution: young, healthy individuals can maintain blood pressure during circulatory collapse with ­ cardiac output and ­ vasoconstriction; do not use blood pressure as an indicator of shock severity in children Carotid sinus baroreceptors sense low blood pressure ↓ Carotid sinus inhibition of sympathetic nervous system Release of sympathetic catecholamines (epinephrine and ↓ Pressure in venous circulation Brain Heart Kidneys ↓ Blood in the right internal jugular vein ↓ Oxygen delivery to the brain ↓ Myocardial contractility (from lactic acidosis) ↓ Blood flow to kidneys ↓ Jugular Venous Pressure Catecholamines bind to beta-1 receptors in the sinoatrial node of the heart Beta-1 receptor activation causes ↑ heart rate Tachycardia norepinephrine) Catecholamines bind to and stimulate alpha-1 receptors in peripheral vessels Vasoconstriction of peripheral vessels ↓ Blood flow to peripheral tissue Catecholamines bind to and stimulate beta receptors in sweat glands Diaphoresis (sweating) In all body tissues Inadequate oxygen delivery ↓ ATP production ↑ Anaerobic metabolism ↓ Body temperature Impaired neurological functioning Renal ischemia Activation of the renin-angiotensin aldosterone system ↓ Glomerular filtration rate ↓ Clearance of lactic acid by the kidney ↑ Lactic acid production ↓ Rate of activity of clotting enzymes Lactic Acidosis Unknown mechanism Coagulopathy Hypothermia Trauma Triad of Death ↑ Capillary Cold, mottled refill time extremities Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 24, 2013, updated December 4, 2022 on www.thecalgaryguide.com

Ischemic Stroke: Pathogenesis

Ischemic Stroke: Pathogenesis Small artery occlusion Acute injury (<20mm diameter) of basal or brainstem penetrating arteries Large artery atherosclerosis Cholesterol plaque ↓ diameter of intra- or extracranial vessel Cardiac embolism Blood clot in heart breaks free, travels to brain Other E.g. volume loss, severe infection Unknown E.g. 2 or more mechanisms Modest ↓ in O2 at penumbra (see figure) Authors: Mizuki Lopez Andrea Kuczynski Illustrator: Mizuki Lopez Reviewers: Sina Marzoughi Usama Malik Hannah Mathew Ran (Marissa) Zhang Andrew M Demchuk* Gary M. Klein* * MD at time of publication Significant ↓ in O2 at ischemic core (see figure) ↑ Anaerobic metabolism ↓ ATP Production Dysfunction of Na+/K+ ATPase pump (for 1 ATP molecule, 3 Na+ moved out of cell, 2 K+ moved into cell) H2O influx following Na+ Cerebral edema Compression of vessels and surrounding tissue damages blood-brain barrier ↑ Permeability of damaged blood-brain barrier Infiltration by peripheral immune cells Immune cells release inflammatory cytokines ↓ Cerebral Blood Flow Penumbra Ischemic core Metabolic demands are greater than supply of ATP Cell death Microglia (resident neural immune cells) activate to clean dead cell debris Microglia release inflammatory cytokines (TNFα, IFγ, IL-1β) Cytokines lead to astrocyte activation (support cells for neurons) Astrocytes release more inflammatory cytokines Inflammation of brain tissue ↑ Na+, Ca2+ influx, K+ outflux ↓ Glutamate (excitatory neurotransmitter) reuptake by astrocytes (support cells for neurons) ↑ Glutamate in extracellular fluid Spreading depolarization from core (unclear mechanism) Activate biochemical pathways including glutamate receptor activation ↑ Glutamate activity Activate glutamate receptors that conduct Ca2+ ↑ Ca2+ influx into neuron Activation of catabolic proteases, lipases, nucleases in neuron Dysfunction of neuronal protein synthesis and activity Neuronal cell death ↑ Volume of dead (infarcted) brain tissue Neurons depolarize and release glutamate Reversal of Na+ Dependent Glutamate Reuptake Transporters on astrocytes (normally 3 Na++ 1 H+ + 1 glutamate into cell, for 2 K+ out) ↑ Glutamate in extracellular fluid Stroke symptoms (e.g. weakness, slurred speech, visual field losses, autonomic dysfunction) (see Ischemic Stroke: Impairment by Localization stroke slide) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 14, 2017; updated November 6, 2022 on www.thecalgaryguide.com

Cirrhosis

Cirrhosis: pathogenesis and complications Author: Chunpeng Nie Yan Yu Reviewers: Paul Ratti, Amy Maghera, Vina Fan, Ben Campbell, Sam Lee*, Mayur Brahmania* *MD at time of publication Chronic viral hepatitis (B, C, or D) Hepatitis D occurs with hepatitis B Alcohol related liver disease Non-alcoholic steatohepatitis Autoimmune: autoimmune hepatitis, primary biliary & sclerosing cholangitis Genetic: hemochromatosis, Wilson’s disease, α1- antitrypsin deficiency Toxic: drugs may rarely cause chronic liver disease or cirrhosis Severe or chronic hepatocyte injury overrides regenerative capacity → Fibrosis Cirrhosis Mild fibrosis may reverse with treatment of underlying cause Nodular/shrunken liver on ultrasound ↑ Liver stiffness on transient elastography Diffuse fibrosis with nodular regeneration on biopsy Fibrotic liver provides ↑ resistance to blood flow Portal hypertension Irreversible formation of fibrosis, within which hepatic cell regeneration is restricted to form nodules of poorly-functioning cells Inflammation → epigenetic changes, oncogene mutations Hepatocellular carcinoma ↑ Serum α-fetoprotein (sensitivity 50%, specificity 99%) Fibrosis disrupts normal function of hepatic lobules Hepatic insufficiency ↓ Liver synthetic function ↓ Thrombopoietin synthesis Thrombocytopenia ↓ Conjugation of bilirubin, ↓ secretion of bilirubin into bile ducts, and ↓ drainage of bilirubin into hepatic duct Accumulation of serum bilirubin >30 μmol/L Jaundice Scleral icterus, jaundiced frenulum ↑ Pressure in portal venous circulation Portosystemic shunts Increased flow to esophageal, rectal, and splenic veins Vascular stretch → endothelial vasodilator (e.g. NO) release Vasodilators enter systemic circulation Pulmonary vasodilation Blood cells in pulmonary vasculature have ↓ time for gas exchange Hepatopulmonary syndrome (rare) Dyspnea or hypoxemia, worsened when upright ↓ Synthesis of clotting factors (V, VII, IX, X, XI, XII, fibrinogen, prothrombin) and anticoagulant proteins (antithrombin, proteins C/S) Unpredictable imbalance of hemostatic and anticoagulant factors Elevated INR ± coagulopathy Impaired metabolism of waste products and toxins Toxins (mainly ammonia) accumulate and cross the blood- brain barrier Hepatic encephalopathy Day-night reversal, asterixis, delirium Varices (dilated veins in the esophagus, stomach, or rectum) Variceal bleed GI bleed and hypovolemia Backflow of blood into spleen Splenomegaly Enlarged spleen sequesters (traps) blood cells Cytopenias (eg. thrombocytopenia or anemia), petechiae, easy bruising ↓ Blood flow to kidneys, which sense ↓ effective blood volume Kidneys retain water and Na+ ↑ Hydrostatic pressure in splanchnic vessels ↓ Albumin synthesis ↓ Capillary oncotic pressure Net fluid flux out of vasculature into interstitial space Ascites (fluid in peritoneal cavity) Peripheral edema Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 7, 2022, updated November 6, 2022 on www.thecalgaryguide.com

Farmakodinamik: Prinsip Dasar

Farmakodinamik: Prinsip Dasar

Aterosklerosis: Patogenesis

Aterosklerosis: Patogenesis

Aterosklerosis: Komplikasi

Aterosklerosis: Komplikasi

Approach to Arterial Blood Gases ABGs

Approach to Arterial Blood Gases (ABGs) Normal pO2 should be FiO2 x 4-5 (FiO2 in room air= 21%) pH >7.40 = Alkalemia 1. Adequate oxygenation? 2. Define the acid-base disturbance Diarrhea (Loss of electrolytes not reabsorbed through bowel) Normal ABG on Room Air = 7.40 / 40 / 90 / 24 pO2 ↓ than expected Possible hypoxemia See slide on Hypoxemia: Pathogenesis and Clinical Findings (pH) (Loss of acidic fluids from stomach) (HCO3-) (pCO2) (pO2) Renal Tubular Acidosis (RTA) pH <7.40 = Acidemia Metabolic derangement (Due to poisons, infection, or ketones) Gain of acid (H+) Brain unable to promote respiratory drive (ex. drugs, trauma) Inability for chest wall to expand (ex. obesity, neuromuscular weakness, pleural or chest wall abnormalities) Vomiting or nasogastric suction Impaired tubular transport of H+ (Due to loop/thiazide diuretics, hypomagnesemia, congenital abnormalities) 1o Hyperaldosteronism = ↑ H+ ion secretion at distal tubule (Due to tumours, congenital abnormalities , malignant hypertension, etc) Type II RTA = HCO3- not reabsorbed Type I or IV RTA = H+ not secreted GI or renal loss of HCO3- Hypoventilation ↑ CO2 from ↓ exhalation Respiratory Acidosis Acute= ↑10:↑1, Chronic= ↑10:↑3 GI or renal loss of acid (H+) ↑ HCO3- from ↓ H+ to bind with Metabolic Alkalosis ↑7:↑10 ↑ Ventilation from stress, trauma, infection ↓ CO2 from ↑ exhalation Respiratory Alkalosis Acute= ↓10:↓2, Chronic= ↓10:↓4 3. Identify the primary (1o) process 4. Compensatory mechanisms in lungs and kidneys attempt to lose/retain CO2 or HCO3- to maintain normal pH. Determine if compensation is appropriate (approximate normal ratio of change in pCO2 : HCO3- is shown in green boxes). If inappropriate, there is a secondary (2o) process occurring HCO3- binds with extra H+ ↓ HCO3- Metabolic Acidosis ↓12 :↓10 Less CO2 than expected, due to ↑ exhalation = Less acid in serum 2o Respiratory alkalosis More CO2 than expected, due to ↓ exhalation = More acid in serum 2o Respiratory acidosis Less HCO3- than expected, due to 2o gain of H+ or loss of HCO3- 2o Metabolic acidosis More HCO3- than expected, due to 2o loss of H+ 2o Metabolic alkalosis Less CO2 than expected, due to ↑ exhalation = Less acid in serum 2o Respiratory alkalosis ↑ CO2 than expected, due to ↓ exhalation = More acid in serum 2o Respiratory acidosis Less HCO3- than expected, due to 2o gain of H+ or loss of HCO3- 2o Metabolic acidosis More HCO3- than expected, due to 2o loss of H+ 2o Metabolic alkalosis 5. Calculate anion gap (AG) to determine the presence and type of metabolic acidosis. This is done regardlessofthe1o or2oprocess, as there may also be a hidden metabolic acidosis 6. HAGMA only: In normal blood buffer system, acid gain should match bicarbonate lost. If not, identify if another process is causing an inappropriate loss or gain of HCO3- Gain of acid (∆AG) = AG-12 LossofHCO3- (∆HCO3-)=24-HCO3- 7. Calculate Osmolar Gap (for HAGMA) or Urine net charge (for NAGMA) to narrow the etiology Authors: Sravya Kakumanu Reviewers: Huneza Nadeem, Ben Campbell *Adam Bass, *Yan Yu * MD at time of publication (normal is ~12) Calculate AG = Na+- Cl- - HCO3- If a metabolic acidosis is present, ↓ HCO3- is compensatedby↑otherserumanionstomaintain neutral charge If no metabolic acidosis was identified in steps 2-4: No Metabolic acidosis present Classically, the compensating anion is Cl-,maintaininganormalAG AG ≤ 12 If a 1o or 2o metabolic acidosis was identified in steps 2-4: Normal Anion Gap Metabolic Acidosis (NAGMA) In this scenario, a normal distal nephron should be excreting excess acid Excess acid is normally excreted as ammonium (NH +) with Cl- 4 The more Cl- in the urine relative to cations, the more acid is being excreted Calculate urine (U) net charge to determine cause of NAGMA = UNa+ + UK+ - UCl- When the cause is addition of an abnormal acid, HCO3- is used up asabuffer,andthecompensatinganionistheabnormalacid's conjugate base – which is not measured in the AG calculation ↓ HCO3- is compensated by unmeasured anionsà the AG ↑ AG>12 High Anion Gap Metabolic Acidosis (HAGMA) Calculate ∆AG = AG-12 Calculate ∆HCO3- = 24-HCO3- ∆HCO3- > ∆AG Loss of HCO3- > Gain of acid Additional process causing further loss of HCO3- HAGMA + NAGMA ∆HCO3- = ∆AG Loss of HCO3- = Gain of acid Only acid gain from HAGMA causing HCO3- loss HAGMA only ∆HCO3- < ∆AG Loss of HCO3- < Gain of acid Additional process causing gain of HCO3- despite losses due to HAGMA HAGMA + Metabolic alkalosis See slide on Metabolic Alkalosis: Pathogenesis -ve U net charge Appropriately large Cl- excretionà Toxic alcohol ingestion ↑ serum osmolality (and H+) from metabolites produced, so osmolality helps identify etiology Calculate osmolar gap to determine cause of HAGMA = (measured serum osm) – (expected serum osm) = (measured serum osm) – (2(Na+) + urea + serum glucose) +ve U net charge Inappropriately small Cl- excretionà impaired acid excretion is the issue Type IV or Type I RTA See slide on Normal Anion Gap Metabolic Acidosis: Pathogenesis and Laboratory Findings HCO3 GI losses or Type II RTA - loss is the issue Osmolar gap > 10 (extra osmoles present) Toxic alcohol poisoning Osmolar gap ≤10 (normal) Test for other causes See slide on High Anion Gap Metabolic Acidosis: Pathogenesis and Laboratory Findings Legend: Disease State Mechanism Lab Finding/Calculation Published January 29, 2023 on www.thecalgaryguide.com

Hidradenitis Suppurativa

Genetic mutations causing impaired function of gamma-secretase (NCSTN, PSEN1 or PSENEN genes) Defective notch signaling pathway (a regulator of many cell processes) Hormones (excess androgen activity) Smoking (nicotine exposure) Skin to skin friction Systemic inflammation Hidradenitis Suppurativa: Pathogenesis and Clinical Findings Other unknown genetic factors Follicular occlusion HS nodule Epidermal layer Dermal- Epidermal Junction Dermal layer Inflammatory cytokine- mediated activation of nociceptors Inflammatory cytokines Sebaceous gland Apocrine sweat gland Hair follicle Pilosebaceous- apocrine unit Changes in gene expression of hair follicle and apocrine gland anti-microbial peptides Accumulation of corneocytes (dead keratinocytes) and sebum àfollicular occlusion and rupture ↑ Interleukin-36 (IL-36, a cytokine) Altered keratinocyte differentiation Hair follicle hyperkeratinization Abnormal structure and function of the pilosebaceous- apocrine unit Infiltration of normal skin flora microbes, macrophages, dendritic cells, and Th17 cells Increased density of nicotinic acetylcholine receptors in pilosebaceous-apocrine unit (see figure) Mechanism not fully understood Hyperhidrosis Pain Innate immune cells produce inflammatory cytokines: tumour necrosis factor alpha (TNF-α) and various interleukins (IL-1, IL-6, IL-12, IL-17, IL-22 and IL-23) IL-17 promotes neutrophil migration into the skin Formation of neutrophil extracellular traps (NETs) B-cell activation and IgG autoantibody formation against skin tissue antigens Scarring Ongoing inflammation impairs wound healing Granulocyte infiltration and activation, release of granulocyte colony-stimulating factor Accumulation of keratin, purulent and/or serosanguinous fluid in dermis Inflammatory papules, nodules, and abscesses Pro-inflammatory cytokine-mediated response, leading to epithelial hyperplasia with increased fibrosis and collagen remodelling in the dermis Formation of epithelial tissue tunnels in the dermis with two cavities on either end that open to the skin surface and fill with fluid or keratin Hidradenitis Suppurativa Chronic Inflammatory skin disease that occurs in areas with a high density of apocrine sweat glands, including the axilla, underneath the breasts, groin, and buttocks Sinus tracts (dermal connections between lesions) Double-ended comedones Authors: Leah Johnston Reviewers: Mehul Gupta Lauren Lee Stephen Williams Ben Campbell Laurie Parsons* * MD at time of publication Wound drainage and odour Psychological distress Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 30, 2023 on www.thecalgaryguide.com

Pityriasis Rosea

Pityriasis Rosea: Pathogenesis and clinical findings Authors: Leah Johnston Reviewers: Lauren Lee Stephen Williams Ben Campbell Laurie Parsons* * MD at time of publication Pityriasis Rosea Epidermal layer Dermal-Epidermal Junction Dermal layer Psoriasiform hyperplasia, parakeratosis, spongiosis and Preceding viral infection, reactivation of latent Human Herpesvirus (HHV-6 or HHV-7) Female sex (2:1 female to male ratio) Risk factors Recent vaccinations: Bacillus Calmette-Guerin (BCG), influenza, H1N1, diphtheria, smallpox, hepatitis B, and Pneumococcus Red blood cell lymphocytes extravasation Perivascular dermal infiltrates: lymphocytes, monocytes, and eosinophils Spongiosis (intercellular fluid accumulation in epidermis) Erythematous, pink-salmon or brown coloured lesions Altered production of melanin by epidermal melanocytes Post-inflammatory hyperpigmentation or hypopigmentation Prodromal symptoms: fatigue, nausea, headaches, joint pain, enlarged lymph nodes, fever, and/or sore throat Age 10 to 35 Exact mechanism unknown Activation of T-cell mediated host immune response ↑ Signal proteins in serum including interleukin 17 (IL-17), interferon gamma (IFN-γ), vascular endothelial growth factor (VEGF), and induced protein 10 (IP-10), leading to increased capillary permeability Spring and fall seasons Fluid extravasation from blood vessels Red blood cell extravasation Often asymptomatic, can be pruritic Cell infiltration isn’t as intense or doesn’t produce as dramatic an inflammatory response as other skin conditions ↑ CD4 lymphocytes, monocytes, eosinophils and Langerhans cell infiltration into the dermis and epidermis Pityriasis Rosea Activation of B cells and production of anti- keratinocyte IgM antibodies Parakeratosis (incomplete keratinocyte maturation) and proliferation of epidermal cells (known as psoriasiform hyperplasia) Thickened epidermal layer Scale A self-limited, papulosquamous eruption that is characterized by round or oval-shaped, erythematous to brown patches or plaques with scaling borders that typically occur on the trunk and proximal extremities and tend to follow Langer’s lines. Often initially presents with a larger herald patch as the first sign. Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 30, 2023 on www.thecalgaryguide.com

Kejang Demam Sederhana: Patogenesis dan temuan klinis

Kejang Demam Sederhana: Patogenesis dan temuan klinis

Inhalational Injury

Inhalation Injury: Pathogenesis and complications Authors: Marshall Thibedeau, W Fraser Hill, Paloma Arteaga Juarez Reviewers: Spencer Yakaback, Tony Gu, Dami Omotajo, Ben Campbell, Yan Yu*, Michael Liss*, Duncan Nickerson*, Donald McPhalen* * MD at time of publication Smoke Inhalation Suspect if patient found unconscious, history of fire in a confined space and presence of facial burns Convective heat transfer Exposure to chemical irritants Tracheobronchial injury Injury stimulates vasomotor and sensory nerves of the trachea and bronchi Neuropeptides from neurons are released into local circulation and activate nitric oxide Inhalation of toxins Lack of O2 in an enclosed space Asphyxiation (O2 deprivation in lungs) Acute hypoxemia Loss of consciousness Death Upper airway injury (above vocal cords) Cell lysis & necrosis Local release of inflammatory substances ↑ Vascular permeability à edema of tissues in upper airway Damage to lower respiratory tract cilia ↓ Mucus clearance from alveoli Parenchymal injury (delayed reaction dependent on severity of burn) Alveolar epithelial and endothelial barrier irritation/damage Inflammatory response Carbon monoxide poisoning Cyanide poisoning Cyanide binds to mitochondrial cytochrome oxidase a3 CO binds more strongly to hemoglobin than O2 ↑ Carboxyhemoglobin in blood, ↓ free hemoglobin available to bind O2 in the lungs ↑ Affinity for O2 on remaining binding sites in hemoglobin (i.e. hemoglobin binds O2 more strongly and is slow to release it) ↓ O2 delivered to tissues Inhibition of cytochrome c oxidase Mucous obstructs airways Air retained distal to the obstruction is resorbed from nonventilated alveoli Regions without gas collapse i.e atelectasis ↑ Risk of infection ↓ Mitochondrial respiratory chain function Impaired oxidative phosphorylation & cellular energy production Cellular dysfunction in high metabolic tissues Nitric oxide acts as a vasodilator in alveolar arterioles Loss of hypoxic vasoconstriction (constriction of arterioles in alveoli due to ↓ O2) Reactive inflammation & bronchoconstriction Stridor Complete airway obstruction ↑ Vascular permeability leading to fluid leakage into interstitium and alveoli Blood flow to poorly ventilated alveoli is maintained Ventilation/perfusion (V/Q) mismatch (regions of lung not effectively ventilated despite being well perfused by blood) Acute Respiratory Distress Syndrome See ARDS Pathogenesis slide Hypoxemia Lower airway edema Wheezing Coughing Impaired brain function Muscle weakness Impaired heart function Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications First published November 10, 2019; Updated on February 12, 2023 on www.thecalgaryguide.com

Large Bowel Obstruction: Findings on Abdominal X-ray

Large Bowel Obstruction: Findings on Abdominal X-ray Authors: Shayan Hemmati Reviewers: Reshma Sirajee, Tara Shannon, *Stephanie Nguyen, *MD at the time of publication Radiopaedia, rID:18015 Common causes of obstruction are colorectal carcinoma (60-80%) and cecal or sigmoid volvulus (11-15%) Obstruction from mechanical causes such as physical blockade of bowel lumen or twisting of the large bowel Bowel Obstruction *See Mechanical Bowel Obstruction and Ileus: Pathogenesis and clinical findings Large bowel contents cannot pass the obstructionàgas buildup in colon from swallowed air, bacterial fermentation, CO2 from acid + bicarbonate reaction Colon intraluminal pressure overcomes venous and lymphatic pressure Impaired venous outflowàbowel wall edema/thickening ↑ Vascular resistance eventually impedes arterial inflowàbowel wall ischemia Ischemia can progress to bowel infarction and necrosis Large bowel loops are anatomically peripheral to the small bowel Evacuation of gas and water reabsorption distal to obstruction If ileocecal (IC) valve incompetent or sufficient pressure buildup in large bowel can overcome IC valve ↑ intraluminal pressure Gas dissects into bowel wall from mucosal disruption Pneumatosis coli (air within bowel wall) Bowel wall perforation (especially when cecum diameter > 10-12cm) Dilated large bowel loops located peripherally (highlighted yellow) Collapsed distal colon (few or no air-fluid levels in the large bowel as water is reabsorbed) Small bowel dilatation (> 3 cm) Colonic dilatation (> 6 cm) Cecum dilatation (> 9 cm) Haustra (anatomical folds of the large bowel) become visible as it is distended Pneumoperitoneum (sub-diaphragmatic air on erect chest x-ray) Release of gas into peritoneum PA Radiopaedia, rID:17957 PA Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 16, 2023 on www.thecalgaryguide.com

Ischemic Stroke Impairment by Localization

Ischemic Stroke: Impairment by localization Contralateral weakness and sensory loss in the lower extremity Authors: Andrea Kuczynski Yvette Ysabel Yao Reviewers: Sina Marzoughi Usama Malik Mao Ding Andrew M Demchuk* * MD at time of publication Ischemia in the anterior cerebral artery Motor and sensory cortices of lower limb damage Hypertension, dyslipidemias, diabetes, smoking Atherosclerosis, thrombosis, or stenosis (narrowing) in respective blood vessels Ischemia: ↓ blood flow (See Ischemic Stroke: Pathogenesis slide) Left hemisphere damage Right hemisphere damage Motor and sensory cortices of upper limb and face damage Urinary incontinence Aphasia (inability to comprehend or produce Ischemia in the middle cerebral artery (MCA) MCA divides into segments language) (See Aphasia slide) Left sided agnosia (visual perceptual deficits) Contralateral hemiparesis (weakness on side of body opposite to injury) & sensory deficits, visual field deficits, aphasia, agnosia (inability to process sensory information), apraxia (motor planning deficits) & agraphia (inability to communicate by writing) M1-MCA (sphenoidal segment) M2-MCA (insular segment) Ischemia in the posterior cerebral artery Spares the lower extremity, affects the upper extremity and face Lesion to frontal lobe (Broca area) Infarction of occipital cortex Lesion to superior temporal gyrus of temporal lobe (Wernicke area) No homonymous hemianopsia (one-sided visual field loss) Expressive Broca’s/motor aphasia (inability to produce language) Contralateral homonymous hemianopsia (visual field loss on opposite side) Receptive Wernicke’s/sensory aphasia (inability to comprehend language) Sensory loss, memory loss, contralateral homonymous hemianopsia & alexia (reading difficulty) Ischemia of the occipital lobe, posteromedial temporal lobes, midbrain & thalamus Ischemia in the vertebral basilar artery Ischemia in the basilar artery Ischemia of brainstem & medulla Ischemia of midbrain, thalami, inferior temporal & occipital lobes Cranial nerve disorders: dysarthria (slurred/slowed speech) (IX, X), diplopia (double vision), facial numbness or paresthesia (VII), Foville’s syndrome (ipsilateral cerebellar ataxia), Horner's syndrome, (paresis of conjugate gaze and contralateral hemiparesis, facial palsy, pain & thermal hypoesthesia) Motor deficits: Millard-Gubler syndrome (pons lesion), Raymond’s syndrome (ipsilateral abducens impairment, contralateral central facial paresis & contralateral hemiparesis), Wallenburg syndrome (sensory deficits in the contralateral limb, ipsilateral face), ataxia (abnormal gait), unilateral or bilateral sensory loss of position & vibration Cranial nerve disorders: dysconjugate gaze (unpaired eye movements) (III, IV, VI), ipsilateral facial hypoalgesia (↓ pain sensitivity) (V), unilateral lower motor neuron face paralysis (VII), vertigo (spinning sensation), dysarthria (weak speech muscles) (IX, X) Motor deficits: contralateral hemiparesis, quadriplegia (paralysis of all 4 limbs), contralateral limb hypoalgesia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications First published February 3, 2018, updated February 28, 2023 on www.thecalgaryguide.com

Hemorrhagic Stroke

Hemorrhagic Stroke: Pathogenesis and clinical findings Authors: Andrea Kuczynski Oswald Chen Reviewers: Sina Marzoughi Usama Malik Anjali Arora Ran (Marissa) Zhang Mao Ding Michael D Hill* Gary Klein* * MD at time of publication Primary Intracerebral Hemorrhage (~75%) Secondary Intracerebral Hemorrhage (~25%) Amyloid Angiopathy Amyloid deposits in blood vessels and weakens vessel walls Hypertension Lipohyalinosis (lipid and protein aggregation in arterial walls) weakens blood vessels Unknown Aneurysm Dilation of a weakened blood vessel Drugs (e.g., cocaine, crystal meth, decongestants, anticoagulants) Vascular Malformations Note: the pathophysiology and exact mechanism is not well known Release of toxic blood plasma components (coagulation factors, immunoglobins) Red blood cell lysis Cytotoxic hemoglobin (heme, iron) release Fenton-type free radical generation (Fe(II) + H2O2 → Fe(III) + OH− + OH•) Oxidative damage to carbohydrates, lipids, nucleic acids, and proteins in brain Necrosis of hypoxic brain tissue Neurological signs: focal motor weakness, aphasia, vision loss, sensory loss, imbalance/incoordination, altered LOC Rupture of blood vessel(s) Accumulation of blood → hematoma formation ↓ Cerebral tissue perfusion (↓ O2 availability) ↓ Mitochondrial oxidative phosphorylation (final step in aerobic glucose metabolism) ↓ Adenosine triphosphate (ATP) production ↑ Anaerobic glucose metabolism → ↑ Cerebral lactate production Cerebral lactic acidosis Impaired cellular metabolism Death of neurons and glia Microglia clear debris and release inflammatory markers (TNFα, IFγ, IL-1β) ↑ Endothelial cell apoptosis and ↑ blood-brain barrier permeability Cerebral edema Increased intracranial pressure: papilledema, sudden headache, non-reactive pupils, ↓ level of consciousness (LOC), nausea/vomiting Astrocytes release glutamate (main excitatory neurotransmitter) Activation of neuronal metabotropic glutamate receptors ↑ Ca2+ influx into neurons Excitotoxicity (excess stimulation of glutamate receptors leading to neuronal death) Dysfunction of Na+/K+ ATPase pump (moves 3 Na+ out of cell and 2 K+ into cell) on neurons ↓ Na+ efflux and ↓ K+ influx Neuronal membrane potential becomes less negative (closer to threshold potential) Neurons depolarize → ↑ Glutamate release General findings: Seizures, lethargy Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications First published June 6, 2018, updated February 28, 2023 on www.thecalgaryguide.com

Myelodysplastic Syndrome Pathogenesis and clinical findings

Myelodysplastic Syndrome (MDS): Pathogenesis and clinical findings Authors: Mao Ding Reviewers: Ashar Memon Man-Chiu Poon Yan Yu* * MD at time of publication Stem cells differentiateà accumulation of bone marrow cells with aberrant morphology & maturation Idiopathic (unknown cause) Treatment related: exposure to ionizing radiation, chemotherapeutic agents (e.g., alkylating agents, anti- metabolite, topoisomerase II inhibitors) Environmental toxins (e.g., tobacco, benzene & other organic solvents) Familial predisposition to MDS Acquired somatic (non- reproductive) gene mutations (DNA alterations) Inherited germline (reproductive cells) gene mutations Recurrent mutations cause alteration(s) in one or more protein functions with/without chromosomal abnormalities in hematopoietic stem cell (earliest cell of blood cell differentiation): Mutation in the transcription factor gene RUNX1 impairs regulation of normal hematopoietic (blood cell) development Mutation(s) in epigenetic regulator genes (DNMT3A, TET2) impairs regulation of DNA methylation Mutation in splicing regulator genes (SF3B1) causes mistakes in splicing mRNA moleculesàaberrant translation (production) of proteins Chromosomal abnormalities: deletions (chromosome 5, 7, and/or 20), duplications (chromosome 8), structural abnormalities (inversion of a gene segment) Myelodysplastic Syndrome Mutation-associated clonal disorders of hematopoietic stem cells, causing dysplasia (abnormal development) of one or more myeloid cell lineages (granulocytes, monocytes, red blood cells & platelets) in the bone marrow Genetic mutations or chromosomal abnormalities occur in hematopoietic stem cellsàclonal expansion of abnormal cells in bone marrow Apoptosis (programed cell death) of clonal cells, inhibiting development of granulocytes, monocytes, red blood cells & platelets in the bone marrow Neoplastic myeloid precursor cells (blasts) accumulate in the bone marrow Acute Myeloid Leukemia (AML) > 20% Blasts in the bone marrow Excessive blasts displace other precursor cells & inhibit differentiation Pancytopenia (↓ number of cells of ALL 3 cell lines: platelets, white blood cells & red blood cells) (see Acute Myeloid Leukemia for signs/symptoms/complications) ↓ Number of mature functional blood cells leave the bone marrow to go to peripheral bloodà↓ number of cells of one or more cell lines Bone marrow’s inability to make sufficient blood cells cause extramedullary hematopoiesis (formation/activation of blood cells outside the medulla of bone) at sites such as liver and/or spleen Hematopoietic stem cells migrate to the spleen/liver & differentiate into blood cells Expanding bone marrow physically pushes on bone’s cortex from within, activating nociceptors Multifactorial causes mostly with unclear mechanisms Intracellular granules precipitate inside blasts & the precipitate spills into the blood ↑Division & death of cancerous cells → ↑ cell lysis & release of intracellular contents into plasma Bone pain B symptoms: Weight loss, fever, night sweats Auer Rods (needle- like crystals) seen on blood smear ↑ Serum levels of uric acid, K+, LDH ↓ Red blood cells Anemia fatigue, pallor ↓ White blood cells Leukopenia Recurrent infections ↓ Platelets Thrombo- cytopenia Bruising, bleeding Accumulation of cells within the spleen/liver increase the size of the organ Splenomegaly Hepatomegaly Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 4, 2023 on www.thecalgaryguide.com

Central Retinal Vein Occlusion

Central Retinal Vein Occlusion: Pathogenesis and clinical findings Authors: Graeme Prosperi-Porta Mina Mina Reviewers: Stephanie Cote Usama Malik Mao Ding Johnathan Wong* *MD at time of publication Hypercoagulable state (pathologic state where there is an exaggerated tendency for the blood to clot) ↓ Anticoagulation (e.g., Protein C or S def) and/or ↑ coagulation (e.g., malignancy, Polycythemia Vera) Non-ischemic (perfused) CRVO Glaucoma (a disease characterized by ↑ intraocular pressure) Optic disc drusen (calcified nodules located within the optic disk – the most anterior part of the optic nerve) Diabetes Dyslipidemia Hypertension Vasculitis (inflammation of blood vessels; e.g., sarcoid, Systemic Lupus Erythematosus) Endothelial damage Pupillary responses do not vary between both eyes when a light is shone in one eye at a time Relative afferent pupillary defect (RAPD) mild or absent Lost vascular wall integrity Normal retinal electrical response to a light stimuli Normal electro- retinography (ERG) with b- wave >60% Few scattered Intra-retinal hemorrhages ↓ In retinal electrical response to a light stimuli Pupils respond differently to a light stimulus shone in one eye at a time Severe ↓ in visual acuity (Snellen acuity of <20/400) Visual field deficits ↓ b-wave amplitude (<60%) on ERG RAPD present ↑ Pressure compromises retinal vein outflow Central retinal atherosclerosis (build-up of fat & cholesterol plaque in arteries) & hardening Atherosclerotic changes in the central retinal artery compress the central retinal vein (since they are both held together in region of the optic disc) Venous stasis (stagnation of blood flow) ↑ Likelihood of thrombus formation Central Retinal Vein Occlusion (CRVO) A common retinal vascular disease characterized by blockage of the main vein that drains blood from the retina CRVO classified based on the degree of perfusion (as seen through retinal angiography) Ischemic (nonperfused) CRVO ↑ Intraluminal venous pressure Dilated tortuous retinal veins Normal visual fields Vascular wall integrity lost Four-quadrant hemorrhages described as “blood and thunder” on fundus exam Obstruction due to thrombus ↓ Retinal capillary perfusion causes ischemia Hypoxia in the retinal tissues ↑ Release of vascular endothelial growth factor to revascularize diseased tissue & overcome hypoxic conditions Angiogenesis (formation of new blood vessels) Intraretinal infarcts “Cotton wool spots” on fundus exam Venous capillary fluid/protein leakage Mild retina, macula and disc edema Moderate ↓in visual acuity often (Snellen acuity >20/400) New vessel proliferation can occur in the anterior chamber of the eye This change can block the outflow path of the aqueous humor in the eye Neovascular glaucoma Neovascular vessels are structurally different in comparison to regular retinal vasculature Neovascular vessels are more fragile ↑ Likelihood of rupture Vitreous hemorrhage Neovascular vessels lack tight junctions ↑ Fluid leakage Retina, macula and disc edema Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications First Published June 28, 2017, updated March 4, 2023 on www.thecalgaryguide.com

Syndrome de détresse respiratoire aigu: Pathogenèse et trouvailles cliniques

reaction-transfusionnelle-hemolytique-aigue-signes-et-symptomes

Réaction transfusionnelle hémolytique aigue: Signes et symptômes

Douleur somatique aigue

Douleur somatique aigue: Auteurs: Lisa Murphy, Yan Yu* Rédacteurs: Mackenzie Gault, Melinda Davis* Traducteur/Traductrice: Ovidiu Croitoru Sylvain Coderre* * MD au moment de la publication Nocicepteurs: Neurones qui détectent les stimulis nocifs ou douloureux et transmettent ces informations à la moelle épinière. Il existe deux grands types: - A∂ fibres: Myélinisés, sensation initiale nette et rapide. - C fibres: amyélinisés, sensation retardée, terne, brûlante. Vers l’hypothalamus Les neurones de 2e ordre synapsent dans l’hypothalamus Les neurones hypothalamiques coordonnent la réponse viscérale du corps à la douleur Pathophysiologie Lésions tissulaires aigues, trois types de causes: Mécanique (ex: piqure) Thermique (ex: poêle chaude activé) Chimique (ex: inflammation) Nocicepteurs activités au site de blessure (Neurones sensoriels de 1er ordre) Fibres nociceptives (A∂ et C) transportent l’information sensorielle nocive vers la corne dorsale ipsilatérale de la moelle épinière Les neurotransmetteurs excitateurs sont libérés et stimulent les neurones sensoriels de 2ème ordre. Les neurones sensoriels de 2ème ordre décussent immédiatement dans la moelle épinière et remontent via les voies antérolatérales (spinothalamiques) du côté opposé, se terminant à divers endroits Vers le thalamus Les neurones de 2e ordre synapsent dans le thalamus Dans le thalamus, les neurones sensoriels de 2ème ordre synapsent avec les neurones sensoriels de 3e ordre, qui transmettent le signal au cortex cérébral Vers le tronc cérébral Les neurones de 2e ordre synapsent dans la formation réticulaire du tronc cérébral Vers le mésencéphale Les neurones de 2e ordre synapsent dans la zone grise périaqueducale (PGA) du mésencéphale Localisation et sensation douleur Réponse émotionnelle et comportementale Stimule les voies descendantes pour moduler le signal de douleur Diminution ou augmentation de la perception de la douleur ↑ Rythme cardiaque Nausée Légende: Pathophysiologie Mécanisme Signes/Symptôme/Labo Complications Publié 25 avril 2019 sur www.thecalgaryguide.com

варикозное-расширение-вен-пищевода-ж

Варикозное Расширение Вен Пищевода/Желудка: Патогенез и Клинические Данные

язвенная-болезнь-патогенез-и-клиниче

Язвенная Болезнь: Патогенез и клинические данные

синдром-меллори-вейса-патогенез-и-кли

Синдром Меллори-Вейса: Патогенез и Клинические Данные

Skin Grafts Transplant physiology and clinical findings

Skin Grafts: Transplant physiology and clinical findings Authors: Ruchika Sharma Shyla Bharadia Reviewers: Mao Ding Ryan T. Lewinson A. Rob Harrop* *MD at time of publication STSGs may be meshed for greater coverage of surface area Split thickness donor sites may be re- harvested 6. Graft maturation (months-years) Skin anatomy Sebaceous gland alongside hair follicle Hair Follicle Sweat gland Blood vessels Full thickness donor sites cannot be re-harvested Epidermis Dermis Subcutaneous tissue Full thickness skin graft (FTSG) including the epidermis and entire dermis The full thickness donor site is closed by primary intention (sutured) Skin grafts Indicated when healing by secondary intention (natural closure) is not possible. The graft consists of avascular skin harvested from an uninjured donor site Split thickness skin graft (STSG) including the epidermis and a portion of the dermis The split thickness donor site heals by re- epithelialization Donor grafts are applied to the injured area 1. Initial adherence (8 hrs) A fibrin network fastens the graft to the wound bed Fibroblasts, leukocytes & phagocytes from the wound bed enter the fibrin network, building a fibrous connection between the graft & wound bed 2. Plasmatic imbibition (24-48 hrs) The graft absorbs nutrients and dissolved oxygen from plasma in the recipient wound bed The graft appears white in color 3. Inosculation and capillary ingrowth (2-4 days) Capillary buds from the recipient wound bed anastomose with vessels on underside of graft Physiology of graft take 4. Revascularization (5-7 days) 5. Graft contraction (6-18 months) Actin in myofibroblasts contract & approximate the wound edges Angiogenic factors enable revascularization allowing rapid, high-volume flow through large vessels Lymphatic drainage established Dermal structures such as hair follicles, sweat & sebaceous glands may be partially restored Grafts are pruritic (itchy), discoloured, and do not function or look like normal skin Grafts are reinnervated from periphery to center STSGs are reinnervated faster than FTSGs, though incompletely Graft fails (does not adhere) with a poorly vascularized and unclean wound bed Restoration of vasculature returns color to the graft Successfully adhered grafts are pink (STSG) or marginally paler (FTSGs) and immobile The deep dermal layer in FTSGs better inhibits myofibroblast action STSGs heal with significant contracture, limiting function & mobility Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications First published February 6, 2017, updated March 12, 2023 on www.thecalgaryguide.com

