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Clinical Findings of Androgen Deficiency

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

cirrhosis

Primary Biliary Cirrhosis (PBC)

esophageal-gastric-varices

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

Hepatitis C (HCV) Infections: Explaining Serology Patterns

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

Hepatitis C (HCV) Infection: Explaining Serology Patterns

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

Hepatic Encephalopathy: Pathogenesis and Clinical Findings

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

Hyponatremia- Physiology

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

Biliary Atresia (BA)- Pathogenesis and clinical findings

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

Hemorrhoids - Pathogenesis and Clinical Findings

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

Wilson's Disease

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

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

A1AT-Deficiency

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

Viral-Hepatitis

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

leberzirrhose-pathogenese-und-komplikationen

NSAIDs and the Kidney mechanism of action and side effects

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

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

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

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

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

lower-gi-bleed-risk-factors

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

Acute Liver Failure: Pathogenesis and clinical findings

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

hypovolemic-shock

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

Cirrhosis

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

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

Carbonic Anhydrase Inhibitor Diuretics

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

Gynecomastia

Gynecomastia: Pathogenesis Authors: Sara Cho Reviewers: Michelle J. Chen Samuel Fineblit* *MD at time of publication Physiologic causes Puberty Placenta transfers maternal estrogens to newborn male babies Older age (>60 years) Hyperthyroidism Klinefelter Syndrome (males with > 1 X chromosome) Liver cirrhosis Certain tumors (e.g., germ cell, adrenal, Leydig cell, Sertoli cell) Anabolic steroid usage (containing testosterone) Finasteride (treatment for benign prostate hyperplasia and male pattern baldness) Cimetidine - inhibits stomach acid production Spironolactone (diuretic used to treat high blood pressure and heart failure) Ketoconazole (antifungal) Cytotoxic agents (e.g. alkylating agents, vincristine, methotrexate) Imbalance between estrogens and androgens Estrogen stimulates breast tissue growth in newborn Changes in metabolic rate ↑ fat production Unclear mechanism ↑ Proinflammatory mediators and cytokines (e.g. prostaglandin E2, TNF⍺, IL-1, IL-6, cyclooxygenase-2) Prostaglandin E2 and IL- 6 upregulate aromatase enzyme expression Available estrogen is higher than available testosterone ↑ Aromatase enzyme activity, converting androgens to estrogen ↓ Testosterone release from the testes ↓ Testosterone ↑ Serum sex hormone binding globulin (SHBG) SHBG binds estrogen with less affinity to testosterone Thyroid hormone stimulates liver to express more sex hormone binding globulin Thyroid hormone stimulates aromatase activity Overexpression of aromatase enzyme Seminiferous tubules in the testes hyalinize and fibrose Suppression of the hypothalamic pituitary thyroid axis through an unclear mechanism Tumor may produce estradiol Tumor produces β- human chorionic gonadotropin (β-HCG) ↑ serum testosterone Inhibits 5-α reductase Blocks binding of 5-DHT to androgen receptors ↓ 2-hydroxylation of estradiol Mimics structures of testosterone Inhibits 17,20 desmolase and 17α-hydroxylase Damage to Leydig cells in testes ↑ Estrogen to androgen ratio Pathological causes Impaired spermatogenesis and testosterone production ↓ GnRH secretion from hypothalamus ↓ Testosterone ↓ Luteinizing hormone (LH) release from anterior pituitary ↓ 5-DHT and/or testosterone binding to androgen receptors in chest tissue ↓ inhibition of breast development Normal or increased estrogen acts on estrogen receptor on chest tissue Estrogen receptors stimulate breast development Estradiol negatively feedbacks on luteinizing hormone β-HCG stimulates LH receptors on Leydig cells in the testes Aromatase enzyme converts excess testosterone into estrogen and estradiol ↓ conversion of testosterone to 5- dihydrotestosterone (5-DHT), a more potent form of testosterone Glandular proliferation in male breasts Gynecomastia (development of breast tissue in males) Drug side- effects ↓ Metabolism of estradiol Competitively binds to androgen receptors ↑ Serum estradiol levels Exhibits physical attributes that do not align with gender identity Psychological distress In some cases, hormones stabilize Involution and atrophy of ducts Gynecomastia resolves ↓ Steroid synthesis ↓ Androstenedione produced (testosterone precursors) ↓ Serum testosterone levels ↓ Testosterone production Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Jun 9, 2024 on www.thecalgaryguide.com

Underfill Edema Pathogenesis

Underfill Edema: Pathogenesis Acute respiratory Sepsis, burns, distress syndrome, trauma anaphylaxis ↑ Inflammatory mediators Gaps form between epithelial cells lining blood vessels ↑ Capillary permeability Fluid extravasation into interstitial space Blood backing up in vena cava ↑ capillary hydrostatic pressure in venous system Pressure creates net fluid movement from vascular space into interstitial space Authors: Matthew Hobart Richard Chan Nojan Mannani Michelle J. Chen Reviewers: Raafi Ali Varun Suresh Saif Zahir Andrew Wade* Adam Bass* * MD at time of publication Nephrotic syndrome ↑ Renal albumin loss Scarring of liver tissue (cirrhosis) Vasodilatory medications Various mechanisms Right-sided heart failure Compromised right heart function ↓ forward flow ↓ Hepatic albumin synthesis Blood is unable to pass through hepatic vessels disrupted by cirrhosis and backs up in portal vein ↑ Blood pressure in portal vein (portal hypertension) Less blood volume in hepatic veins and vena cava (underfilling) Pregnancy ↑ Estrogen, progesterone and relaxin Vasodilation Gravity causes fluid accumulation in peripheral veins ↑ Capillary hydrostatic pressure ↑ Net fluid movement into interstitial space ↓ Serum albumin ↓ Capillary oncotic pressure Fluid extravasation into interstitial space More blood in portal vein ↑ capillary hydrostatic pressure in venous system Pressure creates net fluid movement from vascular space into interstitial space Less blood volume in arteries (underfilling) ↓ Effective arterial blood volume (EABV) ↓ Renal blood flow activates the renin-angiotensin-aldosterone system (RAAS) Angiotensin and aldosterone ↑ Anti-diuretic hormone released by tubular Na+ and H2O resorption posterior pituitary ↑ H2O resorption ↑ Fluid in circulation, worsening existing venous congestion ↑ Hydrostatic capillary pressure and fluid extravasation into interstitial space Underfill edema (edema worsened by activation of RAAS) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Aug 19, 2015; updated Aug 5, 2024 on www.thecalgaryguide.com