Cirrhosis PDF - Liver Disease

## III. CIRRHOSIS - End-stage liver damage characterized by disruption of the normal hepatic parenchyma by bands of fibrosis and regenerative nodules of hepatocytes (Fig. 11.8) - Fibrosis is mediated by TGF-β from stellate cells which lie beneath the endothelial cells that line the sinusoids. - **C...

## III. CIRRHOSIS - End-stage liver damage characterized by disruption of the normal hepatic parenchyma by bands of fibrosis and regenerative nodules of hepatocytes (Fig. 11.8) - Fibrosis is mediated by TGF-β from stellate cells which lie beneath the endothelial cells that line the sinusoids. - **Clinical features** - Portal hypertension leads to: - Ascites (fluid in the peritoneal cavity) - Congestive splenomegaly/hypersplenism - Portosystemic shunts (esophageal varices, hemorrhoids, and caput medusae) - Hepatorenal syndrome (rapidly developing renal failure secondary to cirrhosis) - Decreased detoxification results in: - Mental status changes, asterixis, and eventual coma (due to ↑ serum ammonia); metabolic, hence reversible - Gynecomastia, spider angiomata, and palmar erythema due to hyperestrinism - Jaundice - Decreased protein synthesis leads to: - Hypoalbuminemia with edema - Coagulopathy due to decreased synthesis of clotting factors; degree of deficiency is followed by PT. ## IV. ALCOHOL-RELATED LIVER DISEASE - Damage to hepatic parenchyma due to consumption of alcohol - Most common cause of liver disease in the West - Fatty liver is the accumulation of fat in hepatocytes (Fig. 11.9A). - Results in a heavy, greasy liver; resolves with abstinence (Fig. 11.9B) - Alcoholic hepatitis results from chemical injury to hepatocytes; generally seen with binge drinking - Acetaldehyde (metabolite of alcohol) mediates damage. - Characterized by swelling of hepatocytes with formation of Mallory bodies (damaged cytokeratin filaments, Fig. 11.10), necrosis, and acute inflammation - Presents with painful hepatomegaly and elevated liver enzymes (AST > ALT); may result in death - Cirrhosis is a complication of long-term, chronic alcohol-induced liver damage; occurs in 10-20% of alcoholics ## V. NONALCOHOLIC FATTY LIVER DISEASE - Fatty change, hepatitis, and/or cirrhosis that develop without exposure to alcohol (or other known insult) - Associated with obesity - Diagnosis of exclusion; ALT > AST ## VI. HEMOCHROMATOSIS - Excess body iron leading to deposition in tissues (hemosiderosis) and organ damage (hemochromatosis) - Tissue damage is mediated by generation of free radicals. - Due to autosomal recessive defect in iron absorption (primary) or chronic transfusions (secondary) - Primary hemochromatosis is due to mutations in the HFE gene, usually C282Y (cysteine is replaced by tyrosine at amino acid 282). - Presents in late adulthood - Classic triad is cirrhosis, secondary diabetes mellitus, and bronze skin; other findings include dilated cardiomyopathy, cardiac arrhythmias and gonadal dysfunction (due to testicular atrophy). - Labs show↑ ferritin,↓ TIBC, ↑ serum iron, and ↑ % saturation. - Liver biopsy reveals accumulation of brown pigment in hepatocytes (Fig. 11.11A); Prussian blue stain distinguishes iron (blue) from lipofuscin (Fig. 11.11B). - Lipofuscin is a brown pigment that is a by-product from the turnover ('wear and tear') of peroxidized lipids; it is commonly present in hepatocytes (Fig. 11.11C). - Increased risk of hepatocellular carcinoma - Treatment is phlebotomy. ## VII. WILSON DISEASE - Autosomal recessive defect (ATP7B gene) in ATP-mediated hepatocyte copper transport - Results in lack of copper transport into bile and lack of copper incorporation into ceruloplasmin - Copper builds up in hepatocytes, leaks into serum, and deposits in tissues. - Copper-mediated production of hydroxyl free radicals leads to tissue damage. - Presents in childhood with: - Cirrhosis - Neurologic manifestations (behavioral changes, dementia, chorea, and Parkinsonian symptoms due to deposition of copper in basal ganglia) - Kayser-Fleisher rings in the cornea - Labs show ↑ urinary copper, ↓ serum ceruloplasmin, and ↑ copper on liver biopsy. - Increased risk of hepatocellular carcinoma - Treatment is D-penicillamine (chelates copper). ## VIII. PRIMARY BILIARY CIRRHOSIS - Autoimmune granulomatous destruction of intrahepatic bile ducts - Classically arises in women (average age is 40 years) - Associated with other autoimmune diseases - Etiology is unknown; antimitochondrial antibody is present. - Presents with features of obstructive jaundice - Cirrhosis is a late complication. ## IX. PRIMARY SCLEROSING CHOLANGITIS - Inflammation and fibrosis of intrahepatic and extrahepatic bile ducts - Periductal fibrosis with an 'onion-skin' appearance (Fig. 11.12) - Uninvolved regions are dilated resulting in a "beaded" appearance on contrast imaging. - Etiology is unknown, but associated with ulcerative colitis; p-ANCA is often positive. - Presents with obstructive jaundice; cirrhosis is a late complication. - Increased risk for cholangiocarcinoma ## X. REYE SYNDROME - Fulminant liver failure and encephalopathy in children with viral illness who take aspirin - Likely related to mitochondrial damage of hepatocytes - Presents with hypoglycemia, elevated liver enzymes, and nausea with vomiting; may progress to coma and death ## XI. HEPATIC ADENOMA - Benign tumor of hepatocytes - Associated with oral contraceptive use; regresses upon cessation of drug - Risk of rupture and intraperitoneal bleeding, especially during pregnancy - Tumors are subcapsular and grow with exposure to estrogen. ## XII. HEPATOCELLULAR CARCINOMA - Malignant tumor of hepatocytes - **Risk factors include:** - Chronic hepatitis (e.g., HBV and HCV) - Cirrhosis (e.g., alcohol, nonalcoholic fatty liver disease, hemochromatosis, Wilson disease, and A1AT deficiency) - Aflatoxins derived from Aspergillus (induce p53 mutations) - Increased risk for Budd-Chiari syndrome - Liver infarction secondary to hepatic vein obstruction - Presents with painful hepatomegaly and ascites - Tumors are often detected late because symptoms are masked by cirrhosis; poor prognosis - Serum tumor marker is alpha-fetoprotein. ## XIII. METASTASIS TO LIVER - More common than primary liver tumors; most common sources include colon, pancreas, lung, and breast carcinomas. - Results in multiple nodules in the liver (Fig. 11.13) - Clinically may be detected as hepatomegaly with a nodular free edge of the liver