Until recently, it was unclear whether calcium is more than a bystander in the development of acute pancreatitis. Now important evidence has been accumulated supporting a pivotal role of intracellular levels of calcium in the early pathogenesis of the disease. A sustained increase of cytosolic calcium concentrations, as observed in various models of acute pancreatitis, was identified as sabotaging crucial cellular defense mechanisms and initiating premature trypsinogen activation. These processes lead the acinar cell to necrosis, with spillage of activated proteases into the interstitial space, affecting surrounding acinar cells and initiating a vicious circle that ends in macroscopic acute pancreatitis and systemic inflammatory response syndrome. Comprehensive knowledge of the pathobiology of cytosolic calcium in the pancreatic acinar cell is leading to the understanding of coherent molecular pathways of early events in the pathogenesis of acute pancreatitis and is opening horizons for research into directly targeted therapeutic agents.
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