Acute Pancreatitis.
Gardner Timothy B
Annals of internal medicine
Acute pancreatitis is one of the most common reasons for gastroenterology-related hospitalization in the United States. With significant morbidity and subsequent mortality related to both the acute presentation and subsequent sequelae, prompt diagnosis and appropriate management are critical, especially in the first 24 hours of illness. It is also important to accurately recognize complications, such as pancreatic fluid collections and vascular events, and identify a definitive cause so that a strategy to prevent future attacks can be implemented.
10.7326/AITC202102160
The roles of calcium and ATP in the physiology and pathology of the exocrine pancreas.
Petersen Ole H,Gerasimenko Julia V,Gerasimenko Oleg V,Gryshchenko Oleksiy,Peng Shuang
Physiological reviews
This review deals with the roles of calcium ions and ATP in the control of the normal functions of the different cell types in the exocrine pancreas as well as the roles of these molecules in the pathophysiology of acute pancreatitis. Repetitive rises in the local cytosolic calcium ion concentration in the apical part of the acinar cells not only activate exocytosis but also, via an increase in the intramitochondrial calcium ion concentration, stimulate the ATP formation that is needed to fuel the energy-requiring secretion process. However, intracellular calcium overload, resulting in a global sustained elevation of the cytosolic calcium ion concentration, has the opposite effect of decreasing mitochondrial ATP production, and this initiates processes that lead to necrosis. In the last few years it has become possible to image calcium signaling events simultaneously in acinar, stellate, and immune cells in intact lobules of the exocrine pancreas. This has disclosed processes by which these cells interact with each other, particularly in relation to the initiation and development of acute pancreatitis. By unraveling the molecular mechanisms underlying this disease, several promising therapeutic intervention sites have been identified. This provides hope that we may soon be able to effectively treat this often fatal disease.
10.1152/physrev.00003.2021
Genetics, Cell Biology, and Pathophysiology of Pancreatitis.
Mayerle Julia,Sendler Matthias,Hegyi Eszter,Beyer Georg,Lerch Markus M,Sahin-Tóth Miklós
Gastroenterology
Since the discovery of the first trypsinogen mutation in families with hereditary pancreatitis, pancreatic genetics has made rapid progress. The identification of mutations in genes involved in the digestive protease-antiprotease pathway has lent additional support to the notion that pancreatitis is a disease of autodigestion. Clinical and experimental observations have provided compelling evidence that premature intrapancreatic activation of digestive proteases is critical in pancreatitis onset. However, disease course and severity are mostly governed by inflammatory cells that drive local and systemic immune responses. In this article, we review the genetics, cell biology, and immunology of pancreatitis with a focus on protease activation pathways and other early events.
10.1053/j.gastro.2018.11.081
New insights into acute pancreatitis.
Lee Peter J,Papachristou Georgios I
Nature reviews. Gastroenterology & hepatology
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.
10.1038/s41575-019-0158-2