SEARCH RESULTS FOR: 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

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

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

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

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

Cystic Fibrosis

Authors: Navdeep Goraya, Spencer Montgomery Reviewers: Yan Yu, Kayla Nelson, Emily J. Doucette, Mark Montgomery*, Danielle Nelson* *MD at time of publication Reproductive Manifestations Incomplete development of Wolffian duct derivatives (vas deferens, epididymis, & seminal vesicles) Cystic Fibrosis (CF): Pathogenesis, clinical findings, and complications Cystic Fibrosis Transmembrane Regulator (CFTR) autosomal recessive gene mutation on chromosome 7 CFTR protein (transmembrane chloride ion channel found in exocrine tissue) dysfunction Mutated CFTR proteins prevent Cl- reabsorption in sweat glands ↑ Secretion of Cl- into sweat ↑ Sweat Cl- concentration Mutated CFTR proteins in duct epithelial tissue of other parts of the body prevent diffusion of Cl- into secretions ↓ Cl- diffusion into peri-ciliary fluid ↓ Water composition of peri-ciliary fluid ↓ Clearance of mucociliary secretions Secretions accumulate in secretory passages throughout the body Inhibition of sperm transport (obstructive azoospermia) Male infertility Upper Respiratory Tract Manifestations Retained secretions in sinuses Failure to clear bacteria in sinuses Persistent neutrophilic inflammation triggers tissue remodeling & mucosal overgrowth Bacterial proliferation Nasal polyps Chronic sinusitis Pancreatic Manifestations Trapped digestive enzymes degrade pancreatic tissue Pancreatic tissue damage triggers inflammation, scarring & fatty tissue replacement Islet cell damage & destruction Cystic-fibrosis related diabetes (CFRD) Lower Respiratory Tract Manifestations Retained secretions in airways Bacterial proliferation in lower airway Airway infection & inflammation Chronic productive cough Signs of obstructive lung disease (lung hyperinflation on x-ray & abnormal pulmonary function tests) Bronchitis ± bronchiectasis** ↓ Production & secretion of pancreatic enzymes into GI tract (pancreatic insufficiency) Fat & protein malabsorption Failure to thrive ↓ Absorption of fat-soluble vitamins Steatorrhea (↑ fat in stool) Vitamin D deficiency Vitamin K deficiency** Rickets** Osteoporosis** Coagulopathies Hepatic Manifestations Delayed passage of bile through biliary tree ↑ Loss of bile acids in stool Inflammatory hepatic response ↑ Production of lithogenic bile (bile supersaturated with cholesterol) Biliary cirrhosis with portal hypertension Cholelithiasis** Gastrointestinal (GI) Manifestations ↓ Movement of intestinal contents In newborns: Meconium ileus In children/adults: Distal ileal obstruction syndrome (DIOS) ↑ Retention of meconium ↑ Reabsorption of bilirubin Prolonged jaundice in neonates **See corresponding Calgary Guide slide Legend: Sign/Symptom/Lab Finding Complications Pathophysiology Mechanism Published Jan 21, 2013; updated Aug 20, 2025 on www.thecalgaryguide.com Reproductive Manifestations Degeneration of Wolffian duct derivatives (vas deferens, epididymis, & seminal vesicles) Inhibition of sperm transport (obstructive azoospermia) Male infertility Cystic Fibrosis (CF): Pathogenesis, clinical findings, and complications Cystic Fibrosis Transmembrane Regulator (CFTR) autosomal recessive gene mutation on chromosome 7 CFTR protein (a transmembrane chloride ion channel that is found in exocrine tissue) dysfunction Authors: Navdeep Goraya, Spencer Montgomery Reviewers: Yan Yu, Kayla Nelson, Emily J. Doucette, Mark Montgomery*, Danielle Nelson* *MD at time of publication Mutated CFTR proteins prevent Cl- reabsorption in sweat glands ↑ Secretion of Cl- into sweat ↑ Sweat Cl- concentration Mutated CFTR proteins in duct epithelial tissue of other parts of the body prevent diffusion of Cl- into secretions ↓ Cl- diffusion into peri-ciliary fluid ↓ Water composition of peri-ciliary fluid ↓ Clearance of mucociliary secretions Secretions accumulate in secretory passages throughout the body Upper Respiratory Tract Manifestations Retained secretions in sinuses Failure to clear bacteria in sinuses Persistent neutrophilic inflammation triggers tissue remodeling & mucosal