The Enhancement of Maximal Bilirubin Excretion with Taurocholate–Induced Increments in Bile Flow

Abstract

Of the processes involved in the handling of a bilirubin load, the biliary secretory maximum or Tm for bilirubin has been regarded as rate limiting, and as a characteristic of liver function. In the present study, bile flow was varied by use of bile acid infusions, in order to determine whether the Tm is indeed constant or whether it varies with flow. Anesthetized dogs, with bile flow stabilized by cholinergic blockade, were studied during taurocholate infusions. In these animals the ductular component of flow is relatively inhibited and the bile flow rate increases approximately in proportion to the rate of excretion of taurocholate. The maximal biliary excretion rate of bilirubin was found to increase linearly with flow and taurocholate excretion, in a significant fashion, but, in contrast to the relation between taurocholate excretion and flow, a significantly large intercept remained on linear extrapolation towards zero flow. The basis for the large intercept is a great increase in the bilirubin concentration in bile as the flow is decreased. This results in a simultaneous sharp increase in the molar ratio (bilirubin/taurocholate) at very low flow rates.We have inferred, on the basis of the preceding data, that the capacity for bilirubin transport is linked to the secretion of bile acids into bile. At low rates of supply of bile acids, little of the material will reach the centers of the hepatic lobules, and the contribution of bile acids to bile flow at that site will be relatively low. At higher rates of bile acid infusion or supply, increased amounts of the bile acids will reach the centers of the lobules and contribute to increased bile formation in these areas. It appears that this is the mechanism which underlies the change in the transport maximum for bilirubin with change in the rate of bile salt excretion.