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Gallstone Disease pp 3–10Cite as

Increased Biliary Lithogenicity Through Cholesterol Supersaturation

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Abstract

Cholesterol monohydrate (ChM) is the major organic component of most gallbladder stones in Western populations [1]. An essential thermodynamic prerequisite for the precipitation of cholesterol (Ch) from bile is that bile becomes supersaturated with Ch [2]. Although Ch is virtually insoluble in water, it is present in high concentrations in the hepatic and gallbladder biles of adult human beings [2], where it is solubilized in thermodynamically stable bile salt (BS) and BS-phospholipid (PL) micelles and dispersed in a thermodynamically metastable state by unilamellar PL-Ch vesicles [3]. Hepatic secretion of vesicles appears to be the principal conduit for PL and Ch secretion into bile [4]. Since the transhepatic flux of BS drives PL-Ch secretion, i.e., vesicle exocytosis [5], the origin of supersaturated bile must perforce lie in the hypersecretion of Ch-enriched vesicles in the face of normal BS secretion or the normal secretion of Ch-enriched vesicles in the face of BS hyposecretion [6].

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References

  1. Carey MC, O’Donovan MA (1984) Gallstone disease: current concepts on the epidemiology, pathogenesis and management. In: Petersdorf RG et al. (eds) Harrison’s principles of internal medicine. Update V. McGraw-Hill, New York, pp 139–168

    Google Scholar 

  2. Carey MC, Small DM (1978) Physical-chemistry of cholesterol solubility in bile. Relationship to gallstone formation and dissolution in man. J Clin Invest 61: 998–1026

    Article  PubMed  CAS  Google Scholar 

  3. Carey MC, Cohen DE (1987) Biliary transport of cholesterol in vesicles, micelles and liquid crystals. In: Paumgartner G, Stiehl A, Gerok W (eds) Bile acids and the liver. MTP Press, Lancaster, pp 287–300

    Google Scholar 

  4. Cohen DE, Angélico M, Carey MC (1989) Quasielastic light scattering evidence for vesicular secretion of biliary lipids. Am J Physiol 20: G1–G8

    Google Scholar 

  5. Mazer NA, Carey MC (1984) Mathematical model of biliary lipid secretion: a quantitative analysis of physiological and biochemical data from man and other species. J Lipid Res 25: 932–953

    PubMed  CAS  Google Scholar 

  6. Hofmann AF (1988) Pathogenesis of cholesterol gallstones. J Clin Gastroenterol 10: S1–S11

    Article  PubMed  Google Scholar 

  7. Carey MC, Cahalane MJ (1988) Enterohepatic circulation. In: Arias IM, Jacoby WB, Popper H, Schacter D, Shafritz D (eds) The liver: biology and pathobiology, 2nd ed. Raven, New York, pp 573–616

    Google Scholar 

  8. Pattinson NR, Chapman BA (1986) Distribution of biliary cholesterol between mixed micelles and non-micelles in relation to fasting and feeding in humans. Gastroenterology 91: 697–702

    PubMed  CAS  Google Scholar 

  9. Carey MC (1989) Formation of cholesterol gallstones: the new paradigms. In: Paumgartner G, Stiehl A, Gerok W (eds) Trends in bile acid research. Kluwer, Dordrecht, pp 259–281

    Google Scholar 

  10. Bilhartz LE, Spady DK, Dietschy JM (1989) Inappropriate hepatic cholesterol synthesis expands the cellular pool of sterol available for recruitment by bile acids in the rat. J Clin Invest 84: 1181–1187

    Article  PubMed  CAS  Google Scholar 

  11. Turley SD, Dietschy JM (1988) The metabolism and excretion of cholesterol by the liver. In: Arias IM, Jacoby WB, Popper H, Schacter D, Shafritz D (eds) The liver: biology and pathobiology, 2nd ed. Raven, New York, pp 617–641

    Google Scholar 

  12. Small DM (1968) A classification of biologic lipids based upon their interaction in aqueous systems. J Am Oil Chem Soc 45: 108–119

    Article  PubMed  CAS  Google Scholar 

  13. Lange Y, Swaisgood MH, Ramos BV, Steck TL (1989) Plasma membranes contain half the phospholipid and 90% of the cholesterol and sphingomyelin in cultured human fibroblasts. J Biol Chem 264: 3786–3793

