Bile Calcium Research Articles

Limy bile syndrome or milk of calcium bile: An unexpected encounter

IntroductionLimy bile or milk of calcium bile caused due to precipitation of calcium salts in bile is an extremely rare condition of gall bladder, wherein the lumen of gall bladder is filled with chalky white paste like material. Not many cases have been reported till date.AimIn this exceptional case, we tried to correlate the radiological and surgical findings with the histopathology.Case studyWe hereby present an interesting case of a 59-year-old male who presented with dyspepsia and painful abdomen and was finally diagnosed with limy bile syndrome.Results and discussionThe etiology of this rare entity is not fully understood, but it certainly has strong association with impacted stone at the neck of gall bladder and hyperparathyroidism. Females are more commonly affected than males. Patients usually present with complaints of painful abdomen and are commonly diagnosed radiologically, as a radiopacity in gall bladder. Cholecystectomy is the preferred method of treatment for this unusual condition and histopathologically chronic cholecystitis is seen along with presence of slender needle shaped crystals of calcium salts.ConclusionsA thorough evaluation of the clinicoradiological and histopathological findings can sometimes bring to light many uncommon variants of common looking pathologies.

S1427 Lime-A-Way: Limy Bile Syndrome Complicated by Biliary Obstruction

INTRODUCTION: Limy bile syndrome (LBS), also known as milk of calcium bile, is a rare disorder of unclear etiology, characterized by the accumulation of thick, paste-like radiopaque calcium salts in the gallbladder and common bile duct (CBD). It is prevalent in 0.1% of patients that undergo cholecystectomies and can lead to life-threatening complications, necessitating early recognition. We report a case of this rare clinical entity presenting with obstructive jaundice and causing debilitating abdominal pain and chronic cholecystitis. CASE DESCRIPTION/METHODS: A 51-year-old man with no past medical history presented with 4 months of worsening sharp, post-prandial right upper quadrant abdominal pain and nausea. Vital signs were normal. Physical exam was notable for scleral icterus, jaundice, tenderness to palpation in the right upper quadrant of his abdomen and negative Murphy’s sign. Laboratory data was notable for AST 195 U/L, ALT 520 U/L, alkaline phosphatase 186 U/L, total bilirubin 6.2 mg/dL (conjugated 2.8/unconjugated 0.9). Abdominal ultrasound showed CBD dilation to 10 mm without gallstones. Abdominal CT showed a dilated CBD and densely hyperattenuating material along the inferior gallbladder wall and within the CBD (Figure 1). Given the absence of stones, the diagnosis of LBS was suspected. He underwent ERCP with sphincterotomy and copious amounts of thick paste-like sludge was swept from the duct, confirming the diagnosis of LBS (Figures 2, 3). His symptoms and biochemical abnormalities resolved rapidly following ERCP, and he underwent laparoscopic cholecystectomy with pathology confirming chronic cholecystitis. DISCUSSION: LBS is a rare disorder with poorly defined pathogenesis. Abnormalities in calcium metabolism, variable gallbladder pH and gallbladder stasis are factors that may cause calcium salt precipitation. Most patients present with biliary colic or cholecystitis. LBS can also present as incidental radiopaque shadows below the liver on abdominal x-rays in asymptomatic individuals. The identification of these calcifications should prompt further investigation with ultrasound and CT to distinguish LBS from other calcifying pathologies such as porcelain gallbladder in which gallbladder wall calcification is demonstrated as opposed to radiopaque material within the gallbladder itself. Timely recognition of this rare syndrome and early cholecystectomy is crucial as it can lead to complications such as biliary obstruction, cholangitis, biliary pancreatitis and cholecystitis.Figure 1.: CT showing hyperattenuating material along the inferior gallbladder wall.Figure 2.: EGD showing thick paste-like sludge.Figure 3.: ERCP images.

