Causes and Clinical Features of Hepatic Failure

The most common causes of hepatic failure when 80-90% of hepatic function is gone are massive hepatic necrosis, fulminant viral hepatitis, and drugs/chemicals (e.g. phenacetin, halothane, anti-TB medications, antidepressants, Amanita phalloides mushrooms).

The clinical features of hepatic failure include jaundice, edema, spider angiomas, hypogonadism, gynecomastia, encephalopathy, coagulopathy, and hepatorenal syndrome.

During cirrhosis, stellate cells or Ito cells transform into myofibroblasts that make and deposit collagen types I and III throughout the liver lobule, replacing the normal type IV reticulin between sinusoidal endothelial cells and hepatocytes.

In cirrhosis, there is disorganization of the circulation, with portal to hepatic vein shunts and hepatic artery to portal vein shunts, leading to increased resistance to portal blood flow and portal hypertension.

The major clinical consequences of portal hypertension in cirrhosis are ascites (fluid in the peritoneum), portosystemic shunts (e.g. hemorrhoids, varices), congestive splenomegaly, and hepatic encephalopathy (confusion, stupor, coma).

In cirrhosis, the disorganization of the hepatic circulation, including the loss of fenestrations in the sinusoidal endothelial cells and the formation of high-pressure, fast-flow shunts, impairs the synthesis and movement of proteins between the hepatocytes and the plasma.