Similarities and differences between models of extrahepatic biliary obstruction and complete biliary retention...

Biliary obstruction in the rat causes known biochemical and morphological abnormalities. These abnormalities might be caused simply by retention of biliary constituents or might require other factors such as high biliary pressure, interruption of the normal flux of fluid, ions, and other biliary constituents through the hepatocyte and/or changes in intracellular concentrations, binding, and distribution of biliary constituents. We studied a choledochocaval (CC) fistula rat model characterized by complete biliary retention without bile stasis. CC fistula animals were compared with biliary obstructed rats over a 46-hr period. Bile flow and bile acid excretion rate reached high levels by hour 5 and remained high in CC fistula rats. Urinary bile acid excretion, shrinkage of the rapidly exchangeable bile acid pool, and serum bile acid and bilirubin concentrations were equivalent in the two models. Serum cholesterol concentration was higher and serum alkaline phosphatase and 5'-nucleotidase activities lower in obstructed rats. The percentage of beta-muricholate rose and the percentage of cholate decreased in bile acid from obstructed rats. This was associated with increased microsomal 6 beta-hydroxylase activity. Bile acid composition and microsomal 6 beta-hydroxylase activity changed little in CC fistula rats. Morphological examination revealed greater damage in obstructed rat livers. These data indicate that factors other than simple retention of biliary constituents contribute to the abnormalities observed in extrahepatic biliary obstruction.