Bilirubin metabolism in the rat at high altitude.

Bilirubin metabolism was studied in rats injected with unconjugated bilirubin (0, 0.5, 1.5, 3.0, or 4.5 mg X 100 g-1) after 2 and 6 weeks continuous exposure to 4,600 m (15,000 ft) simulated altitude. Exogenous loads of bilirubin were used to exceed any effect of polycythemia, thereby allowing assessment of defects in conjugation and excretion due to the exposure to high altitude. Rats given no exogenous bilirubin showed polycythemia when exposed to high altitude which may have contributed to the small but significant elevations in their serum bilirubin levels. Compared to sea-level controls, mean serum concentrations of total and unconjugated bilirubin were significantly elevated in altitude-exposed rats given exogenous bilirubin. Mean serum conjugated bilirubin levels did not rise at any dose. Thus, bilirubin uptake and/or conjugation rather than excretion are impaired in rats at high altitude. We conclude that while polycythemia may contribute to high altitude-induced bilirubinemia, an impairment in uptake and/or conjugation also exists.