Abstract
A simple method for the rigorous derivation of lithogenic index or percent cholesterol saturation, embodying both relative and total lipid concentrations, is described. We recently demonstrated that under physiological conditions only two key physical-chemical variables, the bile salt-lecithin ratio and the total lipid (bile salts + lecithin + cholesterol) concentration determine the equilibrium cholesterol solubility of bile. Of relevance to gallstone formation and dissolution in man is that the influence of variations in total lipid concentration on cholesterol solubility is quantitatively more important but has essentially been ignored. Using model biliary lipid systems, we experimentally determined a family of cholesterol solubility curves to encompass a wide range of bile salt-lecithin ratios for physiological variations in total lipid concentration (0.3--30 g/dl) at 37 degrees C (pH 7.0, 0.15 M NaCl) and accurately fitted these with fifth degree polynomial equations. We have now solved these equations for moles percent cholesterol, i.e., [cholesterol] X 100/[bile salt] + [lecithin] + [cholesterol] employing physiological values (0.085--0.425) for molar [lecithini]/[bile salt] + [lecithin] ratios. The resulting tables provide precise values for the maximal amount of cholesterol that would be soluble in bile at any total lipid concentration and bile salt-lecithin ratio and allow for rapid and accurate calculation of lithogenic index or percent cholesterol saturation from the moles percent cholesterol actually present in hepatic, gallbladder, and duodenal biles.
Highlights
+cholesterol) concentration determine the equilibrium cholesterol solubility of bile
(3-5), the influence of this variable becomes the predominant determinant of cholesterol solubility. These results demonstrate that for the precise determination of the degree of cholesterol saturation of native bile, the appropriate maximal cholesterol solubility value experimentally determined for the bile salt-lecithin ratio and the total lipid concentration of each sample must be employed
A familv of curves delineating the limits of cholesterol solubility in bile as a function of physiological bile salt-lecithin ratios and total lipid concentrations were accurately fitted by fifth degree polynomial regressions and plotted in rectangular format relating moles percent cholesterol, [cho
Summary
Once a threshold total lipid concentration is exceeded the maximum cholesterol solubility in bile increases linearly with the logarithm of the total lipid concentration over the range of physiological bile salt-lecithin ratios (3). + thin] [cholesterol] could be derived from the molar + [lecithin]/[bile salt] [lecithin] ratio and total lipid concentration (3).Samples3of these polynomial regressions for four total lipid concentrations are plotted (Calcomp 960 computer plots) in rectangular format in Fig. 1 together with the corresponding experimental cholesterol solubilities. With the use of a mini-computer, we solved to four significant figures all fifth degree polynomial equations for moles percent cholesterol, employing the physiological range of molar [lecithin]/[bile salt]. E Values appearing as numbers of larger size at the tops of the columns represent the total lipid concentration (bile salt plus lecithin plus cholesterol) expressed in g/dl of bile.
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