Specific enzymes are needed for digestion and help provide optimal gastric pH. Gastric acid stimulates secretion of secretin, an enzyme necessary for stimulation of pancreatic juice. Cholecystokinin is secreted from the duodenum and jejunum and is triggered by long-chain fatty acids. It is controlled by the parasympathetic nervous system.

The leading cause of acute pancreatitis is a gallstone (>6.5 mm diameter) causing an obstruction of the pancreatic duct at its entrance to the duodenum. As the common bile duct and the common pancreatic duct enter into the duodenum through a common channel (the ampulla of Vater), a stone lodged in the ampulla causes pancreatic juices to back up. Eventually, the pressure in the pancreatic ducts results in their rupture, and pancreatic enzymes leak into the surrounding pancreatic tissues. The enzymes cause autodigestion, inflammation, edema, and necrosis of pancreatic cells.

A second cause is excessive alcohol consumption. Alcohol forms plugs in the pancreatic ducts, causing edema and spasm of the pancreatic sphincter in the ampulla of Vater. It also activates the release of
proteolytic enzymes. The obstruction of the duct and the excessive production of enzymes have the same result as above. Together, gallstones and alcohol account for about 80% of acute pancreatic attacks. Other causes include infection, hyperlipidemia, trauma, an idiosyncratic reaction to drugs, and heredity.