SEARCH RESULTS FOR: diabetes mellitus

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

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

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

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

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

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

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

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

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

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

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

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

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

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