Early hepatobiliary dysfunction during total parenteral nutrition: an experimental study

The etiology and pathophysiology of the liver disease associated with total parenteral nutrition (TPN) are unknown. In this study, we have attempted to define the early changes in hepatobiliary function during TPN in young rabbits nourished totally by the intravenous route for 3, 5, and 15 days, with age-matched rabbits on lab chow serving as controls. A decrease in basal bile flow along with elevations of serum bile acids and cholesterol was seen. The capacity for biliary secretion of sulfobromophthalein and of ursodeoxycholic acid was measured at the end of each diet regimen. Early impairment of biliary sulfobromophthalein (BSP) secretion was seen after 5 days of TPN, with no further deterioration after 15 days. Maximal bile acid secretory rate and bile flow, in response to the ursodeoxycholic acid load, were decreased after 15 days of TPN. Furthermore, after 15 days of TPN, both the volume of gallbladder bile and its bile acid content increased. The combined effects of the enteral fast and the intravenous administration of all nutrients were bile acid sequestration in an adynamic gallbladder with interruption of the enterohepatic circulation. In the parenterally fed rabbit, we have demonstrated bile secretory failure and gallbladder sludge, the two common complications of clinical TPN. These may be the early events that subsequently lead to cholestasis and liver damage in neonates maintained on prolonged TPN.