Microscopic structure of liver histology 5m answer
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Microscopic Structure of the Liver
Yamada's Textbook of Gastroenterology, 7th ed.; Sleisenger & Fordtran's GI and Liver Disease
1. Hepatic Lobule - Structural Models
Two models describe the liver's microscopic organization:
Classic (Hexagonal) Lobule
- A hexagonal unit centered on a central vein (terminal hepatic venule), surrounded by six peripheral portal tracts at each corner.
- Hepatocyte plates radiate from the central vein toward the portal triads.
Rappaport Acinus (functional model)
- Based on blood supply; centers on the portal tract.
- Divided into three zones based on oxygen gradient:
- Zone 1 (periportal) - best oxygenated; first to receive portal blood; resistant to ischemia; first affected in viral hepatitis.
- Zone 2 (mid-zonal) - intermediate.
- Zone 3 (centrilobular/perivenular) - least oxygenated; most susceptible to ischemic/toxic injury; highest cytochrome P450 activity; first to show centrilobular necrosis in CCl4 toxicity or right heart failure.
2. Portal Tract (Portal Triad)
Each portal tract contains three structures - the "portal triad":
- Portal venule - largest of the three; ~3x the diameter of the arteriole or bile duct
- Hepatic arteriole - approximately the same caliber as the bile duct (useful diagnostically)
- Interlobular bile duct - lined by a single layer of cuboidal cells; contains cytokeratins 7 and 19
The portal tract is surrounded by a limiting plate - the interface between portal connective tissue and the hepatic parenchyma. Inflammatory cells crossing this plate produce "interface hepatitis."
3. Parenchyma - Hepatocytes
Hepatocytes make up ~80% of liver cells. Key features:
- Arranged in cords (trabeculae) 1-2 cells thick in adults, each flanked by sinusoids on both sides
- Nucleus: centrally placed, round, ~10 µm, with clumped chromatin and prominent nucleoli; binucleate forms seen in zone 3 of elderly
- Cytoplasm: contains abundant organelles:
- ~2200 mitochondria per hepatocyte (larger in zone 3, more numerous in zone 1)
- Rough ER - protein synthesis (albumin, coagulation factors)
- Smooth ER - fatty acid metabolism, drug detoxification via cytochrome P450 (highest in zone 3)
- Golgi apparatus - glycoprotein and lipoprotein processing
- Bile canaliculi: grooves (hemicanaliculi) between adjacent hepatocytes fuse to form canaliculi; surrounded by actin microfilaments enabling peristaltic bile propulsion; visible on scanning EM
4. Sinusoids and Space of Disse
- Sinusoids are wide, irregular vascular channels that carry mixed portal and arterial blood from the portal tracts toward the central vein.
- Lined by discontinuous, fenestrated endothelial cells (no basement membrane), allowing direct plasma-hepatocyte contact.
- The Space of Disse lies between the sinusoidal endothelium and the hepatocyte surface. It contains:
- Plasma (not blood cells)
- Reticulin fibers (type III collagen) maintaining the lobular framework
- Hepatic stellate cells (Ito cells/fat-storing cells) in a resting state
5. Sinusoidal Cell Types
| Cell Type | Location | Function |
|---|---|---|
| Kupffer cells | Lining sinusoids | Resident macrophages; phagocytosis of debris, bacteria, endotoxins |
| Hepatic stellate cells (Ito cells) | Space of Disse | Store vitamin A (lipid droplets) in resting state; activated → myofibroblasts → collagen synthesis → fibrosis |
| Pit cells | Sinusoid lumen | Large granular lymphocytes; liver-specific NK cells |
| Sinusoidal endothelial cells | Sinusoid lining | Fenestrated, no basal lamina; facilitate exchange |
6. Biliary Network
Bile flows counter to blood flow, from hepatocytes outward toward portal tracts:
- Bile canaliculi - between hepatocyte surfaces (not a separate structure)
- Canals of Hering - near the limiting plate; lined partly by hepatocytes and partly by biliary epithelium; serve as the hepatic stem cell niche
- Terminal bile ductules (cholangioles)
- Interlobular bile ducts in portal tracts (15-20 µm diameter; cuboidal epithelium; CK7/CK19 positive)
7. Stroma (Extracellular Matrix)
- Glisson capsule: dense hypocellular collagen encapsulating the entire liver; extends into portal tracts
- Reticulin framework (types I and III collagen > 95% of total): demonstrated by reticulin stain - useful for detecting architectural distortion in pathology
- Type IV collagen, laminin, fibronectin, and elastin complete the matrix
Key clinical correlations for exam:
- Zone 3 necrosis: ischemia, paracetamol toxicity, CCl4
- Zone 1 necrosis: phosphorus poisoning, eclampsia
- Interface hepatitis (breach of limiting plate): autoimmune hepatitis, chronic viral hepatitis
- Stellate cell activation: key step in hepatic fibrosis/cirrhosis
- Canals of Hering: site of hepatic progenitor cells; proliferate in ductular reaction
Sources: Yamada's Textbook of Gastroenterology, 7th ed. (pp. 239-244); Sleisenger & Fordtran's GI and Liver Disease
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