Pancreatic calcification and stone formation: a thermodynamic model of calcium in pancreatic juice

Abstract

CaCO3 is a major constituent of pancreatic stones, salivary stones, and many pigment gallstones. Elucidation of the physicochemical state of calcium is necessary for definition of calcium solubility in these systems. Pancreatic stones are observed in both humans and cattle, and are approximately 95% CaCO3 (calcite) in both species. Despite its importance, little is known about the physicochemical state of calcium in pancreatic juice. This paper presents an a priori model, based on established physicochemical principles, for the state of calcium in the juice at all levels of secretion. Two postulates of the model are the following: the limiting free [Ca2+] in the juice is governed by the solubility product (K' sp) for CaCO3; if K' sp is exceeded, the juice is supersaturated and precipitation of CaCO3 is thermodynamically possible; total calcium, [Ca], in the juice is the sum of four distinct species: free ionized calcium, Ca2+; calcium-bicarbonate complex, CaHCO3+; calcium carbonate ion-pair, CaCO3(0); and protein-bound calcium, CaProt. Overall equations of the model and graphical corollaries are presented. The model predicts an inverse hyperbolic relationship between [Ca2+] or [Ca] and [HCO3-]. Calcium solubility is maximal at low [HCO3-]; as [HCO3-] increases, both [Ca2+] and [Ca] decline to respective limiting values of approximately 0.015 and 0.15 mM. At low [HCO3-], most of [Ca] is present as Ca2+ and CaProt, whereas at high [HCO3-], most [Ca] is CaHCO3+ and CaCO3(0). Protein, HCO3-, and CO3(2-) ions are thus important buffers for Ca2+ in the juice. The model provides a quantitative framework for further elucidation of calcium lithogenicity in the pancreas, salivary gland, and biliary tract.