Chronic pancreatitis pathophysiology: Difference between revisions

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==== (f) Necrosis and fibrosis ====
==== (f) Necrosis and fibrosis ====
Recurrent acute pancreatitis can lead to necrosis and fibrosis leading to structural damage to pancreas causing chronic pancreatitis


==Genetics==
==Genetics==

Revision as of 19:00, 3 November 2017

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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]
    • 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
2) Intraductal obstruction due to other causes
  • Stones
  • Tumors
  • Ethanol abuse

(b) Direct injury to pancreatic cells induced by toxins and toxic metabolites

  • Alcohol is proposed to have a direct toxic effect on the pancreas.
  • It is metabolized by the pancreas and may result in oxidative stress and induce the release of pancreatic enzymes. This excessive release may result in autodigestion of the gland.
  • Additionally, alcohol may result in activation of pancreatic stellate cells which are primarily responsible for fibrosis of the gland and weakening of the intracellular membranes, which results in anatomical changes in the pancreas, further predisposing to pathological autodigestion.[5][6]

(c) Antioxidants

(d) Ischemia

(e) Autoimmune disorders

(f) Necrosis and fibrosis

Recurrent acute pancreatitis can lead to necrosis and fibrosis leading to structural damage to pancreas causing chronic pancreatitis

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

  1. Steer ML, Waxman I, Freedman S (1995). "Chronic pancreatitis". N. Engl. J. Med. 332 (22): 1482–90. doi:10.1056/NEJM199506013322206. PMID 7739686.
  2. 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.
  3. 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.
  4. 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.
  5. Apte MV, Pirola RC, Wilson JS (2010). "Mechanisms of alcoholic pancreatitis". J Gastroenterol Hepatol. 25 (12): 1816–26. doi:10.1111/j.1440-1746.2010.06445.x. PMID 21091991.
  6. Forsmark CE, Vege SS, Wilcox M (November 17,2016). "Acute Pancreatitis". The New England Journal of Medicine: 1972–1981. doi:10.1056/NEJMra1505202. Retrieved November 25,2016. Check date values in: |access-date=, |date= (help)


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