Metabolism and disposition of C14-bilirubin in congenital non-hemolytic jaundice.

In mammals, unconjugated bilirubin is rapidly cleared from the circulation and almost quantitatively excreted as a conjugate in the bile (2-4). The efficiency and rapidity of this process indicate that conjugation and subsequent biliary excretion represent the principal pathway of bilirubin disposition. If alternate pathways of bilirubin metabolism exist under physiologic conditions, their level of functional efficiency must be so low as to render detection difficult. When hepatic dysfunction causes interference with the efficiency of conjugation and excretion of bilirubin, however, resulting in hyperbilirubinemia, such alternate metabolic pathways may be expected to play a more important role in disposing of the accumulated pigment load (5). Moreover, when formation and hence biliary excretion of conjugated pigment is virtually abolished owing to an enzymatic defect in the hepatic conjugating apparatus, alternate pathways of bilirubin metabolism must assume the principal role in disposing of the bile pigment formed from the continuous breakdown of hemoglobin (6). Such metabolic anomalies associated with severe unconjugated hyperbilirubinemia exist as a rare congenital syndrome in man (Crigler-Najjar syndrome) (7, 8) and as a recessively inherited enzymatic defect in a mutant strain of Wistar rats (Gunn rats) (8, 9). In both instances, the level of unconjugated hyperbilirubinemia remains remarkably constant over months and years (8), indicating that a "steady state" has been established between pigment production and disposition. In the present investigation, a patient with congenital unconjugated hyperbilirubinemia and a group of hyperbilirubinemic Gunn rats were in-