Solubility of cholesterol in bile salt-lecithin model systems

Cholesterol solubility was determined in model systems of unconjugated and conjugated bile salts and lecithin at physiologic concentrations. Conjugated bile salts had somewhat less dissolving power than unconjugated forms, with taurine conjugates showing less power than glycine conjugates. Lecithin increased the dissolving power of each bile salt species proportionally up to a lecithin-bile salt molar ratio of 1.0, at which point the amount of cholesterol dissolved was triple that in the absence of lecithin. At most physiologic ratios of lecithin-bile salt, however, lecithin only doubles the amount of cholesterol dissolved. Lecithin reduces, but does not eliminate, significant differences in the cholesterol dissolving power of both unconjugated and conjugated bile salt species. Mixtures of unconjugated bile salts show a simple additive effect in the absence of lecithin, but when lecithin is present the dissolving power of deoxycholate predominates over cholate, and of cholate over chenodeoxycholate. Mixtures of conjugated bile salt species produce a simple additive effect on dissolving power in both the presence and the absence of lecithin. Our cholesterol saturation curves for glycodeoxycholate and glycocholate at a total bile salt concentration of 150 mM, which we consider representative of the cholesterol dissolving power of human gallbladder bile, showed less dissolving power at lecithin-bile salt ratios of 0.25 to 0.50 than did the curve of Adminrand and Small; our curves were reasonably similar to those of Hegardt and Dam on the trilinear graph. Our studies show that changes in total bile salt concentration encountered in human gallbladder bile do produce significant shifts in the saturation curve.Supported by Research Grant AM-09368 and Training Grant T1-AM-05314 from the National Institute of Arthritis and Metabolic Diseases, US Department of Health, Education and Welfare.Presented in part at the annual meeting of the Southern Society for Clinical Research on January 28, 1967, at New Orleans, Louisiana.     

The effect of sodium oleate on cholesterol solubility in bile salt-lecithin model systems

Reflux of pancreatic secretions and bacterial infection have been suggested as important factors in gallstone formation in some instances by introducing into bile phospholipases hydrolyzing lecithin to lysolecithin, mono- and diglycerides, and free fatty acids. Since there is little data on free fatty acids, we studied the effect of sodium oleate, the soap of one of the major fatty acid derivatives of lecithin, on cholesterol solubility in unconjugated bile salt-lecithin model solutions to see if an increase in this component might lead to saturation of bile with cholesterol. In the absence of lecithin, sodium oleate decreased cholesterol solubility in bile salt solutions at concentrations physiologic for bile, although cholesterol solubility was increased by oleate at higher oleate-bile salt ratios. In the presence of lecithin, sodium oleate decreased cholesterol solubility at all concentrations studied. Significant differences in cholesterol solubility were found for all comparable concentrations of sodium cholate and deoxycholate studied, both in the presence and absence of lecithin. Our studies showed that an increase in free fatty acid concentration can increase cholesterol saturation significantly in unconjugated bile salt-lecithin model solutions. Whether or not free fatty acid concentrations in pathologic bile reach levels sufficient to contribute to cholesterol saturation and gallstone formation cannot be determined until more adequate data on the minor lipid composition of bile becomes available.Supported by Research Grant AM-09368 and Training Grant T1-AM-05314 from the National Institute of Arthritis and Metabolic Diseases U.S. Department of Health, Education and Welfare.     

