Signs characteristic of the defeat of the hematopoietic system. Diseases of the blood and blood-forming organs
anemia
Anemia, or anemia, is a condition characterized by a decrease in the number of red blood cells and a decrease in hemoglobin content per unit volume of blood. In some cases, with anemia, qualitative changes in erythrocytes are also detected.
With anemia as a result of a violation of the transport function develop hypoxic phenomena, the signs of which are shortness of breath, tachycardia, discomfort in the region of the heart, dizziness, weakness, fatigue, pallor of the skin and visible mucous membranes. The severity of these symptoms depends on the degree of anemia and the speed of its development. With deep anemia, along with the indicated symptoms, there are also visual impairment.
By color index anemias are divided into hypochromic, normochromic and hyperchromic. According to the size of the average diameter of erythrocytes, anemias are divided into microcytic, normocytic and macrocytic. According to the nature of regeneration, anemias are regenerative, hyporegenerative, hypo- and aplastic, dysplastic or dyserythropoietic.
Currently generally accepted classification, built according to the pathogenetic principle, taking into account the etiological and most important clinical and morphological forms, is the classification proposed by G. A. Alekseev (1970).
I. Anemia due to blood loss (posthemorrhagic).
II. anemia due to impaired circulation:
A. Iron deficiency anemia ("chloranemia").
B. Iron-saturated, sideroahrestic anemia.
B. B12 (folic)-deficient, "pernicious" anemia:
1. Exogenous deficiency of vitamin B12 (folic acid).
2. Endogenous deficiency of vitamin B12 (folic acid):
a) impaired assimilation of food vitamin B12 due to loss of gastric mucoprotein secretion;
b) impaired assimilation of vitamin B12 (folic acid) in the intestine;
c) increased consumption of vitamin B12 (folic acid).
D. B12 (folic) - "achrestic" anemia.
D. Hypoaplastic anemias:
1. Due to the influence of exogenous factors.
2. Due to endogenous aplasia bone marrow.
E. Metaplastic anemias.
III. Anemia due to increased hemorrhage (hemolytic):
A. Anemia due to exoerythrocyte hemolytic factors.
B. Anemia due to endoerythrocyte factors:
1. Erythrocytopathies.
2. Enzymopenia:
a) deficiency of glucose-6-phosphate dehydrogenase;
b) deficiency of pyruvate kinase;
c) deficiency of glutathione reductase.
3. Hemoglobinopathies.
The characteristic features of individual forms of anemia, in which eye symptoms are most common, are described below.
Acute posthemorrhagic anemia develops as a result of acute single and repeated blood loss from injuries, bleeding from the gastrointestinal tract, with ectopic pregnancy, uterine bleeding, etc. The symptoms of the disease are pathogenetically associated with a decrease in the mass of circulating blood and oxygen deficiency. The clinical picture in the first moments after massive blood loss fits into the clinic of post-hemorrhagic shock or collapse: pallor of the skin, fainting, dizziness, cold sweat, frequent thready pulse, sometimes vomiting, convulsions. In the future, as the improvement general condition and stabilization blood pressure symptoms of anemia and hypoxia begin to predominate in the clinical picture. It is during this period that signs of visual impairment up to complete amaurosis are most often detected, since specific elements of the retina are very sensitive to anemia.
With chronic hypochromic iron deficiency anemia, including early and late chlorosis, symptomatic iron deficiency anemia (chronic enteritis, agastric chloranemia, hernia esophageal opening diaphragm, malignant neoplasms, chronic infections), as well as chronically occurring hypochromic megaloblastic anemia (pernicious anemia various genesis- Addison-Birmer anemia, helminthic, spruanemia, celiac disease, etc.) the severity of eye symptoms depends on the degree of anemia, which, however, varies widely individually. Especially often changes in the fundus occur when the hemoglobin concentration is below 5 g% and less often 7 g%.
Ocular fundus looks pale when anemic. This symptom cannot always be assessed due to differences in pigmentation of the retina and choroid. Decoloration of the optic disc and retinal vessels is more easily detected. Wherein arterial vessels tend to expand and approach similar venous branches in caliber. Multiple hemorrhages into the retina - the most characteristic symptom of retinopathy in anemia (Fig. 34).
Rice. 34. The fundus of the eye in pernicious anemia.
The cause of the hemorrhage is not entirely clear. Apparently lack of oxygen causes increased capillary permeability. With pernicious anemia, concomitant thrombocytopenia is also important.
Banded or flame shaped hemorrhages are located in layer nerve fibers. They can be localized in any part of the retina, but they are not in yellow spot. Therefore, visual acuity is usually preserved. Sometimes a white center is seen in the extravasations. This symptom is more common in pernicious anemia. In some cases, ischemia can cause swelling of the optic disc and the adjacent retina. The edema is usually mild, but cases of congestive disc have also been described. In addition to swelling in the layer of nerve fibers, there may be small white foci, which consist of fibrin and usually dissolve well when the patient's condition improves.
Significantly more heavy changes retinas are seen sickle cell (drepanocytic) anemia. This disease refers to hereditary-familial hemolytic anemia, a characteristic feature of which is the property of erythrocytes to take a crescent shape - this disease affects mainly blacks and rarely whites. Isolated cases are described in the Soviet Union.
The disease belongs to the group hemoglobinopathies with congenital inferiority of erythrocytes, in particular with the presence of pathological globulin in them.
The disease manifests itself in childhood and is characterized chronic course with frequent exacerbations in the form of hemolytic regenerating, thrombotic and sequestral crises.
For hemolytic crises the content of erythrocytes can decrease to 1-2 million in 1 mm3 of blood for a short period. The crisis is accompanied by the development of jaundice and abdominal syndrome. Regenerative crises are a temporary, functional depletion of bone marrow hematopoiesis. Thrombotic or pain crises, which sometimes dominate the manifestations of the disease, occur on the basis of generalized thrombosis of small vessels, especially the abdominal cavity and extremities. Sequestration crises are states resembling shock with sudden development anemia without hemolysis [Tokarev Yu. N., 1966].
As with other congenital hemolytic anemias, sick sickle cell anemia infantile, suffer from hypogonadism, have a towering skull, etc. In this disease, the osteoarticular syndrome is especially pronounced (dactylitis, pain, deformities, necrosis of the articular heads and bones). On the shins often develop chronic ulcers. The spleen and liver are enlarged. Thrombosis and embolism are a very characteristic feature. Retinal lesions are localized mainly in the equatorial and peripheral zones and go through 5 stages. Stage I is characterized by peripheral arteriolar obstruction, stage II - by the appearance of arteriovenous anastomoses. In stage III, neovascular and fibrous proliferation develops, which leads to hemorrhages in stage IV. vitreous body. Ultimately (stage V) retinal detachment develops.
Leukemia
By leukemia is meant neoplastic diseases, the tumor mass of which consists of blood cells or, apparently, more precisely, of cells similar in appearance to blood cells.
Some scientists blood tumors are classified on hemoblastomas and hematosarcomas on the basis that in some cases the bone marrow can be ubiquitously populated by these tumor cells, and in other cases their growth is extramedullary. In our opinion, such a subdivision is often very difficult to implement, since tumor growths of leukemic cells can also have extramedullary localization in patients in whom the disease began with bone marrow damage. And, conversely, in some cases, hematosarcomas may subsequently involve the bone marrow in the process, and clinicians are forced in these cases to talk about leukemization of the process. In our opinion, it is more correct to combine all tumors of the hematopoietic tissue under the name "leukemia", since the neoplastic nature of these diseases, emphasized in the names "hemoblastosis" or "hematosarcomatosis", is practically beyond doubt.
Etiology of leukemia cannot be considered definitively clarified, which applies, however, to other tumors equally. However, at present it can be considered established that such factors as a virus, ionizing radiation, certain chemical substances, including some medicinal substances such as levomycetin, butadione and cytostatics, can have a certain stimulating effect on the occurrence of these diseases. About the role hereditary factors in the occurrence of leukemia, there are also well-founded opinions. They are confirmed by cases of the same type of leukemia in identical twins, a high susceptibility to the development of leukemia in patients with hereditary disorders genetic apparatus - Down's disease, Turner's syndromes, .. Klinefelter, etc. It was noted that certain types of leukemia tend to be combined with certain types genetic disorders. It must be borne in mind that modern scientific data are very convincing in favor of the previously put forward assumption about the origin of the entire leukemic mass from one mutated cell that has gone out of control of the patient's body. These are the presence of a ring chromosome in tumor cells of patients with acute leukemia that developed in persons treated with radioactive phosphorus, a sharp increase in the content of a protein of the same type in terms of physicochemical properties in patients with paraproteinemic hemoblastoses. Philadelphia chromosome in patients with chronic myeloid leukemia.
In clinical practice leukemias are usually subdivided depending on the type of cell that forms the basis of the tumor mass. Those leukemias that occur with the proliferation of cells that are poorly differentiated and not capable of further differentiation are usually very malignant without treatment and are called acute. Leukemias, the tumor mass of which is made up of differentiating and mature cells, usually have a relatively benign course and are called chronic leukemia.
Acute and chronic leukemias in turn, they are subdivided depending on which cell makes up the tumor substrate. Currently, leukemias are described that develop from cells of all hematopoietic germs - erythroid, platelet,. granulocytic and agranulocytic type. At the same time, acute leukemias of myelo-, mono-, megakaryo-, erythro- and plasmablastic types are distinguished. Since the differentiation of acute leukemia is carried out only on the basis of cytochemical methods of research, and cytochemical methods for identifying cells are carried out using an empirically selected set of methods, there have been reports of the existence of such a form of acute leukemia as undifferentiated. The origin of the latter, apparently, can be attributed to the proliferation of cells derived from earlier, undifferentiated hematopoietic cells. Among chronic leukemias, forms of leukemias, which are based on the proliferation of any mature blood cell, have been identified and continue to be distinguished. Here and chronic lymphocytic leukemia, chronic myeloid leukemia, chronic monocytic leukemia, chronic megakaryocytic leukemia, erythromyelosis, erythremia, plasmacytoma, chronic basophilic cell leukemia; there are also reports of the presence of chronic eosinophilic leukemia.
At modern level medical science, which makes it possible to distinguish the finest details of cells, divisions are made within the framework of supposedly long-established forms of leukemia. Thus, among the group of patients with chronic lymphocytic leukemia at present, groups of persons suffering from the proliferation of both T- and B-lymphocytes are already distinguished, and among patients chronic myeloid leukemia distinguish between groups with proliferation of cells that have the Philadelphia chromosome and do not have it. It is possible that the identification of leukemias will continue in the future, and this will allow more specific and more effective treatment of patients.
Based on the above, it is quite easy to talk about the diagnosis of both the leukemia itself and its specific form. Diagnosis of this disease carried out when ascertaining hyperplasia of the hematopoietic tissue, which can occur both in peripheral blood and in the bone marrow. At the same time, in some individuals, hyperplasia of leukemic cells occurs only in the bone marrow, and in the peripheral blood, these cells appear only at later stages of the disease. In this regard, studies of bone marrow hematopoiesis using the analysis of sternal punctate data, and sometimes the structure of bone tissue using trepanobiopsy, should be carried out in the diagnostic process. The use of cytochemical and cytogenetic research methods usually leads only to clarifying the variant of leukemia.
Possibility of existence leukemoid reactions, i.e., such growths of hematopoietic tissue that occur in response to the presence in the patient's body of some factor that activates hematopoiesis, sometimes makes it necessary to conduct special studies that exclude the presence of these causes of hematopoietic tissue hyperplasia.
Clinical picture leukemia is very diverse. At the same time, a variety of clinical manifestations is present in a patient with both acute and chronic leukemia. predict further clinical course, the clinical manifestations of leukemia in an individual patient, apparently, will not be resolved by any experienced clinician. It is practically impossible to do this due to the fact that high morphodynamics and the almost ubiquitous possible spread of leukemic tissue in the patient's body can demonstrate the most diverse symptoms, simulating, especially in initial stages, diseases of various kinds. An example of this is the work of one of the founders of Russian hematology, Acad. I. A. Kassirsky, who, together with his colleagues, when analyzing the primary diagnoses with which patients were admitted to the clinic and in whom acute leukemia was subsequently verified, discovered more than 60 different nosological forms, including sepsis, stomach cancer, rheumatism and acute intestinal obstruction, myocardial infarction, rheumatoid arthritis, acute meningitis and many other diseases.
At the same time, one can talk about the clinic of leukemia and quite simply due to the fact that all the clinical manifestations of these diseases can be combined and understood on the basis of the recognition of the main syndromes, which usually occur in the clinical picture with one or another predominance depending on the type of leukemia. diseases. Among these syndromes the most common are the following: 1) general toxic syndrome (or intoxication); its manifestation is fever, weakness, sweating, weight loss, lack of appetite, etc.; 2) hemorrhagic syndrome. Its manifestations are extremely diverse, including menorrhagia, skin hemorrhages and hemorrhages in the brain; 3) syndrome of toxic-necrotic lesions of the mucous membranes of the gastrointestinal tract; 4) anemic syndrome; 5) tumor growth syndrome, characterized by the growth of leukemic tissue in the body. This should also include an increase in the lymph nodes, liver, spleen, dysfunction of internal organs due to their compression or violation of the integrity of the growing leukemic tissue.
In addition to the manifestations of these syndromes, characteristic of all leukemias, certain types of leukemias, in particular paraproteinemic hemoblastoses(plasmocytoma, Waldenström's disease, heavy and light chain diseases), erythremia, have a number of features in the clinical picture, which will be described in separate sections. A special coloring of the clinical picture of leukemia (lymphatic type) can sometimes be given autoimmune reactions manifested by hemolytic anemia, fever, skin changes, etc.
Not stopping at external manifestations of each of the syndromes listed above, I would like to note that in recent years, manifestations have begun to be noted in the clinical picture of leukemia, which can be explained as cytostatic therapy and lengthening the life span of patients with this pathology. These include an increase in infectious complications, which are the cause of death in almost 40% of patients with chronic lymphocytic leukemia, an increase in neurological symptoms (especially in patients with acute leukemia, called goat neuroleukemia), as well as the frequent development of uric acid nephropathy in patients with leukemia with symptoms of nephrolithiasis.
Thus, the clinic of leukemia can be characterized by the most varied symptoms, which is a consequence of a diverse combination of the above syndromes. Of course, with certain types of leukemia, one can note the predominance of one or another syndrome from those listed above, however, no clinician can underestimate the possibility of including any of them in the clinical picture for any type of leukemia.
Speaking of leukemia, one cannot but mention the great progress that has been made by modern medicine in the treatment of these diseases. After all, it is with this type of tumors that results have been obtained that allow us to talk about a fundamental cure for a person from a malignant neoplastic disease. The cure of patients with acute lymphoblastic leukemia, lymphogranulomatosis allows us to hope that these successes will extend to the treatment of other forms of leukemia.
Acute and chronic forms of leukemia are accompanied by the same eye manifestations caused by increased blood viscosity, hypoxia and leukemic tissue infiltration. These changes include the formation of microaneurysms in retinal vessels, hemorrhages, and cellular infiltration of the choroid, retina, optic nerve, and periorbital structures. Infiltration of the meninges can lead to paralysis of the extraocular muscles and the development of a congestive disc. Also described is infiltration of the eyelids, conjunctiva, orbital tissue with the development of exophthalmos.
Ophthalmoscopy reveals pale fundus background. The retinal veins are dilated, tortuous, and whitish streaks are often seen in the retina along their course, representing perivascular leukemic infiltration. Arteries are much less changed than veins.
The size and shape of hemorrhages varies. They can be deep, superficial or even preretinal. It is not uncommon to see a white area in the center of a retinal hemorrhage caused by the accumulation of leukocytes. In the most severe cases, ischemic cotton-wool lesions appear in the layer of nerve fibers, marked edema of the optic disc and peripapillary retina, and newly formed retinal vessels.
Changes in the fundus in leukemia occur in about 70% of cases, especially often in acute forms. The severity of the changes more or less correlates with the severity of the disease, and effective treatment the underlying disease improves and the condition of the fundus.
Polycythemia
The term "polycythemia" includes group of diseases, which are manifested by an increase in the mass of red blood cells in the body, i.e., an increase in their volume per 1 kg of body weight. The number of erythrocytes in 1 mm3 of blood with polycythemia rises to 7-10 million, and the hemoglobin content up to 180-240 g/l. There are "true" polycythemia (erythremia, Wakez's disease) and secondary (symptomatic) erythrocytosis.
erythremia- primary myeloproliferative disease of the hematopoietic system, which is based on total hyperplasia of the cellular elements of the bone marrow, especially its visual germ. Therefore, an increased content of leukocytes (up to 9000-15,000 million per 1 mm3 of blood) and platelets (up to 1 million or more) in the blood, along with a more noticeable increase in the number of erythrocytes, is a very characteristic sign of erythremia. G. F. Stroebe (1951) identified three hematological variants of erythremia: 1) without a significant increase in the number of leukocytes and Changes in the blood count; 2) with moderate leukocytosis, neutrophilia and stab shift; 3) with high leukocytosis, neutrophilia and a shift in the blood count to myelocytes. With "true" polycythemia, signs of myelofibrosis and osteomyelosclerosis with myeloid metaplasia of the spleen are found. As with other myeloproliferative diseases, in the blood serum of patients with polycythemia, an increase in the concentration of alkaline phosphatase, uric acid and vitamin B12. The clinical picture of polycythemia vera varies depending on the phase of the disease and the severity of the course.
