Etiopathogenesis of chronic pancreatitis

Abstract

Chronic pancreatitis is a progressive inflammatory disease, which leads to destruction of pancreatic parenchyma and its replacement with fibrotic tissue. Subsequently it is associated with exogenous and later endogenous alteration of pancreatic function. The most prevalent cause of chronic pancreatitis in western countries is alcohol overconsumption. However, etiology of the disease of most patients is multi-factorial and the disease is a result of combined actions of genetic, metabolical factors and also of the influence of external environment. Formertheories explaining mechanisms of genesis of chronic pancreatitis as an effect of toxins, metabolites, oxidative stress, obstruction or necrosis, are supported by many observations, but they are also partially inconsistent. Recently, there has been a major advance in the understanding of the genetic predisposition of chronic pancreatitis. Mutations causing alteration in regulation of trypsin activity or secretion of ductal cells contributes to the origin of chronic pancreatitis and modify the course of the disease. Newer SAPE hypothesis links knowledge of previous theories into a step-wise model of chronic pancreatitis origin. Pathogenesis, similarly to etiology, is probably complex with involvement of various pathogenetic mechanisms, depending on the cause. A key moment in understanding the disease pathogenesis was the characterization of pancreatic stellate cells as effector elements of fibrogenesis. They represent central cells, which activate themselves and create fibrotic tissue as a response to different pathological events. Better understanding of pathogenetic mechanisms of chronic pancreatitis gives hope for new causal modalities for treatment.