    PubMed  CAS  Google Scholar 

  14. Lange Y, Ramos BV (1983) Analysis of the distribution of cholesterol in the intact cell. J Biol Chem 258: 15130–15134

    PubMed  CAS  Google Scholar 

  15. Small DM (1977) Liquid crystals in living and dying systems. J Colloid Interface Sci 58: 581–602

    Article  CAS  Google Scholar 

  16. Yeagle PL (1988) Biology of cholesterol. CRC Press, Boca Raton

    Google Scholar 

  17. Clarke CF, Edwards PA, Fogelman AM (1987) Cellular regulation of cholesterol metabolism. In: Gotto AM Jr (ed) Plasma lipoproteins. Elsevier, Amsterdam, pp 261–276

    Chapter  Google Scholar 

  18. Myant NB (1981) The biology of cholesterol and related steroids. Heinemann, London, p 275

    Google Scholar 

  19. Fears R, Sabine JR (eds) (1986) Cholesterol 7α-hydroxylase (7α-monooxygenase). CRC Press, Boca Raton, pp 3–204

    Google Scholar 

  20. Scheibner J, Stange EF (1989) Elimination of secondary bile acids by colectomy induces bile acid synthesis in the rat. In: Paumgartner G, Stiehl A, Gerok W (eds) Trends in bile acid research. Kluwer, Dordrecht, pp 67–73

    Google Scholar 

  21. Einarsson K, Angelin B (1988) Pathogenesis of cholesterol gallstone disease: the secretory defect. In: Northfield T, Jazrawi R, Zentler-Munro P (eds) Bile acids in health and disease. Kluwer, Dordrecht, pp 99–116

    Chapter  Google Scholar 

  22. Eriksson M, Berglund L, Rudling M, Henriksson P, Angelin B (1989) Effects of estrogen on low density lipoprotein metabolism in males. J Clin Invest 84: 802–810

    Article  PubMed  CAS  Google Scholar 

  23. Henriksson P, Einarsson K, Eriksson A, Kelter U, Angelin B (1989) Estrogen-induced gallstone formation in males. J Clin Invest 84: 811–816

    Article  PubMed  CAS  Google Scholar 

  24. DenBesten L, Connor WE, Bell S (1973) The effect of dietary cholesterol on the composition of human bile. Surgery 73: 266–273

    PubMed  CAS  Google Scholar 

  25. Lee DWT, Gilmore CJ, Bonorris G, Cohen H, Marks JW, Cho-Sue M, Meiselman M, Schoenfield LJ (1985) Effect of dietary cholesterol on biliary lipids in patients with gallstones and normal subjects. Am J Clin Nutr 42: 414–420

    PubMed  CAS  Google Scholar 

  26. Angelin B, Backman L, Einarsson K, Eriksson L, Ewerth S (1981) Hepatic cholesterol metabolism in obesity: activity of microsomal 3-hydroxy 3-methylglutaryl coenzyme A reductase. J Lipid Res 23: 770–773

    Google Scholar 

  27. Miettinen TA (1970) Cholesterol production in obesity. Circulation 44: 842–850

    Google Scholar 

  28. Ahlberg J, Angelin B, Björkhem I, Einarsson K, Leijd B (1979) Hepatic cholesterol metabolism in normo- and hyperlipidemic patients with cholesterol gallstones. J Lipid Res 20: 107–115

    PubMed  CAS  Google Scholar 

  29. Nervi F, Marinovic I, Rigotti A, Ulloa N (1988) Regulation of biliary cholesterol secretion: functional relationship between the canalicular and sinusoidal cholesterol secretory pathways in the rat. J Clin Invest 82: 1818–1825

    Article  PubMed  CAS  Google Scholar 

  30. Nervi F, Bronfman M, Allalon W, Depiereux E, DelPozo R (1984) Regulation of biliary cholesterol secretion in the rat: role of hepatic cholesterol esterification. J Clin Invest 74: 2226–2237

    Article  PubMed  CAS  Google Scholar 

  31. Stone BG, Erickson SK, Craig WY, Cooper AD (1985) Regulation of rat biliary cholesterol secretion by agents that allow intrahepatic cholesterol metabolism: evidence for a distinct biliary precursor pool. J Clin Invest 76: 1773–1781

