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At least 127 records · Page 7Linked to original sources
PubMed1975

Effect of primary bile acid ingestion on bile acid metabolism and biliary lipid secretion in gallstone patients.

Bile acid kinetics were measured by isotope dilution, and hourly outputs of bile acid, cholesterol, and phospholipid were quantified by duodenal perfusion over 24 hr including three liquid meals and an overnight fast in 6 gallstone patients during a pretreatment period and two randomized treatment periods with chenodeoxycholic (chenic) acid or cholic acid. During chenic acid ingestion, bile contained predominantly chenyl conjugates. During cholic acid ingestion, bile was composed of about equal amounts of cholyl and deoxycholyl conjugates; chenyl conjugates decreased markedly due in part to a 50% decrease in chenic acid synthesis. Total bile acid pool size doubled in half the patients receiving either bile acid and was not different during treatment with chenic or cholic acid. Compared to cholic acid, chenic acid caused decreased cholesterol output with no difference in bile acid or phospholipid output. Therefore, bile unsaturated with cholesterol entered the duodenum for more hours per day during chenic acid ingestion than during the cholic or pretreatment periods. There was no relationship among bile acid pool size, bile acid output, and hours per day of supersaturated bile; there was an inverse relationship between total pool size and recycling frequency such that bile acid output remained stable over a wide range of pool sizes. Fasting-state gallbladder bile was supersaturated during the cholic and pretreatment periods, but became unsaturated during chenic acid ingestion. However, hours per day of supersaturated bile could not be reliably predicted from the degree of saturation of fasting-state gallbladder bile (r = 0.62). The efficacy of chenic acid and the lack of efficacy of cholic acid for gallstone dissolution appear related to their different specific effects on biliary cholesterol secretion and not to any effect on bile acid and phospholipid secretion or bile acid pool size.

Bile↗
PubMed1984

Biliary secretion and hepatic metabolism of taurine-conjugated 7 alpha-hydroxy and 7 beta-hydroxy bile acids in the dog. Defective hepatic transport and bile hyposecretion.

Experiments were carried out using chronic bile fistula dogs to define the physiologic properties and metabolism of two unnatural epimeric monohydroxy conjugated bile acids, 7 alpha-hydroxy cholanoyltaurine and 7 beta-hydroxy cholanoyltaurine. The compounds, labeled with 14C, were infused intravenously at a rate of 1 mumol/kg X min; effects on bile flow and biliary lipid secretion as well as hepatic biotransformation were defined. The 7-monohydroxy bile acids were secreted quite slowly in bile: recovery during the 90-min infusion interval averaged 16% for the 7 alpha compound and 23% for the 7 beta compound, and after 6 h was only about 60% for the 7 alpha compound and 80% for the 7 beta compound. Uptake by tissues, presumably the liver, appeared to be efficient, as the level of radioactivity in peripheral blood remained quite low. Both bile acids failed to induce the anticipated increase in bile flow; canalicular bile flow, which was assessed using erythritol clearance, was about half the value observed when cholyltaurine was infused at a similar rate. The "hyposecretion" of bile, which was thought likely to be caused by impaired canalicular transport of the monohydroxy conjugates, was fully reversible, as a subsequent cholyltaurine infusion at a rate of 1 mumol/min X kg immediately restored bile flow and the infused cholyltaurine was secreted normally. Each compound was partly 3-hydroxylated during hepatic passage: the 7 alpha compound, about 36% (to form chenodeoxycholyltaurine); the 7 beta compound, about 23% (to form ursodeoxycholyltaurine). No other biotransformation occurred. Each compound induced phospholipid and cholesterol secretion, but compared to the effects of cholyltaurine, the amount of phospholipid secretion induced (per micromole of secreted bile acid) was less, and that of cholesterol, greater. Thus, the two 7-monohydroxy taurine-conjugated bile acids caused a striking dissociation of induced phospholipid and cholesterol secretion. The results indicate that taurine-conjugated 7-monohydroxy bile acids are poorly secreted by the liver and that their impaired transport is associated with bile hyposecretion, possibly reflecting decreased bile acid-dependent flow; the configuration of their 7-hydroxy group influences their rate of secretion into bile. The results also establish a novel type of bile acid biotransformation (3-hydroxylation) in the dog.

