Oral calcium promotes pigment gallstone formation

doi:10.1016/0022-4804(89)90188-1

Journal of Surgical Research

Volume 46, Issue 4, April 1989, Pages 286-291

https://doi.org/10.1016/0022-4804(89)90188-1 Get rights and content

Abstract

Dietary calcium supplementation has been recommended for prevention of osteoporosis and has become a standard component of most “health food” diets. Biliary calcium has been recognized to play a central role in the formation of pigment gallstones. We have recently demonstrated that 5 days of oral calcium supplementation significantly increases biliary calcium in the prairie dog (K. D. Lillemoe, T. H. Magnuson, G. E. Peoples, et al., Gastroenterology94: A563, 1988). We hypothesized, therefore, that long-term oral calcium supplementation would promote pigment gallstone formation. Sixteen adult male prairie dogs were maintained on a standard nonlithogenic diet. Eight animals received calcium supplementation (2.5× control levels) in their water, while the remaining eight animals served as controls. After 8 weeks, cholecystectomy was performed, and the common bile duct was cannulated. Bile was examined microscopically and analyzed for ionized calcium, bilirubin, glycoprotein, and biliary lipids. The cholesterol saturation index (CSI) was calculated. Pigment stones and calcium bilirubinate sludge were present in all animals receiving calcium supplementation. Only one control animal had evidence of pigment stones (P < 0.001). Biochemical analysis of gallbladder bile demonstrated a significant increase in total bilirubin and bilirubin monoglucuronide (P < 0.01) as well as bile glycoprotein content (P < 0.05) after oral calcium supplementation. Gallbladder bile ionized calcium was also increased although not significantly. These data suggest that oral calcium supplementation promotes gallbladder sludge and pigment gallstone formation in the prairie dog. This observation raises concern that oral calcium supplementation, especially in the older female population, may enhance gallstone formation.

