Metabolic factors in pathogenesis of cholesterol gallstones: implications for gallstone prevention

  • S. M. Grundy


Current treatment of clinical gallstone disease is generally successful. Cholecystectomy carries a low mortality and usually effects a complete cure. The recent introduction of pharmacological dissolution of cholesterol gallstones with oral administration of bile acids (chenodeoxycholic acid and ursodeoxycholic acid) appears to be an important addition to therapy of gallstones1. Despite these good therapeutic modalities for treatment of existing cholelithiasis, gallstones remain an important cause of morbidity and mortality. The prevalence of gallstones in many populations is enormous. Cholecystitis and obstructive jaundice are common clinical problems throughout the world. Although the risks for mortality from gallbladder disease and cholecystectomy are relatively lower in young and middle-aged adults, the risk increases greatly with advancing years. Gallstone disease is also costly both in financial terms and in time lost from work. For these reasons consideration must be given to whether gallstones can be prevented. If prevention is both possible and practical, the benefits would be great. The purpose of this review is to examine the question of gallstone prevention in the light of current knowledge about the pathogenesis of cholesterol stones. Therefore the mechanisms responsible for gallstone formation will be reviewed first, and the concept of risk factors for gallstone disease will be developed. If risk factors working through known pathogenic mechanisms can be identified and modified, they might provide a foundation upon which to develop a programme of gallstone prevention.


Bile Acid Mixed Micelle Gallstone Disease Chenodeoxycholic Acid Gallstone Formation 
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  1. 1.
    Schoenfield, L. J. and Lachin, J. M.; The Steering Committee, and the National Cooperative Gallstone Study Group. National Cooperative Gallstone Study (1981). Chenodiol (chenode-oxycholic acid) for dissolution of gallstones: The National Cooperative Gallstone Study. Ann, Intern, Med,, 95, 257–282Google Scholar
  2. 2.
    Admirand, W. H. and Small, D. M. (1968). The physicocochemical basis of cholesterol gallstone formation in man. J. Clin. Invest., 47, 1043–1052PubMedCrossRefGoogle Scholar
  3. 3.
    Carey, M. C. and Small, D. M. (1978). The physical chemistry of cholesterol solubility in bile. Relationship to gallstone formation and dissolution in man. J. Clin. Invest., 61, 998–1026PubMedCrossRefGoogle Scholar
  4. 4.
    Metzger, A. L., Adler, R. A., Heymsfield, S. and Grundy, S. M. (1973). Diurnal variation in biliary lipid composition: possible role in cholesterol gallstone formation. N. Engl. J. Med., 288, 333–336PubMedCrossRefGoogle Scholar
  5. 5.
    Mok, H. Y. I., von Bergmann, K. and Grundy, S. M. (1978). Factors affecting bile saturation at low outputs of bile acids. In Paumgartner, G., Stiehl, A. and Gerok, W. (eds.) Biological Effects of Bile Acids, pp. 39–51. ( Lancaster: MTP Press )Google Scholar
  6. 6.
    Mok, H. Y. I., von Bergmann, K. and Grundy, S. M. (1978). Effects of interruption of enterohepatic circulation on biliary lipid secretion in man. Am. J. Dig. Dis., 23, 1067–1075PubMedCrossRefGoogle Scholar
  7. 7.
    Sedaghat, A. and Grundy, S. M. (1980). Cholesterol crystals and the formation of cholesterol gallstones. N. Engl. J. Med., 302, 1274–1277PubMedCrossRefGoogle Scholar
  8. 8.
    Sedaghat, A., Kesaniemi, Y. A. and Grundy, S. M. (1983). Cholesterol crystals — a crucial link in the formation of cholesterol gallstones. In Paumgartner, G. Stiehl, A. and Gerok, W. (eds.) Bile Acids and Cholesterol in Health and Disease. ( Lancaster: MTP Press )Google Scholar
  9. 9.
    Burnstein, M. J., Ilson, R. G., Petrunka, C. N., Taylor, R. D. and Strasberg, S. M. (1983). Evidence for a potent nucleating factor in the gallbladder bile of patients with cholesterol gallstones. Gastroenterology, 85, 801–807PubMedGoogle Scholar
  10. 10.
    Bennion, L. J. and Grundy, S. M. (1975). Effects of diabetes mellitus on cholesterol metabolism in man. J. Clin. Invest., 56, 996–1011PubMedCrossRefGoogle Scholar
  11. 11.
    Grundy, S. M., Metzger, A. I. and Alder, R. D. (1972). Mechanisms of lithogenic bile formation in American Indian women with cholesterol gallstones. J. Clin. Invest., 51, 3026–3043PubMedCrossRefGoogle Scholar
  12. 12.
    Bennion, L. J., Ginsberg, R. L., Garnick, M. B. and Bennett, P. H. (1976). Effects of oral contraceptives on the gallbladder bile of normal women. N. Engl. J. Med., 294, 189–192PubMedCrossRefGoogle Scholar
  13. 13.
    Nilsson, S. and Stattin, S. (1967). Gallbladder emptying during the normal menstrual cycle: a cholecystographic study. Acta. Chir. Scand., 133, 648–652PubMedGoogle Scholar
  14. 14.
    Sampliner, R. E., Bennett, P. H., Comess, I. H., Rose, F. A. and Burch, T. A. (1970). Gallbladder disease in Pima Indians. N. Engl. J. Med., 283, 1358–1364PubMedCrossRefGoogle Scholar
  15. 15.
    Heaton, K. W. and Read, A. E. (1969). Gallstones in patients with disorders of the terminal ileum and distributed bile salt metabolism. Br. Med. J., 3, 494–496PubMedCrossRefGoogle Scholar
  16. 16.
    Rovsing, H. and Sloth, K. (1973). Micro gallbladder and biliary calculi in mucoviscidosis. Acta Radiol., 14, 588–592Google Scholar
  17. 17.
    Roy, C. C., Weber, A. M. and Morin, C. L. (1977). Abnormal biliary lipid composition in cystic fibrosis: Effects of pancreatic enzymes. N. Engl. J. Med., 297, 1301–1305PubMedCrossRefGoogle Scholar
  18. 18.
    Grundy, S. M., Ahrens, E. H. Jr., Salen, G., Schreibman, P. H. and Nestel, P. J. (1972). Mechanisms of action of Clofibrate on cholesterol metabolism in patients with hyper-lipidemia. J. Lipid Res., 13, 531–551PubMedGoogle Scholar
  19. 19.
    Grundy, S. M. and Mok, H. Y. I. (1977). Colestipol, Clofibrate and phytosterols in combined therapy of hyperlipidemia. J. Lab. Clin. Med., 89, 354–366PubMedGoogle Scholar
  20. 20.
    Pertsemlidis, D., Panveliwalla, D. and Ahrens, E. H. Jr. (1974). Effects of Clofibrate and of an esterogen-progestin combination on fasting biliary lipids and cholic acid kinetics in man. Gastroenterology, 66, 565–573PubMedGoogle Scholar
  21. 21.
    von Bergmann, K., Fierer, J., Mok, H. Y. I. and Grundy, S. M. (1981). Effects of rifampin on biliary lipids in man. Antimicrobial Agents Chemother., 19, 342–345Google Scholar

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© MTP Press Limited 1984

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  • S. M. Grundy

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