Carbon monoxide is readily absorbed into the bloodstream through the alveolar capillary network.

As with uptake, the main route of excretion is also pulmonary and depends on many factors, one of the most important of which is minute ventilation. Once in the bloodstream, CO reversibly binds to hemoglo­bin with an affinity approximately 240 times that of oxygen, leading to a reduction in the total oxygen- carrying capacity of the blood, with resultant tissue hypoxia. With affinity of this magnitude, even low- level exposure is associated with severe toxicity. Breathing air with CO concentrations of as little as 0.1 percent for only minutes may result in COHb levels of greater than 50 percent.

While CO concentrations are more significant, an increased minute ventilation will also lead to increased CO uptake. In this case, central respiratory control mechanisms are trying to raise the Pa02 in response to reduced oxygen delivery to the tissues; however, a vicious cycle develops where increasing respiration leads to greater and greater CO intake in a positive feedback loop, further complicating any hypoxia al­ready present.

Since the shape of the COHb dissociation curve is very similar to that of oxyhemoglobin, although shifted to the right, thus saturating at much lower levels, even small increases in CO levels in inspired air rapidly lead to dangerous CO levels in the blood; however, more important are the effects of any CO present on the oxyhemoglobin dissociation curve and peripheral tissue oxygenation. With increasing concentrations of CO leading to a greater and greater number of binding sites unavailable for oxygen, the oxyhemoglobin curve shifts to the left, resulting in lowered Pa02 for any given level of hemoglobin saturation and thus resulting in less oxygen delivery to the periphery. generic cialis 20mg

Interference with oxygen delivery to tissues is only partially explained by the competitive inhibition of oxygen uptake of hemoglobin by CO. Binding of CO to hemoglobin causes an allosteric change in the oxyhemoglobin complex and shifts the oxyhemoglobin dissociation curve to the left. This shift increases the affinity of hemoglobin for any bound oxygen, resulting in reduced peripheral hemoglobin desaturation and oxygen release. Thus, tissue hypoxia due to CO poisoning is greater than that expected with simple reductions in Pa02.

In addition to hemoglobin, other heme-containing proteins are affected by CO. Located in the extravas- cular tissues, these proteins account for approximately 10 to 15 percent of the total body CO. These include cytochrome oxidase and myoglobin. Inhibition of cel­lular respiration by CO binding to cytochrome oxidase has been thought to play a role in tissue damage; however, the fact that this heme protein has an affinity for oxygen nine times greater than for CO has cast doubt on this hypothesis. Binding of CO to myoglo­bin is postulated to reduce available oxygen stores in muscle tissue. In the myocardium, this can be disas­trous, leading to arrhythmias and cardiac arrest. Furthermore, cerebral ischemia resulting from de­creased cardiac performance, although transient in nature, may underlie some of the neurologic sequelae of CO intoxication.