Animals↗
PubMed1996

Plasma lathosterol as a screening test for bile acid malabsorption due to ileal resection: correlation with 75SeHCAT test and faecal bile acid excretion.

1. Plasma lathosterol concentration, known to reflect cholesterol and bile acid synthesis, was evaluated as a screening test for bile acid malabsorption, comparing it with faecal bile acid measurements, SeHCAT test and Schilling test in 22 subjects of whom six were healthy controls and 16 had Crohn's disease with ileal resections of varying length. 2. Plasma lathosterols and other non-cholesterol sterols were determined by GLC. Faecal bile acids were measured by GLC, and SeHCAT retention times by gamma camera. The study subjects were divided into two groups according to the degree of bile acid malabsorption: controls (faecal bile acids < 10 mg day-1 kg-1, n = 9) and bile acid malabsorption (faecal bile acids > 10 mg day-1 kg-1, n = 13). 3. Faecal bile acid excretion was 5.9 +/- 1.0 mg day-1 kg-1 in control subjects and 45.7 +/- 6.1 mg day-1 kg-1 in the bile acid malabsorption group. The biological half-life of 75SeHCAT (T1/2) was 95.6 +/- 16.3 h and 14.1 +/- 4.1 h, respectively. Plasma lathosterol levels were significantly elevated in patients with bile acid malabsorption (742 +/- 84 micrograms/ml compared with 400 +/- 59 micrograms/ml in control subjects) and correlated closely with faecal bile acid levels (r = 0.779, P < 0.001), with 75SeHCAT T1/2 (r = -0.524, P < 0.05) and with Schilling test (r = -0.591, P < 0.05). Significant correlations were also obtained for delta 8-cholestenol with faecal bile acids (r = 0.784, P < 0.001) and 75SeHCAT (r = -0.505, P < 0.05). The biological half-life of SeHCAT correlated with faecal bile acid excretion (r = -0.702, P < 0.001). Using mean+2 SD of lathosterol (In micrograms/ml cholesterol) as a cut-off value and 10 mg day-1 kg-1 as the upper limit for faecal bile acid excretion, the test gives 100% sensitivity and 82% specificity for plasma lathosterol determination to detect bile acid malabsorption. 4. The results indicate that both the 75SeHCAT test and plasma lathosterol detect bile acid malabsorption in patients with ileal resections for Crohn's disease. However, plasma lathosterol is a simpler and less expensive method.

Adult↗
PubMed1991

Unchanged levels of keto bile acids in bile after cholecystectomy.

Cholecystectomy has been hypothesized to cause increased levels of potentially harmful secondary bile acids due to prolonged exposure of primary bile acids to intestinal bacteria. In the present study, we analyzed duodenal bile of the same patients before and after cholecystectomy for keto bile acids and hydroxy bile acids. The ratios of individual keto bile acids to their corresponding precursor hydroxy bile acids were not significantly different before and after cholecystectomy. Keto bile acids constituted 2.5 +/- 1.3 and 2.2 +/- 0.9 mol% of hydroxy bile acids in duodenal bile. 3 alpha-Hydroxy-12-oxo-5 beta-cholanoic acid derived from deoxycholic acid was the main keto bile acid in bile contributing 80 mol% to total keto bile acids. There was a strong positive correlation between 3 alpha-hydroxy-12-oxo-5 beta-cholanoic acid and its precursor deoxycholic acid in bile (r = 0.88; p less than 0.0005). Our findings prove that 7 weeks after cholecystectomy the percentage of keto bile acids in bile as compared to hydroxy bile acids is not increased.

