The effect of parenteral nutrition on biliary calcium and bilirubin

Recent studies have suggested that patients maintained on prolonged total parenteral nutrition (TPN) are at increased risk for gallstone formation. Animal and human data suggest that TPN causes calcium bilirubinate sludge and pigment gallstones. However, the effect of TPN on bile bilirubin and calcium concentrations has not previously been investigated. We, therefore, tested the hypothesis that TPN alters biliary bilirubin and calcium. Eight adult male prairie dogs received TPN (dextrose 15%, FreAmine III 4.25%, Intralipid 10%, insulin 25 U, electrolytes, and vitamins) at a rate of 80 cc/kg/day for 10 days. Eight additional animals maintained on a trace cholesterol diet served as controls. Gallbladder and hepatic bile samples were assayed for bilirubin and calcium. Cholesterol saturation index (CSI) and R_sa, a measure of gallbladder stasis, were also calculated. Calcium bilirubinate crystals were seen in gallbladder bile or wall scrapings of 7 of 8 TPN animals but in none of the controls (P < 0.001). Animals that received TPN had bilirubin levels that were significantly higher in gallbladder bile (24.8 ± 7.0 vs 5.1 ± 0.9, P < 0.05). Similarly, TPN animals had calcium levels that were significantly higher in gallbladder (30.0 ± 3.6 vs 13.9 ± 2.1, P < 0.005) as well as hepatic (10.5 ± 0.6 vs 7.4 ± 0.6, P < 0.005) bile. The R_sa values were also significantly lower (P < 0.01) in TPN animals (0.57 ± 0.07 vs 1.06 ± 0.14). CSI, serum bilirubin, serum calcium, hematocrit, and reticulocyte counts did not differ between groups. These data indicate that TPN alters gallbladder bile concentrations of bilirubin and calcium and causes gallbladder stasis. Further concentration of bile by the gallbladder results in bilirubin supersaturation, precipitation of calcium bilirubinate crystals and, ultimately, pigment gallstone formation.