Which of the following statement(s) is/are true concerning the multiorgan failure syndrome (MOFS)?

a. Changes in the splanchnic and pulmonary microcirculation are critical to the development of MOFS

c. MOFS represents systemic consequences of loss of homeostatic control of local inflammation and microcirculatory hypoperfusion

The nature of multiorgan failure syndrome (MOFS) is that of a diffuse cellular injury, developing systemically as a consequence of losing homeostatic control of local inflammation and microcirculatory hypoperfusion. Endothelial injury, platelet aggregation and activation of macrophages and neutrophils occur, and the clotting, fibrinolytic, kinin, and complement cascades are activated, along with the release of potent inflammatory cytokines. The effects of shock, resuscitation, and reperfusion, and the subsequent development of MOFS appear to be critically dependent on changes in the splanchnic and pulmonary microcirculations. These vascular beds appear to be major sites of activation of subsequent inflammatory mediator production that underlies the diffuse systemic inflammatory response. Extensive activation of the liver Kupffer cell and release of inflammatory mediators coupled with the ongoing release of activated neutrophils and byproducts of activated gut macrophages is responsible for the injury to the pulmonary microcirculation and secondary induction of alveolar macrophage and additional inflammatory mediator systems. Excessive and persistent macrophage activation plays an essential role in MOFS and is hypothesized to represent the penultimate step in a series of continuous immuno-inflammatory stimulatory events, including local hypoxia, exposure to bacteria and toxins, and mediator release from localized areas of inflammation. When infection is the underlying or major contributing process, the diffuse inflammatory response develops independently of the specific type of microorganism. In noninfectious cases, the response also appears independent of the specific underlying cause.