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  • Review Article
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New insights into acute pancreatitis

Nature Reviews Gastroenterology & Hepatology volume 16, pages 479–496 (2019)Cite this article

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Abstract

The incidence of acute pancreatitis continues to increase worldwide, and it is one of the most common gastrointestinal causes for hospital admission in the USA. In the past decade, substantial advancements have been made in our understanding of the pathophysiological mechanisms of acute pancreatitis. Studies have elucidated mechanisms of calcium-mediated acinar cell injury and death and the importance of store-operated calcium entry channels and mitochondrial permeability transition pores. The cytoprotective role of the unfolded protein response and autophagy in preventing sustained endoplasmic reticulum stress, apoptosis and necrosis has also been characterized, as has the central role of unsaturated fatty acids in causing pancreatic organ failure. Characterization of these pathways has led to the identification of potential molecular targets for future therapeutic trials. At the patient level, two classification systems have been developed to classify the severity of acute pancreatitis into prognostically meaningful groups, and several landmark clinical trials have informed management strategies in areas of nutritional support and interventions for infected pancreatic necrosis that have resulted in important changes to acute pancreatitis management paradigms. In this Review, we provide a summary of recent advances in acute pancreatitis with a special emphasis on pathophysiological mechanisms and clinical management of the disorder.

Key points

  • The incidence of acute pancreatitis is 34 per 100,000 people in the general population, and it is rising worldwide.

  • In addition to premature trypsinogen activation, dysfunctional calcium signalling, impaired autophagy, endoplasmic reticulum stress, the unfolded protein response and mitochondrial dysfunction are key cellular processes in the pathogenesis of acute pancreatitis.

  • Well-designed, adequately powered trials are needed to define and examine the efficacy of aggressive fluid resuscitation.

  • Infected walled-off pancreatic necrosis should be managed with an endoscopic step-up strategy.

  • Diabetes and exocrine pancreatic insufficiency are common complications after an episode of acute pancreatitis, occurring in up to one in five patients following acute pancreatitis.

  • Acute pancreatitis impairs long-term quality of life, and many patients experience repeated hospitalizations.

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Fig. 1: Calcium-mediated mitochondrial dysfunction and cell death in acute pancreatitis.
Fig. 2: Premature trypsinogen activation in acute pancreatitis.
Fig. 3: Endoplasmic reticulum stress, the unfolded protein response and autophagy in acute pancreatitis.
Fig. 4: Immune response to acinar cell injury and necrosis in acute pancreatitis.
Fig. 5: Acute pancreatitis management algorithm.

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Authors and Affiliations

  1. Division of Gastroenterology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA

    Peter J. Lee

  2. Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Georgios I. Papachristou

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  1. Peter J. Lee
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P.J.L. researched data for the article. Both authors contributed equally to all other aspects of the manuscript.

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Correspondence to Georgios I. Papachristou.

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Glossary

Mitochondrial permeability transition pores

Proteins located in the inner membrane of the mitochondrion, which when open can cause rapid mitochondrial depolarization and dysfunction.

Calcium release-activated channels

Calcium ion channels that are activated when calcium stores are depleted from the endoplasmic reticulum.

Local complications

A collective term to denote collections that form within and/or around pancreatic parenchyma as a result of acute pancreatitis.

Unfolded protein response

(UPR). A collective term to denote a set of compensatory cellular responses to endoplasmic reticulum stress

Autophagy

An orderly mechanism that processes, degrades and recycles various unwanted cellular components.

ER stress

A state in which the demand of cellular machinery overwhelms the capacity of the endoplasmic reticulum (ER), leading to accumulation of misfolded proteins.

Cholecystokinin

A hormone that causes gallbladder contraction and pancreatic enzyme secretion.

Nuclear factor-κB

(NF-κB). A transcription factor that can cause production of pro-inflammatory cytokines and chemokines.

Inositol 1,4,5-trisphosphate receptor

(Ins(1,4,5,)P3R). A glycoprotein complex located in the endoplasmic reticulum that can operate as a calcium channel.

Zymogen granules

Vesicles that contain various pancreatic enzyme precursors.

Cathepsin B

A lysosomal protease.

Necroptosis

A regulated form of cell death.

Receptor-interacting protein kinase

(RIP). A type of protein kinase that is implicated in regulation of cell death.

Cystic fibrosis transmembrane regulator

(CFTR). A chloride channel located in pancreatic duct cells that enables passage of anions and water.

Monocyte chemoattractant protein 1

(MCP1). A chemokine that is involved in facilitating migration and recruitment of monocytes.

Damage-associated molecular patterns

(DAMPs). A variety of substances released by damaged cells that can activate an immune response.

Systemic inflammatory response syndrome

(SIRS). A host immune response to an inflammatory or infectious insult that is often characterized by fevers, leukocytosis, tachycardia, tachypnea and hypotension.

Cystenterostomy

The creation of a connection between a cyst wall and the wall of the gastrointestinal tract.

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Lee, P.J., Papachristou, G.I. New insights into acute pancreatitis. Nat Rev Gastroenterol Hepatol 16, 479–496 (2019). https://doi.org/10.1038/s41575-019-0158-2

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