There are three clinical stages of SIRS described from 1-3. Stage one is in the main a local response with increased recruitment of neutrophils and monocytes. In stage two there is a spill over of activated cytokines into the circulation but balance is retained by the dampening effects of anti-inflammatory cytokines. In stage three balance is lost and there is a massive pro-inflammatory swing. There is generalised loss in capillary barrier function and generalised organ dysfunction.
In severe SIRS there is systemic vasodilatation (histamine, prostaglandins) with a fall in systemic vascular resistance and blood pressure. Widespread leaky capillaries lead to extensive third space extra-cellular fluid loss with hypovolemia. Myocardial function is impaired due to leucocyte induced myocardial cell dysfucntion and to the effects of myocardial hypo-perfusion.
The terminal state is characterised by severe hypotension, refractory to fluid and inotropic support. There is severe worsening lactic acidosis due to impaired tissue perfusion.