Evaluation of Bilirubin, Phosphorus, Calcium and Cholesterol Levels in Bile of Livers Consistent with Hepatic Fascioliasis

Evaluation of Bilirubin, Phosphorus, Calcium and Cholesterol Levels in Bile of Livers Consistent with Hepatic Fascioliasis

Effects of calcium on lipid digestion in nanoemulsions stabilized by modified starch: Implications for bioaccessibility of β-carotene

The aim of this study was to investigate the influence of calcium on and its mechanism in the digestion and bioaccessibility of β-carotene in nanoemulsions stabilized by modified starch, using an in vitro digestion model. Higher concentrations of calcium ions resulted in more irregular aggregates, a greater rate and extent of lipid digestion but a lower bioaccessibility of β-carotene. The major components of the mixed micelles were analyzed to explain the relationship between lipolysis and bioaccessibility. The lipolytic products and bile salts in the mixed micelles decreased with an increase in the calcium concentration because of the formation of calcium soaps and calcium–bile acid complexes. A correlation analysis showed that the bioaccessibility of β-carotene had a highly statistically significant positive linear correlation with both lipolytic products (r = 0.943) and bile salts (r = 0.896) in mixed micelles with calcium. These results illustrated that the lipolytic products and the bile salts in the micelles were the critical factors contributing to the bioaccessibility of β-carotene. This study could help in an understanding of the function of calcium in the digestion of delivery systems and the bioaccessibility of encapsulated lipophilic functional ingredients.

Variation of calcium, copper and iron levels in serum, bile and stone samples of patients having different types of gallstone: A comparative study

BackgroundEpidemiological data among the human population has shown a significantly increased incidence of gallstone (GS) disease worldwide. It was studied that some essential (calcium) and transition elements (iron and copper) in bile play an important role in the development of GS. MethodThe estimation of calcium, copper and iron were carried out in the serum, gall bladder bile and different types of GS (cholesterol, mixed and pigmented) of 172 patients, age ranged 20–55years. For comparative purpose age matched referents not suffering from GS diseases were also selected. Biliary concentrations of calcium (Ca), iron (Fe) and copper (Cu) were correlated with their concentrations in serum and different types of GS samples. The ratio of Ca, Fe and Cu in bile with serum was also calculated. Understudy metals were determined by flame atomic absorption spectroscopy after acid decomposition of matrices of selected samples. ResultsThe Ca concentrations in serum samples were significantly higher in patients with pigmented GS as compared to controls (p<0.005), whereas for patients having cholesterol and mixed GS the concentrations were on the lower side. Biliary Ca concentrations of patients were found to be higher than controls, but difference was significant for pigmented GS patients (p>0.001). The contents of Cu and Fe in serum and bile of all patients (except female cholesterol GS patient have low serum iron concentration) were found to be higher than control, but difference was significant in those patients who have pigmented GS. The concentration of Ca, Fe and Cu in different types GS were found in the order, Pigmented>mixed>cholesterol. The bile/serum ratio for Ca, Cu and Fe was found to be significantly higher in pigmented GS patients. Gall bladder bile was slightly alkaline in patients as compared to referents. The density of bile was found to be higher in patients as compared to the referents. Various functional groups present in different types of GS samples were confirmed by Fourier transform infra-red spectroscopy. ConclusionThe higher density and pH of bile, elevated concentrations of transition elements in all types of biological samples (serum, bile and GS), could be an important factor for the formation of different types of GS.

Clinical value of spectral CT in diagnosis of negative gallstones and common bile duct stones.

To investigate the clinical value of spectral CT in diagnosis of negative gallstones and common bile duct stones primarily. All patients diagnosed with negative biliary stones were analyzed and examined by spectral CT scanner retrospectively. Based on acquired raw imaging data, image series were reconstructed as described below: the optimal contrast-to-noise ratio monochromatic energy images, calcium- and fat- based material decomposition images and spectral curve images. All these imaging series were analyzed quantitatively and qualitatively. The contrast between negative stones and adjacent bile was 6.87 ± 5.48 HU on hybrid energy CT images and 47.30 ± 24.05 HU on optimal monochromatic energy CT images. The mean concentration of calcium in bile and negative stones was 19.36 ± 5.12 and 3.88 ± 6.60 mg/mL, and the fat in bile and negative stones was 998.48 ± 11.79 and 1035.68 ± 15.36 mg/mL. Effective atomic number Z of negative stones (6.60 ± 0.45) was lower than that of bile (7.65 ± 0.13). The slopes of the spectral curves for negative stones were k 90-40KeV = 1.43 ± 0.63 and k 140-90KeV = 0.19 ± 0.08, and for bile, they were k 90-40KeV = -0.27 ± 0.09 and k 140-90KeV = -0.04 ± 0.01. The same stone showed different densities in different imaging groups. The positive rate of conventional CT images was lower than that of other imaging groups. Spectral CT has a high diagnostic value for negative gallstones or bile duct stones, and material decomposition CT images and spectral curves can make an accurate diagnosis.

