Which of the following statements are true of the multiple organ dysfunction syndrome (MODS)?

A. The “two-hit” model proposes that secondary MODS may be produced when even a relatively minor second insult reactivates, in a more amplified form, the systemic inflammatory response that was primed by an initial insult to the host.

B. The systemic inflammatory response syndrome (SIRS), shock due to sepsis or SIRS, and MODS may be regarded as a continuum of illness severity.

C. Prolonged stimulation or activation of Kupffer cells in the liver is thought to be a critical factor in the sustained, uncontrolled release of inflammatory mediators.

DISCUSSION: MODS is part of a clinical continuum that begins with the systemic inflammatory response syndrome, which is the host's stress response to any major insult such as injury or infection. MODS may develop as a result of the initial insult, but more commonly, it develops following a second or subsequent insult to the host. The two-hit theory holds that the systemic inflammatory response is amplified following the second hit, such as nosocomial pneumonia, leading to exaggerated, persistent release of inflammatory mediators that contribute to the pathogenesis of MODS. The liver appears to be a pivotal organ in the progression and outcome of MODS, partly because of the activation and prolonged stimulation of the Kupffer cells, which comprise the majority of the body's macrophage population. Macrophages are known to play a critical role in the elaboration of numerous inflammatory mediators. Despite advances in critical care and in the understanding of the pathogenesis of MODS, the incidence of MODS continues to increase without a significant improvement in outcome.