Biliary lipid excretion in patients with pigment gallstones

Pigment gallstone patients are believed to have normal biliary lipid excretion. In order to measure this and to better understand cholesterol gallstone formation, the kinetics of biliary lipid excretion were studied in three patients who had been cholecystectomized for pigment gallstones and the results compared to those previously obtained in patients cholecystectomized for cholesterol gallstones. Pigment-stone patients had hyperbolic relationships between cholesterol and phospholipid outputs and bile salt output which were similar to those seen in cholesterol-stone patients. However, pigment-stone patients excreted more cholesterol and phospholipid at high bile salt output but approached those levels more gradually than cholesterol-stone patients. As a result, pigment-stone patients produced bile undersaturated with cholesterol at a lower bile salt output than cholesterolstone patients, and thus they would be less likely to produce supersaturated bile during low bile salt output such as that occurring during an overnight fast. The data suggest that cholesterol-stone patients, in addition to excreting more cholesterol and less bile salts than normals, have a defect in the rate of lipid output in response to decreasing bile salt output.This work was presented in part at the meeting of the American Gastroenterological Association, San Antonio, Texas, May, 1975, and published in abstract form inGastroenterology 68:1085, 1975.This work was supported in part by research, training, and facilities grants from the U.S. Public Helath Service, National Institutes of Health AM 05462, AM 16549, RR 1512 and FR-40, and the U.S. Veterans Administration TR-15.     

Hepatic lipid secretion and cholelithiasis

Summary Recent work has suggested that secretion of lithogenic hepatic bile is a major factor in the etiology, and a prerequisite abnormality to the growth and maturation of cholesterol gallstones. Cholesterol is normally solubilized in bile by mixed micelles of bile acids and lecithin. A decreased bile acid pool or a decrease in the ratio of bile acid and lecithin to cholesterol characterizes lithogenic bile. These observations have stimulated investigation of biliary lipid secretion, relevant to pursuing the genesis of the alterations. This review summarizes current knowledge of the individual and interrelated biosynthesis, kinetics, biliary secretion, and regulation of cholesterol, bile acid and lecithin. Investigations of induced alterations by drugs, hormones and diet are also reviewed. The lithogenic potential of bile can be decreased by chenodeoxycholic acid, but more work is needed, in particular, to define the hepatic enzymatic abnormality that causes the secretion of lithogenic bile.Supported in part by Research Grant AM-6908 from the National Institutes of Health, Public Health Service.     

Human gallbladder mucosal function. Effect of concentration and acidification of bile on cholesterol and calcium solubility

The most recognized function of the human gallbladder is to store bile. However, this organ is not a static reservoir. It actively modifies bile by two processes: concentration and acidification. This study was designed to simultaneously evaluate the relationship between these two physiological processes in the normal human gallbladder and to define their effects on biliary cholesterol and calcium solubility. Bile was sampled directly from the gallbladder of 78 morbidly obese patients undergoing elective gastric bypass procedures. All had negative results of intra-operative ultrasound examinations for sludge and gallstones, normal liver function tests, and no history of hepatobiliary disease. Bile salt concentrations, an indirect index of concentration by the gallbladder, ranged from 15.1-272.8 mmol/L. As [bile salt] increased, [Na+], [K+], free [Ca2+], [cholesterol], [phospholipid], and [total lipid] increased linearly; [Cl-1] decreased linearly. Molar percent cholesterol decreased from 17.2% in dilute bile to 10.1% in fully concentrated bile, suggesting that cholesterol was absorbed by the gallbladder. As bile was concentrated, cholesterol saturation index decreased curvilinearly from a maximum of 3.7 in dilute bile to 1.0-1.5 in concentrated bile. Concentration of gallbladder bile was accompanied by progressive acidification. Bile pH decreased linearly with increasing [bile salt]; [CO3(2-)] decreased curvilinearly. Despite increasing [Ca2+], CaCO3 saturation index decreased curvilinearly with increasing [bile salt] from a maximum of 3.62 in dilute bile to a minimum of 0.12 in concentrated and acidified bile. CaCO3 saturation index also decreased exponentially with decreasing pH. This study concludes that concentration of bile enhances cholesterol solubility while acidification enhances calcium salt solubility. By increasing the solubilities of these two species, gallbladder mucosal function may play a key role in preventing gallstone formation.     

