List the 3 steps of events.
Intrapancreatic activation of pancreatic enzymes: secondary to pancreatic ductal outflow obstruction (e.g., gallstones, cystic fibrosis) or direct injury to pancreatic acinar cells (e.g., alcohol, drugs)
Increased proteolytic and lipolytic enzyme activity → destruction of pancreatic parenchyma
Attraction of inflammatory cells (neutrophils, macrophages) → release of inflammatory cytokines → pancreatic inflammation (pancreatitis)
Describe the sequelae of pancreatitis.
Capillary leakage: release of inflammatory cytokines and vascular injury by pancreatic enzymes → vasodilation and increased vascular permeability → shift of fluid from the intravascular space into the interstitial space (third-space fluid loss) → hypotension, tachycardia, warm and flushed skin → distributive shock
In severe cases, the third spacing of fluid from this inflammatory response can lead to hypovolemic shock.
Pancreatic necrosis: uncorrected hypotension and third-spacing → decreased end-organ perfusion → multiorgan dysfunction (mainly renal) and pancreatic necrosis
Hypocalcemia: lipase breaks down peripancreatic and mesenteric fat → release of free fatty acids that bind calcium → hypocalcemia (fatty saponification)