Methemoglobinemia

METHEMOGLOBINEMIA, the presence of methemoglobin (MtHb) in the blood, is caused by a whole series of toxic substances, which include baryta chloride, hypochlorous salts, nitrates and nitrites, arsine, pyrogallol, hydroquinone, hydrazine and its derivatives, amines and diamines, phenylenediamine, aniline (see), phenacetin, antifebrin, nitrobenzene (see), amyl nitrite, and others. Some of these substances are used as therapeutic agents and, with prolonged use, occasionally lead to chronic poisoning with the development of M. Others (for example, baryta chloride) cause M. upon accidental ingestion or with the intent of suicide. The majority of these substances have significant distribution in the chemical industry and can cause industrial poisoning. The main pathways of entry into the body for these substances are the lungs and the skin. The formation of MtHb is a constant factor in such poisonings, and MtHb is formed intracellularly, in the erythrocytes, and is not usually accompanied by immediate hemolysis. Thus, toxic substances causing M. are not hemolytic poisons in the strict sense of the word; free Hb in the blood plasma is usually not detected; however, erythrocytes become less stable and die faster than under normal conditions. Arsine occupies a special place among the aforementioned toxic substances (see). If the amount of MtHb is large, a sharp cyanosis occurs with severe phenomena up to a comatose state with loss of consciousness. Establishing M. in acute cases is easy by spectroscopic analysis of the blood. In chronic poisoning by poisons forming MtHb, the amount of MtHb is often not large enough to give a characteristic absorption band in the red part of the spectrum; in these cases, morphological examination of the blood is used for diagnosis, in which characteristic changes in erythrocytes are revealed—Heinz bodies.

E. Freyfel'd. MtHb was detected in some cases of eclampsia, during infection with Vas. emphysematosus E. Frankel. The acid MtHb, usually occurring in the body under the influence of poisons and also called neutral MtHb, gives a characteristic narrow absorption band between C and D with an absorption maximum λ = 626 nm. The blood at this time has a brown, chocolate color. Another modification is alkaline MtHb. Its spectrum is distinguished by a broader band at the D line (λ = 589–579) (E. Ziemke). The blood in this type of M. has a bright red color. From a toxicological point of view, these varieties of MtHb have different significance. In particular, M. in the presence of alkaline MtHb is less dangerous, since the latter is easily converted by the organism into Hb. Saturation of the blood with methemoglobin to 66% leads to asphyxial phenomena due to the loss of oxidative capacity by the blood. Methemoglobinemia itself is usually easily tolerated by the organism, and in poisonings with the formation of MtHb, the general action of the taken substance plays a large role. Along with MtHb, hematine is also found in the blood, and therefore some authors have raised the question of whether one should speak of M. at all and whether MtHb is only an intermediate stage in the decomposition of Hb (J. Feigl). The formation of MtHb depends on the concentration and duration of the action of poisons, temperature, the state of the erythrocytes, and the species of animal. When baryta chloride is administered intravenously to cats and dogs in an amount of 0.01 g, a spectrum of MtHb is already obtained. M. is obtained not immediately, but after some time. In rabbits, under normal conditions, it is not possible to obtain MtHb (Robert), although changes in erythrocytes in the form of Heinz bodies are very pronounced. Some poisons, for example potassium ferrocyanide, form MtHb quickly in the blood in vitro, but do not give M. in the organism of animals. This depends on the fact that these poisons act only on the Hb released after the disintegration of erythrocytes, while other poisons forming MtHb, for example baryta chloride, act on the Hb of intact erythrocytes (Kobert); aniline and some other poisonous substances act completely not on the blood pigment in vitro, while in the organism after oxidation in the liver they become active formers of MtHb. In the first hours of poisoning, the blood elements appear unchanged, although a distinct spectrum of MtHb is already obtained. Subsequently, sharp changes in the shape of erythrocytes and their disintegration occur. Heinz bodies appear in the erythrocytes. They are easily detected by vital staining (see Blood, morphological composition of blood and methodology of its study). In erythrocytes, one, rarely 2–3, round bodies are detected, intensely stained in a dark violet color (see Blood, separate color, table, fig. 4). They are obtained quite well sometimes with ordinary staining without fixation in a thick drop. In a fixed preparation, they are perfectly revealed by fixation with 1% osmic acid and staining with acid fuchsin and picric acid. Heinz bodies represent a degeneratively altered part of the erythrocytes. In experiments on animals, it is necessary to take into account that cats normally have a significant number of erythrocytes with Heinz bodies. In fixed blood smears stained by Giemsa or carbol-fuchsin-methylene blue, Heinz bodies are not visible; however, in individual, mainly leached erythrocytes, on a pale background of protoplasm, several small formations, as if spots, intensely stained with eosin, so-called internal Ehrlich bodies are detected. In cases where they are well expressed, the bodies are also an important diagnostic sign (Freyfel'd). One of the consequences of poisoning by poisons forming MtHb in cases where poisoning is accompanied by hemolysis is damage to the kidneys. In the urine, protein, various cylinders, blood pigment, MtHb (methemoglobinuria) and even hematine are found; by the end of the first days, more often on the second, anuria may occur. In such cases, swelling of the liver, spleen, jaundice is also observed. In acute poisonings, MtHb usually persists in the blood only for the first few days. On the third day, sometimes earlier, MtHb can no longer be detected in the blood. With intravenous administration of poisons, MtHb disappears faster from the blood. The disappearance of MtHb from the blood is due to various factors; with hemolysis, MtHb is partly excreted by the kidneys (methemoglobinuria), partly processed in the reticuloendothelial system and in the liver, being excreted with bile, partly decomposed, and the blood serum itself plays a large role in this regard. Crystalline MtHb, introduced into the blood, causes no changes and quickly disappears from the blood (Dietrich). In significantly pronounced M., the following tests can be used for diagnosis: the brown color of the blood caused by the presence of neutral MtHb, upon the addition of a few drops of bitter almond water, quickly turns red due to the formation of cyanmethemoglobin; upon the addition of a drop of soda solution to several drops of brown blood solution, a red color is obtained due to the formation of alkaline MtHb (Robert), z. Morgenstern.