In the advanced, actually erythremic phase of the disease characteristic symptoms are: 1) discoloration of the skin and visible mucous membranes; 2) enlargement of the spleen and liver; 3) increased blood pressure; 4) thrombosis and hemorrhage.
The skin is changed in the vast majority of patients. They acquire a red-cyanotic hue. The coloration of the cheeks, tips of the ears, lips and palms changes especially clearly. We emphasize that the color of the skin is dominated by a red tone, but not bright, but cherry. The visible mucous membranes of the lips, tongue and soft palate acquire a similar shade. Vessels of the sclera are visibly injected (rabbit eye symptom). On the cheeks, lips, tip of the nose, especially in women, telangiectasias are often found.
Very characteristic symptom erythremia is splenomegaly, which is associated with its myeloma metaplasia and increased blood supply. Patients with polycythemia vera usually enlarged and liver. An increase in its size is also associated with increased blood supply, myeloid metaplasia, growth connective tissue up to the development of cirrhosis or thrombosis of intrahepatic veins (Budd-Chiari syndrome). In a number of patients, the course of the disease is complicated by the development of cholelithiasis and chronic cholecystohepatitis. The bile plenochromia characteristic of patients with erythremia leads to the development of these complications.
Nearly half of patients with erythremia hypertension is detected, the pathogenesis of which is considered in terms of a compensatory reaction of the body in response to a decrease in stroke and minute blood volume, an increase in its viscosity and an increase in peripheral resistance (A. V. Demidova, E. M. Shcherbak). The combination of high blood pressure with an enlarged spleen is a cardinal sign of polycythemia vera. If at the same time the mass of erythrocytes increases in the patient, then the diagnosis of polycythemia becomes undeniable.
Characterized by a paradoxical susceptibility of patients with polycythemia and thrombosis (large arterial and venous vessels of the brain, heart, liver and spleen, small vessels of the hands and feet) and increased bleeding (from stomach and duodenal ulcers, after extraction of teeth, skin hemorrhages and bleeding from mucous membranes). The cause of bleeding in true polycythemia is an increase in the mass of circulating blood with overflow of blood vessels and paretic expansion of capillaries, as well as a deficiency of plasma coagulation factors, in particular fibrinogen [Machabeli M. S., 1962], serotonin [Matveenko JI. A., 1965].
The development of thrombosis in erythremia associated with an increase in blood viscosity, a slowdown in blood flow, an increase in the number of platelets and erythrocytes, with a sclerotic lesion of the walls of blood vessels, and a general hypercoagulability of the blood.
In patients with erythremia, the kidneys are often affected (infarcts develop in them due to vascular thrombosis or nephrolithiasis as a result of a violation of purine metabolism, which is characteristic of myeloproliferative diseases).
True polycythemia characterized by long duration which can be mild, moderate or severe. In the development of the disease, three periods, or phases, are distinguished. The first phase of the disease for a long period may be latent or with mild clinical symptoms. In the early stages, the disease is often mistaken for hypertension.
The clinical picture described above characterizes the expanded second, so-called erythremic phase. And in this phase, the course of the disease can be varied.
The terminal phase is characterized by the development of secondary lshelofibrosis with anemia and the disappearance of external signs of erythremia or the development of acute hemocytoblastosis, less often reticulosis.
Unlike true polycythemia, secondary erythrocytosis are not independent nosological units, but only symptoms of other diseases. An increase in the number of red blood cells and hemoglobin is not associated with a proliferative process in the bone marrow, but with its functional irritation (absolute erythrocytosis) or with thickening of the blood without increasing erythropoiesis (relative erythrocytosis). The classification below shows the main types of secondary erythrocytosis, their course options, the main pathogenetic mechanisms underlying their development, and specific diseases accompanied by the development of secondary erythrocytosis.
The most conspicuous symptom of polycythemia is plethora of the face and conjunctiva. Conjunctival and episcleral vessels, especially veins, are dilated, tortuous, deep red. The vessels of the retina have the same appearance (Fig. 35).
Rice. 35. The fundus of the eye in polycythemia.
Attracts attention dark red color of the fundus. The optic disc is also unusually red. It is often possible to see more or less pronounced edema of the optic disc and peripapillary retina and single hemorrhages.
In some cases it develops occlusion central vein retina. The occlusion appears to be incomplete. The prognosis in such cases is usually favorable, in any case, much better than with occlusion of the central retinal vein of another etiology.
Paraproteinemia
This group of diseases primarily includes myeloma(plasma cell paraproteinemic reticulosis or Rusticki's disease) and macroglobulin reticulolymphomatosis(Waldenström's disease, or macroglobulinemic purpura).
multiple myeloma is a systemic blood disease of the tumor-hyperplastic type with malignant proliferation of cells of the reticuloplasmic type. This is leukemia-reticulosis, in particular, plasma cell para- (or patho-) proteinemic reticulosis.
Depending on the predominant cell type, three types of myeloma: 1) reticuloplasmocytoma, 2) plasmablastoma and 3) plasmacytoma.
Proteinuria- a very common symptom of multiple myeloma. As a rule, a micromolecular protein (Bence-Jones protein) is excreted in the urine. Proteinuria is associated with the development of myeloma nephropathy - paraproteinemic nephrosis, usually ending in death with symptoms of azotemia uremia.
With a high concentration of protein in the blood is associated and characteristic of multiple myeloma high blood viscosity.
Waldenström's disease currently considered as macroglobulin reticulolymphomatosis, a characteristic feature of which is the ability synthesize macroglobulins: globulins with a molecular weight of more than 1,000,000 appear in the blood. The elderly are predominantly ill. In clinical practice, hemorrhagic syndrome predominates, sometimes with extremely heavy nosebleeds. The mechanism of hemorrhagic syndrome is complex and not fully understood. It is believed that it is associated, on the one hand, with the inferiority of platelets interacting with macroglobulins, and on the other hand, with increased permeability of the walls of blood vessels due to their infiltration with pathological proteins, high blood viscosity and intravascular agglutination of erythrocytes.
Allocate mainly skeletal forms and skeletal-visceral forms of the disease. In pathogenetic terms, the clinical picture of the disease is reduced to two syndromes, namely, bone damage and pathology of blood proteins. Bone damage is manifested by pain, fractures and the development of tumors. The spine, pelvic bones, ribs and skull are especially often affected with the development of appropriate neurological symptoms.
Visceral pathology manifests itself mainly affecting the liver, spleen, lymph nodes and kidneys. Its development is associated both with specific cellular infiltration of these organs, and with pronounced changes in blood proteins, with the accumulation in the blood of an abnormal protein - a paraprotein produced by myeloma cells. With myeloma, proteinemia can reach 12-18 g%.
retinopathy in the initial forms of multiple myeloma and Waldenström's disease is absent. In a number of patients, the fundus of the eye is a kind of picture of the fundus paraproteinemicus. Characterized by the expansion of the retinal veins and an increase in their tortuosity. The arteries also dilate, but to a much lesser extent. Then the symptom of decussation (squeezing of the vein under the artery), microaneurysms, occlusion of small veins, hemorrhages into the retina appear. In some cases, there are also cotton-like foci in the layer of nerve fibers of the retina and swelling of the optic nerve head.
It is believed that the changes in the retina are associated both with hyperparaproteinemia and with high blood viscosity. In the azotemic stage of the disease, retinopathy, which is characteristic of chronic kidney diseases, develops.
As for changes in retinal vessels, their relationship with increased blood plasma viscosity has been experimentally demonstrated. After the introduction of dextran with a high relative mass into the blood of monkeys, dilated and tortuous retinal vessels, especially veins, microaneurysms and hemorrhages, were detected in the fundus.
Myeloma can affect also the bones of the orbit, eyelids, lacrimal gland, lacrimal sac and conjunctiva, infiltrate the sclera, iris, choroid, retina and optic nerve. These lesions, however, are not associated with increased blood viscosity.
Hemorrhagic diathesis
Hemorrhagic diathesis refers to such pathological conditions, which appear in increased bleeding in the absence of significant damage to the vascular wall, i.e., bleeding develops in situations where other healthy people in this regard do not have them.
Importance of the problem hemorrhagic diathesis is very high. Firstly, this is due to the fact that the number of people suffering from increased bleeding in the world has exceeded the six-figure figure. Secondly, people suffering from hemorrhagic diathesis cannot be considered full-fledged members of society, since their potential capabilities are sharply limited both by anemia, which often accompanies this pathology, and by those activities that protect the patient's vessels from various damages.
Thirdly, the importance of information about the presence of hemorrhagic diathesis in patients is determined by the fact that many forms of this suffering are hidden or manifest weakly, having a monosymptomatic clinic. If needed surgical interventions, even such minor ones as tooth extraction or tonsillectomy, as well as when prescribing certain drugs, such as acetylsalicylic acid, hemorrhagic diathesis can threaten the very life of the patient.
The pathogenesis of hemorrhagic diathesis can now be considered fairly well studied. As is known, bleeding limitation at healthy person in case of damage to the vascular wall, it is carried out due to the following mechanisms: contraction of the vessel at the site of its damage, settling at the site of damage to the vessel of circulating platelets and the formation of a primary hemostatic plug by them and fixing it with a fibrin wall with the formation of the final "secondary" hemostatic plug. Violation of any of these mechanisms leads to disruption of the process of hemostasis and the development of hemorrhagic diathesis.
Modern ideas about the mechanisms of blood coagulation allow us to propose the following working classification of hemorrhagic diathesis.
CLASSIFICATION OF HEMORRHAGIC DIATHESIS
I. Hemorrhagic diathesis due to a defect in procoagulants (hemophilia):
a) an insufficient amount one or more factors involved in the formation of fibrin;
b) insufficient activity of procoagulant factors;
c) the presence of inhibitors of individual procoagulants in the patient's blood.
II. Hemorrhagic diathesis caused by a defect in the platelet link of hemostasis:
a) insufficient number of platelets (thrombocytopenia);
b) functional inferiority of platelets (thrombocytopathy);
c) a combination of quantitative and qualitative pathology of platelets.
III. Hemorrhagic diathesis, manifested as a result of excessive fpbrinolysis:
a) endogenous;
b) exogenous.
IV. Hemorrhagic diathesis manifested as a result of the pathology of the vascular wall:
a) congenital;
b) purchased.
V. Hemorrhagic diathesis developing as a result of a combination of several causes (thrombotic hemorrhagic syndrome, von Willebrand disease).
Most common cause hemorrhagic diathesis is a defect in the platelet link of hemostasis, which is the cause of bleeding in 80% of patients [Marquardt F., 1976]. In the group of patients with hemorrhagic diathesis, developing with an inferiority of the procoagulant link of hemostasis, hemophilia A (65-80%), hemophilia B (13-18%) and hemophilia C (1.4-9%) are most often diagnosed.
Historically, it so happened that hemorrhagic diathesis, caused by fibrin formation defect. It is now known that the formation of fibrin is ensured by the correct interaction of procoagulant proteins, most of which have their own number, indicated by a Roman numeral. There are 13 substances, including fibrinogen (factor I), prothrombin (II), proaccelerin-accelerin (V), proconvertin (VII), antihemophilic globulin A (VIII), Christmas factor (IX), Stuart-Prawer factor (X) , plasma thromboplastin precursor (XI), Hageman factor (XII), fibrin stabilizing factor (XIII). In addition to them, three recently discovered factors do not have a numerical designation. These are the Fletcher, Fitzgeralz and Passova factors.
A quantitative or qualitative defect of any of the above procoagulants, as well as the appearance of an inhibitor of this factor in the blood of a patient, can cause a hemorrhagic condition in a patient.
A large number of these conditions, which approaches the number 30, as well as the great similarity of their clinical manifestations, allow us to combine these diseases under the general name " hemophilia».
Hemophilia is characterized extensive, deep, usually isolated, spontaneous bruises and hematomas, frequent hemorrhages in the joints with the extremely rare development of skin and mucous membranes "purpura" in rare and mild bleeding with superficial skin lesions. Rough laboratory tests demonstrate prolongation of clotting time in the absence of impaired bleeding time. Practitioners should clearly understand that an accurate diagnosis of the cause of hemorrhagic diathesis is possible only with the use of special laboratory methods studies, without which adequate therapy is almost impossible.
Among hemorrhagic diatheses that develop with inferiority of the platelet link of hemostasis, the most common are those that are caused by a decrease in the number of platelets in the patient's bloodstream. These conditions, called Werlhof's syndrome, are heterogeneous in their cause. The number of platelets can decrease both as a result of the formation of autoantibodies against them (autoimmune thrombocytopenia), and as a result of their defective formation in the bone marrow. Inferiority of the platelet membrane and their cytolysis are also possible.
The attention of clinicians in recent years has been riveted to such hemorrhagic conditions; which are caused by the functional inferiority of platelets, which are not able to provide full-fledged hemostasis even with a sufficient number of them in the patient's bloodstream. After such a pathology was first described by Glyantsman, a large number of pathological forms, which are caused by a violation of one or another stage of platelet plug formation, carried out by platelets: their adhesion, aggregation, activation of the procoagulant link, retraction of the blood clot.
Finding these defects, identification of their combinations with some other manifestations of the disease led to the description of a number of individual nosological forms. At the same time, the study of platelet function in a number of described diseases made it possible to note the absence of a relationship between platelet function disorders and other symptoms that are not related to hemostasis.
Various combinations of defects in platelet functions made it possible to speak about the presence of a whole groups of thrombocytopathies, manifested by a wide variety of compounds, violations of platelet functions such as adhesion, aggregation, release reaction, activation of procoagulants, retraction. When clarifying the cause of hemorrhagic diathesis, a detailed study of both the quantitative and qualitative state of platelets in the laboratory is necessary.
The clinical picture of these diseases is characterized by frequent prolonged bleeding with superficial skin lesions, frequent skin and mucous "purpura", while hemorrhages in the joints, spontaneous bruising and hematomas are quite rare.
Hemostasis defects, caused by the pathology of the vascular wall, are diagnosed quite easily in cases where this pathology is available for visual observation: with Rendu-Osler disease, Ehlers-Danlos syndrome, Hippel-Lindau disease, Kasabach-Merritt syndrome, etc. Currently, there are indications that hemorrhagic diathesis can develop with inferiority of vascular wall collagen and impaired platelet adhesion as a result. However, this pathology can only be diagnosed using sophisticated laboratory methods.
Recently, much attention has been attracted by clinicians cases of hemorrhage in patients with multiple microthrombosis of capillaries of internal organs. These conditions are called thrombohemorrhagic syndrome. Its pathogenesis is explained by the fact that with massive rapid thrombus formation in a clot, many blood clotting factors are consumed, especially platelets and fibrinogen. In addition, hypoxia of the vascular wall leads to the release of a large number of plasminogen activators into the bloodstream and an increase in the fibrinolytic activity of the blood. The diagnosis of these conditions is very important, as it requires the "paradoxical" use of anticoagulants for the treatment of hemorrhages.
Interesting findings were found while studying pathogenesis of bleeding in patients with von Willebrandt's disease, which is characterized by a combination of symptoms that reflect disorders of both procoagulant and platelet hemostasis. It was found that the antigen factor VIII is essential for triggering platelet adhesion to the damaged surface and showed the importance of the relationship of these leading mechanisms to stop bleeding.
A wide variety of causes of hemorrhagic diathesis, the creation of specific methods for the treatment of these conditions oblige practitioners to study in detail the issues of diagnosis and treatment of patients with increased bleeding.
The most common ocular manifestations in purpura are subcutaneous and conjunctival hemorrhages. Retinal hemorrhages are very rare. In cases where they do exist, hemorrhages are located in the layer of nerve fibers. It should be borne in mind that with an eye injury, including surgical, profuse bleeding is possible, especially with hemophilia.
And an example of a blood disease caused by a change in the structure and functions of cellular elements is sickle cell anemia, lazy leukocyte syndrome, etc.
Analysis of urine. Conducted to identify concomitant pathology(diseases). Bloodletting is performed in order to normalize the number of blood cells and reduce its viscosity. Before bloodletting, drugs are prescribed that improve blood flow and reduce blood clotting.
An excess number of red blood cells appears in the blood, but the number of platelets and neutrophilic leukocytes also increases (to a lesser extent). The clinical manifestations of the disease are dominated by manifestations of plethora (plethora) and complications associated with vascular thrombosis. The tongue and lips are bluish-red in color, the eyes are as if bloodshot (the conjunctiva of the eyes is hyperemic). This is due to excessive blood supply and the participation of the hepatolienal system in the myeloproliferative process.
