SEARCH RESULTS FOR: diabetes

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)

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" />

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" />

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 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

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

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.

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 " />

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

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 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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Operative Vaginal Delivery Indications

Operative Vaginal Delivery (forceps/vacuum): Indications Authors: Taylor Pigott Akaya Blair Reviewers: Michelle J. Chen Sylvie Bowden* Stephanie Cooper* Sarah Glaze* * MD at time of publication Abnormal fetal heart rate/fetal distress ↓ Risk of maternal and fetal morbidity/ morality Rupture of membranes without fetal head adequately applied to maternal pelvis Small pelvic outlet Narrow vaginal canal Cardiovascular disease Diabetes Hypertension Abdominal trauma Short umbilical cord Large for gestational age (LGA) fetus Neurological/ muscular disease ↑ Pain during labor Maternal contraindication to Valsalva maneuver (e.g., cardiac disease, cystic lung) Rush of fluid past the fetal head out through cervix Umbilical cord prolapse Umbilical vasoconstriction Umbilical cord compression ↓ Blood flow through umbilical cord Fetal presenting part applies pressure on umbilical cord Impaired vascular function and narrowed vessels ↓ blood flow around the body ↓ Oxygen transfer across the placenta Fetal oxygen deprivation and hypoxia Operative vaginal delivery with forceps or vacuum expedites delivery Placenta partially or completely separates from uterine wall (abruption) Increased tension of umbilical cord on placenta Fetal shoulder is lodged behind maternal pubic symphysis Delivery of the body is delayed Inability to adequately bear down to push Myometrium runs out of energy from repeated contractions and becomes less able to contract (↓ uterine tone) Uterine spiral arteries dependent on contractions for vasoconstriction remain dilated, allowing blood flow Postpartum hemorrhage Uterine rupture ↑ Risk of future pelvic organ prolapse ↑ Risk of future incontinence Prolonged labour Repeated contraction/ relaxation of the uterus without progress tears and damages uterine muscles ↓ Maternal endurance Inadequate fluid and food intake prior to/ during labor Multiples ↑ Sympathetic nervous system activation during labor Maternal exhaustion Uterine muscles stretch to accommodate multiple growing fetuses ↑ Pushing against pelvic floor and perineum Pushing force damages pelvic floor muscles and nerves ↓ Myometrial contractility ↑ Need for vaginal exams to check on labour progress Bacterial overgrowth in vagina and/or uterus Maternal infection Fetal infection ↓ Strength of contractions Epidural anesthetic Inability to ambulate to urinate ↑ Urinary catheterizations ↑ Epinephrine secretion from adrenal cortex Blood is shunted away from uterus/internal organs and towards heart and skeletal muscle Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published 03, ##, 2023 on www.thecalgaryguide.com

Diabetes Mellitus Pathophysiology Behind Lab Findings

Diabetes Mellitus: Pathophysiology behind laboratory findings Author: Nathan Archibald Reviewers: Gurreet Bhandal, Julia Gospodinov, Luiza Radu Samuel Fineblit* * MD at time of publication ↓ Transit of glucose transporter GLUT4 to cell surface (mainly adipose & muscle cells) ↓ Glucose uptake into cells Autoimmune destruction of pancreatic beta cells (type 1 diabetes mellitus) Insulin resistance (type 2 diabetes mellitus) Other causes of diabetes mellitus (genetic, drug- induced, pregnancy, etc.) ↑ Lipolysis (fat breakdown) in adipose tissue ↑ Free fatty acids & glycerol in bloodstream ↑ Oxidation of fatty acids in liver to form acetyl CoA ↑ Conversion of acetyl CoA to ketone bodies (ketogenesis) to be used as fuel for the brain Relative or absolute insulin deficiency ↓ Activation of adipose (fat tissue) & muscle cell transmembrane insulin receptors ↓ Activation of intracellular insulin signaling pathways (PI3K & MAP kinase) Cells cannot use glucose as a source of energy; thus body reacts as if it is starving ↑ Protein breakdown in muscle tissue ↑ Amino acids & lactate in bloodstream ↑ Substrates (glycerol, amino acids & lactate) available to produce glucose in the liver ↑ Glycogenolysis (breakdown of stored glucose - glycogen) & gluconeogenesis (production of glucose) in liver Glucose in bloodstream glycates (coats) hemoglobin in red blood cells; thus ↑ blood glucose leads to ↑ glycated hemoglobin ↑ Hemoglobin A1C ↑ Fasting blood glucose level ↑ Random blood glucose level ↑ Blood glucose following oral glucose tolerance test Diabetic ketoacidosis (DKA) in absolute insulin deficiency *See DKA slide Filtered ketone bodies exceed the reabsorption capacity of renal tubules Ketonuria (↑ ketones in urine) ↑ Glucose in bloodstream Build-up of glycation end products causes damage to glomerular tissue Transient glomerular hyperfiltration followed by long-term ↓ in glomerular filtration rate Albuminuria (↑ albumin in urine) Diabetic nephropathy *See slide Filtered glucose exceeds reabsorption capacity of renal tubules in the kidney Glucosuria (↑ glucose in urine) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 8, 2024 on www.thecalgaryguide.com

