Methemoglobin and methemoglobinemia

Methemoglobin is a protein similar to hemoglobin, from which it differs for the different oxidation state of iron. In fact, the iron present in the -EME group of methemoglobin is oxidized to ferric ion (Fe3 +), while in hemoglobin it is found in the form of ferrous ion (Fe2 +). The passage of iron oxidation from a divalent to a trivalent state makes methemoglobin unable to transport 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 the erythrocytes can occur for acquired or hereditary causes. The acquired causes are the exposure of the organism to oxidizing chemicals and drugs, while the congenital ones are mainly due to an enzyme deficiency (deficiency of the methemoglobin-reductase enzyme ).
In our organism, in order not to run into unpleasant consequences, methemoglobin must have a maximum concentration equal to 1% of the total hemoglobin. When methemoglobin greatly exceeds this threshold value, it can be referred to as methemoglobinemia.Fortunately, as anticipated, our organism 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 share of methemoglobin is constantly kept below 1%.

Causes

The possible causes responsible for the excessive formation or accumulation of methemolgobin, and the consequent onset of methemoglobinemia, are:

• REDUCED CELL 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, sulfonamides and all compounds used in local anesthesia;
• ENVIRONMENTAL AGENTS such as aromatic amines (for example p-nitroaniline), arsine, chlorobenzolo, chromic acid salts and finally nitrites and nitrates;

Symptoms of methemoglobinemia

Patients with methemoglobinemia have no 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 color 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, dyspnoea and finally asthenia.

Diagnosis

The only laboratory tests useful for the diagnosis of methemoglobinemia are the spectroscopy of the liquid derived from the hemolysis of erythrocytes and the electrophoresis of hemoglobin.

Therapy

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 ferric ion to ferrous. Depending on the severity, the methylene blue dosage administered can range from 60 to 70 mg per day. Given its dangerousness, the dose 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, similar to methylene blue, it has a reducing activity on iron (transforming it from ferric to ferrous).