The effects of intraduodenal bile acid administration on biliary secretion of ionized calcium and carbonate in man

Abstract

The importance of calcium in gallstone formation is increasingly recognized. Calcium carbonate is an important constituent of gallbladder stones and may be present in the nidus of cholesterol stones. Secondary deposition of calcium carbonate on the surface of cholesterol gallstones is an important reason for failure of oral bile acid dissolution therapy. We sought to determine the effects of bile acids on the crystallization conditions of calcium carbonate in bile. We studied 18 patients with choledocholithiasis with a percutaneous or endoscopically placed catheter high in the biliary tree. Samples of bile in the basal state and following replacement of the bile acid pool with cholic acid, chenodeoxycholic acid and ursodeoxycholic acid were analyzed for total calcium, ionized calcium, bicarbonate and carbonate, and the saturation index for calcium carbonate was calculated. Hepatic bile in the basal state was supersaturated with calcium carbonate. Total calcium concentrations rose linearly with rising bile acid concentrations but ionized calcium was maintained in a relatively narrow range. These data are consistent with an important role for bile acids in binding calcium. Extrapolation of the linear regressions between bile acid concentration and calcium concentrations suggested that in the absence of bile acids, biliary calcium concentrations are in passive equilibrium with plasma. Chenodeoxycholic acid and ursodeoxycholic acid caused a bicarbonate-rich choleresis and significantly augmented the saturation index for calcium carbonate, whereas cholic acid caused no change. In contrast with animal models, the apparent choleretic activity of cholic acid, chenodeoxycholic acid and ursodeoxycholic acid was similar, and no hyper-choleresis was observed with ursodeoxycholic acid. Chenodeoxycholic acid and ursodeoxycholic acid therefore increase the thermodynamic possibility for calcium carbonate precipitation.

The Effect of Biliary Bile Acid Concentration and Composition on the Calcium Level in Human Gallbladder Bile.

“…Anaerobic condition was not maintained during measurement of biliary pH, which was ranged 7.15 to 8.45. No correlation was observed between pH and ionized calcium levels in our study, and biliary calcium levels were in agreement with previous reports (Sutor et al 1980; Knyrim et al 1989). As all bile acids are already ionized within the range of pH 6.5 to 8.5 (Gleeson et al 1990), biliary pH are proposed not to have much influence on calcium ion binding of bile acids.…”

“…2). This finding was compatible with the previous reports (Knyrim et al 1989;Yoneda et al 1991). Non-ionized calcium may be solubilized by binding mainly to bile acid mixed micelles which may play an important buffer-like role in keeping the constant ionized calcium level to minimize the risk of calcium precipitation in bile (Moore et al 1982;Moore 1984).…”

“…Raedsch et al (1981) reported that calcium solubility decreased in UDCArich bile compared to that of CDCA-rich bile in in vitro experiment. Knyrim et al (1989) demonstrated that UDCA replacement resulted in an increase in the relative proportion of ionized calcium compared to CA and CDCA in human. They proposed that UDCA may bind calcium ions weakly and increase calcium activity in bile compared to other bile acids.…”

“…Knyrim et al (1989) demonstrated that replacement of the bile acid pool with CDCA and UDCA resulted in a significant rise in the concentration of bicarbonate and carbonate in bile. However, we could not investigate biliary bicarbonate concentration in this study.…”

Combination of ursodeoxycholic acid and glucocorticoids upregulates the AE2 alternate promoter in human liver cells

“…Among other effects, UDCA administration is known to result in bicarbonate-rich choleresis (16,17), although this bile acid has been reported to exert modulatory effects in the particular BDL rat model, in which obstructive cholestasis is associated with bile ductular cell hyperplasia and increased secretinstimulated ductal secretory activity (18). In any case, PET technology in untreated PBC patients (and other cholestatic patients) indicates that they have impaired biliary bicarbonate excretion in response to secretin and that UDCA may restore the secretin response in those patients with PBC (19).…”