Pathophysiology

The understanding of the various pathological mechanisms involved in sepsis and SIRS is continuously evolving. Many of the actions of the identified pleiotrophic mediators are

Figure 5.1. Local and systemic response to infection and progression either to successful resolution or deterioration/death. SIRS: systemic inflammatory response syndrome; MODS: multiple organ dysfunctional syndrome.

being unraveled while others remain poorly understood. It is known that an overwhelming release of these mediators occurs as a result of an inciting event such as trauma and infection. Usually, the initial injury causes a localized inflammatory reaction classically characterized by rubor (redness), calor (heat), dolor (pain), tumor (swelling) and functio laesii (loss of function). This is due to the activation of the coagulation and complement cascades, in particular C3-C5, the cleavage products of which are potent chemoactivators and attractants of macrophages, polymorphonuclear leukocytes and platelets. The release by the activated cells of more kinins, histamines, prostaglandins, cytokines, oxygen-derived free radicals and other products leads to increased capillary permeability and oedema. This chain of events is the natural defense of the host against invading organisms and is a prerequisite for normal healing. It is only when this response is exaggerated with systemic spillage of the mediators that a generalized inflammatory response occurs, resulting in sepsis, septic shock and MODS. A continuum of host reaction therefore exists in response to infection ranging from a localized inflammatory process to multiple organ dysfunction with its associated high mortality (Fig. 5.1).

Many factors predispose to the development of sepsis, SIRS or MODS, including:

• changes in the microenvironment;

• disruption of intestinal mucosal barrier function;

• ischaemia-reperfusion injury;

• blood loss and transfusion;

• malnutrition.

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