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

Robert V Rege, E. W. Moore

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Abstract

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++]·[CO3 --] 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°C and total ionic strength = 0.16 M. Gallbaldder (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 [HCO3 -] and [CO3 --], 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 [CO3 --] 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 ~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.

Original languageEnglish (US)
Pages (from-to)21-26
Number of pages6
JournalJournal of Clinical Investigation
Volume77
Issue number1
StatePublished - 1986

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Calcium Carbonate
Gallstones
Gallbladder
Bile
Canidae
Calcium
Bile Acids and Salts
Solubility
Dogs
Ions
Bile Ducts
Pancreatic Juice
Taurocholic Acid
Partial Pressure
Carbon Dioxide
Osmolar Concentration
Buffers

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{1005969cfc6a42278aed7e08449361ff,
title = "Pathogenesis of calcium-containing gallstones. Canine ductular bile, but not gallbladder bile, is supersaturated with calcium carbonate",
abstract = "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++]·[CO3 --] 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°C and total ionic strength = 0.16 M. Gallbaldder (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 [HCO3 -] and [CO3 --], 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 [CO3 --] 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 ~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.",
author = "Rege, {Robert V} and Moore, {E. W.}",
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TY - JOUR

T1 - Pathogenesis of calcium-containing gallstones. Canine ductular bile, but not gallbladder bile, is supersaturated with calcium carbonate

AU - Rege, Robert V

AU - Moore, E. W.

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N2 - 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++]·[CO3 --] 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°C and total ionic strength = 0.16 M. Gallbaldder (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 [HCO3 -] and [CO3 --], 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 [CO3 --] 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 ~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.

AB - 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++]·[CO3 --] 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°C and total ionic strength = 0.16 M. Gallbaldder (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 [HCO3 -] and [CO3 --], 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 [CO3 --] 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 ~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.

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