Pathogenesis Mediators

The physiological response to infection includes the activation of defense mechanisms including the activation and influx of neutrophils and monocytes, the release of inflammatory mediators, local vasodilation and increased endothelial permeability, as well as the activation of the coagulation cascade . Sepsis is characterized by a similar response to infection, albeit at a systemic level, which results in diffuse endothelial dysfunction. In the case of bacterial infection, the inflammatory event is the interaction of endotoxins contained within the bacterial cell wall of Gram-negative organisms with cell receptors buildings. In gram-positive organisms, this interaction occurs because either cell wall components and exotoxins released by the microorganism.
As a result of these interactions, cell activation occurs with the release of cytokines and mediators, cytokines, the most notable of which are tumor necrosis factor-alpha (TNF-alpha), interleukin 1 (IL-1), and interleukin 6 (IL – 6). These factors are involved in the activation of a systemic inflammatory response. As a result, mediators with vasodilating properties and endotoxic are released throughout the body, including prostaglandins, thromboxane A2, and nitric oxide. This resulting in endothelial damage and vasodilation, leading to hypoperfusion and capillary leak fluid. In addition, cytokines activate the coagulation cascade, resulting in capillary microtrombos and end ischemia of various organs .
The complex interaction of cells and inflammatory mediators leads to dysfunction of the endothelium of the capillaries leading to arterial vasodilation, high cardiac output and capillary leakage of liquid. This starts a cascade of endothelial damage, global tissue hypoxia, microtrombos formation, abnormal oxygen utilization due to mitochondrial dysfunction, all potentially leading to organ dysfunction and eventual failure. The insidious nature of the dysfunction in sepsis is the microcirculation that may occur while general hemodynamic parameters such as blood pressure may remain normal.