Abstract

The cholestasis are defined as blockade or secretory distrubance of bile and appearance of bile in hepatocytes, Kupffer cells and biliary passages, usually associated with dilated bile canaliculi. Intra-and extraheptic cholestasis were induced by 17-ethinyl estradiol, or chlorpromazine hydrochloride and by ligation of bile duct to investigate the mechanism of the hepatic injury, ultrastructural changes of liver and alterations of liver function. The results obtained were as follows. 1) Functional and histological changes of intra-and extrahepatic cholestasis differed in various experimental groups. The liver weight is increased in 17-ethinyl estradiol treated group and ligation of bile duct group (5.6+/-0.15, P<0.001, 5.3+/-0.19 gm/100 gm body weight, P<0.001). The common features of intra-and extrahepatic cholestasis were double membrane bounded amorphous vesicular material infiltrations in the cytoplasm of hepatocyte, partial loss of microvilli of bile canaliculi, anf focal thickening of pericanalicular ectoplasm on electron microscopy. 2) Intrahepatic cholestasis induced by 17-ethinyl estradiol show significantly increased serum level of alkaline phosphatase and total bile aicd (134.0+/-16.82 IU/L, 29.5+/-4.68 umol/l). Kupffer cell proliferation and focal cytoplasmic degradation with myelin figures are characteristic features on electron microscopy. Chlorpromazine hydrochloride induced intrahepatic cholestasis show increased serum level of AST, ALT, Cholesterol and bilirubin (156.9+/-11.32, 49.0+/-2.83 IU/L, 59.3+/-6.73 mg/dl, 1.8+/-.043 mg/dl). Inflammatory cell infiltration, chiefly lymphocytes and esoinophils are seen in periportal area. Prominent vesiculation and vacuolations of smooth endoplasmic reticulum are characteristic feature on electron microscopy. 3) Extrahepatic cholestasis induced by ligation of bile duct show increase serum level of AST, ALT, GGT, cholesterol, total bile acid, and bilirubin (290.2+/-50.24, 171.5+/-47.17, 159.3+/-24.54, 33.7+/-1.47 IU/L, 86.6+/-9.18 mg/dl, 246.6+/-27.34 umol/l, 13.9+/-0.83 mg/dl). Light microscopically, morphologic alterations are feathery degeneration of hepatocytes, proliferation of bile ducts, bile infarct and prominent intracytoplasmic lipid droplets. Electron microscopically, electron dense acidophilic body, bile casts and complete loss of microvilli are seen in dilated bile canaliculi. Also noted are hypertrophy of cannalicular ectoplasm. Finely granular materials are infiltrated in degenerative cytoplasm.

• Keywords: Intra and Extrahepatic cholestatis;Biochemical and ultrastructural change;