overgrowth Bacterial proliferation Nasal polyps Chronic sinusitis Lower Respiratory Tract Manifestations Retained secretions in airways Bacterial proliferation in lower airway Airway infection & inflammation Chronic productive cough Signs of obstructive lung disease (lung hyperinflation on x-ray & abnormal pulmonary function tests) Bronchitis ± bronchiectasis** Pancreatic Manifestations Pancreas unable to secrete digestive enzymes into GI tract (pancreatic insufficiency) Fat & protein malabsorption ↓ Absorption of fat-soluble vitamins Failure to thrive ↓ Serum Vitamin D Osteoporosis** Trapped digestive enzymes degrade pancreatic tissue Tissue damage triggers inflammation, scarring & fatty tissue replacement Islet cell destruction Cystic-fibrosis related diabetes (CFRD) Hepatic Manifestations Delayed passage of bile through biliary tree Inflammatory hepatic response Cirrhosis** & portal hypertension Gastrointestinal Manifestations ↓ Movement of intestinal contents In newborns: Meconium ileus In children/adults: Distal ileal obstruction syndrome (DIOS) ↑ Retention of meconium ↑ Reabsorption of bilirubin Prolonged jaundice in neonates Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications **See corresponding Calgary Guide slide Published January 21, 2013 on www.thecalgaryguide.com Please only review slide 1 – slides 3-7 are previous draft versions. Thank you! Authors: Spencer Montgomery, Navdeep Goraya Reviewers: Yan Yu, Kayla Nelson, Emily J. Doucette, Mark Montgomery*, Name Name* *MD at time of publication In the vas deferens in utero Cystic Fibrosis: Pathogenesis, clinical findings, and complications Cystic Fibrosis Transmembrane Regulator (CFTR) autosomal recessive gene mutation on chromosome 7 CFTR protein (a transmembrane chloride ion channel that is found in exocrine tissue) dysfunction Mutated CFTR proteins prevent Cl- reabsorption in sweat glands ↑ Secretion of Cl- into sweat ↑ Sweat Cl- concentration Mutated CFTR proteins in duct epithelial tissue of other parts of the body prevent diffusion of Cl- into secretions ↓ Cl- diffusion into peri-ciliary fluid ↓ Water composition of peri-ciliary fluid ↓ Clearance of mucociliary secretions Secretions accumulate in secretory passages throughout the body Degeneration of vas deferens, Wolffian ducts & associated structures Infertility in affected males In upper respiratory tract Retained secretions in sinuses Failure to clear bacteria in airways Persistent neutrophilic inflammation triggers tissue remodeling & mucosal overgrowth Bacterial proliferation Chronic sinusitis Nasal polyps In lower respiratory tract Chronic productive cough Retained secretions in airways Bacterial proliferation Airway infection & inflammation Signs of obstructive lung disease (lung hyperinflation on x-ray & abnormal pulmonary function tests) Bronchitis ± bronchiectasis** In pancreas Pancreas unable to secrete digestive enzymes into GI tract (pancreatic insufficiency) Fat & protein malabsorption ↓ Absorption of fat- soluble vitamins Failure to thrive ↓ Serum Vitamin D Osteoporosis** Trapped digestive enzymes degrade pancreatic tissue Tissue damage triggers inflammation, scarring & fatty tissue replacement Islet cell destruction Cystic-fibrosis related diabetes (CFRD) In biliary tree Delayed passage of bile Inflammatory hepatic response Cirrhosis** & portal hypertension In GI tract ↓ Movement of intestinal contents In children/adults: Distal ileal obstruction syndrome (DIOS) In newborns: Meconium ileus ↑ Retention of meconium ↑ Reabsorption of bilirubin Prolonged jaundice in neonates Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 21, 2013 on www.thecalgaryguide.com Authors: Spencer Montgomery, Navdeep Goraya Reviewers: Yan Yu, Kayla Nelson, Emily J. Doucette, Mark Montgomery*, Name Name* *MD at time of publication In the vas deferens in utero Cystic Fibrosis: Pathogenesis, clinical findings, and complications Cystic Fibrosis Transmembrane Regulator (CFTR) autosomal recessive gene mutation on chromosome 7 CFTR protein (a transmembrane chloride ion channel that is found in exocrine tissue) dysfunction Mutated CFTR proteins prevent Cl- reabsorption in sweat glands ↑ Secretion of Cl- into sweat ↑ Sweat Cl- concentration Mutated CFTR proteins in duct epithelial tissue of other parts of the body prevent