Surviving CO poisoning, brain damage
https://www.headway.org.uk/about-brain-injury/individuals/types-of-brain-injury/carbon-monoxide-poisoning/carbon-monoxide-poisoning-symptoms-and-treatment/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2707118/
https://www.neuroskills.com/about-us/delayed-neurological-syndrome-following-carbon-monoxide-poisoning.php
https://emedicine.medscape.com/article/819987-overview#a5
Excerpt (for those without a login)
'Pathophysiology
CO toxicity causes impaired oxygen delivery and utilization at the cellular level. CO affects several different sites within the body but has its most profound impact on the organs (eg, brain, heart) with the highest oxygen requirement.
Cellular hypoxia from CO toxicity is caused by impedance of oxygen delivery. CO reversibly binds hemoglobin, resulting in relative functional anemia. Because it binds hemoglobin 230-270 times more avidly than oxygen, even small concentrations can result in significant levels of carboxyhemoglobin (HbCO).
An ambient CO level of 100 ppm produces an HbCO of 16% at equilibration, which is enough to produce clinical symptoms. Binding of CO to hemoglobin causes an increased binding of oxygen molecules at the three other oxygen-binding sites, resulting in a leftward shift in the oxyhemoglobin dissociation curve and decreasing the availability of oxygen to the already hypoxic tissues.
CO binds to cardiac myoglobin with an even greater affinity than to hemoglobin; the resulting myocardial depression and hypotension exacerbates the tissue hypoxia. Decrease in oxygen delivery is insufficient, however, to explain the extent of the CO toxicity. Clinical status often does not correlate well with HbCO level, leading some to postulate an additional impairment of cellular respiration.
CO can produce direct cellular changes involving immunological or inflammatory damage by a variety of mechanisms, including the following [
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- Binding to intracellular proteins (myoglobin, cytochrome a,a3)
- Nitric oxide generation leading to peroxynitrite production
- Lipid peroxidation by neutrophils
- Mitochondrial oxidative stress
- Apoptosis
- Immune-mediated injury
- Delayed inflammation
Studies have indicated that CO may cause brain lipid peroxidation and leukocyte-mediated inflammatory changes in the brain, a process that may be inhibited by hyperbaric oxygen therapy. Following severe intoxication, patients display central nervous system (CNS) pathology, including white matter demyelination. This leads to edema and focal areas of necrosis, typically of the bilateral globus pallidus. Interestingly, the pallidus lesions, as well as the other lesions, are watershed area tissues with relatively low oxygen demand, suggesting elements of hypoperfusion and hypoxia. [
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Studies have demonstrated release of nitric oxide free radicals (implicated in the pathophysiology of atherosclerosis) from platelet and vascular endothelium, following exposure to CO concentrations of 100 ppm. One study suggests a direct toxicity of CO on myocardium that is separate from the effect of hypoxia. [
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HbCO levels often do not reflect the clinical picture, yet symptoms typically begin with headaches at levels around 10%. Levels of 50-70% may result in seizure, coma, and fatality.'