Liver Histology, Physiology and Pathology — OmpathStudy

1. LIVER HISTOLOGY & PHYSIOLOGY Structural Units Lobule : Hexagonal structure with a central vein in the middle and portal triads at the periphery. Acinus : Functional unit based on microcirculation. Portal Triad : Contains a bile duct, hepatic artery branch, and portal vein branch. Central Vein : Tributary of the hepatic vein. Acinar Zones Zone Location Oxygenation Affected by --- --- --- --- Zone 1 Periportal Best Phosphorus poisoning, eclampsia Zone 2 Midzonal Intermediate Yellow fever Zone 3 Centrilobular Worst Alcohol, CCl4, ischemia, shock, right heart failure Liver Functions Bilirubin metabolism and excretion. Bile acid synthesis (12-36g/day): Cholic acid and chenodeoxycholic acid. Secreted as taurine and glycine conjugates. 10-20% deconjugated in ileum (enterohepatic circulation). Functions of bile : 1. Elimination of water-insoluble bilirubin, excess cholesterol, and xenobiotics. 2. Emulsification of dietary fat in the gut. 2. BILIRUBIN METABOLISM Pathway Aging RBCs → Heme → (Heme oxygenase) → Biliverdin → (Biliverdin reductase) → Bilirubin. Bilirubin binds to albumin → liver → conjugated with glucuronic acid (UDP-glucuronosyltransferase). Bilirubin glucuronides → excreted in bile → gut → urobilinogen → stercobilin (stool). Some urobilinogen is reabsorbed via enterohepatic circulation and excreted in urine. Jaundice Bilirubin 2 mg/dl results in jaundice (icterus). Kernicterus : Unconjugated bilirubin accumulation in the brain; highly toxic. Causes of Jaundice 1. Excessive production (hemolysis). 2. Reduced hepatocellular uptake. 3. Impaired conjugation (Gilbert's, Crigler-Najjar syndromes). 4. Decreased hepatocellular excretion. 5. Impaired bile flow (cholestasis). Types of Bilirubin Feature Unconjugated Conjugated --- --- --- Water solubility Insoluble Soluble Albumin binding Tight Loose Urine Absent Present (tea-colored) Toxicity Toxic (kernicterus) Nontoxic Lab Total minus direct Direct bilirubin Cause Hemolysis, impaired conjugation Cholestasis, hepatocellular disease 3. LIVER FUNCTION TESTS (LFTs) Category Tests --- --- Hepatocyte integrity AST (SGOT), ALT (SGPT), LDH Biliary excretory function Serum bilirubin, Alkaline phosphatase (ALP), GGT Hepatocyte synthetic function Albumin, Prothrombin time (PT), Ammonia Key Clinical Correlations ALT is more specific for liver injury than AST. AST:ALT 2:1 suggests alcoholic liver disease. Isolated elevation of Alkaline phosphatase suggests cholestasis or biliary obstruction. Low Albumin + prolonged PT indicates severe hepatocellular dysfunction. 4. HISTOLOGIC PATTERNS OF HEPATIC INJURY Pattern Description Associated with --- --- --- Steatosis Fat (TG) in hepatocytes Alcohol, NAFLD, obesity, drugs Ballooning degeneration Hydropic swelling Alcoholic/viral hepatitis Councilman bodies Acidophilic apoptotic hepatocytes Acute viral hepatitis Mallory bodies Eosinophilic cytokeratin inclusions Alcoholic hepatitis, Wilson's, NASH Piecemeal necrosis Periportal necrosis Chronic hepatitis Bridging necrosis Portal-portal or portal-central Severe hepatitis Massive necrosis Entire lobules Fulminant hepatitis Fibrosis Collagen deposition Chronic liver disease Cirrhosis Regenerative nodules + fibrosis End-stage liver disease 5. CHOLESTASIS Definition Systemic retention of bilirubin and other solutes (bile salts, cholesterol) due to hepatocellular dysfunction or biliary obstruction. Clinical Features Jaundice and dark urine. Pruritis (bile salt deposition in skin). Skin xanthomas (cholesterol deposits). Malabsorption of fat-soluble vitamins (A, D, E, K). Pale/clay-colored stools. Laboratory Findings Elevated conjugated bilirubin. Significantly elevated Alkaline phosphatase (ALP) and GGT. 6. HEPATIC FAILURE Definition Loss of 80-90% of hepatic functional capacity. Causes 1. Chronic liver disease : Cirrhosis. 2. Massive hepatic necrosis : Viral hepatitis, drugs (Acetaminophen, Halothane, Rifampicin), or mushroom toxins (Amanita phalloides). 3. Dysfunction without necrosis : Reye's syndrome, acute fatty liver of pregnancy. Clinical Consequences Encephalopathy : Due to hyperammonemia; characterized by Asterixis (flapping tremor). Portal Hypertension : Ascites, splenomegaly, esophageal varices, and caput medusae. Synthetic Failure : Hypoalbuminemia (edema), coagulopathy (bleeding), and hypoglycemia. Endocrine : Gynecomastia and palmar erythema (impaired estrogen metabolism). Hepatorenal Syndrome : Renal failure secondary to severe liver disease without intrinsic kidney pathology; characterized by low urinary sodium. 7. CIRRHOSIS Histologic Features 1. Bridging fibrous septa (Collagen types I & III). 2. Disruption of the entire liver architecture. 3. Parenchymal regenerative nodules. Pathogenesis Key cell: Ito cell (hepatic stellate cell) . Stimulated by TGF-β, TNF, and IL-1 to produce collagen. Classification Micronodular (<3mm) : Classically associated with Alcohol. Macronodular ( 3mm) : Classically associated with Viral Hepatitis. 8. VIRAL HEPATITIS Feature HAV HBV HCV HDV