Patients have a tendency to form blood clots due to increased blood viscosity, thrombocytosis and changes in the vascular wall. Along with increased blood clotting and thrombosis in polycythemia, bleeding from the gums and dilated veins of the esophagus are observed. The treatment is based on a decrease in blood viscosity and the fight against complications - thrombosis and bleeding.
Bloodletting reduces blood volume and normalizes hematocrit. The outcome of the disease may be the development of myelofibrosis and cirrhosis of the liver, and with progressive anemia of the hypoplastic type, the transformation of the disease into chronic myeloid leukemia.
Typical examples of blood diseases caused by a change in the number of cellular elements are, for example, anemia or erythremia (increased number of red blood cells in the blood).
Blood disease syndromes
Diseases of the blood system and diseases of the blood are different names for the same set of pathologies. But blood diseases are a pathology of its immediate components, such as red blood cells, white blood cells, platelets or plasma.
Hemorrhagic diathesis or pathology of the hemostasis system (blood clotting disorders); 3. Other blood diseases (diseases that do not belong to either hemorrhagic diathesis, or anemia, or hemoblastoses). This classification is very general, dividing all blood diseases into groups based on which general pathological process is the leading one and which cells have been affected by the changes.
The second most common anemia associated with a violation of the synthesis of hemoglobin and erythrocytes is a form that develops in severe chronic diseases. Hemolytic anemia, caused by increased breakdown of red blood cells, are divided into hereditary and acquired.
Anemia syndrome
II A - polycythemic (that is, with an increase in the number of all blood cells) stage. In the general blood test, an increase in the number of erythrocytes, platelets ( platelets), leukocytes (except lymphocytes). Palpation (palpation) and percussion (tapping) revealed an increase in the liver and spleen.
The number of leukocytes (white blood cells, the norm is 4-9x109g / l) can be increased, normal or reduced. The number of platelets (platelets, the adhesion of which ensures blood clotting) initially remains normal, then increases and then decreases again (normal 150-400x109g / l). The erythrocyte sedimentation rate (ESR, a non-specific laboratory indicator that reflects the ratio of blood protein varieties) usually decreases. Ultrasound procedure(ultrasound) of the internal organs evaluates the size of the liver and spleen, their structure for damage by tumor cells and the presence of hemorrhages.
Diseases of the blood system constitute the content of clinical hematology, the founders of which in our country are I.I. Mechnikov, S.P. Botkin, M.I. Arinkin, A.I. Kryukov, I.A. Cashier. These diseases develop as a result of dysregulation of hematopoiesis and blood destruction, which affects the composition of peripheral blood. Therefore, on the basis of data from the study of the composition of peripheral blood, one can roughly judge the state of the hematopoietic system as a whole. We can talk about changes in red and white germs, as well as blood plasma - both quantitative and qualitative.
Changes red sprout blood systems can be represented by a decrease in hemoglobin content and the number of red blood cells (but not- mii) or their increase (true polycythemia, or erythremia); violation of the shape of erythrocytes - erythrocytopathies(microspherocytosis, ovalocytosis) or hemoglobin synthesis - hemoglobinopathies, or hemoglobinoses(thalassemia, sickle cell anemia).
Changes white sprout blood systems can touch both leukocytes and platelets. The number of leukocytes in the peripheral blood may increase (leukocytosis) or decrease (leukopenia), they can take on the qualities of a tumor cell (hemoblastosis). Equally, we can talk about an increase in the number of platelets (thrombocytosis) or about their reduction (thrombocytopenia) in peripheral blood, as well as changes in their quality (thrombocytopathy).
Changes blood plasma concern mainly its proteins. Their number may increase. (hyperproteinemia) or decrease (hypoproteinemia); the quality of plasma proteins can also change, then they talk about dysproteinemias.
The most complete picture of the state of the hematopoietic system is given by the study bone marrow punctate (sternum) and trepanobiopsy (iliac crest), which are widely used in the hematology clinic.
Diseases of the blood system are extremely diverse. Highest value have anemia, hemoblastoses (tumor diseases arising from hematopoietic cells), thrombocytopenia and thrombocytopathy.
Anemia
Anemia(gr. an- negative prefix and haima- blood), or anemia,- a group of diseases and conditions characterized by a decrease in the total amount of hemoglobin; usually it manifests itself in a decrease in its content per unit volume of blood. In most cases, anemia is accompanied by a decrease in the number of red blood cells per unit volume of blood (with the exception of iron deficiency states and thalassemia). With anemia, erythrocytes of various sizes often appear in the peripheral blood. (poikilocytosis), forms (anisocytosis), varying degrees of color (hypochromia, hyperchromia); sometimes found in erythrocytes inclusion- basophilic grains (the so-called Jolly bodies), basophilic rings (the so-called Kabo rings), etc. In some anemias, blood nuclear representatives(erythroblasts, normoblasts, megaloblasts) and immature forms(polychromatophiles) of erythrocytes.
Based on the study of the punctate of the sternum, one can judge the condition (hyper- or hyporegeneration) and type of erythropoiesis (erythroblastic, normoblastic, megaloblastic), characteristic of some form of anemia.
Etiology and pathogenesis. The causes of anemia can be blood loss, insufficient erythropoietic function of the bone marrow, increased blood destruction.
At blood loss anemia occurs when the loss of erythrocytes in the blood exceeds the regenerative capacity of the bone marrow. The same should be said about hemorrhage, those. hemolysis, which may be associated with exogenous and endogenous factors. Insufficiency of erythropoietic function of the bone marrow depends on the deficiency of substances necessary for normal hematopoiesis: iron, vitamin B 12, folic acid (the so-called deficiency anemia) or from non-assimilation of these substances by the bone marrow (the so-called achrestic anemia).
Classification. Depending on the etiology and mainly pathogenesis, there are three main groups of anemia (G.A. Alekseev, 1970): 1) due to blood loss (posthemorrhagic anemia); 2) due to impaired blood formation; 3) due to increased blood destruction (hemolytic anemia). In each group, forms of anemia are distinguished. According to the nature of the course of anemia, they are divided into sharp and chronic. In accordance with the morphological and functional state of the bone marrow, which reflects its regenerative capabilities, anemia can be regenerative, hyporegenerative, hypoplastic, aplastic, dysplastic.
Anemia due to blood loss (posthemorrhagic)
Anemia due to blood loss may be acute or chronic.
Acute posthemorrhagic anemia observed after massive bleeding from the vessels of the stomach with peptic ulcer, from an ulcer of the small intestine with typhoid fever, with a rupture of the fallopian tube in the case of an ectopic pregnancy, corroding a branch of the pulmonary artery with pulmonary tuberculosis, rupture of an aortic aneurysm or injury to its wall and large branches extending from the aorta.
The larger the caliber of the affected vessel and the closer to the heart it is located, the more life-threatening bleeding. So, with a rupture of the aortic arch, it is enough to lose less than 1 liter of blood for death to occur due to a sharp drop in blood pressure and a deficiency in filling the heart cavities. Death in such cases occurs before the bleeding of the organs occurs, and at the autopsy of the corpses, the anemization of the organs is hardly noticeable. With bleeding from small vessels, death usually occurs when more than half of the total amount of blood is lost. In such cases posthemorrhagic anemia pallor of the skin and internal organs is noted; postmortem hypostases are weakly expressed.
Pathological anatomy. If the bleeding turned out to be non-fatal, then the blood loss is compensated due to regenerative processes in the bone marrow. Bone marrow cells of flat and epiphyses tubular bones intensively proliferate, the bone marrow becomes juicy and bright. Fatty (yellow) bone marrow of tubular bones also becomes red, rich in erythropoietic and myeloid cells. In addition, foci of extramedullary (extramedullary) hematopoiesis appear in the spleen, lymph nodes, thymus, perivascular tissue, cellular tissue of the hilum of the kidneys, mucous and serous membranes, and skin.
Chronic posthemorrhagic anemia develops when there is a slow but prolonged loss of blood. This is observed with small bleeding from a decaying tumor of the gastrointestinal tract, a bleeding stomach ulcer, hemorrhoidal veins of the intestine, from the uterine cavity, with hemorrhagic syndrome, hemophilia, etc.
Pathological anatomy. The skin and internal organs are pale. Bone marrow of flat bones of the usual type; in the bone marrow of tubular bones, phenomena of regeneration and the transformation of fatty marrow into red are observed, expressed to one degree or another. Often there are multiple foci of extramedullary hematopoiesis. In connection with chronic blood loss, hypoxia of tissues and organs occurs, which causes the development of fatty degeneration of the myocardium, liver, kidneys, and degenerative changes in brain cells. There are multiple petechial hemorrhages in the serous and mucous membranes, in the internal organs.
Anemia due to impaired blood formation are represented by the so-called deficiency anemia that occurs with a lack of iron, vitamin B 12, folic acid, hypo- and aplastic anemia.
Anemia due to iron deficiency or iron deficiency anemia. They can develop primarily with insufficient intake of iron from food. (alimentary iron deficiency anemia of childhood). They also occur with exogenous iron deficiency due to increased demands of the body in pregnant and lactating women, with some infectious diseases, in girls with "pale urination" (juvenile chlorosis). Iron deficiency anemia may also be based on iron resorption deficiency, which occurs in diseases of the gastrointestinal tract, as well as after gastric resection. (agastic anemia) or intestines (anenteric anemia). Anemia due to iron deficiency hypochromic.
Recently, allocate anemia associated with impaired synthesis or utilization of porphyrins. Among them, there are hereditary (X-linked) and acquired (lead intoxication).
Anemia due to lack of vitamin B 12 and/or folic acid. Them
characterizes the perversion of erythropoiesis. it megaloblastic hyperchromic anemia.
Vitamin B 12 and folic acid are essential factors for hematopoiesis. Vitamin B 12 enters the body through the gastrointestinal tract ( external factor). Absorption of vitamin B 12 in the stomach is possible only in the presence of the intrinsic factor of Castle, or gastromucoprotein, which is produced by additional cells of the fundic glands of the stomach. The combination of vitamin B 12 with gastromucoprotein leads to the formation of a protein-vitamin complex, which is absorbed by the mucous membrane of the stomach and small intestine, deposited in the liver and activates folic acid. The supply of vitamin B 12 and activated folic acid to the bone marrow determines normal hormonal erythropoiesis and stimulates the maturation of red blood cells.
Endogenous deficiency of vitamin B 12 and / or folic acid due to loss of gastromucoprotein secretion and impaired assimilation of dietary vitamin B 12 leads to the development pernicious and pernicious anemia.
pernicious anemia first described in 1855 by Addison, in 1868 it was described by Birmer (Addison-Birmer anemia). The disease usually develops in adulthood(after 40 years). For a long time, before the role of vitamin B 12, folic acid and gastromucoprotein in the pathogenesis of pernicious anemia was established, it proceeded malignantly. (pernicious anemia) and, as a rule, ended with the death of patients.
Etiology and pathogenesis. The development of the disease is due to the loss of secretion of gastromucoprotein due to hereditary inferiority of the fundic glands of the stomach, culminating in their premature
involution (cases of family pernicious anemia are described). Of great importance are autoimmune processes - the appearance of three types of autoantibodies: the first block the connection of vitamin B 12 with gastromucoprotein, the second - gastromucoprotein or the complex gastromucoprotein - vitamin B 12, the third - parietal cells. These antibodies are found in 50-90% of patients with pernicious anemia. As a result of the blockade of gastromucoprotein and vitamin B 12, hematopoiesis is perverted, erythropoiesis occurs according to megaloblastic type, and the processes of blood destruction prevail over the processes of hematopoiesis. The disintegration of megaloblasts and megalocytes occurs primarily in the bone marrow and foci of extramedullary hematopoiesis even before the release of cells into the peripheral blood. Therefore, erythrophagocytosis in Addison-Birmer anemia is especially well expressed in the bone marrow, a significant part of hemoglobinogenic pigments (porphyrin, hematin) is not used, but only circulates in the blood and is excreted from the body.
General hemosiderosis is associated with the destruction of red blood elements, and with increasing hypoxia - fatty degeneration parenchymal organs and often general obesity. A lack of vitamin B 12 leads to changes in the formation of myelin in the spinal cord.
Pathological anatomy. An external examination of the corpse determines the pallor of the skin (skin with a lemon-yellow tint), yellowness of the sclera. The subcutaneous fat layer is usually well developed. Cadaveric hypostases are not expressed. The amount of blood in the heart and large vessels reduced, watery blood. Pinpoint hemorrhages are visible in the skin, mucous membranes and serous membranes. Internal organs, especially the spleen, liver, kidneys, on the cut of a rusty appearance (hemosiderosis). The changes are most pronounced in the gastrointestinal tract, bone and spinal cord.
AT gastrointestinal tract there are atrophic changes. Language smooth, shiny, as if polished, covered with red spots. Microscopic examination reveals a sharp atrophy of the epithelium and lymphoid follicles, diffuse infiltration of the subepithelial tissue with lymphoid and plasma cells. These changes are referred to as hunter's glossitis(named after Gunter, who first described these changes). The mucous membrane of the stomach (Fig. 127), especially the fundus, thinned, smooth, devoid of folds. The glands are reduced and located at a considerable distance from each other; their epithelium is atrophic, only the main cells are preserved. Lymphoid follicles are also atrophic. These changes in the gastric mucosa culminate in sclerosis. In the mucous membrane intestines the same atrophic changes develop.
Liver enlarged, dense, on the cut has a brown-rusty hue (hemosiderosis). Iron deposits are found not only in stellate reticuloendotheliocytes, but also in hepatocytes. Pancreas dense, sclerotic.
Rice. 127. Pernicious anemia:
a - atrophy of the gastric mucosa; b - bone marrow (trepanobiopsy); many megaloblasts among cellular elements
Bone marrow flat bones crimson red, juicy; in tubular bones it looks like raspberry jelly. In hyperplastic bone marrow, immature forms of erythropoiesis predominate - erythroblasts, normoblasts and especially megaloblasts(see Fig. 127), which are also in the peripheral blood. These blood elements undergo phagocytosis by macrophages (erythrophagy) not only in the bone marrow, but also in the spleen, liver, and lymph nodes, which leads to the development of general hemosiderosis.
Spleen enlarged, but slightly, flabby, wrinkled capsule, tissue pink-red, with a rusty tint. Histological examination reveals atrophic follicles with mild germinal centers, and in the red pulp - foci of extramedullary hematopoiesis and a large number of siderophages.
The lymph nodes not enlarged, soft, with foci of extramedullary hematopoiesis, sometimes displacing lymphoid tissue for a considerable extent.
in the spinal cord, especially in the posterior and lateral columns, the breakdown of myelin and axial cylinders is pronounced.
This process is called funicular myelosis. Sometimes foci of ischemia and softening appear in the spinal cord. The same changes are rarely observed in the cerebral cortex.
The course of Addison-Birmer anemia is usually progressive, but periods of exacerbation of the disease alternate with remissions. In recent years, both clinical and morphological picture pernicious anemia
due to treatment with vitamin B 12 and folic acid preparations has changed dramatically. Lethal cases are rare.
Gastromucoprotein deficiency is associated with the development pernicious B 12 deficiency anemia with cancer, lymphogranulomatosis, syphilis, polyposis, corrosive gastritis and other pathological processes in the stomach. With these pathological processes in the stomach, inflammatory, dystrophic and atrophic changes in the glands of the bottom occur again with a violation of the secretion of gastromucoprotein and endogenous deficiency of vitamin B 12 . The same genesis has pernicious anemia, which occurs several years after the removal of the stomach. (gastric B^-deficiency anemia).
Malabsorption of vitamin B12 and/or folic acid in the gut underlies a number of In 12 (folic) deficiency anemias. This is worm- diphyllobothriasis- anemia with invasion with a wide tapeworm, anemia with sprue - sprue anemia, as well as anemia after resection of the small intestine - anenteric B 12 (folic) deficiency anemia.
The reason for the development of B 12 (folic) deficiency anemia can also be an exogenous deficiency of vitamin B 12 and / or folic acid of a nutritional nature, for example, in children when breastfeeding goat milk (alimentary anemia) or when taking certain medications (drug anemia).
Hypo- and aplastic anemias. These anemias are the result of a deep inhibition of hematopoiesis, especially of young elements of hematopoiesis.
Cause development of such anemia can be both endogenous and exogenous factors. Among endogenous factors great place occupy hereditary, which is associated with the development of familial aplastic anemia (Fanconi) and hypoplastic anemia (Ehrlich).
Familial aplastic anemia(Fanconi) is very rare, usually in children, more often in several family members. Severe chronic hyperchromic anemia is characterized by megalocytosis, reticulocytosis and microcytosis, leuko- and thrombopenia, hemorrhages, bone marrow aplasia. It is often combined with malformations.
hypoplastic anemia(Erlich) has a sharp and subacute course, characterized by progressive death of the active bone marrow, accompanied by bleeding, sometimes with the addition of sepsis. In the blood, there is a decrease in the number of all blood cells without signs of regeneration.
