Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1992 Sep;90(3):859–868. doi: 10.1172/JCI115961

Disorders of bile acid metabolism in cholesterol gallstone disease.

F Berr 1, E Pratschke 1, S Fischer 1, G Paumgartner 1
PMCID: PMC329940  PMID: 1522238

Abstract

The aim of the study was to evaluate the metabolism of individual bile acids in patients with cholesterol gallstone disease. Therefore, we determined pool size and turnover of deoxycholic (DCA), cholic (CA), and chenodeoxycholic acid (CDCA) in 23 female gallstone patients classified according to their gallbladder function and in 15 healthy female controls. Gallstone patients had normal hepatic bile acid synthesis, but, depending on gallbladder function, differed with respect to turnover and size of the bile acid pools: Patients with well-emptying gallbladder (group A, n = 9) had enhanced turnover and reduced pools of CA (-46%; P less than 0.01 vs. controls) and CDCA (-24%; P less than 0.05), but normal input and size of the DCA pool. With reduced gallbladder emptying (less than 50% of volume; group B, n = 6), turnover and pools of CA, CDCA, and DCA were similar as in controls. Patients with loss of gallbladder reservoir (group C, n = 8) had increased input (+100%; P less than 0.01) and pool size of DCA (+45%; P = 0.07) caused by rapid conversion of CA to DCA, while the pools of CA (-71%; P less than 0.001 vs. controls) and CDCA (-36%; P less than 0.05) were reduced by enhanced turnover. Thus, in patients with cholesterol gallstones, the pools of primary bile acids are diminished, unless gallbladder emptying is reduced. Furthermore, in a subgroup of gallstone patients, who had completely lost gallbladder function, the CA pool is largely replaced by DCA owing to rapid transfer of CA to the DCA pool. This probably contributes to supersaturation of bile with cholesterol.