Osteopontin and integrin are involved in cholesterol gallstone formation

SummaryBackgroundThis study aimed to investigate the role of osteopontin and its receptor, integrin αv, in gallstone formation using human tissue specimens and a guinea pig lithogenic model.Material/MethodsThe nucleation role of osteopontin was determined in patients’ and normal gallbladder bile samples in vitro. Normal gallbladder was the control, and gallstone gallbladders were divided into group I (with normal epithelia) and group II (with degenerated epithelia) based on pathology change. Immunostaining, mRNA and protein expressions of osteopontin and integrin αv were analyzed. The animals were randomly divided into a lithogenic diet group and a normal diet group; the osteopontin mRNA expression in gallbladder and liver and osteopontin concentrations were determined.ResultsOsteopontin prolonged nucleation time and inhibited the pro-nucleating role induced by calcium in human bile in vitro. Immunostaining for osteopontin and integrin αv in human gallbladder tissues showed a higher reactivity in Group I than control group and Group II. The immunostaining in Group II was weaker than control group; similar results were observed for mRNA and protein expression of osteopontin and integrin αv. In the animal assay, the mRNA expression and concentration of osteopontin in gallbladder and liver gradually increased at initial stages and decreased in later stages. The concentrations of osteopontin in bile and serum of guinea pig showed similar trends.ConclusionsOur results suggest that osteopontin is involved in cholesterol gallstone formation, and the role of osteopontin might correlate with integrin αv and calcium.

Hereditary liver disease: Gallstones

Gallstones are common in Western countries and due to pain and complications pose a substantial burden on health care systems. In general, cholesterol gallstones are distinguished from bilirubin gallstones. Bilirubin gallstones form if the ion product of unconjugated bilirubin and calcium in gallbladder bile exceeds the solubilisation capacities of mixed micelles and vesicles. Cholesterol gallstones develop if the amount of cholesterol in gallbladder bile exceeds the maximum concentration that is soluble at the given concentration of bile salts and phospholipids. In addition, cholesterol gallstone formation requires hypomotility of the gallbladder and a mucin gel as nucleation matrix for monohydrate crystals. The individual risk of gallstone formation is determined by interactions of lithogenic alleles of gallstone susceptibility genes and multiple environmental factors. For asymptomatic gallstones, expectant management is recommended, whereas an episode of gallstone-associated pain substantially increases the risk of complications such as cholecystitis, cholangitis and pancreatitis and therefore necessitates cholecystectomy.

Intermittent ischaemia maintains function after ischaemia reperfusion in steatotic livers

BackgroundIschaemic preconditioning (IPC) and intermittent ischaemia (INT) reduce liver injury after ischaemia reperfusion (IR). Steatotic livers are at a higher risk of IR injury, but the protection offered by IPC and INT is not well understood. The aim of the present study was to determine the effectiveness of IPC and INT in maintaining liver function in steatotic livers. Material and methodsA model of segmental hepatic ischaemia (45min) and reperfusion (60min) was employed using lean and obese Zucker rats. Bile flow recovery was measured to assess dynamic liver function, hepatocyte fat content quantified and blood electrolytes, metabolites and bile calcium measured to assess liver and whole body physiology. Liver marker enzymes and light and electron microscopy were employed to assess hepatocyte injury. ResultsIPC was not effective in promoting bile flow recovery after IR in either lean or steatotic livers, whereas INT promoted good bile flow recovery in steatotic as well as lean livers. However, the bile flow recovery in steatotic livers was less than that in lean livers. In steatotic livers, ischaemia led to a rapid and substantial decrease in fat content. Steatotic livers were more susceptible to IR injury than lean livers, as indicated by increased blood ALT concentrations and major histological injury. ConclusionINT is more effective than IPC in restoring liver function in the acute phase of IR in steatotic livers. In obese patients, INT may be useful in promoting better liver function after IR after liver resection.

Limy bile syndrome: review of seven cases

Milk of calcium bile or limy bile is a rare disorder in which the gall bladder is filled with a thick, paste-like, radiopaque material. Seven patients with limy bile syndrome were treated in our department from 1980 to 2003. There were five women and two men, and their age ranged from 30 to 64 years. A retrospective analysis of clinical symptoms, diagnostic work-up, treatment approach and operative findings was performed. All patients presented with intermittent right upper abdominal quadrant pain. Three of the seven patients (42.85%) presented with complications like acute cholecystitis (two of seven patients) and obstructive jaundice (one of seven patients). Diagnosis was based on clinical findings, plain abdominal X-rays, ultrasonography and computed tomography scanning. Surgery was the treatment of choice and cholecystectomy alone or in combination with common bile duct exploration and drainage (if needed) was performed. The clinical aspect of the disease is similar to that of biliary lithiasis and the diagnosis is easily made by the characteristic spontaneous opacification of the gall bladder on plain abdominal X-rays. Complications such as acute cholecystitis, pancreatitis or obstructive jaundice can also be present. Although some cases of conservative pharmaceutical treatment as well as cases of spontaneous disappearance of limy bile have been reported, surgical treatment remains the treatment of choice.