For endogenous hypo- and aplastic anemias, the most characteristic lesion erythroblastic germ blood (erythron) with loss of the ability of the bone marrow to regenerate. The death of the active bone marrow of flat and tubular bones occurs, it is replaced by yellow, fatty (Fig. 128). Among the mass of fat in the bone marrow, there are single hematopoietic cells. In cases of complete devastation of the bone marrow and its replacement with fat, they speak of "consumption" of the bone marrow - panmyelophtis.
As exogenous factors leading to the development of hypoplastic and aplastic anemia, radiation energy can act (radio
cationic anemia), toxic substances (toxic, for example, benzene anemia) drugs such as cytostatic, amidopyrine, atofan, barbiturates, etc. (drug anemia).
With exogenous hypo- and aplastic anemia, unlike endogenous anemia, complete suppression of hematopoiesis does not occur, only inhibition of the regenerative capacity of the bone marrow is noted. Therefore, young cells can be found in the punctate from the sternum.
Rice. 128. Aplastic anemia. Active bone marrow replaced by fat
exact forms of erythro- and myelopo-
ethical line. However, with prolonged exposure, the active bone marrow is emptied and replaced by fat, panmyelophthisis develops. Hemolysis joins, multiple hemorrhages occur in serous and mucous membranes, phenomena of general hemosiderosis, fatty degeneration of the myocardium, liver, kidneys, ulcerative necrotic and purulent processes, especially in the gastrointestinal tract.
Hypo- and aplastic anemia also occur with substitution bone marrow with leukemia cells, metastases of a malignant tumor, usually cancer (cancer of the prostate, breast, thyroid gland, stomach), or bone tissue in osteosclerosis (osteosclerotic anemia). Anemia due to osteosclerosis occurs in osteomyelopoietic dysplasia, marble disease(osteosclerotic anemia of Albers-Schoenberg), etc. (see. Diseases of the musculoskeletal system).
Anemia due to increased blood destruction (hemolytic anemia)
Hemolytic anemia- a large group of blood diseases in which the processes of hemorrhage prevail over the processes of hemogenesis. The destruction of red blood cells, or hemolysis, can be either intravascular or extravascular (intracellular). In connection with hemolysis in hemolytic anemias, there are constantly general hemosiderosis and suprahepatic (hemolytic) jaundice, expressed to varying degrees, depending on the intensity of hemolysis. In some cases, "acute nephrosis of excretion" of hemolysis products develops - hemoglobinuric nephrosis. The bone marrow responds to the destruction of red blood cells hyperplasia and therefore becomes pink-red, juicy in spongy bones and red in tubular ones. Foci appear in the spleen, lymph nodes, loose connective tissue extramedullary hematopoiesis.
Hemolytic anemias are divided into anemias caused mainly by intravascular or predominantly extravascular (intracellular) hemolysis (Kassirsky I.A., Alekseev G.A., 1970).
Hemolytic anemia due mainly to intravascular hemolysis. They arise from various reasons. These include hemolytic poisons, severe burns (toxic anemia), malaria, sepsis (infectious anemia), transfusion of incompatible blood group and Rh factor (post-transfusion anemia). Immunopathological processes play an important role in the development of hemolytic anemias. (immune hemolytic anemia). These anemias include isoimmune hemolytic anemia(hemolytic disease of the newborn) and autoimmune hemolytic anemia(with chronic lymphocytic leukemia, bone marrow carcinomatosis, systemic lupus erythematosus, viral infections, treatment with certain drugs; paroxysmal cold hemoglobinuria).
Hemolytic anemia due predominantly to extravascular (intracellular) hemolysis. They are hereditary (family) in nature. The breakdown of erythrocytes in these cases occurs in macrophages, mainly in the spleen, to a lesser extent in the bone marrow, liver and lymph nodes. Splenomegaly becomes a striking clinical and morphological sign of anemia. Hemolysis explains the early appearance of jaundice, hemosiderosis. Thus, this group of anemias is characterized by a triad - anemia, splenomegaly and jaundice.
Hemolytic anemias, caused mainly by intracellular hemolysis, are divided into erythrocytopathies, erythrocytofermentopathies and hemoglobinopathies (hemoglobinoses).
To erythrocytopathies include hereditary microspherocytosis (microspherocytic hemolytic anemia) and hereditary ovalocytosis, or elliptocytosis (hereditary ovalocytic hemolytic anemia). These types of anemia are based on a defect in the structure of the erythrocyte membrane, which causes their instability and hemolysis.
Erythrocytofermentopathy occur when the activity of erythrocyte enzymes is impaired. Deficiency in erythrocytes of glucose-6-phosphate dehydrogenase, the main enzyme of the pentose phosphate pathway, is characterized by acute hemolytic crises with viral infections, taking medications, eating the fruits of some legumes (favism). A similar picture develops with a deficiency of glycolysis enzymes (pyruvate kinase) in erythrocytes. In some cases, with a deficiency of glucose-6-phosphate dehydrogenase, chronic hemolytic anemia develops.
hemoglobinopathies, or hemoglobinosis, associated with impaired hemoglobin synthesis (α- and β-thalassemia) and its chains, which leads to the appearance of abnormal hemoglobins - S (sickle cell anemia), C, D, E, etc. Often a combination of sickle cell anemia (Fig. 129) with other forms of hemoglobinopathy (S-group hemoglobinosis). Naru-
Rice. 129. Sickle cell anemia (scanning electron microscope examination):
a - normal erythrocytes. x5000; b - crescent-shaped erythrocytes. x1075; c - sickle-shaped erythrocyte. x8930 (according to Bessie et al.)
The decrease in hemoglobin synthesis, the appearance of abnormal hemoglobins are accompanied by the breakdown of red blood cells and the development of hemolytic anemia.
Tumors of the blood system, or hemoblastoses
Tumors of the blood system, or hemoblastosis, are divided into two groups: 1) leukemia - systemic tumor diseases of the hematopoietic tissue; 2) lymphomas - regional tumor diseases of the hematopoietic and / or lymphatic tissue.
Classification of tumors of hematopoietic and lymphatic tissueI. Leukemias- systemic tumor diseases. A. Acute leukemias: 1) undifferentiated; 2) myeloid; 3) lymphoblastic; 4) plasmablastic; 5) monoblastic (myelomonoblastic); 6) erythromyeloblastic (di Guglielmo); 7) megakaryoblast. B. Chronic leukemia. Myelocytic origin: 1) chronic myeloid; 2) chronic erythromyelosis; 3) erythremia; 4) true polycythemia (Vakez-Osler syndrome). Lymphocytic origin: 1) chronic lymphocytic leukemia; 2) lymphomatosis of the skin (Cesari's disease); 3) paraproteinemic leukemias: a) multiple myeloma; b) primary macroglobulinemia (Waldenström's disease); c) heavy chain disease (Franklin's disease).
monocytic origin: 1) chronic monocytic leukemia; 2) histiocytosis (Histiocytosis X).
II. Lymphomas- regional tumor diseases.
1. Lymphosarcoma: lymphocytic, prolymphocytic, lymphoblastic, immunoblastic, lymphoplasmacytic, African lymphoma (Burkitt's tumor).
2. Fungal mycosis.
3. Cesari's disease.
4. Reticulosarcoma.
5. Lymphogranulomatosis (Hodgkin's disease).
Leukemia - systemic tumor diseases of the hematopoietic tissue
Leukemia (leukemia) characterized by a systemic progressive proliferation of hematopoietic cells of a tumor nature - leukemic cells. First, tumor cells grow in the hematopoietic organs (bone marrow, spleen, lymph nodes), then hematogenously migrate to other organs and tissues, forming leukemic (leukemic) infiltrates along the interstitium around the vessels, in their walls; parenchymal elements at the same time undergo dystrophy, atrophy and die. Tumor cell infiltration can be diffuse (for example, leukemic infiltration of the spleen, liver, kidneys, mesentery), which leads to a sharp increase in organs and tissues, or focal - with the formation of tumor nodes that germinate the capsule of the organ and the surrounding tissues. Typically, tumor nodes appear against the background of diffuse leukemic infiltration, but they can occur primarily and be a source of diffuse leukemic infiltration.
Very characteristic of leukemia the appearance of leukemia cells in the blood.
The uncontrolled growth of leukemia cells in organs and tissues, their “flooding” of blood leads to anemia and hemorrhagic syndrome, severe dystrophic changes in parenchymal organs. As a result of immune suppression in leukemia, severe ulcerative necrotic changes and complications infectious nature - sepsis.
Etiology and pathogenesis. Questions of the etiology of leukemia and tumors are inseparable, since the tumor nature of leukemia is beyond doubt. Leukemias are polyetiological diseases. Various factors that can cause mutation of the cells of the hematopoietic system.
Mutagens include viruses, ionizing radiation, and a number of chemicals.
Role viruses in the development of leukemia is shown in animal experiments. In humans, it has been proven for acute endemic T-lymphocytic leukemia (HTLV-I retrovirus), hairy cell leukemia (HTLV-II retrovirus), and Burkitt's lymphoma (Epstein-Barr DNA virus).
It is known that ionizing radiation capable of causing the development of leukemia (radiation, or radiation, leukemia), and the frequency of mutations depends directly on the dose of ionizing radiation. After the atom
In the aftermath of the explosion in Hiroshima and Nagasaki, the incidence of acute leukemia and chronic myelosis among those exposed increased approximately 7.5 times.
Among chemical substances with the help of which leukemia can be induced, dibenzanthracene, benzpyrene, methylcholanthrene are of great importance, i.e. blastogenic substances.
The pathogenesis of leukemia is associated with the activation of cellular oncogenes (proto-oncogenes) under the influence of various etiological factors, which leads to impaired proliferation and differentiation of hematopoietic cells and their malignant transformation. In humans, an increase in the expression of a number of proto-oncogenes in leukemia has been registered; ras(1st chromosome) - with various leukemias; sis(chromosome 22) - with chronic leukemia; myc(8th chromosome) - with Burkitt's lymphoma.
Meaning hereditary factors in the development of leukemia is often emphasized by the family nature of the disease. When studying the karyotypes of leukemia cells, changes are found in the set of their chromosomes - chromosomal aberrations. In chronic myeloid leukemia, for example, a decrease in the autosome of the 22nd pair of chromosomes of leukemia cells (Ph "-chromosome, or Philadelphia chromosome) is constantly detected. In children with Down's disease, in which Ph"-chromosome is also found, leukemia occurs in 10-15 times more often.
In this way, mutation theory pathogenesis of leukemia can be considered the most likely. At the same time, the development of leukemia (though not all) is subject to the rules tumor progression(Vorobiev A.I., 1965). The change of monoclonal leukemia cells by polyclonalism underlies the appearance of power cells, their eviction from the bone marrow and the progression of the disease - blast crisis.
Classification. Given the degree of increase in the total number of leukocytes in the blood, including leukemic cells, there are leukemic(tens and hundreds of thousands of leukocytes in 1 µl of blood), subleukemic(no more than 15,000-25,000 in 1 µl of blood), leukopenic(the number of leukocytes is reduced, but leukemia cells are detected) and aleukemic(no leukemic cells in the blood) options leukemia.
Depending on the degree of differentiation (maturity) of tumor blood cells and the nature of the flow (malignant and benign) leukemias are divided into acute and chronic.
For acute leukemia characteristic proliferation of undifferentiated or poorly differentiated, blast, cells ("blast" leukemias) and malignancy of the course, for chronic leukemia- proliferation of differentiated leukemic cells ("cytic" leukemias) and the relative good quality of the course.
Guided histo(cyto)genesis of leukemic cells, allocate histo(cyto)genetic forms of both acute and chronic leukemia. The histogenetic classification of leukemia has recently undergone significant changes due to new ideas about hematopoiesis. The fundamental difference between the new scheme of hematopoiesis
(Chertkov I.L., Vorobyov A.P., 1973) is the allocation of classes of precursor cells of different hematopoietic lineages.
It is believed that the stem lymphocyte-like pluripotent cell of the bone marrow is the only cambial element for all germs of hematopoiesis. The reticular cell has lost the meaning of "maternal", it is not a hematopoietic, but a specialized stromal cell of the bone marrow. The hematopoietic stem cell belongs to the class I pluripotent progenitor cells. Class II is represented by partially determined pluripotent precursor cells of myelo- and lymphopoiesis. Class III consists of unipotent progenitor cells of B-lymphocytes, T-lymphocytes, leukopoiesis, erythropoiesis and thrombocytopoiesis. Progenitor cells of the first three classes do not have morphological features that would allow them to be assigned to a specific lineage of hematopoiesis. Class IV is formed by proliferating cells - primarily blasts (myeloblast, lymphoblast, plasmablast, monoblast, erythroblast, megakaryoblast), which have a characteristic morphological, including cytochemical, characteristic (the content of a number of enzymes, glycogen, glycosaminoglycans, lipids). Class V is represented by maturing and VI - mature cells of hematopoiesis.
Based on modern ideas about hematopoiesis among acute leukemia distinguish the following histogenetic forms: undifferentiated, myeloblastic, lymphoblastic, monoblastic (myelomonoblastic), erythromyeloblastic and megakaryoblastic. Undifferentiated acute leukemia develops from progenitor cells of the first three classes, devoid of morphological signs of belonging to one or another series of hematopoiesis. The remaining forms of acute leukemia are derived from class IV progenitor cells, i.e. from blast cells.
Chronic leukemia depending on the number of maturing hematopoietic cells from which they arise, they are divided into: 1) leukemia of myelocytic origin; 2) leukemia of lymphocytic origin; 3) leukemia of monocytic origin. to chronic leukemia myelocytic origin include: chronic myeloid leukemia, chronic erythromyelosis, erythremia, polycythemia vera. to chronic leukemia lymphocytic series include: chronic lymphocytic leukemia, skin lymphomatosis (Cesari's disease) and paraproteinemic leukemias (multiple myeloma; Waldenström's primary macroglobulinemia; Franklin's heavy chain disease). to chronic leukemia monocytic origin include monocytic (myelomonocytic) leukemia and histiocytosis (histiocytosis X) (see the classification of tumors of the hematopoietic and lymphatic tissues).
Pathological anatomy has a certain originality, concerning both acute and chronic leukemias, there is also a certain specificity of their diverse forms.
Acute leukemia
The diagnosis of acute leukemia is made on the basis of detection in the bone marrow (puncture from the sternum) blast cells. Sometimes their number is
may be 10-20%, but then in the trepanate of the ilium, an accumulation of many dozens of blasts is found. In acute leukemia, both in the peripheral blood and in the myelogram, the so-called leukemic failure (hiatus leucemicus)- sharp rise the number of blasts and single mature elements in the absence of transitional maturing forms.
Acute leukemias are characterized by the replacement of the bone marrow by young power elements and their infiltration of the spleen, liver, lymph nodes, kidneys, brain, its membranes, and other organs, the degree of which is different in different forms of leukemia. The form of acute leukemia is established on the basis of the cytochemical characteristics of blast cells (Table 11). In the treatment of acute leukemia with cytostatic agents, bone marrow aplasia and pancytopenia often develop.
acute leukemia in children have some features. Compared with acute leukemia in adults, they are much more common and are characterized by a wider spread of leukemic infiltration in both hematopoietic and non-hematopoietic organs (with the exception of the sex glands). In children, more often than in adults, leukemias with nodular (tumor-like) infiltrates are observed, especially in the thymus gland. Acute lymphoblastic (T-dependent) leukemia is more common; myeloblastic leukemia, like other forms of acute leukemia, is less common. Special forms of acute leukemia in children are congenital leukemia and chloroleukemia.
Acute undifferentiated leukemia. It is characterized by infiltration of the bone marrow (Fig. 130), spleen, lymph nodes and lymphoid formations (tonsils, group lymphatic and solitary follicles), mucous membranes, vessel walls, myocardium, kidneys, brain, meninges and other organs of a homogeneous type with undifferentiated cells hematopoiesis. The histological picture of this leukemic infiltration is very uniform. The spleen and liver are enlarged, but only slightly. The bone marrow of flat and tubular bones is red, juicy, sometimes with a grayish tint. In connection with leukemic infiltration of the oral mucosa and tonsil tissue, necrotic gingivitis, tonsillitis appear - necrotic angina. Sometimes a secondary infection joins, and undifferentiated acute leukemia proceeds as septic disease.
Leukemic infiltration of organs and tissues is combined with the phenomena hemorrhagic syndrome, the development of which is explained not only by the destruction of vascular walls by leukemic cells, but also by anemia, a violation of platelet formation as a result of the replacement of the bone marrow by undifferentiated hematopoietic cells. hemorrhages of a different nature occur in the skin, mucous membranes, internal organs, quite often in the brain (see Fig. 130). Patients die from cerebral hemorrhage, gastrointestinal bleeding, ulcerative necrotic complications, sepsis.