diffusion of Cl- into secretions ↓ Cl- diffusion into peri-ciliary fluid ↓ Water composition of peri-ciliary fluid ↓ Clearance of mucociliary secretions Secretions accumulate in secretory passages throughout the body Degeneration of vas deferens, Wolffian ducts & associated structures Infertility in affected males In upper respiratory tract Retained secretions in sinuses Failure to clear bacteria in airways Persistent neutrophilic inflammation triggers tissue remodeling & mucosal overgrowth Bacterial proliferation Chronic sinusitis Nasal polyps In lower respiratory tract Chronic productive cough Retained secretions in airways Bacterial proliferation Airway infection & inflammation Signs of obstructive lung disease (lung hyperinflation on x-ray & abnormal pulmonary function tests) Bronchitis ± bronchiectasis** Trapped digestive enzymes degrade pancreatic tissue Inflammation Scarring & fatty tissue infiltration Islet cell destruction Type II Diabetes Mellitus** In pancreas Pancreas unable to secrete digestive enzymes into GI tract (pancreatic insufficiency) Fat & protein malabsorption ↓ Absorption of fat- soluble vitamins Failure to thrive ↓ Serum Vitamin D Osteoporosis** In biliary tree Delayed passage of bile Inflammatory hepatic response Cirrhosis** & portal hypertension In GI tract ↓ Movement of intestinal contents In children/adults: Distal ileal obstruction syndrome (DIOS) In newborns: Meconium ileus ↑ Retention of meconium ↑ Reabsorption of bilirubin Prolonged jaundice in neonates Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 21, 2013 on www.thecalgaryguide.com In the vas deferens in utero Retained secretions in sinuses Cystic Fibrosis: Pathogenesis, clinical findings, and complications Cystic Fibrosis Transmembrane Regulator (CFTR) autosomal recessive gene mutation on chromosome 7 CFTR protein (a transmembrane chloride ion channel that is found in exocrine tissue) dysfunction Mutated CFTR proteins prevent Cl- reabsorption in sweat glands ↑ Secretion of Cl- into sweat ↑ Sweat Cl- concentration Mutated CFTR proteins in duct epithelial tissue of other parts of the body prevent diffusion of Cl- into secretions ↓ Cl- diffusion into peri-ciliary fluid ↓ Water composition of peri-ciliary fluid ↓ Clearance of mucociliary secretions Accumulation of secretions in secretory passages throughout the body obstructing these passages Authors: Spencer Montgomery, Navdeep Goraya Reviewers: Yan Yu, Kayla Nelson, Emily J. Doucette, Mark Montgomery* *MD at time of publication Degeneration of vas deferens, Wolffian ducts & associated structures Infertility in affected males In upper respiratory tract Failure to clear bacteria in airways Bacterial proliferation Chronic sinusitis Nasal polyps In lower respiratory tract Chronic productive cough Retained secretions in airways Bacterial proliferation Airway infection & inflammation Signs of obstructive lung disease i.e. lung hyperinflation on x-ray & abnormal pulmonary function tests Bronchitis ± bronchiectasis Trapped digestive enzymes degrade pancreatic tissue Inflammation Scarring & fatty tissue infiltration Islet cell destruction Type II Diabetes Mellitus In pancreas Pancreas unable to secrete digestive enzymes into GI tract (pancreatic insufficiency) Fat and protein malabsorption ↓ Absorption of fat- soluble vitamins Failure to thrive ↓Serum Vitamin D Osteoporosis In biliary tree Delayed passage of bile Inflammatory hepatic response Cirrhosis & portal hypertension In GI tract ↓ Movement of intestinal contents In children/adults: Distal ileal obstruction syndrome (DIOS) In newborns: Meconium ileus ↑ Retention of meconium ↑ Reabsorption of bilirubin Prolonged jaundice in neonates Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 21, 2013 on www.thecalgaryguide.com In the vas deferens in utero Cystic Fibrosis: Pathogenesis, clinical findings, and complications Cystic Fibrosis Transmembrane Regulator (CFTR) autosomal recessive gene mutation on chromosome 7 CFTR protein (a transmembrane chloride ion channel that is found in exocrine tissue) dysfunction Chloride channel no longer allows Cl- transport CFTR proteins in sweat glands reabsorb Cl- CFTR proteins in duct epithelial tissue of other parts of the body facilitate diffusion of Cl- into secretions ↓Reabsorption ↓Cl- diffusion into