Chronic pancreatitis pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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Overview

Chronic pancreatitis is a progressive inflammatory process leading to irreversible structural damage to pancreas resulting in exocrine and endocrine dysfunction^[1]
The pathogenesis is still unclear but two findings consistently seen in the pathogenesis of chronic pancreatitis are:
- Protein hypersecretion resulting in proteinaceous ductal plugs leading to ductal blockage and obstruction^[2]
- Patchy inflammatory lesions in exocrine pancreas seen on microscopic examination

Following factors are thought to play an important role in the pathogenesis of chronic pancreatitis:

Interlobular and intralobular duct blockage due to abnormal secretion of pancreatic proteins in the pancreatic juice^[2]
- GP2, a glycosyl phosphatidylinositol anchored protein is found to be a major component of plugs.^[3]
- Low levels of lithostathine in alcoholics, a protective protein secreted by pancreatic acinar cells that prevent stone (calcium carbonate) formation.^[4]

These proteinaceous plugs are the major sites for calification and stone formation leading to
- Ductal epithelial lesions and inflammatory changes
- Scarring
- Obstruction

Genes involved in the pathogenesis of chronic pancreatitis include:

Autoimmune conditions
- Primary biliary cirrhosis
- Primary sclerosing cholangitis
- Sjögren syndrome
- Renal tubular acidosis

On microscopic histopathological analysis:
- Patchy focal disease characterized by a mononuclear infiltrate
- Fibrosis
- Necrosis

↑ Steer ML, Waxman I, Freedman S (1995). "Chronic pancreatitis". N. Engl. J. Med. 332 (22): 1482–90. doi:10.1056/NEJM199506013322206. PMID 7739686.
↑ ^2.0 ^2.1 Sahel J, Sarles H (1979). "Modifications of pure human pancreatic juice induced by chronic alcohol consumption". Dig. Dis. Sci. 24 (12): 897–905. PMID 510088.
↑ Freedman SD, Sakamoto K, Venu RP (1993). "GP2, the homologue to the renal cast protein uromodulin, is a major component of intraductal plugs in chronic pancreatitis". J. Clin. Invest. 92 (1): 83–90. doi:10.1172/JCI116602. PMC 293537. PMID 8326020.
↑ Guy O, Robles-Diaz G, Adrich Z, Sahel J, Sarles H (1983). "Protein content of precipitates present in pancreatic juice of alcoholic subjects and patients with chronic calcifying pancreatitis". Gastroenterology. 84 (1): 102–7. PMID 6401181.