What is Methemoglobinemia: Causes, Diagnosis, and Treatment
Methemoglobin is a protein similar to hemoglobin, from which it differs due to the different oxidation state of iron. In fact, the iron present in the -HEME group of methemoglobin is oxidized to a ferric ion (Fe3+), while in hemoglobin it is found in the form of ferrous ion (Fe2+). The passage of iron oxidation from a bivalent state to a trivalent state makes methemoglobin incapable of transporting oxygen in our organism.
Inside the red blood cell, under normal conditions, small quantities of methemoglobin are always formed, promptly eliminated by particular enzymatic systems.
The accumulation of methemoglobin in erythrocytes can occur due to acquired or hereditary causes. The acquired causes are the exposure of the organism to oxidizing chemical substances and drugs, while the congenital ones are mainly due to an enzymatic deficiency (deficiency of the methemoglobin-reductase enzyme).
In our body, in order to avoid unpleasant consequences, methemoglobin must have a maximum concentration equal to 1% of total hemoglobin. When methemoglobin greatly exceeds this threshold value, we can speak of methemoglobinemia. Fortunately, as anticipated, our body has mechanisms capable of reducing spontaneously oxidized methemoglobin (about 3% per day); these mechanisms involve the intervention of the enzyme NADH cytochrome-b5 reductase, present in erythrocytes and otherwise known as methemoglobin-reductase. Thanks to the intervention of this enzyme, the amount of methemoglobin is constantly kept below 1%.
Causes
The possible causes responsible for the excessive formation or accumulation of methemoglobin, and the consequent onset of methemoglobinemia, are:
- REDUCED CELLULAR DEFENSE MECHANISMS induced by a hereditary deficiency of the NADH cytochrome-b5 reductase enzyme and/or by exposure to dangerous chemicals;
- PHARMACEUTICAL COMPONENTS such as amyl nitrite, chloroquine, dapsone, nitrites, nitrates, nitroglycerin, nitroprusside, quinones, sulphonamides and all compounds used in local anesthesia;
- ENVIRONMENTAL AGENTS such as aromatic amines (for example p-nitroaniline), arsine, chlorobenzene, chromic acid salts and finally nitrites and nitrates;
Symptoms of methemoglobinemia
Patients suffering from methemoglobinemia do not present particular symptoms. A characteristic sign of methemoglobinemia is cyanosis, with or without cardiac and/or respiratory phenomena. The term cyanosis indicates a particular blue-brown coloration of the blood, which gives the skin and mucous membranes a bluish color.
The increase in blood levels of methemoglobin can also lead to the onset of headache, dyspnea and finally asthenia.
Diagnosis
The only laboratory tests useful for the diagnosis of methemoglobinemia are spectroscopy of the liquid derived from the hemolysis of erythrocytes and hemoglobin electrophoresis
Therapy
The treatment of methemoglobinemia involves the intravenous administration of two substances, ascorbic acid or methylene blue.
Methylene blue is an organic substance that has a strong reducing activity, capable of transforming iron from a ferric ion to a ferrous one. Depending on the severity, the dosage of methylene blue administered can vary from 60 to 70 mg per day. The dose, given its danger, must always be decided by a doctor.
Ascorbic acid, also known as vitamin C, is one of the substances useful in the treatment of methemoglobinemia, because, similarly to methylene blue, it has a reducing activity on iron (transforming it from ferric to ferrous).