Neonatal Hypoglycemia Pathogenesis

Neonatal Hypoglycemia: Pathogenesis Normal physiology Placenta supplies fetal circulation with glucose Clamping of the umbilical cord stops the source of glucose Blood glucose level declines rapidly in the first 2-3 hours of life Low glucose causes an ↓ in insulin and an ↑ in epinephrine, cortisol and glucagon Glucagon and epinephrine act on receptors in the liver and skeletal muscle to promote gluconeogenesis (glucose production from non- carbohydrate sources), glycogenolysis (breakdown of glycogen into glucose), and fatty acid oxidation (conversation of fatty acids to ATP) Low glucose levels stimulate the neonate’s appetite, allowing them to adapt to intermittent feeds Infant feeding regularly on a diet with sufficient carbohydrates creates a consistent plasma glucose concentration Pregnant Parent Causes Impaired Glucose Production Inadequate Glucose Supply Pregnant parent using β-blockers β-blockers prevent epinephrine from binding to adrenergic receptors in skeletal muscle and liver Blocked sympathetic signaling in these organs prevents glycogenolysis ↓ Breakdown of glycogen into glucose Infant of a parent with diabetes Parent has a high level of glucose in their blood The fetus receives a glucose-rich blood supply Fetal pancreatic β cells ↑ insulin production Post-birth, glucose levels in the infant’s circulation ↓ but insulin levels remain high Excessive glucose uptake into cells Fetus born with a metabolism disorder (e.g. organic amino acid disorder, disorder of glycogen metabolism, disorder of gluconeogenesis) Genes that make proteins or hormones responsible for production, breakdown and regulation of glycogen are mutated Fetus born with an endocrine disorder (e.g. congenital adrenal hyperplasia, hypopituitarism, Turner Syndrome) Pituitary and/or adrenal gland dysfunction ↓ release of hormones that regulate glucose balance Fetal growth is restricted, fetus is small for gestational age, or is premature (<37 weeks gestation) Glycogen is deposited during the 3rd trimester of pregnancy. Infants born early have fewer stores; smaller infants born at term have ↓ stores, ↑ insulin sensitivity, & poorly coordinated counter- regulatory hormones ↑ Glucose demand for the transition to life out of the womb Glycogen stores used up quickly Perinatal stress (e.g. sepsis, asphyxia) Stress stimulates fetal adrenal glands to ↑ epinephrine secretion Fetal pancreatic ⍺- cells ↑ glucagon secretion ↑ Breakdown of muscles and fat for glucose- building blocks Glycogen stores used up quickly ↑ Glucose usage as fetal metabolic demands ↑ to manage stress Fetal β-cells secrete inappropriately high levels of insulin despite hypoglycemic state; this hyperinsulinism state can last for months & resolve spontaneously ↓ Serum glucose Neonatal hypoglycemia Authors: Dasha Mori Reviewers: Michelle J. Chen *Dr. Danielle Nelson *MD at time of publication Blood glucose < 2.6 mmol/L in term & preterm infants within 72 hours of birth or < 3.3 mmol/L after 72 hours of birth Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 19, 2024 on www.thecalgaryguide.com