Table 11 Cytochemical characterization various forms leukemia
A form of acute leukemia | Reactions to nutrients | Reactions to enzymes |
|||||
glycogen (SHI reaction) | glycosaminoglycans | lipids (black sudan) | peroxidase | acid phosphatase | a-naphthylesterase | chloroacetate esterase |
|
undifferentiated | negative | negative | negative | negative | negative | negative | negative |
Myeloblastic | Positive | Same | Positive | Positive | Positive | Weakly positive | Positive |
promyelocytic | Strongly positive | Positive | Same | Strongly positive | Weakly positive | Same | Strongly positive |
lymphoblastic | Positive in the form of lumps | negative | negative | negative | Sometimes positive | negative | negative |
monoblastic | Weakly positive | Same | Weakly positive | Weakly positive | highly positive | Positive | Same |
Myelomonoblastic | Positive diffuse | » » | Same | highly positive | Positive | Same | Weakly positive |
erythromyeloblastic | Positive | » » | Reactions depend on the belonging of blast elements to a particular series (myeloblasts, monoblasts, undifferentiated blasts) |
||||
plasmablastic | It is distinguished by the characteristic cell morphology and the presence of a paraprotein in the blood serum |
||||||
Megakaryoblastic | Distinguished by characteristic cell morphology |
||||||
Rice. 130. Acute leukemia:
a - bone marrow, consisting of homogeneous undifferentiated cells; b - hemorrhage in the frontal lobe of the brain
A type of undifferentiated acute leukemia is chloroleukemia, which is often found in children (usually boys up to 2-3 years). Chloroleukemia is manifested by tumor growths in the bones facial skull, less often - in other bones of the skeleton and very rarely - in the internal organs (liver, spleen, kidneys). Tumor nodes have greenish color, which served as the basis for such a name for this type of leukemia. The color of the tumor is associated with the presence in it of products of hemoglobin synthesis - protoporphyrins. Tumor nodes consist of atypical undifferentiated cells of the myeloid germ.
Acute myeloid leukemia (acute myeloid leukemia). This form of acute leukemia is manifested by infiltration of the bone marrow, spleen, liver, kidneys, mucous membranes, less often lymph nodes and skin with tumor cells such as myeloblasts. These cells have a number of cytochemical features (see Table 11): contain glycogen and sudanophilic inclusions, give a positive reaction to peroxidase, α-naphthylesterase, and chloroacetate esterase.
Bone marrow becomes red or grayish, sometimes it acquires a greenish (purulent) hue (pyoid bone marrow). The spleen and liver as a result of leukemic infiltration increase, but do not reach large sizes. The same can be said about the lymph nodes. Very characteristic is the infiltration of blast cells not only in the bone marrow, spleen and liver, but also in the mucous membrane of the gastrointestinal tract, in connection with which necrosis occurs in the oral cavity, tonsils, pharynx (Fig. 131), and stomach. In the kidneys they are found as diffuse,
and focal (tumor) infiltrates. In 1/3 of cases, leukemic infiltration of the lungs ("leukemic pneumonitis") develops, in 1/4 of cases - leukemic infiltration of the meninges ("leukemic meningitis"). The phenomena of hemorrhagic diathesis are sharply expressed. Hemorrhages are observed in the mucous and serous membranes, in the parenchyma of internal organs, often in the brain. Patients die from bleeding, ulcerative necrotic processes, associated infection, sepsis.
In recent years, active therapy (cytostatic agents, Υ-irradiation, antibiotics, anti-
brinolytic drugs) significantly changed the picture of acute
undifferentiated and myeloid leukemia. Extensive necrosis in the oral cavity and pharynx disappeared, the phenomena of hemorrhagic diathesis became less pronounced. At the same time, as a result of an increase in the life expectancy of patients with acute leukemia, such extra-medullary lesions as “leukemic pneumonitis”, “leukemic meningitis”, etc., began to occur more often. In connection with the therapy with cytostatic agents, cases of ulcerative-necrotic lesions of the stomach and intestines have become more frequent.
Acute promyelocytic leukemia. It is distinguished by malignancy, rapid flow and severity of hemorrhagic syndrome (thrombocytopenia and hypofibrinogenemia). Leukemic cells infiltrating organs and tissues are characterized by the following morphological features: nuclear and cellular polymorphism, the presence of pseudopodia and glycosaminoglycan granules in the cytoplasm (see Table 11). Almost all patients with this form of acute leukemia die from cerebral hemorrhage or gastrointestinal bleeding.
Acute lymphoblastic leukemia. It occurs much more often in children (in 80% of cases) than in adults. Leukemic infiltration is most pronounced in the bone marrow, spleen, lymph nodes, lymphatic apparatus of the gastrointestinal tract, kidneys and thymus. The bone marrow of spongy and tubular bones is raspberry red, juicy. The spleen sharply increases, becomes juicy and red, its pattern is erased. The lymph nodes (mediastinum, mesenteric) are also significantly enlarged; on the cut, their tissue is white-pink, juicy. The thymus gland has the same appearance, which reaches a different
some gigantic sizes. Often, the leukemic infiltrate extends beyond the thymus gland and grows into tissues anterior mediastinum squeezing organs chest cavity(Fig. 132).
Leukemic infiltrates in this form of leukemia consist of lymphoblasts, a characteristic cytochemical feature of which is the presence of glycogen around the nucleus (see Table 11). Lymphoblasts belong to the T-system of lymphopoiesis, which can explain both the rapid settlement of blasts in the T-dependent zones of the lymph nodes and spleen, and the increase in their size simultaneously with leukemic infiltration of the bone marrow. Lymphoblastic infiltrates should be considered an expression of the progression of leukemia. metastatic nature, appearing outside the lymphatic tissue. Especially often such infiltrates are found in the membranes and substance of the head and spinal cord what is called neuroleukemia.
Acute lymphoblastic leukemia responds well to treatment with cytostatic agents. In 90% of children, it is possible to obtain a stable, often long-term (5-10 years) remission. Without therapy, the course of this form, like other forms of acute leukemia, progresses: anemia increases, hemorrhagic syndrome develops, complications of an infectious nature appear, etc.
Acute plasmablastic leukemia. This form of acute leukemia arises from precursor cells of B-lymphocytes capable of producing immunoglobulins. This ability is also retained by tumor plasmablasts. They secrete pathological immunoglobulins - paraproteins, so acute plasmablastic leukemia belongs to the group paraproteinemic hemoblastoses. Plasmablastic leukemic infiltration is found in the bone marrow, spleen, lymph nodes, liver, skin and other organs. A large number of plasmablasts are also found in the blood.
Acute monoblastic (myelomonoblastic) leukemia. It is not much different from acute myeloid leukemia.
Acute erythromyeloblastic leukemia (acute erythromyelosis di Guglielmo). This is a rare form (1-3% of all acute leukemias), in which both erythroblasts and other erythropoiesis nucleated cells, and myeloblasts, monoblasts grow in the bone marrow.
Rice. 132. Tumor growths in the thymus gland in acute lymphoblastic leukemia
and undifferentiated blasts. As a result of oppression of hematopoiesis, anemia, leuko- and thrombocytopenia occur. The spleen and liver are enlarged.
Acute megakaryoblastic leukemia. One of the rarest forms of acute leukemia, which is characterized by the presence in the blood and bone marrow, along with undifferentiated blasts, also of megakaryoblasts, malformed megakaryocytes and platelet aggregations. The number of platelets in the blood increases to 1000-1500x10 9 /l.
congenital leukemia, detected within the first month after birth, is an exceptional rarity. It usually occurs in the form of myeloid leukemia, flows extremely quickly, with spleno- and hepatomegaly, swollen lymph nodes, severe diffuse and nodular leukemic infiltration of many organs (liver, pancreas, stomach, kidneys, skin, serous membranes). Severe leukemic infiltration along the course umbilical vein and portal tracts of the liver indicates hematogenous spread of the process from mother to fetus, although mothers of children with congenital leukemia rarely suffer from leukemia. Usually children die from manifestations of hemorrhagic syndrome.
Chronic leukemia
Chronic leukemias of myelocytic origin
These leukemias are diverse, but the main place among them is occupied by chronic myeloid leukemia, chronic erythromyelosis, erythremia and true polycythemia.
Chronic myeloid leukemia (chronic myelosis). This leukemia goes through two stages: monoclonal benign and polyclonal malignant. The first stage, which takes several years, is characterized by increasing neutrophilic leukocytosis with a shift to myelocytes and promyelocytes, and an enlarged spleen. Bone marrow cells at this stage of leukemia do not differ morphologically and in terms of their ability to phagocytosis from normal ones, however, they contain the so-called Ph-chromosome (Philadelphia), resulting from the deletion of chromosomes of the 22nd pair. In the second stage, which lasts from 3 to 6 months (terminal stage), monoclonalism is replaced by polyclonalism. As a result, blast forms appear (myeloblasts, less often erythroblasts, monoblasts and undifferentiated blast cells), the number of which increases both in the bone marrow and in the blood (blast crisis). There is a rapid increase in the number of leukocytes in the blood (up to several million in 1 μl), an increase in the spleen, liver, lymph nodes, leukemic infiltration of the skin, nerve trunks, meninges, thrombocytopenia appears, hemorrhagic syndrome develops.
At autopsy of those who died from chronic myeloid leukemia in the terminal stage, especially pronounced changes are found in the bone marrow, blood, spleen, liver, and lymph nodes. Bone marrow flat bones, epiphyses and diaphyses of tubular bones juicy, gray-red or gray-yellow purulent! (pyoid bone marrow). At
histological examination of the bone marrow revealed promyelocytes and myelocytes, as well as blast cells. There are cells with changes in nuclei (malformed nuclei) and cytoplasm, pycnosis or karyolysis. In the bone tissue, signs of reactive osteosclerosis are sometimes noted. Blood gray-red, organs are anemic.
Spleen sharply increased (Fig. 133), sometimes occupies almost the entire abdominal cavity; its mass reaches 6-8 kg. On the cut, it is dark red, sometimes ischemic infarctions are found. The spleen tissue displaces the leukemic infiltrate mainly from the cells of the myeloid series, among which blasts are visible; follicles are atrophic. Often find sclerosis and hemosiderosis of the pulp. Leukemic thrombi are found in the vessels.
Liver significantly increased (its mass reaches 5-6 kg). Its surface is smooth, the tissue on the cut is gray-brown. Leukemic infiltration is usually observed along the sinusoids, much less often it is visible in the portal tracts and capsule. Hepatocytes in a state of fatty degeneration; sometimes there is hemosiderosis of the liver.
The lymph nodes enlarged significantly, soft, gray-red. Leukemic infiltration of their tissue is expressed to one degree or another; it is also observed in tonsils, group and solitary lymph-
Rice. 133.
Chronic myeloid leukemia:
a - enlargement of the spleen (weight 2800 g); b - leukemic stasis and thrombi in the vessels of the heart
intestinal follicles, kidneys, skin, sometimes brain and its shells (neuroleukemia). A large number of leukemia cells appear in the lumen of the vessels, they form leukemic stasis and thrombi(see Fig. 133) and infiltrate the vascular wall. In connection with these changes in blood vessels, both heart attacks and hemorrhages are not uncommon. Quite often, in chronic myeloid leukemia, manifestations are found autoinfection.
A group related to chronic myeloid leukemia is made up of osteomyeloid leukemia and myelofibrosis, in which, along with signs of myeloid leukemia, there is a replacement of the bone marrow with bone or connective tissue. The process is characterized by a long benign course.
Therapy with cytostatic agents leads to changes in the morphology of chronic myelogenous leukemia. Along with the suppression of foci of leukemic infiltration and the development of fibrosis in their place, rejuvenation of cellular forms, the appearance of metastatic foci and tumor growths, or bone marrow aplasia and pancytopenia are noted.
Chronic erythromyelosis is a rare form of leukemia. This is a tumor of the red and white germs of the hematopoietic tissue, in which erythrokaryocytes, myelocytes, promyelocytes and blasts grow in the bone marrow, spleen and liver. A large number of these cells are found in the blood. Marked splenomegaly is noted. In some cases, myelofibrosis (Vagan's form of chronic erythromyelosis) joins.
Erythremia. It usually occurs in the elderly and is characterized by an increase in the mass of red blood cells in the bloodstream, plethora. The number of platelets and granulocytes also increases, arterial hypertension, a tendency to thrombosis, and splenomegaly appear. In the bone marrow, all sprouts grow, but predominantly erythrocyte. The process is benign for a long time, but usually ends with a transformation into chronic myeloid leukemia with the appearance of foci of leukemic infiltration in the organs.
Pathological picture erythremia is quite typical. All organs are sharply full-blooded, often blood clots form in the arteries and veins. The fatty bone marrow of tubular bones becomes red. The spleen is enlarged. There is hypertrophy of the myocardium, especially of the left ventricle. In the bone marrow, spleen and liver in the early stage of erythremia, foci of extramedullary hematopoiesis with a large number of megakaryocytes are found, and in late stage, with the transformation of the process into myeloid leukemia, - foci of leukemic infiltration.
True polycythemia(Vakez-Osler disease) is close to erythremia. There is also a chronic megakaryocytic leukemia, which is extremely rare.
Chronic leukemia of lymphocytic origin
These forms are divided into two groups: the first is chronic lymphocytic leukemia and adjoining lymphomatosis of the skin (Cesari's disease), the second is paraproteinemic leukemia.
Chronic lymphocytic leukemia.It usually occurs in middle-aged and elderly people, in some cases in members of the same family, develops from B-lymphocytes and is characterized by a long benign course. The content of leukocytes in the blood increases sharply (up to 100x10 9 /l), lymphocytes predominate among them. Leukemic infiltrates from tumor lymphocytes are most pronounced in the bone marrow, lymph nodes, spleen, and liver, which leads to an increase in these organs. Tumor B-lymphocytes produce very few immunoglobulins. In this regard, humoral immunity in chronic lymphocytic leukemia is sharply suppressed, patients often have complications of an infectious nature. This form of leukemia is characterized by the development and autoimmune reactions, especially autoimmune hemolytic and thrombocytopenic conditions.
Against the background of a benign course of chronic lymphocytic leukemia, blast crisis and generalization of the process, which in some cases leads to death. However, more often patients die from infection and complications of an autoimmune nature.
On the autopsy the main changes are found in the bone marrow, lymph nodes, spleen, liver and kidneys.
Bone marrow flat and tubular bones are red, but unlike myeloid leukemia, in the diaphysis of tubular bones, among the red bone marrow, there are areas of yellow color. Histological examination in the tissue of the bone marrow revealed foci of growth of tumor cells (Fig. 134). In extreme cases, all myeloid tissue
Rice. 134. Chronic lymphocytic leukemia:
a - bone marrow, tumor lymphocytes; b - packets of enlarged lymph nodes along the aorta
the bone marrow is displaced by leukemic lymphocytic infiltrate and only small islands of myeloid hematopoiesis remain intact.
The lymph nodes all areas of the body are sharply enlarged, merge into huge soft or dense packages (see Fig. 134). On the cut they are juicy, white-pink. The size of the tonsils, group and solitary lymphatic follicles of the intestine, which also represent a juicy white-pink tissue, increase. An increase in lymph nodes and lymphatic formations is associated with their leukemic infiltration, which leads to a sharp violation of the structure of these organs and tissues; often lymphocytes infiltrate the capsule of the lymph nodes and surrounding tissues.
Spleen reaches a significant size, its mass increases (up to 1 kg). It has a fleshy texture, red in color on the cut; follicles are preserved or lost in the pulp. Leukemic lymphocytic infiltrate primarily covers the follicles, which become large and merge. The lymphocytes then proliferate in the red pulp, vessel walls, trabeculae, and splenic capsule.
Liver enlarged, dense, light brown in section. Often, small gray-white nodules are visible from the surface and on the cut. Lymphocytic infiltration occurs mainly along the portal tracts (Fig. 135). Hepatocytes in a state of protein or fatty degeneration.
kidneys enlarged, dense, gray-brown. Their leukemic infiltration is so pronounced that the structure of the kidneys on the cut is not detected.
Leukemic infiltration is also noted in many organs and tissues (mediastinum, mesentery, myocardium, serous and mucous membranes), and it can be not only diffuse, but also focal with the formation of various sizes of nodes.
Rice. 135. Leukemic infiltration of the portal tracts of the liver in chronic lymphocytic leukemia
The described changes characteristic of chronic lymphocytic leukemia are supplemented infectious complications, such as pneumonia, and manifestations hemolytic conditions- hemolytic jaundice, diapedetic hemorrhages, general hemosiderosis.
