Severe sepsis is classified when there is sepsis and hypo-perfusion with organ dysfunction that is unresponsive to fluid resuscitation. It has more recently been viewed as endothelial dysfunction resulting from overwhelming inflammatory mediation, in conjunction with profound, unopposed coagulation. The capillary vasculature sustains a significant injury due to the cascade of events that ends in capillary occlusion. The greater the occlusion, the greater risk for organ failure because cellular level circulation requires a functional capillary network for delivery of oxygen and nutrients and removal of cellular metabolic waste products.
When infection or injury prompts an initially widespread inflammatory response (SIRS), the normally smooth surface of the microvascular endothelium is roughened and damaged by the response. In addition, the release of inflammatory mediations promotes vasodilation with an increase in capillary permeability. This causes little holes in the endothelium that the systemic mediators try to facilitate the healing of. The four main factors associated with severe sepsis is hyperinflammation, hypercoagulation, microvascular obstruction, and endothelial responses that leads to accelerated formation of microclots on the non-smooth surface of the endothelium. This consumes plates and inhibits clot lysis. This progresses to uncontrolled alterations in the vascular tone with vasodilation. In severe sepsis, the balance between vasodilators(nitric oxide) and vasoconstrictors(endothelin) cannot be maintained. Consequently, the maldistribution of blood flow in addition to loss of vascular tone at the macro and microvascular levels results in ischemia and hyperemia in the cells. Myocardial depressant factor is also released and may contribute to the loss of the compensatory CO that is required to keep blood moving through the vascular beds.
Septic shock is a subset of sepsis(4th on the continuum), in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality. It is a type of vasodilatory or distributive shock that is severe sepsis with cardiovascular dysfunction(primary loss of vascular tone). Patients with septic shock can be identified with a clinical construct of sepsis with persisting hypotension requiring vasopressors to maintain MAP >65mmHg and having a serum lactate level >2mmol/L(18mg/dL) despite adequate volume resuscitation.
MODS(Multiple organ dysfunction syndrome) refers to a progressive organ dysfunction in an acutely ill patient, in which homeostasis cannot be maintained without interventions. It is at the severe end of the sepsis spectrum because it involves both infectious(sepsis, septic shock) and noninfectious conditions(SIRS