METHEMOGLOBINEMIA (methaemoglobinemia; a methemoglobin + Greek haima blood) — the increased maintenance of a methemoglobin in blood (it is more than 1% of the general maintenance of Hb). The m arises owing to hereditary insufficiency of the recovering fermental systems of erythrocytes (methemoglobin reductases, or met-Hb-reductases) or as a result of their exceeding funkts, opportunities at hit in an organism of the high doses of nek-ry toxic agents which are methemoglobin formers. Also hereditary defect of a molecule of a globin — so-called can be one of the reasons of M. A M-hemoglobinopathy (see. Hemoglobinopathies ).
The etiology and a pathogeny
Distinguish primary (hereditary) and secondary (acquired) M. Primary M. subdivide on: 1) hereditary (inborn) Enzimopenicheskiye M., caused by falloff or total absence in erythrocytes of activity of NAD enzyme + (NADF +) - a dependent methemoglobin reductase [KF 220.127.116.11; a lipoamid-dehydrogenase (OVER + , NADF +)]; 2) the hereditary M-hemoglobinopathies (a hemoglobinosis of M) caused by existence of unstable or abnormal haemo globins of M - group M., in to-rykh genovariations replacement of the amino-acid remains in wasps - or in p-chains of a globin resulted (see. Gemoglobin ).
The secondary (acquired) M. divide on: 1) the toxic M. of an exogenous origin arising at action of chemical agents (oxidizers, amido-and nitroderivative benzene, aniline, phenylhydrazine, nitric oxides, nitrates of well water, quinones, metilnitrofos, nek-ry synthetic paints) or at poisoning with pharmaceuticals (acetphenetidiene, antipyrine, nitrites, Vikasolum, sulphones, nek-ry streptocides and antimalarial means); 2) the toxic M. of an endogenous origin caused by disturbance of products and absorption of nitrates at coloenterites (so-called enterogenous cyanosis).
In nek-ry cases the mixed forms, napr, the hereditary Enzimopenicheskaya M. who is shown at almost healthy people (heterozygous carriers of genes) only after reception of a high dose of sulfanamide drugs can be observed.
The pathogeny a wedge, M.'s manifestations is usually connected with hron, hypoxia (see) since saturation of an arterial blood oxygen at patients is reduced.
The hereditary Enzimopenicheskaya M. observed at homozygous carriers of genes is hron, a disease, is inherited on autosomal recessively type. In the world literature it is described apprx. 500 cases, from them St. 50 in the USSR (including 40 in Yakut by the ASSR). This form M. is caused by deficit of activity of a methemoglobin reductase, to-ry can have the isolated or generalized character; in the first case deficit comes to light in erythrocytes, and in the second (meets less often) also in leukocytes and, perhaps, is available in cells of tissue of brain that can cause delay of mental development and mental retardation of nek-ry patients.
The hereditary M-hemoglobinopathy is transferred on autosomal dominantly type and occurs only at heterozygous carriers of abnormal or unstable Hb.
The clinical picture
Degree of manifestation of symptoms depends on quantity of a methemoglobin in blood, the speed of development of M. and compensatory abilities of cardiovascular, respiratory systems and a hemogenesis in the course of adaptation to a hypoxia. At the maintenance of a methemoglobin in blood less than 20% of total quantity of Hb M.'s symptoms usually are absent. At increase in its contents within 20 — 50% there are the general weakness, an indisposition, an asthma at an exercise stress, irritability, easing of memory, headaches and dizziness.
Hereditary Enzimopenicheskaya M. at gomozitotny carriers of genes comes to light in the period of a neonatality and is characterized by the cyanosis of skin and visible mucous membranes especially noticeable in the field of a nasolabial triangle, lobes of ears, a nail bed, an oral cavity. Coloring of skin and visible mucous membranes varies from serozemlisty to dark-violet. Cyanosis (see) amplifies during the overcooling, reception of the nek-ry pharmaceuticals and foodstuff containing nitrates, and at pregnant women at development of toxicosis.
According to M. S. Kushakovsky (1968) and other researchers, patients have changes of a hemodynamics (tachycardia, increases in minute volume of heart) having compensatory character.
Quite often M. is combined with other congenital anomalies (an atresia of a vagina and uterus, an underdevelopment of hands, changes of a shape of a skull, deformation and dysfunction went. - kish. path, thalassemia, deficit of enzyme glyukozo-6-phosphate of a dehydrogenase, etc.).
A venous blood of unusually dark color with a brownish shade, does not redden during the stirring. Changes gemogramma (see) and the morphology of erythrocytes is not noted, however at patients with rather high content of a methemoglobin (more than 20%) the secondary compensatory hyperglobulia (to 6,0 — 7.0 million cells in 1 mkl) with increase in the general maintenance of H b up to 17,0 — 24,0 g of %, increase in viscosity of blood and delay of ROE is observed. The quantity of active Hb is reduced, and even in the presence of a hyperglobulia at patients oxygen insufficiency comes to light. A curve of dissociation of oxyhemoglobin (see. Blood ) sometimes it is shifted to the left. At nek-ry patients are noted an easy reticulocytosis and increase (to 1,5 — 2.0 mg of %) an indirect bilirubin of blood serum that allows to assume existence of insignificant hemolysis; at intensive hemolysis the methemoglobin can be present at urine (see. Metgemoglobinuriya ).