Primary Hemostasis

Primary Hemostasis: Normal physiology, disorders, and clinical findings Authors: Mina Mina Reviewers: Parker Lieb Mao Ding Kareem Jamani* *MD at time of publication Normal physiology: Injury to blood vessels from trauma (blunt or penetrating injury) Disorders of primary hemostasis: Collagen and microfibrils (subendothelial elements that are normally protected) are exposed to circulating blood due to vessel injury Storage granules in endothelial cells release large multimers of clotting factor von Willebrand (vWF) when damaged Acquired or inherited reduction in vWF quantity or quality (see vWF deficiency slide) von Willebrand Disease Defect in expression of GpIb interferes with platelet ability to bind to vWF Bernard-Soulier syndrome Defect in platelet membrane glycoproteins IIb and IIIa Glanzmann’s Thrombasthenia Insufficient platelets to form a platelet plug Thrombocytopenia (low platelet count) Disorders of primary hemostasis: problems with formation of a platelet plug Platelet adhesion: vWF binds to collagen and interacts with the platelet surface receptor glycoprotein Ib (GpIb) allowing platelet adhesion Platelet activation: mediated by agonists like ADP, thrombin and collagen Mucocutaneous bleeding (bleeding of the skin and mucous membrane) ↑ Closure time, ↑ bleeding time Platelets change shape and release substances from their granules Conformational changes in platelet cell surface glycoprotein IIb/IIIa ↑Affinity for fibrinogen through GpIIb/IIIa ADP Fibrinogen, vWF, and other substances Thromboxane A2 (see note) Induces aggregation Epistaxis Menorrhagia Note: Petechiae Platelet aggregation: fibrinogen forms bridges between adjacent platelets by binding to activated glycoprotein IIb/IIIa Interaction with coagulation factors: platelets provide a scaffold that allows the activation of phospholipid-dependent coagulation factors Primary hemostasis (formation of a platelet plug) Secondary hemostasis (see slide for normal physiology) Drugs like Aspirin and NSAIDs inhibit Thromboxane A2 synthesis (by inhibiting cyclooxygenase) and thereby inhibit platelet aggregation Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 30, 2023 on www.thecalgaryguide.com

Concussion

Concussion: Acute pathophysiology and findings Authors: Calvin Howard Cormac Southam Yvette Ysabel Yao Reviewers: Emily Ryznar Mao Ding, Gary Klein* * MD at time of publication Activation of inhibitory cholinergic system of dorsal pontine tegmentum (structure with role in sleep- wake regulation) Disruption of reticular activating system (brain area that regulates arousal) Altered level of consciousness Direct blow to the head or the body that causes an impulsive force to the head (i.e., falls, motor vehicle accidents, sports, assaults) Skull acceleration / deceleration Coup (brain strikes skull on side of impact) Brain tissue swelling Cerebral edema (fluid build up around brain) ↑ Intracranial pressure Cerebral herniation (shifting of brain tissue into adjacent space) Contrecoup (brain strikes skull on opposite side of impact) Anatomical damage Skull fracture Broken bone fragments ruptures blood vessels Intracranial hemorrhage (bleeding into brain tissue) Papilledema (swelling around optic disk, where optic nerve enters eyeball) Disruption of messages from eye to brain Vision problems (i.e., blurred or double vision) Cellular damage Indiscriminate, rapid neurotransmitter release ↑Extracellular K+ and glutamate, accumulation of intracellular calcium Ionic disequilibrium across neuronal membrane Energy consumed by Na+/K+ ATPase pumps to re-establish ionic homeostasis ↑ Cerebral glucose metabolism ↑ Energy demand Brain injury Axonal stretch due to biomechanical forces Microtubule disruption Structural (cytoskeletal) disturbance Axonal degeneration Impaired neural communication Broken bone fragments Ruptures blood vessels Compresses blood vessels ↓ Cerebral blood flow ↓ Cerebral glucose supply ↓ Energy supply ↓ Oxygenated blood to brain Brain cell death Chronic brain atrophy Persistent impaired cognition Cellular energy crisis (mismatch between energy supply and demand due to effort in restoring homeostasis) Nausea, vomiting ↓ Participation in daily Confusion, disorientation, unsteadiness, headache activities and work Death Anxiety, depression Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 12, 2019, updated March 27, 2023 on www.thecalgaryguide.com

Pyogenic Brain Abscess on MRI

Pyogenic Brain Abscess on MRI: Findings and Pathogenesis Common pathogens such as staphylococcus and streptococcus bacteria exist in the outside environment or on the skin Hematogenous Spread Direct Spread Pathogen travels to brain by bloodstream Pathogen travels to brain by ears or sinus Pathogen enters the brain parenchyma by crossing the blood brain barrier (BBB) transcellularly, paracellularly or by a Trojan Horse mechanism Authors: Omer Mansoor, Aly Valji, Nameerah Wajahat Reviewers: Mao Ding, Reshma Sirajee, James Scott* *MD at time of publication R Transcellular Pathogen invades BBB cell directly to enter Paracellular Pathogen goes between BBB cells by disrupting tight junctions Trojan Horse Pathogen bypasses BBB by hiding inside a macrophage cell Ring Enhancing Lesion Sensitive, but not specific for a Brain Abscess Pathogen causes parenchymal inflammation and progresses through four stages of infection Axial T1 + Gadolinium MRI Head. Pyogenic Brain Abscess showing infection at Stage 3 or 4. T1 highlights fat, whereas T2 highlights fat and water*. R Stage 1: Early Cerebritis Focal infection (2-3 days) with no pus formation Stage 2: Late Cerebritis Progressive (1 week) infection of abscess Stage 3: Early Encapsulation In 1-2 weeks, pus is formed from the pathogen Stage 4: Late Encapsulation After 2 weeks, abscess shrinks in size as it necroses Pathogen causes acute inflammatory changes of swelling (edema) and vascular congestion No fibrous capsule is formed yet and infection is not well localized on a T1 MRI Increased edema could be seen on T2 MRI Poor Demarcation and Vasogenic Edema Abscess is not well-defined with minimal enhancement on T1 but can have increased signal on T2 Fibrous capsule is formed by surrounding healthy brain tissue that walls off abscess Capsule is made of granulation tissue and fat, which lights up non-specifically on a T1 MRI Use Diffusion Weighted Imaging (DWI) to distinguish abscess from other brain lesions DWI measures water diffusion in different directions, specifically diseased areas where water movement is restricted Restricted Diffusion Edema and inflammation allow water to move freely (hyperintense signal) *Imaging Source: Feraco et al., 2020: https://jptcp.com/index.php/jptcp/article/download/688/685?inline=1 DWI Sequence Axial MRI Head. Same Pyogenic Brain Abscess as above. DWI is the mainstay imaging sequence for diagnosing a pyogenic brain abscess*. Legend: Pathophysiology Mechanism Radiographic Findings Complications Published Mar 25, 2023 on www.thecalgaryguide.com

Carpal Tunnel Syndrome

Carpal Tunnel Syndrome: Pathogenesis and clinical findings Diabetes Mellitus (See Pathogenesis Slide) ↑ Blood sugar: deposition of advanced glycation end (AGE) products (proteins or lipids glycated when exposed to sugar) AGE attaches to and prevents tendons from moving properly Authors: Amanda Eslinger Yvette Ysabel Yao Reviewers: Matthew Harding Owen Stechishin Mao Ding, Cory Toth* * MD at time of publication Wrist trauma (distal radius fractures, carpal/metacarpal fractures, tendon ruptures) Repetitive Strain Injury (repetitive hand & wrist movements) Irritation, swelling & thickening of tendons in carpal tunnel Calcium deposits Calcifica tion Deposition Amyloidosis Amyloid (protein aggregates) deposition Gout (See Gout Slide) Uric acid crystal deposition Pregnancy ↑ Concentration of hormones & uterine pressure on inferior vena cava Backup of blood into systemic circulation Autoimmune (i.e. Rheumatoid arthritis, scleroderma, lupus, Sjogren’s syndrome) ↑ Inflammatory cytokines causing inflammation Hypo- thyroidism Myxedema (swelling of skin and underlying tissues) in carpal tunnel Idiopathic or Congenital Edema Narrowed carpal tunnel leads to ↑ internal pressure Carpal Tunnel Syndrome Vascular: median artery thrombosis in carpal tunnel Median nerve compression inside the carpal tunnel Mechanical disruption of median nerve Compression exacerbated with flexed wrists (i.e. sleep, driving, holding phone/cup) Disruption of daily activities and sleep Ischemia (↓ blood supply) to median nerve Hypoxia (↓ oxygenated blood flow) Metabolic conduction block (impaired axonal transport due to ischemia) Nerve conduction study (show sensory nerve impulses slowing across the wrist, followed by mild / moderate / severe loss of sensory nerve amplitude Damage to the myelin sheath ↓ Saltatory conduction (action potential propagation along myelinated axons) Neuropraxia (nerve compression blocks conduction) Interruption in axonal continuity Axonotmesis (endoneural tube stays intact but myelin & distal axon degenerates) Recovery possible Full disruption of myelin, axon & nerve sheath Neurotmesis (axons no longer have an endoneural tube to guide regrowth) Recovery impossible ↓ Ability to contract and use abductor pollicis brevis muscle ↓ Signals through median nerve Interference with signals to the brain causes unusual sensations Hypoalgesia (↓ pain Dysesthesia (tingling, burning, or sensitivity at 1st 3 1⁄2 digits) painful sensation at 1st 3 1⁄2 digits) Thenar muscle wasting Reduced hand dexterity Weak thumb abduction Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 2nd, 2013, updated March 22, 2023 on www.thecalgaryguide.com

Complications of Prematurity

Prematurity: Overview of complications Premature babies born <37 weeks of pregnancy Author: Elizabeth de Klerk Simran Sandhu Reviewers: Yan Yu, Mao Ding Nick Baldwin* *MD at time of publication Immature immune system Prematurity Structurally immature lungs Immature retinal vessels are more sensitive to O2 Supplemental O2 makes retinal environment hyperoxic (excessive supply of O2) Hyperoxia vasoconstricts retinal blood vessels leading to retinal ischemia Ischemic retina produces vascular endothelial growth factor (VEGF) to generate new blood vessels + improve retinal perfusion Excess VEGF causes abnormal blood vessel proliferation Abnormal vessels are fragile + prone to hemorrhage which can lead to retinal distortion Retinopathy of Prematurity (ROP) (See relevant slide) Poor structural support to blood vessels of the germinal matrix (the tissue surrounding the lateral ventricles of the brain) Vessels are vulnerable to hemodynamic instability Abrupt changes to cerebral blood flow damage blood vessels Vessels bleed into germinal matrix and lateral ventricles Intraventricular Hemorrhage (IVH) (See relevant slide) Note: Pre-term complications not discussed here include hypothermia, hypoglycemia, apnea, patent ductus arteriosus Low quantity: ↓ surfactant production Low quality: ↓ surfactant activity (different lipid + protein composition compared to full-term infants) ↑ Infections ↓ Number of white blood cells and complement protein ↑ Bacterial colonization of GI tract + penetration of intestinal wall Abnormally high surface tension of alveoli Alveoli spontaneously collapse (diffuse alveolar atelectasis) Ineffective ventilation of alveoli (V)ànot supplying pulmonary blood (Q) with oxygen (V-Q mismatch) Respiratory Distress Syndrome (RDS) (See relevant slide) Positive pressure ventilation (PPV) used therapeutically PPV disrupts lung development & damages lung tissue Bronchopulmonary Dysplasia (BPD) (See relevant slide) Intestinal ischemia, or Formula Feeds (unclear mechanisms) Activation of inflammatory cascade releases cytokines (peptides that help activate immune response) Cytokines cause bowel necrosis (tissue death) Necrotizing Enterocolitis (NEC) (See relevant slide) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 31, 2013, updated March 25, 2023 on www.thecalgaryguide.com

Acute Pulmonary Embolism on CTPA

Acute Pulmonary Embolism: Computed Tomography Pulmonary Angiogram (CTPA/CTPE) Virchow’s Triad: Hypercoagulability, venous stasis, vascular endothelial injury Image Source: European Society of Radiology Image: Polo mint sign on axial CTPA. Image Source: Journal of The Indian Academy of Echocardiography Image: Railway sign on axial CTPA. Image Source: Moore et al. 2018 Image: Pleural effusion and pulmonary infarction on axial CTPA. Authors: Aly Valji, Nameerah Wajahat, Omer Mansoor Reviewers: Reshma Sirajee, Sravya Kakumanu, Victória Silva, Mao Ding Vincent Dinculescu* *MD at time of publication Deep Vein Thrombosis (DVT): Majority of pulmonary embolism (PE) arise from DVT: Clot travels via inferior vena cava → right atrium → right ventricle → pulmonary arteries/arterioles See “Virchow’s Triad and Deep Vein Thrombosis” for full pathogenesis Polo Mint Sign Clot visualized in short axis, Filling defect entirely surrounded by IV contrast creating a circle (polo mint) Railway Sign Clot visualized in long axis, Filling defect surrounded by IV contrast on two sides creating the appearance of a railway track Type I or II Ventilation/Perfusion respiratory failure (V/Q) mismatch Reverse Halo Sign Pulmonary infarction leads to wedge shaped opacity with a rim of consolidation (black arrows) surrounding “ground glass” (red arrows) Pulmonary Embolism: Clot in pulmonary arteries See “Signs and Symptoms of Pulmonary Embolism” for full presentation Saddle Embolus: Large clot over the pulmonary trunk bifurcation Lobar/Segmental/Subsegmental Embolus: Clot within the pulmonary arteries of the lungs Blockage of pulmonary arteries = ↓ Blood flow, ↑ Right heart pressure ↓ Gas exchange b/w lungs and blood Ischemia of lung tissue → infarction → inflammation of dead tissue ↑ Right heart filling and expansion Left heart filling impaired ↓ Cardiac output due to ↓ Left heart filling “Massive PE” = sustained systemic hypotension or bradycardia (SBP < 90 mmhg, HR < 40 bpm) Saddle Embolus Filling defect due to blockage of bifurcation. IV contrast appears white, and embolus appears grey Pleural Effusion Exudative Pleural Effusion Tissue inflammation → ↑ blood vessel permeability = Leakage of fluid into pleural space Transudative Pleural Effusion ↑ Hydrostatic pressure from right heart congestion = Pushes fluid into pleural space Image Source: Samra et al. 2017 Image: Saddle embolus on axial CTPA. Legend: Pathophysiology Mechanism Radiographic Findings Complications Published March 28, 2023 on www.thecalgaryguide.com

Wstrząs obturacyjny: Patogeneza, powikłania oraz zmiany kliniczne

Wstrząs obturacyjny: Patogeneza, powikłania oraz zmiany kliniczne

Wstrząs dystrybucyjny: Patogeneza, powikłania oraz zmiany kliniczne

Wstrząs dystrybucyjny: Patogeneza, powikłania oraz zmiany kliniczne

Wstrząs kardiogenny: Patogeneza, powikłania oraz zmiany kliniczne

Wstrząs kardiogenny: Patogeneza, powikłania oraz zmiany kliniczne

Wstrząs oparzeniowy: patogeneza, powikłania i zmiany kliniczne

Wstrząs oparzeniowy: patogeneza, powikłania i zmiany kliniczne

Leczenie wstrząsu: wyjaśnienie podstawowych mechanizmów

Leczenie wstrząsu: wyjaśnienie podstawowych mechanizmów

Rozwarstwienie aorty: Patogeneza, powikłania i zmiany kliniczne

Rozwarstwienie aorty: Patogeneza, powikłania i zmiany kliniczne

Tętniak aorty brzusznej: Patogeneza

Tętniak aorty brzusznej: Patogeneza

Tętniak aorty brzusznej: Obraz kliniczny, powikłania

Tętniak aorty brzusznej: Obraz kliniczny, powikłania

Sarcoidosis pathogenesis and CXR findings

Sarcoidosis: Pathogenesis and chest X-Ray findings Authors: Harshil Shah Reviewers: Mao Ding Tara Shannon Vincent Dinculescu* * MD at time of publication Genetic predisposition Unknown sarcoid antigens Sarcoid antigens interact with pattern recognition receptors on macrophages in the lungs Macrophages become activated Helper T cells and macrophages release cytokines (proteins made by immune cells that modulate cell growth and division) such as tumor necrosis factor to neighboring cells Tumor necrosis factor is a pro- inflammatory cytokine promoting cell survival and proliferation, predominantly in the upper/middle lung for unknown causes More macrophages and helper T cells are activated and accumulate in the mediastinum, peritracheal region, and the upper/middle lung Macrophages and helper T cells promote fibroblasts (cells that produce collagen) in the upper and middle lungs Macrophages in the lungs present the antigen to the helper T cells in lymph nodes Helper T cells become activated and accumulate in the lungs Image Credit: Radiopaedia The right peritracheal and bilateral hilar lymph nodes becomes swollen Inflammatory signals stimulate macrophages to form granulomas (clusters of white blood cells) in the lungs, peritracheal and bilateral hilar lymph nodes X-ray images show visible white opacities in areas of increased densities, such as areas of macrophage and helper T cell concentration Enlarged peritracheal lymph node Stage 1 and 2 Enlarged bilateral hilar lymph node Stage 1 and 2 Interstitial Opacities Stage 2 and 3 Bilateral and symmetric lacey lung markings in upper/middle lungs Decreased lung volume on either sides (higher than normal diaphragm) Collagen accumulate which causes fibrotic tissue (scarred and thickened), replacing healthy tissue Pulmonary fibrosis of upper and middle lung Stage 4 The fibrotic tissue is stiffer, reduces amount of air held in lungs, and has a higher density (appearing white) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 7, 2023 on www.thecalgaryguide.com

Coronary Artery Bypass Graft CABG Indications

Coronary Artery Bypass Graft (CABG): Indications Author: Breanne Gordulic Reviewers: Miranda Schmidt Ben Campbell Sunawer Aujla Angela Kealey* * MD at time of publication Symptomatic multivessel (≥ 3 vessels) coronary artery disease (MVCAD) or complex MVCAD Acute coronary syndrome (ACS) Left main coronary artery disease Multivessel (≥ 3 vessels) CAD and diabetes Cardiac surgery required for other pathology Multivessel CAD, LV dysfunction and congestive heart failure (CHF) Complex CAD includes stenosed vein grafts, bifurcation lesions, calcified lesions, total occlusions, ostial lesions STEMI initial treatment is PCI/thrombolysis CABG outcomes compared to percutaneous coronary intervention (PCI) in MVCAD include ↑ survival in diabetes, ↑ survival with LV dysfunction, ↓ repeat revascularization, ↓ myocardial infarction, ↓ stroke ↑ Risk of failure in complex CAD with PCI Rapid reperfusion to myocardium most important in STEMI to decrease myocardial damage CABG can be considered for residual stenoses 6-8 weeks later NSTEMI or unstable angina (UA) with MVCAD involving at least three vessels including the proximal left anterior descending (LAD) Left main coronary artery divides into left anterior descending (LAD) and left circumflex (LCx) which supplies 2/3 of myocardium ↑ Survival Myocardial infarction from left main artery occlusion Death Left main stenosis Ventricular dysrhythmias Ongoing ischemia LV dysfunction Hemodynamic instability ↑ risk of PCI CABG has mortality benefit ↓ Number of operations ↑ Risk of cardiovascular disease in diabetes Revascularization indicated along with other cardiac surgery Multivessel CAD with >90% stenosis and CHF LV ejection fraction <35% ↑ Risk of atherosclerosis from hyperglycemia and dyslipidemia CABG bypasses several atherosclerotic plaques in coronary arteries ↑ Durability ↑ Complete perfusion Valve stenosis or regurgitation Septal defect Aortic root or arch pathology Combination procedure Evidence of ischemia at rest Evidence of impaired LV function at rest ↓ All-cause mortality in CABG vs medical management Chronic obstructive pulmonary disease Abbreviations: • ACS- acute coronary syndrome. Acute reduction in blood flow to heart muscle resulting in cell death. • CAD- coronary artery disease. Narrowing or blockage of the coronary arteries by plaque • NSTEMI- myocardial infarction (heart attack) with no ST elevation on electrocardiogram • PCI- percutaneous coronary intervention. A balloon tipped catheter is used to open blocked coronary arteries; a stent may be placed. • STEMI- myocardial infarction with ST segment elevation on electrocardiogram Consider revascularization (restore blood flow to blocked or narrowed blood vessels) of coronary arteries to increase perfusion to myocardium (heart muscle) Coronary artery bypass graft recommended Assess surgical risk and comorbidities with evaluation by heart team that includes both a cardiac surgeon and interventional cardiologist (SYNTAX Trial) Individual management plan for patients with comorbidities that increase mortality Frailty Chronic Renal Failure ↑ Inflammation and deregulated angiogenesis affects all organ systems ↓ Physiologic reserve and ↓ ability to recover from acute stress ↑ Pneumonia ↑ Respiratory and Renal Failure ↑ Stroke ↑ In hospital mortality ↓ Survival two years after surgery Use Society of Thoracic Surgeons Score, EuroSCORE, or SYNTAX II Score to predict patient outcome with anatomy, disease severity, and preoperative characteristics Coronary Artery Bypass Graft Surgery to take healthy blood vessels from the body and connect them proximally and distally to blocked coronary arteries Cardiopulmonary bypass, fluid overload, ↑ renal vasoconstriction and ↓ renal oxygenation from rewarming Kidney injury ↑ End stage kidney disease Blood flow restored to ischemic myocardium ↓ Angina ↑ Quality of life ↑ LV function ↑ Survival Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 12, 2023 on www.thecalgaryguide.com

Benzodiazepine Mechanism of Action

Benzodiazepine: Mechanism of action Anesthetic composed of a fused benzene and diazepine ring that is administered orally or intravenously to produce a sedative or hypnotic effect Ex. Lorazepam, Midazolam, Diazepam Binds to Gamma- aminobutyric acid (GABAA) receptor in vascular smooth muscle and the central nervous system (CNS) APs inhibited in vascular smooth muscle Vascular smooth muscle relaxes Vasodilation ↓ Blood pressure Authors: Victoria Silva Travis Novak Reviewers: Billy Sun Mao Ding Melinda Davis* *MD at time of publication ↑ Frequency of chloride channel opening Hyperpolarization of nerve membrane Action potential (AP) inhibited APs inhibited in the medulla oblongata (the respiratory center) ↓ Respiratory drive: the body fails to ↑ depth and rate of respirations when arterial CO2 ↑ General CNS inhibition Anti-convulsion (Seizures are caused by a burst of uncontrollable, electrical activity in the brain) APs inhibited in the thalamus and hypothalamus (play a role in memory) APs inhibited in the limbic system (the behavioral and emotional response centers in the brain) Hypotension ↓ Cerebral blood flow ↓CO2 diffusion from arterial blood to alveoli ↓O2 diffusion from alveoli to arterial blood Pharyngeal muscle relaxation ↑ Arterial CO2 ↓ Arterial O2 Airway obstruction Amnesia ↑ PaCO2 ↓ PaO2 ↓ Anxiety Anxiolysis Hypercapnia Hypoxemia In high doses: Depression of arousal and loss of consciousness Induction of general anesthesia (No analgesic effect) ↓ Intracranial pressure Benzodiazepine reversal: Temporary cessation of breathing Apnea Flumazenil competitively binds to GABAA Flumazenil reverses the binding of benzodiazepine to GABAA ↓ Frequency of chloride channel opening Depolarization of nerve membrane Benzodiazepine reversal Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Aug 09, 2018, updated April 25, 2023 on www.thecalgaryguide.com

急性胸部综合征镰状细胞贫血发病机制和临床表现

急性胸部综合征(镰状细胞贫血):发病机制和临床表现

Subdural Hematoma on CT

Acute and Chronic Subdural Hematoma on CT: Pathogenesis and findings Brain shrinkage with age or alcohol misuse Head trauma Congenital or acquired coagulopathy (i.e. anticoagulant use) Other (i.e. brain mass) Stretching & tearing of bridging cortical veins that cross from the cortex to dural sinuses Crescent shape Blood accumulation in the potential space between the dura mater & the arachnoid mater As the blood clots over time, its appearance varies on CT and is measured as different radiodensities (MRI may be needed to detect subtle bleeds) Acute < 3 days Subacute 3 days to 3 weeks Chronic > 3 weeks Acute on Chronic Acute blood (50-60 HU) is hyperdense to the surrounding cortex As blood clot ages and protein degradation occurs, the density drops to 35-40 HU The collection of blood becomes hypodense (~0 HU) to adjacent cortex Both hypodense & hyperdense collections visible forming a hematocrit level Hounsfield units (HU) are a measure of radiodensity (Air -1000 HU appears black, CSF is 0 HU appears dark, and cortical bone is >1000 HU appears white) Hypodense collection A pre-existing chronic hematoma Hematocrit level Fluid-fluid level in the case of an acute bleed into a pre-existing chronic subdural collection. This can also be seen in patients with coagulopathy as blood clots improperly, allowing for dependent blood layering Hyperdense collection Acute blood sinks inferiorly (as CT is taken with patient supine) Authors: Nameerah Wajahat, Aly Valji, Omer Mansoor Reviewers: Reshma Sirajee, Tara Shannon, Mao Ding, Petra Cimflova* *MD at time of publication Subdural hemorrhages spread past suture lines to take on a crescent shape (seen bilaterally on this CT), but limited by dural reflections (falx cerebri, tentorium) R Intracranial pressure ↑ Mass effect on the brain tissue Midline shift Shift of brain tissue across the center line of the brain (dashed line shows ideal midline) Ventricular effacement (partial) Ventricles appear smaller as some cerebrospinal fluid (CSF) is pushed out Sulcal effacement CSF filled sulci become less apparent as CSF is squeezed out and gyri are lying on each other Herniation Protrusion of brain through rigid membranes or foramina of skull Axial CT Head: Acute on Chronic Bilateral Subdural Hematoma showing features of both acute and chronic bleeding. Image Source: Radiopaedia.org Legend: Pathophysiology Mechanism Radiographic Findings Complications Published May 10, 2023 on www.thecalgaryguide.com

Telogen Effluvium

Authors: Ayaa Alkhaleefa Telogen effluvium (TE): Causes, pathophysiology, and clinical findings Reviewers: Elise Hansen, Sunawer Aujla, Dr. Jori Hardin* *MD at time of publication Telogen effluvium: non-scarring alopecia characterized by diffuse shedding of telogen-phase hair due to a reactive process Hypothyroidism ↓ Thyroid hormones (T3,T4) ↓ Binding of thyroid hormone to receptors in the skin and hair Cell division ceases in keratinocytes The catagen phase of the hair cycle is triggered (involuting phase where hair enters apoptosis) Delayed re-entry of telogen (resting) hair into the anagen (growing) phase Post-partum hair loss (telogen gravidarum) ↑ Circulating placental estrogen Prolonged anagen phase ↑ Hair growth during pregnancy Baby is delivered ↓ Estrogen and other trophic hormones postpartum The increased amount of anagen hairs from pregnancy all enter catagen phase simultaneously Nutritional deficiencies i.e. iron deficiency Critical illness Fever triggers various pro- inflammatory cytokines (tumor necrosis factor, interleukin 1b, interleukin 6, and interferon types 1 and 2) Premature entry into catagen phase (the body induces cell-cycle arrest in all non-essential structures) Hair follicle keratinocytes undergo apoptosis in response to inflammation Ribonucleotide reductase (an enzyme involved in DNA synthesis) cannot utilize iron as a co-factor ↓Iron stores ↓ Expression of iron- dependent genes (CDC2, NDRG1, ALAD, and RRM2) ↓ Expression of matrix genes of a healthy hair follicle (Decorin and DCT) ↓ Production of matrix keratinocytes (cells that form the hair shaft of growing hair) Arrest of matrix proliferation Hair shedding commonly occurs in the bitemporal areas 2-3 months after triggering event Hair shaft Hair follicle Telogen phase Skin Epidermis Dermal- Anagen phase Epidermal Junction Dermis Catagen phase Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 10, 2023 on www.thecalgaryguide.com

Diabetic Retinopathy

Diabetic Retinopathy: Pathogenesis and clinical findings Authors: Graeme Prosperi-Porta Lucy Yang Reviewers: Stephanie Cote Usama Malik Mao Ding Johnathan Wong* * MD at time of publication Family history of T1DM Genetics: (DR3, DR4, DQ non-asp genes) Ethnicity: White youth, African American, Hispanic, Asian-Pacific Islanders, and American Indigenous Type 1 Diabetes Mellitus (T1DM) (see Diabetes Mellitus, Type I for pathogenesis) Type 2 Diabetes Mellitus (T2DM) (see Diabetes Mellitus, Type II for pathogenesis) Polycystic Ovarian Syndrome Family history of T2DM History of Gestational Diabetes ↑ Body Mass Index ↑ Age Ethnicity: Indigenous Americans, African American, Hispanic Poor glycemic control Chronic high blood sugaràinflammatory response ↑ cytokines and growth factors including vascular endothelial growth factor (VEGF) Vascular permeability Retinal neovascularization Vascular endothelial dysfunction: basement membrane thickening, vascular cell death, vascular occlusion from platelet aggregation Retinal hypoxia Outpouchings of the weakened capillary walls or endothelial buds attempting to re-vascularize the ischemic retina Weakened blood-retinal barrier (BRB) allows for rupture into the deeper retinal layers Lipid deposits with sharp margins due to lipoproteins & other proteins leaking through the damaged blood-retinal barrier Nerve fiber layer infarcts from occlusions of the precapillary arterioles Retinal hemorrhages occur in the more superficial nerve layer Focal areas of saccular venous bulges due to significant retinal ischemia & endothelial wall weakening and damage Diabetic Retinopathy (DR) A complication of diabetes due to chronic hyperglycemia resulting in abnormal permeability and ischemia of retinal vessels Micro-aneurysms Dot/blot hemorrhages Hard exudates (yellow opaque solids on retina) Cotton-wool spots (cloudy translucent patches on retina) Flame hemorrhages (multiple opaque red patches) Venous beading (veins with areas of narrowing forming bead-like segments) Traction retinal detachment Bleeding into the vitreous humor Pericyte death, breakdown of endothelial tight junctions & basement membrane thickening damages blood-retinal barrier Damaged blood- retinal border leaks fluid into the retinal tissues Macular edema (swelling of macula) Mild Non-proliferative DR Moderate Non-proliferative DR Severe Non-proliferative DR Proliferative DR Presence of neovascularization Localized retinal ischemia causes upregulation of vascular endothelial growth factor causing fine, irregular & easily friable neovascularization in the disc, macula, and/or retina Neovascularization (fine loop networks of new blood vessels) Neovascular membranes in vitreous gel form vitreoretinal adhesions and contract Fragile vessels extending into the vitreous humor Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published June 28, 2017, updated May 18, 2023 on www.thecalgaryguide.com

OA Clinical findings

Osteoarthritis: Pathogenesis and clinical findings Ehlers-Danlos Syndromes (connective tissue disorders, e.g., Familial Hypermobility Syndromes) Damage of normal cartilage under abnormal loading Authors: Sean Spence Modhawi Alqanaie Reviewers: Yan Yu Jennifer Au Mao Ding Gary Morris* * MD at time of publication Single large traumatic event or repeated microtrauma Damage to normal articular cartilage under normal loading (force put on a joint) Genetic anomalies in cartilage production and inborn errors of cartilage metabolism Damage of abnormal cartilage under normal joint loading Destruction/attrition of articular cartilage Osteoarthritis A degenerative joint disease that can affect both load bearing joints (knee, hip) as well as in smaller joints (proximal inter-phalangeal, carpometacarpal joints in hand) Repeated physical joint trauma Aberrant bone deposition secondary to wear on subchondral bone Formation of osteophytes (bony projections) and subchondral sclerosis (bone thickening) Lack of cartilage Direct contact between bony processes with movement of the joint Inflammation alters the chemical milieu of joint tissue Synovial fluid forced into bone Damage to subchondral (under cartilage) blood vessels Subchondral fractures cytokines regulate hyaluronic acid synthase Synovium makes lower molecular weight hyaluronic acids (a potent proinflammatory molecule) ↓ synovial fluid viscosity ↑ risk of infection Increased secretion of proteolytic enzymes ↑ joint fluid production Joint effusion Disruption of normal joint architecture Palpable bony hypertrophy (ex. Bouchard’s nodes (bony bumps on the middle joints of the finger)) Impaction of osteophyte with normal joint structures during movement Physical disability Crepitus (grating sound in a joint) Joint movement with reduced lubrication stimulates joint nociceptors Stimulation of joint nociceptors (sensory receptors that detect damaging stimuli) in subchondral bone Pain with use of joint Pain with motion ↓ Range of motion Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 1, 2012, updated May 18, 2023 on www.thecalgaryguide.com

Digestion and Absorption of Macromolecules

Digestion and Absorption of Macromolecules Authors: Krisha Patel Reviewers: Parker Lieb, Sunawer Aujla Ran (Marissa) Zhang, Shyla Bharadia, Mao Ding Sylvain Coderre* *MD at time of publication Lipids (triglycerides) Gastric lipase breaks down triglycerides into diglycerides and fatty acids (little digestion of triglycerides occur in stomach) Bile, produced by the liver, and pancreatic lipase enter the small intestine through the common bile duct The hydrophobic and hydrophilic properties of bile allow it to effectively bind hydrophobic fats with hydrophilic pancreatic lipases Pancreatic lipases break down triglycerides into monoglycerides, fatty acids, and glycerol as a result of emulsification by bile Monoglycerides and fatty acids are absorbed through bile-stabilized chylomicrons (lipid molecules arranged in spherical form) Triglyceride-rich chylomicrons are transported through the lymphatic system and require the activity of tissue lipoprotein lipase when they arrive at the tissue Triglycerides enter systemic circulation for metabolism, energy source, and fat storage Ingestion of nutrition sources containing macromolecules Carbohydrates (oligosaccharide) Salivary amylases in the mouth break down oligosaccharides and starch into shorter polysaccharides Pancreatic amylases break down polysaccharides into monosaccharides, disaccharides, and oligosaccharides in the stomach Brush border enzymes in small intestinal villi break down disaccharides into Proteins (peptides) Pepsinogen is secreted by the stomach wall Hydrochloric acid activates pepsinogen to pepsin in the stomach Pepsin breaks down protein peptides into oligopeptides and amino acid chains The pancreas generates trypsinogen and other enzymes to be released into the duodenum Trypsinogen undergoes cleavage in the duodenum through the action of duodenal enteropeptidases to form trypsin Intravenous proton pump inhibitors used in upper gastrointestinal bleeds stabilize pepsinogen, and prevent pepsin from breaking down clotting factors (proteins) enabling clotting Maltose Maltase monosaccharides: Sucrose Sucrase Glucose + fructose Lactose Lactase Glucose + galactose Glucose + glucose Conditions affecting the duodenum (e.g., Celiac disease) can lead to lower enteropeptidase levels, resulting in impaired protein digestion Activation of trypsinogen to trypsin within the pancreas, rather than in the duodenum, contributes to autodigestion observed in acute pancreatitis Absorption of glucose and galactose through active transport via SGLT-1 carrier protein in the Jejunum and Ileum Absorption of fructose through facilitative diffusion via transporter GLUT5 in the Jejunum and Ileum Pancreatic enzymes (trypsin, chymotrypsin, carboxypeptidase) break down oligopeptides and amino acid chains into amino acids, dipeptides, and tripeptides in the duodenum Monosaccharides enter systemic circulation for energy use and storage Active Na+ cotransporters facilitate amino acid absorption in the jejunum and ileum PEPT1 enzymes facilitate absorption of dipeptides and tripeptides, which are then immediately cleaved into amino acids in the jejunum and ileum Amino acids enter systemic circulation for building & repairing muscles Legend: Pathophysiology Mechanism Treatment Effect Complications Published May 18, 2023 on www.thecalgaryguide.com

Physiology of Anti-diuretic hormone

Physiology of Anti-diuretic Hormone (ADH)/Arginine Vasopressin (AVP) Authors: Manaswi Yerrabattini Reviewers: Parker Lieb Mao Ding Shyla Bharadia Laura Hinz* * MD at time of publication Limbic activation (e.g., pain, nausea) Placental production of vasopressinase during pregnancy catalyzes the breakdown of ADH, leading to a temporary Diabetes Insipidus state (see Diabetes Insipidus: Pathogenesis and Clinical Findings slide) Systemic arteriole vasoconstriction Hypovolemia/Hypotension Hyperosmolar state (i.e., extracellular fluid osmolarity above a certain threshold, most commonly due to hypernatremia) Sensed by osmoreceptors in hypothalamus Angiotensin II synthesized through activation of Renin- Angiotensin-Aldosterone System (RAAS) (see Physiology of RAAS slide) Binds to receptors located in the hypothalamus ↓ pressure sensed by baroreceptors in the heart (left atrium and large veins) Receptors transmit signals to brain via the vagus nerve ↓ Arterial baroreceptor firing ↑ Sympathetic activity of nerves innervating afferent arterioles ↑ Hypothalamic secretion of ADH (peptide hormone), transportation to posterior pituitary, and release from posterior pituitary into blood circulation Blood Vessels (Minor role) Kidneys (Main role) ADH binds to to Vasopressin-2 receptors on basolateral side of principal cells in kidneys ↑ Insertion of aquaporin II channels onto apical membrane of late distal tubule and collecting ducts ↑ Water reabsorption ↓ Urine Output and Maintains narrow range of serum osmolarity ↑ Urine Osmolarity and preserves sodium homeostasis ADH binds to Vasopressin-1 receptors on smooth muscle of blood vessels ADH activates calcium signaling pathway ↑ Blood Pressure Maintains overall fluid volume status Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 20, 2023 on www.thecalgaryguide.com

Oxygen-Hemoglobin-Dissociation-Curve

Physiology of Oxygen-Hemoglobin Dissociation Curve Authors: Sravya Kakumanu Kayleigh Yang Victoria Silva O2 Remaining T-state subunits destabilizeàAll subunits convert to R-state to stabilize HbA (Positive cooperativity) Normal physiology of hemoglobin: α α β β Adult hemoglobin, Hemoglobin A (HbA), is made up of two α- subunits and two β- subunits When partial pressure of O2 (pO2) is ↓, bonds between subunits are strainedàHbA subunits stabilized in this deoxygenated tense state (T- state)àHas ↓ O2 affinity O2 O2 As pO2 ↑, O2 binds a T-state subunit àSubunit destabilizesàSubunit changes shapeàBecomes oxygenated relaxed state (R-state)à Has ↑ O2 affinity O2 O2 O2 O2 O2 rapidly binds to R-state subunits, saturating HbA Reviewers: Parker Lieb, Sunawer Aujla, Marissa Zhang, Tara Lohmann* * MD at time of publication Normal physiology of hemoglobin in the body: In lungs: In tissues: ↑ O2 consumption due to cellular respiration ↑ pO2 during respiration (~100mmHg) HbA is in its deoxygenated, T-state HbA is in its oxygenated, R-state O2 O2 O2 O2 T-state subunits favor O2 binding When pO2 > 60, O2 binds to a circulating subunit in the T-state Subunit destabilizesà Subunit changes shape to R- stateà↑ O2 affinity Positive cooperativity: All subunits transition from T- to R-state O2 quickly binds remaining subunits ↓ pO2 (~40mmHg) R-statesubunitsfavorO2 unloading O2 O2 O2 O2 O2 O2 O2 In some HbA molecules, O2 remains bound Reserve oxyhemoglobin is available for higher O2 demand states Certain disease processes (i.e., Hypoventilation, V/Q mismatch, impaired O2 diffusion) cause pathologically ↓ pO2 states ↑↑ Deoxygenated T-state HbA Rapid desaturation of remaining oxyhemoglobin due to positive cooperativity Rapid hypoxia onset at low pO2 When ↓ pO2 in tissues, O2 unloads from a R-state subunit Subunit destabilizesà Subunit changes shape to T- stateà↓ O2 affinity Positive cooperativity: All subunits transition from R- to T-state and release O2 O2 unloading in peripheral tissue O2 O2 O O2 O2 2 O O2 O2 O 2 2 Sigmoid-shape oxyhemoglobin ↑↑ O2 loading in dissociation curve pulmonary capillaries Legend: Pathophysiology Mechanism Final effect Complications Published , 2022 on www.thecalgaryguide.com

