Methemoglobin pathophysiology.

The biochemical processes involved in the formation of methemoglobin, in the protection of hemoglobin against oxidation to methemoglobin, and in the reduction of methemoglobin to hemoglobin are reviewed. Special emphasis is directed to the major and minor metabolic pathways in human erythrocytes that are involved in the reduction of methemoglobin, and evidence is presented that the NADH-methemoglobin reductase system, involving a soluble cytochrome b5 and NADH-cytochrome b5 reductase, it is the most important reductive mechanism. Toxic methemoglobinemia, methemoglobinemia due to hemoglobin M's, and hereditary methemoglobinemia due to deficiency in NADH-methemoglobin reductase activity are considered. Their clinical manifestations, diagnosis, and treatment are discussed briefly.