Abstract
Maximal hepatic uptake, conjugation and excretion of bilirubin was studied simultaneously in 12 newborn rhesus monkeys ranging in age from 4 hours to 19 days. In this model of human physiologic jaundice, maximum serum bilirubin concentrations prior to infusion of bilirubin were 4.5 mg/100 ml between 12 and 36 hours of life and less than 1.0 mg/100 ml by 48 hours. Endogenous bilirubin excretion in bile in monkeys 12 hours to 19 days of age was 2 to 10 times greater than in normal adult rhesus monkeys. During the first 36 hours of life maximal cumulative hepatic uptake of bilirubin was 35% of adult capacity; hepatic conjugation of bilirubin in vitro and in vivo was 5% of adult capacity; and hepatic excretory capacity was 10% of adult capacity. Each of these functions increased rapidly to adult levels by the fourth day of life. The rate-limiting step in the transfer of bilirubin from blood to bile at 12 to 36 hours of age is the capacity to conjugate bilirubin with glucuronic acid. In the period immediately following this, significant accumulation of direct-reacting bilirubin occurs in liver and sera during infusion of unconjugated bilirubin, indicating that excretion is the rate-limiting process after 36 hours of age. These studies suggest that physiologic jaundice results from a markedly increased load of bilirubin presented to the liver either from increased bilirubin synthesis or enhanced intestinal reabsorbtion and marked limitation in the capacity to conjugate.
Studies performed at 4 hours of age in a monkey born 2 weeks post-maturely revealed that hepatic transport and conjugation of bilirubin was fully mature, indicating that maturation of each of these functions may occur in utero.
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Gartner, L., Lane, D. Hepatic metabolism and transport of bilirubin during physiologic jaundice in the newborn rhesusmonkey. Pediatr Res 5, 413 (1971). https://doi.org/10.1203/00006450-197108000-00175
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DOI: https://doi.org/10.1203/00006450-197108000-00175