Adult↗
PubMed1995

Association of canalicular membrane enzymes with bile acid micelles and lipid aggregates in human and rat bile.

This study was undertaken to gain insights into the characteristics of the polymolecular association between canalicular membrane enzymes, bile acids, cholesterol and phospholipids in bile and into the celular mechanisms whereby the enzymes are secreted into bile. With this purpose, we studied the distribution of bile acids, cholesterol, phospholipids, proteins and representative canalicular membrane enzymes (alkaline phosphatase, 5'-nucleotidase and gamma-glutamyl transpeptidase), which can be considered specific marker constituents, in bile fractions enriched in phospholipid-cholesterol lamellar structures (multilamellar and unilamellar vesicles) and bile acid-mixed micelles. These fractions were isolated by ultracentrifugation from human hepatic bile, normal rat bile and bile of rats treated with diosgenin, a steroid that induces a marked increase in biliary cholesterol secretion, and were characterized by density, lipid composition and transmission electron microscopy. These studies demonstrate that alkaline phosphatase, 5'-nucleotidase and gamma-glutamyl transpeptidase are secreted into both human and rat bile where they are preferentially associated with bile acid-mixed micelles, suggesting a role for bile acids in both release of these enzymes and lipids from the canalicular membrane and solubilization in bile. In addition, heterogeneous association of these enzymes with nonmicellar, lamellar structures in human and rat bile is consistent with the hypothesis that processes independent of the detergent effects of bile acids might also result in the release of specific intrinsic membrane proteins into bile.

5'-Nucleotidase↗
PubMed2004

Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation.

BACKGROUND/AIMS: Biliary strictures are a serious cause of morbidity after liver transplantation. We have studied the role of altered bile composition as a mechanism of bile duct injury after human liver transplantation. METHODS: In 28 liver transplant recipients, bile samples were collected daily posttransplantation for determination of bile composition. Hepatic expression of bile transporters was studied before and after transplantation. Histopathological criteria as well as biliary concentrations of alkaline phosphatase (ALP) and gamma-glutamyltransferase (gamma-GT) were used to quantify bile duct injury. RESULTS: Early after transplantation, bile salt secretion increased more rapidly than phospholipid secretion, resulting in high biliary bile salt/phospholipid ratio (BA/PL). In parallel with this, mRNA levels of the bile salt transporters NTCP and BSEP increased significantly after transplantation, whereas phospholipid translocator MDR3 mRNA levels remained unchanged. Bile duct injury correlated significantly with bile salt secretion and was associated with a high biliary BA/PL ratio. CONCLUSIONS: Bile salt secretion after human liver transplantation recovers more rapidly than phospholipid secretion. This results in cytotoxic bile formation and correlates with bile duct injury. These findings suggest that endogenous bile salts have a role in the pathogenesis of bile duct injury after liver transplantation.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1996

Simultaneous bacteriologic assessment of bile from gallbladder and common bile duct in control subjects and patients with gallstones and common duct stones.

OBJECTIVES: To determine the simultaneous prevalence of bacteria in bile from the gallbladder and common bile duct and to determine the influence of the number of stones present on bacteriologic findings. METHODS: A prospective study was performed in 467 subjects divided into seven groups: 42 control subjects with normal biliary tracts, 221 patients with symptomatic gallstone disease, 12 patients with hydropic gallbladder, 52 patients with acute cholecystitis, 67 patients with common bile duct stones without cholangitis, 49 patients with common bile duct stones and acute cholangitis, and 24 patients with previous cholecystectomy and common bile duct stones. In all except controls, bile samples from the gallbladder and common bile duct were taken simultaneously for aerobic and anaerobic cultures. RESULTS: Control subjects had no bacteria in gallbladder bile. Patients with gallstones, acute cholecystitis, and hydropic gallbladder had similar rates of positive cultures in the gallbladder and common bile duct, ranging from 22% to 46%, but the rate was significantly higher in patients with common bile duct stones without cholangitis (58.2%). Patients with cholangitis or previous cholecystectomy had a high rate of positive cultures of common duct bile (93% to 100%). Age greater than 60 years had a significant influence on the rate of positive bile cultures. There was no relationship between the number of stones in the gallbladder or common bile duct and the percentage of positive cultures. In 98% of the patients, the same bacteria were isolated from gallbladder and common duct bile. CONCLUSIONS: In normal subjects, no bacteria were present in the biliary tract. Among patients with common bile duct stones, there was an increasing percentage of positive cultures according to the severity of the disease. Age had an important influence, but sex and the number of common bile duct stones had no influence on positive cultures.

