Abstract
Most patients with cholesterol gallstone disease have supersaturated gallbladder bile, i.e. the amount of cholesterol is in excess of what can theoretically be kept in solution. Saturated bile is also more common among races and populations with a high frequency of gallstones1, 2. The development of supersaturated bile appears to be a necessary step for the subsequent precipitation of cholesterol, and may thus be considered a major risk factor for cholesterol gallstones. Many individuals without gallstone disease, however, also have supersaturated bile3, 4 (Figure 1). It has therefore become evident that other factors are required for crystallisation of cholesterol and aggregation of the crystals to occur. This chapter summarises and discusses recent studies of the mechanisms leading to the supersaturation of bile in situations where cholesterol gallstones are common.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Bennion, L.J. and Grundy, S.M. (1978). Risk factors for the development of cholelithiasis in man. N. Engl. I. Med., 299, 1161–7, 1221–7
Oviedo, M.A., Ho, KJ., Biss, K., Soong, SJ., Mikkelson, B. and Taylor, C.B. (1977). Gallbladder bile composition in different ethnic groups. Arch. Pathol. Lab. Med., 101, 208–12
Holzbach, R.T., Marsh, M., Olszewski, M. and Holan, K. (1973). Cholesterol solubility in bile: Evidence that supersaturated bile is frequent in healthy man. J. Clin. Invest, 52, 1467–79
Ahlberg, J., Angelin, B. and Einarsson, K. (1981). Hepatic 3-hydroxy-3-methyl-glutaryl coenzyme A reductase activity and biliary lipid composition in man: Relation to cholesterol gallstone disease and effects of cholic acid and chenodeoxycholic acid treatment. Lipid. Res., 22, 410–22
Lindstrom, C.G. (1977). Frequency of gallstone disease in a welldefined Swedish population: A prospective necropsy study in Malmo Scand. J. Gastroenterol, 12, 341–6
Einarsson, K., Nilsell, K., Leijd, B. and Angelin, B. (1985). Influence of age on secretion of cholesterol and synthesis of bile acids by the liver. N. Engl. Med., 313, 277–82
Angelin, B., Einarsson, K., Ewerth, S. and Leijd, B. (1981). Biliary lipid composition in obesity. Scand. I. Gastroenterol, 16, 1015–9
Bennion, LJ. and Grundy, S.M. (1975). Effects of obesity and caloric intake on biliary lipid metabolism in man./. Clin. Invest., 56, 996–1011
Whiting, M.J. and Watts, J.McK. (1984). Supersaturated bile from obese patients without gallstones supports cholesterol crystal growth but not nucleation. Gastroenterology, 86, 243–8
Einarsson, K., Hellstrom, K. and Kallner, M. (1975). Gallbladder disease in hyperlipoproteinemia. Lancet, 1, 484–7
Einarsson, K. and Angelin, B. (1986). Hyperlipoproteinemia, hypolipidemic treatment and gallstone disease. In Grundy, S.M. (ed.) Bile Acids and Atherosclerosis, pp. 66–97, (New York: Raven Press)
Angelico, M. and the GREPCO Group (1984). Relationships between serum lipids and cholelithiasis: Observations in the GREPCO study. In Capocaccia, L., Ricci, G., Angelico, F., Angelico, M. and Attili, A.F. (eds)Epidemiology and Prevention of Gallstone Disease, pp. 77–84 (Lancaster: MTP Press)
Angelico, M. and the GREPCO Group (1984). Factors associated with gallstone disease: Observations in the GREPCO study. In Capocaccia, L., Ricci, G., Angelico, F., Angelico, M. and Attili, A.F. (eds) Epidemiology and Prevention of Gallstone Disease, pp. 185–192 (Lancaster: MTP Press)
Roda, E., “for the Progetto Sirmione”. (1984). Factors associated with gallstone disease: Observations in the “Sirmione Study”. In Capocaccia, L., Ricci, G., Angelico, F., Angelico, M. and Attili, A.F. (eds)Epidemiology and Prevention of Gallstone Disease, pp. 207–9 (Lancaster: MTP Press)
Scragg, R.K., Calvert, G.D. and Oliver, J.R. (1984). Plasma lipids and insulin in gallstone disease: A case-control study. Br. Med.J., 289, 523–5
Kadziolka, R., Nilsson, S. and Schersten, T. (1977). Prevalence of hyper-lipoproteinaemia in men with gallstone disease. Scand. J. Gastroenterol 12, 353–5
Ahlberg, J. (1979). Serum lipid levels and hyperlipoproteinemia in gallstone patients. Acta Chir. Scand., 145, 373–7
Ahlberg, J., Angelin, B., Einarsson, K., Hellström, K. and Leijd, B. (1980). Biliary lipid composition in normo- and hyperlipoproteinemia. Gastroenterology, 79, 90–4
