Methemoglobinemia is a condition characterized by an increased content of methemoglobin (oxidized hemoglobin) in the blood and tissue hypoxia. The development of the disease is accompanied by acrocyanosis, weakness, headaches, dizziness, palpitations, shortness of breath during exercise. A characteristic feature of the pathology is the brown-chocolate color of the blood. To confirm the diagnosis, an assessment of symptoms, laboratory tests are carried out. With a severe degree of methemoglobinemia, oxygen therapy, the introduction of ascorbic acid, a solution of methylene blue, in some cases, exchange hemotransfusion is indicated.
ICD 10
D74 Methemoglobinemia
Meaning
Methemoglobinemia is an increase in the level of hemoglobin containing oxidized iron (methemoglobin – MtHb) in red blood cells. Methemoglobin refers to the so-called dyshemoglobins – derivatives of hemoglobin that are unable to transport oxygen. Under normal conditions, a small amount of methemoglobin is present in the blood – no more than 1% of the total Hb content. With methemoglobinemia, endogenous mechanisms are unable to regulate the concentration of dyshemoglobin, as a result of which the oxygen transport function of erythrocytes suffers. In hematology, methemoglobinemia is divided into hereditary and acquired. The first of them are common among the indigenous population of Alaska, Greenland; the frequency of acquired methemoglobinemia is unknown.
Methemoglobinemia causes
In the process of metabolic transformations in the blood of healthy people, dyshemoglobins are formed in very small quantities: carboxyhemoglobin, sulfhemoglobin, methemoglobin (0.1-1%). At the same time, erythrocytes contain a number of factors that maintain the proportion of the methemoglobin fraction at a level not exceeding 1.0-1.5% of the total Hb. In particular, the enzyme methemoglobin-reductase participates in the reaction of reducing methemoglobin to hemoglobin. Unlike oxyhemoglobin (HbO2), which contains reduced iron (Fe++), methemoglobin contains oxidized iron (Fe+++), which is not able to carry oxygen. Therefore, with methemoglobinemia, first of all, the oxygen-transport function of the blood suffers, the consequence of which is tissue hypoxia.
Hereditary forms of methemoglobinemia are represented by either fermentopathies (congenital low activity or absence of the enzyme methemoglobin reductase) or M-hemoglobinopathies (synthesis of abnormal proteins containing oxidized iron).
In the structure of acquired (secondary) methemoglobinemia, toxic exogenous and toxic endogenous forms are distinguished. Methemoglobinemia of exogenous origin may be associated with an overdose of drugs (sulfonamides, nitrites, vicasol, antimalarial drugs, lidocaine, novocaine, etc.) or poisoning with chemical agents (aniline dyes, silver nitrate, trinitrotoluene, chlorobenzene, drinking water and foods with a high content of nitrates, etc.).
Elevated levels of MtHb in the blood are observed in premature and full-term newborns, which is associated with low activity of the enzyme methemoglobin reductase and oxidative stress in childbirth. However, even with severe hypoxia and neonatal jaundice, the rise in MtHb is not so pronounced and clinically significant as to cause methemoglobinemia. However, with diarrhea, bacterial and viral enterocolitis, in conditions of metabolic acidosis, acquired endogenous methemoglobinemia can easily develop in children of the first year of life.
A mixed form of pathology is indicated if methemoglobinemia develops under the influence of exogenous factors in healthy individuals who are heterozygous carriers of the genes of the hereditary form of the disease.
Methemoglobinemia symptoms
Signs of hereditary methemoglobinemia become noticeable during the newborn period. Cyanosis is noticeable on the skin and visible mucous membranes of the child (in the area of the lips, nasolabial triangle, earlobes, nail bed). In addition to hereditary methemoglobinemia, other congenital anomalies are often detected in children – changes in the configuration of the skull, underdevelopment of the upper extremities, vaginal atresia, thalassemia, etc. Often children lag behind in psychomotor development.
Depending on the level of the MtHb fraction, the severity of manifestations of congenital and acquired methemoglobinemia can vary significantly.
At the concentration of MtHb in the blood:
- <3% there are no clinical manifestations
- 3-15% – the skin becomes grayish
- 15-30% – cyanosis develops, the blood becomes chocolate brown
- 30-50% – weakness, headache, tachycardia, shortness of breath during exercise, dizziness, fainting occurs
- 50-70% – arrhythmia, rapid breathing occurs, convulsions; metabolic acidosis develops; signs of central nervous system depression are noted, coma is possible
- >70% – severe hypoxia, fatal outcome.
For all forms of methemoglobinemia, the slate-gray color of the skin is characteristic, but there are no changes in the nail phalanges of the type of “drumsticks” characteristic of cardiopulmonary diseases. Acrocyanosis increases with cooling, eating nitrate-containing foods, with toxicosis of pregnancy in women, as well as taking methemoglobin-forming medications.
Diagnostics
An important diagnostic sign of methemoglobinemia is the dark cinnamon color of blood, which, when placed in a test tube or on filter paper, does not change its color to red. If the test is positive, spectroscopy is performed, the concentration of MtHb, the activity of NAD-dependent methemoglobin reductase, and hemoglobin electrophoresis are determined.
Compensatory erythrocytosis, an increase in Hb, reticulocytosis, and a decrease in ESR may be present in the blood test. When studying the biochemical parameters of the blood, a slight bilirubinemia is determined due to an increase in the indirect fraction of the pigment. For chronic methemoglobinemia, the appearance of Heinz-Ehrlich corpuscles in erythrocytes is typical.
In patients with enzymopenic or toxic methemoglobinemia, a therapeutic test with intravenous administration of methylene blue is indicative – after injection, cyanosis quickly disappears, and the skin and visible mucous membranes turn pink.
When analyzing the causes of methemoglobinemia, it is important to find out whether the patient had contact with toxic substances, whether he took methemoglobin-forming medications. If congenital methemoglobinemia is suspected, the pedigree is studied, a geneticist is consulted, the type of inheritance of blood pathology is determined. Hereditary methemoglobinemia requires differentiation with congenital heart defects of the blue type, abnormalities of lung development and other conditions accompanied by hypoxia.
Treatment and prevention
Patients with the absence of clinical manifestations do not need special therapy. With a significant concentration of MtHb in the blood and extensive symptoms of methemoglobinemia, drug therapy is prescribed that promotes the conversion of methemoglobin into hemoglobin. Ascorbic acid and methylene blue have such regenerating properties. Ascorbic acid is administered orally first in large doses, and as the condition normalizes, in maintenance doses. A solution of methylene blue is administered intravenously. With severe cyanosis, oxygen therapy is performed. Severe form is an indication for exchange blood transfusion.
The course of hereditary and drug methemoglobinemia is usually benign. An unfavorable outcome is possible in severe forms of toxic methemoglobinemia with a high content of MtHb in red blood cells. Patients with such pathology should avoid contact with methemoglobin-forming substances, hypothermia and other provoking factors. Prevention of congenital methemoglobinemia consists in conducting a medical and genetic consultation to identify heterozygous carriers among future parents.
Literature
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- Novaro, G. M. Benzocaine-induced methemoglobinemia: experience from a high-volume transesophageal echocardiography laboratory / G. M. Novaro, H. D. Aronow, M. A. Militello et al. // J Am Soc Echocardiogr.— 2003 — № 16 — p.170-175.
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- Vallurupalli, S. Methemoglobinemia due to topical pharyngeal anesthesia during endoscopic procedures / S. Vallurupalli // Local Reg Anesth.— 2010.— № 3.— p. 137-142.