Shock, Septic

DEFINITION
Develops as a complication of overwhelming systemic infection. Sepsis is defined as a systemic inflammatory response to infection. Occurs in severe sepsis and is associated with hypoperfusion or hypotension that may or may not respond to fluids or pharmacologic cardiovascular support to maintain arterial pressure.

PATHOPHYSIOLOGY
Results from cardiovascular and/or vasomotor failure caused by circulating endotoxin and inflammatory mediator release. Gram-positive or Gram-negative, aerobic or anaerobic, systemic bacterial infection is the most common underlying cause. The primary event is hypovolemia caused by pyrexia, dehydration, and vascular fluid leakage (because of increased microvascular permeability). Differential vasoconstriction and vasodilation of microvascular beds causes pooling of blood and differential tissue perfusion. Vasculitis and thromboembolic events further compromise tissue perfusion. The ultimate result is tissue hypoxemia and metabolic acidosis, leading to multiple organ failure. In Gram-negative bacterial sepsis, endotoxin (a lipopolysaccharide component of the outer bacterial membrane) plays a key role in the activation of the complement and fibrinolytic pathways. Endotoxin also stimulates macrophages to release cytokines, including tumor necrosis factor and interleukin-1, which in turn amplify the systemic response to endotoxin by stimulating neutrophils, endothelial cells, and platelets, and the release of other cellular mediators that are ultimately responsible for the cardiorespiratory and systemic manifestations of septic shock. Gram-positive bacteria produce other bacterial products capable of activating the same mediator responses.
SYSTEMS AFFECTED