Monday 23 February 2015

PATHOGENESIS OF LIVER CIRRHOSIS

In simple words , 'Liver cirrhosis' means fibrosis of liver and formation of nodules on its surface .

Before we see about the pathogenesis of liver cirrhosis . Let's review about the structure of liver .














Above picture shows that liver gains nutrients from hepatic artery and portal vein , And venous blood is drained by hepatic vein . Bile duct is draining bile from the liver .







This is a simplified diagram showing the course of hepatic artery , portal vein and bile duct inside the liver parenchyma . 
Hepatic artery and portal vein form a sinusoid and drain into the central vein. Central veins will join together to form the hepatic vein . 
In the sinusoid KUFFER CELLS(macrophages) are present.
There is a space between the sinusoids and hepatocytes . It is called as SPACE OF DISSE . It contains STELLATE CELLS. Nutrients from the sinusoids reaches hepatocyte passing through the space of disse .

CAUSATIVE AGENTS:
  1. Chronic Alcoholism
  2. Hepatitis B & C
  3. Hemochromatosis
  4. Genetic factor
PATHOGENESIS:

  1. Due to the causative agents , hepatocytes gets destroyed
  2. Damaged hepatocyte will produce CYTOKINES
  3. Cytokines will activate the kuffer cells present in the sinusoids.
  4. Activated Kuffer cells will produce GROWTH FACTOR and TNF.
  5. GF and TNF will activate the stellate cell . Stellate cell now will convert into a myofibroblast.    
  6. Myofibroblast will produce collagen which accumulates in the space of disse
  7. Thus space of disse gets thickened due to accumulation of collagen . So transfer of nutrients from the sinusoids to hepatocyte becomes difficult. 
  8. This will lead to death of hepatocytes 
  9. Some hepatocytes are spared . They will multiple profusely to compensate the lost liver function .
  10. This compensatory multiplication leads to the formation of nodules on the liver surface .


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