The Effect of Intravenous Fat and Total Parenteral Nutrition on Biliary Physiology

Abstract

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.

Altered Gallbladder Bile Acidification with Long-Term Total Parenteral Nutrition

“…Hepatic cholesterol concentration decreases in miniswine on TPN and is less than half that seen in pigs on an oral diet. Similar reductions in biliary cholesterol have been observed in prairie dogs [7] and rats on total parenteral nutrition [13]. Consistent with other models of TPN-associated gallstones, bilirubin, not cholesterol, is increased in this model.…”

“…The percentage with sludge is nearly 100% if patients are on TPN for more than 6 weeks [5]. This clinical observation of TPN-associated gallstones has been reproduced in animal models [7,32]. We previously have found that miniswine on TPN for 1 to 2 weeks had a 10% incidence of gallbladder sludge formation [9].…”

“…With gallbladder stasis and a prolonged residence time in the gallbladder which is presumed to occur with long-term intravenous feeding [7], it would be expected that the gallbladder bile would be more concentrated and more acidified. The pH of the bile in TPN animals followed a relationship with the bile salt concentration similar to controls, but bile from TPN animals was not as acidified.…”

“…TPN for more than 6 weeks resulted in abnormal particulate matter in the gallbladder observed in all of their patients [5]. The etiology of this sludge formation is incompletely understood, yet may be influenced by prolonged gallbladder stasis [6 -8], increased biliary bilirubin [7,9], or reduced enterohepatic cycling of bile acids [10 -12].…”

Sludge and stone formation in the gallbladder in bedridden elderly patients with cerebrovascular disease: influence of feeding method

“…The predisposition of CVD patients on TPN to gallbladder disease is probably caused by failure of gallbladder contraction, and gallstone. 10,11 Although the underlying mechanisms of TPN-related gallbladder sludge and gallstone formation are not conclusive, several factors, including gallbladder stasis 10,12 and an altered profile of bile content, 13,14 have been suggested. The association between intermittent NF and gallbladder sludge or gallstone formation is unclear, although gallbladder motility 15 and CCK level 16 in continuous or cyclic enteral nutrition have been implicated in these processes.…”