Acute Disease↗
PubMed1990

Cholesterol and bile acid metabolism in cultures of primary rat bile ductular epithelial cells.

The role of hepatocytes in bile acid and cholesterol metabolism has been extensively studied. By contrast, nothing is known about the role of bile ductular epithelial cells in cholesterol and bile acid metabolism. The purpose of the current studies was to establish whether bile ductular epithelial cells synthesize cholesterol, bile acids or both and to determine whether these cells are capable of metabolizing (hydroxylating, conjugating) bile acids. Bile ductular epithelial cells were isolated from rat liver after ligation of the common bile duct for 6 to 8 wk. Bile ductular epithelial cells were essentially free (greater than 99%) of hepatocytes and were histochemically positive (greater than 80%) for gamma-glutamyl transpeptidase activity. Cholestatic hepatocytes were simultaneously isolated and characterized with regard to their ability to synthesize and metabolize bile acids. Incubation of bile ductular epithelial cells with [14C]-acetate resulted in rapid labeling of cellular cholesterol, suggesting that these cells have a complete cholesterol biosynthetic pathway. The addition of [4-14C]-cholesterol to bile ductular epithelial cells did not lead to detectable synthesis of [14C]-bile acids. [24-14C]-Cholic acid, [24-14C]-deoxycholic acid, [24-14C]-lithocholic acid and [3H]-ursodeoxycholic acid were individually added to bile ductular epithelial cells and incubated for 24 or 48 hr. Bile acid metabolites were extracted and separated by C-18 reverse-phase high-performance liquid chromatography or thin-layer chromatography. Bile ductular epithelial cells conjugated deoxycholic acid, ursodeoxycholic acid and lithocholic acid to glycine and taurine. Surprisingly, no conjugation of cholic acid was detected. Conjugated lithocholic acid was further metabolized to highly polar metabolite(s), possibly beta-muricholic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Loss of zonal heterogeneity and cell polarity in rat liver with respect to bile acid secretion after bile drainage.

Functional liver heterogeneity depends on the current perihepatic environment. The effect of chronic bile drainage on hepatic secretion of bile acids in periportal and pericentral rat liver cells was studied. After 4 days of biliary drainage, rat livers were perfused in vitro in either forward (through the portal vein) or backward direction (through the vena cava) in single-pass arrangement with taurodeoxycholate (32 nmol.min-1.g liver-1). Tritium-labeled taurodeoxycholate (0.5 muCi) was injected as a pulse to determine uptake, biotransformation, and hepatic secretion. During bile drainage, bile flow fell from 1.8 microL.min-1.g liver-1 to approximately 0.6 microL.min-1.g liver-1. Bile acid secretion rate dropped from initially 50 nmol.min-1.g liver-1 to approximately 5 nmol.min-1.g liver-1 within 24 hours and remained at this level for the next 3 days. After bile drainage, liver histology was well preserved and was indistinguishable from controls. During liver perfusion of controls in both directions, bile flow exceeded 1 microL.min-1.g liver-1, whereas bile-drained animals demonstrated a bile flow between 0.4 and 0.6 microL.min-1.g liver-1. In contrast to controls, the drained-animal liver did not excrete label exclusively in bile but simultaneously excreted about one third back to the perfusate medium (regurgitation). Biliary bile acid recovery within the first 10 minutes after 3H-taurodeoxycholate bolus injection was 90% (of label taken up) in forward-perfused controls but only 40% in forward-perfused drained animals. Backward-perfused control and drained animals. Backward-perfused control and drained animals excreted about 20% in this time interval and did not differ significantly. T50, the time to excrete 50% of label taken up in bile or both bile and effluent, increased from 4.3 +/- 0.36 minutes (SD) in forward-perfused controls to 13.2 +/- 2.28 minutes in forward-perfused, drained animals. T50 of backward-perfused controls and backward-perfused drained animals did not differ significantly (17.8 +/- 1.75 minutes vs. 21.0 +/- 3.95 minutes). In conclusion, chronic bile drainage reduces liver heterogeneity with respect to velocity of bile acid excretion and cell polarity is lost with respect to hepatocellular translocation of bile acids.

