.jpg)
Acute Pancreatitis: Modern Aspects of Pathogenesis and Classification
There has been considered the pathogenesis of acute pancreatitis. Various mechanisms have been shown to lead to pancreatic cell damage of the same type. Intracellular activation of proteolytic and other enzymes (elastase, phospholipases A2) lead to the release of preexisting cytokines — interleukins IL-1β, IL-6, IL-8, platelet-activating factor, tumour necrosis factor (TNF-α), some of which through the system of receptor-interreacting protein kinases cause the activation of the nuclear factor κβ that is responsible for the synthesis of pro-inflammatory and anti-inflammatory cytokines, as well 128 the apoptosis. TNF-α, IL-1β, intracellular adhesion-1 molecule, and probably, IL-18 have the marked local and remote damaging effect on organs and tissues. Phospholipase A2 takes part in the metabolism of fatty acids Omega-6 and Omega-3, the metabolites of the former (leukotriene B4 and thromboxane A2) enhance an inflammatory reaction, while the metabolites of the latter (leukotriene B5 and thromboxane A3) are responsible for an anti-inflammatory response. Matrix metalloproteinase-9 of neutrophils causes the rupture of basal membrane of the endothelium of capillaries of the pancreas, lungs, liver, kidneys, adrenals, the blood components coming into interstitium. The present enzyme is a mediator of neutrophils migration into various organs and their adhesion. The endothelial barrier destruction leads to mast cells activation and the release of biogenic amines that is accompanied by multi-organ dysfunction. Intraluminal accumulation of leukocytes is a potentially lifesaving mechanism and depends on the expression of certain genes. The severity of experimental pancreatitis is directly correlates with necrosis extent and conversely — with apoptosis intensity mediated by cytochrome C release into cytosol.
Pathogenesis mechanisms knowledge enables to understand why the course of the disease can vary due to a rapid relief of all manifestations up to massive necrosis with severe multi-organ failure.
