MedLecturesMadeEasy's video: Cirrhosis mechanism of disease

This is a mechanism of disease flowchart for cirrhosis, covering the etiology, pathophysiology, and manifestations. ADDITIONAL TAGS: Nonalcoholic steatohepatitis Obesity Diabetes mellitus Hyperlipidemia Primary sclerosing cholangitis Primary biliary cholangitis Autoimmune hepatitis Cell / tissue damage Signs / symptoms Labs / tests / imaging results Cirrhosis Core concepts Social determinants of health / risk factors Pharmacology / toxicity Microbial pathogenesis Biochemistry Flow gradients Genetics / hereditary Inflammation Pathophysiology Etiology Manifestations Kupffer cells (liver macrophages) destroy hepatocytes → activate hepatic stellate cells → trigger inflammation Cytokines (PDGF, TGF-B) Collagen / fibrotic tissue replaces the liver parenchyma (fibrosis) Excessive connective tissue in periportal and centrilobular zones Regenerative nodules and fibrous septa compres hepatic sinusoids and venules → loss of fenestrations Elevated portal vein hydrostatic pressure → intrasinusoidal hypertension → poor blood flow Impaired substrate exchange Loss of exocrine and metabolic functions Stimulate hepatocyte apoptosis Activate stellate cells → activate myofibroblasts → produce excess collagen / connective tissue Long-standing alcohol use Medications (amiodarone, acetaminophen, methotrexate) Chemicals (pesticides, tetrachloromethane) Ingestion of aflatoxin, produced by Aspergillus Hepatotoxicity Hepatitis Parasitic infections (schistosomiasis, leishmaniasis, malaria in India, Africa) Chronic viral infection (Hep C B D) Thrombosis → occludes hepatic veins (Budd-Chiari syndrome) Osler-Weber-Rendu (HHT) → vascular dysplasia → high fibrous septa in liver CHF → congestive hepatopathy (cardiac cirrhosis) Hemochromatosis Wilson disease α1-antitrypsin def Vitamin deficiency B12 or folate def Anemia Chronic blood loss ↓ vit D3 hydroxylation Secondary hyperparathyroidism Portal hypertension Esophageal varices Caput medusa Thrombocytopenia Splenomegaly Fatigue / weakness ↓ synthetic function ↓ detoxification Jaundice Med / metabolite accumulation ↓ urea synthesis ↑ ammonia Hepatic encephalopathy ↓ coagulation factors Bleeding diathesis +/- petechiae, purpura ↓ bile acids ↓ absorb fat-soluble vitamins ↓ albumin Ascites +/- peripheral edema ↑ SHBG ↑ estrogen effect (feminization) Gynecomastia ↓ body hair ↓ libido Erectile dysfunction Hypogonadism Hepatopulm. syndrome Hepatorenal syndrome Hepatocellular carcinoma Spider telangiectasia Palmar erythema Hypoxemia Nail clubbing Ascites +/- peripheral edema Amenorrhea Asterixis