INVESTIGATIONS INTO HYPERLIPIDEMIA AND ITS POSSIBLE ...
INVESTIGATIONS INTO HYPERLIPIDEMIA AND ITS POSSIBLE ...
INVESTIGATIONS INTO HYPERLIPIDEMIA AND ITS POSSIBLE ...
You also want an ePaper? Increase the reach of your titles
YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.
28<br />
this theory, zymogen granules that are accumulating in acinar cells co-localize with<br />
lysosomes. Lysosomal enzymes, such as cathepsin B, are then thought to activate<br />
trypsinogen into trypsin, which subsequently activates other zymogens. Evidence from<br />
other studies indicate that the cytosolic concentration of free ionized calcium also plays<br />
an important role in the intracellular activation of zymogens. 157-159 In addition to the<br />
decreased secretion and intracellular activation of pancreatic enzymes, there is evidence<br />
of disruption of the paracellular barrier in the pancreatic duct that allows its contents to<br />
leak into the paracellular space, and also redirect the secretion of zymogen granules from<br />
the apical pole to the basolateral region of the acinar cell and into the interstitial space. 156<br />
Once intracellular activation of pancreatic enzymes has taken place, autodigestion of the<br />
acinar cell follows and activated enzymes escape, initially into the pancreatic tissue<br />
(leading to local effects) and subsequently into the peritoneal cavity and the systemic<br />
circulation (potentially contributing to systemic effects). Local effects vary and can<br />
range from mild interstitial edema to severe acinar cell necrosis, hemorrhage, and<br />
peripancreatic fat necrosis. The extent and severity of local effects determine to a large<br />
degree the systemic response. Acinar cell injury leads to recruitment and activation of<br />
inflammatory cells (most importantly neutrophils and macrophages), which release<br />
proinflammatory cytokines and other inflammatory mediators (such as interleukin [IL]-<br />
1, IL-2, IL-6, IL-18, tumor necrosis factor-α, substance P, platelet-activating factor<br />
[PAF]) that play a crucial role in modulating systemic complications of the disease. 155,160<br />
Such systemic complications can include cardiovascular shock, acute renal failure,<br />
neurologic abnormalities, disseminated intravascular coagulation (DIC), systemic