Methemoglobinemia Hemoglobin

St. Louis )828 Leu Gin (3 heme in permanent ferric state, methemoglobinemia (hemoglobin M group) (6)... 

Furthermore, an increased oxidation rate of Hb—the reduction capacity remaining normal—will result in methemoglobinemia (H23, K13, K20). By this, two essentially different forms of methemoglobinemia can occur (a) deficiency in MHb reducing system and (b) acceleration of Hb oxidation. The question, whether or not the latter form of methemoglobinemia is identical with the so-called hemoglobin-M disease must be clarified by futher investigations. As yet, abnormal spectra of Hb as well as of MHb have been reported in such cases (H23, K13, K20, P3). 

Continuous exposure of rats by inhalation to 0.0055 and 0.3mg/m for 100 days resulted in methemoglobinemia, lowered erythrocyte hemoglobin, leukopenia and reticulocytosis, and reduced muscle chronaxie. Doses up to 500mg/kg administered by gavage to rats and mice for 13 weeks caused cyanosis and decreased motor activity, as well as hemosiderosis in the spleen liver, kidney, and testes. Bone marrow hyperplasia was observed in rats, and mice had increased hematopoiesis in the liver. In general, all toxic effects could be attributed to chronic methemoglobinemia, erythrocyte destruction, and erythrophagocytosis. 

Since nitrite ions oxidize the iron atoms of hemoglobin and convert it to methemoglobin, there may be a loss in oxygen delivery to tissues. While methemoglobinemia does not follow therapeutic doses of organic nitrates, it can be observed after overdosage or accidental poisoning. 

Clinical use Due to the low lipophilicity and therefore the low ability to penetrate neuronal membranes, the clinical use of benzocaine is limited to topical anesthesia such as mucous membrane anesthesia prior to endoscopic examination or for temporary relief of oral or dental pain. With higher doses, oxidation of the ferric form of hemoglobin to the ferrous form can occur the resulting methemoglobinemia is usually benign and can be reversed with methylene blue. Benzocaine is more likely to cause contact sensitization than amide-type LAs. 

Aniline must undergo biotransformation to cause methemoglobinemia because pure aniline does not oxidize iron(II) in hemoglobin to iron(III) in vitro. It is believed that the actual toxic agents... 

Nitrate accumulation may occur in plants growing on soil fertilized with nitrate under moisture-deficient conditions. In the stomachs of ruminant animals, nitrate (NOj) ingested with plant material is reduced to nitrite (N02). The nitrite product enters the bloodstream and oxidizes the iron(II) in hemoglobin to iron(III). The condition that results is methemoglobinemia, which was discussed in Section 15.3 in connection with aniline poisoning. 

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