Chronic pancreatitis pathophysiology

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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
• 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
  • 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
  • GP2, a glycosyl phosphatidylinositol anchored protein is found to be a major component of plugs
  • Low levels of lithostathine in alcoholics, a protective protein secreted by pancreatic acinar cells that prevent stone (calcium carbonate) formation

• 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

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