What Causes Acute Pancreatitis?

Acute pancreatitis (AP) is a condition in which activated enzymes and inflammatory mediators released from the pancreas cause damage to the pancreas and surrounding tissues. AP is further divided into two main categories, a mild form called interstitial oedematous pancreatitis or a severe form called necrotising pancreatitis. Interstitial oedematous pancreatitis accounts for 80% of AP cases and the pancreatic inflammation involved usually resolves itself. However, necrotising pancreatitis resembles necrosis of the pancreas which can result in further complications.

AP starts with inflammation which can lead to damage of affected organs through multiple organ failure (MOF) and death if not treated appropriately. AP can cause acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), acute liver failure (ALF), systemic inflammatory response syndrome (SIRS), acute hepatic encephalopathy and disseminated intravascular coagulation (DIC). AP is associated with intense abdominal pain that often comes on suddenly. The normal pancreas measures approximately 12 x 6 x 2 cm but can increase up to 20 x 11 x 10 cm in the case of severe pancreatitis.

There are no currently approved therapies for treating AP. AP models that mimic human AP are a useful tool for studying the intricate overlapping processes and developing new therapies to improve AP prognosis. L-Arginine-prompted AP is one of the most commonly used in vivo model of pancreatitis, with a high degree of reliability.

AP is diagnosed based on pain criteria, lipase level and through an ultrasound. Firstly, an abdominal pain which is consistent with AP is investigated whereby the pain experienced is persistent, severe and often radiates along the back. Secondly, an increase in lipase or serum amylase levels three times the upper limit of normal lipase and amylase can be used to establish pancreatitis as the source of abdominal discomfort. Lastly, imaging evidence of AP through an ultrasound can be used to help diagnose AP.

AP is often triggered by gallstones that lodge within the pancreas or common bile duct, causing obstruction of the passage of digestive juices necessary for proper digestion. This results in the premature intracellular activation of digestive enzymes resulting in autodigestion of pancreatic cells causing an inflammatory response to be generated. Alcohol usage is also another cause of AP which can result in permanent damage. A major factor in determining severity of acute pancreatitis is related to whether persistent damage has occurred due to repeated bouts of injury over time.

AP results in an inflammatory response characterized by cells, cytokines, chemokines, extracellular matrix components and active proteases. AP is associated with elevated levels of interleukin-1 (IL-1), IL-6, tumor necrosis factor (TNF), monocyte chemoattractant protein (MCP)-1 and MIP-2. AP also causes infiltration of activated macrophages and neutrophils into the peripancreatic tissue, promoting the expression of chemokine ligand 2 (CCL2), inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor. AP often causes accumulation of matrix metalloproteinases in the pancreas, which can lead to further damage of the pancreatic tissues. The increased expression of matrix metalloproteinases in islets and endothelial cells could be exploited as a molecular marker for AP severity.

The high-mobility group protein B1 (HMGB1) is a member of the nuclear family of DNA/RNA-binding proteins. HMGB1 is a major histone-like protein present in most eukaryotic cells and it is released from necrotic cells. AP patients have elevated plasma concentrations of HMGB1, which can be used to differentiate AP from chronic pancreatitis, alcohol intoxication and other types of pancreatitis.