Bile acid metabolism in the cirrhotic rat.

Bile acid metabolism was studied in rats with cirrhosis induced by carbon tetrachloride (CCl4). Although the typical histologic features of cirrhosis were seen, cholestasis was not present in these animals as evidenced by a normal total serum bilirubin concentration and by a normal hepatic capacity to remove taurocholate infused intravenously. The cirrhotic rats also secreted taurocholate into bile at a normal rate. The total bile salt pool size in the cirrhotic rats was not significantly different from the pool size in normal rats (10.59 +/- 1.19 mumoles per gm. of liver (+/- 1 standard error of the mean) and 10.43 +/- 0.92 mumoles per gm. of liver, respectively). When the bile was drained externally through a chronic bile fistula, the normal rats increased the bile salt synthetic rate approximately 3-fold after 48 hours of drainage. However, the cirrhotic rats failed to significantly increase the synthetic rate for bile salts in response to biliary drainage. The normal rats also had a significant increase in cholic acid synthesis at the maximal synthetic rate, whereas the cirrhotic rats did not. These findings indicate that (when feedback inhibition is removed) CCl4 cirrhotic rats lack the ability to normally increase the activity of 7 alpha-hydroxylase and 12 alpha-hydroxylase, rate-limiting enzymes in the synthesis of bile salts.