pH regulation in human gallbladder bile: study in patients with and without gallstones.

Samples of gallbladder bile obtained from 25 controls and 34 patients with pigment (28 cases) or cholesterol (6 cases) gallstones were studied to establish whether disturbances in regulation of the biliary pH are likely to play a role in the pathogenesis of gallstones. Samples were assayed for pH, PCO2 and concentrations of sodium, bicarbonate and calcium (total and ionized). Saturation of bile in calcium carbonate was calculated. The main results of the study were as follows: (a) mean (+/- S.D.) PCO2 was significantly higher in gallbladder bile (6.72 +/- 0.36 kPa (in controls) and 7.63 +/- 0.29 kPa in patients) than in blood. This is consonant with previous results in animal species; it suggests that also in man a mucosal Na+ H+ antiport acidifies the gallbladder bile generating CO2 from biliary bicarbonate. (b) Biliary pH decreased when sodium concentration increased over a range of 140 to 280 mM. The pH decreased slightly when sodium increased from 140 to 200 mM and rapidly beyond this value; the rapid pH decrease in concentrated bile was associated with bicarbonate concentrations lower than 1 to 2 mM. The results showed that bicarbonate is the main buffer of gallbladder bile. (c) The pH decrease during bile concentration was similar in patients and controls. In both groups, fully concentrated bile was unsaturated in calcium carbonate. The results suggest that gallstone formation is not due to disturbances of biliary pH regulation. However, the normal concentration process that increases Ca++ concentration up to 4 mM and lowers pH values is likely to favor, in fully concentrated biles, the precipitation of calcium salts such as calcium bilirubinate.