Acute Laryngitis

Acute Laryngitis: Pathogenesis and clinical findings Infectious Author: Charmaine Szalay-Anderson Reviewers: Shayan Hemmati, Sunawer Aujla, Derrick Randall*, Viral (most common) Malaise Fever Fungal Atopy (asthma, allergy) Non-infectious Gastroesophageal Reflux Trauma or damage to larynx Smoking Yan Yu* * MD at time of publication Environmental Pollution/Inhalants Bacterial (S. pneumoniae, H. influenzae, M. catarrhalis) Systemic immune response Spread of infection to larynx through upper respiratory tract Infection of the vocal folds and surrounding tissue Mechanical (vocal misuse/ trauma) (Area in the neck that contains the structures for voice production, anatomically anterior to the esophagus, inferior to the pharynx and superior to the trachea) Irritation of the vocal folds and surrounding tissue Inflammatory cascade triggered Acute Laryngitis Symptoms for <3 weeks Acute injury to vocal folds Vocal fold lesions (i.e., vocal polyps) Laryngeal inflammation Neutrophils and macrophages release inflammatory cytokines Local laryngeal inflammationà↑ vascular permeability ↑ Secretion of mucous leading to airway congestion Cough reflex initiated to clear airway congestion Cough Edema of vocal folds and surrounding tissue Dysphagia (difficulty swallowing) Dysphonia (difficulty speaking) Odynophagia (painful swallowing) Swelling impairs vocal cord vibration Frank aphonia (loss of voice) Progressive worsening of edema Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 24, 2023 on www.thecalgaryguide.com

Neonatal Sepsis

Neonatal Sepsis: Pathogenesis and overview of clinical findings Maternal Risk Factors Author: Nick Baldwin, Daria Mori Reviewers: Elizabeth de Klerk, Jody Platt, Mao Ding, Yan Yu Naminder Sandhu* *MD at time of publication Neonate Risk Factors Prolonged rupture of membranes > 18 hours prior to delivery Untreated bacteria in urine during pregnancy Poor prenatal care (mechanism unclear; multifactorial) Group B Strep vaginal colonization Intra- amniotic infection Prematurity (< 37 weeks) or low birth weight (< 2500 gm) Under- developed immune system Predisposed to infection Congenital anomaly that disrupts skin Birth asphyxia (lack of oxygen and blood flow to brain) Male gender (mechanism unclear) Invasive Procedures Direct introduction of bacteria to neonate’s blood ↑ likelihood of introducing bacteria to the fetus Vertical transmission of maternal bacteria from lower genital tract to uterus Contamination of amniotic fluid Fetal bacteremia (presence of bacteria in bloodstream Direct transmission of bacteria from maternal birth canal to fetal blood during delivery Disruption in neonatal host defenses Neonatal Sepsis An invasive infection, usually bacterial, occurring during the neonatal period (<4 weeks of age for term infants, or <4 weeks after the due date for preterm infants) Note: *APGAR = appearance, pulse, grimace, activity and respirations at 1-, 5-, and 10-min post birth Gastrointestinal Poor feeding Vomiting Diarrhea, constipation, or bloody stool Urological ↓ Urine output Note: See relevant slide(s) for mechanisms of how each sign and symptom comes about. CVS/RESP Apnea/tachypnea Labored breathing Pallor or cyanosis Brady-/tachycardia Hypotension Metabolic Jaundice Hypo- or hyper-glycemia Metabolic acidosis CNS Lethargy Irritability Focal neurological signs Seizure General Low APGAR* Temperature instability Bulging or sunken fontanels Rash Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published June 3, 2013, updated June 7, 2023 on www.thecalgaryguide.com

Menopause

Menopause: Pathogenesis and Clinical Findings Perimenopause/Menopausal Transition: Phase preceding last menstrual period in which the first symptoms may occur. Many clinical findings of menopause can occur in perimenopause. 1-2 million primordial follicles first appear in fetal ovaries in the end of the first trimester of the mother’s pregnancy Typically beginning in adolescence, puberty triggers physiological and anatomical changes Menarche (commencement of menstrual cycles) See relevant slide: Menstrual Cycle Physiology: Ovarian Cycle – Brief Overview Each cycle involves ovulation, during which an oocyte is released from the ovary’s dominant follicle into the Fallopian tube Some non-dominant follicles degenerate in a process known as atresia Menstrual cycle stops Menopause marks 1 year since last menstrual cycle ↓ Fluid transudatio n from blood vessels of vaginal wall ↓ Vaginal lubrication Vaginal tissue becomes thinner and more easily irritated Over time, fewer follicles remain in the ovary Some cycles become anovulatory (no oocyte is released from ovary) ↓ Ovulation causes prevents thickening of the endometrial lining ↓ regularity and frequency of periods Ovaries eventually stop releasing oocytes ↑ Oxidative stress- induced apoptosis of dermal fibroblasts Remaining non-dominant follicles become less sensitive to LH and FSH Since follicular cells are responsible for estrogen production, less follicles result in reduced estrogen production ↓ Expression of serotonin receptors in the CNS ↓ LDL receptor expression and ↑HMG- CoA reductase activity ↓ Regulation of the production and clearance of LDL ↑ LDL Cholesterol levels Author: Sunawer Aujla Reviewers: Ashar Memon Yan Yu* * MD at time of publication ↓ Serotonin activity ↓ Density of ↓ Healthy vaginal flora ↑ pH of vaginal fluid ↑ Spread of bacteria otherwise unable to survive in low pH environment Recurrent urinary tract infections ↓ Calcitonin ↑ Sensitivity of bone mass to Parathyroid Hormone ↑ Activation of osteoclasts Mechanism is likely multifactorial and the subjective symptoms of menopause may contribute Depression 5HT receptors in thermoregulatory region of hypothalamus ↑ Inhibition of sexual responses initiated in prefrontal cortex ↓ Libido 2A ↓ Collagen, elastin, and hyaluronic acid ↓ Proliferation of smooth muscle fibers ↓ Inhibition of osteoclasts Narrower thermoregulatory zone Injury to epithelial tissue in multiple areas of the body Atrophy of bladder and urethra epithelium Urinary incontinence More bone resorption than formation Osteoporosis See relevant slide: Osteoporosis: Pathogenesis and risk factors Sometimes, for unknown reasons, core body temperature increases above upper threshold of narrowed thermoregulatory zone Hot Flashes Sudden, temporary onset of body warmth, flushing, and sweating Sometimes, for unknown reasons, core body temperature decreases below lower threshold of narrowed thermoregulatory zone Chills Sudden, temporary onset of shivering, tingling, cold feeling Atrophy of vaginal epithelium Dyspareunia Pain during sexual intercourse ↓ Integrity of of blood vessels Atherosclerosis ↑ Risk for cardiovascular disease Genitourinary Syndrome of Menopause Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published June 7, 2023 on www.thecalgaryguide.com

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MPOC Conclusions des enquêtes

Burns - Full Thickness - Pathogenesis and Clinical Findings 2023

Full Thickness Burns: Pathogenesis and clinical findings Radiation Sunlight, x-ray, nuclear Emission/explosion can cause damage to keratinocytes (see Calgary Guide Slide: Superficial Thickness Burns: Pathogenesis and Clinical Findings) Author and Illustrator: Amanda Eslinger Tracey Rice Reviewers: Sunawer Aujla Alexander Arnold Duncan Nickerson* Jori Hardin* * MD at time of publication Epidermis Dermis Sub-cutaneous tissue Fire Contact Scald Chemical Electrical Transfer of heat energy causes direct injury to keratinocytes Hypoxic injury (lack of oxygen) causes ischemia-related cell death leading to necrosis Full thickness burn Non-uniform damage to the epidermal, dermal & subcutaneous layers at varying widths & depths due to unpredictable injury pattern Degraded epidermal & dermal layers cover granulated tissue Ulceration covered by eschar: a thick, dried, black (necrotic) layer Long-term risk of ulcers & infections ↑ Vascular permeability in subcutaneous layers ↑ Intravascular fluid leaves capillaries, ↓ uptake by lymph vessels Edema Compression of surrounding muscles, nerves & vessels Ischemia and/or necrosis ↓ Immunologic response due to impaired epidermal barrier function ↑ Microbial growth creating biofilm & secretion of chemicals that inhibit natural protective process Irritated, inflamed wound bed +/- exudate ↑ Risk of infection & septic shock Destruction of somatosensory structures Hypoesthesia (↓ sensation to stimuli) ↑ Risk of repeated injury due to ↓ response to noxious stimuli Destruction of cutaneous capillary beds ↓ Healing due to ↓ dermal structures throughout wound White or leathery appearance Chronic wounds require surgical interventions ↑ Risk of contractures & skin barrier weakness Legend: Mechanism of Injury Pathophysiology Sign/Symptom Complication Published December 2, 2013, updated June 26, 2023 on www.thecalgaryguide.com

Burns - Full Thickness - Pathogenesis and Clinical Findings

Full Thickness Burns: Pathogenesis and clinical findings Radiation Sunlight, x-ray, nuclear Emission/explosion can cause damage to keratinocytes (see Calgary Guide Slide: Superficial Thickness Burns: Pathogenesis and Clinical Findings) Author and Illustrator: Amanda Eslinger Tracey Rice Reviewers: Sunawer Aujla Alexander Arnold Duncan Nickerson* Jori Hardin* * MD at time of publication Epidermis Dermis Sub-cutaneous tissue Fire Contact Scald Chemical Electrical Transfer of heat energy causes direct injury to keratinocytes Hypoxic injury (lack of oxygen) causes ischemia-related cell death leading to necrosis Full thickness burn Non-uniform damage to the epidermal, dermal & subcutaneous layers at varying widths & depths due to unpredictable injury pattern Degraded epidermal & dermal layers cover granulated tissue Ulceration covered by eschar: a thick, dried, black (necrotic) layer Long-term risk of ulcers & infections ↑ Vascular permeability in subcutaneous layers ↑ Intravascular fluid leaves capillaries, ↓ uptake by lymph vessels Edema Compression of surrounding muscles, nerves & vessels Ischemia and/or necrosis ↓ Immunologic response due to impaired epidermal barrier function ↑ Microbial growth creating biofilm & secretion of chemicals that inhibit natural protective process Irritated, inflamed wound bed +/- exudate ↑ Risk of infection & septic shock Destruction of somatosensory structures Hypoesthesia (↓ sensation to stimuli) ↑ Risk of repeated injury due to ↓ response to noxious stimuli Destruction of cutaneous capillary beds ↓ Healing due to ↓ dermal structures throughout wound White or leathery appearance Chronic wounds require surgical interventions ↑ Risk of contractures & skin barrier weakness Legend: Mechanism of Injury Pathophysiology Sign/Symptom Complication Published December 2, 2013, updated June 26, 2023 on www.thecalgaryguide.com

diverticulosis-vs-diverticulitis-distinguishing-features

Diverticulosis vs. Diverticulitis: Distinguishing features Authors: Sahil Prabhnoor Sidhu, Vadim Iablokov, Vina Fan Reviewers: Brandon Hisey, Laura Byford-Richardson, Raafi Ali Dr. Sylvain Coderre* * MD at time of publication Local inflammation Diverticulitis Inflammation of diverticuli Conditions causing inherent weakness in bowel wall, i.e. aging, Ehlers-Danlos syndrome, Marfan syndrome Risk factors (i.e. low fiber diet, obesity, inactivity, smoking) contributing to reduced gut motility ↑Intraluminal pressure in the colon Herniation of colonic mucosa and submucosa through circular muscle at points of weakness to form outpouchings Diverticulosis Presence of outpouchings in the colon (diverticuli) Note: In Western populations, most diverticulosis is left-sided, whereas in Asian populations, these outpouchings are more often right-sided. Mucosal abrasion or micro-perforation by ↑ intraluminal pressure or dense food particles Bacterial overgrowth, dysbiosis and passage into the lamina propria Feces collects in diverticuli Gut bacteria metabolize undigested material and produce gas Stretching of colon Bloating wall irritates and visceral afferent flatulence nerves Episodic abdominal discomfort and cramping Blood vessels in the mucosa and submucosa (vasa recta) are stretched over the diverticuli, and may rupture from ↑ pressure Diverticular bleed Painless hematochezia (passage of fresh blood from the rectum) Inflammatory cytokines activate clotting factors Clotting of blood in vessels supplying diverticula Inflammatory cytokine release (IL-6, TNF-α) Cytokines enter systemic circulation Edema in the bowel wall Irritation of adjacent parietal peritoneum and somatic nerves Left lower quadrant (LLQ) pain, guarding Small abrasions are walled off by pericolic fat and mesentery ↑WBC Fever Inflammation may spread to nearby organs, leading to ulceration and abnormal connections between organs Pericolic abscess No hematochezia Local ischemia and focal necrosis resulting in loss of integrity of the bowel wall Perforation Generalized peritonitis Colonic obstruction (rare) Fistulae (rare): i.e. colovesical, coloenteric Stricture/fibros is formation with healing Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 12, 2016; Updated July 30, 2023 on www.thecalgaryguide.com

diverticulosis-vs-diverticulitis-caracteristicas-distintivas

Diverticulosis vs. Diverticulitis: Características distintivas

Knee Osteoarthritis

Authors: Jared Topham Knee Osteoarthritis: Pathogenesis and clinical findings Reviewers: Liam Thompson, Raafi Ali Yan Yu*, Kelley DeSouza* * MD at time of publication Primary Causes Secondary Causes Aging ↓ Synovial fluid in joint Gender Females > males Genetics Family history of osteoarthritis Race Black > Caucasian Joint malposition (e.g. valgus or varus) Articular trauma Inflammatory disease or infection (e.g. Rheumatoid or septic arthritis) Obesity and ↑leptin ↑ Chondrocytes, inflammatory mediators, and metalloproteinases Extracellular matrix degradation ↑ Knee joint loading forces Metabolic syndromes (e.g. diabetes mellitus) ↑ Oxidative stress and insulin resistance Low-grade systemic inflammation ↓ Elasticity and ↑ degradation of cartilage ↑ Friction in knee joint with movement ↓ Cartilage along femoral groove and posterior surface of patella Pain, catching, and crepitus (crackling/clicking sound) in the patellofemoral joint Inability/difficulty with kneeling or climbing stairs Abnormal distribution of forces accumulate and stress articular surface ↑ Damage/laxity to soft tissue structures stabilizing knee joint Knee Osteoarthritis (Multifactorial entity characterized by cartilage breakdown, deterioration of connective tissue, and bone deformities) ↓ Cartilage between distal femur and proximal tibia ↓ Joint spaceàto articular dysfunction Radiographic changes See Osteoarthritis (OA): X-Ray Features slide Repeated attempts to repair cartilage and joint disruption Subchondral bone thickening (sclerosis) under joint cartilage and bone spur (osteophyte) formation around joint line Rotational/antero-posterior instability and ↑ external adduction moments during walking Alterations in proteoglycans, fiber arrangement, and collagen composition in soft tissue structures within/around knee joint ↑ Shear forces and medial compartment narrowing erode and pinch soft tissue structures within the knee joint Cruciate ligament degeneration Weakened passive stabilizers of the knee joint Knee giving way and instability (falls) Meniscal tears, if large àprevents knee extension/flexion Locking of the knee Joint line tenderness: Patient points to area of tenderness/pain reproducible upon palpation Anatomical axis of hip, knee, and ankle joints ↑ loading medially Medial > lateral joint line tenderness ↑ Joint friction activating nociceptors in the surrounding anatomical tissues Injury and inflammation ↑ nociceptive responses in soft tissue structures and subchondral bone within knee joint Nociceptive feedback to brain inhibits activity of motor cortex neurons controlling muscles around the knee ↓ Motor output and muscle activation over time ↓ Muscle strength/endurance, lower limb muscle use, functional ability (walking, stairs, etc.) Joint inflammationà accumulation of fluid within joint Stiffness, swelling, redness, and pain Limited joint space reduces range of motion for femur to roll/slide on tibia ↓ Knee flexion and extension Flexion contracture and antalgic gait Reduced weight acceptance of the joint and surrounding muscles/tendons ↓ Mobility and physical dysfunction Muscular atrophy Reduced function of active stabilizers of the knee joint (quadriceps, adductors, hamstrings) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 30, 2023 on www.thecalgaryguide.com

Rotator Cuff Disease

Rotator Cuff Disease: Pathogenesis and clinical findings Authors: Jared Topham Reviewers: Raafi Ali, Yan Yu*, Kelley DeSouza* * MD at time of publication Aging Collagen fiber disorientation and myxoid degeneration Tendons, ligaments, and connective tissue are replaced by gelatinous and/or mucoid substance Obesity ↑ Loading on shoulder structures ↓ Static stability (from glenoid labrum and ligamentous components) of glenohumeral joint Tensile forces Repeated eccentric tension from overhead activities Trauma, sports, and occupation ↑ Torque, compression, and translational stresses Metabolic syndromes Reactive oxygen species interact with ↑ glucose forming advanced glycation end-products (AGEs) which accumulate in soft tissues Smoking Impingement syndromes Vessel damage, ischemia, tenocyte apoptosis Macro-trauma causing an acute, complete tear in the rotator cuff muscle(s) ↓Dynamic stability (from rotator cuff and periscapular muscles) and range of motion of the shoulder at the glenohumeral joint ↑ Bone on bone contact of proximal humeral head and boney structures of the scapula Subacromial bursa degeneration ↓ Protection of underlying supraspinatus muscle from attrition between humeral head and acromion Rotator Cuff Syndrome (Inflammation, impingement, or tearing of one or more of the four muscles/tendons of the rotator cuff: supraspinatus, subscapularis, infraspinatus, teres minor) Repetitive loading and micro-tearing of tendon/muscle fibers ↑ Oxidative stressors and inflammatory cascades ↓ Vascularity of rotator cuff structures Radiographic changes: See Rotator Cuff Disease: X-ray and ultrasound features slide, in addition to: calcific tendonitis, calcification of in the coracohumeral ligament, and hooked acromion (calcification from tendon pulling) In some cases, soft tissues enclose/surround shoulder joint capsule thicken (fibrose) and tighten Degenerative joint disease and rotator cuff arthropathy Proximal humeral head migration and ↓ subacromial space Inflammation and insufficient healing of rotator cuff structures, which may lead to: Supraspinatus (shoulder abduction) degeneration Pain, shoulder stiffness, ↓ active AND passive range of motion Adhesive Capsulitis (frozen shoulder) Infraspinatus and teres minor (external rotation) degeneration Rotator cuff tendons become inflamed and irritated as they rub against acromion Subacromial impingement Subscapularis (internal rotation) degeneration +Lift-off test: Inability to hold dorsum of the hand off lumbar spine while internally rotating shoulder ↓ Shoulder strength and muscular atrophy Pain with passive shoulder flexion beyond 90° Winging of the scapula during arm adduction +Empty-can test: Weakness and/or arm depression with resisted abduction with arm internally rotated in 90° +Drop-arm test: Inability to maintain shoulder in abducted position at 90° and/or adduct the arm in a controlled manner (resulting in ”dropping”) Weakness to resisted external rotation with elbow in 90° flexion, inability to keep arm externally rotated (infraspinatus) +Hornblower’s sign: decreased external rotation strength in arm abduction (suggests additional teres minor tear) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 30, 2023 on www.thecalgaryguide.com

Miocarditis

Miocarditis: Patogénesis y hallazgos clínicos

Shock por quemaduras

Shock por quemaduras: Patogénesis, Complicaciones, y Hallazgos clínicos

Angiotensin Converting Enzyme (ACE) inhibitors: Mekanisme Kerja dan Temuan Klinis

Angiotensin Converting Enzyme (ACE) inhibitors: Mekanisme Kerja dan Temuan Klinis

Infark Miokard: Komplikasi

Infark Miokard: Komplikasi

Angina Pektoris Angina Stabil: Patogenesis dan Temuan Klinis

Angina Pektoris/Angina Stabil: Patogenesis dan Temuan Klinis

Infark Miokard: Temuan Pemeriksaan Penunjang

Infark Miokard: Temuan Pemeriksaan Penunjang

Infark Miokard: Temuan pada Pemeriksaan Fisik

Infark Miokard: Temuan pada Pemeriksaan Fisik

Epilepsi: Patogenesis

Epilepsi: Patogenesis

Penyakit Jantung Iskemik (PJI): Patogenesis berbagai jenis PJI

Penyakit Jantung Iskemik (PJI): Patogenesis berbagai jenis PJI

Infark Miokard: Temuan pada Anamnesis

Infark Miokard: Temuan pada Anamnesis

Anatomi Koroner pada EKG: Iskemia Lokal

Anatomi Koroner pada EKG: Iskemia Lokal

Statin: Mekanisme & Efek Samping

Statin: Mekanisme & Efek Samping

Keratosis pilaris

Keratosis Pilaris (KP): Risk factors, pathophysiology, and clinical findings Authors: Ayaa Alkhaleefa Reviewers: Tracey Rice Sunawer Aujla Jori Hardin* MD at time of publication* Loss-of-function mutation in filaggrin (a multifunctional structural protein expressed in the epidermis) Inhibits the release of specific amino acids that maintain Keratin (a protein critical to the integrity of the skin barrier) cannot aggregate to align intermediate filaments within corneocytes (cells that comprise the stratum corneum) the natural moisture of the skin ↑ Skin pH (normal pH is 5.5) Distention of the follicular opening ↑ Surface area for hair to sprout Growth of multiple hairs from the distended follicle Development of thick, coiled hairs Rupture of follicular epithelium by the circular hair shaft Skin Epidermal layer Dermal-Epidermal Junction Dermal layer Mutation in filaggrin Keratin accumulation in corneocytes with hair Grouped keratotic follicular papules Excessive keratin accumulates in the follicular spaces ↑ Keratinization of the follicular epithelium forms a keratinous plug in the infundibulum (funnel-shaped epithelial segment of the hair follicle) Irritation of the hair follicle Excess irritation triggers release of inflammatory cytokines FLG FLG Inflammatory cascade creates edematous environment Symmetrical keratotic papules are commonly grouped along extensor surfaces of the upper arms, thighs, and buttocks Perifollicular edema Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Published 27, JUNE, 2023 on www.thecalgaryguide.com

Low Ankle Sprain

Low Ankle Sprain: Pathomechanics and Clinical Findings Authors: Parker Lieb, Joseph Kendal Reviewers: Liam Thompson, Tara Shannon, Sunawer Aujla, Stephanie de Waal, Amanda Eslinger, Dave Nicholl, Maninder Longowal Gerhard Kiefer* * MD at time of publication Talus subluxation with anterior force on heel + Anterior drawer test Recurrent sprains Synovial inflammation & hypertrophy Remodeling of collagen and bone Degenerative changes (e.g., osteophytes, subchondral sclerosis) Ankle eversion beyond normal range (less common) Excessive stress to medial ankle deltoid ligament Ankle plantar flexion and inversion beyond normal range (most common) Excessive stress to lateral ankle ligament(s) Associated fracture of malleolus or subtalar joint Bone pain, inability to weight bear Recruitment of inflammatory cells to damaged area ↑ Local pro- inflammatory cytokines ↑ Capillary permeability & vasodilation to damaged area Collagen fibers in ligament(s) rupture Low Ankle Sprain (medial or lateral) Local blood vessels tear Blood leaks into surrounding tissue Grade I Mild injury Grade II Moderate injury Grade III Severe injury Minimal ligament disruption Incomplete ligament tear Complete ligament tear No joint laxity Joint laxity Gross joint laxity Mechanical and functional instability Decreased ankle joint space Ankle Impingement (compression of soft and/or bony structures in joint) Chronic ankle instability Damage to mechanoreceptors in muscles surrounding ankle joint Bruising Swelling Focal tenderness over torn ligament(s) Pain on injury and with weight bearing Impaired proprioception & neuromuscular control Nociceptors activated by trauma and inflammatory factors Falls Antalgic gait Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Nov 9, 2014; updated Aug 15, 2023 on www.thecalgaryguide.com

Zystische Fibrose: Pathogenese, klinische Befunde und Komplikationen

Zystische Fibrose: Pathogenese, klinische Befunde und Komplikationen

Infektiose Endokarditis

Infektiöse Endokarditis: Pathogenese, klinische Befunde und Komplikationen

Kindliche Asthma Exazerbation: Pathogenese und klinische Befunde bei Kindern

Kindliche Asthma Exazerbation: Pathogenese und klinische Befunde bei Kindern

Mitralklappeninsuffizienz: Pathogenese und klinische Befunde

Mitralklappeninsuffizienz: Pathogenese und klinische Befunde

Extrauteringraviditat: Pathogenese und klinische Befunde

Extrauteringravidität: Pathogenese und klinische Befunde

Ovarialtorsion: Pathogenese und klinische Befunde

Ovarialtorsion: Pathogenese und klinische Befunde

Dermatitis herpetiformis

Dermatitis Herpetiformis: Pathogenesis and clinical findings Genetic predisposition, HLA-DQ2 and HLA-DQ8 Long term exposure to gliadin, a component of gluten, via dietary gluten ingestion Tissue transglutaminase (TTG) in gut lumen is cross linked to gliadin HLA-DQ2 on antigen presenting cells recognizes gliadin antigen Gliadin antigen is presented to sensitized T helper cells and epitope spreading occurs Authors: Elise Hansen Reviewers: Sunawer Aujla Jori Hardin* * MD at time of publication Type 1 T helper cells and plasma cells produce IgA antibody with gliadin antigen Type 1 T helper cells and plasma cells produce IgA antibody with gliadin crosslinked to TTG Type 1 T helper cells and plasma cells produce IgA antibody with gliadin crosslinked to epidermal transglutaminase 3 (TG3) IgA anti-TTG and IgA anti-TG3 circulate in bloodstream IgA anti-TG3 antibodies reach dermis TG3-IgA complex forms and deposits in papillary dermis TG3-IgA complex and Interleukin 8 stimulate neutrophil chemotaxis Neutrophils infiltrate papillary dermis Neutrophils produce proteases Proteases destroy the basement membrane of the dermis Epidermis no longer adheres to dermis Epidermal transglutaminase 3 (TG3) is released from superficial keratinocytes Vesicles filled with IgA deposits and neutrophils Epidermal layer Destruction of dermal papillae/ basement membrane Dermal layer Y Grouped vesicles on extensor surfaces Pruritus TG3-IgA complex Grouped excoriations on extensor surfaces Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 25, 2023 on www.thecalgaryguide.com

Superficial thickness burns

Superficial Thickness Burns: Pathogenesis and clinical findings Author: Amanda Eslinger Elise Hansen Illustrator: Amanda Eslinger Reviewers: Alexander Arnold Sunawer Aujla Yan Yu* Duncan Nickerson* * MD at time of publication Epidermis (Penetrated by superficial burns) Dermis Sub-cutaneous tissue Erythema Radiation Sunlight (most common), x-ray, nuclear emission/explosion Specific to sunlight radiation, UV rays reach keratinocytes in the epidermis p53 tumor suppressor protein is induced in keratinocytes Transient cell cycle arrest Apoptotic pathway is Fire Contact Scald Chemical Electrical Direct damage to keratinocytes Skin erosion and sloughing of skin cells Direct stimulation of nociceptive nerve endings in the epidermis DNA repair mechanisms are activated Mistakes in repair process Malignancy (See ‘Basal Cell Carcinoma’ Slide & ‘Squamous Cell Carcinoma’ Slide) Fluid leaves vasculature and enters interstitial tissues of the skin, causing it to swell Edema Triggers release of endothelin A proalgesic protein Selective excitement of nociceptive nerve ending in epidermis Pain initiated in keratinocytes Keratinocytes apoptose Prostaglandins, arachidonic acid metabolites, substance P & proinflammatory cytokines are released into surrounding tissue ↑ Vascular permeability ↑ bloodflow carries warmth to body area Irritation of endothelial cells in the dermal vascular plexus Release of endothelium derived vasodilators such as nitric oxide Vasodilation, ↑ blood flow through vessels ↑ blood under skin leads to skin appearing red Warmth Pressing on skin occludes blood vessels temporarily, making skin Blanchable underneath appear white immediately after pressure is lifted Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Dec 2, 2013, updated Aug 25, 2023 on www.thecalgaryguide.com

Netzhautablosung: klinische Befunde

Netzhautablösung: klinische Befunde

Netzhautablosung: Pathogenese

Netzhautablösung: Pathogenese

Uterusmyom (Leiomyom): Pathogenese und klinische Befunde

Uterusmyom (Leiomyom): Pathogenese und klinische Befunde

Quadrizepssehnenruptur: Pathogenese und klinische Befunde

Quadrizepssehnenruptur: Pathogenese und klinische Befunde

Klassifikation der Beckenringfrakturen: Mechanismen, klinische Merkmale und Komplikationen

Klassifikation der Beckenringfrakturen: Mechanismen, klinische Merkmale und Komplikationen

Polyzystisches Ovarialsyndrom (PCOS): Pathogenese und klinische Befunde

Polyzystisches Ovarialsyndrom (PCOS): Pathogenese und klinische Befunde

Ketamin

Ketamin

Epitheliale Ovarialkarzinome: Subtypen, Mutationen & Risikofaktoren

Epitheliale Ovarialkarzinome: Subtypen, Mutationen & Risikofaktoren

Beckenentzundung: Pathogenese und klinische Befunde

Beckenentzündung (Pelvic Inflammatory Disease (PID)): Pathogenese und klinische Befunde

Mastitis puerperalis und Mammaabszess: Pathogenese und klinische Befunde

Mastitis puerperalis und Mammaabszess: Pathogenese und klinische Befunde

Offene Frakturen: Mechanismen, klinische Befunde und Komplikationen

Offene Frakturen: Mechanismen, klinische Befunde und Komplikationen

Subtrochantare Femurfrakturen: Pathogenese und klinische Befunde

Subtrochantäre Femurfrakturen: Pathogenese und klinische Befunde

Rotator Cuff Disease Xray and Ultrasound Features

Rotator Cuff Disease: X-ray and ultrasound features Rotator cuff tears can affect each of the muscles making up the rotator cuff individually, or in combination Authors: Jared Topham Reviewers: Raafi Ali, Kelley DeSouza* * MD at time of publication Supraspinatus tear (most common) Chronic (>3 months) tear with degenerative-type changes Rotator cuff insufficiency, loss of supporting structures holding humeral head inferiorly Displacement of the humeral head anterosuperiorly and instability of joint Microtrauma affecting superior aspect of glenohumeral joint “Acetabularization” or coracoacromial arch: concave acromial erosion and increased sclerosis (hardening) Subscapularis tear (second most common) Teres minor tear Infraspinatus tear Rotator Cuff Syndrome (Inflammation, impingement, or tearing of one or more of the four muscles/tendons of the rotator cuff: supraspinatus, subscapularis, infraspinatus, teres minor) Acute (partial or full thickness) tear of rotator cuff tendons Humeral subluxation (partial displacement of humeral head relative to glenoid) High riding humerus: decreased acromial humeral distance Decreased acromial humeral interval/space (impinging tendons of rotator cuff) Full: Defect extends from the subacromial bursa (fluid filled sack beneath the acromion and above the rotator cuff tendons) to the articular surface of the glenohumeral joint Tendon/muscle fibers completely separated from bone and/or muscle fiber connections severed Partial: Focal defect affecting a portion of the tendon which may involve the bursa or glenohumeral articular surface Non-visualization of the tendon Acetabularization of glenoid Fluid replaces empty space of tendon tear Overlying fat around the sub acromial bursa falls into tendon gap Sagging peribursal fat sign on ultrasound “Femoralization” of the humerus: bone erosion (destruction) and rounding of greater tuberosity Osteoarthritis of glenohumeral joint: See Osteoarthritis (OA): X-ray features slide Hyperechoic (brightened) line between articular cartilage of humeral head and muscle tendon on ultrasound Cartilage interface sign on ultrasound Hypoechoic (darkened) tendon outline discontinuity on ultrasound imaging Femoralization (rounding) of greater tuberosity Subluxation of the humeral head relative to the glenoid Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 6, 2023 on www.thecalgaryguide.com

5HT3 Antagonists

5-HT3 Antagonists: Mechanism of action and adverse side effects A class of medications that are used for the prevention and treatment of nausea and vomiting caused by chemotherapy, radiation, or postoperatively. Authors: Arzina Jaffer Madison Amyotte Reviewers: Jasleen Brar Mao Ding Karl Darcus* * MD at time of publication ↓ Postoperative nausea & vomiting Central Actions Binds to 5-HT3 (serotonin) receptors in the area postrema within the brainstem containing the chemoreceptor trigger zone ↓ Binding of serotonin which is released from the raphe nucleus in the brainstem ↓ Stimulation of vomiting center (medulla) supressing the vomiting reflex ↓ Stimulation of vagus nerve resulting in ↓ signals to chemoreceptor trigger zone ↓ Abdominal pain signals to the brain ↓ Levels of serotonin uptake in gastrointestinal tract ↓ Stimulation of gastrointestinal tract, diaphragm, and abdominal muscles Peripheral Actions Binds to 5-HT3 (serotonin) receptors on the vagus nerve terminals Other Actions Unknown mechanism for patients with significant cardiac history (e.g., congenital long QT syndrome, bradycardia, electrolyte abnormalities) Unknown mechanism Unknown mechanism ↓ Binding of serotonin which is released from enterochromaffin cells in the gastrointestinal tract Potential blockage of K+ channels in the heart ↓ Visceral sensation associated with irritable bowel syndrome ↓ Colonic motility slowing the rate of digestion ↓ Diarrhea Constipation Alters depolarization and repolarization of the heart Prolongation of QT interval Headache Drowsiness Torsades de Pointes arrhythmia Cardiac arrest Death Rare complications Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 6, 2023 on www.thecalgaryguide.com

Strabismus

Strabismus: Pathogenesis and clinical findings Microvascular dysfunction, trauma, or compression of oculomotor nerve Oculomotor nerve palsy: Dysfunction of the nerve innervating the superior rectus (elevation), inferior rectus (depression), medial rectus (adduction), and inferior oblique muscles (excyclotorsion) Thyroid eye disease (see Thyroid Eye Disease slide for pathogenesis) Inflammatory processes Thickening & fibrosis of extraocular muscles, most commonly the inferior rectus muscle (functions to rotate the eye and depress the gaze) Brown syndrome (congenital) Anomalous interaction between the trochlea and superior oblique muscle tendon Restriction of normal movement of the superior oblique tendon through the trochlea Trochlear palsy (Dysfunction of the trochlear nerve (CN IV)) Weakness of the superior oblique muscle innervated by CN IV (responsible for depression of the gaze and incyclotorsion & rotation of the eye) Near reflex: convergence (eyes adduct), accommodati on (thickening of the lens) & miosis (constriction of the pupil) Excessive accommodation in hyperopic (farsighted) eyes Over-activation of near reflex Accommodative esotropia Aneurysm, infection, iatrogenic injury to cranial nerve (CN) VI Abducens palsy: ocular motor paralysis Failure of CN VI to develop normally in utero Duane syndrome: congenital malformation of CN VI Congenital fibrosis of the extraocular muscles (CFEOM) Restrictive global paralysis of the extraocular muscles that control the movements of the eye Phenotype CFEOM2 Phenotype CFEOM1 & 3 Dysfunction of the abducens nerve (CN VI: innervates the ipsilateral lateral rectus muscle which abducts the eye [turns it laterally]) Orbital fracture (fracture of the orbital floor) Intraorbital contents (inferior rectus muscle and/or surrounding tissue) herniate through the fractured site & are entrapped Idiopathic infantile esotropia Intermittent exotropia Unclear process Exotropia: affected eye is rotated laterally Esotropia: affected eye is rotated medially Hypotropia: affected eye is rotated downward compared to non-affected eye Hypertropia: affected eye is rotated upward compared to non-affected eye Horizontal Strabismus Two different images are received by the eye that cannot be fused together Visual cortex suppresses the input from one eye in order to avoid having diplopia Amblyopia/lazy eye: visual cortex diminishes neural inputs from the corresponding cortical areas of affected eye ↓ Spatial awareness Vertical Strabismus Binocular diplopia: double vision when both eyes are open, and absent when either eye is closed Atypical alignment of the eye Psychosocial consequences: negative impact to mental health due to social bias or abuse, social anxiety, and difficulties with self-image Authors: Mina Mina Lucy Yang Reviewers: Mao Ding William Stell* * MD at time of publication ↓ Visual acuity ↓ Oculomotor control Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 6, 2023 on www.thecalgaryguide.com

سندرم-زجر-تنفسی-حاد-ards

سندرم-زجر-تنفسی-حاد-ards

کمبود-آلفا-یک-آنتیتریپسین-α1at

!مبود آلفا +ک آن.ت321س 56 α1AT

سرفه-مزمن-سیر-بیماری

سرفه مزمن: سیر بیماری

سرفه-فیزیولوژی

سرفه: فیزیولوژی

ketamine-francais

ketamine francais

hypersensibilite-resume

Hypersensibilité: Résumé

hypersensibilite-de-type-iv-pathogenese-et-resultats-cliniques

Hypersensibilité de type IV: Pathogénèse et résultats cliniques

Rhumatisme psoriasique Complications

Rhumatisme psoriasique: Complications

normal neonatal changes pathogenesis and clinical findings

Normal Neonatal Changes: Physiology and Clinical Findings The neonatal period is between infants’ time of birth and 4 weeks gestational age. This slide focuses only on changes that are part of the normal growth and development of neonates born at full term (38-42 weeks). Authors: Erin Auld, Dasha Mori Reviewers: Kayla Feragen Mao Ding Danielle Nelson* *MD at time of publication Birth weight: Loss of birth weight up to 10%; should be re-gained within 10-14 days (30 g/day) Stool: transitions from meconium (first stool of neonate that is black, tarry and sticky) to normal (green/brown or yellow mustard) within 2-3 days Meconium passage: within 24 hours of birth Growth • Height: 2.5 cm/month • Head Circumference: Average 1 cm/month in the first year with greatest growth in the first month • Weight: 20-30 g/day for the first 3 months Urination: within the first 24 hours Mother receives intravenous fluids during delivery Colostrum (first milk secretion that contains antibodies) produced in first 2-3 days of lactation post-partum (Lactogenesis I) GI tract maturation Adequate dietary intake Maturation of urinary tract Adequate fluid intake ↑ maternal blood volume Fluid moves between fetus and mother through placenta Fetus’s fluid volume ↑ Infant’s urine output ↑ in first 24 hours post-partum Low breast milk intake in first 2-3 days ↓ progesterone, ↑ prolactin in mother at birth Infant ingests colostrum Mostly water loss, some fat loss ↑ Breast Milk Production (Lactogenesis II) Stomach stretches ↑ in gastrointestinal tract motility (gastrocolic reflex) Ingestion of milk post-partum further stimulates GI maturation 110-120 kilocalories/kg/day Gastrointestinal tract formation begins when the fetus is 4 weeks old. Maturation continues into infancy. Normal gestational age (38-42 weeks) Fetus ingests amniotic fluid in utero Stimulates structural changes, enzymatic activity, and metabolic activity of GI tract Mature detrusor sphincter complex, appropriate bladder capacity, proper renal perfusion, and regular arousal of the neonate Breast milk: Feeding when infant demands it, approximately every 2-3 hours Formula: Feeding when infant demands it, approximately every 4 hours Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Oct 24, 2015, updated Sept 28, 2023 on www.thecalgaryguide.com

کارسینوم اولیھ ریھ

کارسینوم اولیھ ریھ )برونکوژنیک( - تومورھای پانکواست

سرطان ریھ: یافتھ ھای بالینی و نشانگان ھای پارانئوپلاستیک

سرطان ریھ: یافتھ ھای بالینی و نشانگان ھای پارانئوپلاستیک

Hipoglikemia Diabetik: Patogenesis dan Temuan Klinis

Hipoglikemia Diabetik: Patogenesis dan Temuan Klinis

Gambaran Umum tentang Keganasan Sel Darah

Gambaran Umum tentang Keganasan Sel Darah

корь-осложнения

Корь: Осложнения

Ишемическии-колит

Ишемический колит: Патогенез и клинические проявления

Obstructive Hydrocephalus on CT MRI Pathogenesis and findings

Obstructive Hydrocephalus on CT/MRI: Pathogenesis and findings Authors: Nathan Archibald Reviewers: Matthew Hobart, Mao Ding James Scott* * MD at time of publication Congenital Causes: Arnold-Chiari malformation, Dandy-Walker malformation, intrauterine infections, aqueductal stenosis Acquired Causes: Tumor, trauma, hemorrhage, infection Flow in cerebrospinal fluid pathway is obstructed (most commonly at the foramina Monro, aqueduct of Sylvius, fourth ventricle, and foramen magnum) Acute: Lateral walls and inferior surface of the third ventricle bulge out Temporal horns Temporal horns of the lateral of the lateral ventricles dilate ventricles dilate Cerebrospinal fluid accumulates upstream ↑ Ventricular pressure Ventricles dilate (ventriculomegaly) ↑ Intracranial Pressure (See Increased Intracranial Pressure: Clinical Findings Slide) Headache Papilledema Impaired consciousness Nausea and vomiting Image Credit: Radiopaedia Image Credit: radRounds Ventricular ependymal lining is disrupted Cerebrospinal fluid migrates into the surrounding brain parenchyma Transependymal edema Fourth ventricle may Fourth ventricle may Chronic: Septum pellucidum becomes fenestrated Pronounced dilation of the ventricles, especially the lateral and third ventricles Fornices become depressed Corpus callosum thins and elevates dilate, although the dilate, although the posterior fossa often posterior fossa often Distended ventricles compress overlying cortex prevents it from prevents it from getting too large getting too large High T2 or FLAIR High T2 or FLAIR signal around the signal around the lateral ventricles on lateral ventricles on MRI MRI Image Credit: Cumming School of Medicine Image Credit: Radiology Key Third ventricle, pineal, infundibular and supra- optic recesses balloon out Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Oct 10, 2023 on www.thecalgaryguide.com

