TY - JOUR
T1 - Hypercalcemia decreases bile flow and increases biliary calcium in the prairie dog
AU - Ahrendt, Steven A.
AU - Ahrendt, Gretchen M.
AU - Pitt, Henry A.
AU - Moore, Edward W.
AU - Lillemoe, Keith D.
N1 - Funding Information:
CALCIUM PLAYS A CRITICAL role in the formation of most, if not all, gallstones. Precipitation of the calcium salts of bilirubinate, carbonate, phosphate, and palmitate is a necessary step in the pathogenesis of pigment gallstones\] Moreover, calcium salts have been found at the core of most cholesterol gallstones and may play a role in their formation. 2' 3 The addition of calcium to dilute model bile accelerates cholesterol-containing phospholipid vesicle aggregation and cholesterol monohydrate crystal nucleation. 4 Evidence also suggests that oral calcium supplementation increases biliary calcium in the prairie dog model and prolonged administration leads to pigment gallstone formation. 5' 6 These findings suggest that an increase in the secretion of calcium into bile may promote gallstone formation. Despite the significance of the calcium ion in gallstone pathogenesis, the complex interrelationships between biliary and serum free ionized calcium, bile salt concen- Supported in part by National Institutes of Health grant R-29-DK 41889. Presented in part at the 91st Annual Meeting of the American Gastroenterologieal Association, San Antonio, Texas, 1990. Accepted for publication Sept. 2, 1994. Reprint requests: Keith D. Lillemoe, MD, The Johns Hopkins Hospital, Department of Surgery, 600 N. Wolfe St., Blalock 603, Baltimore, MD 21287. Copyright 9 1995 by Mosby-Year Book, Inc. 0039-6060/95/$3.00 + 0 11/56/60468 tration, and bile flow remain incompletely defined. Free calcium ions enter canalicular bile passively across paracellular channels in response to bile salt secretion.V, s Theoretically, biliary ionized calcium concentration is a function of serum ionized calcium and biliary bile salt concentration as determined by Gibbs-Donnan forces. 9 In these experiments we sought to examine the effect of hypercalcemia on bile flow and biliary calcium secretion in the prairie dog, a commonly used model of gallstone pathogenesis.
PY - 1995/4
Y1 - 1995/4
N2 - 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.
AB - 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.
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U2 - 10.1016/S0039-6060(05)80064-9
DO - 10.1016/S0039-6060(05)80064-9
M3 - Article
C2 - 7716726
AN - SCOPUS:0028926825
SN - 0039-6060
VL - 117
SP - 435
EP - 442
JO - Surgery
JF - Surgery
IS - 4
ER -