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.
- acute pancreatitis
- pancreatic islet cell
- pancreatic disorders
- pancreatic secretion
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Correction notice This article has been corrected since it published Online First. All author affiliations have been updated.
Contributors SGB: conceptualisation and design, literature search, drafting the manuscript and final approval. AH, AL, AG, CJ, DY, PH, VV and RS: literature search, drafting the manuscript, critical revision of manuscript and final approval. SJP: design of the study, literature search, critical revision of manuscript and final approval.
Funding DY support—UO1 DK108306; DoD PR182623. PH and VV support—National Research, Development and Innovation Office project grants (FK123982 to VV and K131996 to PH). PH support—GINOP 2.3.2-15-2016-00048 STAY ALIVE (PH). SJP support—US NIH: R01 AA024464, P01 DK098108, P50 AA0119991, U01 DK108314 US DoD: W81XWH1910888. RS support—funded by the U.K. Medical Research Council and National Institute for Health Research (EME 15/20/01), European Union Innovative Medicines Initiative, GlaxoSmithKline PLC and Hampson Trust, and is an NIHR Senior Investigator. AH support—NIH U01 DK108300, NIH DK092421 and DOD W81XWH-17-1-0339. CJ support—U01DK108314, DoD: W81XWH1910888.
Competing interests RS has received research support and/or funding from Calcimedica, Cypralis, GlaxoSmithKline, MSD/Merck and Novartis, has been a consultant for AbbVie, Calcimedica, Cypralis, Eagle Pharmaceuticals, Novartis and Takeda (all funds to the University of Liverpool), and is collaborating in the IMI2 TransBioLine project with multiple public and private institutions including Janssen, Lilly, MSD/Merck, Novartis, Pfizer, Roche and Sanofi-Aventis.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
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