Abstract
To understand better the mechanisms involved in biliary lipid excretion and to evaluate their role in cholesterol gallstone formation, the rates of biliary excretion of bile salts, cholesterol, and phospholipids were measured in two species, man and dog. Seven cholecystectomized patients with balloon-occludable reinfusion T-tubes were studied during intact and interrupted enterohepatic circulation and four cholecystectomized dogs were studied during interrupted enterohepatic circulation. In man and dog both cholesterol and phospholipid outputs were hyperbolically related to bile salt output by the equation y = x/(a + bx). The output curves intersected the origin and showed an initial rapid rise, followed by a slower increase to a maximum, suggesting a rate-limited mechanism. The shape of the curves permitted calculation of the theoretical maximal outputs and the rates of rise to those outputs. Comparison of these values showed that in both man and dog phospholipid output was greater than cholesterol output and that cholesterol and phospholipid were excreted at different rates. These studies (a) indicate that cholesterol, phospholipids, and bile salts are not excreted in a fixed relationship and (b) demonstrate the usefulness of the derived theoretical maximal lipid output, and the rate of rise of lipid excretion to a maximum, in evaluating the kinetics of biliary lipid excretion.
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- 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]
- Bennion L. J., Grundy S. M. Effects of obesity and caloric intake on biliary lipid metabolism in man. J Clin Invest. 1975 Oct;56(4):996–1011. doi: 10.1172/JCI108180. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DenBesten L., Connor W. E., Bell S. The effect of dietary cholesterol on the composition of human bile. Surgery. 1973 Feb;73(2):266–273. [PubMed] [Google Scholar]
- DenBesten L., Safaie-Shirazi S., Connor W. E., Bell S. Early changes in bile composition and gallstone formation induced by a high cholesterol diet in prairie dogs. Gastroenterology. 1974 May;66(5):1036–1045. [PubMed] [Google Scholar]
- Grundy S. M., Metzger A. L., Adler R. D. Mechanisms of lithogenic bile formation in American Indian women with cholesterol gallstones. J Clin Invest. 1972 Dec;51(12):3026–3043. doi: 10.1172/JCI107130. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hardison W. G., Apter J. T. Micellar theory of biliary cholesterol excretion. Am J Physiol. 1972 Jan;222(1):61–67. doi: 10.1152/ajplegacy.1972.222.1.61. [DOI] [PubMed] [Google Scholar]
- KAY R. E., ENTENMAN C. Stimulation of taurocholic acid synthesis and biliary excretion of lipids. Am J Physiol. 1961 Apr;200:855–859. doi: 10.1152/ajplegacy.1961.200.4.855. [DOI] [PubMed] [Google Scholar]
- Lynn J., Williams L., O'Brien J., Wittenberg J., Egdahl R. H. Effects of estrogen upon bile: implications with respect to gallstone formation. Ann Surg. 1973 Oct;178(4):514–524. doi: 10.1097/00000658-197310000-00014. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Metzger A. L., Adler R., Heymsfield S., Grundy S. M. Diurnal variation in biliary lipid composition. Possible role in cholesterol gallstone formation. N Engl J Med. 1973 Feb 15;288(7):333–336. doi: 10.1056/NEJM197302152880702. [DOI] [PubMed] [Google Scholar]
- 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]
- Northfield T. C., LaRusso N. F., Hofmann A. F., Thistle J. L. Biliary lipid output during three meals and an overnight fast. II. Effect of chenodeoxycholic acid treatment in gallstone subjects. Gut. 1975 Jan;16(1):12–17. doi: 10.1136/gut.16.1.12. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sarfeh I. J., Beeler D. A., Treble D. H., Balint J. A. Studies of the hepatic excretory defects in essential fatty acid deficiency. Their possible relationship to the genesis of cholesterol gallstones. J Clin Invest. 1974 Feb;53(2):423–430. doi: 10.1172/JCI107576. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scherstén T., Nilsson S., Cahlin E., Filipson M., Brodin-Persson G. Relationship between the biliary excretion of bile acids and the excretion of water, lecithin, and cholesterol in man. Eur J Clin Invest. 1971 Jan;1(4):242–247. doi: 10.1111/eci.1971.1.4.242. [DOI] [PubMed] [Google Scholar]
- Soloway R. D., Carlson H. C., Schoenfield L. J. A balloon-occludable T-tube for cholangiography and quantitative collection and reinfusion of bile in man. J Lab Clin Med. 1972 Mar;79(3):500–504. [PubMed] [Google Scholar]
- Soloway R. D., Powell K. M., Senior J. R., Brooks F. P. Interrelationship of bile salts, phospholipids, and cholesterol in bile during manipulation of the enterohepatic circulation in the conscious dog. Gastroenterology. 1973 Jun;64(6):1156–1162. [PubMed] [Google Scholar]
- Soloway R. D., Schoenfield L. J. Effects of meals and interruption of enterohepatic circulation on flow, lipid composition, and cholesterol saturation of bile in man after cholecystectomy. Am J Dig Dis. 1975 Feb;20(2):99–109. doi: 10.1007/BF01072334. [DOI] [PubMed] [Google Scholar]
- Swell L., Bell C. C., Jr, Entenman C. Bile acids and lipid metabolism. 3. Influence of bile acids on phospholipids in liver and bile of the isolated perfused dog liver. Biochim Biophys Acta. 1968 Oct 22;164(2):278–284. [PubMed] [Google Scholar]
- Swell L., Entenman C., Leong G. F., Holloway R. J. Bile acids and lipid metabolism. IV. Influence of bile acids on biliary and liver organelle phospholipids and cholesterol. Am J Physiol. 1968 Dec;215(6):1390–1396. doi: 10.1152/ajplegacy.1968.215.6.1390. [DOI] [PubMed] [Google Scholar]
- TALALAY P. Enzymic analysis of steroid hormones. Methods Biochem Anal. 1960;8:119–143. doi: 10.1002/9780470110249.ch3. [DOI] [PubMed] [Google Scholar]
- Wheeler H. O. Biliary excretion of bile acids, lecithin, and cholesterol in hamsters with gallstones. Gastroenterology. 1973 Jul;65(1):92–103. [PubMed] [Google Scholar]
- Wheeler H. O., King K. K. Biliary excretion of lecithin and cholesterol in the dog. J Clin Invest. 1972 Jun;51(6):1337–1350. doi: 10.1172/JCI106930. [DOI] [PMC free article] [PubMed] [Google Scholar]