It should be borne in mind that, in addition to generalized lesions of the lymph nodes, moderate enlargement of the spleen and liver in chronic lymphocytic leukemia, there are cases of a sharp increase only certain groups of lymph nodes(eg mediastinal, mesenteric, cervical, inguinal). In such cases, there is a danger of compression of neighboring organs (for example, compression of the heart, esophagus, trachea with damage to the lymph nodes of the mediastinum; compression of the portal vein and its branches with the development of portal hypertension and ascites with damage to the lymph nodes of the mesentery and the gate of the liver).
Lymphomatosis of the skin, or Cesari's disease. This is a peculiar form of chronic lymphocytic leukemia, which is characterized by infiltration of tumor T-lymphocytes, primarily of the skin. Over time, the bone marrow is involved in the process, the content of leukocytes in the blood increases, characteristic cells (Cesari cells) appear, peripheral lymph nodes and the spleen increase.
Paraproteinemic leukemias. This group includes tumors originating from cells of the B-lymphocyte system (precursors of plasma cells), with the function of which, as is known, humoral immunity reactions are associated. The main feature of paraproteinemic leukemias, which are also called malignant immunoproliferative diseases, is the ability of tumor cells to synthesize homogeneous immunoglobulins or their fragments - paraproteins(P/g-pathological, or monoclonal, immunoglobulins). The pathology of immunoglobulins determines both the clinical and morphological peculiarity of paraproteinemic leukemias, which include multiple myeloma, primary macroglobulinemia (Waldenström) and heavy chain disease (Franklin).
Myeloma is the most important among paraproteinemic leukemias.
multiple myeloma- a fairly common disease, described for the first time by O.A. Rustitsky (1873) and Kahler (1887). The disease is based on the proliferation of tumor cells of the lymphoplasmacytic series - myeloma cells(Fig. 136) both in the bone marrow and outside it. Myelomatosis of the bone marrow leads to the destruction of bones.
Depending on the nature of myeloma cells, there are plasmacytic, plasmablastic, polymorphocellular and small cell myeloma(Strukov A.I., 1959). Polymorphocellular and small cell myelomas are classified as poorly differentiated tumors. Myeloma cells secrete paraproteins, which are found in the blood and urine of patients, as well as in the myeloma cells themselves. Due to the fact that with multiple myeloma in the blood serum and in the urine biochemically detected
Rice. 136. myeloma cell. Sharply dilated tubules of the endoplasmic reticulum (ER) are filled with accumulations of protein - paraprotein.
I am the core. electronogram. x23,000.
different types of pathological immunoglobulins live, there are several biochemical options myeloma (A-, D-, E-myeloma, Bence-Jones myeloma). The Bence-Jones protein found in the urine is a type of paraprotein secreted by the myeloma cell, it freely passes the glomerular filter of the kidneys, as it has an extremely low molecular weight.
Myeloma usually proceeds according to the aleukemic variant, but the presence of myeloma cells in the blood is also possible.
Morphologically depending on the nature of myeloma infiltrates, which are usually localized in the bone marrow and bones, there are diffuse, diffuse nodular and multiple nodular forms of myeloma.
O diffuse form they say when diffuse myeloma infiltration of the bone marrow is combined with osteoporosis. At diffuse nodular form against the background of diffuse myelomatosis of the bone marrow, tumor nodes appear; at multi-nodal form diffuse myeloma infiltration is absent.
The growth of myeloma cells is observed more often in flat bones (ribs, skull bones) and spine, less often in tubular bones (humerus, femur). It leads to destruction bone tissue (Fig. 137).
In areas of myeloma cell growth in the lumen of the central canal of the osteon or in the bone beam under the endosteum, the bone substance becomes fine-grained, then liquefies, osteoclasts appear in it, and the endosteum exfoliates. Gradually, the entire bone beam turns into the so-called liquid bone and completely dissolves, the osteon channels become wide. "Axillary resorption" of the bone develops, which explains the characteristic of multiple myeloma osteolysis and osteoporosis- the formation of smooth-walled, as if stamped defects in the absence or very mild bone formation. Bones become
Rice. 137. Myeloma:
a - the spine on the cut - hemorrhages in the intervertebral discs; b - radiograph of the same spine: osteoporosis; c - histological picture: infiltration by myeloma cells; g - bones of the skull with multiple, as if stamped defects in the bone substance; e - axillary resorption of the bone beam; e - paraproteinemic nephrosis, accumulation of protein masses in the lumen of the tubules of the kidney; g - myelomatosis of the ribs
brittle, which explains the frequent fractures in multiple myeloma. In connection with the destruction of bones in myeloma, hypercalcemia develops, which is associated with the frequent development of calcareous metastases.
In addition to the bone marrow and bones, myeloma cell infiltration is almost constantly noted in internal organs: spleen, lymph nodes, liver, kidneys, lungs, etc.
A number of changes in multiple myeloma are associated with secretion by tumor cells paraprotein. These include: 1) amyloidosis (AL- amyloidosis); 2) deposition in the tissues of amyloid-like and crystalline substances; 3) the development of paraproteinemic edema, or paraproteinosis of organs (paraproteinosis of the myocardium, lungs, paraproteinemic nephrosis), which is accompanied by their functional insufficiency. The most important among paraproteinemic changes is paraproteinemic nephrosis, or myeloma nephropathy, which is the cause of death of 1/3 of patients with myeloma. At the heart of paraproteinemic nephrosis is the "clogging" of the kidneys with Bence-Jones paraprotein (see Fig. 137), leading to sclerosis of the brain, and then the cortical substance and wrinkling of the kidneys (myeloma shriveled kidneys). In some cases, paraproteinemic nephrosis is combined with renal amyloidosis.
In multiple myeloma, due to the accumulation of paraproteins in the blood, protein stasis in the vessels, a peculiar hyperviscosity syndrome and paraproteinemic coma.
Due to immunological defenselessness in plasmacytoma, it is not uncommon inflammatory changes (pneumonia, pyelonephritis), which occur against the background of tissue paraproteinosis and are an expression of autoinfection.
Primary macroglobulinemia- rare disease, which was first described by Waldenström in 1944. This is one of the varieties of chronic leukemia of lymphocytic origin, in which tumor cells secrete pathological macroglobulin - IgM. The disease is characterized by an increase in the spleen, liver, lymph nodes, which is associated with their leuosis infiltration. Bone destruction is rare. A very typical hemorrhagic syndrome develops due to hyperproteinemia, a sharp increase in blood viscosity, functional inferiority of platelets, slowing of blood flow and stasis in small vessels. The most frequent complications are hemorrhages, paraproteinemic retinopathy, paraproteinemic coma; possible amyloidosis.
heavy chain disease described by Franklin in 1963. In this disease, tumor cells of the lymphoplasmacytic series produce a kind of paraprotein corresponding to the Fc fragment of the IgG heavy chain (hence the name of the disease). As a rule, there is an increase in the lymph nodes, liver, spleen as a result of infiltration of these organs by tumor cells. There are no bone changes, bone marrow damage is not the rule. The sick are dying
from an attached infection (sepsis) due to hypogammaglobulinemia (immunodeficiency state).
Chronic leukemia of monocytic origin
These leukemias include chronic monocytic leukemia and histiocytosis.
Chronic monocytic leukemia usually occurs in elderly people, proceeds for a long time and benignly, sometimes with an enlarged spleen, but without disturbing bone marrow hematopoiesis. However, this leukemia usually ends with a blast crisis with the growth of blast cells in the bone marrow, their appearance in the blood and internal organs.
Histiocytosis (Histiocytosis X) unite a group of so-called borderline lymphoproliferative diseases of the hematopoietic tissue. It includes eosinophilic granuloma, Letterer-Zive disease, Hand-Schüller-Christian disease.
Lymphomas - regional tumor diseases of the hematopoietic and lymphatic tissue
This group of diseases includes lymphosarcoma, mycosis fungoides, Cesari's disease, reticulosarcoma, lymphogranulomatosis (Hodgkin's disease).
Lymphomas can be of B-cell and T-cell origin. This is the basis for the classification of lymphomas proposed by Lukes and Collins. According to this classification, B-cell lymphomas can be: small cell (B), centrocytic, immunoblastic (B), plasma-lymphocytic, and T-cell lymphomas - small cell (T), from lymphocytes with twisted nuclei, immunoblastic (T), and are also represented mycosis fungoides and Cesari's disease. In addition, unclassified lymphomas are isolated. From this classification it follows that small cell and immunoblastic lymphomas can originate from both B- and T-cells. Only B-cells develop centrocytic and plasma-lymphocytic lymphomas, and only T-cells develop lymphoma from lymphocytes with twisted nuclei, mycosis fungoides and Sezary's disease.
Etiology and pathogenesis. Lymphomas do not have any features compared to leukemias. It should be emphasized that under the conditions of modern therapy with cytostatic agents, some lymphomas (lymphosarcoma) often "complete" the terminal stage of leukemia. However, they themselves are able to "transform" into leukemia. From this it follows that the distinction between tumors of the blood system into "diffuse" and "regional", necessary in the interests of nosology, is very conditional from the standpoint of oncogenesis.
Pathological anatomy. Each of the lymphomas has a characteristic morphological picture.
Lymphosarcoma- malignant tumor arising from cells of the lymphocytic series. This tumor affects the lymphatic
nodes, and more often - mediastinal and retroperitoneal, less often - inguinal and axillary. It is possible to develop a tumor in the lymphatic tissue of the gastrointestinal tract, spleen and other organs. Initially, the tumor is local, limited. Lymph nodes sharply increase, solder to each other and form packages that squeeze the surrounding tissues. The nodes are dense, gray-pink on the cut, with areas of necrosis and hemorrhages. In the future, the process is generalized, i.e. lymphogenous and hematogenous metastasis with the formation of multiple screenings in the lymph nodes, lungs, skin, bones and other organs. Tumor cells such as B- or T-lymphocytes, prolymphocytes, lymphoblasts, immunoblasts grow in the lymph nodes.
On this basis, the following histo(cyto)logical variants lymphomas: lymphocytic, prolymphocytic, lymphoblastic, immunoblastic, lymphoplasmacytic, African lymphoma (Burkitt's tumor). Tumors consisting of mature lymphocytes and prolymphocytes are called lymphocytomas, those of lymphoblasts and immunoblasts are called lymphosarcomas (Vorobiev A.I., 1985).
Among lymphosarcomas, African lymphoma, or Burkitt's tumor, deserves special attention.
Burkitt's tumor- an endemic disease that occurs among the population of Equatorial Africa (Uganda, Guinea-Bissau, Nigeria), sporadic cases are observed in different countries. Usually sick children aged 4-8 years. Most often, the tumor is localized in the upper or lower jaw (Fig. 138), as well as the ovaries. Less commonly, the kidneys, adrenal glands, and lymph nodes are involved in the process. Quite often there is a generalization of the tumor with damage to many organs. The tumor consists of small lymphocyte-like cells, among which large macrophages with light cytoplasm are scattered, which creates a peculiar picture of the "starry sky" (starry sky)(see fig. 138). The development of African lymphoma is associated with a herpes-like virus that was detected from the lymph nodes of patients with this tumor. Virus-like inclusions are found in the lymphoblasts of lymphoma.
Fungal mycosis- relatively benign T-cell lymphoma of the skin, refers to the so-called lymphomatosis of the skin. Multiple tumor nodes in the skin consist of proliferating large cells with a large number of mitoses. Plasma cells, histiocytes, eosinophils, and fibroblasts are also found in the tumor infiltrate. Nodules of soft consistency, protrude above the surface of the skin, sometimes resembling the shape of a fungus, have a bluish color, easily ulcerate. Tumor nodes are found not only in the skin, but also in the mucous membranes, muscles, and internal organs. Previously, the development of the tumor was associated with the invasion of fungal mycelium, hence the erroneous name of the disease.
Cesari disease- T-lymphocytic lymphoma of the skin with leukemization; refers to lymphomatosis of the skin. Bone marrow damage,
Rice. 138. African lymphoma (Burkitt's tumor):
a - localization of the tumor in upper jaw; b - histological picture of the tumor - "starry sky" (G.V. Saveliev's preparation)
tumor cells in the blood, observed in Cesari's disease, served as the basis for classifying it in some cases as chronic lymphocytic leukemia.
Lymphocytic infiltration of the skin ends with the formation of tumor nodes more often on the face, back, legs. In the tumor infiltrate of the skin, bone marrow and blood, atypical mononuclear cells with crescent nuclei are found - Cesari cells. Tumor infiltration of the lymph nodes, spleen, liver, kidneys is possible, but it is never significant.
Reticulosarcoma- a malignant tumor reticular cells and histiocytes. It should be noted that the morphological criteria for belonging of tumor cells to reticular and histiocytes are very unreliable. The main histological difference between reticulosarcoma and lymphosarcoma is the production of reticular fibers by tumor cells that wrap around reticulosarcoma cells.
Lymphogranulomatosis (Hodgkin's disease)- a chronic relapsing, less often acute disease, in which the growth of the tumor occurs mainly in the lymph nodes.
Morphologically distinguish between isolated and generalized lymphogranulomatosis. At isolated (local) lymphogranulomatosis one group of lymph nodes is affected. More often it is cervical, media-
sternal or retroperitoneal, less often - axillary, inguinal lymph nodes, which increase in size and become soldered to each other. At first they are soft, juicy, gray or gray-pink, on the cut with an erased pattern of the structure. In the future, the nodes become dense, dryish, with areas of necrosis and sclerosis. The primary localization of the tumor is possible not in the lymph nodes, but in the spleen, liver, lungs, stomach, and skin. At generalized lymphogranulomatosis the growth of tumor tissue is found not only in the focus of primary localization, but also far beyond it. As a rule, this increases spleen. Its pulp on the cut is red, with multiple white-yellow foci of necrosis and sclerosis, which gives the spleen tissue a variegated, “porphyritic” appearance (“porphyritic spleen”). The development of generalized lymphogranulomatosis is explained by metastasis of the tumor from the primary focus.
At microscopic examination both in the foci of the primary localization of the tumor (more often in the lymph nodes), and in its metastatic screenings, proliferation of lymphocytes, histiocytes, reticular cells, among which giant cells, eosinophils, plasma cells, neutrophilic leukocytes are found. Proliferating polymorphic cellular elements form nodules, exposed to sclerosis and necrosis, often caseous (Fig. 139). The most characteristic sign for lymphogranulomatosis is proliferation atypical cells, among which there are: 1) small Hodgkin cells (similar to lymphoblasts); 2) single core-
Rice. 139. Lymphogranulomatosis:
a - granulomatous formations from polymorphic cells in the lymph node; b - necrosis and proliferation of granulation tissue with atypical cells
nye giant cells, or large Hodgkin cells; 3) multinucleated Reed-Berezovsky-Sternberg cells, which usually take on gigantic sizes. The origin of these cells is probably lymphocytic, although their macrophage nature cannot be ruled out, since enzymes that are markers for macrophages, acid phosphatase and nonspecific esterase, were found in the cells.
Lymphogranulomatous foci undergo a certain evolution, reflecting the progression of the tumor, while the cellular composition of the foci naturally changes. Using a biopsy (often a lymph node), it is possible to compare the histological and clinical features of Hodgkin's disease. Such comparisons formed the basis of modern clinical and morphological classifications of Hodgkin's disease.
Clinical and morphological classification. There are 4 variants (stages) of the disease: 1) a variant with a predominance of lymphoid tissue (lymphohistiocytic); 2) nodular (knotty) sclerosis; 3) mixed cell variant; 4) option with suppression lymphoid tissue.
Variant with a predominance of lymphoid tissue characteristic of the early phase of the disease and its localized forms. It corresponds to I-II stages of the disease. Microscopic examination reveals only the proliferation of mature lymphocytes and partly histiocytes, which leads to the erasure of the pattern of the lymph node. With the progression of the disease, the lymphohistiocytic variant becomes mixed-cellular.
Nodular (nodular) sclerosis characteristic of a relatively benign course of the disease, and the primary process is often localized in the mediastinum. Microscopic examination reveals the growth of fibrous tissue surrounding the foci of cell clusters, among which are Reed-Berezovsky-Sternberg cells, and along the periphery - lymphocytes and other cells.
Mixed cell variant reflects the generalization of the disease and corresponds to II-III of its stage. Microscopic examination reveals characteristic features: proliferation of lymphoid elements of varying degrees of maturity, giant cells of Hodgkin and Reed-Berezovsky-Sternberg; accumulations of lymphocytes, eosinophils, plasma cells, neutrophilic leukocytes; foci of necrosis and fibrosis.
Option with suppression (displacement) of lymphoid tissue occurs with an unfavorable course of the disease. It reflects the generalization of Hodgkin's disease. At the same time, in some cases, there is a diffuse proliferation of connective tissue, among the fibers of which there are a few atypical cells, in others, the lymphoid tissue is displaced by atypical cells, among which Hodgkin cells and giant Reed-Berezovsky-Sternberg cells predominate; sclerosis is absent. The variant with the displacement of lymphoid tissue by extremely atypical cells is called Hodgkin's sarcomas.