Studies on the pathogenesis of diet-induced dog gallstones

Experimental diet-induced dog gallstones contained mainly protein, mucous substances, bile salts, bilirubin, an insoluble pigment which formed an insoluble black residue after acid hydrolysis, and only traces of cholesterol. Added dietary cholesterol was necessary to pigmented gallstone production and led to hypercholesterolemia. In bile, the ratio of cholesterol to bile salts was increased, but phospholipids were increased and cholesterol insolubility was not found. Dry weight, osmolality, and concentration of sodium and potassium in bile were reduced, but were not considered sufficient to influence micelle formation or lipid-pigment solubility. Taurine was reduced in serum and bile and unconjugated bile acids appeared in gallbladder bile; the pKa of these acids is near the pH of bile in these animals and may have caused precipitation of bile acids, accounting for their presence in the stones. Bile cultures were sterile. Total bilirubin content was unaltered but the methods used did not exclude the presence of unconjugated bilirubin as a potential cause of pigment precipitation in aqueous bile. Increased numbers of secretory vesicles occurred in gallbladder epithelium and large amounts of mucus were in the epithelial crypts. These observations suggest that bile proteins or mucous substances are important to lithogenesis in this model.With the Technical Assistance of P.N. SineSupported in part by Graduate Training Grant in Gastroenterology 5T01-AM5206 and Research Grant AM 08708 from the National Institutes of Health, U.S. Public Health Grant Service, Bethesda, Maryland, and in part by a Veterans Administration Research and Education Associateship Award, and by the Medical Research Service.Dr. Freston is a Burroughs-Wellcom Scholar in Clinical Pharmacology     

Molecular composition of biliary phosphatidylcholines, as related to cholesterol saturation, transport and nucleation in human gallbladder bile.

It has been suggested that qualitative changes in bile phosphatidylcholine (lecithin) play a role in the pathogenesis of cholesterol gallstones. We investigated the possible relationship between the molecular composition and hydrophobicity of biliary lecithins and bile cholesterol saturation, nucleation time and the mode of cholesterol transport in human gallbladder bile. Nineteen patients (12 with and seven without gallstones) undergoing abdominal surgery were studied. Bile cholesterol saturation ranged from 77% to 186% (median: 123%) and nucleation time from 1 to 24 days (median: 3 days). Biliary lipid carriers (vesicles and mixed micelles) were separated using Superose-6 gel chromatography and their lipid content was quantitated. Biliary lecithin composition was analyzed by HPLC. Fourteen individual molecular species were detected in the bile: none were related to cholesterol saturation or nucleation time. An arbitrary cumulative index of lecithin hydrophobicity was computed for each bile sample, based on the HPLC capacity factor of the individual species and their percent mole fraction: this index ranged from 47.0 and 58.5 (median: 49) and was unrelated to cholesterol saturation and nucleation time. The biliary concentration of sn-1 palmitoyl:sn-2 arachidonoyl lecithin was significantly correlated (p less than 0.01) with the fraction of cholesterol carried by mixed micelles. This finding suggests that arachidonoyl lecithin may play a modulatory role in the partitioning of cholesterol among biliary carriers. We conclude that major abnormalities in the composition of biliary lecithins are unlikely to play a causative role in the pathogenesis of cholesterol gallstone, although the role of arachidonoyl species requires further investigation.     

Cholesterol and bile salt studies on the bile of patients with cholesterol gallstones

Gallbladder bile from patients with cholesterol stones and control patients without cholesterol stones was analysed for the relative concentrations of bile salts, phospholipids, and cholesterol. It was not possible to distinguish stone-forming from control biles when these were plotted on triangular coordinates. There was a significant increase in the dihydroxy: trihydroxy bile salt ratio in the patients with cholesterol gallstones. The maximum cholesterol holding capacity for the bile salts was determined and no difference could be detected in the ability of the bile salts from either cholesterol stone-containing and control bile samples to dissolve cholesterol.     

