Neurological Damage and Duodenopancreatic Reflux in the Pathogenesis of Alcoholic Pancreatitis

Abstract

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 pan-creatitis, 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.

Interaction of Protein C Inhibitor with the Type II Transmembrane Serine Protease Enteropeptidase

“…So far, it is not fully understood how trypsinogen is activated prematurely within the pancreas. Some authors believe that this activation might origin from reflux of EP-containing duodenal fluid into the pancreatic duct [37]. Though, this theory remains controversial and it is not clear if duodenopancreatic reflux occurs in vivo and, if it does, whether it is really able to damage the pancreas profoundly.…”

“…This function might be executed intracellularly by cathepsin B [36]. Some authors also suggest a role of EP by reflux of duodenal fluid into the pancreatic duct [37]. However, this theory remains controversial.…”

Phosphatidylcholine and lysophosphatidylcholine in intestinal mucus of ulcerative colitis patients. A quantitative approach by nanoelectrospray‐tandem mass spectrometry

“…LPC has a higher solubilization power on biological membranes and is assumed to promote development of gastritis type C and pancreatitis (22)(23)(24). The shift of phospholipid composition in intestinal mucus towards increased solubilization properties might therefore impair the protective capacity of the mucus gel, thus promoting chronic inflammatory disease.…”

“…In addition, mucus aliquots of three patients with slightly active colitis (CAI < 4) were analysed showing a total PC concentration of 438, 140 and 172 pmol/mg dry weight and, thus, were in the range of patients in clinical remission. LPC is a more effective detergent for solubilization of lipid membranes than PC and is therefore assumed to be one of the active principles responsible for cell destruction in various diseases (22)(23)(24). A higher relative mucosal LPC level probably reduces the protective properties of the intestinal gel layer.…”