Anastomosis, Surgical↗
PubMed1986

Effects of bile salts on bile formation in rabbits.

The effects of different species of bile salts: deoxycholate, taurochenodeoxycholate, ursodeoxycholate, glycodeoxycholate, tauroursodeoxycholate, chenodeoxycholate and cholate (DCA, TCDC, UDCA, GDCA, TUDC, CDCA, CA) on bile secretion were examined in anesthetized rabbits using two different infusion routes. When bile salts were infused intravenously, all bile salts (except for TCDC) significantly increased the volume of bile and bile salt excretion, but their respective efficiency for bile formation was different. The concentration of bicarbonate ion in the bile significantly increased during the choleretic periods induced by DCA, UDCA, GDCA and CDCA but remained unchanged with the other bile salts (CA, TCDC, TUDC). In rabbits, where a bile salt solution was infused in the duodenum and then drained from the intestine through an incision in the distal part of duodenum, none of these bile salts affected bile secretion. The effects of intravenously administered bile salts on rabbit bile secretion are different in terms of their choleretic potency and bicarbonate excretion depending on the species of bile salts used. Furthermore, it was concluded that the intraduodenal infusion of UDCA, which was found to stimulate the pancreatic exocrine function, did not affect bile secretion.

Animals↗
PubMed1998

Bile salt hydrophobicity modulates subselection of biliary lecithin species in rats depleted of bile salt pool.

Although bile salts play an important role in the secretion of biliary lipid, little is known about the relationship between bile salt hydrophobicity and the selection of lecithin species to be secreted into bile. We therefore investigated whether bile salts modulate the selection of biliary lecithin subspecies. Rats that were depleted of the bile salt pool were infused with taurocholate (50, 100, 200, and 400 nmol/min/100 g body weight), taurochenodeoxycholate (25, 50, 100, and 200 nmol/min/100 g body weight), tauroursodeoxycholate (100, 200, 400, and 800 nmol/min/100 g body weight), or taurobetamuricholate (100, 200, 400, and 800 nmol/min/100 g body weight). Bile was collected to analyze bile flow, bile acid output, cholesterol levels, and lecithin levels. The hydrophobic-hydrophilic balance of the bile salts and biliary lecithin species was assessed by determining the retention times during reverse-phase high-performance liquid chromatography. Biliary lecithin secretion rates correlated with the hydrophobicity index of the biliary bile salts administered. Thus, biliary lecithin hydrophobicity increased with increasing bile salt hydrophobicity, whereas the molar cholesterol-lecithin ratio in the bile decreased. In conclusion, bile salt hydrophobicity regulates the selection of biliary lecithin subspecies during biliary secretion and thereby modulates, at least in part, bile cholesterol metastability. Thus, bile salt hydrophobicity accounts for the physicochemical conditions determining bile lipid metastability.

Animals↗
PubMed1999

Relationships amongst liver bile salt clearance, bile secretion and infusion of lipids in calves.