Full text

PDF
864

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ABEL L. L., LEVY B. B., BRODIE B. B., KENDALL F. E. A simplified method for the estimation of total cholesterol in serum and demonstration of its specificity. J Biol Chem. 1952 Mar;195(1):357–366. [PubMed] [Google Scholar]
  2. Abaurre R., Gordon S. G., Mann J. G., Kern F., Jr Fasting bile salt pool size and composition after ileal resection. Gastroenterology. 1969 Dec;57(6):679–688. [PubMed] [Google Scholar]
  3. Ahlberg J., Angelin B., Einarsson K., Hellström K., Leijd B. Biliary lipid composition in normo- and hyperlipoproteinemia. Gastroenterology. 1980 Jul;79(1):90–94. [PubMed] [Google Scholar]
  4. BARTLETT G. R. Phosphorus assay in column chromatography. J Biol Chem. 1959 Mar;234(3):466–468. [PubMed] [Google Scholar]
  5. Berr F., Stellaard F., Goetz A., Hammer C., Paumgartner G. Ethinylestradiol stimulates a biliary cholesterol-phospholipid cosecretion mechanism in the hamster. Hepatology. 1988 May-Jun;8(3):619–624. doi: 10.1002/hep.1840080330. [DOI] [PubMed] [Google Scholar]
  6. Berr F., Stellaard F., Pratschke E., Paumgartner G. Effects of cholecystectomy on the kinetics of primary and secondary bile acids. J Clin Invest. 1989 May;83(5):1541–1550. doi: 10.1172/JCI114050. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Carey M. C. Critical tables for calculating the cholesterol saturation of native bile. J Lipid Res. 1978 Nov;19(8):945–955. [PubMed] [Google Scholar]
  8. Carulli N., Loria P., Bertolotti M., Ponz de Leon M., Menozzi D., Medici G., Piccagli I. Effects of acute changes of bile acid pool composition on biliary lipid secretion. J Clin Invest. 1984 Aug;74(2):614–624. doi: 10.1172/JCI111459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Duane W. C., Hanson K. C. Role of gallbladder emptying and small bowel transit in regulation of bile acid pool size in man. J Lab Clin Med. 1978 Dec;92(6):858–872. [PubMed] [Google Scholar]
  10. Everson G. T., Braverman D. Z., Johnson M. L., Kern F., Jr A critical evaluation of real-time ultrasonography for the study of gallbladder volume and contraction. Gastroenterology. 1980 Jul;79(1):40–46. [PubMed] [Google Scholar]
  11. Festi D., Frabboni R., Bazzoli F., Sangermano A., Ronchi M., Rossi L., Parini P., Orsini M., Primerano A. M., Mazzella G. Gallbladder motility in cholesterol gallstone disease. Effect of ursodeoxycholic acid administration and gallstone dissolution. Gastroenterology. 1990 Dec;99(6):1779–1785. doi: 10.1016/0016-5085(90)90487-l. [DOI] [PubMed] [Google Scholar]
  12. Fisher R. S., Stelzer F., Rock E., Malmud L. S. Abnormal gallbladder emptying in patients with gallstones. Dig Dis Sci. 1982 Nov;27(11):1019–1024. doi: 10.1007/BF01391749. [DOI] [PubMed] [Google Scholar]
  13. Hepner G. W. Effect of decreased gallbladder stimulation on enterohepatic cycling and kinetics of bile acids. Gastroenterology. 1975 Jun;68(6):1574–1581. [PubMed] [Google Scholar]
  14. Hepner G. W., Hofmann A. F., Malagelada J. R., Szczepanik P. A., Klein P. D. Increased bacterial degradation of bile acids in cholecystectomized patients. Gastroenterology. 1974 Apr;66(4):556–564. [PubMed] [Google Scholar]
  15. Heuman D. M., Vlahcevic Z. R., Bailey M. L., Hylemon P. B. Regulation of bile acid synthesis. II. Effect of bile acid feeding on enzymes regulating hepatic cholesterol and bile acid synthesis in the rat. Hepatology. 1988 Jul-Aug;8(4):892–897. doi: 10.1002/hep.1840080431. [DOI] [PubMed] [Google Scholar]
  16. Hofmann A. F., Hoffman N. Measurement of bile and acid kinetics by isotope dilution in man. Gastroenterology. 1974 Aug;67(2):314–323. [PubMed] [Google Scholar]
  17. Hopman W. P., Kerstens P. J., Jansen J. B., Rosenbusch G., Lamers C. B. Effect of graded physiologic doses of cholecystokinin on gallbladder contraction measured by ultrasonography. Determination of threshold, dose-response relationships and comparison with intraduodenal bilirubin output. Gastroenterology. 1985 Dec;89(6):1242–1247. doi: 10.1016/0016-5085(85)90639-0. [DOI] [PubMed] [Google Scholar]
  18. Krag E., Phillips S. F. Active and passive bile acid absorption in man. Perfusion studies of the ileum and jejunum. J Clin Invest. 1974 Jun;53(6):1686–1694. doi: 10.1172/JCI107720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kuroki S., Cohen B. I., Carey M. C., Mosbach E. H. Rapid computation with the personal computer of the percent cholesterol saturation of bile samples. J Lipid Res. 1986 Apr;27(4):442–446. [PubMed] [Google Scholar]
  20. Malagelada J. R., Go V. L., Summerskill W. H., Gamble W. S. Bile acid secretion and biliary bile acid composition altered by cholecystectomy. Am J Dig Dis. 1973 Jun;18(6):455–459. doi: 10.1007/BF01076595. [DOI] [PubMed] [Google Scholar]
