Equine fasting hyperbilirubinemia.

Abstract

It appears that different mechanisms responsible for fasting hyperbilirubinemia may be operative in different mammalian species (and subspecies). An increase in bilirubin production does not seem to occur in the horse, but a decrease in the hepatic uptake of bilirubin has been supported by a number of studies. Even though the delay in plasma elimination could also result from a decrease in hepatic blood flow, this possibility does not seem to play a major role since the hepatic uptake of compounds with low intrinsic hepatic clearance (e.g., ICG and bilirubin) appear to be affected more during fasting than those with higher clearances (e.g., BSP, bile acid, antipyrine, acetaminophen, and lidocaine) (Table I). Other possibilities such as a decrease in the affinity of hepatocellular membrane carriers involved in the uptake of these compounds or altered content of intracellular proteins involved in cellular transport or storage of bilirubin have not been investigated in horses. Competition with free fatty acids for these carrier-mediated events seems likely, particularly because horses and ponies experience high degrees of hyperlipidemia during fasting. However, studies that have explored the competition hypothesis, while not entirely negative, do not fully support it as being the sole mechanism responsible for this phenomenon. Hepatocellular UDPGT activities have not been adequately investigated in horses, but it is apparent that intraduodenal infusion of glucose is effective in reducing fasting hyperbilirubinemia and also in increasing biliary bilirubin excretion. It therefore seems possible that UDP-glucose and UDPGA levels in the livers of horses could be reduced during fasting, thus resulting in substrate depletion for the conjugating enzymes. As pointed out by Freedland et al. (1991), it is also possible that the horse, like the Bolivian squirrel monkey, might also have a relatively high apparent Km and low Vmax for UDPGT, thus resulting in high steady-state levels of plasma bilirubin, particularly during fasting. Although little is known about the cause of equine fasting hyperbilirubinemia and the subtle factors that may be modulating slight changes in the production, hepatocellular uptake, binding, conjugation, and/or biliary excretion of this pigment, it is known that it can be rapidly reversed by refeeding native hay. Perhaps one direction for future research could point toward more fully exploring what aspects of feeding are responsible for reversing this intriguing physiological phenomenon.