Diabete Gestazionale fattori di rischio e patogenesi

Diabete Gestazionale: fattori di rischio e patogenesi

Obesity Pathogenesis

Obesity: Pathogenesis Authors: Angela Mak, Run Xuan (Karen) Zeng Reviewers: Gurreet Bhandal, Raafi Ali, Mizuki Lopez Energy homeostasis dysregulation (Peptide hormones regulating hunger/satiety that influence the hypothalamic control of eating behaviours) Luiza Radu, Dr. Sam Fineblit* * MD at time of publication Endocrine dysregulation Neurological (↓ caloric reserve activates the neurological system) Adiposity-related Hypothalamus (hemostatic area) ↑ Production of ghrelin (peptide hormone) ↑ Activation of agouti-related protein (A Neuropeptide Y (NPY) neuron clusters in the hypothalamus via vagus nerve ↑ Appetite Mesolimbic area (hedonic area) Reward Driven Eating (meso-limbic region of brain) ↑ Food consumption ↑ Dopamine & endogenous opioid signals ↑ Pleasure & desire to consume more food Prefrontal cortex (executive functioning) ↓ Glucagon-like peptide-1 (GLP-1) & pancreatic peptide YY (PYY) secretion post- meal ↓ Stimulation of Proopiomelanocortin (POMC) neuron clusters in hypothalamus ↓ Beta-melanocyte stimulating hormone (MSH) (endogenous peptide) production Defect in leptin receptor gene ↓ Circulating soluble leptin receptors (SLR) ↑ Serum leptin levels Leptin resistance Inactive leptin gene ↓ Adipocyte leptin production & secretion ↓ Leptin transport across blood brain barrier ↓ Hypothalamus suppression of hunger ↓ Satiety sensation ↑ Caloric intake & weight gain ↑ Dietary carbohydrate intake ↑ Insulin production & secretion ↓ Cellular response to insulin ↑ Insulin resistance ↑ Insulin production & secretion to compensate for insulin resistance Impaired glycemic control Metabolic syndrome, type 2 diabetes mellitus and cardiovascular disease ** Metabolic adaptation to reduced-caloric intake efforts ↑ Body energy conservation ↓ Baseline energy expenditure ↓ Resting metabolic rate (the amount of energy body requires to function while at rest) ↓ Ability to lose weight & fat mass ↑ Hunger ↑ Caloric intake & weight gain Obesity (A combination of metrics including ↑ BMI, ↑ weight circumference, ↑ waist-to-hip ratio, skinfold thickness, and other standardized measures varied by equipment available at various institutions resulting in a negative impact on the health of the individual) **See slide on Pathogenesis of Type II Diabetes Mellitus Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Aug 13, 2024 on www.thecalgaryguide.com

Transient Tachypnea of the Newborn

Transient Tachypnea of the Newborn: Pathogenesis and clinical findings Cesarean delivery without labour Author: Tanis Orsetti Reviewers: Annie Pham Michelle J. Chen Dr. Jean Mah* * MD at time of publication Smoking during pregnancy Uncontrolled maternal asthma Uncontrolled maternal diabetes Dilution of surfactant ↑ Surface tension in alveoli ↓ Expansion/contraction of lungs (↓ pulmonary compliance) ↑ Work of breathing Maternal factors leading to impaired fetal lung development Lack of labour-induced hormone changes (i.e. cortisol, catecholamines) ↓ Alveolar fluid reabsorption through epithelial aquaporin channels ↑ Alveolar fluid in lungs Disruption of laminar flow in airways ↑ Resistance to airflow ↑ Lung expansion to compensate Limited surface area for gas exchange in the alveoli ↓ Ventilation Fluid buildup in the major bronchi in the perihilar region Prominent perihilar streaking on chest x-ray ↑ Intrathoracic pressure pushes the diaphragm down Blunting of costophrenic angle on chest x-ray Hyperinflation of lungs Expanded lung fields on chest x-ray ↑ Deoxygenated hemoglobin in the bloodstream Blue/purple discoloration of the skin particularly around the lips & fingers (cyanosis) ↓ Oxygenated hemoglobin in the bloodstream ↑ Nasal passage size allows for more air to enter the lungs with each breath Nasal flaring Scalene/intercostal/ sternocleidomastoid /abdominal muscle activation to assist with breathing Accessory muscle use ↓Oxygen saturation (SpO2) Neonate takes more breaths to compensate for limited oxygenation Respiratory rate > 60 breaths/minute (tachypnea) Transient Tachypnea of the Newborn Temporary respiratory condition in newborns characterized by impaired lung function and rapid breathing Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Oct 4, 2024 on www.thecalgaryguide.com