Cooper, J., Ceizerova, H. and Oliver, M.F. (1975). Clofibrate and gallstones. Lancet, 1, 1083
Coronary Drug Project Research Group (1977). Gallbladder disease as a side effect of drugs influencing lipid metabolism. N. Engl. I. Med., 296 1185–90
Thistle, J.L. and Schoenfield, LJ. (1971). Induced alterations in composition of bile of persons having cholelithiasis. Gastroenterology, 61, 488–96
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, 531–51
Pertsemlidis, D., Panveliwalla, D. and Ahrens, E.H., Jr. (1974). Effects of Clofibrate and of an ostrogen-progestin combination on fasting biliary lipids and cholic acid kinetics in man. Gastroenterology, 66, 565–73
Bateson, M.C., Maclean, D. Ross, P.E. and Bouchier, I.A.D. (1978). Clofibrate therapy and gallstone induction. Dig. Dis., 23, 623–8
Grundy, S.M. and Mok, H.Y.I. (1979). Effects of diets and drugs on biliary cholesterol secretion in man. In Fisher, M.M., Goresky, C.A., Shaffer, E.A. and Strasberg, S.M. (eds.) Gallstones, pp. 283–98 (New York: Plenum Press)
Angelin, B., Einarsson, K. and Leijd, B. (1979). Biliary lipid composition during treament with different hypolipidaemic drugs. Eur. J. Clin. Invest., 9, 185–90
Angelin, B., Einarsson, K. and Leijd, B. (1981). Clofibrate treatment and bile cholesterol saturation: Short-term and long-term effects and influence of combination with ehenodeoxycholic acid. Eur. I. Clin. Invest., 11, 185–9
Kesäniemi, Y.A. and Grundy, S.M. (1983). Clofibrate, caloric restriction, supersatura- tion of bile, and cholesterol crystals. Scand. J. Gastroenterol., 18, 897–902
Von Bergmann, K. and Leiss, O. (1984). Effects of short-term treatment with bezafibrate and fenofibrate on biliary lipid metabolism in patients with hyperlipidaemia. Eur. I. Clin. Invest., 14, 150–4
Eriksson, M. and Angelin, B. (1987). Bezefibrate therapy and biliary lipids : effects of short-term and long-term treatment in patients with various forms of hyperlipoproteinemia. Eur. J. Clin. Invest., 17, 396–401
Leiss, O., von Bergmann, K., Gnasso, A. and Augustin, J. (1985). Effect of gemofibrozil on biliary lipid metabolism in normolipidaemic subjects. Metabolism, 34, 74–82
Angelin, B., Einarsson, K. and Leijd, B. (1984). Effects of ciprofibrate treatment on biliary lipids in patients with hyperlipoproteinaemia. Eur. J. Clin. Invest., 14, 73–8
Boston Collaborative Drug Surveillance Program. (1974). Surgically confirmed gallbladder disease, venous thrombo-embolism, and breast tumors in relation to postmenopausal oestrogen therapy. N. Engl. J. Med., 290, 15–9
Stolley, P.D., Tonascia, J.A., Tockman, M.S., Sartwell, P.E., Rutledge, A.H. and Jacobs, M.P. (1975). Thrombosis with low-oestrogen oral contraceptives. Am. J. Epidemiol., 102, 197–208
Bennion, L.J., Ginsberg, R.L., Garnick, M.B. and Bennet, P.H. (1976). Effects of oral contraceptives on the gallbladder bile of normal women. N. Engl. J. Med., 294, 189–92
Andersson, A., James, O.F.W., MacDonald, H.S., Snowball, S. and Taylor, W. (1980). The effects of ethinyloestradiol on biliary lipid composition in young men. Eur. J. Clin. Invest., 10, 77–80
Holzbach, R.T. and Kibe, A. (1985). Pathogenesis of cholesterol gallstones. In Cohen, S. and Soloway, R.D. (eds) Gallstones, pp. 73–100, (New York: Churchill Livingstone)
Shaffer, E.A. and Small, D.M. (1977). Biliary lipid secretion in cholesterol gallstone disease: The effect of cholecystectomy and obesity./. Clin. Invest., 59, 828–40
Reuben, A., Maton, P.N., Murphy, G.M. and Dowling, R.H. (1985). Bile lipid secretion in obese and non-obese individuals with and without gallstones. Clin. Sci., 69, 71–9
Nilsell, K., Angelin, B., Liljeqvist, L. and Einarsson, K. (1985). Biliary lipid output and bile acid kinetics in cholesterol gallstone disease: Evidence for an increased hepatic secretion of cholesterol in Swedish patients. Gastroenterology, 89, 287–93
Leiss, O. and von Bergmann, K. (1985). Comparison of biliary lipid secretion in non- obese cholesterol gallstone patients with normal, young, male volunteers. Klin. Wochensehr., 63, 1163–9
Valdivieso, V.D., Palma, R., Nervi, F., Covarrubias, C., Severin, C. and Antezana, C. (1979). Secretion of biliary lipids in young Chilean women with cholesterol gallstones. Gut, 20, 997–1000
