Bile acid kinetics

K. Einarsson, K. Hellstrom, and M. Kallner, Bile acid kinetics in relation to sex, serum lipids, body weights, and gallbladder disease in patients with various types of hyperlipoproteinemia, J. Clin. Invest. 54 1301 (1974). 

The mechanism for the inhibition of cholesterol absorption is thought to involve competitive transfer to the micellar phase during absorption from the intestinal lumen. Phytosterols in the micellar phase may also act as emulsifying agents that selectively inhibit the transfer of cholesterol and other lipids (e.g., carotenoids and vitamins) and, thereby, limit their absorption. The exact kinetics governing the sterol competition for transfer are not known, but dietary sterols are absorbed differently in the digestive tract 40-50% for cholesterol, 12-16% for campesterol, 4-5% sitosterol, and <0.5% for phytostanols (37). Before absorption, esterified sterols are hydrolysed effectively in the upper intestine (191). Absorbed phytosterols are excreted by the liver into the bile but are hardly converted to bile acids (192). Numerous studies in animals and humans approved the safety of phytosterols and phytostanols (37). 

Kinetics of Bile Acid Metabolism. Using an isotope dilution technique, the bile acid pool in normal adults has been found to average from 2 to 4g. Steady state is reached when hepatic synthesis and fecal loss are in balance. In health, the magnitude of each process is 0.3 to 0.8g/day. There are usually 4 to 10 enterohepatic cycles per day. Because of this recycling mechanism, the jejunal concentration of bile acids is maintained at -5 to lOmmol/L during the postprandial state, much higher than the critical micellar concentration of 2mmol/L. Between meals, with decreased entry of bile acids into the intestine, the intraluminal concentration... 

The isotope dilution method is relatively easy to perform technically. The procedure has been widely used for measurement of cholesterol catabolism in different conditions (69-74) and of bile salt kinetics in gastrointestinal disorders (75-78). Markedly augmented loss of bile acids in ileopathy makes the procedure less reliable because the administered isotope may disappear totally into feces during the first day, sometimes even during the first enterohepatic circulation of the bile acid pool after administration of the label. Under these conditions, no quantitative figures are obtained, the method being suitable for screening of this disorder. 

H. Kwan, W. I. Higuchi, A. M. Molokhia, and A. F. Hofmann, Dissolution kinetics of cholesterol monohydrate in simulated bile. I. Influence of bile acid type and concentration, bile acid-lecithin ratio and added electrolyte, J.Pharm.Sci., 66 1094 (1977). 

Schreibinan et al -studied cholesterol kinetics in very obese patients with normal cholesterol levels, and found cholesterol turnover rates 2 1/2 times normal. Excretions of both neutral sterols and bile acids were increased. Analysis of plasma labeled-cholesterol decay curves showed normal size of the readily exchangeable cholesterol pool (pool A), but the slowly exchanging pool (pool B) was doubled. The extra mass of cholesterol in pool B could be accounted for by the cholesterol content of excess adipose tissue. 

Data on absorption of non-micellar lipids in the presence of bile salts is available from the study )y Knoebel [79]. The lymphatic transport of absorbed oleic acid and site of uptake from the intestinal lumen was measured in bile fistula rats. It was found that the concentration of bile salts in a continuous intraduodenal infusion did not affect the steady-state level of lipid appearing in the lymph until the bile salt concentration was as low as 1 mM, which represented a molar ratio of 20 1 of lipid to bile salt. In the case of infusates with relatively low concentrations of bile salts it was found that a larger part of the available surface area of the small intestine was utilized. The main conclusion is that lipids are equally well absorbed in vivo from non-micellar dispersions of lipids and bile salts as from solutions where the lipids are completely solubilized by bile salt mixed micelles. However, a detailed analysis of kinetics of uptake from non-micellar phases in vitro with isolated intestinal segments has not yet been done. 

This was confirmed in dogs (57) in a study which also demonstrated (for cholic, taurocholic, and glycocholic acids) that reabsorption occurs in the proximal tubule (Fig. 7) and that the reabsorptive process involves active transport. The latter conclusion was based on estimates of the tubular fluid/ ultrafiltrable plasma concentration ratio for taurocholate and an estimate of transtubular electrical potential taken from the literature. In addition, it was shown that the reabsorptive process for bile salts had a maximal rate (saturation kinetics) (Fig. 8). 

---