Carbon Monoxide Poisoning
Probable/Hypothesized Mechanisms of Brain Damage:
Reduced brain oxygen delivery resulting in tissue hypoxemia.
Generalized hypotension - cerebral blood flow becomes purely blood pressure dependent due to loss of autoregulatory control leading to ischemia (oligemia).
Role of the limited vasodilatory capability of some portions of the cerebral arterial architecture (ie. anatomy).
Metabolic acidosis resulting in edema, metabolic shut-down, membrane damage, etc.
Hemoconcentration leading to decreased blood flow (i.e. impaired rheology).
Binding of CO to intracellular components (e.g. cytochromes, myoglobin) inhibiting metabolic energy release.
Stimulation of free radical formation (ie. reactive oxygen species = ROS), eg. superoxide anion, O2-; hydrogen peroxide, H2O2; and hydroxyl radical, OH..
Release by nerve cells of excitatory amino acids (EAA) (glutamate & other dicarboxylic amino acids) which have neurotoxic properties.
Release of catecholamines (CAT = epinephrine, norepinephrine).
Excessive uptake of Ca++ by nerve cells.
Excessive stimulation of NMDA (N-methyl-D-aspartic acid), AMPA (D-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid), and KA (kainic acid) receptors.
Damage to mitochondria and energy generating machinery of the cell by above mechanisms (??).
Interference with the normal vasoregulatory control of the blood supply involving endogenous NO and CO (eg. increased nitric oxide synthase = NOS).
...... last changed 10/05/00
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