The effect of intravenous fat and total parenteral nutrition on biliary physiology

Patients on long-term total parenteral nutrition (TPN) have an increased incidence of gallstones. To determine the pathophysiologic mechanisms responsible for gallstone formation in these patients, we fed three groups of prairie dogs intravenously for 10 days with continuous infusions of isocaloric, isovolemic, and isonitrogenous solutions with either 0, 25, or 50% of nonprotein calories provided as Intralipid. A fourth group of prairie dogs was hyperalimented with the 25% solution for 28 days. Control animals were fed Purina rat Chow ad libitum. Each animal's bile salt pool was labeled with iv 3H-cholic acid 16 hr prior to collecting gallbladder and hepatic bile specimens. The ratio of gallbladder to hepatic bile 3H-cholic acid specific activity (dpm/mol of bile acid), an index of gallbladder stasis, was significantly (p less than 0.05) lower in TPN animals (less than 0.65 +/- 0.19) compared to controls (1.07 +/- 0.11). This finding indicates that gallbladder stasis developed in all animals fed by TPN. TPN did not alter gallbladder or hepatic bile lithogenic index. Two of five 28-day TPN animals developed biliary sludge, and one of these animals formed pigment gallstones. TPN without lipid decreased serum cholesterol concentration. As the lipid concentration of the TPN solution was increased, serum cholesterol increased. These data indicate that TPN induces gallbladder stasis regardless of caloric source but does not increase bile lithogenic index despite a dose-related rise in serum cholesterol as the percent of calories provided as lipid is increased. We conclude that TPN-induced gallbladder disease results from gallbladder stasis and not from increased bile cholesterol saturation.