Sunday, October 26, 2008

How a normal liver becomes cirrhotic:
3 major components

1. SEVERE, DIFFUSE, HEPATIC FIBROSIS

  • a post-necrotic and post-inflammatory response.
  • hepatocyte injury causes release of IGF-1, which acts as a mitogen for stellate cells.
  • Kupffer (and other) cells make TGF-beta, prompting stellate cells to turn into myofibroblasts
  • fibroblasts and myofibroblasts proliferate. Collagen (types I, III, XVIII) and fibronectin are produced.
  • because the myofibroblasts produce collagen and ECM in the space of Disse, the normal fenestrations in hepatic endothelium become closed.
  • closure of fenestrations causes blood to be shunted through the liver and into the hepatic vein, functionally bypassing hepatocytes.
  • eventually fibrosis will connect portal and central areas.

2. NODULAR REGENERATION

  • a post-necrotic response.
  • 75% of liver can be removed before liver dysfunction occurs
  • liver can regenerate up to 80% of its mass and will function if the connective tissue framework remains intact

3. BILE DUCT HYPERPLASIA

  • may be associated with necrosis, inflammation, toxins, blockage of bile ducts
  • proliferation of bile duct epithelium is concentrated in portal areas.

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