Hemolytic Jaundice

HEMOLYTIC JAUNDICE, a defined disease, in which two forms are distinguished: hereditary (Minkowski, 1900) and acquired (Chauffard, 1897-99). From this disease, which can also be called idiopathic H. j., one should distinguish jaundices that are a consequence of increased hemolysis in various diseases (see below), sometimes designated as secondary H. j. Hereditary H. j. is a disease affecting members of one family and transmitted from one generation to another. Its main manifestations are: on the one hand, increased breakdown of red blood cells, causing jaundice distinguished by the absence of signs of retention of bile acids in the body (itching, bradycardia); on the other hand, changes in erythrocytes are observed: decrease in their diameter, with a shape approaching spherical (pseudomicrocytosis), and reduction of their osmotic stability. The acquired form differs from the familial form only in the absence of data on heredity of the disease. Usually in acquired H. j., the etiology cannot be established, and some authors consider such cryptogenetic cases of H. j. as the first manifestation of "mutation in the family," i.e., also attribute them to genotypic, denying the existence of the acquired form altogether. Secondary acquired H. j., accompanying, for example, lobar pneumonia, malaria, tbc, syphilis, are also caused by increased breakdown of blood, but such H. j., accompanying these and other infectious diseases, differs from idiopathic H. j. in that it does not present typical changes in erythrocytes. Regarding the frequency of familial H. j., there is disagreement, apparently depending on the uneven geographical distribution of the disease; for example, Meulengracht observed 50 cases of H. j. over 3-4 years, Eppinger over several years - only 3 cases. In particular in the USSR, the disease H. j. occurs quite rarely; there are no exact data on the frequency of H. j. in the USSR. Patho-anatomical changes in H. j. are uniform. The spleen is enlarged, hyperemic, its pulp is filled with erythrocytes, while the number of the latter in the sinuses is small. According to Eppinger, the iron content in the spleen is increased. All authors note significant deposition of iron in the kidneys, bone marrow, and liver. In the liver, in addition, are determined: proliferation and increase of Kupffer cells phagocytosing erythrocytes and their fragments in large quantities, dilation of bile capillaries, thrombi in them and in places ruptures of their walls (Eppinger). In the bone marrow - phenomena of intensified erythropoiesis. Hemochromatosis of the organs, just mentioned phenomena on the part of Kupffer cells, as well as clinical data (increase of the indirect diazo reaction by Hymans v. d. Bergh of bilirubin in the serum, increase of urobilinogen content in excretions up to 3,000 mg per day instead of normal 120 mg, richness of the contents of the duodenum with pigments) reveal the hemolytic nature of the disease. The question of the cause of increased blood breakdown is controversial. According to one hypothesis, it depends on hyperfunction of the spleen in the sense of its secretion into the circulating blood of hemolysins or in the sense of increased erythrophagocytosis in the spleen (Minkowski, Eppinger, Meulengracht, Banti and others). In favor of this theory is the finding of free hemolysins in the blood of patients and the beneficial effect of splenectomy. However, changes in erythrocytes, microcytosis with change in shape and reduction of osmotic stability remain (at least partly) even after splenectomy; this corresponds more to the concept of primary (constitutional) insufficiency of the bone marrow in the sense of production of erythrocytes with reduced stability, and therefore subject to increased breakdown (Naegeli). Proponents of this viewpoint emphasize that patients with congenital hemolytic jaundice, as well as members of their families, often present other congenital degenerative signs (anomalies of skull structure-"Turmschädel", eyes, ears, skin, etc.). In addition, H. j. is often combined with diseases of metabolism, internal secretion organs, and mental diseases. Two substantial objections raised against the theory of primary damage to erythrocytes as the cause of H. j. are: 1) absence (it is true, in rare cases) of reduction of osmotic stability and 2) gradual disappearance (also in individual cases) of the peculiarities of erythrocytes characteristic of H. j. after splenectomy. The pathogenesis of jaundice itself is not entirely clear from the