Acute Respiratory Distress Syndrome

Acute Respiratory Distress Syndrome: Pathogenesis and clinical findings Acute respiratory distress syndrome (ARDS) is a clinical syndrome involving acute lung injury. It results in severe hypoxemia and bilateral Authors: David Olmstead Mao Ding Reviewers: Midas (Kening) Kang Usama Malik Kevin Solverson* * MD at time of publication ↓ PaO2 (Partial pressure of oxygen in arterial blood ↓SpO2 (Peripheral oxygen saturation) Tachypnea (↑ RR) Tachycardia (↑ HR) Dyspnea Bilateral Opacity on chest radiograph ↓ PaO2, ↓SpO2 ↑ PaCO 2 ↑ PaO2, ↓PaCO2 Eupnea (normal breathing) ↓ O2 Requirements Depression, Anxiety, PTSD Neuromuscular Weakness Chronic Respiratory Dysfunction airspace disease in the absence of elevated left-heart pressures. Direct Lung Injury Causes include pneumonia and pulmonary sepsis (community- acquired, hospital-acquired, aspiration, viral), drowning, and chemical pneumonitis from aspiration or direct inhalational injury Indirect Lung Injury Causes include sepsis with a non-pulmonary source, trauma, severe burns, transfusion- related acute lung injury (TRALI) and pancreatitis Lung Tissue Inflammation Exudative: Neutrophils migrate into the alveoli in response to inflammatory stimulus Note: While the three phases of ARDS take place in sequence, all areas of the lung may not be in the same phase at the same time. For this reason, the processes can be thought of as overlapping. Proliferative: Body attempts to heal damage. If it is not successful, the tissue transitions to the fibrotic phase Neutrophil-containing pulmonary exudate interferes with surfactant function Neutrophil infiltration and proinflammatory cytokines lead to tissue edema, dysfunction and subsequent destruction of pulmonary epithelium Residual debris in alveoli are cleared by phagocytic cells Restoration of alveolar epithelial cells. Alveoli collapse in absence of working surfactant Damaged epithelium impairs gas exchange Pulmonary capillaries do not adequately absorb fluid The body’s attempts to heal lung tissue result in deposition of hyaline membranes in the alveoli Ventilation- Perfusion Mismatch Pulmonary Edema Impaired Gas Diffusion Functional epithelium is able to absorb fluid back into circulation ↑ useful surface area for gas exchange Clearing of CXR Impaired Function After Prolonged Illness Pulmonary Hypertension Fibrotic: Inadequate healing results in long-term pulmonary damage (rare) Fibroblast activity leads to deposition of collagen in alveoli and alveolar capillaries Fatigue Pulmonary Fibrosis Nail Clubbing (nails appear wider & swollen) Cough/Dyspnea Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Feb 6, 2018, updated Oct 10, 2023 on www.thecalgaryguide.com Acute Respiratory Distress Syndrome: Note: Acute respiratory distress syndrome is a clinical Authors: David Olmstead Reviewers: Midas (Kening) Kang Usama Malik Kevin Solverson* * MD at time of publication Pathogenesis and clinical findings Direct Lung Injury Causes include pneumonia and pulmonary sepsis (community-acquired, hospital-acquired, aspiration, viral), drowning, and chemical pneumonitis from aspiration or direct inhalational injury Indirect Lung Injury syndrome involving acute lung injury. It results in severe hypoxemia and bilateral airspace disease in the absence of elevated left-heart pressures. Causes include sepsis with a non-pulmonary source, trauma, severe burns, transfusion-related acute lung injury (TRALI) and pancreatitis Lung Tissue Inflammation Exudative: Neutrophils migrate into the alveoli in response to inflammatory stimulus Note: While the three phases of ARDS take place in sequence, all areas of the lung may not be in the same phase at the same time. For this reason, the processes can be thought of as overlapping. Proliferative: Body attempts to heal damage. If it is not successful, the tissue transitions to the fibrotic phase Neutrophil-containing pulmonary exudate interferes with surfactant function Neutrophil infiltration and proinflammatory cytokines lead to tissue edema, dysfunction and subsequent destruction of pulmonary epithelium Abbreviations: PaO2: Partial pressure of oxygen in arterial blood SpO2: Peripheral oxygen saturation. CXR: Chest radiograph. Residual debris in alveoli are cleared by phagocytic cells Restoration of alveolar epithelial cells. Alveoli collapse in absence of working surfactant Damaged epithelium impairs gas exchange Pulmonary capillaries do not adequately absorb fluid The body’s attempts to heal lung tissue result in deposition of hyaline membranes in the alveoli Ventilation- Perfusion Mismatch Pulmonary Edema Impaired Gas Diffusion ↓ PaO2, ↓SpO2 Tachypnea Tachycardia Dyspnea Bilateral Opacity on CXR ↓ PaO , ↓SpO 2 2 ↑ PaCO2 ↑ PaO2, ↓PaCO2 Eupnea ↓ O2 Requirements Clearing of CXR Depression, Anxiety, PTSD Neuromuscular Weakness Chronic Respiratory Dysfunction ↑ useful surface area for gas exchange Functional epithelium is able to absorb fluid back into circulation Impaired Function After Prolonged Illness Fibrotic: Inadequate healing results in long-term pulmonary damage (rare) Fibroblast activity leads to deposition of collagen in alveoli and alveolar capillaries Pulmonary Fibrosis Pulmonary Hypertension Cough/Dyspnea Nail Clubbing Fatigue Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 06, 2018 on www.thecalgaryguide.com

Bronkiolitis Patogenesis dan temuan klinis

Bronkiolitis: Patogenesis dan temuan klinis

Asma Eksaserbasi Patogenesis dan temuan klinis pada anak

Asma Eksaserbasi: Patogenesis dan temuan klinis pada anak

Kelahiran Prematur Tinjauan Komplikasi

Kelahiran Prematur: Tinjauan Komplikasi

Pneumonia Pediatri Patogenesis dan Temuan klinis

Pneumonia Pediatri: Patogenesis dan Temuan klinis

Tatalaksana Syok Penjelasan dari mekanisme dasar

Tatalaksana Syok: Penjelasan dari mekanisme dasar

Spondilosis Patogenesis dan komplikasi

Spondilosis: Patogenesis dan komplikasi

تشدید آسم حاد بیماریزایی و درمان

تشدید آسم حاد: بیماریزایی و درمان

آسم بیماریزایی

آسم: بیماریزایی

آسم یافتھ ھای بالینی

آسم: یافتھ ھای بالینی

آسم یافتھ ھای تحقیقاتی

آسم: یافتھ ھای تحقیقاتی

Approach To Dementia

Approach to Dementia/Major Neurocognitive Disorder (NCD) Authors: Iqra Rahamatullah Mahrukh Kaimkhani Reviewers: Yvette Ysabel Yao Mao Ding Gary Michael Klein* *MD at time of publication 1) Changes noticed? Modest ↓cognitive performance from previous, DOES NOT interfere with daily independence MILD COGNITIVE IMPAIRMENT More pronounced ↓cognitive performance from previous, DOES interfere with daily independence MILD TO MODERATE DEMENTIA ↓Cognitive performance, difficulty with ≥1 basic activities of daily living (ADL) or ≥2 instrumental ADLs MODERATE TO SEVERE DEMENTIA DEMENTIA Fluctuating course, acute onset, inattention WITH either disorganized thinking or altered level of consciousness DELIRIUM 2) Is it dementia? Normal, age-related: ↓focus, ↓cognitive speed, ↓reaction time, ↓memory NORMAL COGNITIVE DECLINE 3) What is the cause of the dementia? (main causes discussed here) Loss of cognitive functioning, including memory, language, problem solving, and other thinking abilities, that interferes with independence in everyday activities Beta-secretase cleaves beta amyloid protein Atherosclerosis or thrombosis Misfolded alpha- synuclein Toxic beta amyloid plaque and tau tangle (sticky) formation Ischemia to areas of brain (strokes) Build ups and deposition within neurons (Lewy bodies) Disrupted signaling, inflammation, hippocampal and cerebral impairment Necrosis of brain tissue in areas impacted by strokes Neuronal impairment and atrophy (especially in substantia nigra) Neuronal atrophyàfrontal + temporal lobe atrophy Progressive atrophy of basal ganglia and dorsal striatum + lateral ventricles expanding Death of dopaminergic neurons in substantia nigra Alzheimer’s Dementia Vascular Dementia Lewy Body Dementia Frontotemporal Dementia Huntington’s Disease Parkinson’s Disease ↓Memory, ↓learning, ↓language skills, disorientation, inattention Total debilitation, fatal infections Findings vary depending on area Step-wise worsening impairment Parkinsonism, hallucinations, REM- sleep behavior disorder Total debilitation, dependence Personality and behavioral changes Mental status changes Chorea, ↓cognition, mood changes Aspiration, dementia, suicide Resting tremor, rigidity, anosmia Depression, dementia, falls Abnormal protein inclusions and tangles (usually tau) form in neurons Autosomal dominant disease (with anticipation) with ↑CAG repeats in Huntingtin gene Genetic mutations, environmental exposures, or idiopathic cause Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 17, 2023 on www.thecalgaryguide.com Approach to Dementia/Major Neurocognitive Disorder (NCD) Authors: Iqra Rahamatullah Mahrukh Kaimkhani Reviewers: Yvette Ysabel Yao Fluctuating course, acute onset, inattention WITH either disorganized thinking or altered level of consciousness (LOC)? DELIRIUM 1) Changes noticed? 2) Is it dementia? Normal, age-related: ↓focus, ↓cognitive speed, ↓reaction time, ↓memory NORMAL COGNITIVE DECLINE Modest ↓cognitive performance from previous, DOES NOT interfere with daily independence MILD COGNITIVE IMPAIRMENT More pronounced ↓cognitive performance from previous, DOES interfere with daily independence MILD TO MODERATE DEMENTIA ↓Cognitive performance, difficulty with ≥1 basic activities of daily living (ADL) or ≥2 instrumental ADLs MODERATE TO SEVERE DEMENTIA 3) What is the cause of the dementia? (main causes discussed here) Beta-secretase cleaves beta amyloid protein Atherosclerosis or thrombosis Misfolded alpha-synuclein Toxic beta amyloid plaque and tau tangle (sticky) formation Ischemia to areas of brain (strokes) Build ups and deposition within neurons (Lewy bodies) Disrupted signaling, inflammation, hippocampal and cerebral impairment Necrosis of brain tissue in areas impacted by strokes Neuronal impairment and atrophy (especially in substantia nigra) Neuronal atrophyàfrontal + temporal lobe atrophy Progressive atrophy of basal ganglia and dorsal striatum + lateral ventricles expanding Death of dopaminergic neurons in substantia nigra Alzheimer’s Dementia Vascular Dementia Lewy Body Dementia Frontotemporal Dementia Huntington’s Disease Parkinson’s Disease ↓Memory, ↓learning, ↓language skills, disorientation, inattention Total debilitation, fatal infections Findings vary depending on area Step-wise worsening impairment Parkinsonism, hallucinations, REM- sleep behavior disorder Total debilitation, dependence Personality and behavioral changes Mental status changes Chorea, ↓cognition, mood changes Aspiration, dementia, suicide Resting tremor, rigidity, anosmia Depression, dementia, falls DEMENTIA Loss of cognitive functioning, including memory, language, problem solving, and other thinking abilities, that interferes with independence in everyday activities Abnormal protein inclusions and tangles (usually tau) form in neurons Autosomal dominant disease (with anticipation) with ↑CAG repeats in Huntingtin gene Genetic mutations, environmental exposures, or idiopathic cause Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 17, 2023 on www.thecalgaryguide.com

Guillain-Barre Syndrome

Guillain-Barré Syndrome: Pathogenesis and clinical findings Author: Nissi Wei Mao Ding Reviewers: Owen Stechishin Matthew Harding Cory Toth* * MD at time of publication ↑ Protein in cerebrospinal fluid (CSF) Minor triggers surgery, trauma, bone marrow transplant Initiate immune response (unknown mechanism) GI/respiratory infection (1-3 weeks prior) Campylobacter jejuni, cytomegalovirus, HIV, Epstein-Barr Virus Molecular mimicry: shared ganglioside antigens between peripheral nerve and pathogen coat proteins IgG antibodies to ganglioside antibodies in serum Nerve Conduction Study : ↓ conduction velocity, conduction block Triggered immune response cross-reacts with peripheral nerves, beginning at nerve roots ↑ permeability of blood- nerve barrier at level of proximal nerve roots Demyelination: antibodies attack Schwann cells secondary damage Axonal damage: antibodies attack nodes of Ranvier Nerve Conduction Study: ↓ CMAP (compound muscle action potential) amplitude, normal conduction velocity Acute inflammatory demyelinating polyneuropathy (AIDP) (80-90%) Acute motor axonal neuropathy (AMAN) Acute motor sensory axonal neuropathy (AMSAN) Acute immune-mediated polyneuropathy Tachycardia & Dysrhythmias (Needs cardiac monitoring) Sudden Death Dysautonomia: disruption of the autonomic nervous system responsible for involuntary functions Sensory deficits Motor deficits Universal Areflexia (loss of deep tendon reflexes) Phrenic nerve involvement Diaphragm paralysis Cranial Nerve (CN) involvement Bulbar palsy (CN IX, X, XI,XII) Oculomotor weakness (CN III, IV, VI) Eye Movement Abnormalities (Miller Fisher Syndrome – rare form of regionally- restricted AIDP) BP Fluctuation/ Orthostatic Hypotension (drop of blood pressure from seated/lying to standing) Urinary Retention (transient, late-course) Limb Weakness (legs usually affected first) Impaired swallowing àaspiration pneumonia ↓ ability to clear airway secretions Pain & Paresthesia (in back and extremities) Respiratory Failure (Life threatening: needs ventilatory observation and possibly support) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Nov 1, 2013, updated Oct 15, 2023 on www.thecalgaryguide.com Guillain-Barré Syndrome Minor triggers (surgery, trauma, GI/respiratory infection Campylobacter jejuni, CMV, HIV , EBV (1-3 weeks prior) Molecular mimicry: shared ganglioside antigens between peripheral nerve and pathogen coat proteins Author: Nissi Wei Reviewers: Owen Stechishin Matthew Harding Cory Toth* * MD at time of publication ↑ Protein in CSF bone marrow transplant) Initiate immune response (unknown mechanism) IgG antibodies to ganglioside antibodies in serum NCS: ↓ conduction velocity, conduction block Triggered immune response cross-reacts with peripheral nerves, beginning at nerve roots ↑ permeability of blood- nerve barrier at level of proximal nerve roots NCS: ↓ CMAP amplitude, normal conduction velocity Demyelination: antibodies attack Schwann cells secondary damage Axonal damage: antibodies attack nodes of Ranvier Acute inflammatory demyelinating polyneuropathy (AIDP) (80-90%) Acute motor axonal neuropathy (AMAN) Cranial nerve involvement Dysautonomia Acute motor sensory axonal neuropathy (AMSAN) Eye Movement Abnormalities (Miller Fisher Syndrome – rare form of regionally-restricted AIDP) Acute immune-mediated polyneuropathy Oculomotor weakness (CN III, IV, VI) Bulbar palsy (CN IX, X, XI,XII) Phrenic nerve involvement ↓ ability to clear airway secretions Impaired swallowingà aspiration pneumonia Diaphragm paralysis Respiratory Failure (Life threatening: needs ventilatory observation and possibly support) Motor deficits Sensory deficits Pain & Paresthesias in back and extremities Limb Weakness (legs usually affected first) Universal Areflexia Urinary Retention (transient, late-course) Sudden Death BP Fluctuation, Orthostatic Hypotension Tachycardia, Dysrhythmias (Needs cardiac monitoring) Abbreviations: • NCS - nerve conduction study • CMAP - compound muscle action potential • EBV - Epstein-Barr Virus • CMV - cytomegalovirus • CN - cranial nerve Note: Aα, Aβ peripheral nerve fibres (large, fast-conducting, heavily myelinated axons for muscle stretch, light touch & proprioception) are more affected than Aδ and C fibres (small, less myelinated, slowly-conducting fibres for pain and temperature) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 1, 2013 on www.thecalgaryguide.com

Perdarahan Intraventrikuler pada Bayi Prematur Patogenesis

Perdarahan Intraventrikuler pada Bayi Prematur: Patogenesis

Pulmonary Embolism Pathogenesis and Clinical Findings

Pulmonary Embolism: Pathogenesis and Clinical Findings Virchow’s Triad Body attempts to break down clot Fibrinogen breakdown products in blood Lab: Positive D-Dimer D-Dimer only performed if clinical suspicion of PE low (Well’s Criteria) Authors: Mackenzie Gault Mao Ding Reviewers: Midas (Kening) Kang Usama Malik Kevin Solverson* *MD at time of publication Hypercoagulable State Blood clot develops (commonly in deep veins of legs) Venous stasis = Deep Vein Thrombus (95% of PE) Vessel injury Ultrasound: Presence of Clot in Deep Vein of Leg Clot dislodges & migrates to inferior vena cava (IVC)àright atrium of heartàright ventricleàlodges in pulmonary arteries/arterioles Pulmonary Embolism (PE) Thromboembolic blockage of pulmonary vasculature ↓ perfusion to lung parenchyma Clot occludes pulmonary arteries/ arterioles ↑ dead space ventilation and V/Q mismatching Blood pumped from RV to pulmonary arteries cannot pass clot ↑ pulmonary and right ventricle (RV) pressure RV Strain ↑ RV workload, ↓ right coronary artery perfusion Computed Tomography- Pulmonary Angiogram (CTPA): Filling Defect (*see Radiology slide for CTPA findings) Echo: ↑ RV size + ↓ RV function ECG: S1Q3T3 Pattern (McGinn-White Sign: a large S wave in lead I, a Q wave in lead III and an inverted T wave in lead III together indicate acute right heart strain Lab: ↑ Brain natriuretic peptide (BNP) Chest Pain Tachycardia Dyspnea (shortness of breath) Pleuritic chest pain (worsens during breathing) Ischemia of lung tissue distal to clot X-Ray: usually normal, except Hampton’s Hump (↑ opacity in pleural based area), a rare but specific sign of PE) Air flow/ventilation to lungs unaffected VQ Scan (performed when CT contrast is contraindicated): Ventilation- perfusion ratio (V/Q) mismatch Chemoreceptors detect ↑ CO2 and ↓ O2 Signal brain to ↑ breathing rate Tachypnea (rapid breathing) ↓ Arterial O2 Lab: ↑Troponin BP: Hypotension Lab: ↑ Lactate Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Feb 7, 2018, updated Oct 15, 2023 on www.thecalgaryguide.com Pulmonary Embolism: Pathogenesis and Laboratory Findings Virchow’s Triad Authors: Mackenzie Gault Reviewers: Midas (Kening) Kang Usama Malik Kevin Solverson * * MD at time of publication Body attempts to break down clot Fibrinogen breakdown products in blood Positive D-Dimer ↓ perfusion to lung parenchyma Vessel injury = Deep Vein Thrombus (95% of PE) Ultrasound: Presence of Clot in Deep Vein of Leg Notes: Hypercoagulable State Venous stasis Blood clot develops (commonly in deep veins of legs) Clot dislodges, migrates to IVCàright atrium of heartà right ventricleàlodges in pulmonary artery Pulmonary Embolism (PE): Thromboembolic blockage of pulmonary vasculature Clot occludes pulmonary artery/ arterioles • D-Dimer is only performed if clinical suspicion of PE low (Well’s Criteria) • CT-PA is the current diagnostic test for PE • V/Q Scan is performed when CT contrast is contraindicated • X-Ray is usually normal in PE (Except Hampton’s Hump, a rare but specific sign of PE) Ischemia of lung tissue distal to clot X-Ray: Hampton’s Hump pleural based area of ↑ opacity Air flow/ ventilation to lungs unaffected Pleuritic Chest Pain + Dyspnea VQ Scan: V/Q Mismatch ↑ dead space ventilation and V/Q mismatching Chemoreceptors detect ↑ CO2 and ↓ O2 Signal brain to ↑ breathing rate Tachypnea ↓ Arterial O2 Blood pumped from RV to pulmonary arteries cannot pass clot ↑ pulmonary and RV pressure RV Strain CT-PA: Filling Defect Echo: ↑ RV size + ↓ RV Function ECG: S1Q3T3 Pattern Lab:↑ BNP Chest Pain Tachycardia ↑ RV work load, ↓ right coronary artery perfusion Abbreviations: • BNP – Brain Natriuretic Peptide • CT-PA – Computed Tomography-Pulmonary Angiogram • ECG – Electrocardiogram • IVC – Inferior Vena Cava • RV – Right Ventricle • V/Q – Ventilation-Perfusion ratio ↑ Troponin Hypotension ↑ Lactate Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 07, 2018 on www.thecalgaryguide.com

Mitral Regurgitation Pathogenesis and clinical findings

Mitral Regurgitation: Pathogenesis and clinical findings Coronary Artery Disease Authors: Juliette Hall, Victoria Nkunu Reviewers: Raafi Ali, Jack Fu, Usama Malik, Sina Marzoughi, Jason Waechter* * MD at time of publication (Ischemic Heart Disease & Myocardial Infarction) Myocarditis Left ventricular dilation displaces papillary muscles Dilation of the Tethering of mitral valve annulus chordae tendineae ↑ Volume and pressure in left atrium ↑ Volume pushed back into left ventricle Dilated left ventricle Apical impulse on palpation and auscultation ↓ Forward flow of blood out of heart Blood backs up into pulmonary circulation ↑ Intravascular hydrostatic pressure in pulmonary vessels Fluid extravasates out of vessels and into the lungs Papillary muscle rupture Mitral valve leaflets flail Mitral valve prolapse Structurally abnormal valve Connective tissue disorders Weak valve leaflets Rheumatic heart disease Dilatation of the mitral valve annulus, inflammation of leaflets Infective endocarditis Vegetations form on valve leaflets Mitral Regurgitation Blood consistently flows backward throughout systole Holosystolic murmur, radiates to axilla, ↑ with afterload (e.g. making a fist) Backflow of blood from left ventricle to left atrium due to impaired mitral valve closure S3 heart sound Myocardial remodeling ↓ Muscle efficiency ↓ Left ventricle systolic function ↓ O2 saturation, tachypnea, wheeze, ↑ work of breathing, crackles, frothy sputum (if severe) Congestive heart failure ↓ Stroke volume ejected into aorta ↓ Cardiac output ↓ Organ perfusion ↓ O2 to kidney Activation of renin-angiotensin- aldosterone system ↑ Reabsorption of water by kidneys ↑ Intravascular hydrostatic pressure systemically Peripheral edema Injury to kidney parenchyma ↓ ability for kidney to clear creatinine ↑ Serum creatinine Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Feb 3, 2018, updated Oct 15, 2023 on www.thecalgaryguide.com

Alcohol Withdrawal Syndrome

Alcohol Withdrawal Syndrome (AWS): Pathophysiology & clinical findings Authors: Rupali Manek Gurreet Bhandal Erika Russell Reviewers: Harjot Atwal Yvette Ysabel Yao Mao Ding Nureen Pirbhai* * MD at time of publication Chronic alcohol use ↓Autonomic adrenergic systems ↓ Dopamine in the nucleus accumbens ↑ EtOH depressant effects on brain ↓ Glutamate- induced excitation ↑ GABA-induced inhibition ↑ Glutamate receptors in attempt to maintain normal arousal state GABA insensitivity (↑ GABA needed to maintain a constant inhibitory tone) Long-term physical dependence Abrupt alcohol cessation àabrupt ↓ in blood EtOH concentration Alcohol withdrawal Syndrome Symptoms that occur when patients stop drinking or significantly decrease their alcohol intake after long-term dependence ↓ GABA-induced inhibition &↑ glutamate-induced excitation relative to chronic alcohol use Central nervous system overactivity Withdrawal seizures: Generalized tonic-clonic convulsions 24-48 hours after alcohol cessation Fluid and electrolyte abnormalities ↑ Autonomic adrenergic systems (rebound over-activity of the brain and noradrenergic systems) ↑ Sympathetic activity: ↑ Heart rate (HR), ↑respiratory rate (RR) ↑blood pressure (BP), tremor & diaphoresis (↑sweating) Early symptoms: Insomnia, tremulousness, anxiety, digestive upset, anorexia, headache, sweating, palpitations 6-12 hours after alcohol cessation ↑ Dopamine in nucleus accumbens Alcoholic hallucinosis: Usually visual (but can be auditory or tactile), normal vitals 12-24 hours after alcohol cessation, typically resolve within 24-48 hours Alcohol withdrawal delirium (delirium tremens or DT): Hallucinations (mostly visual), disorientation, tachycardia, hypertension, hyperthermia, agitation, and diaphoresis 48-96 hours after alcohol cessation and lasts 1-5 days Hypovolemia (from diaphoresis, hyperthermia, vomiting, ↑RR & ↓oral intake) Metabolic acidosis (from hypoperfusion, infection, alcoholic ketoacidosis, or ↓ thiamine & other B vitamins) ↓ Potassium (K) (renal & extrarenal K losses, alterations in aldosterone concentrations, and changes in K distribution across the cell membrane) ↓ Phosphate (from malnutrition) Cardiac failure, rhabdomyolysis or muscle breakdown ↓ Phosphate available to make ATP ↓ ATP ↓ Magnesium (common in patients with DT) Impaired Na-K ATPase function Dysrhythmias ↑ Glutamate-activated depolarization in the brain ↑ Neuronal excitability Seizures Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Apr 15, 2017, updated Oct 18, 2023 on www.thecalgaryguide.com Alcohol Withdrawal Syndrome (AWS): Pathophysiology & clinical findings Authors: Rupali Manek Gurreet Bhandal Erika Russell Reviewers: Harjot Atwal Yvette Ysabel Yao Mao Ding Nureen Pirbhai* * MD at time of publication Chronic alcohol use ↓Autonomic adrenergic systems ↓ Dopamine in the nucleus accumbens ↑ EtOH depressant effects on brain ↓ Glutamate- induced excitation ↑ GABA-induced inhibition ↑ Glutamate receptors in attempt to maintain normal arousal state GABA insensitivity (↑ GABA needed to maintain a constant inhibitory tone) Long-term physical dependence Abrupt alcohol cessation àabrupt ↓ in blood EtOH concentration Alcohol withdrawal Syndrome Symptoms that occur when patients stop drinking or significantly decrease their alcohol intake after long-term dependence ↓ GABA-induced inhibition &↑ glutamate-induced excitation relative to chronic alcohol use Central nervous system overactivity Withdrawal seizures: Generalized tonic-clonic convulsions 24-48 hours after alcohol cessation Fluid and electrolyte abnormalities ↑ Autonomic adrenergic systems (rebound over-activity of the brain and noradrenergic systems) ↑ Sympathetic activity: ↑ Heart rate (HR), ↑respiratory rate (RR) ↑blood pressure (BP), tremor & diaphoresis (↑sweating) Early symptoms: Insomnia, tremulousness, anxiety, digestive upset, anorexia, headache, sweating, palpitations 6-12 hours after alcohol cessation ↑ Dopamine in nucleus accumbens Alcoholic hallucinosis: Usually visual (but can be auditory or tactile), normal vitals 12-24 hours after alcohol cessation, typically resolve within 24-48 hours Alcohol withdrawal delirium (delirium tremens or DT): Hallucinations (mostly visual), disorientation, tachycardia, hypertension, hyperthermia, agitation, and diaphoresis 48-96 hours after alcohol cessation and lasts 1-5 days Hypovolemia (from diaphoresis, hyperthermia, vomiting, ↑RR & ↓oral intake) Metabolic acidosis (from hypoperfusion, infection, alcoholic ketoacidosis, or ↓ thiamine & other B vitamins) ↓ Potassium (K) (renal & extrarenal K losses, alterations in aldosterone concentrations, and changes in K distribution across the cell membrane) ↓ Magnesium (common in patients with DT) Dysrhythmias, seizures ↓ Phosphate (from malnutrition) ↓ Phosphate available to make ATP ↓ ATP Cardiac failure, rhabdomyolysis or muscle breakdown Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 28th, 2014 on www.thecalgaryguide.com Alcohol Withdrawal: Pathophysiology & clinical findings Authors: Erika Russell Rupali Manek Gurreet Bhandal Reviewers: Yvette Ysabel Yao Harjot Atwal Nureen Pirbhai* * MD at time of publication ↓Autonomic adrenergic systems ↓ Glutamate-induced excitation Chronic alcohol use ↑ EtOH depressant effects on brain ↓ Dopamine in the nucleus accumbens ↑ GABA-induced inhibition ↑ Glutamate receptors in attempt to maintain normal arousal state GABA insensitivity (↑ GABA needed to maintain a constant inhibitory tone) ↑ Autonomic adrenergic systems (rebound over- activity of the brain and noradrenergic systems) ↑ Sympathetic activity: ↑ Heart rate (HR), ↑respiratory rate (RR) ↑blood pressure (BP), tremor & diaphoresis (↑sweating) Physical dependence due to chronic alcohol use Abrupt alcohol cessation Abrupt ↓ in blood EtOH concentration Alcohol withdrawal ↓ GABA-induced inhibition &↑ glutamate-induced excitation relative to chronic alcohol use Central nervous system overactivity Withdrawal seizures: Generalized tonic-clonic convulsions 24-48 hours after alcohol cessation Fluid and electrolyte abnormalities ↑ Dopamine in nucleus accumbens Alcoholic hallucinosis: Usually visual (but can be auditory or tactile), normal vitals 12-24 hours after alcohol cessation, typically resolve within 24-48 hours Early symptoms: Insomnia, tremulousness, anxiety, digestive upset, anorexia, headache, sweating, palpitations 6-12 hours after alcohol cessation Alcohol withdrawal delirium (delirium tremens or DT): Hallucinations (mostly visual), disorientation, tachycardia, hypertension, hyperthermia, agitation, and diaphoresis 48-96 hours after alcohol cessation and lasts 1-5 days Hypovolemia (from diaphoresis, hyperthermia, vomiting, ↑RR & ↓oral intake) Metabolic acidosis (from hypoperfusion, infection, alcoholic ketoacidosis, or ↓ thiamine & other B vitamins) ↓ Potassium (K) (renal & extrarenal K losses, alterations in aldosterone concentrations, and changes in K distribution across the cell membrane) ↓ Magnesium (common in patients with DT) Dysrhythmias, seizures ↓ Phosphate (from malnutrition) ↓ Phosphate available to make ATP ↓ ATP Cardiac failure, rhabdomyolysis or muscle breakdown Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 28th, 2014 on www.thecalgaryguide.com Authors: Erika Russell Rupali Manek Gurreet Bhandal Reviewers: ↓Autonomic adrenergic systems ↓ Dopamine in the nucleus accumbens Yvette Ysabel Yao Harjot Atwal Nureen Pirbhai* * MD at time of publication Alcohol Withdrawal: Pathophysiology & clinical findings Chronic alcohol use ↑ EtOH depressant effects on brain ↓ Glutamate-induced excitation ↑ GABA-induced inhibition ↑ Glutamate receptors in attempt to maintain normal arousal state GABA insensitivity (↑ GABA needed to maintain a constant inhibitory tone) ↑ Autonomic adrenergic systems (rebound over- activity of the brain and noradrenergic systems) ↑ Sympathetic activity: ↑ Heart rate (HR), ↑respiratory rate (RR) ↑blood pressure (BP), tremor & diaphoresis (↑sweating) Physical dependence due to chronic alcohol use Abrupt alcohol cessation Abrupt ↓ in blood EtOH concentration Alcohol withdrawal ↓ GABA-induced inhibition &↑ Glutamate-induced excitation relative to chronic alcohol use Central nervous system overactivity Withdrawal seizures: Generalized tonic-clonic convulsions 24-48 hours after alcohol cessation Fluid and electrolyte abnormalities ↓ Potassium (K) (renal & extrarenal K losses, alterations in aldosterone concentrations, and changes in K distribution across the cell membrane) ↑ Dopamine in nucleus accumbens Alcoholic hallucinosis: Usually visual (but can be auditory or tactile), normal vitals 12-24 hours after alcohol cessation, typically resolve within 24-48 hours Alcohol withdrawal delirium (delirium tremens or DT): Hallucinations (mostly visual), disorientation, tachycardia, hypertension, hyperthermia, agitation, and diaphoresis 48-96 hours after alcohol cessation and lasts 1-5 days Early symptoms: Insomnia, tremulousness, anxiety, digestive upset, anorexia, headache, sweating, palpitations 6-12 hours after alcohol cessation Hypovolemia (from diaphoresis, hyperthermia, vomiting, ↑RR & ↓oral intake) Metabolic acidosis (from hypoperfusion, infection, alcoholic ketoacidosis, or ↓ thiamine & other B vitamins) ↓ Magnesium (common in patients with DT) Dysrhythmias, seizures ↓ Phosphate (from malnutrition) Cardiac failure, rhabdomyolysis or muscle breakdown Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 28th, 2014 on www.thecalgaryguide.com Alcohol Withdrawal: Pathophysiology & clinical findings Chronic alcohol use ↓ Dopamine in the nucleus accumbens ↓Autonomic adrenergic systems Authors: Erika Russell Rupali Manek Gurreet Bhandal Reviewers: Yvette Ysabel Yao Harjot Atwal ↑ GABA-induced inhibition Nureen Pirbhai* * MD at time of publication ↑ EtOH depressant effects on brain ↓ Glutamate-induced excitation ↑ Glutamate receptors in attempt to maintain normal arousal state GABA insensitivity (↑ GABA needed to maintain a constant inhibitory tone) ↑ Autonomic adrenergic systems (rebound over- activity of the brain and noradrenergic systems) ↑ Sympathetic activity: ↑Heart rate (HR), ↑respiratory rate (RR) ↑blood pressure (BP), tremor & diaphoresis (↑sweating) Physical dependence due to chronic alcohol use Abrupt alcohol cessation Abrupt ↓ in blood EtOH concentration Alcohol withdrawal ↓ GABA-induced inhibition &↑ Glutamate-induced excitation relative to chronic alcohol use Central nervous system overactivity Withdrawal seizures: Generalized tonic-clonic convulsions 24-48 hours after alcohol cessation Fluid and electrolyte abnormalities ↑ Dopamine in nucleus accumbens Alcoholic hallucinosis: Usually visual (but can be auditory or tactile), normal vitals 12-24 hours after alcohol cessation, typically resolve within 24-48 hours Alcohol withdrawal delirium (delirium tremens or DT): Hallucinations (mostly visual), disorientation, tachycardia, hypertension, hyperthermia, agitation, and diaphoresis 48-96 hours after alcohol cessation and lasts 1-5 days Early symptoms: Insomnia, tremulousness, anxiety, digestive upset, anorexia, headache, sweating, palpitations 6-12 hours after alcohol cessation Hypovolemia (from diaphoresis, hyperthermia, vomiting, ↑RR & ↓oral intake) Metabolic acidosis (from hypoperfusion, infection, alcoholic ketoacidosis, or ↓ thiamine & other B vitamins) ↓ Potassium (K) (renal & extrarenal K losses, alterations in aldosterone concentrations, and changes in K distribution across the cell membrane) ↓ Magnesium (common in patients with DT) Dysrhythmias, seizures ↓ Phosphate (from malnutrition) Cardiac failure, rhabdomyolysis or muscle breakdown Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 28th, 2014 on www.thecalgaryguide.com Alcohol Withdrawal: Pathophysiology & clinical findings Authors: Erika Russell Rupali Manek Gurreet Bhandal Reviewers: Yvette Ysabel Yao Harjot Atwal Nureen Pirbhai* * MD at time of publication ↑ EtOH depressant effects on brain ↓ Glutamate-induced excitation ↑ Glutamate receptors in attempt to maintain normal arousal state Chronic alcohol use ↑ GABA-induced inhibition GABA insensitivity (↑ GABA needed to maintain a constant inhibitory tone) ↓ Dopamine in the nucleus accumbens ↓Autonomic adrenergic systems Abrupt alcohol cessation Physical dependence due to chronic alcohol use Alcohol withdrawal ↓ GABA-induced inhibition &↑ Glutamate-induced excitation relative to chronic alcohol use Central nervous system overactivity Withdrawal seizures: Generalized tonic-clonic convulsions 24-48 hours after alcohol cessation ↑ Autonomic adrenergic systems (rebound over-activity of the brain and noradrenergic systems) ↑ Sympathetic activity: ↑HR, ↑RR ↑BP, tremor & diaphoresis (↑sweating) Early symptoms: Insomnia, tremulousness, anxiety, digestive upset, anorexia, headache, sweating, palpitations 6-12 hours after alcohol cessation ↑ Dopamine in nucleus accumbens Alcoholic hallucinosis: Usually visual (but can be auditory or tactile), normal vitals 12-24 hours after alcohol cessation, typically resolve within 24-48 hours Alcohol withdrawal delirium (delirium tremens or DT): Hallucinations (predominately visual), disorientation, tachycardia, hypertension, hyperthermia, agitation, and diaphoresis 48-96 hours after alcohol cessation and lasts 1-5 days Fluid and electrolyte abnormalities Hypovolemia (from diaphoresis, hyperthermia, vomiting, ↑ RR & ↓ oral intake) Metabolic acidosis (from hypoperfusion, infection, alcoholic ketoacidosis, or ↓ thiamine & other B vitamins) ↓ Potassium (K) (renal & extrarenal K losses, alterations in aldosterone concentrations, and changes in K distribution across the cell membrane) ↓ Magnesium (common in patients with DT) Dysrhythmias, seizures ↓ Phosphate (from malnutrition) Cardiac failure, rhabdomyolysis or muscle breakdown Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 28th, 2014 on www.thecalgaryguide.com Alcohol Withdrawal: Pathophysiology & clinical findings Authors: Erika Russell Rupali Manek Gurreet Bhandal Reviewers: Yvette Ysabel Yao Harjot Atwal Nureen Pirbhai* * MD at time of publication ↓ GABA-induced inhibition &↑ Glutamate-induced excitation relative to chronic alcohol use CNS overactivity Alcohol withdrawal delirium (delirium tremens or DT): Hallucinations (predominately visual), disorientation, tachycardia, hypertension, hyperthermia, agitation, and diaphoresis 48-96 hours after alcohol cessation and lasts 1-5 days Alcohol cessation ↓ Dopamine Alcohol withdrawal Chronic alcohol use ↑ EtOH depressant effects on brain in the NAc ↓Autonomic adrenergic systems ↑ Dopamine in nucleus accumbens (NAc) relative to chronic alcohol use Alcoholic hallucinosis: Usually visual (but can be auditory or tactile), normal vitals 12-24 hours after alcohol cessation, typically resolve within 24-48 hours ↑ Autonomic adrenergic systems relative to chronic alcohol use ↑ Sympathetic activity: ↑HR, ↑RR ↑BP, tremor & diaphoresis (↑sweating) ↓ Glutamate- induced excitation ↑ Glutamate receptors in attempt to maintain normal arousal state ↑ GABA-induced inhibition GABA insensitivity (↑ GABA needed to maintain a constant inhibitory tone) Early symptoms: Insomnia, tremulousness, anxiety, digestive upset, anorexia, headache, sweating, palpitations 6-12 hours after alcohol cessation Withdrawal seizures: Generalized tonic- clonic convulsions 24-48 hours after alcohol cessation Fluid and electrolyte abnormalities Abbreviations: CNS – Central nervous system K – Potassium DT – Delirium tremens Mg – Magnesium NAc – Nucleus accumbens NMDA – N-methyl-D-aspartate EtOH – Alcohol NT – Neurotransmitter Hypovolemia (from diaphoresis, hyperthermia, vomiting, ↑ RR & ↓ oral intake) Metabolic acidosis (from hypoperfusion, infection, alcoholic ketoacidosis, or ↓ thiamine & other B vitamins) ↓ K (renal & extrarenal K losses, alterations in aldosterone concentrations, and changes in K distribution across the cell membrane) ↓ Mg (common in patients with DT) Dysrhythmias, seizures ↓ Phosphate (from malnutrition) Cardiac failure, rhabdomyolysis or muscle breakdown Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 28th, 2014 on www.thecalgaryguide.com Alcohol Withdrawal: Clinical Findings and Complications Authors: Erika Russell Reviewers: Harjot Atwal Nureen Pirbhai* * MD at time of publication Note: *The onset of alcohol withdrawal generally begins 6-24 hours after the last drink with symptoms peaking between 24-36 hours after and gradually lessening. Symptoms typically progress from early symptoms and increased sympathetic activityà hallucinationsàseizures àpotentially Delirium Tremens. Alcohol withdrawal is mild-moderate in severity for 90% of patients. Those who progressively worsen however can enter Delirium Tremens (DT) which has a mortality rate of up to 20%. More likely to have DT if had DT before, age >30 years, concurrent illness, >2 days after EtOH cessation before seeking help, and history of sustained drinking. Long term, heavy alcohol use that leads to physical dependence Abrupt ↓ in blood EtOH concentration Negative physiological reactions to ↓ alcohol intake Adaptive suppression of GABA activity from chronic alcohol enhancement Alcohol Withdrawal* Withdrawal symptoms alleviated by ingesting alcohol Alcohol taken to relieve withdrawal AND/OR Social and internal relapse cues trigger urge to use alcohol Blood EtOH levels >600 mg% can lead to lethal respiratory depression by suppressing the respiratory centers in the brainstem Upregulated autonomic adrenergic systems from chronic alcohol inhibition Discontinuation of alcohol leads to rebound over- activity of the brain and noradrenergic systems Increased Sympathetic Activity Tachycardia, hypertension, tremor and diaphoresis Generalized Tonic-Clonic Seizures Usually begin within 8-24 hours of alcohol cessation and peak after 24 hours. Risk of having seizures ↑ with repeated withdrawals. 1/3 of people can progress to DT if seizures left untreated. Discontinuation of alcohol causes a sudden relative deficiency in inhibitory GABA activity Reduction in dopamine in the nucleus accumbens (NAc) from chronic alcohol exposure Discontinuation of alcohol causes a increase in dopamine levels in NAc Hallucinations Commonly visual (but can be auditory or tactile), develop 12-24 hours after alcohol cessation. Early Symptoms Anxiety, insomnia, vivid dreams, anorexia, nausea, headache and psychomotor agitation Delirium Tremens (DT) Life-threatening state of greatly exaggerated withdrawal symptoms (severe tachycardia, diaphoresis etc.) with confusion/disorientation and hallucinations that generally appears 72-96 hours after the last drink and lasts 2-3 days. Legend: Published MONTH, DAY, YEAR on www.thecalgaryguide.com Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications

Sustained Monomorphic Ventricular Tachycardia Pathogenesis

Sustained Monomorphic Ventricular Tachycardia: Pathogenesis Structural Heart Disease: (90% of cases) A ventricular scar forms (in the setting of coronary artery disease or cardiomyopathy) that cannot conduct electrical activity The scar is surrounded by a circular conduction pathway consisting of an ⍺- limb (slow conduction with a fast refractory period) and a β-limb (fast conduction but a slow refractory period) A correctly timed depolarization impulse arrives during the refractory period of the β-limb so it can only propagate through the ⍺-limb The β-limb’s refractory period ends just before the impulse leaves the ⍺-limb of the circular pathway Retrograde depolarization occurs into the ⍺ -limb, creating a self-sustaining closed- loop circuit within the ventricle “Re-entry” cause of tachyarrhythmia Idiopathic Causes: (10% of cases) Structurally normal heart on imaging Trigger(s) such as catecholamines ↑ cyclic adenosine monophosphate Intracellular calcium overload occurs in some ventricular myocytes ↑ Intracellular calcium activates sodium- calcium exchangers Sodium influx into the myocytes During normal myocyte repolarization, the net calcium-mediated depolarization reaches the myocyte threshold for an action potential A triggered action potential (termed a “delayed afterdepolarization”) repeatedly occurs within the ventricle “Triggered activity” cause of tachyarrhythmia Authors: Rahim Kanji Reviewers: Stephanie Happ, Raafi Ali, Derek Chew* * MD at time of publication Sustained Monomorphic Ventricular Tachycardia A wide QRS complex tachycardia originating from the ventricles lasting > 30 seconds. Common mechanisms include re-entry (e.g., scar-mediated) or a ventricular ectopic focus with increased automaticity. Refer to Sustained Monomorphic Ventricular Tachycardia: Clinical findings for details Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 22, 2023 on www.thecalgaryguide.com

Sustained Monomorphic Ventricular Tachycardia Clinical findings

Sustained Monomorphic Ventricular Tachycardia: Clinical findings Sustained Monomorphic Ventricular Tachycardia A wide QRS complex tachycardia originating from the ventricles lasting > 30 seconds. Common mechanisms include re-entry (e.g., scar-mediated) or a ventricular ectopic focus with increased automaticity. Refer to Sustained Monomorphic Ventricular Tachycardia: Pathogenesis slide for more details. Authors: Rahim Kanji Reviewers: Stephanie Happ, Raafi Ali, Derek Chew* * MD at time of publication The sinoatrial node continues to depolarize the atria while the ventricles depolarize independently and more rapidly Heart rate > 100 beats per minute The re-entrant circuit/ectopic focus uniformly and consistently depolarizes ventricular myocytes Occasionally, a sinoatrial impulse conducts to the ventricles Loss of coordination between the contractions of the atria and ventricles ECG Finding: AV Dissociation The impulse conducts normally through the His-Purkinje pathway and coincides with abnormal ventricular depolarization ECG Finding: Fusion beat Patient feels a forceful and rapid heart rate Palpitations Right atrium periodically contracts against a closed tricuspid valve Cannon A waves (intermittent irregular jugular venous pulsations with large amplitudes) ↓ Ventricular filling time ↓ Preload ↓ Stroke volume cardiac output Inadequate perfusion to organs ECG Finding: Uniform morphology of QRS complexes Direct myocyte-to- myocyte spread of the electrical impulse proceeds slower than an impulse conducted via the His-Purkinje pathway ECG Finding: Wide QRS complexes (≥ 120 milliseconds) The impulse conducts normally through the His-Purkinje pathway in between abnormal ventricular depolarizations ECG Finding: Capture beat Muscles and other organs General malaise Heart Chest pain Brain Presyncope/ syncope Inability to adequately respond to increased cardiac demand Shortness of breath Hemodynamic collapse Sudden cardiac arrest Death Hypotension Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 22, 2023 on www.thecalgaryguide.com

Limfoma Hodgkin: Patogenesis dan Temuan Klinis

Limfoma Hodgkin: Patogenesis dan Temuan Klinis

Statins Mechanisms and Side Effects

Statins: Mechanisms of action & side effects Authors: Rupali Manek, Julia Iftimie Reviewers: Gurreet Bhandal, Raafi Ali, Joshua Dian, Laura Byford-Richardson Samuel Fineblit*, Alexander Ah-Chi Leung* * MD at time of publication Competitive inhibitors of HMG-CoA reductase (rate-limiting enzyme in cholesterol synthesis) ↓ Coenzyme Q10 (ubiquinone) ↑ Mitochondrial superoxide ↓ Hepatic membrane stability ↓ Conversion of HMG-CoA to mevalonic acid ↑ Hepatic VLDL uptake ↓ Hepatic apolipoprotein B-100 secretion ↓ Oxidative phosphorylation Impaired mitochondrial function ↑ Liver enzyme leakage ↓ Mitochondrial ATP production ↑ Aminotransferases enzymes in liver ↑ Clearance of LDL cholesterol from bloodstream Myopathy/ myalgias (muscle aches) Hepatotoxicity ↓ Circulating LDL cholesterol ↓ LDL, ↑ HDL, ↓ TG ↓ Hepatic cholesterol synthesis ↓ VLDL synthesis ↑ Cell surface LDL receptor expression Statins First line therapy for treating hypercholesterolemia (↑ LDL cholesterol in blood) Common examples: rosuvastatin, atorvastatin, simvastatin, pravastatin, etc. ↑ Apolipoprotein AI production & ↑ hepatic HDL neogenesis ↓ TG ↑ HDL ↑ Vasodilation ↓ C-reactive protein ↓ Impacts of coagulation cascade ↓ Atherosclerosis (plaque along walls of blood vessels) ↓ Cardiovascular disease & mortality Pleotropic effects (i.e. non lipid related effects) Abbreviations: HMG-CoA – Hydroxymethylglutaryl-CoA LDL – Low-density lipoprotein VLDL – Very low density lipoprotein HDL – High density lipoprotein TG – Triglycerides Inhibition of synthesis of isoprenoid intermediates in the mevalonate pathway ↑ Nitric oxide activity ↓ Inflammation ↓ Tissue factor expression ↓ Macrophage proliferation ↓ Tissue factor (promotes macrophage mediated thrombus formation) ↑ Blood flow & endothelial function ↓ Thrombin generation ↓ Metalloproteinases expression ↑ Inhibition of metalloproteinase-1 ↓ Thrombogenicity (production of blood clot/thrombus) Plaque stabilization (↓ risk of atherosclerotic plaque rupture, myocardial infarction, and stroke) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Physiological Outcome Published July 9, 2017, updated Nov 6, 2023 on www.thecalgaryguide.com

Pharmacotherapy for Dyslipidemia Overview

Pharmacotherapy for Dyslipidemia: General overview Dyslipidemia Authors: Rupali Manek Reviewers: Gurreet Bhandal, Raafi Ali, Yan Yu*, Samuel Fineblit* *MD at time of publication Hypolipidemia (↓ HDL or ↓ apoB containing lipoproteins like LDL) Bile-acid sequestrants Bind bile acids in intestinal lumen to prevent reabsorption by enterohepatic (gut-liver) circulation ↑ Excretion of bile acids and cholesterol in stool ↓ LDL in blood Side effects: GI disturbances, commonly interact with other drugs by interfering with absorption See Calgary guide slide on “Bile-acid sequestrants: Mechanisms of action & side effects” for complete description of mechanism and side effects (clinical imbalance of lipids) Hypertriglyceridemia (if VLDL mediated & in need of treatment for pancreatitis prevention) Hypercholesteremia (↑ LDL in blood) Ezetimibe Inhibits cholesterol absorption via NPC1L1 transporter ↑ Hepatic (liver) LDL receptor expression ↑ LDL clearance from blood ↓ LDL in blood Avoid in pregnancy See Calgary guide slide on “Ezetimibe: Mechanisms of action & side effects” for complete description of mechanism and side effects Combined hyperlipidemia (↑ Triglycerides and ↑ cholesterol) Statins (ex. rosuvastatin, atorvastatin, simvastatin, pravastatin) Competitive inhibitors of HMG-CoA reductase (rate-limiting enzyme in cholesterol synthesis) Fibrates (ex. fenofibrate, gemfibrozil) Activate PPAR! (nuclear receptor) ↑ Lipolysis (breakdown of lipids) and free fatty acid oxidation ↓ Triglycerides in blood Side effects: GI discomfort, rash, pruritis Contraindicated in pregnancy, renal failure, liver & gallbladder disease See Calgary guide slide on “Fibrates: Mechanisms of action & side effects” for complete description of mechanism and side effects PCSK9 inhibitors (ex. evolocumab and alirocumab which are monoclonal antibodies) Inhibit PCSK9 (holds the LDL:LDL receptor complex together as it is internalized into the cell for destruction of LDL) LDL receptor returns to surface without being destroyed ↑ LDL receptor expression ↑ LDL clearance from blood ↓ LDL in blood See Calgary guide slide on “PCSK9 Inhibitors: Mechanisms of action & side effects” for complete description of mechanism and side effects ↓ Cholesterol synthesis in liver ↑ LDL receptor expression in liver LDL receptor recognizes apoB100 (structural protein on LDL) and apoE (structural protein found on chylomicron, VLDL, IDL) ↑ Clearance of LDL cholesterol from bloodstream ↓ LDL cholesterol in blood ↑ HDL in blood ↓ Triglycerides in blood ↓ Atherosclerosis (plaque along walls of blood vessels) Abbreviations: HDL – High density lipoprotein; HMG-CoA – Hydroxymethylglutaryl- CoA; LDL – Low-density lipoprotein; PCSK9 – Proprotein convertase subtilisin/kexin type 9; PPAR! – Peroxisome proliferator-activated receptor alpha; NPC1L1 – Niemann-Pick C1-Like 1; VLDL – Very low-density lipoprotein Side effects: Myalgias (muscular aches), rhabdomyolysis (muscle breakdown), transaminitis (liver inflammation), liver failure, ↑ risk of diabetes mellitus Contraindicated in pregnancy See Calgary guide slide on “Statins: Mechanisms of action & side effects” for complete description of mechanism and side effects Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Nov 6, 2023 on www.thecalgaryguide.com

Anesthetic Considerations for Obese Patients

Anesthetic Considerations In Patients With Obesity Pathophysiology Driving Anesthetic Management Goal Anesthetic Intervention Excess body fat in mouth and pharynx ↑ Total body fat & fat-free mass ↑ Mallampati score ↑ Neck circumference Loss of muscle tone in pharynx & tongue following neuromuscular blocking drugs Airway access difficulty & ↑ Intubation time ↑ Respiratory rate ↓ Time to desaturation Hypoventilation while supine ↓ Functional residual capacity ↑ Gastric aspiration risk ↑ Dosage requirements of lipophilic drugs ↑ Drug metabolism & clearance ↑ Energy cost of weight-bearing activity ↑ Basal metabolic rate ↓ Total respiratory compliance Excess weight compresses lungs Airway obstruction ↑ Oxygen required ↓ Functional residual capacity ↑ Work of breathing Secure a patent airway & avoid hypoxemia Optimize positioning Maintain oxygenation & lung protection Aspiration prophylaxis Achieve optimal anesthetic dosing for altered distribution Optimize anesthetic dosing for altered metabolism & clearance Intubate via endotracheal tube, avoid supraglottic airway device Consider video laryngoscopy Use head-elevated laryngoscopy positioning (“sniffing” position) Pre-oxygenate to ↑ oxygen reserve during intubation Avoid supine positioning, in place of alternate positioning (i.e., reverse trendelenburg) Lung-protective ventilation (↓ tidal volume, optimize oxygen levels, positive end expiratory pressure & recruitment maneuvers) Pre-operative fasting, gastric ultrasound to assess volume Rapid sequence induction to reduce aspiration risk Adjust drug dosages based on individual recommendations to account for altered distribution, metabolism & clearance Excess body fat on chest wall Excess intra- abdominal fat ↑ Gastric volume Excess body fat ↑ Circulating blood volume Obesity- related restrictive lung disease ↑ Load compressing chest wall BMI ≥30 kg/m2 Note: effects vary with the severity of obesity ↑ Pressure on diaphragm and lungs ↓ Outward chest wall force ↑ Abdominal pressure ↑ Fat acts as a reservoir for lipophilic drugs ↑ Fat storage in hepatocytes ↑ Cardiac output ↑ Pressure on gastric contents ↑ Distribution half-life of lipophilic drugs ↑ Volume of distribution for lipophilic drugs ↑ Hepatic cytochrome transcription ↑ Glomerular filtration rate and hepatic blood flow Authors: Brianna Rosgen Reviewers: Kayleigh Yang Ran Marissa Zhang Karl Darcus* * MD at time of publication Legend: Pathophysiology Mechanism Goal Anesthetic Intervention Published Nov 8, 2023 on www.thecalgaryguide.com

Overview of burns

Overview of Burns: Pathogenesis and Types Authors: Haley Shade, Amanda Eslinger* Reviewers: Christy Chong, Parker Lieb, Sunawer Aujla, Alexander Arnold*, Yan Yu*,Duncan Nickerson*, Donald McPhalen* Illustrator: Devjyoti Dutta* * MD at time of publication Contact Electrical Chemical Radiation (excluding sunburn) Less common Burns from any source can result in 3 damage zones Common Fire Scald Zone of coagulation: innermost zone; maximum damage through necrosis and irreversible tissue loss Zone of stasis: middle zone; decreased tissue perfusion, potentially salvageable Zone of hyperemia: outermost zone; tissue perfusion is increased, damage is reversible Epidermis, dermis, and subcutaneous tissue Full Thickness (3rd degree burn) Normal Skin Epidermis only Superficial Thickness (1st degree burn) Epidermis and superficial (papillary) dermis Superficial Partial Thickness (2nd degree burn) Epidermis and deep (reticular) dermis Deep Partial Thickness (2nd degree burn) Skin and deep tissues, muscle, fascia, nerves, blood vessels, bone Composite tissue injury (4th degree burn) Compartment syndrome Epidermal layer Dermal-Epidermal Junction Superficial (Papillary) Dermis Deep (Reticular) Dermis Note: The total burn surface area (TBSA) can be estimated using the rule of nines (1st degree burns are not included): Head and Neck: 9% total, Chest and Upper Back: 9% each, Arm: 9% each, Leg: 18% each (front and back), Abdomen and Lower Back: 9% each, Genital Area: 1% Refer to Complications of Burns Burn Shock Refer to Burn Shock: Pathogenesis, Complications, and Clinical Findings Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 8, 2023 on www.thecalgaryguide.com

Death Cardiovascular Respiratory and Neurologic Mechanisms

Death: Cardiovascular, Respiratory and Neurologic Mechanisms Mitochondria in tissues unable to utilize O2 Reduced hemoglobin in blood to carry O2 Low oxygen content in blood (CaO2) Hypoxemia (Type I Respiratory Failure): low dissolved oxygen in blood (PaO2) Lungs can’t oxygenate blood fast enough Lungs can’t rid blood of CO2 fast enough Hypercapnia / hypercarbia (Type II Respiratory Failure): elevated dissolved CO2 in blood (PaCO2) Cerebral vasodilation Toxins: e.g. cyanide, pesticides, arsenic Severe anemia Distributive problems: Systemic inflammation (sepsis, anaphylaxis, pancreatitis), adrenal insufficiency, vasodilatory drugs Obstructive problems: Cardiac tamponade*, tension pneumothorax* or massive pulmonary embolism* Hypovolemic* problems (low blood volume): Hemorrhage, dehydration, widespread skin disruption or burns Cardiac valve dysfunction Myocardial infarction* or cardiomyopathy Cardiac arrhythmia or heart block Disturbed electrical activity in cardiomyocytes Peripheral metabolic disturbances Hypokalemia*, Hyperkalemia* Acidosis* (including renal failure) Hypothermia* Toxins* (e.g. cocaine, beta blockers, tricyclics) Severe thyroid derangement Inappropriate systemic vasodilation Adjacent forces impair heart filling Low cardiac preload Low stroke volume (SV; depends on valves, contractility, preload) Decreased systemic vascular resistance (SVR) Low blood pressure (BP = CO x SVR) Decreased cardiac output (CO = SV x HR) Disseminated intravascular coagulationàwidespread thrombi that occlude blood flow (also causes hemorrhage, see relevant box at left) Methemoglobinemia: some hemoglobin gets stuck in a state that can’t carry O2 Hemoglobin has reduced capacity to carry or release O2 Drugs: e.g. dapsone, nitrates Carbon monoxide poisoning Circulatory collapse / shock: inadequate perfusion of tissue with blood Respiratory collapse: blood has insufficient useable O2 content Ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) Hypoxia*: inadequate O2 delivery or utilization in tissues Hypoxia creates metabolic disturbances that impair cardiac cells. Alternatively, any of the preceding conditions marked with (*) can directly trigger cardiac arrest first Pulseless Electrical Activity (PEA): organized activity on ECG with no cardiac output (can be preceded or mimicked by pseudo-PEA, in which there is still some output on ultrasound) Low atmospheric pressure or oxygen content Severe lung disease Asthma, COPD, interstitial lung disease, congestive heart failure, pulmonary hypertension, pulmonary embolism, lung collapse / atelectasis Acute respiratory distress syndrome Pneumonia, aspiration pneumonitis, inhalational injury, systemic inflammation, drowning Severe hypoventilation Respiratory fatigue, advanced COPD, chest wall disorders, neuromuscular disorders, upper airway obstruction, toxins (e.g. opioids, botulism) Can degenerate at any time Asystole: no cardiac electrical activity or output Death Respiratory arrest: cessation of breathing Inability to protect airway Decreased level of consciousness Note This is a broad overview of the many scenarios that can result in death. For detailed explanations of the various disease mechanisms, refer to the corresponding slides. * = reversible causes of cardiac arrest (Hs and Ts) Author: Ben Campbell Reviewers: Yan Yu* Huma Ali* * MD at time of publication Bradycardia (low heart rate, HR) Unopposed parasympathetic stimulation of heart (can also cause vasodilation, see Distributive problems) Disruption of spinal cord sympathetic control Injury to cervical or upper thoracic spinal cord Irreversible cessation of cardiac, respiratory, and brain function Prolonged seizure initially causes increased cardiovascular activity, until the system fatigues Disruption of respiratory control center in medulla Expanding skull contents squeeze brainstem (herniation) Increased intracranial pressure Edema from intracranial hemorrhage, trauma, brain mass Edema, inflammation, hypoxia and/or metabolic derangements cause diffuse neuron dysfunction Central nervous system infection Dementia, particularly with delirium Massive ischemic stroke Seizure activity prevents or alters breathing Metabolic disturbances that affect the central nervous system Hypoglycemia Hypocalcemia, hypercalcemia Hyponatremia, hypernatremia Uremia Acute liver failure (hyperNH4) Many drugs / toxins Withdrawal (e.g. EtOH) Status epilepticus Brainstem lesion (e.g. stroke, neoplasm, inflammatory) Nervous System Insult Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 11, 2023 on www.thecalgaryguide.com Respiratory System Insult Cardiovascular System Insult Cardiogenic problems

Turner Syndrome Pathogenesis and Clinical Findings

Turner Syndrome: Pathogenesis and clinical findings Author: Simran Pherwani Ashar Memon, Christy Chong Reviewers: Tara Shannon Simran Sandhu, Mao Ding Danielle Nelson* * MD at time of publication Non-disjunction in phenotypically female gametes (i.e. homologous X-chromosomes or sister chromatids fail to separate) Partial or complete absence of second sex chromosome, leaving only one normal X-chromosome Possible Chromosomal Profiles Other meiotic error → deletion or misdivision of X-chromosomal material Complete loss of one X- chromosome in all cells (45,X) (45%) Skeletal Abnormalities ↓ Expression of SHOX gene (present on X- and Y-chromosomes) ↓ Cellular proliferation in growth plates of bones in extremities during embryonic development Short stature High-arched palate Genu valgum (knock knees) Micrognathia (smaller lower jaw) Broad chest Cubitus valgus (forearm angled outward) Mosaicism (complete loss of one X-chromosome in some cells (e.g., 45,X/46,XXX, etc)) (50%) Congenital Heart Defects (most serious) Single copy of TIMP1 gene and presence of risk TIMP3 allele, and differential expression of KDM6A gene Bicuspid aortic valve Aortic coarctation Aortic dilation (worsened by hypertension) One X-chromosome and presence of Y-chromosomal material in some or all cells (e.g., 45,X/46,XY) Presence of an X- isochromosome (most commonly i(Xq)) Other structural abnormalities of X-chromsome (e.g., Ring Chromosome X, partial deletion of X, X or Y marker chromosome) Endocrine Disorders Turner Syndrome The most common sex chromosomal abnormality in females (affects 1/2000-3000) Results in deletion or non- functioning of one X chromosome Clinical presentations vary depending on chromosome profile Aortic dissection Renal disease Neurocognitive Deficits Mechanism unknown Deficit in social skills Specific (non-verbal) learning disorder (otherwise normal intelligence) ↓ Executive function skills ↓ Visuospatial skills ↓ Attention Accelerated follicular apoptosis (i.e., loss of oocytes from ovaries) → streak gonads Ovaries are unable to respond to high gonadotropins (FSH, LH) Hypergonadotropic hypogonadism Premature ovarian insufficiency ↓ Expression of immune- associated genes on X- chromosome ↑ Autoimmunity Autoimmune diseases (celiac, thyroiditis, IBD, metabolic abnormalities) ↓ Estrogen levels Lack of breast development ↑ Liver enzymes (Additional mechanisms likely) ↓ Bone mineral density Other Dysmorphic Features Lymphedema Webbed (buildup of lymph neck fluidàswelling) Primary amenorrhea Infertility Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 25, 2023 on www.thecalgaryguide.com

Non-Alcoholic Fatty Liver Disease

Non-Alcoholic Fatty Liver Disease: Pathogenesis and clinical findings Diagnosis of Metabolic Syndrome when ≥ 3 out of the 5 preceding risk factors are present Authors: Stephanie Happ Reviewers: Obesity Hypertension Diabetes Hypertriglyceridemia Hypercholesterolemia Iffat Naeem Sunawer Aujla Edwin Cheng* * MD at time of publication Insulin resistance develops in adipose tissue and hepatocytes ↓ Ability of insulin to suppress lipolysis of adipose tissue ↑ Delivery of free fatty acids from adipocytes to the liver ↑ De-novo lipogenesis in the liver Hepatic Steatosis: accumulation of fat in the liver (in the absence of alcohol consumption, termed Non-Alcoholic Fatty Liver (NAFL)) Steatohepatitis: chronic inflammatory and apoptotic climate in the hepatocytes (in the absence of alcohol consumption, termed Non-Alcoholic Steatohepatitis (NASH)) Fibrosis of the Liver: excessive scarring of liver tissue resulting from chronic inflammation, although liver architecture is largely intact Fat droplets form and grow in the hepatocytes Hepatic mitochondria increase their workload in attempt to break down the excess free fatty acids through beta-oxidation ↑ in cellular workload creates more reactive oxygen speciesà Inflammation and apoptosis of hepatocytes On-going inflammation damages hepatic stellate cells (the primary extracellular matrix–producing cells of the liver) causing the release of fibrinogenic cytokines Cirrhosis of the liver: normal lobular structure distorts and is replaced by regenerating nodules and bridging septa, disrupting normal liver blood flow Deposition of fibrotic material and collagen within the perisinusoidal spaces of the liver Decompensated Cirrhosis Hepatocellular carcinoma Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 25, 2023 on www.thecalgaryguide.com

Complication of MI - Acute Mitral Regurgitation

Complication of MI: Acute mitral regurgitation Authors: Victória Silva Reviewers: Juliette Hall, Raafi Ali *Angela Kealey * MD at time of publication S3 Indicates rapid overfilling of ventricle S1 S2 S3 Calcified plaque formation (atherosclerosis**) commonly in the posterior descending artery Plaque ruptures Exposed plaque contentsàPlatelet adhesion and aggregation Artery becomes partially or completely occluded Mitral Regurgitation** (Back flow of blood from left ventricle to left atrium during systole) ↑ Left atrial pressure Blood from left atrium backs up into pulmonary venous system ↑ Pulmonary venous pressure ↑ Hydrostatic pressure in alveolar capillaries ↑ Fluid leak from alveolar capillaries to interstitium (pulmonary edema**) ↓ Gas exchange Attempt at physiologic compensation à ↑ Respiratory rate Tachypnea Holosystolic murmur Heard loudest over the mitral valve (5th intercostal space, mid-clavicular line), with radiation to the axilla ↑ Volume of blood to left ventricle during diastole ↓ Blood supply to the portion of the ventricle that supports the papillary muscle à↓ Muscle movement Left ventricle dysfunction ↓ Blood supply to the posterior medial papillary muscle Cell death (myocardial infarction) Papillary muscle ischemia (muscle is intact but cannot contract) ↑ Blood in right atriumà↑ Blood in superior vena cava ↑ Blood in internal jugular vein ↑ Jugular venous pressure (JVP) Redistribution of interstitial fluid when lying flat (reduced effect of gravity) ↓ Forward blood flow from left ventricle to aorta ↓ Stroke volume (SV) ↓ Cardiac output (CO) CO = SV x HR (heart rate) Sympathetic nervous system attempts to physiologically compensate ↑ Heart rate Tachycardia ↓ Blood pressure (BP) because BP = CO X SVR (systemic vascular resistance) Cardiogenic shock** Papillary muscle rupture Papillary muscle unable to provide adequate tension on mitral valve Mitral valve unable to stay closed during systole Orthopnea Difficulty breathing Dyspnea Paroxysmal nocturnal dyspnea **See corresponding Calgary Guide slides for more details Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 25, 2023 on www.thecalgaryguide.com

RICE mechanism of action

Rest, Ice, Compression, Elevation (RICE): Mechanism of action Healing of an injury requires pain and inflammatory control to encourage activity. The goal of Rest, Ice, Compression, Elevation (RICE) is to decrease inflammation. Though activity itself will contribute to pain and inflammation, it is integral to the rehabilitation process. Authors: Matthew Roberts Emma Windfeld Reviewers: Alexander Arnold Amanda Eslinger Shyla Bharadia Mao Ding Bradley Jacobs* * MD at time of publication Rest: (weight bearing or stressful motion discontinued) Further damage to affected tissues from mechanical stress is prevented Ice: (applied to injury) Compression: (wrap applied to injured area) Mechanical force applied to tissue Excess fluid is pushed back into capillaries and lymph network Elevation: (limb raised above heart) Blood flow to tissue is constricted Mechanism not well understood ↓ delivery of inflammatory mediators such as polymorphonuclear neutrophils and macrophages to injured site ↓ production of inflammatory cytokines (pro-inflammatory substances) such as Tumor Necrosis Factor-α, Platelet Derived Growth Factor, Epidermal Growth Factor, and Transforming Growth Factor-β ↓ Inflammation Gravity ↑ venous blood return to systemic circulation ↓ edema (accumulation of fluid in interstitium) Early initiation of injury-specific rehabilitative exercises improves range of motion, strength, and proprioception Stress to targeted area induces inflammation that, when tightly regulated, is integral to repair Injured muscle, tendon, bone, or ligament is strengthened ↓ Pain ↑Range of motion and therefore function Early recovery from injury Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Dec 9, 2013, updated Oct 15, 2023 on www.thecalgaryguide.com Rest, Ice, Compression, Elevation (RICE): Mechanism of action Healing of an injury requires pain and inflammatory control to encourage activity. The goal of Rest, Ice, Compression, Elevation (RICE) is to decrease inflammation. Though activity itself will contribute to pain and inflammation, it is integral to the rehabilitation process. Authors: Matthew Roberts Emma Windfeld Reviewers: Alexander Arnold Amanda Eslinger Shyla Bharadia Bradley Jacobs* * MD at time of publication Rest: (weight bearing or stressful motion discontinued) Further damage to affected tissues from mechanical stress is prevented Ice: (applied to injury) Compression: (wrap applied to injured area) Mechanical force applied to tissue Excess fluid is pushed back into capillaries and lymph network Elevation: (limb raised above heart) Gravity ↑ venous blood return to systemic circulation Blood flow to tissue is constricted ↓ delivery of inflammatory mediators such as polymorphonuclear neutrophils and macrophages to injured site Mechanism not well understood ↓ production of inflammatory cytokines (pro- inflammatory substances) such as Tumor Necorsis Factor-α, Platelet Derived Growth Factor, Epidermal Growth Factor, and Transforming Growth Factor-β ↓ Inflammation ↓ Pain ↓ edema (accumulation of fluid in interstitium) ↑Range of motion and therefore function Early initiation of injury- specific rehabilitative exercises improves range of motion, strength, and proprioception Stress to targeted area induces inflammation that, when tightly regulated, is integral to repair Injured muscle, tendon, bone, or ligament is strengthened Early recovery from injury Legend: Published MONTH, DAY, YEAR on www.thecalgaryguide.com Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications RICE: Mechanism of action Authors: Matthew Roberts Emma Windfeld Reviewers: Alexander Arnold Amanda Eslinger Shyla Bharadia Bradley Jacobs* * MD at time of publication Rest (weight bearing or stressful motion discontinued) Ice (applied to injury) Compression (wrap applied to injured area) Elevation (limb raised above heart) Constricts blood flow to tissue Mechanism not well understood Mechanical force applied to tissue ↓ Delivery of polymorphonuclear neutrophils and macrophages to injured site Excess fluid pushed back into capillaries and lymph network Gravity ↑ venous blood return to systemic circulation Prevents further damage to affected tissues from mechanical stress ↓ Production of inflammatory cytokines ↓ Edema (accumulation of fluid in interstitium) ↓ Inflammation ↓ Pain ↑Range of motion and therefore function Early initiation of injury-specific rehabilitative exercises to improve range of motion, strength, and proprioception Stress to targeted area induces inflammation that, when tightly regulated, is integral to repair Injured muscle, tendon, bone, or ligament is strengthened Early recovery from injury Legend: Published MONTH, DAY, YEAR on www.thecalgaryguide.com Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications

Mechanical Ventilation mechanisms of action and complications

Mechanical Ventilation: Mechanisms of Action and Complications Authors: Madison Amyotte Reviewers: Victória Silva, Mao Ding Eric Leung* * MD at time of publication Mechanical ventilation is a form of life support that helps a patient breathe (ventilate) when they cannot breathe on their own. Invasive: Delivery of positive pressure to the lungs via endotracheal or tracheostomy tube Mechanical ventilation Pressure support ventilation (PSV): Set inspiratory pressure & flow. Patient initiates all breaths unassisted Non-invasive: Delivery of oxygen into the lungs via positive pressure through the mouth No endotracheal or tracheostomy tube Assist/control ventilation (AC): Set respiratory rate & tidal volume (amount of air delivered to the lungs with each breath). Patient can trigger additional assisted breaths Synchronized intermittent mandatory ventilation (SIMV): Set tidal volume & respiratory rate. Patient can trigger additional unassisted breaths 02 mask delivery Continuous positive airway pressure (CPAP) Provides continuous positive ventilatory pressure Bilevel positive airway pressure (BIPAP) Provides positive pressure with two different pressure levels for inhalation and exhalation ↑ Swallow non- inspiratory flow Aspiration Acute rise in airway pressure Barotrauma Patient- triggered breath Ventilator senses negative pressure from inflation of the lungs Time-triggered breath Respiratory rate set at x breaths per min Patient-triggered breath Ventilator senses negative pressure from inflation of the lungs Tidal volume determined by patient’s strength & lung compliance Time-triggered breath Respiratory rate set at x breaths per min Delivery of set tidal volume, inspiratory flow rate & pattern Complete patient- triggered breaths Ventilator senses negative pressure from inflation of the lungs Breathes assisted by set inspiratory pressure Inspiratory flow drops below set inhalational negative pressure threshold Pressure support terminates as exhalation cycle begins Combined with SIMV Inspiratory pressure added to patient triggered breaths Patient can overcome resistance of the endotracheal tube or ↑ volume of spontaneous breathes Delivery of set tidal volume, inspiratory flow rate & pattern Airways remain open & clear of obstruction Forced air into nasal passages Nose bleeds (epistaxis) Maximum tidal volume reached Exhale valve opens Patient exhales actively or passively until set end expiratory pressure in the lungs is reached (PEEP) to prevent alveolar collapse Patient exhales until PEEP reached Patient achieves optimal ventilation throughout respiratory cycles Mouth breathing Dry mouth (xerostomia) Increased work of breathing & muscle fatigue Prolonged weaning & extubation Breath stacking ↑ Volume and pressure in lungs Lung tissue injury (barotrauma) Microorganisms colonize artificial airway Ventilator associated pneumonia if ventilation >48 hrs Tachypnea ↓ CO2in circulation Respiratory alkalosis Legend: Pathophysiology Mechanism Sign/symptom/lab finding Complications Published Nov 25, 2023 on www.thecalgaryguide.com

Acute Respiratory Distress Syndrome ARDS CXR findings

Acute Respiratory Distress Syndrome (ARDS): Chest X-Ray Findings Author: Iffat Naeem Direct or indirect lung injury causing acute respiratory distress syndrome (see Acute Respiratory Distress Syndrome slide for pathogenesis and clinical findings) Activation of dysregulated inflammatory cascade Absent pleural effusion Normal heart size Absent Kerly B lines No perihilar infiltrate pattern Bilateral infiltrate that can present in all regions of lung Air bronchograms Silhouette sign Reviewers: Victória Silva, Mao Ding Tara Lohmann* *MD at the time of publication Edema not due to a cardiogenic cause Damage to alveolar epithelium Necrosis of epithelial cells Erosion of alveolar basement membrane ↑ Alveolar epithelium permeability Damage to lung capillary endothelium Release of inflammatory cytokines Neutrophils migrate into alveoli Fluid-filled alveoli show as white/grey opacities Air-filled bronchi appear dark when surrounded by grey/white opacification of fluid-filled alveoli Increased opacification from fluid-filled alveoli results in lack of differentiation of heart borders Diffuse and widespread damage to alveoli and interstitium that show as white/grey opacities ↑ Capillary endothelium permeability Alveolar edema Degradation of alveolar- capillary barrier Proliferative phase Alveolar epithelium attempts to recover Chronic phase Can either resolve or progress to fibrotic thickening and scaring of alveoli ↑ Leakage of fluid from capillaries into alveoli and lung interstitium Pulmonary fibrosis (scarring) ‘White lung’ appearance Image credit: Radiopaedia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 25, 2023 on www.thecalgaryguide.com Acute Respiratory Distress Syndrome (ARDS): Chest X-Ray Findings Direct or indirect lung injury causing acute Author: Iffat Naeem Reviewers: Victória Silva respiratory distress syndrome* Activation of dysregulated inflammatory cascade Bilateral infiltrate that show as white/grey can present in Damage to alveolar epithelium Necrosis of epithelial cells Erosion of alveolar basement membrane ↑ Alveolar epithelium permeability Damage to lung capillary endothelium Fluid-filled alveoli opacities Air-filled bronchi appear dark when surrounded by grey/white opacification of fluid-filled alveoli Increased opacification from fluid-filled alveoli results in lack of differentiation of heart borders Diffuse and all regions of lung Release of inflammatory cytokines Neutrophils migrate into alveoli Alveolar edema Air bronchograms ↑ Capillary endothelium permeability Degradation of alveolar-capillary barrier Proliferative phase Alveolar epithelium attempts to recover Chronic phase Can either resolve or progress to fibrotic thickening and scaring of alveoli ↑ Leakage of fluid from capillaries into alveoli and lung interstitium Silhouette Sign widespread Pulmonary damage to alveoli ‘White lung’ appearance fibrosis (scarring) and interstitium that show as white/grey opacities *See corresponding Calgary Guide slides for more details Image credit: Radiopaedia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published X, 2023 on www.thecalgaryguide.com Acute Respiratory Distress Syndrome (ARDS): Chest X-Ray Findings Direct or indirect lung injury causing acute respiratory Author: Iffat Naeem Reviewers: Victória Silva distress syndrome* Activation of dysregulated inflammatory cascade Bilateral infiltrate that show as white/grey can present in Damage to alveolar epithelium Necrosis of epithelial cells Denudation of alveolar basement membrane ↑ epithelium permeability Degradation of alveolar-capillary barrier Alveolar epithelium attempts to recover through (proliferative phase) Damage to lung capillary endothelium Fluid-filled alveoli opacities Air-filled bronchi appear dark when surrounded by grey/white opacification of fluid-filled alveoli Increased opacification from fluid-filled alveoli results in lack of differentiation of heart borders Diffuse and all regions of lung Air bronchograms Release of proinflamm atory cytokines Neutrophil migration into airspace Alveolar Edema ↑ capillary endothelium permeability ↑ leakage of fluid from vasculature into airspace and lung interstitium Can either resolve or progress to fibrotic Silhouette Sign widespread Pulmonary damage to alveoli ‘White lung’ appearance thickening and scaring of Fibrosis alveoli (chronic phase) and interstitium that show as white/grey opacities Image credit: Radiopaedia *See corresponding Calgary Guide slides for more details Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published X, 2023 on www.thecalgaryguide.com Acute Respiratory Distress Syndrome (ARDS): Chest X-Ray Findings Absent pleural effusion Normal heart size Absent Kerly B lines No perihilar infiltrate pattern Author: Iffat Naeem Reviewers: Victória Silva Acute Lung Injury (see ‘ARDS: Pathogenesis and Clinical findings’ slide) causing impaired oxygenation Lung injury not due to cardiogenic cause (see ‘ARDS: Pathogenesis and Clinical findings’ slide) Alveolar endothelium damage promotes inflammatory marker release Exudative phase (1-6 days): neutrophils adhere to damaged endothelium and release pro- inflammatory mediators Accumulation of intra-alveolar fluid that is rich in neutrophils, macrophages, and red blood cells Proliferative phase (7-14 days): proliferation of alveolar epithelial Fibroblasts deposit collagen tissue in alveolar walls and spaces Can either resolve or progress to fibrotic thickening and scaring Alveolar Edema Fluid-filled alveoli show as white/grey opacities Air-filled bronchi appear dark when surrounded by grey/white opacification of fluid-filled alveoli Increased opacification from fluid-filled alveoli Bilateral infiltrate present in all regions Air bronchograms results in lack of Silhouette Sign differentiation of heart borders Diffuse alveolar damage ‘White lung’ appearance Image credit: Radiopaedia *See corresponding Calgary Guide slides for more details Legend: (chronic phase) Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published X, 2023 on www.thecalgaryguide.com Lung injury not due to a cardiogenic cause Absent pleural effusion Normal heart size Absent Kerly B lines No perihilar infiltrate pattern Acute Respiratory Distress Syndrome (ARDS): Chest X-Ray Findings

