Microvascular responses to sepsis: clinical significance.
Sepsis can be defined as a phenomenon related to the host's response to infection. Sepsis is considered an uncontrolled, unregulated, and self-sustaining intravascular inflammation, resulting from an imbalance between systemic proinflammatory reaction and excessive anti-inflammatory response. Microcirculatory dysfunction lies at the center of sepsis pathogenesis and involves all three elements of the microcirculation: arterioles, capillaries, and venules. Endothelium plays a pivotal role in the pathogenesis of sepsis, not only because it modulates the inflammatory response but also because endothelial cells activated with excessive amounts of inflammatory mediators become dysfunctional. In response to various stimuli, the endothelium exhibits a wide range of responses that may lead to local as well as systemic changes, giving rise to the phenotypic heterogeneity seen in sepsis. Therapeutic approaches, such as targeting the coagulation system, nitric oxide synthesis or intracellular signal transduction, have been considered. The administration of activated protein C has been associated with a dramatic reduction in mortality and ongoing studies with tissue factor pathway inhibitor seem promising. Glucocorticoids also seem promising for use in sepsis as a result of their anti-inflammatory effects.
Bauer
Philippe R.
PR
Department of Internal Medicine, University of Missouri-Columbia, MA 406 Health Sciences Center, 65212, Columbia, MO, USA