Studies on the Kinetics of Unconjugated [14C]Bilirubin Metabolism in Normal Subjects and Patients with Compensated Cirrhosis

Abstract

The kinetics of unconjugated [14C]-bilirubin metabolism were investigated and analyzed in terms of a 3-pool model in a group of 7 normal subjects and in a group of 8 cirrhotic patients who had appreciable impairment of liver cell function. In patients with cirrhosis, the plasma unconjugated bilirubin was normal or only slightly increased, but the metabolism of unconjugated bilirubin was deranged. The mean volume of distribution, 4 h retention and mass of the rapidly mixing pool were all significantly greater than in normal subjects. In contrast, mean fractional clearance rate and mean estimated erythrocyte life-span were significantly less than in normal subjects. The mean fractional transfer rates and fluxes from pool 1 (rapidly mixing pool-plasma) to pool 3 (extravascular) and vice versa were significantly greater than corresponding values in normal subjects. In patients with compensated cirrhosis, the efficiency of the liver in extracting unconjugated bilirubin from plasma against a concentration gradient is impaired, even though the liver''s capacity to conjugate bilirubin may be normal. As a consequence of the increased volume of distribution, the absolute hepatic clearance of unconjugated bilirubin is relatively well maintained.