Leukemia Mieloid Kronis Patogenesis dan Presentasi Klinis

Leukemia Mieloid Kronis (CML): Patogenesis dan Presentasi Klinis

Leukemia Limfoblastik Akut Patogenesis dan Temuan Klinis

Leukemia Limfoblastik Akut (LLA): Patogenesis dan Temuan Klinis

Leukemia Limfositik Kronis Patogenesis dan Temuan Klinis

Leukemia Limfositik Kronis: Patogenesis dan Temuan Klinis

COPD - بیماریزایی

COPD - بیماریزایی

COPD - یافتھ ھای بالینی

COPD - یافتھ ھای بالینی

COPD - یافتھ ھای تشخیصی

COPD - یافتھ ھای تشخیصی

COPD - عوارض و عواقب

COPD - عوارض و عواقب

Common Reversible Causes of Cardiac Arrest Hs

Common Reversible Causes of Cardiac Arrest (H’s)

Anesthetic Considerations One Lung Ventilation

Anesthetic Considerations: One-lung ventilation Mechanical separation of the lungs to allow for individualized ventilation of only one lung Positioning: Lateral decubitus position (patient on their side) with dependent lung ventilated Shunt: Non- dependent lung unventilated Perfusion but no ventilation to collapsed lung Hypoxic vasoconstriction decreases but does not stop perfusion to non- dependent lung Right to left intrapulmonary shunt with some perfusion to non- dependent lung V/Q mismatch causes ↑ hypoxemia Increase FiO2 to 1 to maintain SpO2 ≥ 90% Increased FiO2 can allow for toleration of shunt Optimize cardiac output and shunt fraction to maximize PaO2 Author: Aly Valji Reviewers: Jasleen Brar Ryden Armstrong* * MD at time of publication Relative indications Surgical exposure for pulmonary resection, mediastinal, esophageal, vascular, thoracic spine, or cardiac valve surgery Double lumen tube (gold standard) Endotracheal tube (ETT) with two lumens (bronchial and tracheal) Insert longer side to a mainstem bronchus, shorter side ends in distal trachea Absolute Indications Isolation of healthy from contaminated lung (unilateral infection, hemorrhage) Control unilateral disruption of ventilation (bronchopleural fistula, unilateral bullae) Video assisted thoracoscopic surgery Unilateral lung lavage Airway Technique Anesthetic Technique General anesthetic with neuromuscular blockade ↓ Inspiratory muscle tone Intraabdominal contents push up on diaphragm ↓ Functional residual capacity (FRC) ↑ Atelectasis if closing capacity > FRC ↑ Hypoxemia Optimize Altered gravitational forces on thorax ↓ Compliance of dependent lung ↑ Airway pressure required ↑ Risk of lung barotrauma due to ↑ pressure ↑ Perfusion to dependent lung. ↑ Ventilation to nondependent lung (prior to lung isolation) Collapse of nondependent lung using lung isolation causes ↓ ventilation to this lung Optimize tidal volume (6-8 mL/kg), respiratory rate (maintain PaCO2 35-40 mmHg), PEEP (5-10 cm H2O) based on clinical picture Univent tube Single lumen ETT with movable endobronchial blocker in wall Blocker steered after intubation into a mainstem bronchus with fiberoptic bronchoscope Endotracheal tube in mainstem bronchus Single lumen ETT pushed into a mainstem bronchus Bronchial blocker Shaft with an inflatable balloon on distal end Inserted through single lumen ETT into a mainstem bronchus, after intubation positive end- expiratory pressure (PEEP) of 5-10 cm H2O Recruitment of dependent, atelectatic lung with positive pressure Optimize FiO2 ↓ Absorptive atelectasis (from ↑ partial pressure O2 and ↓ N2) Cuff inflated in a mainstem bronchus to isolate respective lung. Placement should be verified using fiberoptic bronchoscope if possible after positioning ↓ Atelectasis and ↑ FRC ↓ Hypoxemia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Management Published December 5, 2023 on www.thecalgaryguide.com Anesthetic Considerations: One-lung ventilation Mechanical separation of the lungs to allow for individualized ventilation of only one lung Positioning: Lateral decubitus position (patient on their side) with dependent lung ventilated Shunt: Non- dependent lung unventilated Perfusion but no ventilation to collapsed lung Hypoxic vasoconstriction decreases but does not stop perfusion to non- dependent lung Right to left intrapulmonary shunt with some perfusion to non- dependent lung V/Q mismatch from shunt causes ↑ hypoxemia Increase FiO2 to 1 to maintain SpO2 ≥ 90% Vasodilation of dependent lung vasculature to compensate for shunt to non- dependent lung ↓ V/Q mismatch Author: Aly Valji Reviewers: Jasleen Brar Dr. Armstrong* * MD at time of publication Relative indications Surgical exposure for pulmonary resection, mediastinal, esophageal, vascular, thoracic spine, or cardiac valve surgery Double lumen tube (DLT) Two endotracheal tubes (ETT) bonded together Insert longer side to a mainstem bronchus, shorter side ends in distal trachea Absolute Indications Isolation of healthy from contaminated lung (unilateral infection, hemorrhage) Control unilateral disruption of ventilation (bronchopleural fistula, unilateral bullae) Video assisted thoracoscopic surgery Unilateral lung lavage Airway Technique Anesthetic Technique General anesthetic with neuromuscular blockade ↓ Inspiratory muscle tone Intraabdominal contents push up on diaphragm ↓ Functional residual capacity (FRC) ↑ Atelectasis if closing capacity > FRC ↑ Hypoxemia Optimize Altered gravitational forces on thorax ↑ Elastance of dependent lung ↑ Airway pressure required ↑ Risk of lung barotrauma due to ↑ pressure ↑ Perfusion to dependent, ventilated lung ↓ Ventilation- perfusion (V/Q) mismatch ↓ Hypoxemia Optimize tidal volume (6-8 mL/kg), respiratory rate (maintain PaCO2 35-40 mmHg), PEEP (5-10 cm H2O) based on clinical picture Univent tube Single lumen ETT with movable endobronchial blocker in wall Blocker steered after intubation into a mainstem bronchus with fiberoptic bronchoscope Endotracheal tube in mainstem bronchus Single lumen ETT pushed into a mainstem bronchus Bronchial blocker Shaft with an inflatable balloon on distal end Inserted through single lumen ETT into a mainstem bronchus, after intubation positive end- expiratory pressure (PEEP) of 5-10 cm H2O Recruitment of dependent, atelectatic lung with positive pressure Optimize FiO 2 ↓ Absorptive atelectasis (from ↑ partial pressure O2 and ↓ N2) Cuff inflated in a mainstem bronchus to isolate respective lung. Placement should be verified using fiberoptic bronchoscope if possible after positioning ↓ Atelectasis and ↑ FRC ↓ Hypoxemia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Management Published MONTH, DAY, YEAR on www.thecalgaryguide.com Anesthetic Considerations: One-lung ventilation Mechanical separation of the lungs to allow for individualized ventilation of only one lung Author: Aly Valji Reviewers: Jasleen Brar Name* * MD at time of publication Non-dependent lung unventilated Hypoxic vasoconstriction decreases but does not stop perfusion to non- dependent lung Right to left intrapulmonary shunt with some perfusion to non- dependent lung V/Q mismatch from shunt causes ↑ hypoxemia Increase FiO2 to maintain SpO2 ≥ 90% Vasodilation of dependent lung vasculature to compensate for shunt to non- dependent lung Positioning: Lateral decubitus position (patient on their side) with dependent lung ventilated Indications Anesthetic General anesthetic with neuromuscular blockade ↓ Inspiratory muscle tone Relative indications Surgical exposure for pulmonary resection, mediastinal, esophageal, vascular, thoracic spine surgery Absolute Indications Isolation of healthy from contaminated lung (Unilateral infection or hemorrhage) Control unilateral disruption of ventilation (Bronchopleural fistula, unilateral bullae) Video assisted thoracoscopic surgery Unilateral lung lavage Intraabdominal contents push up on diaphragm ↓ FRC ↑ Atelectasis if closing capacity > FRC ↑ Hypoxemia Altered gravitational forces on thorax Shaft with an inflatable balloon on distal end. Inserted through a single lumen ETT after intubation into a mainstem bronchi Single lumen ETT pushed into a mainstem bronchus Optimize positive end-expiratory pressure (PEEP)) Recruitment of dependent, atelectatic lung with positive pressure ↑ Elastance of dependent lung ↑ Airway pressure required ↑ Risk of lung barotrauma due to ↑ pressure ↑ Perfusion to dependent, ventilated lung ↓ Ventilation- perfusion (V/Q) mismatch ↓ Hypoxemia Optimize tidal volume, respiratory rate, PEEP based on clinical picture Bronchial blocker Endotracheal tube in mainstem bronchus Technique Univent tube Double lumen tube (DLT) Optimize FiO2 ↓ Absorptive atelectasis (from ↑ partial pressure O2 and ↓ N2) Single lumen ETT with movable endobronchial blocker housed in wall of ETT. Blocker maneuvered after intubation into a mainstem bronchus Two endotracheal tubes (ETT) bonded together. Longer side goes into a mainstem bronchus, shorter side ends in distal trachea ↓ Atelectasis and ↑ FRC ↓ V/Q mismatch Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complication/Intervention Published MONTH, DAY, YEAR on www.thecalgaryguide.com Anesthetic Considerations: One-lung ventilation Mechanical separation of the lungs to allow for individualized ventilation of only one lung Author: Aly Valji Reviewers: Jasleen Brar Name* * MD at time of publication Non-dependent lung unventilated Hypoxic vasoconstriction decreases but does not stop perfusion to non- dependent lung Right to left intrapulmonary shunt with some perfusion to non- dependent lung V/Q mismatch from shunt causes ↑ hypoxemia Increase FiO to 2 maintain SpO2 ≥ 90% Vasodilation of dependent lung vasculature to compensate for shunt to non- dependent lung ↓ V/Q mismatch Positioning: Lateral decubitus position (patient on their side) with dependent lung ventilated Indications Anesthetic General anesthetic with neuromuscular blockade ↓ Inspiratory muscle tone Comorbidity: Likely underlying pulmonary disease Pre-operative evaluation Pulmonary function testing Overall clinical picture, forced expiratory volume (FEV1), and diffusion capacity (DLCO) Multidisciplinary determination of fitness for surgery Pulmonary hemorrhage Whole lung lavage Unilateral infection Bronchopleural fistula Isolation of affected lung from unaffected lung Pulmonary resection Mediastinal, esophageal, vascular, thoracic spine, or cardiac valve surgery Operative lung deflated to expose surgical site Intraabdominal contents push up on diaphragm ↓ FRC ↑ Atelectasis if closing capacity > FRC ↑ Hypoxemia Optimize positive Altered gravitational forces on thorax Contraindications ↑ Elastance of dependent lung ↑ Airway pressure required ↑ Risk of lung barotrauma due to ↑ pressure ↑ Perfusion to dependent, ventilated lung ↓ Ventilation- perfusion (V/Q) mismatch ↓ Hypoxemia Optimize tidal volume, respiratory rate, PEEP based on clinical picture Bilateral lung ventilation dependency Hemodynamic instability Severe hypoxia Severe COPD Severe pulmonary hypertension Potentially unable to tolerate one lung ventilation Intraluminal airway obstruction/mass Known difficult airway Risk of dislodging mass and inability to secure airway Pursue more advanced airway techniques end-expiratory pressure (PEEP) Recruitment of dependent, atelectatic lung with positive pressure Optimize FiO2 ↓ Absorptive atelectasis (from ↑ partial pressure O and ↓ N ) 2 2 ↓ Atelectasis and ↑ FRC Post-operative pain management Thoracotomy or VATS procedure causing ↑ pain along thoracic dermatomes Epidural Paravertebral block Anesthetic injected into epidural space Anesthetic injected into paravertebral spaces Bilateral spinal nerve blockade below desired spinal level Ipsilateral spinal nerve and sympathetic chain blockade in thoracic dermatomes Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complication/Intervention Published MONTH, DAY, YEAR on www.thecalgaryguide.com Anesthetic Considerations: One-lung ventilation Mechanical separation of the lungs to allow for individualized ventilation of only one lung Author: Aly Valji Reviewers: Jasleen Brar Name* * MD at time of publication Non-dependent lung unventilated Hypoxic vasoconstriction decreases but does not stop perfusion to non- dependent lung Right to left intrapulmonary shunt with some perfusion to non- dependent lung V/Q mismatch from shunt causes ↑ hypoxemia Increase FiO2 to maintain SpO2 ≥ 90% Vasodilation of dependent lung vasculature to compensate for shunt to non- dependent lung ↓ V/Q mismatch Indications Anesthetic General anesthetic with neuromuscular blockade ↓ Inspiratory muscle tone Comorbidity: Likely underlying pulmonary disease Pre-operative evaluation Pulmonary function testing Overall clinical picture, forced expiratory volume (FEV1), and diffusion capacity (DLCO) Multidisciplinary determination of fitness for surgery Anesthetic injected into epidural space Anesthetic injected into paravertebral spaces Positioning: Lateral decubitus position (patient on their side) with dependent lung ventilated Pulmonary hemorrhage Whole lung lavage Unilateral infection Bronchopleural fistula Isolation of affected lung and unaffected lung Pulmonary resection Mediastinal, esophageal, vascular, thoracic spine, or cardiac valve surgery Operative lung deflated to expose surgical site Intraabdominal contents push up on diaphragm ↓ FRC ↑ Atelectasis ↑ Hypoxemia Optimize positive end- expiratory pressure (PEEP) Recruitment of dependent, atelectatic lung with positive pressure ↓ Atelectasis and ↑ FRC Altered gravitational forces on thorax Contraindications ↑ Elastance of dependent lung ↑ Airway pressure required ↑ Risk of lung barotrauma due to ↑ pressure Optimize tidal volume, respiratory rate, PEEP based on clinical picture ↑ Perfusion to dependent, ventilated lung ↓ Ventilation- perfusion (V/Q) mismatch ↓ Hypoxemia Bilateral lung ventilation dependency Hemodynamically unstable Severe hypoxia Severe COPD Severe pulmonary hypertension Unable to tolerate one lung ventilation Intraluminal airway obstruction/mass Known difficult airway Risk of dislodging mass and inability to secure airway Pursue more advanced airway techniques Post-operative pain management Thoracotomy or VATS procedure causing ↑ pain along thoracic dermatomes Epidural Paravertebral block Bilateral spinal nerve blockade below desired spinal level Ipsilateral spinal nerve and sympathetic chain blockade in thoracic dermatomes Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complication/Intervention Published MONTH, DAY, YEAR on www.thecalgaryguide.com Anesthetic Considerations: One-lung ventilation Mechanical separation of the lungs to allow for individualized ventilation of only one lung Author: Aly Valji Reviewers: Name* * MD at time of publication Indication Contraindications Comorbidity: Likely underlying pulmonary disease Positioning: Lateral decubitus position (patient on their side) with dependent lung ventilated General anesthetic with neuromuscular blockade Post-operative pain management Pulmonary resection, mediastinal, esophageal, vascular, thoracic spine, or cardiac valve surgery Pulmonary hemorrhage, whole lung lavage, bronchopleural fistula, or unilateral infection Operative lung deflated to expose surgical site Isolation of affected lung and unaffected lung Dependency on bilateral lung ventilation, hemodynamically unstable, severe hypoxia, severe COPD, or severe pulmonary hypertension Unable to tolerate one lung ventilation Intraluminal airway obstruction/mass or known difficult Pursue more advanced Risk of dislodging mass and inability to secure airway Multidisciplinary determination of fitness for surgery airway Pulmonary function testing Hypoxic vasoconstriction decreases but does not stop perfusion to non- dependent lung airway techniques Overall clinical picture, forced expiratory volume (FEV1), and diffusion capacity (DLCO) Pre-operative evaluation Non- dependent lung not ventilated Altered gravitational forces on thorax Intraabdominal contents push up on diaphragm ↓ Inspiratory muscle tone Likely procedure is thoracotomy or VATS causing ↑ pain along thoracic dermatomes Right to left intrapulmonary shunt with some perfusion to non- dependent lung still present V/Q mismatch from shunt causes ↑ hypoxemia Increase FiO2 to maintain SpO2 ≥ 90% Vasodilation of dependent lung vasculature to compensate for shunt to non- dependent lung ↓ V/Q mismatch ↓ Hypoxemia Intervention: Optimize tidal volume, respiratory rate, PEEP based on clinical picture ↓ Atelectasis and ↑ FRC ↑ Perfusion to dependent, ventilated lung ↑ Elastance of dependent lung ↓ FRC ↓ Functional residual capacity (FRC) ↓ Ventilation-perfusion (V/Q) mismatch ↑ Airway pressure required ↑ Atelectasis ↑ Hypoxemia ↑ Risk of lung barotrauma due to ↑ pressure Intervention: Optimize positive end-expiratory pressure (PEEP) Recruitment of dependent, atelectatic lung with positive pressure Epidural Paravertebral block Anesthetic injected into epidural space Bilateral spinal nerve blockade below desired spinal level Anesthetic injected into Ipsilateral spinal nerve and sympathetic chain blockade in thoracic paravertebral spaces dermatomes Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complication/Intervention Published MONTH, DAY, YEAR on www.thecalgaryguide.com Anesthetic Considerations: One-lung ventilation Author: Aly Valji Reviewers: Name* * MD at time of publication One lung ventilation: mechanical separation of the lungs to allow for individualized ventilation of only one lung Indication Pulmonary resection, mediastinal, esophageal, vascular, thoracic spine, or cardiac valve surgery Pulmonary hemorrhage, whole lung lavage, bronchopleural fistula, or unilateral infection Exposure of surgical site by deflation of operative lung Isolation of affected lung and unaffected lung Dependency on bilateral lung ventilation, Contraindications hemodynamically unstable, severe hypoxia, severe COPD, or severe pulmonary hypertension Intraluminal airway obstruction/mass or known difficult airway Pursue more advanced airway techniques Unable to tolerate one lung ventilation Risk of dislodging mass and inability to secure airway Likely underlying Pre-operative Pulmonary pulmonary disease evaluation function testing Overall clinical picture, forced expiratory Determination of volume (FEV1), and diffusion capacity (DLCO) fitness for surgery Right to left intrapulmonary shunt as some perfusion to non- dependent lung is still present ↑ Perfusion to dependent, ventilated lung ↑ Elastance of dependent lung ↓ FRC Non- dependent lung not ventilated Hypoxic vasoconstriction decreases but does not stop perfusion to non- dependent lung V/Q mismatch from shunt increases hypoxemia Intervention: Increase FiO2 to maintain SpO2 ≥ 90% Vasodilation of dependent lung vasculature to compensate for non-dependent lung ↓ V/Q mismatch ↓ Hypoxemia Intervention: Optimize tidal volume, respiratory rate, PEEP ↓ Atelectasis and ↑ FRC Positioning: Lateral position with dependent lung ventilated Altered gravitational forces on thorax ↓ Ventilation-perfusion (V/Q) mismatch General anesthetic with neuromuscular blockade Intraabdominal contents push up on diaphragm ↑ Airway pressure required ↑ Atelectasis ↑ Hypoxemia ↑ Risk of lung barotrauma Intervention: Optimize positive end-expiratory pressure (PEEP) Recruitment of dependent, atelectatic lung from PEEP ↓ Inspiratory muscle tone ↓ Functional residual capacity (FRC) Post- operative pain management Thoracotomy or VATS causes pain along thoracic dermatomes Epidural Paravertebral block Bilateral spinal nerve blockade below desired Anesthetic injected into epidural space spinal level Anesthetic injected into Ipsilateral spinal nerve and sympathetic chain blockade in paravertebral spaces thoracic dermatomes Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complication/Intervention Published MONTH, DAY, YEAR on www.thecalgaryguide.com Anesthetic considerations: one-lung ventilation Author: Aly Valji Reviewers: Name* * MD at time of publication One lung ventilation: mechanical separation of the lungs to allow for individualized ventilation of only one lung Indication Pulmonary resection, mediastinal, esophageal, vascular, thoracic spine, or cardiac valve surgery Pulmonary hemorrhage, whole lung lavage, bronchopleural fistula, or unilateral infection Exposure of surgical site by deflation of one lung Isolation of one lung from other Dependency on bilateral lung ventilation, Contraindications hemodynamically unstable, severe hypoxia, severe COPD, or severe pulmonary hypertension Intraluminal airway obstruction/mass or known difficult airway Pursue more advanced airway techniques Unable to tolerate one lung ventilation Risk of dislodging mass and inability to secure airway Pre-operative evaluation given likely Pulmonary Forced expiratory volume (FEV1) Determination of underlying pulmonary disease function testing Diffusion capacity (DLCO) fitness for surgery Non- dependent lung not ventilated Hypoxic vasoconstriction decreases but does not stop perfusion of non- dependent lung Vasodilation of dependent lung pulmonary vasculature Right to left intrapulmonary shunt causes V/Q mismatch ↑ Perfusion to dependent, ventilated lung ↑ Elastance of dependent lung ↓ FRC ↑ Hypoxemia Intervention: Increase FiO2 to maintain SpO2 ≥ 90% ↓ V/Q mismatch ↓ Hypoxemia Intervention: Optimize tidal volume, respiratory rate, PEEP ↓ Atelectasis and ↑ FRC Positioning: Lateral decubitus with dependent lung ventilated Altered gravitational forces on thorax ↓ Ventilation-perfusion (V/Q) mismatch General anesthetic with neuromuscular blockade Intraabdominal contents push up on diaphragm ↑ Airway pressure required ↑ Atelectasis ↑ Hypoxemia ↑ Risk of lung barotrauma Intervention: Optimize positive end-expiratory pressure (PEEP) Recruitment of dependent lung ↓ Inspiratory muscle tone ↓ Functional residual capacity (FRC) Post- operative pain management Thoracotomy or VATS causes pain along thoracic dermatomes Epidural Paravertebral block Bilateral spinal nerve blockade below desired Anesthetic injected into epidural space spinal level Anesthetic injected into Ipsilateral spinal nerve and sympathetic chain blockade in paravertebral spaces thoracic dermatomes Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complication/Intervention Published MONTH, DAY, YEAR on www.thecalgaryguide.com

Zenkers Diverticulum Pathogenesis and Clinical Findings

Zenker’s Diverticulum: Pathogenesis and Clinical Findings Author: Juliette Hall Reviewers: Sunawer Aujla *Dr. Derrick Randall Illustrator: Erica Lindquist * MD at time of publication Functional pharyngo- esophageal motility disorders. Increased upper esophageal sphincter (UES) resting pressure Inadequate relaxation of the cricopharyngeal muscle of the UES during swallowing Lack of synchronization between UES and hypopharynx during swallowing Outflow obstruction in the esophagus Increased intrabolus pressure with swallowing Increase in hypopharyngeal pressure Note: the pathogenesis of Zenker’s Diverticulum is multifactorial, but this mechanism is thought to be a significant contributor Herniation of the esophagus at a weak point between the inferior pharyngeal constrictor muscle and the cricopharyngeal muscle (Killian’s triangle) Zenker’s Diverticulum Acquired mucosal herniation between the horizontal and oblique fibers of the cricopharyngeus muscle Inability of the the upper esophageal sphincter to completely open Dysphagia Extrinsic compression of the cervical esophagus by the diverticulum Esophageal Obstruction Diverticulum compresses recurrent laryngeal nerve Impaired innervation to the intrinsic muscles of the larynx and other contributing factors False diverticulum retains food and saliva Feeling of needing to clear throat Palpable lump in the neck Halitosis (bad smelling breath) Secretions and food spontaneously empty into the bronchial tree Splashing of the fluid that has accumulated in large diverticula Cricoid Cartilage Cricopharyngeal muscle of the UES Thyroid Gland Boyce’s sign (gurgling sound heard as air passes through the diverticulum) Zenker’s Diverticulum Weight loss and malnutrition Aspiration Cough reflex Chronic cough Regurgitation Hoarseness Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 25, 2023 on www.thecalgaryguide.com

Aspiration Pneumonia

Aspiration Pneumonia: Pathogenesis and clinical findings Intractable vomiting ↑ Likelihood of oropharyngeal and gastric contents exiting the esophagus, entering the trachea to the lung If the acidic gastric contents are sterile, then aspirating this results in inflammation and lung injury without development of infection Aspiration pneumonitis Alveolar macrophages recruit neutrophils to local site of infection. Subsequent cytokine release compromises the vascular endothelial cell wall barrier and ↑ alveolar-capillary permeability ↑ inflammation due to fluid and cellular debris build-up in alveoli overdose (e.g. opioids) (e.g. stroke) Altered level of consciousness and impaired cough/clearance Tube Poor Alcohol and Substance Medications Neurologic diseases Esophageal and gastric motility disorders Impaired swallowing Chronic obstructive pulmonary disorder feeding oral health Bacteria adhere to epithelial surfaces and ↑ risk of airway and lung bacterial colonization Aspirated oropharyngeal and gastric contents can also contain bacteria ↓ Elimination and clearance of foreign bacteria from airway and lung Macroaspiration (large volume aspiration) of oropharyngeal bacteria, during eating and drinking Bacteria and fluid fill bronchi and alveolar space Aspiration Pneumonia Alterations to lung microbial flora An infectious lung process caused by inhalation of foreign bacterial and oropharyngeal and gastric contents Aspiration of acidic fluid and pneumonia causative pathogen (typically anaerobes or bacteria in normal oral flora) with resultant inflammation Infiltrate develops in a gravity-dependent pattern in patches around bronchi segments. Produces proinflammatory cytokines, (e.g. tumor necrosis factor-alpha, and interleukin-1) Hypothalamic production of prostaglandin E2 results in thermogenesis Fever Authors: Luiza Radu Reviewers: Mao Ding, *Yan Yu, *Jonathan Liu *MD at time of publication Aspiration to the right lung more common due to large diameter and more vertical orientation of the right main bronchus Crackles and ↑ lung vibrations (fremitus) on auscultation Productive Cough Impaired alveolar gas exchange Chemoreceptor detection of ↓ pO2 triggers ↑ ventilation Hypoxemia Dyspnea Consolidation in lower lobes (particularly superior segments) and posterior segments of upper lobes If untreated, a pus-filled lung cavity develops (e.g. abscess) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Jan 11, 2024 on www.thecalgaryguide.com

Bacterial Tracheitis

Bacterial Tracheitis: Pathogenesis and Clinical Findings Authors: Fasika Jembere Reviewers: Simran Sandhu Mao Ding Danielle Nelson * MD at time of publication Recent upper respiratory viral infection Age typically <6 years old (more common in males) Children at higher risk due physiologic narrowing of airway Recent upper respiratory viral infection (often in Fall/Winter; respiratory virus season) Damage to airway mucosa Activation of systemic inflammatory response Inflammatory cytokines release into systemic circulation ↑ Thermo-regulatory set- point at the hypothalamus ↑ Work of breathing to adequately ventilate lungs Respiratory distress (nasal flaring, grunting) Activation of local inflammatory response Results in thick mucopurulent secretions, ulcerations, and shedding of tracheal mucosa Mucopurulent discharge secretion of fluid contains mucus and pus ↑ Production of mucous results in more accumulation Predisposition to bacterial infection Bacterial pathogen invades trachea Ex: S. aureus (common), S. pyogenes, M. catarrhalis, or H. influenzae Often high fever Trachea is narrowed with purulent debris Upper airway obstruction causes turbulent airstreams Hoarse voice Tachypnea Stridor (with inhalation & exhalation; may be biphasic) Tracheal tenderness ↓ Mucous clearance from the airways Excess airway mucous triggers cough reflex Cough (may be barky) ↑ Use of accessory respiratory muscles (sternocleidomastoid and scalene muscles) Toxic appearance (lethargy, cyanosis) ↓ Level of consciousness (due to hypoxia & hypercarbia) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Jan 11, 2024 on www.thecalgaryguide.com

Shoulder Impingement Syndrome

Shoulder Impingement Syndrome: Signs and Symptoms Calcific deposition Abnormal shoulder morphology Static subacromial narrowing Abnormal scapular rotation and tilt Scapular winging Weakness Degenerative changes to rotator cuff tendons Weakness Dynamic subacromial narrowing Repetitive overhead activity/shoulder overuse Muscle fatigue Repetitive compression forces on subacromial space Glenohumeral instability or stiffness Authors: Janelle Wai Dalal Awwad Reviewers: M. Patrick Pankow Reza Ojaghi Usama Malik Sunawer Aujla Ryan Shields* * MD at time of publication Internal/ Posterior Impingement Compression of rotator cuff tendons between humeral head and posterosuperior glenoid edge during end stage of throwing Pain with passive extension and lateral rotation + Posterior Internal Impingement Test Instability: Laxity of glenohumera l joint Stiffness: Scapular winging with downward tilt, shoulder protraction Primary/ Structural Impingement Any anatomical abnormalities Secondary/Functional Impingement Normal anatomy with motion abnormalities Impingement of underlying rotator cuff muscle-tendon unit and inflammation of subacromial bursa Rotator Cuff Syndrome External/ Subacromial Impingement Compression of subacromial bursa and rotator cuff (i.e. supraspinatus tendon) on the anterolateral acromion and coracoacromial ligament X-Ray: Normal Ultrasound: +/- Tendinopathy, muscle atrophy Pain with overhead movement Pain at night (e.g., sleep position, gravity) Pain with lifting (e.g., weight- training, groceries) Pain (between 60°-120°) with passive shoulder abduction + Painful arc Test Pain with passive shoulder flexion + Neer’s Test Pain with passive shoulder flexion (to 90°) + internal rotation + Hawkins-Kennedy test Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications First published May 27, 2018; updated Jan 11, 2024 on www.thecalgaryguide.com

Cranial Nerve IV Palsy

Cranial Nerve IV Palsy: Pathogenesis and clinical findings Congenital (e.g. Möbius Syndrome) Dysgenesis (defective development) of CN IV Microvascular Disease (e.g. Stroke) Damage or occlusion (complete or partial blockage) to the blood vessels supplying CN IV Trauma Temporary or permanent damage to the nerve fibers Neoplasm Metastasis (e.g. Leptomeningeal) Compression of the nerve fibers along the nerve tract Primary (e.g. Schwannoma) Tumor develops new blood vessels that redirect blood flow to the malignancy, away from the nerve Ischemia of CN IV Infection (a rare cause) (e.g. Ehrlichia chaffeensis, Tuberculosis meningitis) Infectious process in the subarachnoid space Damage to axons of CN IV Cranial Nerve (CN) IV Palsy Superior oblique musculature weakness due to CN IV dysfunction Lesion to the fascicle of CN IV (extending from midbrain to cavernous sinus) Impaired ability to conduct motor commands from nucleus to superior oblique muscle in the eye Weak superior oblique innervation Difficult abduction and intorsion of the eye Contralateral superior oblique weakness Lesion to the nucleus of CN IV (located in the midbrain) Disturbed signal production occurring prior to demarcation of fibers to contralateral side The pathophysiology above can cause damage to structures surrounding CN IV in the midbrain Impacting ipsilateral sympathetic chain descending from the hypothalamus prior to reaching the superior cervical ganglion Authors: Shahab Marzoughi Reviewers: Sunawer Aujla Yvette Ysabel Yao Yan Yu* Gary Michael Klein* * MD at time of publication Vertical/oblique Diplopia (double vision) Hypertropia (one eye is deviated upward compared to the other) Perinaud’s Syndrome (upgaze palsy, convergence retraction nystagmus, and pupillary hyporeflexia) See relevant Calgary Guide slide on Parinaud’s Syndrome Loss of eye muscle movement coordination and function of other structures relating to gait Ataxia Ipsilateral Primary Horner’s Syndrome (miosis, anhidrosis, ptosis) See relevant Calgary Guide slide on Horner Syndrome Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 16, 2024 on www.thecalgaryguide.com

Sugammadex

Sugammadex: Mechanism of action and adverse side effects A direct reversal agent with a high affinity for rocuronium and lesser affinity for vecuronium, capable of reversing even deep neuromuscular blockade. Binds rocuronium and vecuronium (non-depolarizing neuromuscular blocking drugs (nNMBs)) in plasma when administered IV ↓ Concentration of functional nNMBs in plasma Creates a concentration gradient from muscle tissue (high) to plasma (low) nNMBs move from muscle compartment to plasma Sugammadex in plasma encapsulates nNMBs that moved to the plasma ↓ Concentration of functional nNMBs in the plasma ↓ Concentration of nNMBs at the nicotinic acetylcholine receptor within the skeletal neuromuscular junction Reverses neuromuscular blockade created by nNMBs Sugammadex Progesterone is similar in structure to nNMBs Sugammadex binds progesterone ↓ Progesterone activity in the body Progesterone is critical for maintenance of early pregnancy Unknown significance, avoid use in early pregnancy Sugammadex-nNMB complex is cleared by the kidneys Higher concentrations of sugammadex facilitate faster nNMB clearance Unknown mechanisms Post operative nausea and vomiting Headache Bradycardia Cardiovascular Collapse ↓ Effectiveness of progesterone-based contraception for 7 days ↓ Clearance in patients with severe renal impairment Reversal of profoundly deep neuromuscular blockade at higher doses Binds to IgG or IgE receptors on sensitized basophils/mast cells in allergic reactions Activation of basophils/mast cells Degranulation of basophils/mast cells Release of granulation products Anaphylaxis Bronchospasm Hypotension Authors: Arzina Jaffer, Kayleigh Yang Reviewers: Jasleen Brar, Mao Ding Joseph Ahn* * MD at time of publication Movement of limbs or body during anesthesia Coughing during anesthesia Grimacing or suckling on the endotracheal tube Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 16, 2024 on www.thecalgaryguide.com

تعریف-بیماری-انسدادی-مزمن-ریھ

تعریف ”بیماری انسدادی مزمن ریھ

آسم-چگونگی-اثر-درمان-ھا-و-عوارض-جانبی-ر

آسم: چگونگی اثر درمان ھا و عوارض جانبی رایج آنھا

Arachnoid Cysts MRI Findings

Arachnoid Cysts: Findings on MRI Imaging source: radiopaedia.org Authors: George S. Tadros Reviewers: Matthew Hobart, Shahab Marzoughi, James Scott* * MD at time of publication Extra-Axial Location Cyst is visualized outside of brain parenchyma Clear Demarcation Since the arachnoid cyst is bound by arachnoid membrane, it has well-defined margins CSF collection contained within a split arachnoid membrane that occurs during embryological development (primary) Cerebrospinal Fluid (CSF) collection within arachnoid membrane adhesions following trauma, infection, inflammation or surgery (secondary) Arachnoid cyst (fluid-filled sac) formation within the layers of the arachnoid membrane, outside of brain parenchyma (for full pathogenesis, see Calgary Guide slide Arachnoid Cysts: Pathogenesis and clinical findings) Use Diffusion Weighted Imaging (DWI) and Fluid-Attenuated Inversion Recovery (FLAIR) to distinguish from other cysts Isointense to CSF on T1 and T2 Arachnoid cyst contents should appear isointense to CSF on each MR sequence, including diffusion-weighted imaging Axial T2 MRI Head. Clearly demarcated hyperintense (bright) arachnoid cyst is seen (red arrows) Axial T1 MRI Head. Clearly demarcated hypointense (dark) arachnoid cyst is seen (red arrows) FLAIR allows for suppression of free water signal to enhance fluid with ↑ protein concentration Arachnoid cysts contain CSF-like fluid with very little to no protein Complete suppression on FLAIR Cysts are mostly fluid and contains no protein, so it is suppressed and appears darker in FLAIR images. Axial FLAIR MRI Head. Hypointense cyst is seen on FLAIR (red arrows), showing low protein content in CSF-like fluid inside arachnoid cyst DWI measures water diffusion in different directions and whether there is restriction on the direction of flow Fluid within the cyst can flow freely, with no restriction on the direction of movement Non-restricted diffusion There is no directional restriction on flow within the cyst (unrestricted diffusion), so it appears dark on DWI. Axial DWI MRI Head. Hypointense cyst is seen on DWI (red arrows), showing unrestricted diffusion within arachnoid cyst Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Jan 20, 2024 on www.thecalgaryguide.com

vWF Deficiency

von Willebrand Factor (vWF) Deficiency: Authors: Tristan Jones, Nimaya De Silva Reviewers: Sean Spence, Yan Yu, Paige Shelemey, Tony Gu, Raafi Ali, Man-Chiu Poon*, Lynn Savoie* * MD at time of publication Pathogenesis and clinical findings Inherited Acquired Autosomal dominant inheritance Recessive inheritance Type III: Complete quantitative vWF deficiency Presence of antibodies to vWF (a blood clotting protein involved with platelet adhesion), often in setting of autoimmune disease Antibodies bind and inactivate existing vWF Clonal lympho-proliferative disease (uncontrolled production of lymphocytes, a type of immune cell) Adsorption of vWF multimers on to tumor cells ↑ Plasma clearance of vWF ↓ vWF to stabilize/carry plasma Factor VIII (blood clotting protein) ↓ Plasma Factor VIII Impaired intrinsic pathway of coagulation cascade (see Calgary Guide slide on coagulation cascade) Type I: Partial quantitative vWF deficiency Type II: Impaired vWF function (qualitative deficiency) ↓ Binding to vWF-specific antibody on immunoassay ↓ vWF antigen assay (diagnostic test for quantitative vWF deficiency) ↑ Bleeding/closure time (bleeding time measures the length of time required to form a platelet plug) Spontaneous hematomas (large collection of blood outside the blood vessels) Menorrhagia (heavy menstrual bleeds) vWF Deficiency ↓ vWF quantity and/or function ↓ vWF available to bind to damaged blood vessel collagen to anchor platelets Impaired platelet plug formation Bleeding from mucosal surfaces Easy bruising Gum bleeding ↑ Time for blood clot to form Risk of severe hemorrhage ↑ Partial Thromboplastin Time (PTT) (measures the integrity of the intrinsic pathway) Epistaxis (nose bleed) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-published December 5, 2023 on www.thecalgaryguide.com

Arachnoid Cysts Pathogenesis and clinical findings

Arachnoid Cysts: Pathogenesis and clinical findings Authors: George S. Tadros Reviewers: Yvette Ysabel Yao Shahab Marzoughi Gary Michael Klein* * MD at time of publication Failure in the embryological duplication or division of the arachnoid membrane Cerebrospinal fluid (CSF)-like fluid is trapped within the erroneous membrane Formation of a primary, congenital arachnoid cyst (most common cause) Head trauma, intracranial hemorrhage, or infection Inflammation and deposition of cellular matrix Adhesion of the arachnoid membrane CSF accumulates in the subarachnoid space (space between the arachnoid mater and pia mater) Formation of a secondary arachnoid cyst (less common) Cyst remains stable in size and does not expand (most common) Patients are asymptomatic Arachnoid cyst is diagnosed incidentally on unrelated neuroimaging (see Calgary Guide slide Arachnoid Cysts: Findings on MRI) Arachnoid Cyst Cyst grows in size and expands (rare but more common in children under four years of age) Cyst exerts pressure on other structures (mass effect) Suprasellar region Cyst ruptures into the subdural space (rare) CSF-like fluid accumulates in the subdural space Subdural hygroma (collection of non-bloody CSF) Intracranial hypertension (↑ intracranial pressure) Generalized symptoms Middle fossa Compression and irritation of the temporal cortex Seizures Focal symptoms depending on cyst location Cerebellopontine angle Compression of vestibulocochlear nerve (Cranial Nerve VIII) Compression and interruption of cochlear blood supply Cyst presses on the third ventricle and aqueduct buildup of CSF in the ventricles Obstructive hydrocephalus Cyst presses on the optic chiasm, hypothalamus, and pituitary Visual impairments and endocrinopathies Headache (most common) Vomiting Nausea Progressive hearing loss Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Jan 25, 2024 on www.thecalgaryguide.com

