The patient is
initially injured in some way – this may be, for example, infection,
trauma or inflammation.
The result of this
injury is activation of host defense mechanisms, including release of
inflammatory cytokines, particularly interleukin-6 and tumor necrosis
manifestations of this process include tachypnea, tachycardia,
leucocytosis and pyrexia, and we call this the systemic inflammatory
response. The body is, in effect, responding to the source of
inflammation and making physiologic compensation for the systemic upset.
If the patient is
unable to adequately compensate, and suffers acute organ failure, then
he /she requires critical care interventions – usually mechanical
ventilation, often with cardiovascular support.
The patient has
undergone a “first hit”. He/she is now vulnerable to further injury.
At this point one of
three things may happen: 1) the injury and inflammatory and or
inflammatory response may persist
3) The patient may develop a second (or third or fourth) injury, such as
nosocomial pneumonia, ventilator induced lung injury or bacterial
translocation from the gut, which stokes up the inflammatory response.
leads to widespread endothelial dysfunction, and ischemic tissue injury
(due to hypotension, intravascular thrombosis, tissue edema, abnormal
oxygen extraction etc).
The result of this is
sequential organ damage – multi organ dysfunction. Examples of this are
an increase in the alveolar to arterial oxygen gradient, a reduced
ejection fraction, agitation or coma, a reduction in creatinine
clearance, and increase in serum bilirubin, a decrease in platelets and
clotting factors etc.
As the disease process
progresses, multi-organ dysfunction becomes multi-organ failure. This is
characterized by the requirement for external interventions to maintain
homeostasis – mechanical ventilation, inotropes and vasopressors, renal
replacement therapy, continuing blood product transfusions etc.
The patient becomes
severely catabolic, physiologic reserve deteriorates and neuroendocrine
exhaustion occurs. The latter is characterized by the inability of the
patient to mount an appropriate endocrine response to ongoing stress
The majority of
patients who develop multi organ failure succumb, due to inability to
wean external interventions (usually mechanical ventilation and
Death is inevitably as
a result of withdrawal of this support.
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