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Abstract
The systemic inflammatory response syndrome can be self-limited or can progress to severe sepsis and septic shock. Persons with a weakened immune system are most likely to develop sepsis, but the detrimental processes that may ultimately lead to the death of the patient are mostly caused by an exaggerated, systemic response to an infection.
Infections are fought in the body by both cellular defenses, including monocytes, macrophages, and neutrophils, and humoral defenses incorporating antibodies and the complement pathways. Recognition of pathogens by extracellular CD14 and toll-like receptors (TLR-2 and TLR-4) on the membranes of monocytes and macrophages triggers the release of cytokines to activate cellular defenses.
Cellular activation leads to differentiation of T cells into type 1 helper cells (Th1), which secrete proinflammatory cytokines such as interferon-α (IFN-α), interleukin-1 (IL-1), IL-2, and IL-12, and type 2 helper cells (Th2), which secrete anti-inflammatory cytokines such as IL-4, IL-10, and IL-13.
Degree to which these cytokines are released is a function of many variables, including infectious circumstance, genetic susceptibility, and coexisting conditions. Sepsis results from an imbalance in the host regulation of proinflammatory SIRS and the compensatory antiinflammatory response Syndrome.
Inflammatory mediators, such as cytokines, chemokines, prostaglandins and lipid mediators, and reactive oxygen species induce vasodilatation and upregulation of adhesion molecules, resulting in extravasation of neutrophils and monocytes; activation of leukocytes, lymphocytes, and endothelial cells; and myocardial suppression, Besides alteration of the coagulation system leading to disseminated intravascular coagulopathy (DIC).
DIC causes hypoperfusion and hypoxia. Together with the damage caused by the intra- and extravascular phagocytic cells, these conditions lead to organ failure. This may initiate the often lethal stage of sepsis, in which multiple-organ failure, mostly involving the lungs (acute respiratory distress syndrome), liver, and kidneys develops.