Chronic pancreatitis pathophysiology: Difference between revisions
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===== 1) Proteinaceous ductal plugs ===== | ===== 1) Proteinaceous ductal plugs ===== | ||
* Interlobular and intralobular duct blockage due to abnormal secretion of pancreatic proteins in the pancreatic juice | * Interlobular and intralobular duct blockage due to abnormal secretion of pancreatic proteins in the pancreatic juice<ref name="pmid510088">{{cite journal |vauthors=Sahel J, Sarles H |title=Modifications of pure human pancreatic juice induced by chronic alcohol consumption |journal=Dig. Dis. Sci. |volume=24 |issue=12 |pages=897–905 |year=1979 |pmid=510088 |doi= |url=}}</ref> | ||
** GP2, a glycosyl phosphatidylinositol anchored protein is found to be a major component of plugs | ** GP2, a glycosyl phosphatidylinositol anchored protein is found to be a major component of plugs.<ref name="pmid8326020">{{cite journal |vauthors=Freedman SD, Sakamoto K, Venu RP |title=GP2, the homologue to the renal cast protein uromodulin, is a major component of intraductal plugs in chronic pancreatitis |journal=J. Clin. Invest. |volume=92 |issue=1 |pages=83–90 |year=1993 |pmid=8326020 |pmc=293537 |doi=10.1172/JCI116602 |url=}}</ref> | ||
** Low levels of lithostathine in alcoholics, a protective protein secreted by pancreatic acinar cells that prevent stone (calcium carbonate) formation | ** Low levels of lithostathine in alcoholics, a protective protein secreted by pancreatic acinar cells that prevent stone (calcium carbonate) formation.<ref name="pmid6401181">{{cite journal |vauthors=Guy O, Robles-Diaz G, Adrich Z, Sahel J, Sarles H |title=Protein content of precipitates present in pancreatic juice of alcoholic subjects and patients with chronic calcifying pancreatitis |journal=Gastroenterology |volume=84 |issue=1 |pages=102–7 |year=1983 |pmid=6401181 |doi= |url=}}</ref> | ||
* These proteinaceous plugs are the major sites for calification and stone formation leading to | * These proteinaceous plugs are the major sites for calification and stone formation leading to | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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Overview
Pathophysiology
- 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:
(a) Intraductal plugging and obstruction
1) Proteinaceous ductal plugs
- Interlobular and intralobular duct blockage due to abnormal secretion of pancreatic proteins in the pancreatic juice[2]
- These proteinaceous plugs are the major sites for calification and stone formation leading to
- Ductal epithelial lesions and inflammatory changes
- Scarring
- Obstruction
2) Intraductal obstruction due to other causes
- Stones
- Tumors
- Ethanol abuse
(b) Direct injury to pancreatic cells induced by toxins and toxic metabolites
(c) Antioxidants
(d) Ischemia
(e) Autoimmune disorders
(f) Necrosis and fibrosis
Genetics
Genes involved in the pathogenesis of chronic pancreatitis include:
- Cystic fibrosis gene mutation
- Pancreatitis susceptibility genes
Associated Conditions
- Autoimmune conditions
- Primary biliary cirrhosis
- Primary sclerosing cholangitis
- Sjögren syndrome
- Renal tubular acidosis
Gross Pathology
- Patchy focal disease
- Fibrosis
Microscopic Pathology
- On microscopic histopathological analysis:
- Patchy focal disease characterized by a mononuclear infiltrate
- Fibrosis
- Necrosis
References
- ↑ 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.