الفهرس 
I N T R O D U C T I O NOnly 14 pages are availabe for public view
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Abstract
Despite advances in diagnosis and treatment, mortality rates associated with sepsis and septic shock remain unacceptably high. Unresponsive hypotension is present in half of the patients who die from sepsis and is the number one cause of death in the first week after diagnosis; in the second week, multiple organ failure resulting from prolonged hypotension and maldistribution of blood flow is the leading cause of death (3).
Sepsis - Sepsis is the systemic response to infection. Thus, in sepsis, the clinical signs describing SIRS are present together with definitive evidence of infection.
Severe sepsis — Sepsis is considered severe when it is associated with organ dysfunction, hypoperfusion, or hypotension.
Septic shock — Septic shock is sepsis with hypotension despite adequate fluid resuscitation combined with perfusion abnormalities that may include, but are not limited to, lactic acidosis, oliguria, or an acute alteration in mental status.
Multiple organ failure — Multiple organ failure refers to the presence of altered organ function in an acutely ill patient such that homeostasis cannot be maintained without intervention.
The mechanism of widespread vasodilation and myocardial dysfunction in septic shock involves the activation of the soluble intracellular enzyme guanylate cyclase (GC) by nitric oxide (NO), resulting in the production of cyclic guanosine monophosphate (cGMP). Nitric oxide is made by the enzyme nitric oxide synthase (NOS). There are three isoforms of nitric oxide synthase (NOS): Neuronal (nNOS or NOS1) and Endothelial (eNOS or NOS3) are constitutive isoforms as they are Ca dependent; they synthesise NO in small amounts under normal physiological. Inducible (iNOS or NOS2) is the third isoform, its activity is independent of the level of calcium in the cell & is normally inactive, however, under conditions of stress, including sepsis when certain cells are activated by specific proinflammatory agents such as endotoxin, tumor necrosis factor (TNF), interferon-gamma (IFN), and interleukin-1 (IL-1), iNOS activity is induced leading to the production of large amounts of NO in an unregulated fashion resulting in the hemodynamic manifestations of septic shock (58-60).