Dynamics of the Enterohepatic Circulation of Bile Acids

LaRusso, Nicholas F.; Korman, M. G.; Hoffman, Neville E.; Hofmann, Alan F.

doi:10.1056/nejm197410032911401

Cited by 205 publications

(45 citation statements)

References 16 publications

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“…We found a significant negative correlation between age and integrated postprandial conjugated serum bile acid levels. Since the fraction of bile acids in the portal blood cleared by the liver remains relatively constant and is independent of the load delivered to the liver [24,25] systemic bile acid levels are thought to be proportional to the load of bile acids absorbed from the intestine. Therefore, the observed differences in this study between both age groups suggest that the postprandial conjugated bile acid load in the portal blood is smaller in elderly subjects.…”

Section: Discussionmentioning

confidence: 99%

Effect of ageing on postprandial conjugated and unconjugated serum bile acid levels in healthy subjects

Salemans

Nagengast

Tangerman

et al. 1993

Eur J Clin Investigation

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Abstract. Colorectal cancer is a disease of elderly subjects. A decreased ileal absorption of bile acids in elderly subjects may lead to an increased exposure of the colonic mucosa to secondary bile acids. This may contribute to an enhanced risk of colorectal cancer. In this study fasting and postprandial conjugated and unconjugated serum levels of cholic, chenodeoxycholic, and deoxycholic acid in 12 elderly and 12 younger subjects were investigated. Intestinal transit time, gallbladder emptying and jejunal bacterial flora were also studied in both age groups. Fasting levels of conjugated and unconjugated serum bile acids were similar in both age groups. Postprandial levels of all individual conjugated bile acids increased to a significantly higher extent in the younger subjects. Postprandial unconjugated serum bile acid levels did not differ significantly between both age groups, although unconjugated deoxycholic levels tended to increase to higher levels in the elderly. Results of jejunal bacterial counts, gallbladder emptying and intestinal transit time were similar in both groups. These data suggest that conjugated bile acids are reabsorbed less effectively in elderly subjects.

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Section: Discussionmentioning

confidence: 99%

Effect of ageing on postprandial conjugated and unconjugated serum bile acid levels in healthy subjects

Salemans

Nagengast

Tangerman

et al. 1993

Eur J Clin Investigation

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“…Pool sizes relate inversely to biliary secretion rate, recycling rates, and gall bladder emptying and directly relate to intestinal extraction of bile salts in adults. Consequently, pool size should be inversely related to the fractional turnover rate (3,15,18). Little direct study of these aspects of biliary metabolism has been made in children.…”

Section: Discussionmentioning

confidence: 99%

Bile Salt Metabolism in Infants and Children after Protracted Infantile Diarrhea

Heubi

Balistreri

1980

Pediatr Res

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SummaryTen infants and children (mean age, 44 months), who had recovered from protracted infantile diarrhea with no sequelae, underwent detailed investigations of cholate metabolism using the isotope dilution technique. Cholate pool sue was 1011 f 73 mg/ m2, (2 * S.E.), synthetic rate was 358 f 58 mg/mz/day, and the fractional turnover rate was 0.359 * 0.049 days-'. Pool sue, uncorrected for body surface area differences, was shown to increase directly with body size (r = 0.827; P = 0.002) and age (r = 0.7M, P = 0.009). The fractional turnover rate varied inversely with age (r = -0.656, P = 0.02), surface area (r = -0.642; P = 0.023), and pool size (r = -0.703; P = 0.012) and directly with synthesis (r = 0.878; P<0.001). Infants and children have an intact enterohepatic circulation of cholate; the pool size and the mechanisms which regulate synthesis are similar to adults. The progressive enlargement of pool size with age is associated with an agerelated increase in intraluminal bile salt concentrations which ensures normal intraluminal fat digestion and solubiiation.

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“…The enterohepatic circulation of bile acids has a diurnal rhythm that is determined by eating. When a meal is eaten, there is a three-to sixfold increase in secretion of bile acids (37, 38) which is then reflected by a three-to sixfold postprandial increase in serum bile acid levels (22)(23)(24)(25). Two additional lines of evidence show that this effect is caused by the eating of a meal.…”

Section: Description Of the Model General Descriptionmentioning

confidence: 99%

“…With the development of sensitive specific radioimmunoassays for individual bile acid classes (18)(19)(20)(21), it became possible to detect the pulsatile rhythm of the enterohepatic circulation of bile acids (22)(23)(24)(25). The acceleration of the enterohepatic flow during digestion was signaled by a striking increase in the serum level of bile acids.…”

Section: Introductionmentioning

confidence: 99%

Description and simulation of a physiological pharmacokinetic model for the metabolism and enterohepatic circulation of bile acids in man. Cholic acid in healthy man.

Hofmann¹,

Molino²,

Milanese³

et al. 1983

J. Clin. Invest.

109

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A B S T R A C T A multicompartmental pharmacokinetic model based on physiological principles, experimental data, and the standard mathematical principles of compartmental analysis has been constructed that fully describes the metabolism and enterohepatic cycling in man of cholic acid, a major bile acid. The model features compartments and linear transfer coefficients. The compartments are aggregated into nine spaces based on physiological considerations (liver, gallbladder, bile ducts, jejunum, ileum, colon, portal blood, sinusoidal blood, and general circulation). The transfer coefficients are also categorized according to function: flow, i.e., emptying of gallbladder or intestinal spaces, and circulation of the blood; biotransformation, i.e., conjugation, deconjugation, or dehydroxylation; and transport, i.e., active or passive transport. The model is made time dependent by introducing meals, which trigger discrete increases in gallbladder emptying and intestinal flow. Each space contains three compartments. For cholic acid, these are unconjugated cholic acid, cholylglycine, and cholyltaurine. The model was then used with all existing experimental data to simulate cholic acid metabolism in healthy man over a 24-h period. Satisfactory agreement was obtained between simulated and experimental results for serum bile acid levels, hepatic bile acid secretion, and bile acid secretion into the intestine. The model was also used to classify 16 clinical instances in which the enterohepatic circulation of bile acids is altered

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Dynamics of the Enterohepatic Circulation of Bile Acids

Cited by 205 publications

References 16 publications

Effect of ageing on postprandial conjugated and unconjugated serum bile acid levels in healthy subjects

Effect of ageing on postprandial conjugated and unconjugated serum bile acid levels in healthy subjects

Bile Salt Metabolism in Infants and Children after Protracted Infantile Diarrhea

Description and simulation of a physiological pharmacokinetic model for the metabolism and enterohepatic circulation of bile acids in man. Cholic acid in healthy man.

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