Critical thresholds: key to unlocking the door to the prevention and specific treatments for acute pancreatitis

Savio George Barreto, Aida Habtezion, Anna Gukovskaya, Aurelia Lugea, Christie Jeon, Dhiraj Yadav, Peter Hegyi, Viktória Venglovecz, Robert Sutton, Stephen J. Pandol

Research output: Contribution to journalReview articlepeer-review

34 Citations (Scopus)


Acute pancreatitis (AP), an acute inflammatory disorder of the exocrine pancreas, is one of the most common gastrointestinal diseases encountered in emergency departments with no specific treatments. Laboratory-based research has formed the cornerstone of endeavours to decipher the pathophysiology of AP, because of the limitations of such study in human beings. While this has provided us with substantial understanding, we cannot answer several pressing questions. These are: (a) Why is it that only a minority of individuals with gallstones, or who drink alcohol excessively, or are exposed to other causative factors develop AP? (b) Why do only some develop more severe manifestations of AP with necrosis and/or organ failure? (c) Why have we been unable to find an effective therapeutic for AP? This manuscript provides a state-of-the-art review of our current understanding of the pathophysiology of AP providing insights into the unanswered clinical questions. We describe multiple protective factors operating in most people, and multiple stressors that in a minority induce AP, independently or together, via amplification loops. We present testable hypotheses aimed at halting progression of severity for the development of effective treatments for this common unpredictable disease.

Original languageEnglish
Pages (from-to)194-203
Number of pages10
Issue number1
Publication statusPublished - Jan 2021


  • acute pancreatitis
  • epidemiology
  • pancreatic disorders
  • pancreatic islet cell
  • pancreatic secretion


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