Bile Salt Metabolism:II. Bile Salts and Disease

Bile salt metabolism. II. Bile salts and disease. C. B. Campbell and A. E. Cowen, Aust. N.Z. J. Med., 1977, 7, pp. 587–595. Alterations of bile salt metabolism have been shown in numerous diseases. Liver damage results in elevated serum bile salt concentrations which may be useful as a sensitive index of hepatocellular disease. Changes in the relative proportions of the individual bile salts in serum occur with cholestasis. Urinary excretion of bile salts, largely in the form of sulphates, increases as a compensatory mechanism. Ileal disease or resection causes bile salt ma/absorption. The increase in colonic bile salts produces a watery diarrhoea while the decrease in duodenal levels may cause steatorrhoea. Cholelithiasis may result from alteration in the relative proportions of cholesterol, lecithin and bile salts in bile. The mechanism apparently differs in various conditions predisposing to gallstone formation. A primary alteration of bile salt metabolism has been postulated in several other conditions. Considerable interest centres on the importance of metabolites of bile salts in the pathogenesis of colonic carcinoma. Chenodeoxy-cholic acid is a successful though costly treatment for selected patients with cholesterol gallstones. Bile salt binding agents, such as cholestyramine, are extremely useful especially in the control of pruritus in patients with cholestasis.     

Bile Salt Hydrophobicity Modulates Subselection of Biliary Lecithin Species in Rats Depleted of Bile Salt Pool

Although bile salts play an important role inthe secretion of biliary lipid, little is known aboutthe relationship between bile salt hydrophobicity andthe selection of lecithin species to be secreted into bile. We therefore investigated whetherbile salts modulate the selection of biliary lecithinsubspecies. Rats that were depleted of the bile saltpool were infused with taurocholate (50, 100, 200, and 400 nmol/min/100 g body weight),taurochenodeoxycholate (25, 50, 100, and 200nmol/min/100 g body weight), tauroursodeoxycholate (100,200, 400, and 800 nmol/min/100 g body weight), ortaurobetamuricholate (100, 200, 400, and 800 nmol/min/100 g bodyweight). Bile was collected to analyze bile flow, bileacid output, cholesterol levels, and lecithin levels.The hydrophobic-hydrophilic balance of the bile salts and biliary lecithin species was assessedby determining the retention times during reverse-phasehigh-performance liquid chromatography. Biliary lecithinsecretion rates correlated with the hydrophobicity index of the biliary bile salts administered.Thus, biliary lecithin hydrophobicity increased withincreasing bile salt hydrophobicity, whereas the molarcholesterollecithin ratio in the bile decreased. In conclusion, bile salt hydrophobicityregulates the selection of biliary lecithin subspeciesduring biliary secretion and thereby modulates, at leastin part, bile cholesterol metastability. Thus, bile salt hydrophobicity accounts for thephysicochemical conditions determining bile lipidmetastability.     

Bile Salt Metabolism:I. The Physiology of Bile Salts

Bile salt metabolism. I. The physiology of bile salts. A. E. Cowen and C. B. Campbell, Aust. N.Z. J. Med., 1977, 7, pp. 579–586. Bile salts are synthesized in the liver from cholesterol, conjugated with glycine or taurine and secreted in bile with cholesterol and lecithin. The molar concentrations of these three lipids determine solubility of cholesterol in bile. Within the gastrointestinal lumen bile salts play an essential role in lipid absorption and fat transport. An efficient entero-hepatic circulation maintains hepatic bile salt secretion and provides a “feed-back” control of bile salt and cholesterol metabolism. Potentially hepatotoxic lithocholic acid formed in the intestinal lumen by bacterial action on chenodeoxycholic acid is sulphated in the liver thus decreasing intestinal reabsorption. The total faecal excretion of bile salts balances hepatic synthesis and represents a major catabo/ic path in cholesterol metabolism.     

Pigment gallstones.

