• Infection - invasion of micro-organisms into a normally sterile site, often associated with an inflammatory host response
• Bacteraemia - viable bacteria in the blood stream
• Septicaemia - no uniform definition, often interpreted as bacteraemia plus severe illness
• Sepsis - clinical evidence of infection plus a systemic response indicated by two or more of the following:
• tachypnoea (respiratory rate > 20/minute)
• white blood cells >12 x 109 or <4 x 109 or "left shift"
• Severe sepsis - sepsis associated with organ dysfunction:
• poor urine output
• metabolic acidosis
• disseminated intravascular coagulation
• Septic shock - severe sepsis with hypotension unresponsive to intravascular volume replacement
• Refractory shock - hypotension not responding to vasoactive drugs of cytokines, nitric oxide, thromboxanes, leukotrienes, platelet activating factor, prostaglandins, and complement. There is also activation of coagulation and platelet aggregation. All this leads to:
• increased capillary permeability
• hypovolaemia, hypoperfusion, and a disturbed microcirculation
• development of a metabolic acidosis with increasing blood lactate
• impaired oxygen utilisation
• reduced myocardial contractility caused by circulating myocardial depressants, acidosis, and hypoxaemia
• a reduced systemic vascular resistance (SVR)
• increased pulmonary vascular resistance
• increased oxygen extraction owing to a hypermetabolic state
• coagulopathy with microvascular thrombosis.
The "typical" patient with severe sepsis has a fever and tachycardia, and is vasodilated with an increased cardiac output and low blood pressure. However, poor myocardial function is also part of severe sepsis and may contribute to hypotension. Patients can appear vasoconstricted with cold peripheries especially if there is coexisting hypovolaemia. It is important to recognise that sepsis is a dynamic process with rapid evolution of physical signs covering a wide continuum of physiological responses.
The host response to infection is protective - but in severe sepsis it seems to be stimulated excessively leading to organ dysfunction, multiple organ failure, and death. In simplified terms, severe sepsis can be thought of as dysfunction between the opposing mechanisms that normally maintain homeostasis. The main systems that become dysfunctional in severe sepsis are inflammation, coagulation/fibrinolysis, and the endothelium. Other factors such as mitochondrial dysfunction also play a role.
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