Hemoglobinuria

HEMOGLOBINURIA, HEMOGLOBINEMIA, the appearance of free hemoglobin (Hb) in the urine (or in the blood). Blood Hb, which is closely bound to the erythrocyte stroma, does not circulate in the free state in the blood (according to Hiymans v. d. Bergh, traces of it are present in the plasma under normal conditions) and appears in it as a result of pathological processes that intensively destroy erythrocytes (see Hemolysis in vivo) in the bloodstream (rarely outside of it). This destruction of erythrocytes with subsequent hemoglobinemia is observed 1) during blood transfusion, when the transfused blood undergoes rapid hemolysis in the bloodstream of the person to whom it is transfused, or, conversely, itself rapidly causes the destruction of the erythrocytes of the blood of the latter; 2) upon the introduction into the organism of so-called hemolytic poisons (see); 3) in certain types of anemias (pernicious and hemolytic anemia) and sometimes during pregnancy; 4) in a whole series of infectious diseases (chiefly in malaria, to a lesser extent in sepsis, erysipelas, diphtheria, typhoid fever, scarlet fever, etc.); 5) in so-called paroxysmal hemoglobinuria (see below); 6) in extensive burns of the skin and, finally (rarely), 7) in massive hemorrhages (on the mechanism of the excretion of Hb from the stroma of damaged erythrocytes, see Hemolysis). The blood serum in hemoglobinemia is colored in various shades of red—from pale pink to intense red—and when examined with a spectroscope gives characteristic lines for Hb, oxyhemoglobin, and methemoglobin. The circulating free Hb in the blood is taken up by cells, primarily of the reticuloendothelial system of the liver and spleen, less by lymph nodes, glands, bone marrow, and kidneys, with clinically noticeable swelling of the first two organs sometimes occurring, and is converted in reticuloendothelial cells into bilirubin with subsequent bilirubinemia (see), and in some cases also jaundice. Hemoglobinemia, depending on the number of erythrocytes that have died in a given individual, either passes without noticeable consequences or causes anemia of a certain degree; however, if a very large number of erythrocytes die, hemoglobinemia can even lead to death. As long as the amount of free Hb circulating in the blood does not exceed a certain level (according to Ponfick, Veo the total Hb of the blood of a given individual), it does not penetrate the renal barrier, and it is not possible to find it in the urine. But as soon as this level is exceeded, Hb begins to enter the urine, and hemoglobinuria appears. This term acquired legal status in 1878, after the works of Murri and Lichtheim, who distinguished hemoglobinuria, i.e., the appearance in the urine of free, unbound erythrocyte stroma Hb, from hematuria, in which the appearance in the urine of undissolved erythrocytes is discussed. All factors that give intense hemoglobinemia can also lead to hemoglobinuria. It is necessary, however, to point out that hemoglobin in the urine can also appear in the absence of hemoglobinemia as a result of the dissolution in the urine of erythrocytes both from the blood that has poured into the urinary tract and from those that have penetrated through the kidneys into the urine, i.e., as a result of hematuria. The latter type of hemoglobinuria is called "indirect" by Achard and Saint-Girons, and "false" by Meyer (E. Meyer). The urine in hemoglobinuria has a color from pale pink to intense black. In addition to oxyhemoglobin, a significant amount of methemoglobin can be present in the urine, and sometimes also heme; protein is always present, and sometimes a significant amount of urobilinogen, urobilin, and bilirubin. In the sediment, almost always are lumps and yellow powdery masses of amorphous Hb, rarely whole erythrocytes in small quantities, often hyaline and granular cylinders. Paroxysmal hemoglobinuria. Hemoglobinuria as a main symptom (along with hemoglobinemia) is especially sharply expressed in paroxysmal hemoglobinuria (Garland's disease). Depending on the cause, paroxysmal hemoglobinuria is distinguished resulting from: cooling of the body, muscular work, more or less prolonged walking, etc. The most expressed clinical picture is given by paroxysmal hemoglobinuria on the ground of body cooling. After a slight cooling, sometimes of the whole body or (more often) only of individual parts of the body, among complete health, a chill suddenly appears, a sharp (up to 39-40°) rise in temperature, pains in the