Pigment gallstones are defined as any dark brown-to-black stone, consisting of calcium salts of bilirubin, phosphate, carbonate and other anions, and can be separated into carbonate- and noncarbonate-containing groups. Pigment stones predominate in the rural Orient, in cirrhosis, and in elderly United States patients undergoing cholecystectomy. Clinical associations include bile duct obstruction, stasis, and possibly hemolysis. Of pigment stones, 50% are radioopaque and account for two-thirds of all opaque stones. The concentrations of bile salts, phospholipids,, cholesterol, and total bilirubin in bile are similar to normal levels, but the concentration of unconjugated bilirubin is increased in the bile of some patients. Increased unconjugated bilirubin in bile may be caused by increased hydrolysis of excreted conjugated bilirubin. Unconjugated bilirubin is solubilized by bile salts, but the interaction is primarily nonmicellar. Ionized calcium and pH are important determinants of solubility. Sulfated glycoproteins, excreted in increased amounts in patients with cholelithiasis, may be the site of pigment stone precipitation because these compounds bind calcium salts tightly. E coli is frequently cultured from pigment stones in Japan but not in the United States; thus, bacterial beta-glucuronidase may be important in stone formation in Japan but probably not in the West. Stasis leads to increased calcium secretion and to increases in the concentration of sparingly soluble compounds that may then precipitate. Incomplete emptying of the gallbladder may result in the same concentration process. Unsaturated fats and chronic vagal stimulation cause pigment stone formation in animals. At present, surgery is the only treatment for pigment lithiasis.     

The composition of hepatic and gallbladder bile in patients with gallstones

Bile specimens were obtained from 17 patients with gallstones and 21 patients with duodenal ulcer. The specimens were obtained from the former by needle aspiration of the gallbladder and common bile duct at operation and from the latter by duodenal intubation. The concentrations of bile salt, phospholipid, and cholesterol were measured. Gallbladder bile from gallstone patients contained significantly more cholesterol than did ;duodenal' bile from duodenal ulcer patients. Hepatic bile from gallstone patients contained significantly more cholesterol than did gallbladder bile from the same patients. When the data were plotted on triangular coordinates the relative composition lay within the zone of cholesterol solubility in all 21 ulcer patients. The relative composition of hepatic bile lay outside the zone of cholesterol solubility in five gallstone patients, at the limits of cholesterol solubility in a further three, and within the micellar zone in the remaining nine patients. This suggests that supersaturation of hepatic bile with cholesterol is not the sine qua non for the production of cholesterol gallstones.     

Supersaturated bile from obese patients without gallstones supports cholesterol crystal growth but not nucleation

Cholesterol crystal formation was studied in gallbladder bile samples collected from 18 patients with cholesterol gallstones, 6 patients with black pigment stones, and 14 obese patients without gallstones. In the absence of seed crystals, bile from patients with cholesterol stones showed a much greater tendency to form cholesterol crystals in vitro than bile of similar cholesterol saturation from patients without cholesterol stones. The ability to form crystals was not related to the biliary hexosamine concentration, an indicator of mucin content. When small seed crystals of cholesterol monohydrate were added to each bile, the seed crystals dissolved in all biles (n = 8) with a cholesterol saturation index less than 0.76. In contrast, 29 of 30 biles with a cholesterol saturation index greater than 0.76 supported crystal growth, even when collected from patients without gallstones. These results indicate that the difference between supersaturated biles in the ability to form cholesterol crystals resides at the nucleation, rather than the growth, stage of crystal formation.     

