METABOLISM AND DISPOSITION OF C14-BILIRUBIN IN CONGENITAL NONHEMOLYTIC JAUNDICE*

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Abstract
In a patient with congenital unconjugated hyperbilirubinemia (Crigler-Najjar syndrome) and in 8 rats with hereditary icterus (Gunn rats), tracer techniques were used to estimate the biological half-life, total miscible pool, and fractional turnover of bilirubin. The metabolic disposition of the C14-bilirubin was determined in the feces and urine, and in 5 of the rats, in the bile. In the patient, the total miscible bilirubin pool was distributed about equally between the circulating plasma and extravascular space, which was attributed to the very strong reaction of the pigment with human albumin. In the rats, however, where bilirubin is less tightly bound to albumin, five-sixths of the exchangeable pigment pool was present in the extravascular compartments. In the absence of a functioning conjugating apparatus, elimination of bilirubin is accomplished through alternate metabolic pathways. These include breakdown of the pigment to more polar, diazo-negative derivatives, transfer of pigment across the intestinal mucosa into the gut, and excretion of unconjugated bilirubin in the bile.