Acute Pancreatitis: Bench to the Bedside Stephen J. Pandol, Ashok K. Saluja, Clement W. Imrie, Peter A. Banks  Gastroenterology  Volume 133, Issue 3, Pages 1056.e1-1056.e25 (September 2007) DOI: 10.1053/j.gastro.2007.08.026 Copyright © 2007 AGA Institute Terms and Conditions

Figure 1 Intracellular and extracellular factors and their influence on the pathobiologic processes of acute pancreatitis. This graphic presents the relationships between extracellular and intracellular factors underlying the mechanism of acute pancreatitis and the pathobiological processes of acute pancreatitis. Gastroenterology 2007 133, 1056.e1-1056.e25DOI: (10.1053/j.gastro.2007.08.026) Copyright © 2007 AGA Institute Terms and Conditions

Figure 2 Intracellular mechanisms involved in the death response of pancreatic tissue during acute pancreatitis. The slide depicts both the interrelationship between apoptosis and necrosis pathways and various regulatory systems that may alter the outcome of cell death in pancreatitis. The illustration indicates that in addition to caspase and mitochondrial pathways mediating cell death, endosplasmic reticulum stress pathways can mediate cell death at least in part through release of its stored calcium that can activate mitochondrial death pathways. Lysomal pathways are involved through their cathepsins, which can mediate cell death in many tissues. In the pancreas, cathepsins can also activate digestive enzymes in the cell, which can augment cell damage. Severe mitochondrial dysfunction can lead to ATP depletion, and this de-energinization of the cell can lead to necrosis. In this case, apoptosis will not occur because ATP is necessary for the activation of effector caspases. As shown in the slide, the enzyme, polyADP-ribose polymerase (PARP) decreases ATP. PARP is up-regulated in cell injury where it is involved in DNA repair. PARP utilizes ATP in the repair process resulting in depletion of ATP and further cell vulnerability to necrosis. Phosphatidylinositol 3-kinase (PI 3-kinase), nuclear factor-κB (NF-κB) and inhibitors of apoptosis (IAPs) can inhibit apoptosis, a mechanism of importance in cancer as well as pancreatitis. This inhibitory system represents one pathway for cancer cell resistance to death. Finally, effector caspases can have several effects as indicated in the illustration to modulate the cell injury and death response. Gastroenterology 2007 133, 1056.e1-1056.e25DOI: (10.1053/j.gastro.2007.08.026) Copyright © 2007 AGA Institute Terms and Conditions

Figure 3 Etiologies of acute pancreatitis. The pie graph represents the relative frequencies of the etiologies of acute pancreatitis. Other features of the pancreatitis resulting from these etiologies are discussed in the text. Gastroenterology 2007 133, 1056.e1-1056.e25DOI: (10.1053/j.gastro.2007.08.026) Copyright © 2007 AGA Institute Terms and Conditions

Figure 4 Pathways of ethanol metabolism in the pancreas. The majority of ethanol is metabolized by the liver by the oxidative system in the liver. A small amount of oxidative ethanol metabolism takes place in the pancreas. On the other hand, nonoxidative ethanol metabolism is prominent in the pancreas resulting in the formation of fatty acid ethanol esters. These esters have been demonstrated to have several pathologic effects on the cell biology of pancreatic parenchymal cells. Gastroenterology 2007 133, 1056.e1-1056.e25DOI: (10.1053/j.gastro.2007.08.026) Copyright © 2007 AGA Institute Terms and Conditions

Figure 5 Mechanisms of gallstone pancreatitis. This graphic illustrates the 2 proposed mechanisms of initiation of gallstone pancreatitis. In Opie 1, the obstructing stone creates a common channel and increased pressure between the common bile duct and the pancreatic duct. This results in the potential for reflux of biliary contents into the pancreas. In Opie 2, only obstruction of the ducts occurs. Both mechanisms have the potential for leading to pancreatitis in humans. Gastroenterology 2007 133, 1056.e1-1056.e25DOI: (10.1053/j.gastro.2007.08.026) Copyright © 2007 AGA Institute Terms and Conditions