Serum and Bile Lipids in Young Women with Radiolucent Gallstones

To investigate the relationship between blood and bile lipids, serum cholesterol, high density lipoprotein cholesterol, and triglycerides were correlated with cholesterol saturation index of bile in 21 women-10 with radiolucent gallstones and 11 without stones. All of the women had regular menstrual cycles, were normolipidemic, and on a hospital diet. On the same morning, blood and the darkest duodenal bile were taken after cholecystokinin (CCK) stimulation. Standard laboratory procedures were used to analyze serum and bile lipids. We found: 1) statistically significant (t test, p less than 0.05) but only slight hypercholesterolemia (+ 12%) in patients with gallstones; 2) a negative correlation of serum cholesterol with cholesterol saturation index of bile, both in the control group (r = -0.654, p less than 0.05) and in gallstone patients (r = -0.665, p less than 0.05); 3) a correlation of high density lipoprotein cholesterol with cholesterol saturation index only in normal women (r = -0.619, p less than 0.05); 4) conversely, a correlation of triglycerides with the same index in only gallstone patients (r = 0.641, p less than 0.05). With the stepwise multiple regression analysis (independent variables: diagnosis of gallstones, serum cholesterol, HDL cholesterol, triglycerides; dependent variable: biliary cholesterol saturation index), only gallstone diagnosis and serum cholesterol influenced significantly (F test, p less than 0.05) the biliary cholesterol saturation index. These findings suggest that young women with radiolucent gallstones are slightly hypercholesterolemic, that in women both with and without gallstones there is a negative correlation between serum cholesterol and biliary cholesterol saturation, but women with gallstones have a higher cholesterol saturation index of the bile than women without gallstones with the same level of cholesterol in the blood.     

Lithogenic bile in patients with ileal dysfunction

Ileal disease or resection causes bile salt malabsorption and a reduction in the bile salt content of bile. Since cholesterol solubility requires adequate bile salt concentrations, depletion of the bile salt content of bile might, therefore, jeopardize cholesterol solubility and predispose to cholesterol gallstone formation.To study this, we examined biliary lipid composition in 10 patients with ileal dysfunction and in 25 healthy controls.Biliary lipid composition, as analysed in cholecystokinin-stimulated, bile-rich duodenal fluid, was shown to be representative of gallbladder bile and reproducible on repeat duodenal intubation.Nine of the 10 patients with ileal dysfunction had an abnormal, supersaturated bile in which the limits of cholesterol solubility were exceeded, and while nine of 25 control subjects also had an unstable bile, the mean bile composition in the ileal dysfunction group was significantly different from the control population.These studies provide a physicochemical explanation for the clinical observation that patients with ileal dysfunction have an increased incidence of gallstones.     

Cell type-dependent effect of phospholipid and cholesterol on bile salt cytotoxicity

The effect of phosphatidylcholine and cholesterol on bile salt-induced cytotoxicity was investigated. Experiments were performed in both human erythrocytes and cultured CaCo-2 cells, a model system for gastrointestinal epithelium. Hemolysis induced by 50 mmol/L sodium-taurocholate was reduced by both lecithin and cholesterol in a concentration-dependent manner. Cholesterol was 10 times more effective than phosphatidylcholine. Addition of only small amounts of the sterol to phosphatidylcholine/taurocholate solutions eliminated all cytotoxicity. The protective influence of cholesterol is probably mediated through a direct effect on the membrane. Incubation of erythrocytes with a cholesterol/taurocholate mixture greatly increased the cholesterol content of the membrane. With respect to sensitivity to bile salts and the protective effect of lecithin, CaCo-2 cells behaved very similar to erythrocytes. However, cholesterol failed to have any cytoprotective effect when used in combination with taurocholate or phosphatidylcholine/taurocholate solutions. Interestingly, at relatively high concentrations of cholesterol (cholesterol saturation index greater than 1.0), the sterol even increased cytotoxicity. This correlated with a cholesterol-induced shift of phosphatidylcholine from micelles to vesicles, which normally occurs in supersaturated model and human bile. The different sensitivity of the two cell types to the effect of cholesterol on bile salt damage might be caused by the difference in lipid membrane composition. In conclusion, CaCo-2 cells represent a physiologically more relevant model system to study bile cytotoxicity than erythrocytes. When extrapolated to gallbladder epithelial cells, these results could be relevant for the pathogenesis of gallstone disease. The increased cytotoxicity might be the signal by means of which supersaturated bile induces mucin hypersecretion by gallbladder epithelial cells.     

