Friday 15 April 2005
Definition: Sepsis is a severe bacterial infections with systemic consequences.
In sepsis, the large amounts of organisms and LPS in the blood stimulate the production of enormous quantities of several cytokines, notably TNF and IL-1. As a result, circulating levels of these cytokines increase and the form of the host response changes. High levels of TNF cause disseminated intravascular coagulation (DIC).
Thrombosis results from two simultaneous reactions: LPS and TNF induce tissue factor (TF) expression on endothelial cells, which initiates coagulation; the same agents inhibit natural anticoagulation mechanisms, by decreasing the expression of tissue factor pathway inhibitor (TFPI) and endothelial cell thrombomodulin.
Cytokines cause liver injury and impaired liver function, resulting in a failure to maintain normal blood glucose levels due to a lack of gluconeogenesis from stored glycogen.
Overproduction of NO by cytokine-activated cardiac myocytes and vascular smooth muscle cells leads to heart failure and loss of perfusion pressure, respectively, resulting in hemodynamic shock.
The clinical triad of disseminated intravascular coagulation (DIC), hypoglycemia, and cardiovascular failure classically associate in septic shock.
Multiple organs show inflammation and intravascular thrombosis, which can produce organ failure.
Tissue injury in response to LPS can also result from the activation of neutrophils before they exit the vasculature, thus causing damage to endothelial cells and reduced blood flow.
The lungs and liver are particularly susceptible to injury by neutrophils.
Lung damage in the systemic inflammatory response, commonly called the adult respiratory distress syndrome (ARDS), results when neutrophil-mediated endothelial injury allows fluid to escape from the blood into the airspace.
The kidney and the bowel are also injured, largely due to reduced perfusion. This condition is often fatal.
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