Effect of tamoxifen, raloxifen and tibolon on bile components in ovariectomized rats

The aim of the study was to investigate the effect of ovariectomy on the bile composition in order to estimate the ability of selective estrogen receptor modulators (SERMS) (tibolon, tamoxifen, raloxifen) to modify the ovariectomy-induced disorders. The study was carried out on the ovariectomized female Wistar rats. Tibolon (1 mg kg −1 24 h −1), tamoxifen (5 mg kg −1 24 h −1) and raloxifen (10 mg kg −1 24 h −1) were administered for 42 days. Under anesthesia bile was collected during 6 h period. The ovariectomy increased significantly the excretion of biliary acids and calcium in bile and decreased the excretion of cholesterol and chloride. In rats treated with tamoxifen and raloxifen the excretion and concentration of cholesterol in bile were significantly reduced in comparison with ovariectomized rats. In rats treated with tibolon these values were increased. Moreover in rats treated with tamoxifen and raloxifen the concentrations of calcium in bile were significantly reduced. Tibolon had no significant effect on bile calcium concentrations. The therapy with tamoxifen, raloxifen and tibolon decreased the serum cholesterol concentrations, whereas the bile acid concentrations were increased in comparison with ovariectomized control. The drugs studied had no significant effect on calcium and chloride serum concentrations. Our results suggest that the therapy with tamoxifen and raloxifen may have the positive effect on bile composition in ovariectomized rats and probably may prevent the gallstone formation.

Effects of metronidazole on hyperlipidaemia

We read with interest the paper by Shamkhani et al. on phospholipids, bile salt concentration, and prostaglandins, the effects of metronidazole on hyperlipidaemia [1]. We had performed a study to investigate the effect of metronidazole on the lithogenic potential of rabbit bile [2]. Twenty-five rabbits in the test group were administered metronidazole orally for 21 days whereas 25 rabbits in the control group were administered normal saline. After 21 days, we found a significant increase in the bile cholesterol and bile calcium levels in the test group while the bile bilirubin levels were no different in the two groups. This was accompanied by a significant reduction in the serum lipids in the test group. We concluded that this action might be similar to the drug clofibrate. Hence we suggest that when looking at the hypolipidaemic action of the imidazole derivatives, one should also keep in mind their lithogenic potential and study it fully. A limitation of our study was the lack of estimation of biliary

Asymptomatic Colorectal Neoplasia and Fecal Characteristics

PURPOSE: The results of previous studies of colorectal neoplasia and fecal composition have been inconsistent, in part because the cases have been symptomatic and the studies small. We sought to test hypotheses relating to fecal bile acids, calcium, and pH in a large sample of asymptomatic subjects who had participated in fecal occult blood screening. METHODS: Fecal samples were obtained from 45 cases of cancer, 129 subjects with adenoma, 167 fecal occult blood-negative controls and 155 fecal occult blood-positive subjects in whom no cancer or adenoma was found. Concentrations of fecal bile acids, steroids, calcium, and pH were assessed blind to case-control status and compared between cases and 1) fecal occult blood-negative controls and 2) fecal occult blood-positive subjects. RESULTS: No association between colorectal cancer and fecal bile acids or pH was observed. Although there was no overall association between colorectal adenomas and fecal bile acids or pH, villous adenomas were associated with increasing concentrations of major bile acids and decreasing concentration of minor bile acids, and there was a suggestion of an inverse association with an acid pH. High levels of fecal calcium were associated with a reduced risk of both colorectal cancer and adenoma, but this was not statistically significant. CONCLUSION: The study does not support an association between colorectal cancer and fecal bile acids or pH. However, there is evidence that increases in major bile acids are associated with villous adenomas.

