The normal host response to infection is a complex process which serves to localize and control bacterial invasion and to initiate repair of injured tissue. This inflammatory process is accompanied by activation of circulating and fixed phagocytic cells and generation of pro-inflammatory and anti-inflammatory mediators. Sepsis results when the prerequisite inflammatory response to infection becomes generalized, and thereby extends to involve otherwise normal tissue which is remote from the initial site of injury or infection. Sepsis is typically associated to cardiovascular alterations that have been characterized by increases in oxygen delivery to the tissues. Paradoxically, the host's systemic inflammatory response syndrome may simultaneously disturb the ability to adequately match tissue oxygen needs and availability at a time when tissue oxygen needs are typically increased. Depressed tissue oxygen availability relative to augmented needs may result from dysfunction at all of the central, regional, and microregional levels of the circulation. Significant dysregulation in the process by which oxygen availability is usually matched to changing tissue oxygen needs is typical associated with changes the microvascular blood flow behavior, vascular reactivity and endothelial and leukocyte activation. Specific tools developed to explore the microcirculation have been applied in the setting of both human and animal models sepsis. Abnormalities observed in the septic microvasculature are characterized by reductions in cutaneous and skeletal muscle blood flow and in mucosal intestinal ischemia and hypoxia. Regarding the skeletal muscle organ system, microvascular abnormalities were further characterized by an impairment of blood flow to increase in response to oxygen need increase. Also, microvascular abnormalities in the intestine were associated with evidence of endothelial and leukocyte activation leading to epithelial dysfunction. Thus, sepsis appears to be associated with early onset microvascular dysfunction. The relationship between microvascular dysfunction and endothelial and leukocyte activation leading to organ failure has been suggested by numerous studies.
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