Editing Acute pancreatitis (section)

== '''Pathophysiology''' ==

* Likely the result of inappropriate activation of proenzymes inside acinar cells
* Leads to autodigestion of normal pancreatic parenchyma, which triggers acinar cells releasing proinflammatory cytokines, propagating the response locally and systemically
* In severe cases, the local inflammatory response causes local haemorrhage and pancreatic necrosis
* SIRS can also worsen injury due to pancreatic ischaemia
* 80-90% of patients with acute pancreatitis have a self-limited inflammatory cascade -> mild pancreatitis
* Gallstones
** Caused by either increased pancreatic duct back pressure, or bile salt reflux into the pancreas
** Injury to acinar cells, triggering a cascade of pro-inflammatory changes
* Alcohol
** Only seen in 5-10% of heavy drinkers
** Risk factors - >100g/day for at least 5 years, smoking (RR 4.9), genetic predisposition
** Alcohol probably causes pancreatic injury via a number of mechanisms, although it has not been fully delineated
*** '''Pancreatic processing of alcohol leads to damaging metabolites''' through both oxidative and non-oxidative pathways, such as acetaldehyde and fatty acid ethyl esters
*** Increased synthesis of digestive and lysosomal enzymes
*** Possible chronic sensitisation of acini to CCK
*** '''Precipitation and increased viscosity of pancreatic secretions''' - protein plugs in small ducts - progressive inflammation and fibrosis, leading to loss of acinar, islet and ductal cells
*** Premature activation of trypsinogen and other digestive and lysosomal enzymes
* Anatomical
** Obstructed flow of pancreatic juice, secondary to tumour (uncommon), parasites, or congenital defects (pancreas divisum or annular pancreas)
* Hypercalcaemia - activation of trypsinogen, and intra-ductal precipitation of calcium leading to ductal obstruction
* Lipase release leads to fat necrosis and digestion, with subsequent reaction of fatty acids and calcium to create soaps, or 'saponification'