Methemoglobin occurs when the iron atom in hemoglobin loses one electron to an oxidant, and the ferrous (Fe2+) or oxidized state of iron is transformed into the ferric (Fe3+) state. Although methemoglobin is always present at low concentrations in the body, methemoglobinemia is defined herein as an abnormal elevation of the methemoglobin level above 1%.
The widespread utilization of pulse oximetry in clinical medicine has made it easier to recognize low oxygen saturation, consequently increasing our recognition of methemoglobinemia. The ubiquity of oxidants both in the environment and in the hospital has increased the number of case reports associated with methemoglobin. It is also evident that host factors play a crucial role in the development of methemoglobinemia in many individuals.
Biologic systems have protective cell membrane and intracellular mechanisms that are protective with regard to oxidant stresses. Some are enzyme systems that involved electron transport mechanisms, and others are simple reducers such as ascorbic acid and reduced glutathione. When fully functional, these systems maintain methemoglobin levels under 1%, but with acute and/or chronic stress, they may be overwhelmed, allowing methemoglobin level to increase.
The cellular systems that protect the individual from oxidant stress involve cytochrome b reductase, flavin, nicotinamide adenine dinucleotide (NADH)methemoglobin reductase, nicotinamide adenine dinucleotide phosphate (NADPH) methemoglobin reductase, reduced glutathione and ascorbic acid are interrelated and incompletely understood. Depletion of the reducing power of these systems leads to methemoglobinemia and other disorders of oxidant stress such as hemolysis.
Underlying illnesses,47,57,72,74 the treatment with xenobiotics for these illnesses,3,17,58,73 and the therapeutic and diagnostic modalities involved47,72 in patient care all predispose patients to methemoglobinemia. For many individuals, methemoglobinemia is not caused by one oxidant stressor but rather a series of stressors that makes methemoglobinemia clinically apparent and potentially predictable.
Reduced hemoglobin functions reliably as an oxygen transporter because in its protected heme pocket, it shares an outer valence electron with the oxygen it transports. Normally reduced hemoglobin releases this oxygen without giving up an electron, but occasionally, this electron is lost to the departing oxygen in the process of auto-oxidation. Oxidation is increased in the presence of some hereditary conditions such as hemoglobin M disease. However, oxidizing xenobiotics may produce methemoglobin by direct interaction with the Fe2+ moiety. These exogenous products are a major source of oxidant stress to the individual and the most frequent cause of methemoglobinemia. Although typically not life threatening, methemoglobinemia may produce symptoms of cellular hypoxia and should be considered in the differential diagnosis of cyanotic patients who do not have an apparent cardiovascular cause. In the cases of methemoglobinemia, cyanosis is not caused by deoxyhemoglobin but rather by the color imparted to the skin as a result of oxidized hemoglobin.
Methemoglobin was first described by Felix Hoppe-Seyler in 1864.29 Subsequently, in 1891, a case ...