1. Models of Acute and Chronic Pancreatitis
Markus M. Lerch, Fred S. Gorelick 
Gastroenterology 
Volume 144, Issue 6, Pages (May 2013)
DOI: /j.gastro
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2. Figure 1
Rodent models most commonly used to study acute and chronic pancreatitis. In mice and rats, acute pancreatitis (acute inflammation with hemorrhage when severe) can be induced by injections of caerulein, bile salt infusion, duct obstruction with or without administration of secretagogues, the choline-deficient ethionine-supplemented (CDE) diet, administration of basic amino acids, injection of specific cytokines, or infection with Coxsackie virus group B (CVB). Chronic pancreatitis (chronic inflammation with fibrosis, loss of exocrine and endocrine tissue, duct strictures, and, in some models, intraductal stones) can be induced by repeated injections of caerulein, by alcohol or lipopolysaccharide, by duct infusion with trinitrobenzene sulfonic acid (TNBS), genetic manipulation, administration of dibutyltin dichloride (DBTC), activation of an autoimmune response, or infection with CVB. Whether these models produce all the features of human chronic or acute pancreatitis remains unclear.
Gastroenterology  , DOI: ( /j.gastro )
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3. Figure 2
Sequential cellular and organ responses that produce acute pancreatitis. Pancreatitis begins with various forms of injury, such as acute duct obstruction, which activate signaling pathways in the pancreatic acinar cell. The best-characterized initiating signals are shown in panel 1: increased and prolonged increases in cytosolic calcium and activation of specific protein kinase C (PKC) isoforms and protein kinase D (PKD). Immediately downstream of these signals a number of cellular responses promote cell injury and inflammation (panel 2). These include activation of the transcription factor nuclear factor-κB (NF-κB), which stimulates the production of inflammatory cytokines, activation of digestive enzymes within the acinar cell and inhibition of apical enzyme secretion, and loss of the apical paracellular barrier formed by tight junctions. The increase in paracellular permeability is widespread and observed in acinar and duct cells as well as in vascular endothelium and intestinal mucosal cells. Cellular and organ injury follows the events shown in panel 2 and include the responses in panel 3: cell death, inflammation, edema, and reduced blood flow.
Gastroenterology  , DOI: ( /j.gastro )
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4. Figure 3
Acinar cell responses during the development of acute pancreatitis. Under physiologic conditions (left panel), zymogen granules (ZG, black circles) are secreted from the apical poles of acinar cells (facing lumen), and there is little or no intracellular activation of digestive enzymes (zymogen activation). In the initial phases of acute pancreatitis, apical secretion is blocked (red circles), proteases are activated within acinar cells, and digestive enzymes can access the interstitial space by crossing the disrupted junctional barrier or exiting through the basolateral membrane. The green organelle is a mitochondrium. The blue is an autophagic vacuole (AV), which increase in size and number during acute pancreatitis.
Gastroenterology  , DOI: ( /j.gastro )
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5. Figure 4
Different mechanisms by which gallstone migration could induce pancreatitis. (A) Opie51,52 proposed that obstruction of pancreatic outflow by an impacted gallstone causes pancreatitis; impaired bile flow would not be involved. (B) In Opie's51,52 common channel model, impaction of a gallstone at the papilla creates communication between the pancreatic and bile duct behind it. Bile then can enter the pancreatic duct and potentially reach the acinar cells. (C) The gallstone obstructs both ducts without the potential for bile reflux into the pancreas. Pancreatitis is induced by pancreatic outflow obstruction, but coincident bile duct obstruction could be an aggravating factor, increasing concentrations of circulating or interstitial bile acid.
Modified with permission from Lerch et al.55
Gastroenterology  , DOI: ( /j.gastro )
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6. Gastroenterology 2013 144, 1180-1193DOI: (10. 1053/j. gastro. 2012. 12
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7. Gastroenterology 2013 144, 1180-1193DOI: (10. 1053/j. gastro. 2012. 12
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