Neonatal Hypoglycemia Clinical Presentation

Neonatal Hypoglycemia: Clinical Presentation Normal physiology Glucose is produced from endogenous lactate, glycerol, and amino acids until glucose supply is established through feeds Hepatic glycogen is broken down to produce glucose in the first 8-12 hours of life Glucose is absorbed in the small intestine and transported into the bloodstream The pancreas responds to ↑ glucose blood concentration by releasing insulin Insulin acts on glucose transporters that line the cell membrane to bring glucose into the cell Glucose is broken down into ATP, which is used by cells for energy Authors: Dasha Mori Reviewers: Michelle J. Chen Dr. Ian Mitchell* *MD at time of publication Neonates with predisposing factors that Neonates that are unable to feed for > 60-120 Infant is large for gestational age (> 90th percentile) or was born to pregnant person with diabetes Fetus was exposed to high levels of glucose through placental circulation Fetus adapted to high blood glucose by producing high amounts of insulin After birth, placental glucose supply is stopped but insulin remains high ↑ Insulin promotes inappropriately ↑ uptake of glucose into cells put them at high risk for hypoglycemia Cells cannot produce enough ATP from glucose to power physiological functions Immature nervous system, use of fatty acids or proteins as an alternate ATP source, or adaptation to low glucose in utero can mask symptoms of hypoglycemia Asymptomatic hypoglycemia Neonates with low blood glucose often don’t show any symptoms and are detected by screening infants who are at a high risk for hypoglycemia min are at risk for hypoglycemia Infant is small for gestational age or experienced fetal growth restriction Smaller neonates have smaller glycogen stores Preterm infants born < 37 weeks Glycogen is stored during the 3rd trimester; preterm infants did not have opportunity to build up stores Loss of glucose source from placental circulation after birth puts preterm neonate at risk for low blood sugar Body’s sympathetic system detects low glucose and triggers physical symptoms (neurogenic symptoms) Symptomatic hypoglycemia Neurons in brain are unable to produce enough ATP and thus function properly, triggering symptoms related to low sugar in the CNS (neuroglycopenic symptoms) Non-specific symptoms are not exclusive to hypoglycemia and warrant further investigation to exclude other differential diagnosis (sepsis, inborn errors of metabolism, neonatal abstinence syndrome, neonatal encephalopathy, perinatal asphyxiation) Jitteriness or tremors Sweating Irritability Tachypnea Pallor Pathologic poor feeding Weak or a high- pitched cry Change in level of consciousness (lethargy or coma) Seizures Pathologic hypotonia for gestational age Apnea Bradycardia Cyanosis Hypothermia Neonates with perinatal stress (e.g. birth asphyxia, meconium aspiration) Body uses more glucose to produce ATP to manage condition causing physiological stress Glucose stores are used up more quickly Born to pregnant person with beta-blocker use Body in stress releases epinephrine to promote sympathetic responses including glycogen breakdown into glucose Beta blockers from placental circulation prevent epinephrine from binding to its receptor in infant’s body Neonatal Hypoglycemia: Asymptomatic and symptomatic hypoglycemia satisfy the criteria of blood glucose < 2.6 mmol/L in both term and preterm infants within 72 hours of birth, and after 72 hours of age glucose < 3.3 mmol/L Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Oct 4, 2024 on www.thecalgaryguide.com