Hepatobiliary and pancreatic: Commentary

Journal of Gastroenterology and HepatologyVolume 17, Issue 7 p. 811-811 Free Access Hepatobiliary and pancreatic: Commentary First published: 10 September 2009 https://doi.org/10.1046/j.1440-1746.2002.t01-1-02856.xAboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat INTERPRETATION OF FIGURE 2 (SEE PAGE 806) On the plain abdominal radiograph (Fig. 2), a dilated bile duct and dilated left and right hepatic ducts are seen as radio-opaque structures. This may occur when the biliary system contains multiple stones or when bile has a high calcium content. In this patient, the radio-density of the biliary tree is homogeneous, suggesting the presence of bile with a very high calcium concentration. This finding is called ‘limy bile’ or ‘milk of calcium bile’. Diagnosis: limy bile ‘Limy bile’ is biliary sludge that contains precipitated calcium salts. Predisposing factors include fasting and wasting, as in this patient. It normally forms in the gallbladder and can resolve spontaneously.1 It may also pass into the bile duct and cause abdominal pain and/or changes in liver function tests. Thereafter, sludge may persist in the bile duct or pass through the ampulla of Vater into the duodenum.2 In the illustrated case, ‘limy bile’ was not detected in the gallbladder. The physicochemical conditions of bile that expedite formation of pigment stones and sludge are not established, but it is known that opaqueness of bile is a result of the presence of more than 4% calcium as carbonate and/or phosphate. If the concentration of calcium salts in bile is less than 4%, sludge tends to be brown (rather than black) and radiolucent.3 Images of interest Obviously, serum enzymes improved while ‘limy bile’ was still in the bile duct. Presumably, impaction of sludge was relieved, perhaps by the spontaneous passage of some sludge into the duodenum. A subsequent ultrasound study showed less dilatation of intrahepatic ducts (Fig. 3). Ultrasound studies are often unhelpful for bile duct sludge, but magnetic resonance imaging may show sludge as a gravitation-dependent material, as shown in Figure 4. Figure 3Open in figure viewerPowerPoint Intrahepatic ducts are no longer dilated. Figure 4Open in figure viewerPowerPoint T2-weighted magnetic resonance image of the liver. (→) Sludge as a sediment on the posterior aspect of the bile duct (different case). References 1 Nomura F, Suzuki Y, Suzuki K et al. Spontaneous disappearance of limy bile: report of a case with review of the literature. Am. J. Gastroenterol. 1984; 79: 884– 8. 2 Hokama A, Kinjo F. Biliary sludge extruding into the duodenum. N. Engl. J. Med. 1998; 339: 1210. 3 Trotman BW. Pigment gallstone disease. Semin. Liver Dis. 1983; 3: 112– 19. Volume17, Issue7July 2002Pages 811-811 FiguresReferencesRelatedInformation

The role of biliary calcium in gallstone pathogenesis.

Calcium is an element that is extremely important in the pathogenesis of gallstones. It is present in bile in large quantities since components of bile bind the calcium avidly. Precipitated calcium salts with the calcium sensitive ions, bilirubinate, carbonate and phosphate are major components of pigment gallstones and are present in high concentrations in the centers and rims of cholesterol gallstones. An understanding of the solubility of calcium in bile is thus essential if one is to understand the process that leads to gallstone formation. In addition, calcium also has a very important role in the function of the gallbladder epithelial cell. This manuscript discusses what is known about biliary calcium, the factors that regulate total and free calcium concentrations in bile, the solubility of calcium in both normal and lithogenic bile, and the role calcium plays in epithelial cell function during gallstone formation.

Calcitonin-like substance in the plasma of Cyclostomata and its putative role

The present study indicated that in the lamprey, Lampetra japonica, which undergoes a spawning migration from seawater to freshwater in its life cycle, a calcitonin (CT)-like substance was not detected in the plasma of seawater-adapted specimens (both sexes), but it was detected in the plasma of freshwater-adapted specimens (both sexes) by enzyme-linked immunosorbent assay using anti-salmon CT serum. Furthermore, this substance increased with the gonad somatic index (GSI) in both sexes. In lamprey, therefore, this CT-like substance may have some relationship with gonadal maturation. In the plasma of the hagfish, Eptatretus burgeri, on the other hand, the CT-like substance was always extremely high (47.2±4.2 ng/ml) independently of GSI in both sexes. However, a correlation was found between this substance and plasma calcium. In hagfish, the CT-like substance may participate in calcium homeostasis, as does calcium excretion via bile, because the hagfish has the highest bile calcium concentration determined to date among vertebrates, with a level corresponding to 12-fold that in plasma. This speculation is supported by reports that, in rat and cartilaginous fish, CT acts on calcium excretion via bile. In both fishes, moreover, the molecular weight of these substances was equal to that of salmon CT, which strongly suggests that these substances detected here are their CTs.

