Neurological damage and duodenopancreatic reflux in the pathogenesis of alcoholic pancreatitis.
OBJECTIVE: To present a new theory on the pathogenesis of acute alcoholic pancreatitis based on experimental data, the significance of which has not been recognized, and on evidence from the current literature. HYPOTHESIS: That chronic alcoholism damages muscarinic receptors in the pancreas, duodenum, and Oddi sphincter, producing heightened sensitivity to acetylcholine, stimulation of protein-rich pancreatic juice, hypertonicity of the duodenum and esophagus, relaxation of the Oddi sphincter, and intraduodenal pressures exceeding those shown to cause duodenopancreatic reflux and acute pancreatitis in humans and experimental animals. OUTCOME: The duodenopancreatic reflux mechanism can explain all of the clinical features of acute alcohol pancreatitis, including the intraductal site and rapid activation of zymogens by enterokinase, the recurrent episodes of pancreatitis, the precipitation of protein plugs by partial proteolytic hydrolysis, the severe vascular changes, the relation to infection by the most direct route, and the progression to chronic pancreatitis via the necrosis-fibrosis sequence. CONCLUSIONS: Damage to the nervous system, with a time lag of 5 to 15 years between the onset of heavy drinking and the development of neurological disorders (peripheral neuropathy and cerebellar degeneration), is a characteristic complication of chronic alcoholism. The similarity to events in alcoholic pancreatitis is striking.