Avascular Necrosis AVN of the Femoral Head Findings on MRI

Avascular Necrosis (AVN) of the Femoral Head: Findings on MRI Traumatic or atraumatic disruption of blood supply to the proximal femur (for full pathogenesis, see Calgary Guide slide Avascular Necrosis: Pathogenesis and clinical findings) Ischemia of the femoral head (usually unilateral for traumatic and bilateral for non-traumatic) Prolonged anoxia (total oxygen deprivation) within the femoral head Cell death (necrosis) of osteocytes and marrow cells in the femoral head, forming a focal lesion (sequestrum) Histiocytes and giant cells (immune cells) aggregate around the sequestrum, forming a “reactive zone” around the periphery of the sequestrum Apoptotic osteocytes in the anoxic reactive zone cannot be phagocytosed leading to dysregulated bone remodeling and osteosclerosis (hardening of bone and ↑ bone mineralization and density due to ↓ resorption and ↑ bone formation) Femoral head becomes progressively weaker while the mechanical load on it remains the same Progressive femoral head/subchondral bone collapse Osteoarthritis Areas with ↑ fluid content appear darker on T1w images Areas with ↑ fluid content appear brighter on T2w images Areas with ↑ bone density and ↓ fat content appear darker on T1w images Areas with ↑ bone density and ↓ fat content appear darker on T2w images Basic MRI Physiology Edema and inflammation increases fluid content Sclerotic areas have ↑ bone density and thus ↓ fat content Location of Signs Inflamed reactive zones are darker on T1w images Inflamed reactive zones are brighter on T2w images Sclerotic areas are darker on both T1w and T2w images Authors: George S. Tadros Reviewers: Matthew Hobart, Mao Ding Shahab Marzoughi David Cornell* * MD at time of publication T1w Signs on both T1-weighted and T2-weighted images are most commonly seen on the superior anterolateral aspect of the femoral head Single dark band on T1-weighted MRI A single band-like crescentic lesion of low signal intensity is seen on T1-weighted MRI images (white arrows). This band represents the edematous reactive zone between the necrotic and normal tissue, and typically extends to the subchondral plate Double Line Sign on T2-weighted fat-saturated MRI An outer distal low signal intensity line is seen (white arrows) representing reactive bone sclerosis Image source: radiologymasterclass T2w An inner proximal high signal intensity line is also seen (red arrows) representing vascular and repair tissue at the periphery of the sequestrum Image source: radiologymasterclass Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Jan 27, 2024 on www.thecalgaryguide.com

Bacterial Infections from Transfusion

Bacterial Infections from Transfusion: Signs and Symptoms Caused by bacterial contamination of any blood product, most commonly platelets due to room-temperature storage Bacteria enters bloodstream directly through transfusion Immune cells (ex. macrophages, dendritic cells, monocytes, neutrophils) recognize bacteria Immune cells release pyrogens (either bacterial components or signalling molecules) upon recognition Pyrogens bind to receptors on the hypothalamus Hypothalamus ↑ body temperature set point Body generates and conserves heat to reach set point Immune cells release pro- inflammatory cytokines (messenger protein) Cytokines activate sympathetic nervous system via hypothalamus Adrenal glands release stress hormones (epinephrine and norepinephrine) into bloodstream Stress hormones bind to receptors on cardiomyocytes (heart muscle cells) ↑ Heart contractility ↑ Heart rate Cytokines circulate throughout the body Cytokines interact with endothelial cells of the blood vessels ↑ Nitric oxide production Relaxes smooth muscle cells of blood vessel walls Vasodilation (↑ blood vessel diameter) Hypotension Systemic inflammation Stimulate nerve endings in muscles Stimulate nerve endings in gastrointestinal tract’s lining Blood brain barrier’s integrity is compromised Nitric oxide reacts with oxygen to form reactive nitrogen species Tissue damage Fatigue Weakness Muscle aches Nausea and vomiting Immune and inflammatory cells enter the brain Authors: Arzina Jaffer Kayleigh Yang Reviewers: Nimaya De Silva Raafi Ali Michelle J. Chen Yan Yu* Kareem Jamani* * MD at time of publication Inflammation in the brain Activates pain processing centers in the brain Headache Damages neurons and disrupts cell communication Confusion and altered mental state Shivering Fever Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 30, 2024 on www.thecalgaryguide.com

Acute Wound Healing

↓ Blood supply and oxygenation to local skin tissue Ischemia Degradation of intact skin Abrasion (damage by scrape/rub) Puncture (small piercing caused by sharp object) Acute injury to the skin Crush (damage by compression) Acute Wound Healing: Pathogenesis and clinical findings Author: Amanda Eslinger Mina Youakim Reviewers: Heena Singh Shahab Marzoughi Yan Yu Laurie Parsons* * MD at time of publication 8 – 365+ days post-injury Remodeling (↓ blood vessels & organized collagen) Extensively cross-linked type 1 collagen replaces the disorganized collagen laid down in the proliferative phase ↑ Protein content in collagen Scarring (fibrotic tissue replaces previously healthy tissue) Disruption of structure and function of dermis, epidermis and subdermal tissues Subendothelial and endothelial damage activates the coagulation pathway Formation of a platelet plug Bleeding is slowed or stopped by hemostatic plug (hemostasis) Clot unifies wound edges 0 – 7 days post-injury Inflammation (In disrupted skin layers) 4 - 14 days post-injury Proliferation of collagen, extracellular matrix & blood vessels TGF-β attracts fibroblasts to the site of the wound Fibroblast & macrophage stimulate tissue growth & angiogenesis which replaces hemostatic plug Scabbing (protective crust overlying damaged tissue) Re-epithelialization beneath the scab sloughs it off Healing (newly replaced tissue replaces damaged one) In response to irritant, mast cells release histamine Complement activation causing nearby endothelial cells to release prostaglandins Vasodilation occurs around the wound area Localized ↑ vascular supply (reception of blood and fluid from vessels) ↑ Hydrostatic pressure forces fluid from vessels into surrounding tissue Edema (swelling from fluid buildup) Erythema (redness) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications First Published Sept 19, 2013; updated Jan 30, 2024 on www.thecalgaryguide.com

Carbonic Anhydrase Inhibitor Diuretics

Carbonic Anhydrase Inhibitor Diuretics: Renal mechanism and side effects Authors: Stephanie Happ Reviewers: Matthew Hobart Raafi Ali Adam Bass* * MD at time of publication Carbonic Anhydrase Inhibitors (CAI) Inhibition of carbonic anhydrase on the apical surface of the brush border cells in the proximal convoluted tubule (PCT) Activation of the Renin- Angiotensin-Aldosterone Systemfromvolume depletion Activation of principle cell Epithelial sodium channels (ENaC) on principal cells of the CCD reabsorb ↑ Na+ and waste K+ ↓ K+ in serum Hypokalemia See Hypokalemia: Clinical Findings slide ↑ Na+ delivery to the cortical collecting duct (CCD) H2O follows Na+ into the CCD to maintain a balanced osmotic pressure ↑ H2O available for excretion Mild diuresis (increase in frequencyandvolumeof urine) ↓ Blood volume Hypotension ↓ Na+ and HCO3- reabsorption in the PCT ↑ HCO3- delivery to cortical collecting duct Urine alkalization (increased pH) Chronic urine alkalization ↓Solubilityof citrate ↓ Urinary citrate ↓ Citrate binding with Ca2+à↑ Ca2+ complexing with oxalate ↑ Spontaneous nucleation, growth and agglomeration of calcium oxalate crystals Formation of calcium oxalate renal calculi ↑ HCO3- is lost in the urine ↓ pH of the blood Type II Renal Tubular Acidosis See Type II/Proximal Renal Tubular Acidosis slide CAI prevents the up- regulationofglutamine transporters in the PCT Inability to correct the metabolic acidosis and impaired urinary NH3 excretion Hyperammonemia (↑ serum NH3 ) ↑ Risk of hepatic encephalopathy in individuals with cirrhosis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Feb 3, 2024 on www.thecalgaryguide.com Carbonic Anhydrase Inhibitor Diuretics: Renal Mechanism and Side Effects Carbonic Anhydrase Inhibitors (CAI) Inhibition of carbonic anhydrase on the apical surface of the brush border cells of the proximal convoluted tubule (PCT) Authors: Stephanie Happ Reviewers: Matt Hobart Name Name* * MD at time of publication ↓ Na+ and HCO3- reabsorption in the PCT ↑ Na+ delivery to the cortical collecting duct (CCD) H2O follows Na+ into the CCD to maintain a balanced osmotic pressure ↑ H O available for 2 excretion Mild diuresis ↓ Blood volume Hypotension ↑ HCO3- delivery to cortical collecting duct Epithelial sodium channels (ENaC) on principal cells of the CCD reabsorb ↑ Na+ ↑ Intracellular Na+ drives Na+/K+ ATPase activity on the principal cells (moving 2 K+ into cell and 3 Na+ out into the peritubular capillary) ↑ Intracellular K+ drives H+/K+ ATPase activity on the intercalated cells (moving 1 H+ into cell and 1 K+ out into the tubular filtrate) ↓ K+ in serum Hypokalemia See Hypokalemia: Clinical Findings slide Urine alkalization ↑ HCO3- is lost in the urine, leading to ↓ pH of the blood Renal Tubular Acidosis Type II See Type II/Proximal Renal Tubular Acidosis slide CAI inhibit the up-regulation of glutamine transporters in the PCT Inability to correct the metabolic acidosis and impaired urinary NH3 excretion Hyperammonemia ↑ Risk of hepatic encephalopathy in individuals with cirrhosis Chronic urine alkalization leads to marked ↓ in urinary citrate ↓ Ability of citrate to bind to Ca2+ and calcium oxalate stones ↓ Inhibition of spontaneous nucleation ↓ Prevention of growth and agglomeration of crystals Formation of calcium oxalate renal calculi Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published MONTH, DAY, YEAR on www.thecalgaryguide.com

Epiglottitis

Epiglottitis: Pathogenesis and clinical findings Infectious cause: Bacterial (Staphylococcus aureus, Streptococcus pneumoniae, Neisseria meningitidis, or most commonly Haemophilus influenzae in unimmunized children), viral or fungal Authors: Alisha Ebrahim Reviewers: Simran Sandhu Mao Ding Michelle J. Chen Danielle Nelson* * MD at time of publication Infectious agent invades the bloodstream and/or the epithelial layer of the epiglottis, aryepiglottic folds and adjacent structures, allowing for spread Non-infectious cause: Ingestion of toxin or foreign body, thermal injury, or trauma The potential space between the squamous epithelial layer and the epiglottal cartilage fills with inflammatory cells such as neutrophils and eosinophils Exudate of inflammatory cells spreads through the lymphatic and blood vessels in the lingual surface of the epiglottis and periepiglottic tissues Fluid and inflammatory cells accumulate between the squamous epithelial layer and epiglottal cartilage Swelling of the entire supraglottic larynx Tripod/sniffing position (Anxious- looking and sitting with trunk leaning forward, neck hyper-extended and chin pushed forward to maximize airway diameter) Stridor (High-pitched sound that is produced by obstruction in the larynx or just below) Stertor (Low-pitched noise created in the nose or the back of the throat) Retraction of the intercostal and suprasternal muscles Tachypnea (Rapid breathing) Increased weight and mass of the epiglottis Epiglottis curls posteriorly and inferiorly Ball-valve effect (Airflow obstructed during inspiration as epiglottis is pulled over airway but not during expiration as epiglottis moves back into position) ↓ Diameter of upper airway Epiglottis obstructs the esophagus Dysphagia (Difficulty swallowing) Cyanosis (Blue tint to skin) Turbulent inspiratory airflow Aspiration of oropharyngeal secretions Hypoxemia (Low oxygen levels in blood) ↓ Air entry to lungs Airway obstruction ↑ Work of breathing Drooling Pain when swallowing Muffled/”hot potato” voice Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Feb 5, 2024 on www.thecalgaryguide.com

Stable Angina

Angina Pectoris/Stable Angina: Pathogenesis and clinical findings Authors: Ryan Iwasiw Alexander Arnold Julia Gospodinov Reviewers: Mandy Ang Sarah Weeks* Frank Spence* Shahab Marzoughi * MD at time of publication Atherosclerosis (Fatty plaque accumulates inside the intimal walls of arteries) ↓ Blood vessel lumen diameter ↓ Volume of blood is supplied to the heart Predictable period of physical activity or emotional stress ↑ Heart rate ↓ Time for coronary arteries to fill heart with blood (diastole) ↑ Heart contractility ↑ Oxygen demand of heart muscle tissue (myocardium) ↓ Myocardial blood supply Imbalance between blood supply & oxygen demand causes myocardial ischemia Angina Pectoris/Stable Angina Myocardial ischemia causes cardiac muscle cells (cardiomyocytes) to switch from oxygen-dependent (aerobic) to oxygen-absent (anaerobic) metabolism Anaerobic metabolism produces metabolites that stimulate cardiac spinal afferent nerves Myocardial visceral afferent & somatic sensory nerve fibers mix & enter the spinal cord via T1-T4 nerve roots Brain interprets ↑ nerve signaling as nerve pain coming from the skin of T1-T4 dermatomes (referred pain) ↑ lactic acid production & ↓ cellular pH impairs cardiomyocytes’ function Damaged cardiomyocytes impair myocardial relaxation & cause ↓ left ventricular contractility & cardiac output Blood backs up into left ventricle, atrium, & pulmonary vasculature ↑ Pulmonary capillary pressures pushes fluid out & into the lung’s alveoli ↓ Gas exchange & oxygenation ↑ Respiratory rate & Dyspnea (shortness of breath) Blood flow begins at the epicardium (outer heart layer) & ends at endocardium (inner layer) Subendocardium (innermost heart layer) receives the least blood flow causing non-transmural (partial thickness) heart wall ischemia Anterior/septal & lateral wall ischemia triggers ↑ sympathetic nervous system (SNS) activity given the proximity of cardiac SNS innervation Inferior wall ischemia triggers involuntary ↑ in Vagus nerve activity given the nerve’s proximity Bradycardia (↓ heart rate) Nausea Adrenal medulla releases Norepinephrine hormone Activation of sweat glands via SNS acetylcholine neurotransmitter release Hypotension (↓ blood pressure) Pain radiation to left arm, jaw, abdomen & upper back Chest pain, pressure, or discomfort Unstable Angina (unpredictable & worsening chest pain) See relevant Calgary Guide slide on Unstable Angina Binds arterial smooth muscle α1 receptors ↑ Coronary arteries’ vascular tone (vasoconstriction) Hypertension (↑ blood pressure) Activates β1 receptors in the heart Tachycardia (↑ heart rate) Diaphoresis (↑ sweating) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Aug 8, 2013; updated Feb 5, 2024 on www.thecalgaryguide.com

Acute Otitis Externa Complications

Acute Otitis Externa (Swimmer’s Ear): Complications Acute Otitis Externa (AOE) Authors: Charmaine Szalay-Anderson Vaneeza Moosa Reviewers: Shayan Hemmati Shahab Marzoughi Ben Campbell Justin Lui* * MD at time of publication Spread to subcutaneous tissue Chronic otitis externa (>6 weeks) Chronic inflammation of the outer ear Fibroblast activation for collagen and extracellular matrix components production for tissue repair Excess accumulation of tissue Ear canal fibrosis (thickening) Ear canal stenosis (narrowing) Damage/obstruction to ear canal structures with impaired fluid drainage & pressure buildup Inflammation of the outer ear Recurrent or non-resolving acute otitis externa Dissemination of infection Spread to connective tissue and cartilage Perichondritis (inflammation of ear cartilage) Spread of Pseudomonas aeruginosa in an immunocompromised host or due to antibiotic resistance Rapid infectious spread through soft tissue to mastoid and/or temporal bone Malignant (necrotizing) otitis externa *can be life threatening Inflammation of connective tissue and bony structures Spread to tympanic membrane Myringitis (inflammation of tympanic membrane) Swelling and thinning of tissue Tympanic membrane perforation (tear) Immune reaction with inflammation Dead white blood cell, bacteria & tissue debris accumulation in the ear canal Pus formation with purulent otorrhea (discharge from ear) Localized pus accumulation Abscess Ear canal blockage Periauricular/ pinna (outer ear) cellulitis Facial cellulitis Erosion of temporal bone decreasing bony sound conduction Permanent conductive hearing loss Direct toxicity of pathogens to surrounding nerves Cranial nerve (CN) VII (facial) palsy (+/- CN X, XI, XII) Out-of- proportion primary otalgia (ear pain) Sensation of fullness in the ear Temporary hearing loss Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Dec 4, 2022; updated Feb 7, 2024 on www.thecalgaryguide.com

Chancroid

Chancroid: Pathogenesis and clinical findings Authors: Mina Youakim Reviewers: Elise Hansen Sunawer Aujla Shahab Marzoughi Jori Hardin* * MD at time of publication Condomless sex Multiple sexual partners Genital injury (i.e. cuts, friction) Micro-abrasions occur in the epidermal tissue of the genital area Sexual Transmission of Haemophilus ducreyi (H. ducreyi) bacteria from an infected sexual partner H. ducreyi enters the epidermis through micro abrasions H. ducreyi infects epithelial cells H. ducreyi secretes Large Supernatant Proteins LspA1 and LspA2 (which inhibit phagocytosis by neutrophils and macrophages) T cells activate and release cytokines IL-6 and IL-8 Neutrophils are recruited to the site of infection Local macrophages form a collar around the base of the papule to try to reach and engulf H. ducreyi ↑ Localized buildup of immune cells While infection persists, H. ducreyi release lipooligosaccharides (LOS) LOS travels to lymph nodes in the inguinal region Lymph nodes synthesize and proliferate T cells specific to H. ducreyi antigen Inguinal lymph nodes swell due to ↑ number of T cells Inguinal buboes (swollen inguinal lymph nodes) Neutrophils surround the bacteria and attempt to engulf it Localized epidermal buildup of neutrophils and H. ducreyi Papules (small protrusions on the skin) Continued build-up of H. ducreyi, neutrophils, dead white blood cells (pus), and macrophages Pustules (pus-filled skin lesion) ↑ Local pressure from growing pustule compresses surrounding vessels ↓ Local blood flow erodes and sloughs off the local epidermal roof Ulcers (open skin sore) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Feb 8, 2024 on www.thecalgaryguide.com

Dantrolene

Dantrolene: Mechanism of Action and Adverse Side Effects Medication indicated for the treatment of muscle spasms associated with malignant hyperthermia (reaction to certain anesthetics resulting in a rapid and dangerous increase in body temperature, muscle rigidity, and other symptoms), and spasticity associated with various neurological disorders such as multiple sclerosis, cerebral palsy, and spinal cord injury. Dantrolene Authors: Madison Amyotte, Arzina Jaffer Reviewers: Jasleen Brar, Mao Ding Luiza Radu Joanna Moser* * MD at time of publication Metabolized in the liver by the cytochrome P450 enzyme Metabolic process forms a high concentration of hydroxylamine Hydroxylamine is a highly toxic metabolite associated with dantrolene induced liver injury Impaired Liver Function Binds to ryanodine receptors (RYR1) in the sarcoplasmic reticulum of skeletal muscle cells Prevents ryanodine channel from opening when triggered by the action potential in the muscle Prevents calcium release from the sarcoplasmic reticulum Prevents binding of calcium to troponin on the actin filaments in the cytosol of the skeletal muscle cells Myosin-binding site on the actin remains covered by the tropomyosin Prevents cross-bridge formation between myosin and actin within the sarcomere Prevents muscle contraction ↓ Progression of muscle rigidity and spasms ↓ Heat produced by muscular contraction Skeletal & respiratory muscle weakness ↓ Body temperature ↓ Inspiratory capacity Dyspnea Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Feb 18, 2024 on www.thecalgaryguide.com

Infective endocarditis

Infective Endocarditis: Pathogenesis, complications, and clinical findings Subacute Endocarditis Pre-existing valvular stenosis or regurgitation Non-laminar flow across valve damages valve endothelium A sterile thrombus forms Thrombus forms on the surface of a cardiac valve Acute Endocarditis Poor dental hygiene/recent dental procedure Invasive procedure/indwelling device Positive blood cultures Activation of immune system Valve Trauma Invading bacterium Intravenous (IV) drug use (mostly causes right sided endocarditis) Bacteria enter the bloodstream (bacteremia) In subacute cases, valvular abnormality usually present beforehand In all cases, vegetation forms on affected valve Immune complex deposit in kidney Immune complexes cause vasculitis in retinal vessels Immune complexes deposit subcutaneously ↓ Blood flow to organs perfused by the obstructed arteries Valve endothelium is damaged Bacteria adhere to thrombi on the cardiac valve endothelium Infective Endocarditis Infection of the thrombus typically produces a vegetation on the flow surface of a valve Immune complexes (complexes of antibody bound to antigen) form secondary to infection Generalized immune response Malaise Chills Fever (> 38°C) Author: Sean Spence George S. Tadros Reviewers: Yan Yu Jason Baserman Danny Guo Steve Vaughan* *MD at time of publication Parts of vegetation embolize systemically, obstructing arteries Infection destroys infected valve Smaller emboli block smaller vessels on hands/feet Microinfarctions Mitral regurgitation, Aortic stenosis, Aortic insufficiency (Valve involvement: Mitral > Aortic > Tricuspid) Vegetation seen on ultrasound/echocardiogram Damage to Glomerulonephritis glomeruli (Inflammation of glomeruli) Roth’s spots (retinal hemorrhages with pale centers due to coagulated fibrin) Osler nodes (tender, raised, red lesions found on the hands and feet) Organ infarction (tissue death) Splinter hemorrhages (small red streaks under nails) Janeway lesions (non-tender, red macules/nodules on palms/soles – only a few millimeters wide) Regurgitation (blood leaks back through the insufficient valve despite it being closed) Valve unable to fulfill normal functions (valve insufficiency) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Aug 20, 2013, updated Feb 24, 2024 on www.thecalgaryguide.com

Gestational Diabetes Risk factors and pathogenesis

Gestational Diabetes: Risk factors and pathogenesis Normal metabolic changes occurring in pregnancy (e.g., increased lipid storage, increase renal filtration, increased glucose production etc.) Authors: Amyna Fidai Maharshi Gandhi Reviewers: Laura Byford-Richardson Shahab Marzoughi Yan Yu* Hanan Bassyouni* * MD at time of publication High risk population (Aboriginal, Hispanic, South Asian, Asian, African) Previous or current macrosomia (>4000g) or polyhydramnios Other conditions associated with Diabetes Mellitus such as polycystic ovarian syndrome, hypertension, metabolic syndrome Placental counter regulatory hormones (particularly Human Placental Growth Hormone) oppose the action of insulin ↑ Insulin resistance (liver, muscle, adipose tissues become less responsive to insulin) ↑ Fetal demands after 18 weeks gestation (fetus requires 80% of its energy from maternal glucose) ↑ Carbohydrate intake to keep up with the demands Previous history of gestational diabetes or glucose intolerance Family history of diabetes Advanced maternal age Obesity Previous unexplained stillbirth Multiples (larger placental mass and activity) Corticosteroid use ↑ Risk for pregnancy induced glucose intolerance (mechanism unclear and/or complex) ↑ Insulin requirements Initially pancreatic beta cells work overtime to keep up with the ↑ insulin demands Eventually insulin demands are not met due to the exhaustion of pancreatic beta cells Plasma glucose rises (Fasting plasma glucose ≥5.3 mmol/L) Gestational Diabetes (or exacerbation of pre-existing DM) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Jan 28, 2017, updated Feb 24, 2024 on www.thecalgaryguide.com

Le zona

Le zona

Propofol français

Propofol français

Therapie cognitivo-comportementale

Thérapie cognitivo-comportementale

MPOC Resultats des radiographies du thorax

MPOC: Résultats des radiographies du thorax

Trouble de la personnalite antisociale

Trouble de la personnalité antisociale

Trouble de la personnalite schizotypique

Trouble de la personnalité schizotypique

Granulomatose avec polyangeite

Granulomatose avec polyangéite

Oedeme pulmonaire a pression negative

Œdème pulmonaire à pression négative

Eisenmenger Syndrome

Eisenmenger Syndrome: Pathogenesis and clinical findings Ventricular septal defect Patent ductus arteriosus Authors: George S. Tadros Reviewers: Stephanie Happ Shahab Marzoughi Kim Myers* * MD at time of publication Atrial septal defect Blood shunted from systemic to pulmonary circulation Long-standing “left-to-right” shunt with too much pulmonary blood flow ↑ Flow of blood through the pulmonary circulation (from right ventricle to pulmonary arteries) ↑ Shear stress and circumferential stress on the pulmonary arteries and arterioles Atrioventricular septal defect Truncus arteriosus (Only one common artery arises from the heart rather aorta and pulmonary artery) Long-standing “right-to-left” shunt with too much pulmonary blood flow Structural changes occur in pulmonary arteries and arterioles to adapt to ↑ flow and pressure Hypertrophy of the smooth muscles (media) of pulmonary arteries and arterioles Thickening of the intima (innermost layer) of pulmonary arteries and arterioles ↑ Pulmonary vascular resistance (pressure in the pulmonary arteries) Pressure within the right ventricle gradually ↑ Right ventricular pressure is equal to, or exceeds left ventricular pressure Shunt changes from left-to-right to right-to-left “Right-to-Left” Shunt De-oxygenated blood originating from the right ventricle bypasses the lungs and goes into systemic circulation ↓ Oxygen delivery to tissue across the body Pulmonary hypertension (mean pulmonary artery pressure at rest ≥ 25mmHg) Right ventricular hypertrophy (enlarging) Hypertrophied right ventricle cannot contract effectively Right ventricle loses ability to pump blood efficiently Right heart failure Megakaryocytes (platelet precursors) are shunted away from the capillary beds of the lungs, where they usually get fragmented into platelets Chronic central cyanosis (generalized bluish discoloration) Induction of vascular endothelial growth factor (VEGF) in fingers Terminal digit clubbing (uniform swelling of the fingers and toes) Hypoxemia (<90% O2 saturation) Thrombocytopenia (↓ platelet count) Spontaneous bleeding events Body tries to compensate for ↓ O2 by ↑ oxygen-carrying capacity of the blood Polycythemia (↑ in red cell count) and ↑ hemoglobin concentration ↑ blood viscosity Hypercoagulable and prothrombotic state Not enough O2 to meet the body’s demands Fatigue Epistaxis (nose bleeds) Minor (non-life-threatening) Major (life-threatening) Pulmonary hemorrhage Dental bleeds Menorrhagia (heavy periods) Pulmonary Embolism (clot in pulmonary vessels) Stroke Deep vein thrombosis (clot in deep veins) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Mar 5, 2024 on www.thecalgaryguide.com

Pagets Disease pathogenesis and clinical findings

Paget’s Disease: Pathogenesis and clinical findings Author: Payam Pournazari George S. Tadros Reviewers: Yan Yu Spencer Montgomery Luiza Radu David Hanley* * MD at time of publication Mutations in different genes (SQSTM1 gene most common) Epigenetic modifications of different genes Bone marrow cells (precursor of osteoclasts) get infected with measles or respiratory syncytial virus ↑ Osteoclast formation from progenitor (precursor) cells Malfunction of genes involved in bone remodeling and regulation Genetic predisposition ↑ Osteoclast quantity (10- 100X), size, and activity Release of bone matrix proteins and collagen breakdown products such as C-terminal telopeptide ↑ Serum C-terminal telopeptide (marker of bone resorption) Osteoclasts secrete acid and enzymes that dissolve the mineralized bone and matrix (bone resorption) The breakdown leaves physical holes in the bone that show up as radio-lucent spots on x-ray Radiolucent lytic bone lesions on x-ray (mostly seen in pelvis, vertebral bodies, tibia, femur and skull) ↑ Osteoblast activity as a compensatory mechanism Disorganized new bone formation Abnormal new bone is weak, but bone continues to bear regular stresses Skeletal deformities E.g., Skull involvement (↑ hat size), bowed tibias, kyphosis (excessive forward curve of the upper spine) Osteoblasts release alkaline phosphatase from the bone into the blood ↑ Serum alkaline phosphatase (marker of bone formation) Damage to the auditory labyrinth (bones in the ear) Bilateral progressive hearing loss Disorganized remodeling, lytic lesion expansion and bowing of bone all stimulate nociceptive (pain-sensing) nerve endings on the periosteum (membrane covering the surfaces of bones) Bone pain (dull, often at night-time) Damage to bone surrounding joints Osteoarthritis Bone fractures Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Nov 26, 2012, updated Mar 5, 2024 on www.thecalgaryguide.com Paget’s Disease: Pathogenesis and clinical findings Author: Payam Pournazari George S. Tadros Reviewers: Yan Yu Spencer Montgomery David Hanley* * MD at time of publication Mutations in different genes (SQSTM1 gene most common, but also TNFRSF11A, ZNF687 and PFN1) Epigenetic modifications of different genes (including RANKL, OPG, HDAC2, DNMT1, and SQSTM1) Malfunction of genes involved in bone remodeling and regulation Possible viral exposure (measles or respiratory syncytial virus) Genetic predisposition ↑ Osteoclast quantity (10- 100X), size, and activity Release of bone matrix proteins and collagen breakdown products such as C-terminal telopeptide (CTx) ↑ Serum C-terminal telopeptide marker of bone resorption Osteoclasts secrete acid and enzymes that dissolve the mineralized bone and matrix (bone resorption) The breakdown leaves physical holes in the bone that show up as radio-lucent spots on x-ray Radiolucent Lytic bone lesions on x-ray (mostly seen in pelvis, vertebral bodies, tibia, femur and skull) ↑ Osteoblast activity as a compensatory mechanism Disorganized new bone formation Abnormal new bone is weak, but bone continues to bear regular stresses Skeletal deformities E.g., Skull involvement (↑ hat size), Bowed tibias, kyphosis (excessive forward curve of the upper spine) Osteoblasts release Alkaline Phosphatase (ALP) from the bone into the blood ↑ Serum Alkaline Phosphatase marker of bone formation Damage to the auditory labyrinth (bones in the ear) Bilateral progressive hearing loss Disorganized remodeling, lytic lesion expansion and bowing of bone all stimulate nociceptive (pain-sensing) nerve endings on the periosteum (membrane covering the surfaces of bones) Bone pain (dull, often at night-time) Damage to bone surrounding joints Osteoarthritis Bone fractures Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 26, 2012 on www.thecalgaryguide.com Paget’s disease: Pathogenesis, Clinical Findings Author: Payam Pournazari Reviewers: Yan Yu Spencer Montgomery David Hanley* * MD at time of publication Genetic predisposition (possibly in RANK encoding gene) Possible viral exposure (measles and respiratory syncytial virus) ↑ in number (10-100X), size, and activity of osteoclasts Osteoclasts cause excessive bone resorption, which also stimulates osteoblasts Release of bone matrix proteins and collagen breakdown products such as C-terminal telopeptide of pyridinoline crosslinks (CTx) ↑ serum CTx marker of bone resorption Osteoclasts secrete acid and enzymes that dissolve the mineralized bone and matrix Leaves physical holes in the bone that show up as radio- lucent spots on x-ray Lytic bone lesions (mostly seen in pelvis, vertebral bodies, tibia, femur and skull) Marked ↑ osteoblastic activity results in disorganized new bone formation Abnormal new bone bone is weak, but bone continues to bear regular stresses Skeletal deformities: e.g. Skull involvement (↑ hat size), Bowed tibias, kyphosis and fractures Osteoblasts release Alkaline Phosphatase (ALP) from the bone into the blood ↑ serum ALP marker of bone formation Disorganized bone remodelling, lytic lesion expansion, fracture and bowing of bone all stimulate nociceptive nerve endings on the periosteum Bone pain (dull, often night-time) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 26, 2012 on www.thecalgaryguide.com

Hematoma Epidural

Hematoma Epidural (EDH): Patogenesis dan temuan klinis

Hematoma Epidural Temuan pada CT scan

Hematoma Epidural (EDH) Akut: Temuan pada CT scan

Onychomycosis

Dermatophyte Onychomycosis: Pathogenesis and clinical findings Authors: Holly Zahary Loreman Reviewers: Mina Youakim Elise Hansen Shahab Marzoughi Jodi Hardin* * MD at time of publication Host Risk Factors Environmental Risk Factors Immuno- compromised ↓ Immune response to infection Older age Peripheral vascular disease Reduced blood circulation Diabetes Pre-existing nail dystrophy Previous nail trauma Integrity of nail unit is compromised Micro- traumatic pressure on nail Dark, warm shoe environment Optimal conditions for fugal growth Exposure to tinea pedis or onychomycosis Direct spread of infection to nail unit High blood sugar favoring infection Dermatophytes invade corneocytes on stratum corneum, the uppermost non- living layer of keratinized skin Compromise/breaking of hyponychial seal or cuticle (connection between hyponychium and nail plate) Proximal Subungual White Superficial Tinea infection (e.g. Tinea Pedis, Corporis, Capitis) Infection spreads to distal hyponychial space Dermatophytes colonize local tissue in nail plate and nail bed Dermatophytes feed on keratinized tissue General Symptoms (All Subtypes) Spongiosis (Intercellular edema) Acanthosis (Thickening of stratum spinosum layer of epidermis) Hyperkeratosis (Thickening of stratum corneum In effort to rid infection) Papillomatosis (Projections of dermal papillae) Secondary damage to nail matrix Loss of nail Keratinocytes produce an acute, low-grade inflammatory cytokine response Onychomycosis Dermatophytic infection of the nail bed Inflammation promotes ↑ fluid to tissues for ↑ immune cell delivery Widespread inflammation thickens parts of the epidermis in efforts to shed the infection Inflammation and epidermal hyperplasia (↑ growth of cells) influence local dermal papillae (group of cells just beneath the hair follicle) to proliferate and project above the skin Distal Subungual Superinfecting bacteria or other fungi proliferate beneath the compromised nail imparting a yellowish appearance Distal Subungual Subtype (Thick yellow nails, keratin and debris accumulate distally underneath nail plate) Dermatophytes invade the proximal end of the nail plate Dermatophytes penetrate through the cuticle to the newly forming nail plate moving distally Proximal Subungual Subtype (Whitish discolouration of nail plate that begins proximally and moves distally, indicative of immunosuppression) Fungi predominantly invade various areas of the superficial nail plate layers eventually joining together White Superficial Subtype (Chalky white scale that spreads slowly beneath nail plate, well-defined “white islands” that coalesce as disease progresses) The entirety of the nail plate is infected by the dermatophytes Widespread inflammation thickens the nail plate as well as beneath the nail (subungual hyperkeratosis) in efforts to shed the infection Total Dystrophic Subtype (End-stage nail disease, entire nail becomes thick and dystrophic) Local spread of infection Dermatophytes spread causing cracks in the skin deeper into toe Abnormal keratinization in hyponychium Keratin accumulates between nail plate and hyponychium Fissure (splits in the skin) Bacteria enters lymphatics and bloodstream Cellulitis Sepsis Onycholysis (nail plate separates from nail bed) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Mar 13, 2024 on www.thecalgaryguide.com Dermatophyte Onychomycosis: Pathogenesis and clinical findings Authors: Holly Zahary Loreman Reviewers: Mina Youakim Elise Hansen Shahab Marzoughi Jodi Hardin* * MD at time of publication Host Risk Factors Environmental Risk Factors Immuno- compromised ↓ Immune response to infection Older age Peripheral vascular disease Reduced blood circulation Diabetes Pre-existing nail dystrophy Previous nail trauma Integrity of nail unit is compromised Micro- traumatic pressure on nail Dark, warm shoe environment Optimal conditions for fugal growth Exposure to tinea pedis or onychomycosis Direct spread of infection to nail unit High blood sugar favoring infection Dermatophytes invade corneocytes on stratum corneum, the uppermost non-living layer of keratinized skin Compromise/breaking of hyponychial seal or cuticle (connection between hyponychium and nail plate) Proximal Subungual White Superficial Distal Subungual Superinfecting bacteria or other fungi proliferate beneath the compromised nail imparting a yellowish appearance Distal Subungual Subtype (Thick yellow nails, keratin and debris accumulate distally underneath nail plate) Infection spreads to distal hyponychial space Dermatophytes colonize local tissue in nail plate and nail bed Dermatophytes feed on keratinized tissue Keratinocytes produce an acute, low-grade inflammatory cytokine response Onychomycosis Dermatophytic infection of the nail bed Inflammation promotes ↑ fluid to tissues for ↑ immune cell delivery Widespread inflammation thickens parts of the epidermis in efforts to shed the infection Inflammation and epidermal hyperplasia (↑ growth of cells) influence local dermal papillae (group of cells just beneath the hair follicle) to proliferate and project above the skin General Symptoms (All Subtypes) Spongiosis (Intercellular edema) Acanthosis (Thickening of stratum spinosum layer of epidermis) Hyperkeratosis (Thickening of stratum corneum In effort to rid infection) Papillomatosis (Projections of dermal papillae) Secondary damage to nail matrix Loss of nail Tinea infection (e.g. Tinea Pedis, Corporis, Capitis) Dermatophytes invade the proximal end of the nail plate Dermatophytes penetrate through the cuticle to the newly forming nail plate moving distally Proximal Subungual Subtype (Whitish discolouration of nail plate that begins proximally and moves distally, indicative of immunosuppression) Fungi predominantly invade various areas of the superficial nail plate layers eventually joining together White Superficial Subtype (Chalky white scale that spreads slowly beneath nail plate, well-defined “white islands” that coalesce as disease progresses) The entirety of the nail plate is infected by the dermatophytes Widespread inflammation thickens the nail plate as well as beneath the nail (subungual hyperkeratosis) in efforts to shed the infection Total Dystrophic Subtype (End-stage nail disease, entire nail becomes thick and dystrophic) Dermatophytes spread deeper into toe Bacteria enters lymphatics and bloodstream Abnormal keratinization in hyponychium Keratin accumulates between nail plate and hyponychium Local spread of infection causing cracks in the skin Fissure (splits in the skin) Cellulitis Sepsis Onycholysis (nail plate separates from nail bed) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published MONTH, DAY, YEAR on www.thecalgaryguide.com Dermatophyte Onychomycosis: Pathogenesis and clinical findings Authors: Holly Zahary Loreman Reviewers: Mina Youakim Elise Hansen Shahab Marzoughi Jodi Hardin* * MD at time of publication Host Risk Factors Environmental Risk Factors Immuno- Older compromised age ↓ Immune response to infection Peripheral vascular disease Reduced blood circulation Diabetes Pre-existing nail dystrophy Previous nail trauma Integrity of nail unit is compromised Micro- traumatic pressure on nail Dark, warm shoe environment Optimal conditions for fugal growth Exposure to tinea pedis or onychomycosis Direct spread of infection to nail unit High blood sugar favoring infection Dermatophytes invade corneocytes on stratum corneum, the uppermost non-living layer of keratinized skin Compromise/breaking of hyponychial seal or cuticle (connection between hyponychium and nail plate) Tinea infection (e.g. Tinea Pedis, Corporis, Capitis) Infection spreads to distal hyponychial space Dermatophytes colonize local tissue in nail plate and nail bed Dermatophytes feed on keratinized tissue Keratinocytes produce an acute, low-grade inflammatory cytokine response Onychomycosis Dermatophytic infection of the nail bed General Symptoms (All Subtypes) Spongiosis (Intercellular edema) Acanthosis (Thickening of stratum spinosum layer of epidermis) Papillomatosis (Projections of dermal papillae) Hyperkeratosis (Thickening of stratum corneum In effort to rid infection) Secondary damage to nail matrix Loss of nail Proximal Subungual White Superficial Distal Subungual Distal Subungual Subtype (Thick yellow nails, keratin and debris accumulate distally underneath nail plate) Proximal Subungual Subtype (Whitish discolouration of nail plate that begins proximally and moves distally, indicative of immunosuppression) White Superficial Subtype (Chalky white scale that spreads slowly beneath nail plate, well-defined “white islands” that coalesce as disease progresses) Total Dystrophic Subtype (End-stage nail disease, entire nail becomes thick and dystrophic) Local spread of infection causing cracks in the skin Dermatophytes spread deeper into toe Abnormal keratinization in hyponychium Keratin accumulates between nail plate and hyponychium Onycholysis (nail plate separates from nail bed) Fissure (splits in the skin) Bacteria enters lymphatics and bloodstream Cellulitis Sepsis Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Legend: Published MONTH, DAY, YEAR on www.thecalgaryguide.com Dermatophyte Onychomycosis: Pathogenesis and clinical findings Authors: Holly Zahary Loreman Reviewers: Mina Youakim Elise Hansen Shahab Marzoughi Jodi Hardin* * MD at time of publication Host Risk Factors Environmental Risk Factors Immuno- Older compromised age ↓ Immune response to infection Peripheral vascular disease Reduced blood circulation Diabetes Pre-existing nail dystrophy Previous nail trauma Integrity of nail unit is compromised Micro- traumatic pressure on nail Dark, warm shoe environment Optimal conditions for fugal growth Exposure to tinea pedis or onychomycosis Direct spread of infection to nail unit High blood sugar favoring infection Dermatophytes invade corneocytes on stratum corneum, the uppermost non-living layer of keratinized skin Compromise/breaking of hyponychial seal or cuticle (connection between hyponychium and nail plate) Tinea infection (e.g. Tinea Pedis, Corporis, Capitis) Infection spreads to distal hyponychial space Dermatophytes colonize local tissue in nail plate and nail bed Dermatophytes feed on keratinized tissue Keratinocytes produce an acute, low-grade inflammatory cytokine response Onychomycosis Dermatophytic infection of the nail bed Proximal Subungual White Superficial General Symptoms (All Subtypes) Spongiosis (Intercellular edema) Acanthosis (Thickening of stratum spinosum layer of epidermis) Papillomatosis (Projections of dermal papillae) Hyperkeratosis (Thickening of stratum corneum In effort to rid infection) Secondary damage to nail matrix Loss of nail Distal Subungual Distal Subungual Subtype (Thick yellow nails, keratin and debris accumulate distally underneath nail plate) Proximal Subungual Subtype (Whitish discolouration of nail plate that begins proximally and moves distally, indicative of immunosuppression) White Superficial Subtype (Chalky white scale that spreads slowly beneath nail plate, well- defined “white islands” that coalesce as disease progresses) Total Dystrophic Subtype (End-stage nail disease, entire nail becomes thick and dystrophic) Local spread of infection causing cracks in the skin Dermatophytes spread deeper into toe Abnormal keratinization in hyponychium Keratin accumulates between nail plate and hyponychium Onycholysis (nail plate separates from nail bed) Bacteria enters lymphatics and bloodstream Fissure (splits in the skin) Cellulitis Sepsis Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Legend: Published MONTH, DAY, YEAR on www.thecalgaryguide.com Dermatophyte Onychomycosis (Tinea Unguium): Pathogenesis, clinical findings, Authors: Holly Zahary Loreman Reviewers: Elise Hansen Name Name* * MD at time of publication and complications Host Risk Factors Environmental Risk Factors Immuno- compromised ↓ immune response to infection Older age Peripheral vascular disease Diabetes Pre-existing nail dystrophy Previous Nail Trauma Integrity of nail unit is compromised Micro-traumatic pressure on nail Dark, warm shoe environment Optimal conditions for fugal growth Exposure to tinea pedis or onychomycosis Direct spread of infection to nail unit Reduced blood circulation High blood sugar, favoring infection Tinea pedis infection (see ‘Tinea Capitis, Tinea Corporis, and Tinea Pedis’) Infection spreads to distal hyponychial space Dermatophytes colonize local tissue in nail plate and nail bed Dermatophytes feed on keratinized tissue Proximal Subungual White Superficial Dermatophytes invade corneocytes on stratum corneum, the uppermost non-living layer of keratinized skin Compromise/breaking of hyponychial seal or cuticle (connection between hyponychium and nail plate) Keratinocytes produce an acute, low-grade inflammatory cytokine response Onychomycosis (Tinea Unguium) (dermatophytic infection of the nail bed) Distal Subungual General Symptoms (All Subtypes) Spongiosis Intercellular edema Acanthosis Thickening of stratum spinosum layer of epidermis Papillomatosis Projections of dermal papillae Hyperkeratosis Thickening of stratum corneum In effort to rid infection Secondary damage to nail matrix Loss of nail Distal Subungual Subtype Thick yellow nails, keratin and debris accumulate distally underneath nail plate Proximal Subungual Subtype Whitish discolouration of nail plate that begins proximally and moves distally, indicative of immunosuppression White Superficial Subtype Chalky white scale that spreads slowly beneath nail plate, well-defined “white islands” that coalesce as disease progresses Total Dystrophic Subtype End-stage nail disease, entire nail becomes thick and dystrophic Local spread of infection causing cracks in the skin Dermatophytes spread deeper into toe Abnormal keratinization in hyponychium Keratin accumulates between nail plate and hyponychium Onycholysis (nail plate separates from nail bed) Tissue Damage Cellulitis Sepsis Bacteria enters lymphatics and bloodstream Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Legend: Published MONTH, DAY, YEAR on www.thecalgaryguide.com

