Liver cirrhosis - definition, classification, progression. Microscopic & gross pathomorphology
The major clinical syndromes of liver disease are hepatic failure, cirrhosis, portal hypertension and cholestasis. Hepatic failure is generally the end point of progressive liver damage, either thanks to gradual or sudden destruction of hepatocytes, around 90% of hepatic function should be lost before we call it hepatic failure. Patterns that cause hepatic failure are:
- Acute liver failure with massive hepatic necrosis
- Chronic liver disease (most common route)
- Hepatic dysfunction without overt necrosis
Clinical features are jaundice, hypoalbuminemia, hyperammonemia, palmar erythema, spider angiomas and hypogonadism and gynecomastia in men.
Cirrhosis.
Liver cirrhosis is a diffuse process characterized by fibrosis and conversion of normal liver tissue into abnormal nodules, the main characteristics are:
- Fibrous septa - broad fibrous deposits around multiple adjacent lobules
- Parenchymal nodules - range in size
Remember: the classic morphological classification is by nodule size – micronodular (nodules under 3 mm, e.g. alcoholic cirrhosis), macronodular (over 3 mm, e.g. after chronic hepatitis B or C) and mixed. Most cirrhotic livers become mixed with time, so the cause is decided clinically rather than by the nodule size.
It is the end stage process of liver damage that may have multiple causes, the most common being Hep B, C, alcoholic and nonalcoholic steatohepatitis.
Pathogenesis
- Three main processes, death of hepatocytes, ECM deposition and vascular reorganisation
- Fibrosis is present in liver capsule, portal tracts and around central veins
- Major source of fibrosis is the perisinusoidal stellate cells which transform to myofibroblasts and lay down collagen fibers
- These stellate cells themselves produce growth factors for more stellate cells (transforming growth factor Beta)
- Vascular injuries also occur in cirrhosis, with inflammation and thrombosis of portal veins, hepatic arteries and/or central veins, causing zones of parenchymal hypoperfusion causing atrophy.
- We also see conversion of thin-walled sinusoids into higher-pressure channels, which increases speed of fluid movement and inhibits protein movement.
Clinical feature are that of progressive liver failure, complication related to portal hypertension and development of hepatocellular carcinoma.