Liver Histology & Physiology

## Summary ## 1. LIVER HISTOLOGY & PHYSIOLOGY ## Key Points - ### Structural Units - **Lobule** = hexagonal, central vein in middle, portal triads at periphery - **Acinus** = functional unit based on microcirculation - Portal triad contains: **bile duct + hepatic artery + portal vein branch** - Central vein = tributary of hepatic vein - ### Acinar Zones (CRITICAL FOR EXAMS) ⭐ | 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 & excretion - Bile acid synthesis (12-36g/day): cholic acid + chenodeoxycholic acid - Secreted as taurine & glycine conjugates - 10-20% deconjugated in ileum → enterohepatic circulation - Functions of bile: 1. - Elimination of water-insoluble bilirubin, excess cholesterol, xenobiotics 2. - Emulsification of dietary fat in gut - ### Pathway - Aging RBCs → Heme → (Heme oxygenase) → Biliverdin → (Biliverdin reductase) → Bilirubin - Bilirubin bound to albumin → liver → conjugated with glucuronic acid (UDP-glucuronosyltransferase) - Bilirubin glucuronides → excreted in bile → gut → urobilinogen → stercobilin (stool) - Some urobilinogen reabsorbed → enterohepatic circulation → excreted in urine ## Detailed Notes ### Structural Units - **Lobule** = hexagonal, central vein in middle, portal triads at periphery - **Acinus** = functional unit based on microcirculation - Portal triad contains: **bile duct + hepatic artery + portal vein branch** - Central vein = tributary of hepatic vein ### Acinar Zones (CRITICAL FOR EXAMS) ⭐ | 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 & excretion - Bile acid synthesis (12-36g/day): cholic acid + chenodeoxycholic acid - Secreted as taurine & glycine conjugates - 10-20% deconjugated in ileum → enterohepatic circulation - Functions of bile: 1. Elimination of water-insoluble bilirubin, excess cholesterol, xenobiotics 2. Emulsification of dietary fat in gut ## 2. BILIRUBIN METABOLISM ### Pathway - Aging RBCs → Heme → (Heme oxygenase) → Biliverdin → (Biliverdin reductase) → Bilirubin - Bilirubin bound to albumin → liver → conjugated with glucuronic acid (UDP-glucuronosyltransferase) - Bilirubin glucuronides → excreted in bile → gut → urobilinogen → stercobilin (stool) - Some urobilinogen reabsorbed → enterohepatic circulation → excreted in urine ### Jaundice - Bilirubin > **2 mg/dl** → jaundice (yellowish skin + sclera = icterus) - **Kernicterus** = unconjugated bilirubin accumulation in brain → toxic ⭐ ### Causes of Jaundice 1. Excessive production (hemolysis) 2. Reduced hepatocellular uptake 3. Impaired conjugation (Gilbert's, Crigler-Najjar) 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 urine) | | Toxicity | **Toxic** (kernicterus) | Nontoxic | | Lab | Total minus direct | Direct bilirubin | | Cause | Hemolysis, impaired conjugation | Cholestasis, hepatocellular disease | ## 3. LIVER FUNCTION TESTS | Category | Tests | |---|---| | Hepatocyte integrity | AST (SGOT), ALT (SGPT), LDH | | Biliary excretory function | Serum bilirubin, Alkaline phosphatase, GGT | | Hepatocyte synthetic function | Albumin, Prothrombin time, Ammonia | ### Key Points ⭐ - **ALT more specific** for liver than AST - **AST:ALT > 2:1** = alcoholic liver disease ⭐ - ↑↑ Alkaline phosphatase = cholestasis/biliary obstruction - ↓ Albumin + ↑ PT = severe hepatocellular dysfunction - Aminopyrine breath test + galactose elimination = hepatocyte function ## 4. HISTOLOGIC PATTERNS OF HEPATIC INJURY | Pattern | Description | Associated with | |---|---|---| | Steatosis | Fat (neutral fat/TG) in hepatocytes | Alcohol, NAFLD, obesity, drugs | | Ballooning degeneration | Hydropic swelling of hepatocytes | Alcoholic hepatitis, viral hepatitis | | Councilman bodies | Acidophilic apoptotic hepatocytes | Acute viral hepatitis ⭐ | | Mallory bodies | Eosinophilic cytokeratin inclusions | Alcoholic hepatitis ⭐ (also PBC, Wilson's, NASH) | | Piecemeal necrosis | Periportal necrosis | Chronic hepatitis | | Bridging necrosis | Portal-portal or portal-central | Severe hepatitis | | Massive necrosis | Entire lobules | Fulminant hepatitis | | Coagulative necrosis | Mummified hepatocytes, poorly staining | | | Lytic necrosis | Hepatocytes swell and rupture | | | Fibrosis | Portal, central, bridging | Chronic liver disease | | Cirrhosis | Regenerative nodu