Pathogenesis of acute pancreatitis
- Santhi Swaroop Vege, MD
Santhi Swaroop Vege, MD
- Professor of Medicine
- Mayo Clinic
Acute pancreatitis is an inflammatory condition of the pancreas characterized clinically by abdominal pain and elevated levels of pancreatic enzymes in the blood. A number of conditions are known to induce this disorder with varying degrees of certainty. However, the pathogenesis of this disorder is not fully understood.
This topic review will focus on the current understanding of the pathogenesis of acute pancreatitis. The etiologic conditions associated with this disorder are discussed separately. (See "Etiology of acute pancreatitis".)
A number of animal models have been developed to understand the pathogenesis of acute pancreatitis . None is strictly comparable to the human condition. Gallstones and alcohol abuse, for example, are responsible for 75 percent of cases of acute pancreatitis in humans, but none of the animal models duplicates these situations. In addition, the commonly used agents for inducing pancreatitis in animal models, such as cerulein and a choline-deficient ethionine-supplemented diet, are not recognized causes of human acute pancreatitis.
Nevertheless, the structural and biochemical changes seen in early phases of acute pancreatitis are remarkably constant in different animal models, and similar changes have been demonstrated in human acute pancreatitis. Furthermore, the clinical and pathologic features of human acute pancreatitis, regardless of the inciting event, are very similar.
Thus, despite the limitations of animal models, the data suggest that a similar cascade of events occurs once pancreatitis begins that is independent of the inciting event or initial mechanism. Animal studies have shown that this cascade cannot be halted successfully unless therapy is initiated either prophylactically or within a few hours of the inciting event. It is not clear from these studies why some individuals experience only interstitial or edematous pancreatitis, while others go on to develop the necrotizing form of the disease.
- Rattner DW. Experimental models of acute pancreatitis and their relevance to human disease. Scand J Gastroenterol Suppl 1996; 219:6.
- Moreau JA, Zinsmeister AR, Melton LJ 3rd, DiMagno EP. Gallstone pancreatitis and the effect of cholecystectomy: a population-based cohort study. Mayo Clin Proc 1988; 63:466.
- Dufour MC, Adamson MD. The epidemiology of alcohol-induced pancreatitis. Pancreas 2003; 27:286.
- Bess MA, Edis AJ, van Heerden JA. Hyperparathyroidism and pancreatitis. Chance or a causal association? JAMA 1980; 243:246.
- Mechanisms of alcoholic pancreatitis. Proceedings of a conference. Chicago, Illinois, USA, November 2002. Pancreas 2003; 27:281.
- Opie EL. The etiology of acute hemorrhagic pancreatitis. Bull Johns Hopkins Hosp 1901; 12:182.
- Lerch MM, Saluja AK, Rünzi M, et al. Pancreatic duct obstruction triggers acute necrotizing pancreatitis in the opossum. Gastroenterology 1993; 104:853.
- Toskes PP. Hyperlipidemic pancreatitis. Gastroenterol Clin North Am 1990; 19:783.
- Cohn JA, Friedman KJ, Noone PG, et al. Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis. N Engl J Med 1998; 339:653.
- Sharer N, Schwarz M, Malone G, et al. Mutations of the cystic fibrosis gene in patients with chronic pancreatitis. N Engl J Med 1998; 339:645.
- Choudari CP, Yu AC, Imperiale TF, et al. Significance of heterozygous cystic fibrosis gene (cystic fibrosis transmembrane conductance regulator mutations) in idiopathic pancreatitis (abstract). Gastroenterology 1998; 114:A447.
- Choudari CP, Stewart T, Crabb D, et al. Yield of genetic testing in pancreatic disease as we know it in 1997 (abstract). Gastroenterology 1998; 114:A447.
- Castellani C, Sgarb D, Cavallini G, et al. CFTR mutations and IV658-57 prevalence in chronic and acute idiopathic pancreatitis (abstract). Gastroenterology 1998; 114:A445.