MI Complication Ventricular Wall Rupture

Atrial Septal Defect Pathogenesis and Clinical Findings

Atrial Septal Defect (ASD): Pathogenesis and clinical findings Genetic syndromes (e.g., Holt- Oram, Noonan, and Down) Gene mutations (e.g., TBX5, GATA4, and NKX2-5) Authors: Ryan Wilkie George Tadros Reviewers: Julena Foglia Haotian Wang Shahab Marzoughi Tim Prieur* * MD at time of publication Spontaneous Abnormal formation of the septum of the atria Atrial Septal Defect (ASD) An abnormal connection between the left and right atria of the heart Following birth, lungs fill with air and resistance to blood flow in the lung vasculature ↓ Pressure within the right ventricle and right atrium ↓ Left atrial pressure exceeds right atrial pressure Blood passes from left to right through the ASD (left-to-right shunt) ↑ Blood flow through the right heart ↑ Blood flow through tricuspid valve Mid-diastolic murmur Right-sided heart dilation (enlargement of the right ventricle) Enlarged ventricle cannot pump blood effectively Congestive Heart Failure ↑ Blood flow through pulmonary valve and pulmonary vasculature Right ventricular heave (visible or palpable chest wall impulse around sternum) ↑ Right atrial wall stress Inspiration produces no net pressure change between communicating atria Delayed closure of pulmonary valve (relative to aortic valve) Morphologic changes in pulmonary vasculature from long standing exposure to high blood flow Pulmonary vascular resistanceáover time, may surpass systemic vascular resistance **Pulmonary Hypertension** Mid-systolic ejection murmur Heart is unable to pump enough blood to meet demand during activity (including feeding) ↑ Backup of blood in lungs ↑ Hydrostatic pressure in lung vasculature Pulmonary edema Damage to normal conduction of electrical signal from the atria to the ventricles ECG Changes: Prolonged PR and QRS intervals, right bundle branch block, right axis deviation Fixed split S2 (two distinct sounds are heard as part of S2) Reduced exercise capacity ↓ Eating Failure to thrive Fatigue Atrial arrhythmias (atrial fibrillation or flutter) Irregular beats are felt in the chest wall Palpitations Dyspnea ↓ Ability to clear foreign particles from interstitium due to presence of extra fluid Respiratory tract infections ** See Relevant Calgary Guide Slide ** Pulmonary Hypertension: Pathogenesis and clinical findings Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Nov 1, 2014; updated Mar 21, 2024 on www.thecalgaryguide.com

Angioedema Bradykinin Mediated

Angioedema – Bradykinin Mediated: Pathogenesis and clinical findings Drug Induced Angiotensin converting enzyme inhibitor, dipeptidyl peptidase-4 inhibitor, or neprilysin inhibitor use Hereditary Type II Acquired Thrombolytic use Activate factor XII Factor XII initiates bradykinin synthesis Type I Type III Gain of function gene mutation in bradykinin cascade activators (factor XII) & precursors (kininogen), triggered by ↑ systemic estrogen Rheumatologic disorders & B- cell lymphoproliferative disease Complement cascade activation results in ↑ C1 protease production C1 esterase inhibitor is utilized to neutralize C1 protease, with its consumption exceeding its synthesis Plasma cell proliferation (i.e., dyscrasia/ monoclonal gammopathy) Immunoglobulin G antibodies act against C1 esterase inhibitor to render it non-functional Genetic or spontaneous mutation in C1 esterase inhibitor gene C1 esterase inhibitor deficiency C1 esterase inhibitor dysfunction Inhibition of angiotensin converting enzyme, dipeptidyl peptidase-4, or neprilysin induced metabolism of bradykinin ↓ Bradykinin (peptide hormone) degradation in plasma Misfunctioning C1 esterase inhibiter is unable to inactivate bradykinin cascade members ↓ C1 esterase inhibiter results in inadequate inactivation of bradykinin cascade members ↑ Bradykinin protein production in plasma Cutaneous Tissue Mucosal Tissue Epidermal layer Dermal-Epidermal Junction Dermal layer Subcutaneous layer Systemic bradykinin excess Bradykinin-2 receptor binding on endothelial and vascular smooth muscle cells Hyperpermeability pathway activation, with the transcription of some signalling molecules taking hours Released pro-inflammatory mediators act on venules & arterioles in subcutaneous & submucosa tissues Relaxation of vascular smooth muscle Dissociation of endothelial cell junctions ↑ Capillary blood flow ↑ Vascular permeability ↑ Plasma release into interstitial tissues (specific regions of the body hypothesized to be affected due to local differences in endothelial structure and its response to permeability inducing stimuli) Dilation & ↑ permeability of vasculature results in fluid release into surrounding tissues Mucosal Layer Muscularis mucosae Submucosal layer Muscularis externa Intestinal edema (Fluid buildup in Intestine tissues) Intestinal swelling (↑ intra-abdominal pressure) Laryngeal edema (Fluid buildup in larynx) Swelling in larynx ↓ air flow into & out of lungs Asphyxia (body is deprived of oxygen) Dyspnea (difficult in breathing) Author: Aaron Varga Reviewers: Tracey Rice Sunawer Aujla Shahab Marzoughi Maharshi Gandhi Jori Hardin* Yan Yu* * MD at time of publication Peripheral edema (Fluid buildup in extremities such as the hands, ankles, and feet) Ascites, bowel obstruction, &/or hypovolemic shock Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Mar 21, 2024 on www.thecalgaryguide.com

Macrosomia Pathogenesis and Complications

Macrosomia: Pathogenesis and complications Fetal congenital disorders (e.g. Fragile X syndrome, Weaver syndrome) Genes encoding cellular growth are mutated and induce ↑ cell proliferation Fetus with XY chromosomes Y chromosome predisposes fetus to excess growth factor Pregnancy longer than 42 weeks Birth weight ↑ as gestational age ↑ Pregnant parent with BMI > 30 kg/m2 ↑ Central adipose tissue release insulin- desensitizing factors ↑ Insulin resistance promotes hepatic glucose production Macrosomia Parent has previously had ≥ 2 births Average birth weight ↑ with each successive pregnancy Pregnant parent with type 2 diabetes or gestational diabetes (1-hour 50 g glucose challenge test >140 mg/dL at 24-28 weeks gestation) Parent’s glucose-rich blood is carried to the fetus through the placenta ↑ Levels of glucose present in fetal circulation promotes excessive growth (Fetus grows beyond absolute birth weight (> 4000 g) regardless of gestational age) Fetal dysregulation of glucose and fetal programming of later adiposity Metabolic syndromes (e.g. hypoglycemia, hyperinsulinemia) ↑ Insulin levels delay pulmonary maturation Respiratory distress Large fetal size in the uterus Cardiac mass ↑ in proportion to body size Fetal cardiac remodeling (e.g. ↑ left ventricular mass) Uterine muscle wall stretched beyond optimal range Uterine rupture Parent pushes fetus into birth canal Maternal nutrition supply is unable to meet fetus’ increased metabolic demands ↑ Uterine distension prevents uterine muscles from contracting (uterine atony) Fetus takes longer to descend through the birth canal Large fetal size overstretches pelvic structures Perianal trauma (e.g. lacerations to pelvic floor, vagina, rectum) Less space in birth canal prevents the parent from delivering the anterior fetal shoulder after the fetal head Shoulder dystocia (baby’s shoulder stuck during birth) Arrested labour (slow cervical dilation) Insufficient space in birth canal to deliver fetus Assisted vaginal birth/ cesarian section Protracted labour (slow fetal descent) Stillbirth Fetal distress (↓ heart rate) Lack of mechanical contraction of the spiral arteries, normally provided by uterine muscles Blood loss (≥ 500-1000 mL 24 hours post birth) Postpartum hemorrhage Authors: Akaya Blair Reviewers: Dasha Mori Michelle J. Chen Dr. Ian Mitchell* * MD at time of publication ↑ Frequency/ prolonged admission (≥ 3 days) to neonatal intensive care unit Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Mar 21, 2024 on www.thecalgaryguide.com

Apnea of Prematurity

Apnea of Prematurity: Pathogenesis, Signs & Symptoms, and Complications Physiologic immaturity from birth at < 37 weeks gestation Authors: Akaya Blair Reviewers: Dasha Mori Michelle J. Chen Danielle Nelson* * MD at time of publication ↓ Synaptic connection & poor myelination Fetal brain areas responsible for breathing are poorly developed Immature neurologic respiratory function Immature mechanical respiratory function Poor hypopharyngeal muscle tone (soft upper airway helps with size and compliance of airway) Nasal obstruction (e.g. anatomic and/or iatrogenic [suctioning, NG tubes]) Neonate is reliant on nose breathing Airway is unable to remain open (patent) Laryngeal/tracheal abnormalities (e.g. tracheomalacia, laryngeal edema, tracheal stenosis) Anatomical narrowing leading to ↑ airway resistance ↑ Risk of mechanical airway obstruction Disruption of central respiratory drive ↓ Sensitivity to increased CO2 in the ventral medulla oblongata Disruption of peripheral respiratory reflex pathways ↓ Sensitivity to CO2 levels in peripheral carotid bodies and aortic bodies Large head size forces neck into flexion when laying supine Immature airway sensitive to collapse when in flexion ↑ Hypotonia (decreased muscle tone) in REM sleep ↓ Signaling to brainstem Brainstem unable to mount appropriate ventilatory response to insufficient oxygen Upper airway collapse Apnea of prematurity Respiratory pauses >20 sec or pauses <20 sec with bradycardia (<100 beats per minute), central cyanosis, and/or oxygen saturation <85% in neonates born at <37 weeks gestation and with no underlying disorders causing apnea. Most apneas in apnea of prematurity are central or mixed. ↓ Breathing rate Bradycardia (<100 bpm) ↓ Oxygen to brain Poor neurodevelopmental outcomes (e.g. cognitive function, brain adaptive potential and plasticity) Hypoxemia (↓blood oxygen levels where SpO2 <85%) ↓ Oxygen and hemoglobin to mucous membranes (e.g. lips) & fingers and toes (periphery) Central & peripheral cyanosis (bluish discoloration) ↓ Oxygen to retina Abnormal growth of blood vessels in eyes Retinopathy of prematurity (changes in visual acuity and possible blindness) Death/impairment in cell function from lack of oxygen ↑ Risk of infant mortality Imbalanced oxygen intake and CO2 output in lungs Body transiently ↑ HR to unsuccessfully try to compensate for ↓ tissue oxygenation Respiratory failure Respiratory rate >60 ↓ Heart rate ↓ Blood pressure Head bobbing Abdominal breathing Skin mottling Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Mar 21, 2024 on www.thecalgaryguide.com

Neonatal Necrotising Enterocolitis in Premature Neonates

Neonatal Necrotising Enterocolitis (NEC) in Premature Neonates: Pathogenesis and clinical findings Prematurity risk factors ↓ Intestinal motility ↑ Intestinal stasis allows bacteria more time to proliferate Bacterial overgrowth in gut ↓ Goblet cells in intestinal epithelium ↓ Intestinal mucus layer production leads to impaired mechanical defense against pathogenic bacteria Immature tight junctions in intestinal epithelium ↑ Permeability of intestinal epithelial barrier ↑ Toll-like receptor 4 (TLR4) expression on intestinal epithelial cells Aberrant bacterial colonization of gut Impaired gut barrier allows for ↑ bacterial translocation across intestinal epithelium TLR4 on intestinal mesentery endothelial cells bind lipopolysaccharides (LPS) on Gram-negative gut bacteria Immune cells release proinflammatory mediators (TNF, IL-12, IL-18) Cytokines mediate ↑ enterocyte apoptosis (including enteric stem cells) and ↓ enterocyte proliferation Intestinal mucosa healing is impaired, leading to local inflammation & injury TLR4 on intestinal epithelial cells binds LPS from Gram-negative gut bacteria Authors: Rachel Bethune Naima Riaz Reviewers: Nicola Adderley Michelle J. Chen Kamran Yusuf* Jean Mah* * MD at time of publication Endothelial nitric oxide synthase expression is reduced Vasoconstriction from ↓ NO reduces blood flow to intestines Prolonged ↓ in O2 perfusion results in irreversible intestinal mucosal cell death (necrosis) Gas escapes into abdominal cavity Leakage of intestinal contents irritates parietal peritoneum Bacteria enter bloodstream Pneumo- peritoneum Abdominal distention Peritonitis Sepsis Blood from tissue damage mixes with intestinal contents Bloody stool Intestinal sensory neurons detect damage and send signals to medullary vomiting centre Bilious vomiting Damaged intestinal cells are unable to absorb nutrients Short gut syndrome Persistent intestinal mucosal injury creates penetrating lesions through intestinal wall Intestinal perforation Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 6, 2019; updated Mar 21, 2024 on www.thecalgaryguide.com

Lichen Sclerosus

Lichen Sclerosus (genital manifestation): Pathogenesis and clinical findings Authors: Mina Youakim Reviewers: Elise Hansen Sunawer Aujla Shahab Marzoughi Jori Hardin* * MD at time of publication Histamine receptor binding stimulates sensory nerve endings Pruritus (itching) Unknown triggers Genetic predisposition (HLA-DQ7 and HLA-DR12) Chronic inflammation (i.e. chronic infection, chronic toxin exposure) and trauma Medications (e.g. carbamazepine, pembrolizumab, nivolumab, ipilimumab) ↑ Activation of CD4+ and CD8+ T cells released from macrophages (white blood cell) in the perineum and genital skin tissue infiltrate into the dermal-epidermal junction T-cells proliferate in a horizontal linear formation Pro-inflammatory response activation Fibroblasts (contributes to the formation of connective tissue) proliferate and persist producing altered collagen under the epidermis Collagen deposits and hyalinizes (transforms into acellular translucent material) beneath the epidermal layer Sclerotic plaques (localized areas of thickened skin) T cells release of pro-inflammatory cytokines (interleukins and transforming growth factor β) ↑ Oxidative stress and cell damage Progressive basal layer degeneration thins the overall skin thickness Mast cells respond to increased need for immune cell flow to area Nitric oxide is released when histamine binds to vascular receptors Localized area appears red Erythema (reddening of the skin) Erosion/ulceration Skin fissures (linear cleavage of skin) Localized histamine release Nitric oxide induces localized vasodilation (↑ blood flow) Normal Skin Lichen Sclerosus Epidermal layer Basal layer Dermal-Epidermal Junction Dermal layer Hypopigmented patches (localized, pale areas of skin) Epidermal atrophy (crinkling paper-type skin appearance) Thinned skin is weakened and prone to physical stress or trauma ↑ fluid in the extracellular space due to capillary leakage from ↑ blood flow Superficial dermal edema (swelling) Fibrotic tissue deposition following healing of damaged tissue Atrophic Epidermal layer Hyalinized collagen deposits Basal layer degeneration Band of T-cell infiltrate Dermal layer Scarring Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Mar 25, 2024 on www.thecalgaryguide.com Lichen Sclerosus (genital manifestation): Pathogenesis and clinical findings Authors: Mina Youakim Reviewers: Elise Hansen Sunawer Aujla Shahab Marzoughi Jori Hardin* * MD at time of publication Histamine receptor binding stimulates sensory nerve endings Pruritus (itching) Unknown triggers Genetic predisposition (HLA-DQ7 and HLA-DR12) Chronic inflammation (i.e. chronic infection, chronic toxin exposure) and trauma Medications (e.g. carbamazepine, pembrolizumab, nivolumab, ipilimumab) ↑ Activation of CD4+ and CD8+ T cells released from macrophages (white blood cell) in the perineum and genital skin tissue infiltrate into the dermal-epidermal junction T-cells proliferate in a horizontal linear formation Pro-inflammatory response activation Fibroblasts (contributes to the formation of connective tissue) proliferate and persist producing altered collagen under the epidermis Collagen deposits and hyalinizes (transforms into acellular translucent material) beneath the epidermal layer Sclerotic plaques (localized areas of thickened skin) T cells release of pro-inflammatory cytokines (interleukins and transforming growth factor β) ↑ Oxidative stress and cell damage Mast cells respond to increased need for immune cell flow to area Nitric oxide is released when histamine binds to vascular receptors ↑ fluid in the extracellular space due to capillary leakage from ↑ blood flow Superficial dermal edema (swelling) Epidermal atrophy (crinkling paper- type skin appearance) Thinned skin is weakened and prone to physical stress or trauma Localized histamine release Nitric oxide induces localized vasodilation (↑ blood flow) Localized area appears red Erythema (reddening of the skin) Erosion/ulceration Skin fissures (linear cleavage of skin) Normal Skin Lichen Sclerosus Epidermal layer Basal layer Dermal-Epidermal Junction Dermal layer Atrophic Epidermal layer Hyalinized collagen deposits Basal layer degeneration Band of T-cell infiltrate Dermal layer Progressive basal layer degeneration thins the overall skin thickness Hypopigmented patches (localized, pale areas of skin) Fibrotic tissue deposition following healing of damaged tissue Scarring Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published MONTH, DAY, YEAR on www.thecalgaryguide.com Chronic inflammation (i.e. chronic Reviewers: Dermal layer Unknown triggers Genetic predisposition (HLA-DQ7 and HLA-DR12) infection, chronic toxin exposure) and trauma Medications (e.g. carbamazepine, pembrolizumab, nivolumab, ipilimumab) Elise Hansen Sunawer Aujla Shahab Marzoughi Jori Hardin* * MD at time of publication ↑ Activation of CD4+ and CD8+ T cells released from macrophages (white blood cell) in the perineum and genital skin tissue infiltrate into the dermal-epidermal junction T-cells proliferate in a horizontal linear formation Pro-inflammatory response activation ↑ Expression of MicroRNA-155 (enhances pro-inflammatory response and ↓ expression of tumor suppression genes) Fibroblasts (contributes to the formation of connective tissue) proliferate and persist producing altered collagen Collagen deposits and hyalinizes (transforms into acellular translucent material) beneath the epidermal layer Sclerotic plaques (localized areas of thickened skin) T cells release of pro-inflammatory cytokines (interleukins and transforming growth factor β) ↑ Oxidative stress and cell damage Mast cells respond to increased need for immune cell flow to area Nitric oxide is released when histamine binds to vascular receptors ↑ fluid in the extracellular space due to capillary leakage from ↑ blood flow Superficial dermal edema (swelling) Epidermal atrophy (crinkling paper- type skin appearance) Thinned skin is weakened and prone to physical stress or trauma Lichen Sclerosus Localized histamine release Nitric oxide induces localized vasodilation (↑ blood flow) Localized area appears red Erythema (reddening of the skin) Erosion/ulceration Skin fissures (linear cleavage of skin) Atrophic Epidermal layer Hyalinized collagen deposits Basal layer degeneration Band of T-cell infiltrate Histamine receptor binding stimulates sensory nerve endings Pruritus (itching) Normal Skin Progressive basal layer degeneration thins the overall skin thickness Hypopigmented patches (localized, pale areas of skin) Epidermal layer Basal layer Dermal-Epidermal Junction Fibrotic tissue deposition following healing of damaged tissue Scarring Chronic inflammation (i.e. chronic Reviewers: Dermal layer Unknown triggers Genetic predisposition (HLA-DQ7 and HLA-DR12) infection, chronic toxin exposure) and trauma Medications (e.g. carbamazepine, pembrolizumab, nivolumab, ipilimumab) Elise Hansen Sunawer Aujla Shahab Marzoughi Jori Hardin* * MD at time of publication ↑ Activation of CD4+ and CD8+ T cells released from macrophages in the perineum and genital skin tissue infiltrate into the dermal-epidermal junction T-cells proliferate in a horizontal linear formation Pro-inflammatory response activation ↑ Expression of MicroRNA-155 (short segment of RNA which enhances pro- inflammatory response and ↓ expression of tumor suppression genes) Fibroblasts proliferate and persist producing altered collagen Collagen deposits and hyalinizes (transforms into acellular translucent material) beneath the epidermal layer Sclerotic plaques (localized areas of thickened skin) T cells release of pro-inflammatory cytokines (interleukins and transforming growth factor β) ↑ Oxidative stress and cell damage Progressive basal layer degeneration thins the overall skin thickness Hypopigmented patches (localized, pale areas of skin) Epidermal layer Basal layer Dermal-Epidermal Junction Mast cells respond to increased need for immune cell flow to area Nitric oxide is released when histamine binds to vascular receptors Superficial dermal edema (swelling) Epidermal atrophy (crinkling paper- type skin appearance) Localized histamine release Nitric oxide induces localized vasodilation (↑ blood flow) Localized area appears red Erythema (reddening of the skin) Histamine receptor binding stimulates sensory nerve endings Pruritus (itching) Normal Skin Lichen Sclerosus Skin fissures (linear cleavage of skin) Erosion/ulceration Fibrotic tissue deposition following healing of damaged tissue Scarring Atrophic Epidermal layer Hyalinized collagen deposits Basal layer degeneration Band of T-cell infiltrate Reviewers: Dermal layer Unknown triggers Genetic predisposition (HLA-DQ7 and HLA-DR12) Chronic inflammation (i.e. chronic infection, chronic toxin exposure) and trauma Medications (e.g. carbamazepine, pembrolizumab, nivolumab, ipilimumab) Elise Hansen Sunawer Aujla Shahab Marzoughi Jori Hardin* * MD at time of publication ↑ Activation and infiltration of CD4+ and CD8+ T cells into the dermal-epidermal junction T-cells proliferate in a band (horizontal linear) formation Pro-inflammatory response activation ↑ Expression of MicroRNA-155 (short segment of RNA which enhances pro-inflammatory response and ↓ expression of tumor suppression genes) Fibroblasts proliferate and persist producing altered collagen Collagen deposits and hyalinizes (transforms into acellular translucent material) beneath the epidermal layer Sclerotic plaques (localized areas of thickened skin) T cells release of pro-inflammatory cytokines (interleukins and transforming growth factor β) ↑ Oxidative stress and cell damage Progressive basal layer degeneration thins the epidermis Hypopigmented patches (localized, pale areas of skin) Epidermal layer Basal layer Dermal-Epidermal Junction Mast cells respond to increased need for immune cell flow to area Nitric oxide is released when histamine binds to vascular receptors Superficial dermal edema (swelling) Epidermal atrophy (crinkling paper- type skin appearance) Localized histamine release Histamine receptor binding stimulates sensory nerve endings Pruritus (itching) Skin fissures (linear cleavage of skin) Nitric oxide induces localized vasodilation (↑ blood flow) Localized area appears red Erythema (reddening of the skin) Scarring Atrophic Epidermal layer Hyalinized collagen deposits Basal layer degeneration Band of T-cell infiltrate Erosion/ulceration Fibrotic tissue deposition following healing of damaged tissue Normal Skin Lichen Sclerosus Chronic inflammation (i.e. chronic Elise Hansen Unknown triggers Genetic predisposition infection, chronic toxin exposure) Medications (e.g. carbamazepine, (HLA-DQ7 and HLA-DR12) and trauma pembrolizumab, nivolumab, ipilimumab) ↑ Activation and infiltration of CD4+ and CD8+ T cells into the dermal-epidermal junction Sunawer Aujla Shahab Marzoughi Name Name* * MD at time of publication T-cells proliferate in a band (horizontal linear) formation Pro-inflammatory response activation (increase in pro-inflammatory cytokines such as Interleukins 1-alpha and 1-beta) ↑ Expression of MicroRNA-155 (short segment of RNA which enhances pro-inflammatory response and ↓ expression of tumor suppression genes) Fibroblasts proliferate and persist producing altered collagen T cells release of pro-inflammatory cytokines (interleukins and transforming growth factor β) ↑ Oxidative stress and cell damage Progressive basal layer degeneration thins the epidermis Hypopigmented patches (localized, pale areas of skin) Histamine receptor binding stimulates sensory nerve endings Localized area appears red Localized histamine release Localized vasodilation (↑ blood flow) Superficial dermal edema (swelling) Pruritus Erythema Collagen deposits and hyalinizes (transforms into acellular translucent material) beneath the epidermal layer Normal Skin Sclerotic plaques (localized areas of thickened skin) Epidermal layer Basal layer Dermal-Epidermal Junction Dermal layer Skin fissures (linear cleavage of skin) Bleeding Erosion/Ulceration Epidermal atrophy (crinkling paper- type skin appearance) Lichen Sclerosus Atrophic Epidermal layer Hyalinized collagen deposits Basal layer degeneration Band of T-cell infiltrate Dermal layer Fibrotic tissue deposition following healing of damaged tissue Scarring Lichen Sclerosus (genital manifestation): Pathogenesis and clinical findings Authors: Mina Youakim Reviewers: Elise Hansen Sunawer Aujla Shahab Marzoughi Name Name* * MD at time of publication Pruritus Histamine receptor binding stimulates sensory nerve endings Localized area appears red Erythema Unknown triggers Genetic predisposition (HLA-DQ7 and HLA-DR12) Chronic inflammation and trauma Medications (e.g. carbamazepine, pembrolizumab, nivolumab, ipilimumab) ↑ Activation and infiltration of CD4+ and CD8+ T cells into the dermal-epidermal junction T-cells proliferate in a band formation Pro-inflammatory response activation ↑ Expression of MicroRNA-155 (short segment of RNA which enhances pro-inflammatory response and ↓ expression of tumor suppression genes) Fibroblasts proliferate and persist producing altered collagen T cells release of pro-inflammatory cytokines (interleukins and transforming growth factor β) Localized histamine release Localized vasodilation (↑ blood flow) Superficial dermal edema (swelling) Collagen deposits and hyalinizes beneath the atrophic epidermal layer Hypopigmented patches (localized, pale areas of skin) ↑ Oxidative stress and cell damage Progressive basal layer degeneration thins the epidermis Skin fissures Lichen Sclerosus Epidermal atrophy (crinkling paper- type skin appearance) Sclerotic plaques (localized areas of thickened skin) Bleeding Scarring Erosion/Ulceration Normal Skin Epidermal layer Basal layer Dermal-Epidermal Junction Dermal layer Atrophic Epidermal layer Hyalinized collagen deposits Basal layer degeneration Band of T-cell infiltrate Dermal layer Legend: Published MONTH, DAY, YEAR on www.thecalgaryguide.com Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications

Infectious Small Bowel Diarrhea

Infectious small bowel diarrhea: Pathogenesis and Signs/Symptoms Undercooked poultry, beef, pork, other foods Food, or travel to underdeveloped countries E. coli (ETEC) May produce Shiga toxins (a specific family of toxins that can lead to complications) Authors: Noriyah Al Awadhi Yan Yu Sara Cho Reviewers: Paul Ratti Jason Baserman Shahab Marzoughi Kerri Novak* * Indicates MD at time of publication Y. enterocolitica (also milk, cheese) Shellfish, undercooked seafood V. parahaemolyticus V. cholerae Enterohemorrhagic E. coli (EHEC) Daycare centers/nurseries Drinking/swimming in bad water — mountains/wells S. aureus B. cereus Noroviruses Rotavirus G. lamblia C. parvum May produce emetic toxins (toxins that cause vomiting) Adequate amount of organism and/or toxin is ingested Organism adheres to the intestinal liningàorganism colonizes the small intestine Organism releases enterotoxin (a toxin that affects the intestines) Binds to and disrupts intestinal transporters used in secretion and absorption of water and electrolytes Toxin enters systemic vasculature Shiga toxins inhibit ADAMTS13 (cleaving enzyme) Failure to cleave von Willebrand Factor (vWF) multimers Accumulation of vWF multimers Platelets and thrombi accumulate in microvasculature Hemolytic uremic syndrome (hemolytic anemia, thrombocytopenia, and acute renal damage) ↑ Water and electrolyte secretion ↓ Fluid absorption Chemoreceptor trigger zone in medulla detects circulating emetic toxins Nausea & vomiting Triggers release of inflammatory mediators and cytokines that travel to the central nervous system Prostaglandin is synthesized and released Neurotransmitter cyclic AMP (cAMP) is released cAMP ↑ hypothalamic thermoregulation set point Fever Large volume profuse diarrhea Loss of water Distention (swelling) of intestines stimulates visceral sensory pain fibers Visceral pain fibers crosstalk with somatic nerves from the same spinal cord level Occasional referred pain/cramping (typically diffuse pain around the abdomen) Loss of bicarbonate, sodium, potassium, magnesium, and chloride Dehydration Electrolyte deficiency Metabolic acidosis (pH < 7.4 & serum bicarbonate < 24) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Aug 7, 2012; updated Mar 25, 2024 on www.thecalgaryguide.com

Post-Renal Acute Kidney Injury AKI

Post-Renal Acute Kidney Injury (AKI): Pathogenesis and clinical findings Blood clot or cellular debris Foreign body Neurogenic bladder Obstruction intrinsic to urine excretion system Nephrolithiasis (kidney stones) Anatomical defect(s) Intra- abdominal adhesions Retroperitoneal fibrosis (scar-like tissue) Benign or malignant masses Prostate cancer Benign prostatic hyperplasia ↓ Urine flow across point of obstruction Obstruction extrinsic to urine excretion system Urine buildup distends urine collecting system (hydronephrosis) Compression of renal vasculature due to mass effect ↑ Volume/pressure proximal to obstruction ↑ Intratubular pressure ↓ Pressure gradient between glomerular afferent arteriole and Bowman’s space Casts occlude tubules ↓ Filtration of plasma into nephrons ↓ Glomerular Filtration Rate (GFR) Obstruction is relieved ↓ Intratubular pressure Rapid GFR ↑ Rapid diuresis of fluid and electrolytes Dilated pelvicalyceal system on ultrasound ↓ Urine output ↓ Venous drainage and arterial supply Local ischemia and inflammation of kidney Impaired resorption, excretion, and fine tuning by tubules Acute Tubular Necrosis (ATN) with granular casts ↓ Urine output ↓ Clearance of free water and solutes ↑ Intravascular volume ↑ Serum creatinine ↓ Medullary solute concentration, ischemia, ↓ response of collecting ducts to antidiuretic hormone Lasts > 24hrs Post-obstructive diuresis causes hypovolemia and electrolyte derangements Authors: David Campbell, Matthew Hobart Reviewers: Raafi Ali, Luiza Radu Huneza Nadeem, Marissa Zhang, Julian Midgley* * MD at time of publication Resolves < 24hrs in euvolemia Physiologic post- obstructive diuresis ↑ Na+ and Cl- delivery to distal convoluted tubule is sensed by macula densa Secretion of adenosine by macula densa Adenosine constricts afferent arterioles ↓ GFR ↓ Renal clearance of drugs and waste products ↑ Venous hydrostatic pressure ↑ Volume in arterial system overwhelms pressure regulation mechanisms Hypertension Fluid extravasation from veins and capillaries Generalized Edema Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Mar 25, 2024 on www.thecalgaryguide.com

Irritant Contact Dermatitis Pathogenesis and Clinical Findings

Irritant Contact Dermatitis: Pathogenesis and clinical findings Authors: Zaini Sarwar, Mina Youakim Reviewers: Shahab Marzoughi, Ryan T. Lewinson, Yan Yu*, Laurie M. Parsons* * MD at time of publication Repeated/chronic exposure causes damage to cell membranes Skin barrier disruption Chronic non-specific inflammatory response Repetitive keratinocyte cytokine-mediated injury Keratinocytes exhibit ↑ proliferation as a compensatory response Rapid turnover of stratum corneum (outermost layer of the epidermis) Hyperkeratotic skin is less amenable to skin stretching and pressure Skin fissures (cracks in the skin) Irritant agents (abrasives, cleaning solution, oxidative & reducing agents, dust, soils, water) Acute exposure triggers inflammatory response Keratinocytes undergo cytotoxic damage with ↑ neutrophil & cytokine release Common occupational exposures (housekeeping, cleaning, catering, medical/dental, construction) Risk factors (atopy, fair skin, low temperature, low humidity) Stimulation of local nociceptors (free nerve endings extend into the mid epidermis) Perivascular (around the blood vessel) inflammation causes histamine release from mast cells Damaged keratinocytes are destroyed via apoptosis (programmed cell death) Epidermal Necrosis (death of epidermal tissue) Shedding of necrotic tissue Ulceration (deep open wound on skin) Burning pain (uncomfortable stinging sensation) Pruritus (itching) Histamine causes local blood vessel dilation and ↑ blood flow to the area of skin affected Erythema (area appears red from ↑ blood flow) Burning & Itching Spongiosis Neutrophils Neutrophils Histamine causes local blood vessel walls to have ↑ permeability, thereby ↑ leakage of fluid Spongiosis (↑ fluid between keratinocytes in the epidermis) Fluid continues to build up from ongoing inflammation Vesiculation (fluid collections in the epidermis) Long-term skin scratching causes chronic irritation which eventually hardens the skin Lichenification (thick, hardened patches of skin) ↑ Overall keratin production Hyperkeratosis (thickening of the outermost skin layer) Further fluid buildup bursts vesicles leaving behind erosions and dried crust on the epidermis Crust (scaling over the skin) Lichenification Erosions (open sore on skin) Ulcer Epidermis Perivascular Inflammation Hyperkeratosis Dermis Dermal-epidermal junction Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Oct 19, 2016; updated Mar 30, 2024 on www.thecalgaryguide.com

Febrile Neutropenia Pathogenesis and clinical findings

Febrile Neutropenia (Neutropenic Fever): Pathogenesis and clinical findings Administration of cytotoxic chemotherapy for cancer treatment Acquired aplastic anemia Autoreactive T cells destroy bone marrow stem cells Congenital mutations in ELA2 gene (encodes neutrophil elastase) ↑ Neutrophil apoptosis Chemotherapy eliminates beneficial bacterial species from gut microbiota New microbiota composition allows for growth of colonizing bacteria Indwelling catheters inserted to deliver chemotherapy Skin-colonizing bacteria access tissues through catheters Bacteria penetrate tissue barriers Chemotherapy injures gastrointestinal mucosa Broken mucosal barrier increases susceptibility to infections Chemotherapy destroys circulating neutrophils Chemotherapy impairs bone marrow stem cells ↓ Production of neutrophils Neutropenia (Absolute Neutrophil Count (ANC) < 0.5x109 cells/L ↓ Immune cell ↓ Production of engulfment of microbes inflammatory mediators Fewer circulating neutrophils blunts the innate immune response Pathogens enter bloodstream from tissues Systemic infection Authors: Max Lazar Braxton Phillips Reviewers: Naman Siddique Michelle J. Chen Lynn Savoie* * MD at time of publication Dormant viral infections reactivate (e.g. cytomegalovirus, herpes simplex virus) ↑ Susceptibility to common bacterial infections Positive blood bacterial cultures Fever (T ≥ 38.3 oC or sustained T ≥ 38 oC for 1 hour) Immune system mounts an excessive inflammatory response that damages tissues and organs Sepsis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Dec 5, 2018; updated Mar 30, 2024 on www.thecalgaryguide.com

Overview of Ischemic Heart Disease

Ischemic Heart Disease (IHD): Pathogenesis of the various types of IHD Authors: Sean Spence Vaneeza Moosa Reviewers: Tristan Jones Jason Baserman Yan Yu Michelle J. Chen Frank Spence* * MD at time of publication ↑ Serum low-density lipoprotein (LDL) ↑ Availability of lipids that deposit in arterial wall ↓ Serum high-density lipoprotein (HDL) ↓ LDL removal from coronary artery walls (transport of LDL to liver is impaired) Atherosclerosis Conditions predisposing to vessel wall endothelial cell dysfunction (e.g. metabolic syndrome, smoking, hypertension, physical inactivity) Vessel wall vulnerable to infiltration by LDL and immune cells Arterial wall degeneration, characterized by fat deposition (atheromatous plaque) in and fibrosis of the inner layer of arteries Stable atheromatous plaque in coronary arteries Fibromuscular cap (formed by smooth muscle cells) overlying fatty plaque contents remains intact & plaque contents are not released into vessel lumen Plaque serves as a fixed lumenal obstruction to blood flow If vessel stenosis (narrowing) is significant (≥70%) myocardial oxygen demand starts to exceed supply (especially with exertion) Heart experiences a predictable & transient reduction in blood flow (myocardial ischemia) Unstable atheromatous plaque in coronary arteries The fibromuscular cap overlying fatty plaque ruptures Thrombogenic plaque contents (especially tissue factor) are exposed to the coagulation factors in the vessel lumen Activation of platelets & the clotting cascade at the site of rupture Thrombus forms over already partially occlusive plaque and further partially or completely occludes lumen ↓ Perfusion (blood flow) of myocardium Cardiomyocytes experience a transient decrease in blood flow (transient ischemia) Unstable Angina Cardiomyocytes experience death (infarction) Myocardial Infarction (MI) Stable Angina Acute Coronary Syndromes (ACS) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Jan 8, 2013; updated Mar 30, 2024 on www.thecalgaryguide.com