Cellular hypoxia

The in situ generation of 2,3 BPG is accelerated by low atmospheric Po2, for example at high altitude. Lower Po2 at altitude could compromise tissue oxygenation so to avoid cellular hypoxia, 02 is released from haemoglobin. 

FI.W. Salmon, D.W. Siemann, Utility of F MRS detection of the hypoxic cell marker EF5 to assess cellular hypoxia in solid tumors, Radiother. Oncol. 73 (2004) 359-366. 

Generalized/organ specific (lung disease, anemia, decreased blood supply) Cellular hypoxia (cyanide poisoning of electron transport chain in mitochondria) Inflammatory (pathology from abnormal inflammatory response in the body) Autoimmune and/or chronic diseases (systemic lupus erythmatosus, rheumatoid arthritis)... 

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. 

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. 

Hydrogen cyanide binds cytochrome oxidase, resulting in cellular hypoxia and rapid death. 

Carbon monoxide and methemoglobin-forming agents interfere with oxygen transport, resulting in cellular hypoxia. Cyanide interferes with oxygen use and therefore causes an apparent cellular hypoxia. 

R. S. Hotchkiss and I. E. Karl Reevaluation of the role of cellular hypoxia and bioenergetic failure in sepsis. Journal of the American Medical Association 267, 1503 (1992). 

Cellular hypoxia, which may be present despite a normal arterial blood gas value. 

I. Mechanism of toxicity. Toxicity is a consequence of cellular hypoxia and ischemia. 

A. Symptoms and signs are caused by decreased blood oxygen content and cellular hypoxia and include headache, dizziness, and nausea, progressing to dyspnea, confusion, seizures, and coma. Even at low levels, skin discoloration ( chocolate cyanosis ), especially of the nails, lips, and ears, is striking. 

Differential diagnosis includes other causes of cellular hypoxia (eg, carbon... 

There is evidence that the pathogenesis is predominantly by a combination of direct tubular toxicity and cellular hypoxia, mediated to some degree by reactive oxygen species [14 ]. 

Cellular hypoxia was produced in Sprague-Dawley rat hearts by perfusing with medium equilibrated with 95% Na - 5% CO2. Taurine levels were measured in ventricular tissue after either 5 minutes... 

Cyanide is one of the least toxic of the lethal CWAs. The inhalational LCtso values for AC and CK have been estimated to be 2,500-5,000 and 11,000 mg min/m respectively (Simeonova, 2004). The cyanide ion (CN ) is the toxic moiety, mediated primarily by its great affinity for the heme as moiety of cytochrome c-oxidase in mitochondria, a key component in oxidative respiration. This interaction blocks the last stage in the electron transfer chain, resulting in cellular hypoxia and a shift of aerobic to anaerobic cellular respiration, leading to cellular ATP depletion and lactic acidosis. Therefore, tissues with high metabolic demands, such as neurons and cardiac cells, are key targets for toxicity. At lethal doses, death occurs within 6-8 min (Sidell et al., 1997). 

The ultimate cause of death from all three of these toxic cholinergic mechanisms is type 2 respiratory failure (see below) leading to cellular hypoxia with a failure to produce adenosine triphosphate (ATP), a shift to anaerobic respiration, lactic acidosis and cellular death, with the cardiac and CNS systems being the most immediately vulnerable. 

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