Liver Histology, Physiology and Pathology
Liver Histology, Physiology and Pathology - OMPATH
## 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
### Histo