Severe acute pancreatitis: pathophysiologic mechanisms underlying pancreatic necrosis and remote organ damage

Abstract

Despite advances in surgical and intensive care the mortality of severe acute pancreatitis still ranges between 10 and 20%. Fundamentally, the severity of acute pancreatitis, both in term of propensity and intensity of locoregional and remote complications, relies on the development of regional necrosis, the extent of the necrotizing process and the bacterial contamination of these necrotic areas. Intraacinar activation of pancreatic enzymes, overstimulation of inflammatory effector cells and vascular mechanisms are the 3 inter-related factors, acting sequentially to promote the severity of the inflammatory reaction, the ensuing necrosis and the emergence of locoregional complications. Numerous toxic substances, including inflammatory mediators, are released by this inflammatory retroperitoneal necrotizing process, gain access to the systemic circulation and mediate remote organ dysfunctions. Nowadays, pancreatic infection whose occurrence is mainly dependent upon the volume of necrosis and secondary bacterial translocation from the gut, accounts for 80% of the mortality in acute pancreatitis. The understanding of the pathophysiologic mechanisms underlying the inflammatory necrotizing process is critical so that the extent of necrosis can ultimately be limited at an early stage and these patients may be granted a better outcome.