Practice 17 structured short- and long-answer medical questions on Liver Histology, Physiology and Pathology. Review model answers for exam revision.
Answer: ### 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**:
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Answer: ## 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
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Answer: ### 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
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Answer: ### 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
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Answer: ### 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 | HEV | |---|---|---|---|---|---| | Type | RNA | DNA | RNA | RNA | RNA | | Transmission | Fecal-oral | Parenteral/Sexual | Parenteral | Parenteral | Fecal-oral | | Chronicity | Never | 5-10% (adults) | 85% | Yes | Never | | HCC Risk | No | Yes | Yes | No | No | | Special | - | HBx protein | Lymphoid aggregates | Needs HBV | High mortality in pregnancy | ### HBV Serology - **HBsAg**: Indicates active infection. - **Anti-HBs**: Indicates immunity (recovery or vaccination). - **HBeAg**: Indicates high infectivity/active replication. - **Anti-HBc IgM**: Marker of acute infection. - **Window Period**: Only Anti-HBc IgM is positive; HBsAg and Anti-HBs are negative. ## 9. ALCOHOLIC LIVER DISEASE ### Three Stages
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Answer: ### Pathogenesis - Excess NADH production shifts metabolism toward lipid biosynthesis. - Acetaldehyde causes direct lipid peroxidation and cytoskeletal disruption. ## 10. NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) - Most common metabolic liver disease. - Associated with **Type 2 Diabetes, Obesity, and Insulin Resistance**. - Histology may be identical to alcoholic steatohepatitis (NASH) but occurs in non-drinkers.