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. 2003 May;52(Suppl 2):ii31–ii41. doi: 10.1136/gut.52.suppl_2.ii31

Chronic pancreatitis and cystic fibrosis

H Witt
PMCID: PMC1867753  PMID: 12651880

Abstract

Recent discoveries of trypsinogen and trypsin inhibitor mutations in patients with chronic pancreatitis (CP) support the hypothesis that an inappropriate activation of pancreatic zymogens to active enzymes within the pancreatic parenchyma starts the inflammatory process. Current data suggest that CP may be inherited dominant, recessive, or complex as a result of mutations in the above mentioned or yet unidentified genes. Evaluation of patients with CP should include genetic testing. Cystic fibrosis (CF) is an autosomal recessive inherited disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene and is characterised by pancreatic insufficiency and chronic bronchopulmonary infection. The progression and severity of pulmonary disease differs considerably between people with identical CFTR mutations and does not seem to correlate with the type or class of the CFTR mutation. The identification of further disease modifying genetic factors will increase the pathophysiological understanding and may help to identify new therapeutic targets.

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Figure 1 .

Figure 1

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Model of inherited pancreatitis. (A) Condition in the normal pancreas: trypsin resulting from autoactivation of trypsinogen within the pancreatic parenchyma is inhibited by SPINK1 and in the second line by mesotrypsin or trypsin. This defence mechanism prevents the pancreas from activation of the pancreatic enzyme cascade and autodigestion. (B) Condition in inherited pancreatitis: mutations in PRSS1 or in SPINK1 lead to an imbalance of proteases and their inhibitors within the pancreatic parenchyma resulting in an inappropriate conversion of pancreatic zymogens to active enzymes with autodigestion and inflammation. Mutations in CFTR may disturb this delicate balance by intrapancreatic acidification or by a defective apical trafficking of zymogen granules and thus facilitate the intrapancreatic activation of digestive enzymes. Dark boxes represent products of mutated genes (modified from reference 34). (AP, activation peptide).

Figure 2 .

Figure 2

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Schematic presentation of the influence of different genetic and environmental factors on the pathogenesis of chronic pancreatitis. ACP, alcoholic chronic pancreatitis; TCP, tropical calcific pancreatitis; ICP, idiopathic pancreatitis; HP, hereditary pancreatitis.

Figure 3 .

Figure 3

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CFTR mutations classes. The subdivision reflects the known or predicted biosynthetic and functional consequences.

Selected References

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