- Steer ML. Pathogenesis of acute pancreatitis. Digestion 1997; 58 Suppl 1:46.
- Halangk W, Lerch MM, Brandt-Nedelev B, et al. Role of cathepsin B in intracellular trypsinogen activation and the onset of acute pancreatitis. J Clin Invest 2000; 106:773.
- Grady T, Saluja A, Kaiser A, Steer M. Edema and intrapancreatic trypsinogen activation precede glutathione depletion during caerulein pancreatitis. Am J Physiol 1996; 271:G20.
- Saluja AK, Donovan EA, Yamanaka K, et al. Cerulein-induced in vitro activation of trypsinogen in rat pancreatic acini is mediated by cathepsin B. Gastroenterology 1997; 113:304.
- Prinz RA. Mechanisms of acute pancreatitis. Vascular etiology. Int J Pancreatol 1991; 9:31.
- Klar E, Messmer K, Warshaw AL, Herfarth C. Pancreatic ischaemia in experimental acute pancreatitis: mechanism, significance and therapy. Br J Surg 1990; 77:1205.
- Toyama MT, Lewis MP, Kusske AM, et al. Ischaemia-reperfusion mechanisms in acute pancreatitis. Scand J Gastroenterol Suppl 1996; 219:20.
- Rinderknecht H. Fatal pancreatitis, a consequence of excessive leukocyte stimulation? Int J Pancreatol 1988; 3:105.
- Kingsnorth A. Role of cytokines and their inhibitors in acute pancreatitis. Gut 1997; 40:1.
- Sweiry JH, Mann GE. Role of oxidative stress in the pathogenesis of acute pancreatitis. Scand J Gastroenterol Suppl 1996; 219:10.
- Bhatia M, Saluja AK, Singh VP, et al. Complement factor C5a exerts an anti-inflammatory effect in acute pancreatitis and associated lung injury. Am J Physiol Gastrointest Liver Physiol 2001; 280:G974.
- Chan YC, Leung PS. Acute pancreatitis: animal models and recent advances in basic research. Pancreas 2007; 34:1.
- Agarwal N, Pitchumoni CS. Acute pancreatitis: a multisystem disease. Gastroenterologist 1993; 1:115.
- Tenner S, Sica G, Hughes M, et al. Relationship of necrosis to organ failure in severe acute pancreatitis. Gastroenterology 1997; 113:899.
- Sakai Y, Masamune A, Satoh A, et al. Macrophage migration inhibitory factor is a critical mediator of severe acute pancreatitis. Gastroenterology 2003; 124:725.
- Schmid SW, Uhl W, Friess H, et al. The role of infection in acute pancreatitis. Gut 1999; 45:311.
- Andersson R, Wang XD. Gut barrier dysfunction in experimental acute pancreatitis. Ann Acad Med Singapore 1999; 28:141.
- Kazantsev GB, Hecht DW, Rao R, et al. Plasmid labeling confirms bacterial translocation in pancreatitis. Am J Surg 1994; 167:201.
- Sah RP, Dawra RK, Saluja AK. New insights into the pathogenesis of pancreatitis. Curr Opin Gastroenterol 2013; 29:523.
- Hall JC, Crawford HC. The conspiracy of autophagy, stress and inflammation in acute pancreatitis. Curr Opin Gastroenterol 2014; 30:495.
- ANIMAL MODELS
- INCITING EVENT
- Alcohol-induced pancreatitis
- Gallstone pancreatitis
- Hyperlipidemia-induced pancreatitis
- Genetic mutations in hereditary pancreatitis
- Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations
- EARLY ACUTE CHANGES
- Intraacinar activation of proteolytic enzymes
- Microcirculatory injury
- Leukocyte chemoattraction, release of cytokines, and oxidative stress
- SYSTEMIC RESPONSE
- Bacterial translocation
- Nuclear factor kappa B (NFκB) activation
- INFORMATION FOR PATIENTS