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Citation Excerpt :
In contrast, porcelain gallbladder is a relatively rare entity that has been found in approximately 0.06%–1.1% of gallbladder specimens.1,2 Previous studies indicate that calcium is an important component of bile that plays a role in the formation and growth of several types of gallstones.8,9 However, it is unknown whether calcium levels play a role in the pathogenesis of porcelain gallbladder and there have been no previous studies assessing calcium levels among these patients.
Porcelain gallbladder is characterized by calcification of the gallbladder wall, possibly associated chronic inflammation from cholelithiasis. It is unknown whether porcelain gallbladder is associated with higher rates of hypercalcemia and/or hyperparathyroidism compared to cholelithiasis without porcelain gallbladder.
We searched our patient database for patients with porcelain gallbladder on imaging and patients with cholelithiasis without porcelain gallbladder. We collected data on patient age, gender, calcium levels, parathyroid hormone (PTH) levels, and medications/comorbidities known to cause hypercalcemia.
1000 patients within our database had porcelain gallbladder on imaging. Of these, 661 (245 male) had at least one serum calcium value for analysis. These patients were matched by age and gender with 6610 patients with cholelithiasis who had at least one serum calcium value. Rates of recurrent/persistent hypercalcemia were higher among patients with porcelain gallbladder at 16.8% versus 11.1% (p < 0.01). Rates of hyperparathyroidism were also higher among porcelain gallbladder patients at 12% versus 7.5% (p < 0.01).
Patients with porcelain gallbladder show higher rates of hypercalcemia and hyperparathyroidism than patients with cholelithiasis alone.
Variation of calcium, copper and iron levels in serum, bile and stone samples of patients having different types of gallstone: A comparative study
2017, Clinica Chimica Acta
Citation Excerpt :
Acidified bile plays a crucial role in the prevention of Ca precipitation [35]. It is reported in the literature that the development of GS in some patients may be caused due to the incapacity of mucosal membrane to secrete hydrogen ion into the bile [36]. This is what evident from our study that the bile of the patients having different types of GS was alkaline in nature as compared to the control subjects but for the patients with pigmented GS have a relatively higher alkaline bile as compared to the patients with cholesterol and mixed GS patients.
Epidemiological 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.
The 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 20–55 years. 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.
The 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.
The 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.
Calcium carbonate in cholesterol gallstones: Polymorphism, distribution, and hypotheses about pathogenesis
1995, Hepatology
This study of sets of cholesterol gallstones collected consecutively from 222 patients in La Paz, Bolivia, and Mexico City, Mexico, has developed a reliable infrared (IR) spectroscopic method for the detection of calcium carbonate in cholesterol gallstones and provided the basis for simultaneous identification of each of its three polymorphs: calcite, vaterite, and aragonite. The peaks in the 854 to 876 cm⁻¹ region demonstrated 98% sensitivity and specificity for carbonate detection. As little as 3% carbonate by weight could be detected using these peaks. The overall incidence of carbonate was 19% in these populations containing a high proportion of Amerinds. Infrared microspectroscopy of 10 to 50 μm particles, dissected from stones, allowed a ring-by-ring examination of 11 carbonate-containing stones. It was determined that different carbonate polymorphs, when present in the same gallstone, almost always occurred in separate rings. In approximately half of the gallstones, different polymorphs were present in successive layers in the same stone, indicating that conditions governing stone growth changed cyclically. Carbonates were usually precipitated in peripheral layers rather than in the center, supporting the theory that formation of calcium carbonates may be related to episodes of intermittent obstruction of the cystic duct, as opposed to being a major factor in stone nidation.
Hypercalcemia decreases bile flow and increases biliary calcium in the prairie dog
1995, Surgery
Background. Biliary calcium is known to play an important role in the pathogenesis of gallstones. Calcium salts are present in all pigment gallstones and are also present in the core of most, if not all, cholesterol gallstones.
Methods. The effects of acute hypercalcemia on bile flow and biliary calcium secretion were examined in 22 prairie dogs during intravenous taurocholate infusion (0, 1.0, 2.25, and 4.5 μmol/kg/min).
Results. Bile flow was linearly correlated with bile acid output in both control (y=7.62x+13.5, r=0.98) and hypercalcemic (y=7.00x+10.4, r=0.96) animals At lower bile acid outputs (<3.0 μmol/kg/min), biliary, ionized calcium output per increment bile acid output was significantly increased in hypercalcemic animals (0.016 versus 0.011 μmol Ca⁺⁺ μmol taurocholate, p<0.001). Bile ionized calcium concentrations approximated, Gibbs-Donnan predicted values only at low bile flow rate.
Conclusions. Hypercalcemia decreases bile flow and increases biliary ionized calcium concentration in the prairie dog. These effects favor the precipitation of calcium salts in bile.
The effect of calcium on gallbladder absorption
1990, Journal of Surgical Research
The absorption of water and electrolytes is an important physiologic function of the gallbladder which is altered during gallstone formation. Extracellular calcium and calcium channel antagonists are known to affect intestinal absorption, yet their effect on gallbladder absorption is less well defined. We, therefore, tested the hypothesis that changes in extracellular calcium or in calcium channels would alter gallbladder absorption. New Zealand white rabbit gallbladders were removed, filled with a modified Krebs buffer (Ca²⁺ = 0.7 mM), and suspended in an oxygenated bath of the same buffer. Water absorption was determined gravimetrically by obtaining serial gallbladder weights at 10-min intervals. After a 40-min control period, the serosal bathing solution was changed to one of four experimental solutions (n = 6 for each group): Ca²⁺ = 0.25, 0.7, or 1.2 mM or Ca²⁺ = 0.7 mM plus 0.1 mM verapamil. Absorption was determined during an 80-min experimental period with results expressed as the percentage change in gallbladder absorption compared to that of the control period. The 0.25, 0.7, and 1.2 mM Ca²⁺ groups did not show a significant change in absorption rate from their respective control rates. However, the verapamil group did demonstrate a significant (P < 0.05) decrease in absorption rate of −69 ± 8% by the end of the experimental period. These data demonstrate that verapamil inhibits gallbladder absorption while changes in serosal calcium concentration have no effect. We conclude that calcium channels and intracellular calcium may play an important role in modulating gallbladder absorption.
Short-term calcium intervention studies, in animals and humans, using epithelial proliferation as biomarker of response. The initiation of a calcium intervention trial in adenoma patients
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Regular articleOral calcium promotes pigment gallstone formation

Abstract

Amer. J. Surg.

Gastroenterology

J. Biol. Chem.

J. Lipid Res.

J. Surg. Res.

J. Surg. Res.

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Amer. J. Surg.

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Amer. J. Med. Sci.

Gastroenterology

Amer. J. Surg.

Bile is supersaturated with calcium in most patients with cholesterol and mixed gallstones

Gastroenterology

Oral calcium supplementation increases biliary calcium

Gastroenterology

Regular article
Oral calcium promotes pigment gallstone formation