Pathogenesis of Chronic Pancreatitis

Studies from the Marseille group allowed differentiation of acutepancreatitis (a group of lesions secondary to either extrapancreatic causes such asgallstones or to pancreatic diseases such as cancer and chronic pancreatitis), fromchronic pancreatitis. Two forms of chronic pancreatitis arc easily distinguished: obstructivepancreatitis secondary to pre-existing obstruction on pancreatic ducts (tumours,scars, etc); and the most frequent disease, chronic calcifying pancreatitis, which is apancreatic lithiasis due to a double phenomenon. This double phenomenon is theprecipitation of insoluble calcium salts and the precipitation of degraded fragmentsof a newly discovered secretory protein known as pancreatic stone protein (PSP).This family of glycoproteins, the amino acid sequence of which has been established,is synthesized by the pancreatic acinar cell and its biosynthesis is decreased inpatients presenting with chronic calcifying pancreatitis. The secretory form of PSPprevents the formation of calcium salt crystals in the pancreatic juice which is normallysupersaturated in calcium. Though the lesions and the secretory modificationsof PSP are common to all forms of chronic calcifying pancreatitis, there are differentetiological forms of the disease; alcoholic, tropical, hypercalcemic, hereditary andidiopathic. Alcohol consumption acts on pancreatic secretion by different mechanismsand is responsible for an increased secretion of secretory protein (enzymes)due to cholinergic, vagal reflexes sensitive to ethanol. Alcohol consumption is generallyassociated with protein rich and either fat rich or fat poor diets, both of which arerisk factors. Hypercalcemia also increases the secretion of protein and the viscosity ofpancreatic juice. The tropical form is not due, as previously suggested, to cassava(manioc) consumption or kwashiorkor, but it is endemic in populations submitted tofat poor, protein poor diets. These etiological factors are only acting on predisposedpatients. This suggests chat a low or abnormal biosynthesis of PSP is responsible forthe predisposition