Systemic inflammation

Systemic inflammation - During a severe inflammatory response, systemic release of cytokines and other mediators triggers widespread interaction between the coagulation pathways, platelets, endothelial cells and white blood cells, particularly the polymorphonuclear cells (PMNs). These ‘activated’ PMNs express adhesion factors (selectins), causing them initially to adhere to and roll along the endothelium, then to adhere firmly and migrate through the damaged and disrupted endothelium into the extravascular, interstitial space together with fluid and proteins, resulting in tissue oedema and inflammation.

Systemic Inflamation

Inflammation

A vicious circle of endothelial injury, intravascular coagulation, microvascular occlusion, tissue damage and further release of inflammatory mediators ensues. All organs may become involved. This manifests in the lungs as the acute respiratory distress syndrome (ARDS) and in the kidneys as acute tubular necrosis (ATN), while widespread disruption of the coagulation system results in the clinical picture of DIC.

The endothelium itself produces mediators that control blood vessel tone locally: endothelin 1, a potent vasoconstrictor, and prostacyclin and nitric oxide (NO, p. 82), which are systemic vasodilators. NO (which is also generated outside the endothelium) is implicated in both the myocardial depression and the profound vasodilatation of both arterioles and venules that causes the

relative hypovolaemia and systemic hypotension found in septic/systemic inflammatory response syndrome (SIRS) shock.

A major component of the tissue damage in septic/SIRS shock is the inability to take up and use oxygen at mitochondrial level, even if global oxygen delivery is supranormal. This effective bypassing of the tissues results in a reduced arteriovenous oxygen difference, a low oxygen extraction ratio, a raised plasma lactate and a paradoxically high mixed venous oxygen saturation (SvO