Carbon monoxide hypoxia

Zhang, J., and C.A.Piantadosi. 1992. Mitochondrial oxidative stress after carbon monoxide hypoxia in the rat brain. J. Clin. Invest. 90(4) 1193—1199. 

Brown, S.D., Piantadosi, C.A. (1992). Recovery of energy metabolism in rat brain after carbon monoxide hypoxia. 

Zhang, J. and Piantadosi, C.A. 1992. Mitochondrial oxidative stress after carbon monoxide hypoxia in the rat brain. J. Clin. Invest. 90 1193-1199 Zhang, C., Lambert, M.P, Bunch, C., Barber, K., Wade, W.S., Krafft, G.A. and Klein, W.L. 1994. Focal adhesion kinase expressed by nerve cell lines shows increased tyrosine phosphorylation in response to Alzheimer s AP peptide. J. Biol. Chem. 269 25247-25250 Zhang, R, Phiel, C.J., Spece, L., Gurvich, N. and Klein, PS. 2003. Inhibitory phosphorylation of glycogen synthase ldnase-3 (GSK-3) in response to lithium. Evidence for autoregulation of GSK-3. J. Biol. Chem. 278 33067-33077... 

The nervous system is vulnerable to attack from several directions. Neurons do not divide, and, therefore, death of a neuron always causes a permanent loss of a cell. The brain has a high demand for oxy gen. Lack of oxygen (hypoxia) rapidly causes brain damage. This manifests itself both on neurons and oligodendroglial cells. Anoxic brain damage may result from acute carbon monoxide, cyanide, and hydrogen sulfide poisonings. Carbon monoxide may also be formed in situ in the metabolism of dichloromethylene. 

Methaemoglobin forming compounds should be used cautiously in victims suffering from concurrent carbon monoxide poisoning or hypoxia. The second approach calls for provision of additional sulfur groups to enhance the detoxification of cyanide and thiocyanate by endogenous rhodanese this comes about by giving sodium thiosulphate. 

Toxicology. Carbon monoxide (CO) causes tissue hypoxia by preventing the blood from carrying sufficient oxygen. 

Cellular hypoxia may occur in spite of adequate ventilation and oxygen administration when poisoning is due to cyanide, hydrogen sulfide, carbon monoxide, and other poisons that interfere with transport or utilization of oxygen. Such patients may not be cyanotic, but cellular hypoxia is evident by the development of tachycardia, hypotension, severe lactic acidosis, and signs of ischemia on the electrocardiogram. 

Lactic acidosis Cyanide, carbon monoxide, ibuprofen, isoniazid, metformin, salicylates, valproic acid any drug-induced seizures, hypoxia, or hypotension... 

However, the mathematics describes an idealized situation, and the real situation in vivo may not be so straightforward. For example, with carbon monoxide, as already indicated, the toxicity involves a reversible interaction with a receptor, the protein molecule hemoglobin (see chap. 7 for further details of this example). This interaction will certainly be proportional to the concentration of carbon monoxide in the red blood cell. However, in vivo about 50% occupancy or 50% carboxyhemoglobin may be sufficient for the final toxic effect, which is cellular hypoxia and lethality. Duration of exposure is also a factor here because hypoxic cell death is not an instantaneous response. This time-exposure index is also very important in considerations of chemical carcinogenesis. 

Whether the toxic effects are mainly due to anemic hypoxia or to the histotoxic effects of carbon monoxide on tissue metabolism is a source of controversy. Carbon monoxide will certainly bind to myoglobin and cytochromes such as cytochrome oxidase in the mitochondria and cytochrome P-450 in the endoplasmic reticulum, and the activity of both of these enzymes is decreased by carbon monoxide exposure. However, the general tissue hypoxia will also decrease the activity of these enzymes. 

Carbon monoxide (CO) binds tightly to the Hb iron. It stabilizes the R form of Hb and, thus, prevents release of 02 to the tissues. CO toxicity is, in large part, a result of tissue hypoxia. CO poisoning is treated with 100 percent oxygen therapy, which facilitates the dissociation of CO from the Hb, allowing more 02 to be bound to Hb. 

Parving, H-H. 1972. The effect of hypoxia and carbon monoxide exposure on plasma volume and capillary permeability to albumin. Scand. J. Clin. Lab. Invest. 30(1) 49- 56. 

Burn patients are usually awake and alert after they have been injured. If there is an alteration in mental status, consider the following associated traumatic injury, carbon monoxide poisoning, hypoxia, or preexisting medical conditions (American Burn Association, 2005a). 

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