Early events in sepsis
The intital toxic stimuli, such as endotoxin (LPS), triggers production of proinflammatory cytokines (TNF, IL-1) and monocyte adherence to endothelial cells. TNF and IL-1 also activates neutrophils and endothelial cells for increased adherence. All activated cells release secondary inflammatory mediators, including cytokines. Activation of platelets and increased production of procoagulants by endothelial cells may trigger microthrombosis. In some cases, disseminated intravascular coagulation (DIC) may occur with life-threatening tissue ischemia.
Vessel dilation caused by free radicals, histamine, prostaglandins, prostacyclin, and the kinin and tachykinin family of molecules, combined with the effects of cytokines on the endothelial cells, contribute to increased vascular permeability for fluids and low-molecular weight substances, causing oedema. If the process is wide-spread, a capillary leak syndrome may result. In some cases, erythrocytes may leak out and cause bleeding.
