Pathophysiology of Sepsis

Background: Sepsis, a systemic inflammatory response to infection, resulting in organ failure and death. Pathogenic microbial agents trigger cascades of events in sepsis by stimulating the host’s immune system. Macrophages require surface receptors to present pathogenic molecule to Toll-like receptors (TLRs) to be activated and release proinflammatory cytokines such as tumour necrosis factor (TNFα) and interleukins (IL-1β, IL-6 and IL-8) together with activation of the coagulation cascades. In the last three decade, several basic science and clinical researches have been conducted in order to improve treatment and survival of patients with sepsis. The main aim of this review is, thus, to highlight recent advances in the pathophysiology of sepsis for effective management of the problem. Sources and Methods: More than 200 literatures of both experimental models of sepsis as well as clinical trials that were published from 1990 to 2011 were reviewed. Medline search was done based on the following key words; sepsis, systemic inflammatory response syndrome (SIRS), pathophysiology of sepsis, sepsis and coagulation, treatment of sepsis, mediator cytokines, multiple organ dysfunction syndrome (MODS) were performed. Both original publications and review articles were utilized. Results: Both preclinical and clinical models reserches on sepsis have shown significant development in the identification of diagnostic molecules such as cytokines and cell surface receptors that are potential biomarkers of sepsis in the clinical settings. Certain advancements have also been made in the understanding of the pathophysiologic, immunologic and biochemical pathway of sepsis. Despite these significant advances in the pathophysiology of sepsis, the mortality rate is still high, 30% to 50%. Conclusion: To win the war against sepsis, the pathophysiology of sepsis should be clearly elucidated. Early administration of broad spectrum antibiotics, effective source control, maintenance of normal glucose levels and goal-directed hemodynamic resuscitation are the cornerstone of successful management of sepsis. Copyright © WJMMS, all rights reserved. Key works: SIRS, Sepsis, Severe Sepsis, Septic Shock, Pathophysiology. __________________________________________________________________________________________ World Journal of Medicine and Medical Science Vol. 1, No. 8, December 2013, PP: 159-168, ISSN: 2330-1341 (Online) Available online at http://www.wjmms.com