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An Insight into the Aetiology of Tropical Chronic Pancreatitis and Fibrocalculous Pancreatic Diabetes

Author Affiliations

  • 1 St. Xavier’s College (Autonomous) Kolkata, INDIA

Int. Res. J. Medical Sci., Volume 1, Issue (2), Pages 5-14, March,28 (2013)


Pancreatitis is a heterogeneous diseases with hereditary and non-hereditary transmission, manifesting itself in acute and chronic forms. Tropical chronic Pancreatitis prevalent in the peri-equitorial tropical regions is a juvenile form of non-alcoholic, idiopathic, calcific pancreatitis with progressive deterioration of the endocrine function leading to diabetes, termed as Fibrocalculous Pancreatic Diabetes (FCPD). This review aims to delineate the genetic insight that traces the relationship of TCP and FCPD as well as causal or modifier role of metabolic stress factors and environmental toxins. The review intends to show a three- hit model as the causal strategy for FCPD. Different studies have thrown light on familial aggregation as the probable basis to consider the genetic predisposition of the disease. Majority of studies done on this aspect favour calling FCPD as the later stage of TCP , although some reports from Bangladesh consider TCP and FCPD as two separate entities. If we go by the view of majority, then FCPD is the logical end-point of TCP. Hence, the suspected genes whose malfunctioning leads to TCP and FCPD are SPINK1 N34S mutation, causing inappropriate activation of trypsinogen to trypsin within pancreatic parenchymal cells and prevents maintenance of integrity of pancreatic acinar cells. CTSB (Cathepsin B) polymorphism (Leu26Val, C595T, T663C, and Ser53Gly) is recorded in good number of TCP patients but its involvement in progression to FCPD is still not clear. CASR (calcium sensing receptor) gene mutation increases risk of TCP and its progress to FCPD.CTRC (Chymotrypsin C) gene mutation is recorded both in TCP and FCPD patients preventing protease and anti-protease balance thereby enhancing supertrypsin activity and auto-digestion of pancreatic parenchymal cells. Some epistatic gene interaction is also predicted between SPINK1 and CTSB genes. Hence, defects in the above mentioned genes are considered to be the first hit for initiating TCP and FCPD. Metabolic stress factors like high carbohydrate and low protein diet along with lifestyles such as excessive smoking, drinking dealing with occupational chemicals causes oxidative stress and decrease in total anti-oxidant capacity considered as the second hit for FCPD. Increased amount of free radical due to oxidative stress has a direct bearing on the immunological functioning of the body. Cell-mediated immunity and auto-immunity due to release of sequestered pancreatic antigen was found in FCPD patients. Hence, immunological malfunction acts as the third hit to enhance progress of TCP (clinically symptomised by severe pain, fibrosis, calcification and progressive endocrine malfunction) to FCPD.


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