Individual organs and cells vary considerably in their sensitivity to hypoxia.28 Neurons, cardiomyocytes, and renal tubular cells are exquisitely sensitive to a sudden reduction in oxygen supply and are unable to survive sustained periods of hypoxia, although ischaemic preconditioning does increase tolerance to hypoxia. Following complete cessation of cerebral perfusion, nuclear magnetic resonance (NMR) measurements show a 50% decrease in cellular adenosine triphosphate (ATP) within 30 seconds and irreversible damage occurs within 3 minutes. Mechanisms have developed in other tissues to survive longer without oxygen: the kidneys and liver can tolerate 15-20 minutes of total hypoxia, skeletal muscle 60-90 minutes, and vascular smooth muscle 24-72 hours. The most extreme example of hypoxic tolerance is that of hair and nails which continue to grow for several days after death.
Variation in tissue tolerance to hypoxia has important clinical implications. In an emergency, maintenance of blood flow to the most hypoxia sensitive organs should be the primary goal. Hypoxic brain damage after cardiorespiratory collapse will leave a patient incapable of independent life even if the other organ systems survive. Although tissue death may not occur as rapidly in less oxygen sensitive tissues, prolonged failure to make the diagnosis has equally serious consequences. For example, skeletal muscle may survive severe ischaemia for several hours but failure to remove the causative arterial embolus will result in muscle necrosis with the release into the circulation of myoglobin and other toxins and activation of the inflammatory response.
Tolerance to hypoxia differs in health and disease. In a septic patient inhibition of enzyme systems and oxygen utilisation reduces hypoxic tolerance.29 Methods aimed at enhancing metabolic performance including the use of alternative substrates, techniques to inhibit endotoxin induced cellular damage, and drugs to reduce oxidant induced intracellular damage are currently under investigation. Ischae-mic preconditioning of the heart and skeletal muscle is recognised both in vivo and in experimental models. Progressive or repeated exposure to hypoxia enhances tissue tolerance to oxygen deprivation in much the same way as altitude acclimatisation. An acclimatised mountaineer at the peak of Mount Everest can tolerate a Pao2 of 4-4.5 kPa for several hours, which would result in loss of consciousness within a few minutes in a normal subject at sea level.
What is the critical level of tissue oxygenation below which cellular damage will occur? The answer mainly depends on the patient's circumstances, comorbid factors, and the duration of hypoxia. For example, young previously healthy patients with the acute respiratory distress syndrome tolerate prolonged hypoxaemia with saturations as low as 85% and can recover completely. In the older patient with widespread atheroma, however, prolonged hypoxaemia at such levels would be unacceptable.
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