The key event of acute pancreatitis: pancreatic duct obstruction and bile reflux, not a single one can be omitted

Abstract

Acute pancreatitis (AP) is an acute inflammatory disease of the pancreas. Severe acute pancreatitis (SAP) is the serious forms of AP with high mortality rate. However, the frequency of SAP remains stable over time. Biliary calculi and alcohol abuse are the most common causes of AP. Other causes such as iatrogenic factors, sphincter of Oddi dysfunction (SOD) and eating disorders also cannot be omitted. Blockage of duodenal papilla or ampulla of Vater is common characteristics of AP. Once the blockage appears, the occurrence of pancreatic duct obstruction and bile reflux is inevitable. Obstruction of the pancreatic duct leads to increased intraductal pressure, which results in damage to the integrity of the duct system to a certain extent. Bile reflux can activate trypsin and once trypsin is activated, it activates a variety of injurious pancreatic digestive enzymes with subsequent release of a series of inflammatory mediators. We hypothesized that pancreatic duct obstruction and bile reflux are the key event of AP induced by a variety of other upstream causes. Pancreatic duct obstruction and bile reflux, not a single one can be omitted. Whenever pancreatic duct obstruction and bile reflux are triggered simultaneously, activated digestive enzymes and inflammatory mediators can infiltrate into the parenchyma of the pancreas through impaired pancreatic barrier and induce AP. Blocking the key event of AP is of a great interest with potential therapeutic implications. Endoscopic sphincterotomy (EST) and nasobiliary drainage, which target the cause of AP, may prevent the transformation from AP to SAP and this may be adopted as an essential treatment strategy.