standpoint of the former concept of production of bile pigment by liver cells. One thought of thickening of bile due to its richness in pigments and of the difficulty of its excretion through small-caliber hepatic ducts caused by this thickening. Thickening of bile (pleiochromia) in hemolytic jaundice does indeed occur. If one takes the standpoint of the new concept, according to which bilirubin is produced in reticulo-endothelial cells of bone marrow, spleen, liver, and lymph glands, and only excreted from the blood into bile by liver cells, then jaundice in H. j. can be conceived as a manifestation of insufficiency of liver cells in the sense of excretion of an excessively increased amount of bilirubin formed during intensified breakdown of erythrocytes. The course of the disease is varied. The first signs of the disease can be observed already from the day of birth, but more often appear later. In some cases, patients feel healthy, and only slight yellowness, increased bilirubin content in the serum, increased amount of urobilin in excretions, in the absence of bile acids and bilirubin in urine, reduction of osmotic stability of erythrocytes and their pseudomicrocytosis make diagnosis possible. In almost all cases, enlargement of the spleen is observed, greatly predominating over enlargement of the liver. The function of the latter in regard to carbohydrate and nitrogen metabolism is not disturbed. The composition of the blood depends on the regenerative capacity of the bone marrow. Anemia is more often observed, but sometimes, conversely, even polycythemia (hypercompensation). The number of reticulocytes is particularly sharply increased (sometimes up to 30-50% instead of normal 0.1-0.3%), which speaks of extremely intensified regeneration of red blood cells. In cases of anemia, the color index = 1 or somewhat higher. The white blood presents nothing characteristic. The number of white blood cells is usually normal, sometimes somewhat increased. The number of platelets is normal. In most cases, the disease proceeds with remissions and exacerbations. Exacerbations are observed under the influence of psychic trauma, excessive physical exertion, pregnancy, menstruation, infections, intoxications, sharp changes in external temperature. During exacerbation, sometimes a severe general condition with temperature elevation and development of severe anemia accompanied by shortness of breath, dilation of the heart, appearance of edemas is observed. Often H. j. is accompanied by attacks of gallstone disease, since due to the richness of bile in pigments, stones easily form in it. But often attacks similar to colic in gallstone disease are observed in H. jaundice without the presence of stones; perhaps they depend on the difficulty of emptying it caused by thickening of bile. The prognosis in most cases is favorable, but individual cases of death from H. j. with the picture of severe anemia have been described. Of therapeutic measures, only splenectomy gives definitely favorable results. In most cases after removal of the spleen, blood breakdown returns to normal, jaundice disappears, the amount of Hb and erythrocytes rapidly increases. Proponents of the theory of primary spleen damage consider splenectomy causal therapy; from the standpoint of primary erythrocyte damage, splenectomy is only symptomatic therapy, which, however, does not diminish its importance: the spleen is one of the main organs of hemolysis, and with its removal, the latter, regardless of the cause that caused its increase, will decrease. A direct indication for splenectomy is the development of anemia. The percentage of postoperative mortality is small: Mayo (Mayo, 1924) in 54 cases of splenectomy had 3 cases ending in death, in 51 cases - complete recovery; Eppinger out of 11 splenectomies in seven obtained a good result, no fatal cases directly from the operation itself - 0. (for more details - see Spleen - splenectomy). Difficulties in the operation are sometimes presented by the presence of perisplenitis giving abundant adhesions. Sometimes after splenectomy recurrences of the disease are observed, which apparently depends on the compensatory hyperfunction of the remaining part of the reticulo-endothelial apparatus. Attempts to reduce hemolysis in hemolytic jaundice by blocking the reticulo-endothelial system with colloidal silver and iron were fruitless. The same applies to irradiation of the spleen with X-rays. Systematic treatment of anemia with arsenic, as well as with iron, according to some authors, is beneficial.