Methemoglobinemia

Abstract

The ferrous iron of hemoglobin is exposed continuously to high concentrations of oxygen and, thereby, is oxidized slowly to methemoglobin, a protein unable to carry oxygen. To restore hemoglobin function, methemoglobin (ferrihemoglobin) must be reduced to hemoglobin (ferrohemoglobin). Under physiological conditions, methemoglobin reduction is accomplished mainly by red cell NADH-cytochrome b5 reductase (NADH-methemoglobin reductase) so efficiently that there is insignificant amounts of methemoglobin in the circulating blood. However, should methemoglobin formation be increased--e.g., due to the presence of oxidant drugs, or an abnormal methemoglobin not amenable to reduction (hemoglobin M), or a deficiency in red cell cytochrome b5 reductase--methemoglobinemia will result. Most methemoglobinemias have no adverse clinical consequences and need not be treated. Under certain conditions, such as exposure to large amounts of oxidant or in young infants, rapid treatment is necessary. In hereditary cytochrome b5 deficiency, treatment is often directed at improving the poor cosmetic effect of persistent cyanosis with the minimum amount of drugs to give satisfactory clinical results.

Improving Oxygen Binding of Desiccated Human Red Blood Cells

“…This data supports the results of Figure 2, which indicates that the majority of Hb in the desiccated/resuspended RBCs is functional. Although 4.5% Met-Hb is lower than most desiccation procedures have reported, it is still higher than physiological concentrations (0% -3%) [3].…”

“…The heme group in Met-Hb has been oxidized from the oxygen carrying ferrous (Fe 2+ ) state to ferric (Fe 3+ ). Autoxidation of Hb to Met-Hb occurs naturally under normal physiologic conditions, accounting for around 1% of total Hb [3], but prolonged exposure of stored blood to atmospheric oxygen levels can increase Met-Hb levels. Desiccation of RBCs has been shown to increase the Met-Hb levels to 15% -50% [1] [13].…”

“…Hb inside RBCs is also vulnerable to oxidation in the freeze-drying process. Oxidized Hb (met-hemoglobin) does not bind oxygen [3]. The oxidation of Hb within the RBCs can also lead to formation of intracellular reactive oxygen species that can damage lipids and structural proteins [4].…”

A cyanotic appearing female after laparoscopic hysterectomy: was it methylene blue?

“…A methemoglobin fraction of 3 to 15% may manifest as a slight bluish discoloration to the skin, though the patient can remain asymptomatic. Levels above 15% can confer a deeper cyanotic color, together with symptoms such as lightheadedness, weakness and headache resulting from increasing tissue hypoxia [5,6]. Levels approaching 50% are life threatening, presenting with seizures, coma, profound lactic acidosis and cardiac dysrhythmias.…”

Methemoglobinemia and Eccentrocytosis in Equine Erythrocyte Flavin Adenine Dinucleotide Deficiency

“…25 Methemoglobinemia usually results from either increased production of methemoglobin by oxidants or decreased reduction of methemoglobin because of a deficiency in erythrocyte Cb 5 R. 19 Methemoglobinemia also has been reported in people with various hemoglobinopathies (referred to as hemoglobin M) that result in methemoglobin formation that is not amenable to reduction. 34 No source of exogenous oxidants was found in the mustang, and the rapid reduction of the methemoglobinemia with intravenous methylene blue excluded a similar hemoglobinopathy. The methemoglobinemia in this mustang was attributed to Cb 5 R deficiency caused by an erythrocyte FAD deficiency.…”