Patients with alpha and chained options of the M-hemoglobinopathy are cyanotic from the moment of the birth, and at p-chained options cyanosis develops from 6-month age. In addition to the expressed cyanosis, other symptoms are not observed.
Hereditary Enzimopenicheskaya M. at heterozygous carriers of genes (before hit in an organism of sulfanamide drugs) proceeds asymptomatically; concentration of a methemoglobin in blood normal or is slightly increased (1 — 2%), activity of a methemoglobin reductase is reduced by 50%.
Toxic M. of an exogenous and endogenous origin proceeds sharply or chronically and on symptomatology reminds hereditary enzimopenichesky M.; it is quite often combined with hemolysis (see).
the Diagnosis is established on the basis of data of the anamnesis (contact with toxic agents or reception of pharmaceuticals), by a wedge, pictures, the analysis of a family tree with definition of a mode of inheritance and a lab. tests. The main lab. tests are: 1) determination of content of a methemoglobin (percentage of total quantity of Hb) a tsianmetgemoglobinovy method; 2) definition of activity OVER + - a dependent methemoglobin reductase in erythrocytes it is made by methods, the general for all dehydrogenases (see. Dehydrogenases ); 3) definition of ranges of absorption of Hb with calculation of the relation of optical density; 4) an electrophoresis of Hb after oxidation of a hemolysate red prussiate of potash; 5) therapeutic test with introduction to the patient methylene blue (integuments and visible mucous membranes quickly turn pink).
Treatment of patients of toxic M. and homozygous carriers of genes from hereditary enzimopenichesky M. with considerable (more than 20%) the maintenance of a methemoglobin to blood and the expressed symptomatology carry out treatment by the specific pharmaceuticals promoting its recovery — ascorbic to - that and methylene blue. Intake ascorbic to - you (on 0,15 — 0,3 g 3 times a day) during the first days reduce concentration of a methemoglobin in blood to 10% of total quantity of Hb. Further pass to maintenance doses (0,05 — 0,1 g 3 times a day) for a long time (2 — 3 months); at the same time it is necessary to do breaks lasting 2 — 4 weeks. Long-term treatment ascorbic to - that in such high doses shall be performed under observation of the doctor with periodic check of function of a pancreas, kidneys and measurement of the ABP.
Methylene blue at intravenous administration renders bystry effect and in 1 hour relative concentration of a methemoglobin in blood decreases to 1% and below. It is applied in the form of the drug «Hromosmon», enter intravenously slowly at the rate of 1 mg on 1 kg of body weight or capsular (100 mg) 3 — 4 times a day. Patients with M-hemoglobinopathies do not need treatment also rezistentna to any therapy.
The forecast and Prevention
the Forecast depends on M.'s type and weight a wedge, manifestations.
Prevention. Medicogenetic consultations are necessary for an exception of a possibility of marriage of heterozygous carriers M. It is necessary to avoid contact with chemical agents — methemoglobin formers both on production, and in life.
The methemoglobinemia at newborns
At healthy newborns contains in blood about 0,5% of a methemoglobin. At newborns M. connected with immaturity of system of the enzymes recovering a methemoglobin (methemoglobin reductases), and which is shown hypersensitivity to methemoglobin formers is more often observed. Such newborns at contact with the diapers marked with aniline dyes, giving well water by it, rich with nitrates, purpose of acetphenetidiene, novocaine and nek-ry other pharmaceuticals have a persistent cyanosis, an asthma that is quite often treated by doctors as display of pneumonia or cardiovascular pathology. In hard cases join jaundice, spasms and the child can die.
Treatment: it is applied hromosmon inside and intravenously (0,1 ml of 1% of solution for 1 kg of body weight), methylene blue, ascorbic to - that.
The forecast improves with age.
Bibliography: Andreyeva A. P., etc. Molecular bases of disturbance of functional properties of hemoglobin at patients with an enzimopenichesky methemoglobinemia, Dokl. Academy of Sciences of the USSR, t. 235, No. 6, page 1441, 1977; Badalyan L. O., Tabolin V. A. and Veltishchev Yu. E. Hereditary diseases at children, page 152, M., 1971; D e r in and z G. V. Hereditary Enzimopenichesky methemoglobinemia, Klin, medical, t. 55, No. 5, page 8, 1977, bibliogr.; Kushakovsky M. S. Clinical forms of damage of hemoglobin, L., 1968, bibliogr.; Muromov A. L. and of l at-hovsky N. Ya. Metgemoglobinemiya in clinical toxicology, in book: Acute poisonings. Diagnosis, clinic and treatment, under the editorship of I. I. Shimangko, page 235, M., 1970; Todorov Y. Clinical laboratory trials in pediatrics, the lane with bolg., page 138, 145, Sofia, 1968; Tokarev Yu. H. Diagnosis and treatment of methemoglobinemias, Rubbed. arkh., t. 51, No. 9, page 79, 1979; Cartwright G. E. Methemoglobinemia, sulfhemoglobinemia, in book: Principles of intern, med., ed. by T. R. Harrison, p. 1310, N. Y. a. o., 1962, bibliogr.; Erslev A. J. a. Gabuzda T. G. Pathophysiology of blood, p. 70, Philadelphia, 1975; The metabolic basis of inherited disease, ed. by J. B. Stanbury a. o., N. Y. a. o., 1972.
BB. H. Tokarev; L. H. Sobenevskaya (ped.).