Enzyme changes and morphometric analysis of bile ducts in experimental bile duct obstruction.

Chronic bile duct obstruction causes a marked proliferation of bile ductules within the rat liver plus an increase in the activities of hepatic gamma-glutamyl transpeptidase, 5'-nucleotidase and alkaline phosphatase. To determine if the increase in the activities of these enzymes within the liver simply reflects the increase in bile duct mass, we subjected rats to bile duct ligation for periods up to one week and compared the activities of these enzymes within liver tissue with bile duct volume, determined by morphometric analysis. The activities of two enzymes not useful in the diagnosis of chronic cholestasis, aspartate aminotransferase (GOT) and alanine aminotransferase (GPT), were also measured. There was no correlation between the proliferation of bile ductules and the activity of any of these enzymes. Bile duct volume increased 4.9-fold within 24 h after ligation and rose steadily, reaching a value of 13 times control in one week. Alkaline phosphatase activity increased 3.6-fold within 24 h after bile duct ligation and then was relatively constant. Gamma-glutamyl transpeptidase and 5'-nucleotidase activity both fell 24 h after ligation but were slightly increased after 48 h. Enzyme activities of each were almost twice control at 120 and 168 h. Alanine aminotransferase activity fell steadily during the period of bile duct ligation, while aspartate aminotransferase was unchanged. The change in gamma-glutamyl transpeptidase and 5'-nucleotidase activity within the liver cannot be due simply to hypertrophy of bile duct epithelium.