Normal histology	Histopathology	Pathological basis of disease	Clinical findings	
Tissue architecture:
•	The hepatocytes are arranged into lobules which are bounded by thin septa of collagenous supporting tissue.
•	The hepatic lobules are hexagonal in shape.
•	Terminal branches of the hepatic artery & hepatic portal vein are located at the angles of the lobule boundaries in portal tracts.
•	Blood from the portal tracts converges upon a terminal hepatic venule (centrilobular venule) of each lobule via sinusoids which pass between plates of hepatocytes.
•	The terminal hepatic venules drain to the hepatic vein. 

Portal triad:
•	Hepatic portal vein has a very thin wall lined by flattened endothelial cells.
•	Bile collecting ducts are lined by simple cuboidal or columnar cells.
•	Surrounding the portal tract are anastomosing plates of hepatocytes.
•	Between them are hepatic sinusoids receiving blood from both the hepatic portal & hepatic arterial systems. 

Cellular characteristics:
•	Hepatocytes are large polyhedral cells with large round nuclei (polypoid), dispersed chromatin & prominent nucleoli.
•	Hepatocytes store glycogen & lipids.
•	The cytoplasm is strongly eosinophilic due to numerous mitochondria with a fine basophilic granularity due to extensive free ribosomes.
•	Sinusoid lining cells: flattened condensed nuclei & poorly stained cytoplasm.
•	Kupffer cells: scattered among endothelial cells are large plump phagocytic cells with ovoid nuclei.	Abnormal histology:
•	Presence of nodules.
•	Presence of fibrous septa separating the nodules.
•	Loss of normal hepatic lobular architecture.
•	Portal triads become interconnected by broad bands of fibrous tissue.
•	Hepatocytes exhibit minimal / mild fatty change.
•	Some hepatocytes have large nuclei & prominent nucleoli – hepatocellular dysplasia with higher chance of becoming neoplastic.
•	There is extensive fibroblast proliferation.
•	Lymphocytic cellular infiltrate within fibrous septa.
•	Piecemeal necrosis may be seen: hepatocytes lining the margins of the nodules adjacent to the fibrous septa are invaded by lymphocytic infiltration resulting in patchy areas of hepatocellulcar necrosis.
•	Varying degrees of bile duct proliferation.

Effects of altered liver architecture:
•	Reduced liver cell function.
•	Disturbance of blood flow through the liver from portal vein to hepatic vein.	Defined by:
•	Fibrosis: delicate bands or broad septa.
•	Nodules created by regeneration of hepatocytes.
•	Disruption of parenchyma architecture of the entire liver.

•	The fibrosis is generally irreversible & is accompanied by reorganization of the vascular architecture, with formation of abnormal interconnections between inflow & outflow.

Nodules:
•	Macronodular: > 3mm.
•	Micronodular: < 3mm.

Causes of macronodular cirrhosis:
•	Viral hepatitis (B or C): 5-10%
•	Wilson’s disease
•	1-antitrypsin deficiency

Causes of micronodular cirrhosis:
•	Alcohol liver disease: 60-70%
•	Biliary diseases: 5-10%
•	Primary hemochromatosis: 5%
•	Wilson disease

Pathogenesis:
•	Central process is progressive fibrosis.
•	Types I & III collagen are deposited in all portions of the lobule, & sinusoidal endothelial cells lose fenestrations.
•	Major source of excess collagen is perisinusoidal stellate cell.
•	Collagen synthesis is stimulated by chronic inflammatory conditions, release of cytokines & direct stimulation of stellate cells by toxins.	•	May be clinically silent
•	Anorexia
•	Weight loss
•	Weakness
•	Osteoporosis
•	Debilitation

Causes of death:
•	Hepatic failure
•	Complications of portal hypertension
•	Hepatocellular carcinoma