In order to study the influence of portal lipid loading on the extraction rate of bile salts by the liver, four cholecystectomized calves (mean body weight 103 kg) were fitted with permanent cannulae to the common bile duct, duodenum and portal vein. A venflon catheter was also set up in the jugular vein to collect blood for analysis of fatty acids (FA) and bile salts (PBS) in plasma. The experiments were divided into two parts. In the first part sodium taurocholate (TCHNa) was infused for at least 2 h at a rate of 25 mumol/min into the duodenum to stabilize the bile flow and bile salt output in bile and the concentration in plasma. In the second part, as well as TCHNa, Intralipid (Itlp) (infusible 10% of lipid compounds) was also infused into the portal vein. Itlp was infused for 40 min, starting at a rate of 3 ml/min at the beginning of the 3rd hour of TCHNa infusion followed by a rate of 6 ml/min at the beginning of the 4th hour of TCHNa infusion. During TCHNa infusion the plasma bile salt concentrations were in the range 15.69-20.21 mumol/l, similar to that of the pre-infusion period. Introduction of Itlp to the infusion of TCHNa resulted in a significant (P < 0.05) increase of PBS, about 2 times higher at an Itlp infusion rate of 3 ml/min, and 3 times higher (62.82 +/- 16.42 mumol/l) at 6 ml/min. Under Itlp infusion, all common plasma FA increased, but the largest increases were in levels of linolenic, palmitic and oleic acids. During TCHNa infusion, the bile flow and the content of bile salts in bile did not change. The infusion of TCHNa with Itlp at the rate of 6 ml/min caused a 2-fold decrease both of the bile flow and of the output of bile salts from 18.58 +/- 3.04 microliters/min/kg and from 0.58 +/- 0.07 mumol/min/kg observed at the beginning of both infusions to 9.51 +/- 2.95 microliters/min/kg and 0.28 +/- 0.05 mumol/min/kg, respectively, at the end of the collecting period. When only TCHNa was infused, almost all of it was secreted to the bile, while with the additional infusion of Itlp only about half of the infused TCHNa was secreted to the bile. These results indicate that the extraction rate of PBS by the liver is decreased by loading of the portal blood by lipids, allowing more bile salts to escape into the systemic circulation, and thus reducing bile production.

Animals↗
PubMed1975

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.

Using a duodenal perfusion technique, the biliary output of bile acids, phospholipid, and cholesterol was measured hourly during three meals and an overnight fast in seven Caucasians with radiolucent gallstones in a functioning gallbladder, and in seven health controls without gallstones, closely matched for age, sex, and weight. Before the perfusion, bile acid kinetics were defined by an isotope dilution procedure, and the biliary lipid composition of fasting gallbladder bile was determined. Total daily biliary lipid output was similar in gallstone and control subjects, and was unrelated to cholesterol saturation of fasting gallbladder bile and to bile acid pool size. There was an inverse relationship between the size and recycling frequency of the bile acid pool, so that secretion rate and hepatic return of bile acids remained constant, despite a wide range of pool sizes. The finding of a normal bile acid synthesis rate in subjects with a small pool size therefore indicated normal feedback regulation of bile acid synthesis. Hourly measurements of biliary lipid output showed a linear relationship between bile acid and cholesterol output, with a similar regression line for gallstone and control subjects, but a non-linear relationship between bile acid and phospholipid output. Consequently, samples from all subjects were consistently supersaturated with cholesterol at low bile acid outputs, especially during overnight fasting, but not at high bile acid outputs. These findings indicate that hepatic secretion of bile supersaturated with cholesterol is physiological in man at low bile acid outputs, that bile acid pool size is probably determined in part by its recycling frequency, and that cholesterol cholelithiasis in some Caucasians may be due to an underlying extrahepatic abnormality.

Adult↗
PubMed1972

Effect of bile salts on hepatic phosphatidylcholine synthesis and transport into rat bile.

