Figure 1. Stage 1 begins at a site of local injury or infection. Proinflammatory mediators are released locally to promote wound healing and to combat foreign organisms or antigens. Anti-inflammatory mediators are then released to downregulate this process. If the original insult is small and the patient is healthy, homeostasis will be quickly restored. Stage 2 occurs if local defense mechanisms are insufficient to correct the local injury or eliminate the local infection. Through various mechanisms, proinflammatory mediators are released into the systemic circulation; these recruit additional cells to the local area of injury. Systemic release of anti-inflammatory mediators follows soon thereafter; under normal circumstances, these mediators ameliorate the proinflammatory reaction and restore homeostasis. Stage 3 occurs if the systemic release of proinflammatory mediators is massive or if the anti-inflammatory reaction is insufficient to permit downregulation. It is at this stage that most patients have symptoms of the systemic inflammatory response syndrome (SIRS), as well as incipient evidence of the multiple organ dysfunction syndrome (MODS). Stage 3 can be represented by excessive systemic levels of anti-inflammatory mediators that develop as a response to a massive proinflammatory response; however, these levels can also develop de novo. Patients with a stage 3 compensatory anti-inflammatory response syndrome (CARS) response have marked immunosuppression and thus are at increased risk for infection. If the body can reestablish homeostasis after stage 3 or 4, the patient may survive. Stage 5 is the final stage of MODS. At this stage of immunologic dissonance, the balance between pro- and anti-inflammatory mediators has been lost. Some patients may have persistent, massive inflammation; others may have ongoing immunosuppression and secondary infections. Still others may oscillate between periods of inflammation and immunosuppression.
The five stages in the development of multiple organ dysfunction.Grahic Jump Location