Biliary lipid composition in patients with cholesterol and pigment gallstones and gallstone-free subjects: deoxycholic acid does not contribute to formation of cholesterol gallstones

BACKGROUND: Four main disturbances have been attributed to cholesterol gallstone disease: hypersecretion of cholesterol from the liver with cholesterol supersaturation in bile; disturbed motility with defective absorption and secretion by the gallbladder; increased crystallisation of cholesterol in the gallbladder bile; and slow intestinal transit with increased amount of deoxycholic acid in the bile acid pool. We aimed to evaluate the biliary lipid composition in a large series of gallstone patients, with emphasis on the amount of deoxycholic acid and with respect to number of stones, compared to gallstone free subjects. MATERIALS AND METHODS: Bile was sampled during operations through puncture of the gallbladder from 145 cholesterol gallstone patients, 23 patients with pigment stones and 87 gallstone free patients undergoing cholecystectomy. Biliary lipid composition, cholesterol saturation, bile acid composition, nucleation time and cholesterol crystals were analysed. RESULTS: The patients with cholesterol gallstones showed higher molar percentage of cholesterol, lower total biliary lipid concentration, higher cholesterol saturation, shorter nucleation time and higher proportion of crystals in bile than the other groups. The nucleation time was significantly shorter in multiple cholesterol gallstone patients, but this was not due to higher cholesterol saturation. Male cholesterol gallstone patients showed higher cholesterol levels, lower total biliary lipid concentration, and higher cholesterol saturation in bile than female patients. There was no difference in biliary content of deoxycholic acid, but significantly lower content of cholic acid in gallstone patients compared to gallstone free patients. CONCLUSIONS: We conclude that deoxycholic acid does not contribute to gallstone formation in cholesterol gallstone patients. The short nucleation time in patients with multiple cholesterol stones is not due to higher cholesterol saturation.     

Somatostatin does not block the effect of vasoactive intestinal peptide on bile secretion in man

The effects of intravenously administered somatostatin and vasoactive intestinal peptide (VIP) on bile secretion were studied in 10 patients with complete biliary fistulas. The two peptides were administered both separately and simultaneously. During the infusion of vasoactive intestinal peptide, bile secretion increased by 85%, whereas during somatostatin infusion it decreased by 40%. When the peptides were administered together, the VIP-induced choleretic effect was not reduced by somatostatin. Vasoactive intestinal peptide infusion increased bicarbonate concentration and output, whereas somatostatin had the opposite effect. The output of chloride also increased following vasoactive intestinal peptide infusion but decreased following somatostatin infusion. The concentration of chloride was unaffected by somatostatin whereas it was decreased by vasoactive intestinal peptide. The output of bile acids was unaffected by vasoactive intestinal peptide and decreased by somatostatin infusion, whereas total lipid concentration increased during somatostatin infusion and decreased when vasoactive intestinal peptide was added. It is concluded that, in man, somatostatin acts on the bile acid-dependent canalicular bile secretion and also, to some extent, on the ductular secretion, whereas vasoactive intestinal peptide acts strictly at the ductular level. The effects of the two peptides on bile secretion are independent of each other.     

Effects of bile salt hydrophobicity on crystallization of cholesterol in model bile

Precipitation of cholesterol crystals is an essential step in gallstone formation. In the present study we found much faster and more extensive precipitation of various cholesterol crystal shapes in whole model biles containing the hydrophobic bile salt taurodeoxycholate than in biles containing the relatively hydrophilic taurocholate. Addition of taurodeoxycholate to isolated cholesterol–phospholipid vesicles also induced more crystallization than taurocholate. Crystallization behaviour in whole model biles and in vesicles after addition of corresponding bile salts was very similar. The very hydrophilic bile salts tauroursodeoxycholate and taurohyodeoxycholate never induced crystallization from vesicles, and crystallization in corresponding whole model biles did not occur. These bile salts also reduced crystallization dose dependently after addition of taurodeoxycholate to vesicles. Ultracentrifugation experiments suggested a higher vesicular cholesterol–phospholipid ratio for whole model biles containing more hydrophobic bile salts. These findings indicate that bile salt hydrophobicity influences shape of cholesterol crystals and extent of crystallization, possibly by modulating the vesicular cholesterol–phospholipid ratio.     

The effect of vitamin C in high doses on plasma and biliary lipid composition in patients with cholesterol gallstones: prolongation of the nucleation time

Vitamin C deficiency in guinea pigs leads to cholesterol supersaturation of bile and formation of cholesterol gallstones. It has been suggested that there may also exist an association between vitamin C and cholesterol gallstones in man, but such a relationship has not been studied in gallstone patients. In order to study the possible effects of vitamin C on gallstone disease in humans, plasma lipid levels, hepatic cholesterol metabolism, biliary lipid composition, cholesterol saturation and nucleation time of gallbladder bile were analysed in 16 consecutive gallstone patients, who were planned for laparoscopic cholecystectomy and were treated with vitamin C (500 mg, four times a day) for 2 weeks before surgery. The plasma concentration of vitamin C increased by 42% in the treatment group. The concentrations of plasma lipids did not differ before and after vitamin C treatment; nor did the plasma levels of lathosterol and 7α-hydroxy-4-cholesten-3-one, reflecting cholesterol and bile acid synthesis respectively. The relative concentrations of cholesterol, bile acids and cholesterol concentration of bile did not differ significantly between the two groups, but the relative concentration of phospholipids was slightly higher in the treated group. The bile acid composition was changed; the percentage of cholic acid being lower and those of deoxycholic acid, ursodeoxycholic acid and lithocholic acid higher in the vitamin C-treated patients compared with the untreated group. The nucleation time was significantly longer in the treatment group (7 days) compared with the untreated group (2 days). Our findings indicate that vitamin C supplementation may also influence the conditions for cholesterol gallstone formation in humans.