region of the kidneys, sometimes in the muscles and joints; vomiting is often observed; at the height of the attack, dark red bloody urine appears, sometimes of dark brown color. The chill usually lasts ¹/2-1 hour, while hemoglobinuria, on average, lasts about a day; the attack ends with a drop in temperature with profuse sweating. The attack can be accompanied by a slight yellowish coloration of the mucous membranes, noticeable enlargement of the liver and spleen, and as a result of the attack, anemia of varying intensity. In the urine, in addition to the above-mentioned peculiarities, protein is determined, often in quantities larger than corresponds to the content of blood in the urine. In the blood—Hb, a greater or lesser drop in the number of erythrocytes, on the side of white blood—lymphopenia, hyper-eosinophilia; increased coagulability. Attacks can be very strong and frequent (up to several times a week; especially they become more frequent in winter); along with this, abortive cases with a mild chill, without noticeable rise in temperature, with pulling pains in the extremities and only traces of Hb in the urine are also observed. The etiology of paroxysmal hemoglobinuria has not yet been established with certainty. It should be noted that in the anamnesis of patients with paroxysmal hemoglobinuria, there are almost always indications of syphilis; RW is positive in the vast majority of cases. Cases of hereditary paroxysmal hemoglobinuria in syphilitics have been described (Matsuo). During an attack, hemolysis occurs in the bloodstream, in particular—local hemolysis in the cooled part of the body (Ehrlich); the onset of the attack is connected with the appearance in the blood of a hemolytic amboceptor, first found in the blood of patients with paroxysmal hemoglobinuria by Donath and Landsteiner in 1904. This amboceptor, forming (only in the cold—in the part of the body subjected to cooling) in the blood of a patient with paroxysmal hemoglobinuria, combines with erythrocytes and, in the presence of complement (the latter, C1q, is known to be present in the serum not only of persons with paroxysmal hemoglobinuria, but also of healthy people), causes hemolysis (serum containing a hemolytic amboceptor hemolyzes erythrocytes not only of its own, but also of foreign blood). This amboceptor can sometimes be found in the serum of persons not suffering from paroxysmal hemoglobinuria, but having tabes, progressive paralysis, or cerebrospinal syphilis. This last fact forces one to think that, in addition to the presence in the blood of a patient of a hemolytic amboceptor, there must be some other moment necessary for the onset of the attack. Some authors consider this additional factor to be an imbalance of the vascular-nervous system and an unusually strong reaction to the action of cold, to which there are indeed indications in the anamnesis of many (but not all) patients with paroxysmal hemoglobinuria. The therapy of paroxysmal hemoglobinuria arising in connection with body cooling consists, first and foremost, in eliminating the factors leading to this cooling; in this way it is often possible to achieve the cessation of attacks. Antisyphilitic treatment does not give clear results, and paroxysmal hemoglobinuria can remain even after the disappearance of RW as a result of this treatment. A marked weakening of the intensity of attacks was obtained by Pringsheim after repeated intramuscular injections of 0.5 cholesterol in a physiological salt solution; repeated intravenous injections of the patient's own serum give controversial results. Of other types of paroxysmal hemoglobinuria, those that occur after muscular work, more or less prolonged walking, rowing, are encountered more often; those after horseback riding and cycling are less frequent, and they are caused by a disturbance of renal circulation on the ground of lumbar lordosis. In these cases, attacks proceed without significant disturbance of the general condition of the patients (in particular, without fever). It should also be noted the sometimes observed paroxysmal appearance of Hb in the urine of some patients with anemia of the primary type and of pregnant women. The etiology and pathogenesis of these cases are not sufficiently clear; apparently, toxic factors played a role in the development of the attack in these cases. Hemoglobinuria associated with malaria deserves special attention, the so-called febris biliosa haemoglobinu-rica ("Schwarzwasserfieber"), see Hemoglobinuria fever.