The effect of transport of micelle-forming and non-micelle-forming conjugated bile salts on phosphatidylcholine synthesis and transport into bile was studied in the ex vivo perfused rat liver. Single additions of sodium taurocholate, a good micelle-forming conjugated bile salt, caused an increase in bile flow associated with increased phosphatidylcholine and taurocholate concentration. The specific activity of phosphatidylcholine with respect to incorporated [1,2-(14)C]choline and [(3)H]methyl of l-[Me-(3)H]methionine was not significantly altered by the increased transport of phosphatidylcholine. The data suggested that bile phosphatidylcholine is synthesized to a great extent, although not exclusively, by phosphorylcholine glyceride transferase. Single additions of the glycine conjugate of dehydrocholate, a poor micelle-forming bile salt, caused an increase in bile flow comparable to that seen with sodium taurocholate administration. However, the concentrations of phosphatidylcholine in bile decreased. Thin-layer and gas-liquid chromatographic analyses of bile secreted before and after glycodehydrocholate administration revealed no significant increase in bile salt secretion other than the administered glycodehydrocholate. Investigations utilizing radiochemically pure [(14)C]glycine dehydrocholate revealed that increased bile flow after [(14)C]-glycine dehydrocholate administration occurs concomitantly with the secretion of 75-95% of the administered [(14)C]glycine dehydrocholate as a single peak into bile. Thus the increased bile flow without increased phosphatidylcholine concentration noted after glycodehydrocholate administration is due to transport of an intact, nonmetabolized, conjugated bile salt with poor micelle-forming properties. The data indicate that the formation of a bile salt-phosphatidylcholine micelle is responsible for phosphatidylcholine transport into bile.

Animals↗
PubMed1986

Pathogenesis of calcium-containing gallstones. Canine ductular bile, but not gallbladder bile, is supersaturated with calcium carbonate.

Calcium precipitation in bile is a requisite event in the initiation and growth of all pigment gallstones. Calcium solubility in bile is thus of great importance. This is the first attempt to define the ion-product of CaCO3 in bile in any species. If the ion-product: [Ca++] X [CO = 3] exceeds solubility product (K'sp), the sample is supersaturated and CaCO3 precipitation is thermodynamically possible. We have recently determined K'sp of calcite to be 3.76 X 10(-8) mol/liter at 37 degrees C and total ionic strength = 0.16 M. Gallbladder (GB) bile was obtained from 15 anesthetized dogs after 12-24-h fasts. Duct bile was obtained from three dogs (n = 12) during variable taurocholate infusion. Samples were assayed for pH, partial pressure of carbon dioxide (PCO2), total bile salt concentration ([TBS]), total calcium concentration ([Ca]), and free calcium ion concentration ([Ca++]). With increasing [TBS] in both GB and duct bile, there was a linear decline in pH, a curvilinear decline in [HCO-3] and [CO = 3], and linear increase in [Ca++] and [Ca]. All ductular samples were supersaturated with CaCO3, with saturation indices (SI) as high as 17.5 and a mean of 8.36 +/- 1.43 (SE). In sharp contrast, none of the GB samples were supersaturated, due to the marked decline in [CO = 3] upon concentration and acidification of bile. In GB bile, the SI ranged from 0.006 to 0.126, with a mean of 0.039 +/- 0.011. The gallbladder thus produced a change in the SI from a value as high as 17.5 to a value as low as 0.006 in concentrated GB bile, which is a nearly 3,000-fold change. The average change in the SI was approximately 215-fold. Since all duct samples were supersaturated, and since the dog does not normally form gallstones, the data support our previous hypotheses that: (a) in canine bile, as in canine pancreatic juice, a nucleating factor is necessary for CaCO3 precipitation; (b) bile salts are important buffers for Ca++ in bile; and (c) normal GB mucosal function (concentration and acidification of bile) plays an important role in reducing CaCO3 lithogenicity in GB bile.

Animals↗