FIG. 1.

Microvascular dysfunction during sepsis progression. A septic insult, such as infection by virulent bacteria, triggers a systemic inflammatory response that can cause microvascular dysfunction if it is too exuberant. One component of this dysfunction is an impairment of arteriolar reactivity to vasoconstrictors (e.g., norepinephrine and angiotensin II) that contributes to loss of blood pressure control and eventually to shock. Another component is a disruption of the endothelial barrier that allows extravasation of plasma proteins and fluid from capillaries; this leakage leads to the development of tissue edema and it may also contract blood volume and thereby contribute to shock. A third component of septic microvascular dysfunction is an accumulation of platelets and microthrombi in capillaries that alters the distribution of blood flow, as has been observed in skeletal muscles of septic mice. The edema and maldistribution of capillary blood flow cause tissue hypoxia that may lead to organ failure. Death may result from multiorgan failure even if shock is prevented by interventions such as fluid resuscitation and vasopressor or inotropic-vasopressor therapy.