Sampliner, R.E., Bennett, P.H., Commess, L.J., Rose, F.A. and Burch, T.A. (1970). Gallbladder disease in Pima Indians: Demonstration of high prevalence and early onset by cholecystography. N. Engl. J. Med., 283, 1358–64
Bennion, L.J., Knowler, W.C., Mott, D.M., Spagnola, A.M. and Bennett, P.H. (1979). Development of lithogenic bile during puberty in Pima Indians. N. Engl. J. Med., 300, 873–6
Angelin, B. (1984). Regulation of hepatic lipoprotein receptor expression. In Calandra, S., Carulli, N. and Salvioli, G. (eds.) Liver and Lipid Metabolism, pp. 187–201 (Amsterdam: Elsevier)
Grundy, S.M., Metzger, A.L. and Adler, R.D. (1972). Mechanisms of lithogenic bile formation in American Indian women with cholesterol gallstones. J.Clin. Invest., 51, 3026–43
Angelin, B. and Einarsson, K. (1985). Regulation of HMG Co A reductase in human liver. In Preiss, B. (ed.) Regidation of HMG CoA Reductase, pp. 281–320 (New York: Academic Press)
Suckling, K.E. and Stange, E.F. (1985). Role of acyl-CoA: cholesterol acyltransferase in cellular cholesterol metabolism. J.Lipid. Res., 26, 647–71
Bjorkhem, I. (1985). Mechanism of bile acid synthesis in mammalian liver. In Danielsson, H. and Sjovall, J. (eds.)Sterols and Bile Acids, pp. 231–278, (Amsterdam: Elsevier Scientific Publishing Company)
Einarsson, K., Angelin, B,., Ewerth, S., Nilsell, K. and Bjorkhem, I. (1986). Bile acid synthesis in man: Assay of hepatic microsomal cholesterol 7 alpha-hydroxylase activity by isotope dilution-mass spectrometry. J.Lipid. Res.., 21, 82–8
Lindstedt, S. (1957). The turnover of cholic acid in man Acta Physiol Scand 40, 1–9
Angelin, B. and Einarsson, K. (1986). Bile acids and lipoprotein metabolism. In Grundy, S.M. (ed.) Bile Acids and Atherosclerosis, pp. 41–66 (New York: Raven Press)
Miettinen, T.A. (1970). Cholesterol production in obesity. Circulation, 44, 842–50
Nestel, P.J., Schreibman, P.H. and Ahrens, E.H. Jr. (1973). Cholesterol metabolism in human obesity. J.Clin. Invest., 52, 2389–97
Angelin, B., Backman, L., Einarsson, K., Eriksson, L. and Ewerth, S. (1981). Hepatic cholesterol metabolism in obesity: Activity of microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase. J.Lipid. Res., 23, 770–3
Leijd, B. (1980). Cholesterol and bile acid metabolism in obesity. Clin. Sci., 59, 203–6
Angelin, B., Hershon, K.S. and Brunzell, J.D. (1987). Bile acid metabolism in hereditary forms of hypertriglyceridemia: Evidence for an increased synthesis rate in monogenic familial hypertriglyceridemia. Proc. Natl Acad. Sci. USA., 84, 5434–8
Ahlberg, J., Angelin, B., Bjorkhem, I., Einarsson, K. and Leijd, B. (1979). Hepatic cholesterol metabolism in normo- and hyperlipidemic patients with cholesterol gallstones J.Lipid. Res., 20, 107–15
Einarsson, K., Hellstrom, K. and Kallner, M. (1973). The effect of clofibrate on the elimination of cholesterol as bile acids in patients with hyperlipoproteinaemia type II and IV. Eur. J. Clin. Invest., 3, 345–51
Angelin, B. (1984). Effects of hypolipidemic treatment on bile acid and cholesterol metabolism in man. In Carlson, L.A. and Olsson, A.G. (eds.) Treatment of Hyperlipoproteinemia pp. 121–4 (New York: Raven Press)
Kesäniemi, Y.A. and Grundy, S.M. (1984). Influence of gemfibrozil and Clofibrate on metabolism of cholesterol and plasma triglycerides in man. J. Am. Med. Assoc., 251, 2241–6
Kovanen, P.T., Brown, M.S. and Goldstein, J.L. (1979). Increased binding of low density lipoprotein to liver membranes from rats treated with 17a-ethinyl estradiol. J. Biol Chem., 254, 11367–73
Windler, E.E., Kovanen, P.T., Chao, Y.S., Brown, M.S., Havel, R J. and Goldstein, J.L. (1980). The estradiol-stimulated lipoprotein receptor of rat liver. A binding site that mediates the uptake of rat lipoproteins containing apoproteins B and E. J. Biol Chem., 255, 10464–71
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1988 Kluwer Academic Publishers
About this chapter
Cite this chapter
Einarsson, K., Angelin, B. (1988). The Secretory Defect. In: Northfield, T., Jazrawi, R., Zentler-Munro, P. (eds) Bile Acids in Health and Disease. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-1249-6_7
Download citation
DOI: https://doi.org/10.1007/978-94-009-1249-6_7
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-010-7054-6
Online ISBN: 978-94-009-1249-6
eBook Packages: Springer Book Archive