Thus, the progression of lymphogranulomatosis is morphologically expressed in the successive change of its three variants: with pre-
possession of lymphoid tissue, mixed-cell and with suppression of lymphoid tissue. These clinical and morphological variants can be considered as stages of Hodgkin's disease.
Thrombocytopenia and thrombocytopathy
thrombocytopenia- a group of diseases in which there is a decrease in the number of platelets (the norm is 150x10 9 /l) due to their increased destruction or consumption, as well as insufficient education. Increased destruction of platelets - the most common mechanism for the development of thrombocytopenia.
Classification. There are hereditary and acquired forms of thrombocytopenia. With many hereditary thrombocytopenia observe changes in various properties of platelets, which allows us to consider these diseases in the group of thrombocytopathies (see. thrombocytopathies). Guided by the mechanism of damage to megakaryocytes and platelets, acquired thrombocytopenia divided into immune and non-immune. Among immune thrombocytopenia distinguish alloimmune(incompatibility in one of the blood systems), transimmune(penetration of autoantibodies of a mother suffering from autoimmune thrombocytopenia through the placenta), heteroimmune(violation of the antigenic structure of platelets) and autoimmune(production of antibodies against own unchanged platelet antigens). In cases where the cause of autoaggression against platelets cannot be identified, they speak of idiopathic autoimmune thrombocytopenia. Non-immune thrombocytopenia may be due to mechanical injury of platelets (with splenomegaly), inhibition of bone marrow cell proliferation (with radiation or chemical damage to the bone marrow, aplastic anemia), bone marrow replacement (proliferation of tumor cells), somatic mutation (Marchiafava-Micheli disease), increased consumption of platelets ( thrombosis, see DIC syndrome), lack of vitamin B 12 or folic acid (see anemia). Immune forms of thrombocytopenia are more common than non-immune ones, with the autoimmune form most commonly observed among the former, usually in adults.
Pathological anatomy. Thrombocytopenia is characterized by hemorrhagic syndrome with hemorrhages and bleeding. Hemorrhages occur more often in the skin in the form of petechiae and ecchymosis, less often in the mucous membranes, even more rarely in the parenchyma of internal organs (for example, cerebral hemorrhage). Bleeding is possible both gastric and intestinal, and pulmonary. Often there is an increase in the spleen as a result of hyperplasia of its lymphoid tissue, an increase in the number of megakaryocytes in the bone marrow. Separate forms of thrombocytopenia have their own morphological features. For example, in some autoimmune thrombocytopenias, there is an increase in lymph nodes (lymphadenopathy) and platelet sizes, and an increase in
the spleen is absent. Hemorrhages with thrombocytopenia can lead to the development of anemia (see. anemia).
Thrombocytopathies- a large group of diseases and syndromes, which are based on violations of hemostasis, caused by a qualitative inferiority or dysfunction of platelets. In essence, this is a group of hemorrhagic diathesis with hemorrhagic manifestations at the level of microcirculation vessels.
Classification. Thrombocytopathies are divided into hereditary and acquired. Among hereditary thrombocytopathy allocate a number of forms, guided by the type of dysfunction, morphological changes and biochemical disorders of platelets. Many of these forms are considered as independent diseases or syndromes (for example, Glanzman's thrombasthenia associated with membrane abnormalities of platelets; Chediak-Higashi syndrome, which develops with a lack of type I dense bodies and their components in platelets).
Pathological anatomy. The characteristic of thrombocytopathy is reduced to the morphological manifestations of the hemorrhagic syndrome. It should be borne in mind that thrombocytopathies can occur with more or less severe thrombocytopenia.
When deciding on the priority of thrombocytopathy or thrombocytopenia in the diagnosis, one should be guided by the following provisions (Barkagan Z.S, 1985): blood; 2) thrombocytopathy is characterized by a discrepancy between the severity of the hemorrhagic syndrome and the degree of thrombocytopenia; 3) genetically determined forms of platelet pathology in the vast majority of cases belong to thrombocytopathies, especially if they are combined with other hereditary defects; 4) thrombocytopathy should be considered secondary if the qualitative defect of platelets is unstable, weakens or completely disappears after the elimination of thrombocytopenia.
Blood diseases in adults are considered one of the most formidable, as they develop extremely rapidly and have a severe course, damaging various systems and organs. A person is able to independently suspect a progressive pathology, but it is impossible to differentiate it without a specialist.
The greatest danger in the course of blood diseases is the difficulty of early diagnosis, since most of the symptoms are not specific to this nosological group, and the patient most often attributes various types of ailments to overwork, seasonal vitamin deficiency and considers it a transient phenomenon. In the meantime, the disease continues to progress, and the lack of treatment can be fatal.
A disorder of the hematopoietic system can be assumed by the following signs:
- increased fatigue, drowsiness, not related to the load during the day, psycho-emotional state and quality of rest;
- change in the skin - depending on the diagnosis, the skin and mucous membranes may become pale, gray, or covered with a hemorrhagic rash;
- dry skin and mucous membranes, hair loss, brittle nails;
- dizziness, weakness;
- night sweats;
- swollen lymph nodes;
- the appearance of spontaneous bruising;
- an increase in body temperature without a clinic of a respiratory viral disease;
- bleeding gums, may be nosebleeds.
To make a diagnosis, it is necessary to conduct laboratory tests, which will include clinical and biochemical analysis blood, a coagulogram taking into account the values of RFMK and d-dimer (according to indications), and additionally, pathological markers such as homocysteine, antiphospholipid antibodies, C-reactive protein, some antigens, thromboelastogram, coagulation factors and platelet aggregation can be prescribed.
Classification of blood diseases:
The key point in the development of the disease is pathology at one of the levels of hematopoiesis.
The range of diseases that can be identified include:
Anemia:
- deficiency anemia (iron deficiency, B12 deficiency, folic acid deficiency);
- hereditary dyserythropoietic anemia;
- posthemorrhagic;
- hemolytic;
- hemoglobinopathy (thalassemia, sickle cell anemia, autoimmune, etc.);
- aplastic anemia.
Hemorrhagic diathesis:
- hereditary coagulopathy (hemophilia, von Willebrand disease, rare hereditary coagulopathy);
- acquired coagulopathy (hemorrhagic disease of the newborn, deficiency of K-vitamin-dependent factors, DIC);
- disorders of vascular hemostasis and mixed genesis(Rendu-Osler disease, hemangiomas, hemorrhagic vasculitis, etc.);
- thrombocytopenia (ideopathic thrombocytopenic purpura, alloimmune purpura of newborns, transimmune purpura of newborns, heteroimmune thrombocytopenias);
- thrombocytopathy (hereditary and acquired).
Hemoblastoses:
- myeloproliferative diseases;
- myelodysplastic diseases;
- myelodysplastic syndromes;
- acute myeloid leukemia;
- B-cell neoplasms;
- Histiocytic and dendritic cell neoplasms
Pathologies of the circulatory system are characterized by a change in the number of blood elements, their quality, structure and shape, with a parallel decrease in their functions. Diagnosis is quite complicated, since a deviation from normal blood counts can be in almost any other disease of the body. Diagnosed disease requires immediate medical intervention and changes in diet.
DIC
Disseminated intravascular coagulation develops as a result of concomitant pathology, which stimulates the organs of the circulatory system to hypercoagulation. The long course of the acute stage of DIC leads to complete destabilization of hemostasis, where hypercoagulation is replaced by critical hypocoagulation. In this regard, therapy varies depending on the stage of the disease - at one stage, anticoagulants and antiplatelet agents will be used, while the other stage may require blood transfusion.
Disseminated intravascular coagulation is accompanied by general intoxication, weakness, dizziness, impaired thermoregulation.
DIC can be triggered by:
- acute bacterial infection;
- violation of the gravid period caused by fetal death, placental abruption, eclampsia, amnion embolism;
- serious injury;
- tissue necrosis;
- organ transplantation, transfusion;
- acute radiation sickness, hemoblastosis.
Treatment of the syndrome is aimed at stabilizing the coagulation and anticoagulation system, neutralizing blood clots and microclots, restoring adequate function and platelet count with normalization of the APTT time. The laboratory criteria for the success of therapy is considered to be the entry into the reference values of d-dimer, APTT, RFMK, fibrinogen and platelet count.
Anemia
One of the types of anemia can be found in every fourth person on Earth, and most often it is caused by a deficiency of vitamins or trace elements. Anemia is a disease in which either the number of erythrocytes in the plasma decreases, or the hemoglobin content inside the erythrocytes decreases. Pathology may owe its development to either a poor-quality diet, or damage to the hematopoietic organs, or massive blood loss, in which the level of hemoglobin in the blood cannot be restored to normal after bleeding. There are also other types of anemia, less common, but more formidable (genetic, infectious).
To diagnose anemia, as well as to clarify its type, it is necessary to assess the level of hemoglobin, the number of erythrocytes, hematocrit, the volume of erythrocytes, the average concentration of hemoglobin in the erythrocyte.
anemia caused by helminthic invasion, requires not only anthelmintic treatment, but also the use of a complex of vitamins to eliminate beriberi.
To clarify the nature of anemia, tests are prescribed to assess the level of trace elements in the blood - the amount of cyanocobalamin, folic acid and iron in plasma is considered. If one or another component is missing, medical preparation and nutrition is corrected.
Video - Anemia: how to treat
Thrombophilia
Thrombophilia is a group of diseases in which the blood coagulation system is excessively activated, which causes the pathological formation of clots and blood clots. Thrombophilia can be acquired - such as antiphospholipid syndrome, as well as congenital or genetic - in the presence of active (worked) mutations in hemostasis genes. The presence of predisposition — detected mutant genes, high levels of homocysteine, the presence of antiphospholipid antibodies — is a significant risk factor for the development of thrombosis of various localization.
The risk of thrombosis increases significantly if, in the presence of a predisposition, there is a habit of smoking, overweight, folate deficiency, oral contraceptives are taken, and a sedentary lifestyle is maintained. In pregnant women, the risk of thrombosis in the presence of mutations in hemostasis genes is even higher, in addition, the likelihood of fetal loss at any gestational age increases.
Depending on the type of thrombophilia, it is possible to prevent the development of pathology by taking folic acid and other B vitamins, maintaining an active lifestyle, excluding the use of oral contraception, and monitoring hemostasis in preparation for and during pregnancy. Prophylactic doses of antiplatelet agents and anticoagulants may also be needed - it all depends on the actual situation and history.
To diagnose thrombophilia, the doctor prescribes:
- hemostasis genes: F2, F5, PAI-1, fibrinogen;
- folate cycle genes, homocysteine;
- antibodies to phospholipids, cardiolipin, glycoprotein;
- lupus anticoagulant;
- hemostasiogram with RFMK and d-dimer.
Thrombophilia can be expressed in thrombosis of the veins of the lower extremities, thrombophlebitis, hyperhomocysteinemia, thromboembolism, in pregnant women - gestosis and eclampsia, sclerosis and thrombosis of the chorionic villi, which leads to fetal hypoxia, oligohydramnios and even death of the fetus. If pregnant women with a burdened obstetric history have never experienced thrombosis, then antiplatelet agents may be prescribed to increase the chances of gestation, since this group of patients has excessive aggregation of blood clots from the first trimester.
But hemophilia is a completely opposite disease, and its severe forms, as a rule, end in failure. Hemophilia is a group of hereditary diseases in which there is a mutation of coagulation genes, which leads to high risk development of fatal bleeding.
Thrombocytopenia and thrombocytopenia
Thrombocytopenia can be either an independent disease due to disruption of the bone marrow or spleen, or provoked by taking anticoagulant drugs. Thrombocytopenia is characterized by a decrease in the number of platelets. If a this pathology appeared against the background of taking heparin, especially in the first 15 days from the start of therapy, it is urgent to cancel the drug. Most often, this complication is caused by sodium heparin, therefore, with this kind of anticoagulant treatment, control over the number of platelets, the level of antithrombin 3 and APTT is required to avoid bleeding.
As an independent disease, thrombocytopenia acts as purpura, often of a congenital and autoimmune nature. For treatment, drugs that stabilize hemostasis, as well as drugs that help immune activity, are used.
Thrombocytopathy can act as hereditary disease with little severe symptoms, amenable to treatment with vitamins and dietary changes.
In the case of thrombocytopenia, an adequate amount of blood cells is produced, but they have an altered structure and have inferior functionality. Most often, thrombocytopathy is caused either by taking drugs that thin the blood, or by a violation of the bone marrow. Given the disease, the aggregant ability of platelets and their adhesion are disturbed. Treatment is aimed at reducing blood loss by taking vitamins and aggregates.
Less common blood disorders
There are also blood pathologies that are many times less common than anemia, DIC, and thrombocytopenia. This reduced frequency is related to the specificity of the diseases. Such pathologies include:
- genetic disease thalassemia with impaired hemoglobin production;
- malaria with the destruction of erythrocyte mass;
- leukopenia, neutropenia - a significant pathological decrease in the number of leukocytes - most often acts as a complication of the underlying disease;
- agranulocytosis, which develops against the background of an autoimmune reaction;
- polycythemia - a sharp abnormally high increase in the number of red blood cells and platelets;
- oncological lesions of the blood - leukemia or leukemia, hemoblastoses;
- sepsis is a well-known acute infectious disease, commonly known as blood poisoning.
When clarifying the diagnosis, it should be remembered that one blood disease can gradually transform into another (leukopenia with the progression of lupus erythematosus syndrome can develop into agranulocytosis), and can also be not an independent phenomenon, but a complication or a sign of a certain pathological process.
The search for a disease state by blood tests is a very rewarding business, as it allows you to confirm or exclude serious illnesses circulatory system. Even if hemostasis is within the normal range, but the general clinical analysis indicates the current pathological process, then the search for the source of disorders is greatly facilitated. The symptoms of blood diseases in an adult are very non-specific and can be easily mistaken for signs of another disease, so the study of the main hematological parameters should be the starting point for eliminating the disease.
In clinical practice, the following syndromes are distinguished, reflecting changes in the blood system. Anemic. Hemorrhagic. Hemolytic. DIC syndrome. ANEMIC SYNDROME Anemia is a condition characterized by a decrease in hemoglobin content per unit volume of blood (often with a simultaneous decrease in the number of red blood cells), which accompanies both hematological diseases and many other diseases. When studying the anamnesis, attention is paid to the patient's contact with toxic substances, the use of drugs, symptoms of other diseases that can lead to anemia. In addition, it is necessary to assess the patient's dietary habits, the amount of alcohol consumed. A family history of anemia should also be clarified.
The reasons. Anemia may accompany various diseases infectious and inflammatory nature, diseases of the liver, kidneys, connective tissue, tumors, endocrine diseases. Anemia can occur acutely as a result of blood loss and hemolysis or develop gradually. The causes of microcytic anemia can be iron deficiency in the body, impaired inclusion of iron in erythrocytes due to changes in the synthesis of porphins (sideroblastic anemia), a defect in the synthesis of globin in thalassemia, chronic diseases, lead intoxication. Macrocytic anemia occurs when there is a deficiency of vitamin B 12 or folic acid, as well as due to toxic action medicines.
Manifestations Anemic syndrome is accompanied primarily by clinical signs due to oxygen "starvation" of many organs. Insufficient supply of oxygen to peripheral tissues - pallor of the skin and mucous membranes; symptoms of hypoxia brain - dizziness, fainting. Deterioration of exercise tolerance, weakness, fatigue, shortness of breath. Compensatory changes on the part of the CCC (increased work to improve the supply of oxygen to peripheral tissues). Lab changes(first of all, a decrease in hemoglobin content). At a hemoglobin concentration below 50 hl, the development of heart failure is possible. It should be remembered that in the case of a gradual increase in anemia up to a decrease in hemoglobin content of less than 70-80 hl, the inclusion of compensatory mechanisms will burn to delay the appearance of clinical signs in the patient. In addition to the above manifestations, it is possible to detect lymphadenopathy, enlargement of the spleen and liver.
compensatory changes. For anemia, manifestations from the CCC are very characteristic, associated with a compensatory reaction to an insufficient supply of oxygen to peripheral tissues (usually with a hemoglobin content of less than 100 hl), - heart rate and minute volume increase; often these changes are accompanied by the appearance of a systolic murmur at the apex of the heart. Also characteristic is a decrease in OPSS due to tissue hypoxia and a decrease in blood viscosity. One of these most important compensatory mechanisms is a shift in the oxyhemoglobin dissociation curve, which facilitates the process of oxygen transport into tissues. laboratory changes. In case of anemia, in addition to hemoglobin and the number of red blood cells, it is necessary to have data on hematocrit, the number of reticulocytes, leukocytes, and platelets in peripheral blood. Anemias are classified according to laboratory signs into microcytic, macrocytic and monocytic. Determination of the color index of blood and MSI (this criterion is more objective) makes it possible to classify anemia into hyper-, hypo- and normochromic. By content. Reticulocytes in the blood of anemia are divided into hyporegenerative and hyperregenerative.