Milk of calcium cholelithiasis in children

Milk of calcium bile is uncommon and occurs mainly in the adult population. The authors report on 2 children, each having a distinct clinical history and presentation, and each with milk of calcium bile/calculi possessing differing chemical composition and highly notable gross morphology. J Pediatr Surg 36:644-647. Copyright © 2001 by W.B. Saunders Company.

Enterohepatic cycling of bilirubin: A putative mechanism for pigment gallstone formation in ileal Crohn's disease

Background & Aims: Patients with ileal disease, bypass, or resection are at increased risk for developing gallstones. In ileectomized rats, bilirubin secretion rates into bile are elevated, most likely caused by increased colonic bile salt levels, which solubilize unconjugated bilirubin, prevent calcium complexing, and promote its absorption and enterohepatic cycling. The hypothesis that ileal disease or resection engenders the same pathophysiology in humans was tested. Methods: Sterile gallbladder bile samples were obtained intraoperatively from 29 patients with Crohn's disease and 19 patients with ulcerative colitis. Bilirubin, total calcium, biliary lipids, β-glucuronidase activities, and cholesterol saturation indices in bile were measured, and markers of hemolysis and ineffective erythropoiesis in blood were assessed. Results: Bilirubin conjugates, unconjugated bilirubin, and total calcium levels were increased 3-10-fold in bile of patients with ileal disease and/or resection compared with patients with Crohn's colitis or ulcerative colitis. Biliary bilirubin concentrations correlated positively with the anatomic length and duration of ileal disease. Endogenous biliary β-glucuronidase activities were comparable in all groups, and both the hemogram and serum vitamin B 12 levels were normal. Conclusions: This study establishes that increased bilirubin levels in bile of patients with Crohn's disease are caused by lack of functional ileum, supporting the hypothesis that enterohepatic cycling of bilirubin occurs. GASTROENTEROLOGY 1999;116:1420-1427

Elevated biliary calmodulin during gallstone formation: the role of bile acids.

Hepatic bile synthesis is altered during experimental gallstone formation. In response to cholesterol, there is a hydrophobic shift in hepatic bile acid synthesis and hypersecretion of phospholipids. These changes decrease the vesicular capacity for cholesterol and favor crystallization. The mechanism for these changes in hepatic bile formation is unknown. Calmodulin (CaM), a Ca2+ receptor protein involved in cellular secretion, regulates gallbladder transport and may play an important role in alterations of hepatic bile formation during cholelithiasis. We hypothesized that biliary CaM activity is altered during gallstone formation and may be associated with changes in bile acid and phospholipid synthesis. Prairie dogs were fed either control (N = 22) or 1.2% cholesterol-enriched (N = 26) diets for one to six weeks. Cholecystectomy was performed; the common bile duct was cannulated, and hourly bile samples were collected. CaM was measured in bile and gallbladder tissues by radioimmunoassay. Bile samples were analyzed for cholesterol, phospholipids, total bile acids, total protein, calcium, and individual bile acid composition. Compared to controls, gallstone animals had elevated hepatic bile levels of CaM, phospholipids, and cholesterol. Hydrophobic bile acid synthesis was also stimulated, with increased levels of taurochenodeoxycholic acid (TCDCA) and decreased taurocholic acid (TCA). Gallbladder bile demonstrated similar changes. Although gallbladder bile CaM levels were increased, tissue levels were unchanged, suggesting that increased CaM concentration is a hepatic phenomenon. Hepatic bile CaM activity correlated linearly with TCDCA concentration (r = 0.64, P < 0.004) and phospholipid hypersecretion (r = 0.53, P < 0.03). The relationship between biliary CaM and increased concentrations of TCDCA and phospholipids suggests a role for CaM in alterations of hepatocyte secretion that may promote gallstone formation.

Lack of relationship between serum and gallbladder bile calcium in patients with gallstone disease

Background: Recent studies suggest that alternation in serum calcium influences the level of gallbladder bile ionized calcium (Ca2+). Theoretically, this could increase the risk of calcium precipitation in the gallbladder. Methods: We therefore measured serum and gallbladder bile minerals in patients with gallstones (n=27) and without (n=10, controls). The serum samples were taken just prior to induction of anaesthesia and gallbladder bile was aspirated before any manipulation of the gallbladder. Results: The active molality of Ca2+