peri-ciliary fluid ↓Water composition of peri-ciliary fluid ↑Secretion of Cl- into sweat ↓Clearance of mucociliary secretions ↑Sweat Cl- concentration Accumulation of secretions in secretory passages throughout the body obstructing these passages Degeneration of vas deferens, Wolffian ducts & associated structures Authors: Spencer Montgomery, Navdeep Goraya Reviewers: Yan Yu, Kayla Nelson, Emily J. Doucette, Mark Montgomery* *MD at time of publication Infertility in affected males In upper respiratory tract Retained secretions in sinuses Nasal polyps Bacterial proliferation Chronic sinusitis In lower respiratory tract Chronic productive cough Retained secretions in airways Bacterial proliferation Signs of obstructive lung disease i.e. lung hyperinflation on x-ray & abnormal pulmonary function tests Airway infection & inflammation Bronchitis ± bronchiectasis Trapped digestive enzymes degrade pancreatic tissue Inflammation Scarring & fatty tissue infiltration Islet cell destruction Type II Diabetes Mellitus In pancreas Pancreas unable to secrete digestive enzymes into GI tract (pancreatic insufficiency) Fat and protein malabsorption ↓Absorption of fat- soluble vitamins Failure to thrive ↓Serum Vitamin D Osteoporosis In biliary tree Delayed passage of bile Inflammatory hepatic response Cirrhosis & portal hypertension In GI tract ↓Movement of intestinal contents In children/adults: Distal ileal obstruction syndrome (DIOS) In newborns: Meconium ileus ↑Retention of meconium ↑Reabsorption of bilirubin Prolonged jaundice in neonates Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 21, 2013 on www.thecalgaryguide.com In the vas deferens in utero Degeneration of vas deferens, Wolffian ducts and associated structures Infertility in affected males Legend: Cystic Fibrosis: Pathogenesis, clinical findings, and complications Mutation of Cystic Fibrosis Transmembrane Regulator (CFTR) gene on chromosome 7 à Dysfunction of the CFTR protein (a transmembrane chloride ion channel that is found in exocrine tissue) Author: Spencer Montgomery Reviewers: Yan Yu, Kayla Nelson, Mark Montgomery* * MD at time of publication Chloride channel no longer allows Cl- transport In sweat glands, CFTR proteins are responsible for the reabsorption of Cl- In duct epithelial tissue of other parts of the body, CFTR proteins facilitate diffusion of Cl- into secretions Notes: • The CFTR mutation exhibits an autosomal recessive inheritance pattern • > 1700 different CFTR gene mutations are identified, ∆F508 mutation accounts for ~67% of cases in Caucasians. • Cystic fibrosis is diagnosed based presence of ↑ sweat chloride concentration, disease causing CFTR mutations, & symptoms of ≥ 1 associated organ system ↓ Cl- diffusion into peri-ciliary fluid → ↓water composition of peri-ciliary fluid In children/adults: Distal ileal obstruction syndrome (DIOS) ↓ reabsorption = ↑secretion of Cl- into sweat In GI tract ↓movement of intestinal contents ↓ clearance of mucociliary secretions In newborns: Meconium ileus ↑ retention of meconium → ↑ reabsorption of bilirubin Prolonged jaundice in neonates ↑ Sweat chloride concentration Accumulation of secretions in secretory passages throughout the body, obstructing these passages In biliary tree Delayed passage of bile → inflammatory hepatic response Cirrhosis & portal hypertension In upper respiratory tract In pancreas Trapped digestive enzymes degrade pancreatic tissue Nasal polyps Retained secretions in sinuses → bacterial proliferation Pancreas unable to secrete digestive enzymes into GI tract (pancreatic insufficiency) Fat and protein mal- absorption ↓ absorption of fat soluble vitamins Inflammation → scarring & fatty tissue infiltration → islet cell destruction Chronic sinusitis ↓ serum Vit. D Type II Diabetes Mellitus Failure to thrive Osteoporosis Published January 21, 2013 on www.thecalgaryguide.com In lower respiratory tract Chronic productive cough Retained secretions in airways → bacterial proliferation à Airway infection & inflammation Persistent respiratory tract infections Can progress to chronic bronchitis ± bronchiectasis (This is the biggest cause of death in CF) Pathophysiology Signs of obstructive lung dx: i.e. Lung hyperinflation (on x-ray), Abnormal pulmonary function tests Mechanism Sign/Symptom/Lab Finding Complications