Anemia classification. There are several approaches to the division of anemia. From a practical standpoint, it is convenient to distinguish anemia resulting from: Blood loss (acute and chronic); Insufficient formation of red blood cells; Enhanced their destruction (hemolysis); Combinations of the above factors. Insufficiency of erythropoiesis can lead to the appearance of the following types of anemia. Hypochromic-microcytic anemia: with iron deficiency, violations of its transport and utilization. Normochromic-normocytic anemia: in hypoproliferative conditions (for example, in diseases of the kidneys, endocrine pathology), hypoplasia and aplasia of the bone marrow, myelophthisis (selective violation of myelopoiesis, the process of formation of granulocytes, platelets and erythrocytes in the bone marrow). Hyperchromic macrocytic anemia: with a deficiency of vitamin B 12, folic acid. Hemolysis of erythrocytes is possible with immunological disorders, intrinsic defects of erythrocytes (membranopathy, congenital enzymopathies, hemoglobinopathies).
IRON DEFICIENCY ANEMIA Iron deficiency anemia is hypochromic (microcytic) anemia that occurs as a result of an absolute decrease in iron resources in the body. Iron deficiency in the body (with a decrease in its content in the blood plasma - sideropenia) remains a common phenomenon, often leading to anemia. The reasons. Iron deficiency occurs as a result of three groups of causes. Insufficient intake of iron in the body. - its low content in food. - malabsorption iron - chronic diseases of the gastrointestinal tract, as well as resection of the stomach, malabsorption syndrome, celiac disease. 2. Chronic blood loss. - bleeding from the digestive tract (varicose veins of the esophagus, peptic ulcer of the stomach and duodenum, hemorrhoids, ulcerative colitis, polyposis, cancer, etc.) - lung diseases (for example, malignant lung tumor with decay). - pathology of the gynecological sphere (for example, dysfunctional uterine bleeding). 3. Increased iron consumption: during pregnancy and lactation, during growth and puberty, with chronic infections, oncological diseases during treatment with erythropoietin.
Clinical manifestations. Manifestations of the disease may be associated with the disease that caused the occurrence of anemic syndrome. Iron deficiency is manifested by neurological disorders in the form of paresthesia - primarily a burning sensation of the tongue. Possible atrophy of the mucous membrane of the tongue, esophagus, stomach, intestines. Atrophy of the mucous membrane of the larynx and pharynx can lead to dysphagia; it is considered a precancerous condition. With the gradual development of anemia, as happens in the case of prolonged blood loss, as a result of the inclusion of a number of compensatory mechanisms, complaints may be absent for a long time even with severe anemia, however, exercise tolerance in such individuals is usually reduced and returns to normal after treatment. Complaints. characteristic complaints - increased fatigue and irritability, headaches associated not so much with a decrease in hemoglobin content, but with a deficiency of iron-containing enzymes. This factor is also associated with a perversion of taste in the form of a desire to eat clay, chalk, glue. Physical examination. Pallor of the skin and mucous membranes, atrophic glossitis, stomatitis are detected. Nail deformity is rarely seen in recent years. Typical changes in CCC are also revealed.
Laboratory data found in the blood the following signs iron deficiency anemia. Reducing the number of red blood cells with hypochromia and more often microcytosis. Anisocytosis is possible. Decreased iron content in blood serum (less than 10 µmol). An increase in the content of free transferrin in the blood and a decrease in the saturation of transferrin with iron. Low content of ferritin in blood plasma. With a slight iron deficiency, anemia can be minor, and often normochromic. Notes anisocytosis and poikilocytosis, later appear microcytosis and hypochromia. In some patients, leukopenia occurs, thrombocytopenia and thrombocytosis are possible. The number of reticulocytes is within the normal range and reduced. In the bone marrow, erythroid hyperplasia is possible, the severity of which does not correspond to the severity of anemia. The content of iron in the blood serum is also usually reduced in acute and chronic inflammation, tumor process. In the study of blood after the start of treatment with iron preparations, an increase in its content in the blood serum can be detected. Oral iron supplements should be discontinued at least one day before blood tests.
Diagnostics. In doubtful cases, the results of trial treatment with oral iron preparations are of diagnostic value. Adequate therapy leads to an increase in the number of reticulocytes in the blood with a peak on the 7-10th day of treatment. A significant increase in hemoglobin levels is observed after 3-4 weeks, its normalization occurs within 2 months. Treatment. Prescribe iron supplements. There are a significant number of preparations of iron salts, allowing you to quickly eliminate its deficiency. Iron preparations should be prescribed parenterally only in case of violation of its absorption in the intestine, as well as exacerbations of peptic ulcer. The patient recommends a varied diet containing primarily meat products.
MEGALOBLASTIC ANEMIA This is a group of diseases characterized by a megaloblastic type of hematopoiesis, when peculiar large cells, megaloblasts, appear in the bone marrow. Megaloblastic anemias are caused by impaired DNA synthesis. The main cause of megaloblastic hematopoiesis is a deficiency of vitamin B 12 and folic acid. In each case, it is necessary to clarify the etiology of the deficiency that has arisen.
Normal metabolism of vitamin B 12 and folic acid Vitamin B 12 is present in foods of animal origin - eggs, milk, liver, kidneys. Its absorption in the stomach requires the participation of the so-called Castle factor, a glycoprotein secreted by the parietal cells of the stomach. The minimum daily requirement for vitamin B 12 is 2.5 micrograms. Since its reserves in the body are usually quite large, a deficiency occurs years after the start of a violation of its intake into the body. Lack of B 12 creates a state of folate deficiency in the cell. At the same time, large doses of folic acid can temporarily partially correct megaloblastosis caused by B 12 deficiency. Folic acid (pteroylglutamic acid) is a water-soluble vitamin found in green parts of plants, some fruits, vegetables, cereals, animal products (liver, kidneys) and involved in the biosynthesis of purine and pyrimidine bases. Its absorption occurs in the proximal small intestine. The daily requirement is 50 mg. Folic acid acts as a coenzyme in carbon transfer reactions.
Causes of vitamin B 12 and folic acid deficiency Vitamin B 12 deficiency may occur in the following cases. Limiting the consumption of animal products. Violation of the absorption of vitamin B 12 in the so-called pernicious anemia. With intestinal invasion with a wide tapeworm that absorbs a large amount of vitamin B 12. After operations on the small intestine with the development of blind loop syndrome, in areas of the intestine through which food does not pass, the intestinal microflora absorbs a large amount of vitamin B 12. Gastrectomy. Resection of the small intestine, ileitis, sprue, diseases of the pancreas. The action of certain drugs (for example, anticonvulsants). Causes of folic acid deficiency. Diet errors. Inadequate consumption of plant foods, especially with alcohol abuse and in children. Folic acid malabsorption in small bowel disease (eg, tropical sprue). An increase in the need for vitamin B 12 and folic acid occurs during pregnancy, hyperthyroidism, and tumor diseases.
Clinical manifestations. In the clinical picture of the disease, manifestations of both vitamin B12 deficiency itself and megaloblastic anemia are observed. Manifestations of vitamin B 12 deficiency. With a deficiency of vitamin B 12, a characteristic hunter's glossitis, weight loss, neurological disorders, a positive reaction to the administration of vitamin B 12 with an initially low content in blood serum are noted. Neurological disorders caused by demyelination are very characteristic - the so-called funicular myelosis, manifested primarily by symmetrical paresthesias in the legs and fingers, impaired vibrational sensitivity and proprioception, and progressive spastic ataxia. Also watching increased irritability, drowsiness, changes in taste, smell, vision.
Manifestations of megaloblastic anemia. The main clinical manifestations of megaloblastic anemia of any origin are of the same type and depend on the degree of its severity. The development of anemia usually occurs rather slowly, therefore, an asymptomatic course is possible until the hematocrit decreases significantly. At this stage, the clinical symptoms of anemia are nonspecific - weakness, fatigue, palpitations, shortness of breath during exercise, then there is an increase in damage to the heart muscle with the appearance of various changes on the ECG, expansion of the heart chambers up to the development of congestive heart failure. Patients are pale, subicteric, puffy face. Sometimes there is an increase in body temperature to subfebrile values. Gastric secretion in most patients with vitamin B12 deficiency and megaloblastic anemia is sharply reduced. Gastroscopy reveals atrophy of the mucous membrane, confirmed histologically.
Laboratory and instrumental research methods. The most common changes in megaloblastic anemia in peripheral blood include the following: Macrocytosis - the main sign of megaloblastic anemia - may precede the development of anemia itself and other symptoms vitamin deficiency. Peripheral blood macrocytosis is assessed by color score or, more reliably, by MCV. Poikilocytosis and anisocytosis are also detected. In a blood smear, Jolly bodies are found - the remains of normoblast nuclei detected in erythrocytes (erythrocytes normally do not contain nuclei). Cabot rings are morphological formations in erythrocytes in the form of a ring, figure eight or treble clef, which are probably the remains of the nuclear membrane. Decreased hemoglobin content. Of particular importance is the increase in reticulocytes, which occurs on the 3-5th day of treatment and reaches a maximum on the 10th day.
Bone marrow research. Megaloblasts are found in the bone marrow. Myeloid cells are usually enlarged: giant metamyelocytes, erythroid hyperplasia are detected. An important diagnostic test is the reaction to the administration of vitamin B 12; with repeated sternal puncture after 8-12 hours, a transition from megaloblastic to erythroblastic hematopoiesis is noted. Determination of vitamin B 12 in the blood. In addition to the study of bone marrow hematopoiesis, for the diagnosis of B 12 and folic deficiency conditions, the determination of the blood concentration of these substances is currently used. A low blood level of the vitamin is observed with a deficiency of vitamin B 12 in food, folic acid deficiency, pregnancy, taking oral contraceptives, very large doses vitamin C, transcobalamin deficiency, multiple myeloma. The causes of a false increase in vitamin B 12 in the blood are myeloproliferative diseases, hepatocarcinoma and other liver diseases, autoimmune diseases, and lymphomas.
Pernicious anemia (pernicious anemia) is the classic and most striking example of B12 megaloblastic deficiency anemia. This is a disease that develops as a result of insufficient absorption of vitamin B 12, caused by a violation of the secretion of the internal factor of Castle and manifested by hyperchromic anemia, signs of damage to the gastrointestinal tract and nervous system. Violations of the Castle factor synthesis are associated with autoimmune lesions of the gastric mucosa against the background of hereditary predisposition, atrophy of the gastric mucosa with achlorhydria. The following factors indicate the autoimmune nature of the disease: Detection of antibodies to parietal cells of the gastric mucosa in the blood serum of 90% of patients and only 10% of the control group suffering from atrophic gastritis without anemia. Identification of antibodies that bind to an internal factor or complex "internal factor-vitamin AT 12" . The combination of pernicious anemia with thyrotoxicosis, hypothyroidism and Hoshimoto's goiter, in the pathogenesis of which the autoimmune mechanism takes part, and autoantibodies to thyroglobulin and rheumatoid factor are often detected simultaneously. The reverse development of the signs of the disease under the influence of glucocorticoids.
Enzymopathy of erythrocytes Hereditary deficiency of erythrocyte enzymes manifests itself most often when exposed to certain toxins and medicinal substances in the form of acute hemolysis, less often chronic. Among them, the most common deficiency is the G-6-PD-enzyme, which is involved in maintaining the normal intracellular content of reduced nucleotides. The severity of the disease depends on the severity of the deficiency. A slight deficiency is manifested by acute hemolysis with drugs that exhibit oxidative properties, which was first described in the treatment with prihamin. Later, the effects of other antimalarial drugs, sulfa drugs, and nitrofuran derivatives became known. Liver and kidney failure favors acute hemolysis due to G-6-PD deficiency. Severe enzyme deficiency is characterized by the development of neonatal jaundice, as well as spontaneous chronic hemolysis. A simple indicative diagnostic test is the detection of Heinz-Ehrlich bodies in erythrocytes. Spontaneously or after incubation in the presence of phenylhydrazine, a significant proportion of G-6-PD-deficient erythrocytes show inclusions, which are precipitates of hemoglobin derivatives.
Hematology (from the Greek. blood and doctrine) is a section of internal diseases that studies the etiology, pathomorphology, pathogenesis, clinic and treatment of diseases of the blood system. Hematology studies embryogenesis, morphogenesis, morphology and physiology of cellular elements of blood and hematopoietic organs, properties of blood plasma and serum, symptomatic changes in hematopoiesis in non-hematological diseases and exposure to ionizing radiation. In 1939, G. F. Lang included in the concept of the blood system: blood, hematopoietic organs, blood destruction and the neurohumoral apparatus for regulating hematopoiesis and blood destruction.
Often the main complaint of patients is general weakness, fatigue, drowsiness, headaches, dizziness. An increase in temperature can be with hemolytic anemia due to pyrogenic effects of the breakdown products of erythrocyte products, as well as with leukemia, especially with leukemic forms. Often join septic complications in the form of necrotic tonsillitis, gingivitis, stomatitis. Hodgkin's disease is characterized by undulating undulating fever, with gradual rises over 8-15 days, and then drops in temperature. Typical for blood diseases is hemorrhagic syndrome, which is characterized by a tendency to nasal, gastrointestinal, renal, uterine bleeding, as well as the appearance of hemorrhagic rashes on the skin in the form of punctate elements - petechiae and bruises (ecchymosis). Skin itching may precede the appearance of detailed clinical symptoms, which is especially characteristic of Hodgkin's disease, hematosarcoma, erythremia. Bone pain, mainly flat, is typical of acute leukemia in children. Bone pain and pathological fractures are characteristic of multiple myeloma.
A number of symptoms are associated with an enlarged liver and spleen. Disturbed by pain in the right or left hypochondrium. The pains can be dull, severe sharp pains occur with a spleen infarction, with its rupture, with perisplenitis. With anemia, in particular iron deficiency and chlorosis, taste perversions occur: patients eat chalk, clay, earth (geophagia). There may be disturbances in the sense of smell: patients like to inhale vapors of gasoline, ether and other odorous substances. The patient may notice an increase in lymph nodes and consult a doctor with this complaint. A burning sensation in the tip of the tongue and along its edges occurs periodically and often reaches such a degree that it is difficult to take spicy and hot food. These sensations are associated with inflammatory changes in the mucous membrane of the tongue (Gunter's glossitis), which is typical sign B-12 - folic deficiency anemia. It should be clarified from the anamnesis of the patient's life whether the patient has encountered occupational hazards: work with benzene, mercury salts, lead, phosphorus, which can cause agranulocytosis; Find out the presence of radiation effects (acute leukemia, chronic myeloid leukemia). Some blood diseases such as hemophilia and hemolytic anemia can be inherited. Bleeding and chronic diseases of internal organs play a role in the development of anemia. Taking medications, in particular chloramphenicol, pyryramidone and butadione, can contribute to the development of agranulocytosis.
Thrombocytopenia (thrombopenia) - a decrease in the number of platelets - is characteristic of thrombopenic purpura, often occurs with severe forms anemia and leukemia. It would be wrong to think that on the basis of morphological features blood, you can always make the correct diagnosis and prognosis of the disease; this is possible only in isolated cases. In most cases, the hemogram acquires diagnostic and prognostic value only if all clinical signs are simultaneously assessed; Of particular value is taking into account the dynamics of changes in the blood during the course of the disease. For a correct assessment of the state of hematopoiesis, the study of intravital punctures of the bone marrow (myelogram), lymph nodes and spleen is of particular importance.
Neutropenia (a decrease in the number of neutrophils) is noted in children with lymphatics, with tuberculosis, anaphylactic shock, severe forms of influenza and typhoid fever; neutropenia with leukopenia - in severe forms of various infections and sepsis, as well as with long-term administration of sulfa drugs, embiquine, etc. Neutropenia reaches sharp degrees with agranulocytosis and aleukia. Eosinophilia is pronounced (although not always) with exudative diathesis, bronchial asthma, after injections of foreign sera, with scarlet fever, trichinosis, echinococcus and some other forms of helminthiases, with lymphogranulomatosis and with the so-called "eosinophilic pulmonary infiltrates» . An increase in the number of eosinophils acute infections- a sign in most cases prognostically favorable. Eosinopenia (a decrease in the number of eosinophils) is observed in acute infectious diseases (with the exception of scarlet fever), especially in typhoid fever, measles, sepsis, pneumonia, etc. The complete disappearance of eosinophils (aneosinophilia) is often observed in malaria, leishmaniasis; in other infections, this is an unfavorable prognostic sign.
Lymphocytosis is observed with lymphatic and exudative diathesis, with rickets (often with monocytosis), rubella and some other infections. Lymphopenia occurs with most febrile infectious diseases, with lymphogranulomatosis, miliary tuberculosis and some myelosis. Monocytosis is most pronounced with monocytic angina, often with measles, scarlet fever, malaria and other infections. Monocytopenia occurs in severe septic and infectious diseases, malignant forms of anemia and leukemia. Thrombocytosis often occurs with pneumonia, rheumatism and other infectious diseases.