    Article  PubMed  CAS  Google Scholar 

  32. Coleman R, Rahman K, Bellringer ME, Carrella M (1988) Biliary lipid secretion and its control. In: Northfield T, Jazrawi R, Zentler-Munro P (eds) Bile acids in health and disease. Kluwer, Dordrecht, pp 43–60

    Chapter  Google Scholar 

  33. Meier PJ (1989) The bile salt secretory polarity of hepatocytes. J Hepatol 9: 124–129

    Article  PubMed  CAS  Google Scholar 

  34. Van der Linden W, Bergman F (1977) Formation and dissolution of gallstones in experimental animals. Int Rev Exp Pathol 17: 173–233

    PubMed  Google Scholar 

  35. Lamri Y, Roda A, Dumont M, Feldman G, Erlinger S (1988) Immunoperoxidase localization of bile salts in rat liver cells. Evidence for a role of the Golgi apparatus in bile salt transport. J Clin Invest 82: 1173–1182

    Article  PubMed  CAS  Google Scholar 

  36. Mockel GM, Gorti S, Tanaka T, Carey MC (1988) Microscope laser light scattering of bile formation. Hepatology 8:1367 (Abst)

    Google Scholar 

  37. Somjen GJ, Gilat T (1986) Changing concepts of cholesterol solubility in bile. Gastroenterology 91: 772–775

    PubMed  CAS  Google Scholar 

  38. Cohen DE, Carey MC (1990) Alteration of hepatic lipids in bile ducts and gallbladder. Hepatology (Suppl), in press

    Google Scholar 

  39. Cohen DE (1986) Studies of biliary lipid secretion and aggregation in model and native biles. PhD dissertation, Harvard University, pp 10–207

    Google Scholar 

  40. Cohen DE, Angelico M, Carey MC (1990) Structural alterations in lecithin-cholesterol vesicles following interactions with monomeric and micellar bile salts: physical-chemical basis for subselection of biliary lecithin species and aggregative states of biliary lipids during bile formation. J Lipid Res, in press

    Google Scholar 

  41. Cahalane MJ, Neubrand MW, Carey MC (1988) Physical-chemical pathogenesis of pigment gallstones. Semin Liver Dis 8: 317–328

    Article  PubMed  CAS  Google Scholar 

  42. Holzbach RT, Barnhart RL, Nader JM (1988) Pathogenesis of cholesterol gallstone disease: the physico-chemical defect. In: Northfield T, Jazrawi R, Zentler-Munro P (eds) Bile acids in health and disease. Kluwer, Dordrecht, pp 117–133

    Chapter  Google Scholar 

  43. Robins SJ, Fasulo JM, Patton GM (1982) Lipids of pigment gallstones. Biochim Biophys Acta 712: 21–25

    PubMed  CAS  Google Scholar 

  44. Mazer NA, Carey MC (1983) Quasielastic light scattering studies of aqueous biliary lipid systems. Cholesterol solubilization and precipitation in model bile solutions. Biochemistry 22: 426–442

    Article  PubMed  CAS  Google Scholar 

  45. Magnuson TH, Lillemoe KD, Pitt HA (1989) The relationship of clinical risk factors to gallstone composition. Hepatology 10:738 (Abst)

    Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA, 02115, USA

    M. C. Carey

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  1. M. C. Carey
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Editors and Affiliations

  1. Abteilung Innere Medizin II, Gastroenterologie und Ernährungswissenschaften, Universitätsklinikum Ulm, Robert-Koch-Straße 8, D-7900, Ulm, Germany

    W. Swobodnik  & H. Ditschuneit  & 

  2. Division of Gastroenterology, University of Texas Medical Branch at Galveston, 4.106 McCullough, G-64, 77550, Galveston, TX, USA

    R. D. Soloway

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© 1990 Springer-Verlag, Berlin Heidelberg

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Carey, M.C. (1990). Increased Biliary Lithogenicity Through Cholesterol Supersaturation. In: Swobodnik, W., Soloway, R.D., Ditschuneit, H. (eds) Gallstone Disease. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74619-2_1

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  • DOI: https://doi.org/10.1007/978-3-642-74619-2_1

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-50965-3

  • Online ISBN: 978-3-642-74619-2

  • eBook Packages: Springer Book Archive

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