Paper II
Question
Define and classify cirrhosis of liver. Discuss pathogenesis, histopathology and complications of alcoholic cirrhosis (5+4+3+3)
Answer
Definition: Cirrhosis is the end stage of chronic liver disease, defined morphologically by the triad of: (1) bridging fibrous septa linking portal tracts to each other and to central veins, (2) parenchymal nodules of regenerating hepatocytes encircled by fibrosis, and (3) disruption of the normal lobular architecture of the entire liver.
Classification:
- By morphology: Micronodular (nodules <3mm, classically alcoholic), macronodular (nodules >3mm, classically post-viral hepatitis), and mixed.
- By aetiology: Alcoholic liver disease, chronic viral hepatitis (B, C), non-alcoholic fatty liver disease/NASH, autoimmune hepatitis, biliary cirrhosis (primary/secondary), haemochromatosis, Wilson disease, α1-antitrypsin deficiency, cryptogenic.
Pathogenesis of alcoholic cirrhosis:
- Chronic alcohol intake causes hepatocyte injury through: acetaldehyde-mediated toxicity, oxidative stress from ethanol metabolism (generating reactive oxygen species), and induction of CYP2E1.
- Repeated cycles of hepatocyte fatty change (steatosis) → alcoholic hepatitis (hepatocyte injury, Mallory-Denk hyaline, neutrophilic infiltration) → progressive activation of hepatic stellate cells (Ito cells), which transform into myofibroblast-like cells and deposit collagen.
- Perivenular and pericellular (“chicken-wire”) fibrosis progresses to bridging fibrosis, eventually encircling regenerating hepatocyte nodules and converting the whole liver into a nodular, fibrotic organ — cirrhosis.
Histopathology:
- Micronodular pattern (nodules typically <3mm, fairly uniform in size).
- Bridging fibrous septa (portal-to-portal and portal-to-central).
- Hepatocytes may show residual fatty change, Mallory-Denk bodies, and ballooning degeneration.
- Loss of normal lobular architecture with regenerative nodules lacking central veins.
Complications:
- Portal hypertension → oesophageal varices (with risk of fatal haemorrhage), splenomegaly, ascites, caput medusae, haemorrhoids.
- Hepatic encephalopathy.
- Hepatocellular carcinoma.
- Hepatorenal syndrome.
- Coagulopathy (reduced synthesis of clotting factors) and hypoalbuminemia (oedema).
- Hepatic failure/decompensation.