Patients with uncomplicated cholelithiasis acidify bile normally

Reports have suggested that patients with gallstones have gallbladder bile that is less acidic and more saturated with calcium carbonate than patients without gallstones. This failure to acidify bile may play a role in the formation of gallstones. We, therefore, compared gallbladder bile pH, ionized calcium, and calcium carbonate saturation index from patients undergoing either incidental gallbladder removal (controls, n = 23) or elective cholecystectomy for gallstones (n = 55). Gallstones were classified as either cholesterol (n = 39) or black pigment (n = 16) stones. No difference in gallbladder bile pH was noted among the controls, cholesterol stone, and pigment stone patients. In addition, no difference in ionized calcium concentration or CCSI was noted among the three groups. The pH in additional patients (n = 49) with acute cholecystitis, common bile duct obstruction, biliary tract infection, and cystic duct obstruction was significantly more acidic. We conclude that neither a defect in bile acidification nor increased saturation of calcium carbonate explains why human cholesterol or pigment gallstones form.     

Cholesterol crystals, cholesterol saturation of bile and biliary lithiasis

It has been repeatedly shown that normal human gallbladder bile is commonly supersaturated wih cholesterol. It has been therefore suggested that the crucial step of the formation of cholesterol gallstones might be the nucleation and growth of cholesterol monohydrate crystals. Consequently this work was aimed at determining: 1) if cholesterol crystal formation is really a typical feature of gallbladder bile with cholesterol gallstones; 2) the influence of the degree of cholesterol saturation of bile on the formation of cholesterol crystals. Gallbladder bile from 89 patients (23 from patients with cholesterol gallstones, 7 from patients with non-cholesterol gallstones and 59 from patients free of gallstones) and hepatic bile from 17 previously cholecystectomized patients were studied. Four of these patients had cholesterol stones of the common bile duct. Results: (a) gallbladder bile: cholesterol crystals were present on immediate examination in 19 of the 23 bile samples with cholesterol stones, in 2 of the 7 bile samples with non-cholesterol stones and in 1 of the 59 bile samples without stones. Only 1 bile sample with cholesterol stone developed crystals. Cholesterol saturation of bile with or without crystals did not differ significantly; (b) hepatic bile: cholesterol crystals were detected on immediate examination in one of the 17 bile samples and subsequently appeared in one of the remaining samples. Cholesterol saturation of hepatic bile (2.10 +/- 0.43) was significantly higher (p less than 0.01) than that of gallbladder bile containing cholesterol stones (1.32 +/- 0.43).(ABSTRACT TRUNCATED AT 250 WORDS)     

Biliary lipid composition in patients with nonoperated Crohn's disease

Lipid composition of fasting duodenal bile was studied in 56 patients with nonoperated Crohn's disease, 21 normals matched for age and sex, 13 patients with cholesterol cholelithiasis, and 9 patients with ileal resections. Crohn's patients had a significantly higher mean saturation index, calculated according to Thomas (0.84±0.51) when compared to normal (0.63±0.25). Patients with ileocolonic Crohn's disease and patients with severe bile acid malabsorption, particularly, showed an increased incidence of cholesterol saturated bile. Saturation in patients with nonoperated Crohn's disease was not increased to the levels found in patients with ileal resection or cholesterol gallstones. Bile acid composition of gallbladder bile was characterized by a significant decrease of thedeoxycholate fractions in patients with Crohn's ileocolitis and colitis as well as in ileal resected patients. These qualitative changes of bile acid composition may influence cholesterol solubility. It is concluded that patients with nonoperated Crohn's disease may have an increased risk of developing cholesterol gallstones.