GASTROENTEROLOGY ARTICLE OF THE WEEK
January 6, 2005
Stevens T, Conwell DL, Zuccaro G. Pathogenesis of chronic pancreatitis: An evidence-based review of past theories and recent developments. Am J Gastroenterol 2004;99:2256-70
1. Pancreatic fibrosis
a. may be triggered by activation of pancreatic stellate cells
b. is always triggered by damage to the pancreatic ducts
c. alcohol activates pancreatic stellate cells to produce collagen
d. lipid peroxidation products, a marker of oxidative stress activate pancreatic
stellate cells.
e. TGF-b1 probably plays a major role in pancreatic fibrogenesis and may
explain how acute pancreatitis evolves into chronic pancreatitis
2. Idiopathic pancreatitis
a. Early onset (occurring in the first 2 decades of life) presents with painless
steatorrhea.
b. Late onset (4th-5th decade) presents with minimal pain, often with evidence of pancreatic insufficiency at time of presentations
c. Endocrine pancreatic dysfunction is much more common with early onset disease.
d. SPINK-1 mutation may explain some of the early onset chronic pancreatitis cases
True or False
3. Oxidative stress from metabolism of ethanol likely has a role in the pathogenesis of chronic pancreatitis, but does not appear to be the initiating event.
4. Approximately 50-55% of chronic alcoholics develop alcoholic pancreatitis.
5. The necrosis-fibrosis hypothesis explains progression of disease in hereditary pancreatitis, it is not clear if this applies to other forms of chronic pancreatitis as well.
6. Chronic pancreatitis is increased in incidence among end-stage renal disease patients.
7. The pancreas is capable of metabolizing alcohol, producing reactive radicals as well as lipid accumulation leading to “steatopancreatitis”, which is the precursor of pancreatic fibrosis and chronic pancreatitis.
8. Decreased levels of lithostathine or pancreatic stone protein is the likely mechanism leading to pancreatic duct stone formation.
9. Hypercalcemia causes acute but not chronic pancreatitis.
10. The SAPE hypothesis suggests that the first or “sentinel” episode of acute pancreatitis in an alcoholic occurs in the setting of a normal pancreas, in many, cessation of alcohol use at this point will allow the pancreas to revert to normal.
11. A single severe episode of acute pancreatitis may lead to chronic pancreatitis.