  21. Marcus S. N., Heaton K. W. Deoxycholic acid and the pathogenesis of gall stones. Gut. 1988 Apr;29(4):522–533. doi: 10.1136/gut.29.4.522. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Marcus S. N., Heaton K. W. Intestinal transit, deoxycholic acid and the cholesterol saturation of bile--three inter-related factors. Gut. 1986 May;27(5):550–558. doi: 10.1136/gut.27.5.550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mok H. Y., Von Bergmann K., Grundy S. M. Regulation of pool size of bile acids in man. Gastroenterology. 1977 Oct;73(4 Pt 1):684–690. [PubMed] [Google Scholar]
  24. Morris J. S., Low-Beer T. S., Heaton K. W. Bile salt metabolism and the colon. Scand J Gastroenterol. 1973;8(5):425–431. [PubMed] [Google Scholar]
  25. Nilsell K., Angelin B., Liljeqvist L., Einarsson K. Biliary lipid output and bile acid kinetics in cholesterol gallstone disease. Evidence for an increased hepatic secretion of cholesterol in Swedish patients. Gastroenterology. 1985 Aug;89(2):287–293. doi: 10.1016/0016-5085(85)90328-2. [DOI] [PubMed] [Google Scholar]
  26. Nilsell K. Bile acid pool size and gallbladder storage capacity in gallstone disease. Scand J Gastroenterol. 1990 Apr;25(4):389–394. doi: 10.3109/00365529009095504. [DOI] [PubMed] [Google Scholar]
  27. Northfield T. C., Hofmann A. F. Biliary lipid output during three meals and an overnight fast. I. Relationship to bile acid pool size and cholesterol saturation of bile in gallstone and control subjects. Gut. 1975 Jan;16(1):1–11. doi: 10.1136/gut.16.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Penagini R., Spiller R. C., Misiewicz J. J., Frost P. G., Silk D. B. Effect of cholecystectomy on mouth-to-cecum transit of a liquid meal. Dig Dis Sci. 1988 Jan;33(1):19–22. doi: 10.1007/BF01536625. [DOI] [PubMed] [Google Scholar]
  29. Pomare E. W., Heaton K. W. Bile salt metabolism in patients with gallstones in functioning gallbladders. Gut. 1973 Nov;14(11):885–890. doi: 10.1136/gut.14.11.885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Pomare E. W., Heaton K. W. The effect of cholecystectomy on bile salt metabolism. Gut. 1973 Oct;14(10):753–762. [PMC free article] [PubMed] [Google Scholar]
  31. Pomeranz I. S., Shaffer E. A. Abnormal gallbladder emptying in a subgroup of patients with gallstones. Gastroenterology. 1985 Mar;88(3):787–791. doi: 10.1016/0016-5085(85)90152-0. [DOI] [PubMed] [Google Scholar]
  32. Redinger R. N. The effect of loss of gallbladder function on biliary lipid composition in subjects with cholesterol gallstones. Gastroenterology. 1976 Sep;71(3):470–474. [PubMed] [Google Scholar]
  33. Reuben A., Maton P. N., Murphy G. M., Dowling R. H. Bile lipid secretion in obese and non-obese individuals with and without gallstones. Clin Sci (Lond) 1985 Jul;69(1):71–79. doi: 10.1042/cs0690071. [DOI] [PubMed] [Google Scholar]
  34. Roda E., Aldini R., Mazzella G., Roda A., Sama C., Festi D., Barbara L. Enterohepatic circulation of bile acids after cholecystectomy. Gut. 1978 Jul;19(7):640–649. doi: 10.1136/gut.19.7.640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Shaffer E. A., Small D. M. Biliary lipid secretion in cholesterol gallstone disease. The effect of cholecystectomy and obesity. J Clin Invest. 1977 May;59(5):828–840. doi: 10.1172/JCI108705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Stange E. F., Scheibner J., Ditschuneit H. Role of primary and secondary bile acids as feedback inhibitors of bile acid synthesis in the rat in vivo. J Clin Invest. 1989 Jul;84(1):173–180. doi: 10.1172/JCI114137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Stellaard F., Sackmann M., Berr F., Paumgartner G. Simultaneous determination of pool sizes and fractional turnover rates, of deoxycholic acid, cholic acid and chenodeoxycholic acid in man by isotope dilution with 2H and 13C labels and serum sampling. Biomed Environ Mass Spectrom. 1987 Nov;14(11):609–611. doi: 10.1002/bms.1200141106. [DOI] [PubMed] [Google Scholar]
  38. Swell L., Bell C. C., Jr, Vlahcevic Z. R. Relationship of bile acid pool size to biliary lipid excretion and the formation of lithogenic bile in man. Gastroenterology. 1971 Nov;61(5):716–722. [PubMed] [Google Scholar]
  39. Wagner C. I., Trotman B. W., Soloway R. D. Kinetic analysis of biliary lipid excretion in man and dog. J Clin Invest. 1976 Feb;57(2):473–477. doi: 10.1172/JCI108299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. White E. C., McNamara D. J., Ahrens E. H., Jr Validation of a dietary record system for the estimation of daily cholesterol intake in individual outpatients. Am J Clin Nutr. 1981 Feb;34(2):199–203. doi: 10.1093/ajcn/34.2.199. [DOI] [PubMed] [Google Scholar]
  41. van der Linden W., Katzenstein B., Nakayama F. The possible carcinogenic effect of cholecystectomy. No postoperative increase in the proportion of secondary bile acids. Cancer. 1983 Oct 1;52(7):1265–1268. doi: 10.1002/1097-0142(19831001)52:7<1265::aid-cncr2820520722>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
  42. van der Werf S. D., Huijbregts A. W., Lamers H. L., van Berge Henegouwen G. P., van Tongeren J. H. Age dependent differences in human bile acid metabolism and 7 alpha-dehydroxylation. Eur J Clin Invest. 1981 Dec;11(6):425–431. doi: 10.1111/j.1365-2362.1981.tb02009.x. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES