1) Pathological anemia:

Anemia is a large group of pathological conditions and diseases, for which a common feature is a decrease in the ability of the blood to carry oxygen. As a result, hypoxia develops, its hemic form, which causes the main clinical manifestations and dysfunctions in patients with anemia.

Anemia as a pathological condition can be defined as the inability of circulating red blood cells to meet the oxygen needs of tissues. To determine the pathological nature of anemia, in addition to hemoglobin or hematocrit, it is necessary to take into account the medical history and the objective status of the child.

Pathological anemia in newborns is the result of one or more of the three main causes of bleeding (internal or external), increased destruction of red blood cells (hemolysis), or a consequence of inadequate production of red blood cells (congenital deficiency or secondary suppression of erythropoiesis).

Severe anemia, manifested in the first hours of a child's life, is usually associated with acute bleeding or severe hemolysis caused by isoimmunization. Anemia manifesting after 1-2 days of life may be due to new or ongoing bleeding or non-immune hemolysis.

2) Physiological anemia:

The incorrect term "physiological anemia" is sometimes used to describe the physiological drop in hemoglobin and hematocrit levels after birth, which is observed in both full-term and premature infants. The formation of pulmonary respiration facilitates the saturation of hemoglobin with oxygen and its entry into the tissues. As a result, the formation of new red blood cells almost completely stops in both full-term and premature babies.

A healthy newborn has higher hemoglobin levels and hematocrit than older children and adults. Already in the 1st week of life it begins to decline progressively, which continues for approximately 6-8 weeks. This decrease is considered as physiological anemia of infants. However, the term contains controversy, since the lowest hemoglobin level in a full-term baby is rarely less than 90 g/l.

A number of factors are involved in the pathogenesis of this condition. Firstly, with the onset of spontaneous breathing, arterial blood oxygen saturation increases from 45 to 95% and erythropoiesis abruptly stops. At the same time, the level of erythropoietin, which is high in the fetus, decreases to undetectable. The shortened lifespan of fetal red blood cells also contributes to the development of physiological anemia. Moreover, the significant increase in total blood volume accompanying the rapid increase in body weight in the first 3 months. life, creates a situation that is figuratively called bleeding into the circulatory system. After the age of 2--3 months. the hemoglobin level will reach 100-110 g/l, erythropoiesis resumes. Such anemia should be considered as a physiological adaptive reaction to existence in the extrauterine state.

Prematurely born children also develop physiological anemia; in this case, the same factors operate as in full-term newborns, but more pronounced. Hemoglobin levels decrease more significantly and faster. By the age of 3-6 weeks. the lowest level is 70-90 g/l, and in children with very low body weight it is even lower.

The difference between term and preterm infants is not the ability to produce erythropoietin, but appears to be a lower respiratory quotient and less metabolic activity in preterm infants. Moreover, if a prematurely born baby is transfused with blood from an adult donor containing HbA, his oxygen dissociation curve shifts, resulting in easier transfer of oxygen to the tissues. Therefore, the definition of anemia and the decision about the need for blood transfusion in this case should be based not only on the level of hemoglobin, but also on the oxygen requirements and the affinity of hemoglobin for oxygen. With borderline equilibrium of erythropoiesis, responsible for the development of physiological anemia, conditions associated with increased hemolysis may appear, for example, congenital hemolytic diseases, which may be accompanied by severe anemia in the first weeks of life.

Diet can also increase the manifestations of physiological anemia. Lack of folic acid or vitamin E against the background of physiological anemia can aggravate its course.

In preterm births, vitamin E has been shown to play an important role in maintaining red blood cell stability. They have a poor supply of this vitamin and often develop its deficiency, and during the first months of life its level becomes below 0.5 mg/l. If foods are rich in polyunsaturated fatty acids (as many commercially prepared formulas are) and especially if the child is also receiving iron, he may develop a syndrome consisting of hemolytic anemia, thrombocytosis and edema. Among the red blood cells there are numerous oddly shaped acanthocytes (spike cells). For a child born with very low body weight, it is advisable to consider prophylactic administration of vitamin E at a dose of 5 mg/day; if its deficiency is diagnosed, the vitamin should be administered in therapeutic doses (50 mg). The composition of most commercial milk formulas is selected in such a way that even with the addition of iron in an amount of 10-12 mg/0.14 l, hemolysis does not develop. However, the use of higher doses of iron supplements during the neonatal period is not recommended. Not only can they cause hemolysis, but they also predispose to serious infections, especially when administered parenterally. In patients with impaired fat absorption, vitamin E deficiency may be accompanied by the development of severe hemolytic anemia, which occurs in cystic fibrosis.

Infantile pycnocytosis, a limited hemolytic process accompanied by the appearance of numerous acanthocytes in the peripheral blood, apparently refers to manifestations of vitamin E deficiency. The absence of significant blood loss in the perinatal period and an iron deficiency state as the causes of anemia in the first 3 months. life can be ignored.

Anemia due to impaired blood formation are represented by so-called deficiency anemias that occur with a lack of iron, vitamin B12, 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 (nutritional 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, and in girls with “pale sickness” (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 resection of the stomach (agastric anemia) or intestines (anenteric anemia). Anemia due to iron deficiency is hypochromic.

Recently, anemia associated with impaired synthesis or utilization of porphyrins has been identified. Among them, a distinction is made between hereditary (X-linked) and acquired (lead intoxication).

Anemia due to lack of vitamin B 12 and/or folic acid. They are characterized by a perversion of erythropoiesis. These are megaloblastic hyperchromic anemias. Vitamin B 12 and folic acid are necessary factors for hematopoiesis.

Vitamin B12 enters the body through the gastrointestinal tract (external factor). Absorption of vitamin B 12 in the stomach is possible only in the presence of intrinsic factor Castle, or gastromucoprotein, which is produced by accessory cells of the fundic glands of the stomach. The combination of vitamin Bi2 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 entry of vitamin Bi2 and activated folic acid into 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 of pernicious and pernicious-like 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 had a malignant course (pernicious anemia) and, as a rule, ended in the death of patients.

Etiology and pathogenesis. The development of the disease is caused by loss of gastromucoprotein secretion due to hereditary inferiority of the fundic glands of the stomach, ending with their premature involution (cases of familial pernicious anemia have been described). Autoimmune processes are of great importance - the appearance of three types of autoantibodies: the first block the combination of vitamin B 12 with gastromucoprotein, the second - gastromucoprotein or the gastromucoprotein complex - 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 Bi2, hematopoiesis is distorted, erythropoiesis occurs according to the megaloblastic type, and the processes of hematopoiesis prevail over the processes of hematopoiesis. The disintegration of megaloblasts and megalocytes occurs primarily in the bone marrow and foci of extramarrow hematopoiesis even before the cells enter the peripheral blood. Therefore, erythrophagocytosis in Addison-Biermer anemia is especially well expressed in the bone marrow; a significant part of the 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 of parenchymal organs and often general obesity. A lack of vitamin B 12 leads to changes in myelin formation in the spinal cord.

Pathological anatomy. An external examination of the corpse reveals pallor of the skin (skin with a lemon-yellow tint) and 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 is reduced, the blood is watery. Pinpoint hemorrhages are visible in the skin, mucous and serous membranes. Internal organs, especially the spleen, liver, kidneys, have a rusty appearance when cut (hemosiderosis). The changes are most pronounced in the gastrointestinal tract, bone and spinal cord.

In the gastrointestinal tract there are atrophic changes. The tongue is smooth, shiny, as if polished, covered with red spots. Microscopic examination reveals a sharp atrophy of the epithelium and lymphoid follicles, diffuse infiltration of subepithelial tissue with lymphoid and plasma cells. These changes are referred to as Gunter's glossitis (after the name of Gunter, who first described these changes). The mucous membrane of the stomach, especially the fundic part, is thinned, smooth, and 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. The same atrophic changes develop in the intestinal mucosa.

Liver enlarged, dense, on the section has a brown-rusty tint (hemosiderosis). Iron deposits are found not only in stellate reticuloendotheliocytes, but also in hepatocytes. The pancreas is dense and sclerotic.

Bone marrow flat bones crimson-red, juicy; in tubular bones it has the appearance of raspberry jelly. In gigterplastic bone marrow, immature forms of erythropoiesis predominate - erythroblasts, normoblasts and especially megaloblasts, which are also found in the peripheral blood. These blood elements undergo phagocytosis by macrophages (erythrophagy) not only of the bone marrow, but also of the spleen, liver, and lymph nodes, which causes the development of general hemosiderosis.

Spleen enlarged, but slightly, flabby, the capsule is wrinkled, the tissue is pink-red, with a rusty tint. Histological examination reveals atrophic follicles with weakly defined germinal centers, and in the red pulp there are 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 distance.

In the spinal cord, especially in the posterior and lateral columns, the disintegration of myelin and axial cylinders is pronounced.

This process is called funicular myelosis. Sometimes areas of ischemia and softening appear in the spinal cord. The same changes are rarely observed in the cerebral cortex.

The course of Addison-Biermer anemia is usually progressive, but periods of exacerbation of the disease alternate with remissions. In recent years, both the clinical and morphological picture of pernicious anemia has changed dramatically due to treatment with vitamin B 12 and folic acid preparations. Fatal cases are rare.

Gastromucoprotein deficiency is associated with the development of pernicious-like B 12-deficiency anemia in 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 occur secondarily in the fundus glands with impaired secretion of gastromucoprotein and endogenous deficiency of vitamin B 12. Pernicious-like anemia, which occurs several years after removal of the stomach (agastric B-deficiency anemia), has the same genesis.

Impaired absorption of vitamin B 12 and/or folic acid in the intestine underlies a number of B 12 (folic) deficiency anemias. This is helminthic - diphyllobothriasis - anemia due to infestation by the broad tapeworm, anemia due to sprue - sprue anemia, as well as anemia after resection of the small intestine - anenteral B 12 (folate) deficiency anemia.

The cause of the development of B12-(folate) deficiency anemia can also be an exogenous deficiency of vitamin B12 and/or folic acid of a nutritional nature, for example in children fed with goat milk (nutritional anemia) or when treated with certain medications (medical anemia).

Hypo- and aplastic anemia. These anemias are a consequence of deep inhibition of hematopoiesis, especially young elements of hematopoiesis.

The reason for the development Such anemia can be caused by both endogenous and exogenous factors. Among endogenous factors, a large place is occupied by hereditary ones, which are associated with the development of familial aplastic anemia (Fanconi) and hypoplastic anemia (Ehrlich).

Familial aplastic anemia (Fanconi) is very rare, usually in children, often in several family members. Severe chronic hyperchromic anemia is characterized by megalocytosis, reticulocytosis and microcytosis, leukopenia and thrombopenia, hemorrhages, bone marrow aplasia. It is often combined with developmental defects.

Hypoplastic anemia (Ehrlich) has an acute and subacute course, characterized by the progressive death of active bone marrow, accompanied by bleeding, and sometimes the addition of sepsis. In the blood there is a decrease in the number of all formed blood elements without signs of regeneration.

Endogenous hypo- and aplastic anemias are most characterized by damage to the erythroblastic blood germ (erythron) with loss of bone marrow ability to regenerate. The active bone marrow of flat and tubular bones dies and is replaced by yellow, fatty marrow. Among the mass of fat in the bone marrow, there are single hematopoietic cells. In cases of complete depletion of the bone marrow and its replacement with fat, they speak of “consumption” of the bone marrow - panmyelophthisis.

Exogenous factors leading to the development of hypoplastic and aplastic anemia can include radiation energy (radiation anemia), toxic substances (toxic, for example, benzene anemia), drugs such as cytostatics, amidopyrine, atophan, barbiturates, etc. (medical anemia).

Aplastic anemia is a disease of the blood system characterized by deep pancytopenia, which develops as a result of inhibition of bone marrow hematopoiesis.

Clinical classification

Clinical classification divides all types of aplastic anemia into hereditary and acquired.

Hereditary include anemia with complete damage to hematopoiesis, which has 2 subtypes:

1. Fanconi - in combination with congenital malformations;
2. Estrena-Dameshek - without vices.

As well as anemia with partial or selective damage to only the erythrocyte lineage (Diamond-Blackfan). Macrocytic.

Acquired aplastic anemia (hypoplastic) includes cases of:

• acute, subacute and chronic inhibition of general blood cell production;
• with damage to only red blood cells - partial, red cell anemia.

Causes

According to various statistics, specific causes cannot be identified in 49–78% of cases of the disease.

The most studied were congenital forms: with Fanconi anemia, a clear connection was noted with changes in paired chromosomes No. 1 and No. 7. In cases of Diamond-Blackfan anemia, mutations of genes No. 1, 16, 19 and 13 were found. Exposure to free oxidizing radicals is considered possible activators.

Other causes are divided into external and internal.

Exogenous (external) include:

• Chemical agents - derivatives of benzene, mercury, petroleum products.
• Physical effects of penetrating radiation.
• Medicines - anti-tuberculosis drugs (Isoniazid, PAS), Analgin, cytostatics, sulfonamides, some antibiotics (Streptomycin, Tetracycline, Levomycetin).
• Infection - in some cases, a connection with previous infectious diseases (influenza, sore throat, mononucleosis) has been proven; hepatitis C, herpes, Epstein-Barr, and cytomegalovirus viruses have a suppressive effect on blood cells.

Internal reasons include:

• endocrine disorders - a connection has been identified with decreased thyroid function, cystic changes in the ovaries in women;
• immune changes - due to the loss in old age of the regulatory role of the thymus (thymus gland).

Most scientists are of the opinion that a sick person, in addition to one or more factors, develops an individual reaction to antigens.

The role of endocrine changes is evidenced by the achievement of long-term remission in women with identified aplastic anemia during pregnancy or termination for medical reasons.

Pathogenesis of the disease

Aplastic anemia is caused by suppression of the production of blood cells in the bone marrow. An increased level of destruction and destruction of cells by self-antigens is possible. The mechanism of apoptosis (spontaneous destruction of red blood cells) is being studied. It is equated to “programmed suicide.”
An increased activity of destructive enzymes in the blood and a deficiency of nucleic acids have been established.

Destruction of red blood cells occurs within the bone marrow at all levels of maturation. The lifespan of red blood cells decreases.

Since iron utilization is impaired, excess is deposited in the liver and spleen.

An increase in the level of the hormone erythropoietin is produced, but the bone marrow does not respond to its orders.

With a decrease in granulocytes, their function of participating in the body’s immune defense is blocked. A corresponding manifestation of reduced coagulability occurs due to thrombocytopenic syndrome.

The number of lymphocytes is increased. The bone marrow becomes “empty” (panmyelophthisis).

A pronounced lack of oxygen in tissues causes dystrophic changes in internal organs. The endocrine glands are especially affected.

Clinical manifestations in childhood

Symptoms of aplastic anemia of hereditary origin depend on the form of the disease.

With Fanconi anemia, the child has congenital defects in the skeletal system (the first finger on the hand is missing, the radius bones are bent or missing). The defects include abnormalities of the heart and kidneys, small eyeballs.

Aplastic anemia in children begins to appear at the age of four, less often at an early age. The child complains of headaches and fatigue. Susceptible to frequent colds and nosebleeds. The examination reveals a characteristic blood pattern. The disease takes a chronic course with periods of exacerbations.

Death is possible from infection or acute bleeding.

With Estren-Dameshek anemia, only blood pathology is observed. Cases are very rare.

Diamond-Blackfan anemia affects exclusively the red blood cell lineage. Changes in the bones of the skeleton and eyes were observed less frequently. There is no bleeding. The skin is pale with a grayish tint. The spleen and liver enlarge early. In a blood test, the level of platelets and leukocytes decreases only with significant damage to the spleen. The usual ratio of leukocytes to erythrocytes in a patient is 100:1, with the norm being up to 4:1. Chronic severe course of the disease does not allow one to live beyond the age of 20.

Manifestations of acquired anemia

Symptoms of aplastic anemia appear during periods of exacerbation, and the disease becomes progressively slower. All signs can be divided into main syndromes, depending on the inhibition of a specific blood cell lineage.

• Anemia - characterized by severe weakness, complaints of dizziness, tinnitus, palpitations, shortness of breath.
• Hemorrhagic manifestations- bruises that are not associated with injury are visible on the skin, the gums are loose and bleeding. Patients are bothered by frequent nosebleeds. In severe cases, cerebral hemorrhage may occur.
• Decreased granulocyte count causes a decline in protective immune mechanisms. Patients often become infected with infectious diseases. Any wounds they have are complicated by the addition of suppuration of the surrounding tissues. Angina occurs in an ulcerative-necrotic form. After injections, abscesses form. Stomatitis leads to mouth ulcers. A serious complication is general sepsis. IDS. Malignant neoplasms.

During the examination, the doctor pays attention to pale skin, bluish lips, bruises on the body, and sometimes a pinpoint rash.

Blood pressure is reduced. A characteristic murmur is heard in the heart, the contraction frequency is higher than normal.

Liver enlargement occurs in a severe stage, depending on the severity of heart failure.

Main criteria for the diagnosis of aplastic anemia.

The diagnosis of AA is established on the basis of clinical manifestations and laboratory examination data (A-B).

Trilinear cytopenia: anemia (hemoglobin< 110 г/л), гранулоцитопения (гранулоциты < 2,0: 109 /л), тромбоцитопения (тромбоциты < 100,0: 109 /л).

Decreased bone marrow cellularity and absence of megakaryocytes according to bone marrow puncture.

Bone marrow aplasia in iliac bone biopsy (predominance of fatty marrow).

What diseases should aplastic anemia be distinguished from?

Bone marrow suppression is found not only in aplastic anemia, but also in other diseases. Comparison of symptoms and examination results helps determine the diagnosis correctly.

• Leukemia - an enlarged spleen is more often detected; there are many blast cells of leukocyte precursors in the bone marrow.
• Agranulocytosis - does not cause anemia and a decrease in platelets.
• Diseases with enlargement of the liver and spleen - hepatitis, cirrhosis, thrombophlebitis of the splenic vein - yellowness of the skin and sclera, abnormal liver function tests are detected.
• A rare disease, paroxysmal nocturnal hemoglobinuria (PNH) occurs between the ages of 30 and 35 years. Caused by the lack of certain types of proteins. Cells in which these structures are not found during immunotyping are called PNH clones. Clinically, the disease is manifested by intravascular hemolysis with blood in the urine, decreased hemoglobin, increased bilirubin, and failure of bone marrow cells. In 40% of patients, thrombosis of large veins and arteries is observed. This is the cause of death.

Treatment

Treatment of aplastic anemia, despite the seemingly identical symptoms, is prescribed by doctors depending on the presumed main factor in the etiology of the disease.

Newly identified cases are necessarily treated in the hematology department as an inpatient. Only specialized therapy allows you to choose the right dosage and the optimal drug.

Basic techniques:

• transfusion of donor blood or individual elements for replacement purposes;
• bone marrow transplantation;
• medications that activate hematopoiesis.

For transfusion, whole blood, erythrocyte and platelet mass, and granulocytes are used. They are prepared at “Transfusion Stations” from the blood of donors. The method is considered temporary because it simply replenishes the missing number of one’s own blood cells, but does not affect the bone marrow. If the autoimmune mechanism of the pathology is proven, it cannot be used. The body produces antibodies to foreign cells.

Frequent transfusions lead to the accumulation of iron and its deposition in internal organs, disrupting their functioning. This forces the addition of drugs that help remove iron from the blood.

Bone marrow transplantation is the most effective treatment option. Blood transfusions are stopped before the procedure to reduce the possibility of rejection. A relative with the same blood type and individual compatibility can become a donor. The method is more indicated when the patient is young.

Before transplantation, radiation and chemotherapy are performed. It is necessary to suppress a possible immune response to rejection of the donor's stem cells. The method is carried out only in specialized departments and is expensive.

The following are used as immunosuppressants: Cyclosporine, antimonocyte and antilymphocyte globulins. A complex drug of this group is Atgam (contains the necessary antiglobulins). It is indicated in cases where bone marrow transplantation is not possible. Corticosteroids are used to prevent anaphylactic reactions.

Stimulation of hematopoiesis in the bone marrow is carried out using drugs such as Filgrastim, Leukomax. They activate the production of granulocytes, therefore they are indicated only for leukopenia. The course of treatment is two weeks.

The ability of male sex hormones (androgens) to stimulate all blood growths has been proven. For the treatment of men, long courses of Testosterone propionate and Sustanon are used.

Removal of the spleen is effective in 85% of patients. The method is based on the mechanism of stopping the production of antibodies to one’s own cells. Can be performed on all patients who do not have infectious complications

If the patient has bleeding, hemostatic agents are administered: Dicinone, Aminocaproic acid.

The removal of iron from the body is achieved with the help of Desferal.

Treatment of aplastic anemia with folk remedies should be abandoned. This pathology requires very thoughtful and accurate accounting of medications. How can you calculate the beneficial components in plants? There are references to the stimulating effect of garlic, red clover, radish, carrots and beets. But it is so small that its use only raises unreasonable hopes among patients and relatives.

Forecast

To date, no universal treatment has been found, so the prognosis for the patient’s life remains unfavorable.
The highest mortality rate is in the group of patients with severe forms of the disease. It is not possible to restore hematopoiesis, and patients die from general sepsis.

With a less severe course and a good response to stem cell transplantation and immunosuppressants, positive results are obtained from half to 90% of cases.

The blood system includes:

• organs and tissues of hematopoiesis, or hematopoiesis, in which the formed elements of blood mature;
• peripheral blood, which includes the circulating and deposited fractions in organs and tissues;
• organs of blood destruction;

The blood system is the internal environment of the body and one of its integrating systems. Blood performs numerous functions - respiration, metabolism, excretion, thermoregulation, maintaining water and electrolyte balance. It carries out protective and regulatory functions due to the presence of phagocytes, various antibodies, biologically active substances, and hormones. The processes of hematopoiesis are influenced by many factors. Special substances that regulate the proliferation and maturation of blood cells are important - hematopoietins, but the nervous system has a general regulatory influence. All the numerous functions of the blood are aimed at maintaining homeostasis.

The picture of peripheral blood and bone marrow allows us to judge the functions of many body systems. At the same time, the most complete picture of the state of the hematopoietic system itself can be obtained only by examining the bone marrow. To do this, a special needle (trephine) is used to puncture the sternum or iliac crest and obtain bone marrow tissue, which is then examined under a microscope.

MORPHOLOGY OF HEMOPOISIS

All formed elements of blood under normal conditions are formed in the red bone marrow of flat bones - the sternum, ribs, pelvic bones, and vertebrae. In the tubular bones of an adult, the bone marrow is represented mainly by adipose tissue and is yellow in color. In children, hematopoiesis occurs in the tubular bones, which is why the bone marrow is red.

Morphogenesis of hematopoiesis.

The ancestor of all blood cells is the hematopoietic stem cell of the bone marrow, which transforms into progenitor cells that are morphologically indistinguishable from each other, but give rise to myelo- and lymphopoiesis (Fig. 42). These processes are regulated by hematopoietins, among which erythro-, leuko- and thrombocytopoietins are distinguished. Depending on the predominance of certain poetins, myelopoiesis increases and precursor cells begin to transform into blast forms of myelocytic, erythrocyte and platelet blood lineages. When lymphopoiesis is stimulated, the maturation of lymphocytic as well as monocytic blood lineages begins. Thus, the development of mature cellular forms occurs - T- and B-lymphocytes, monocytes, basophils, eosinophils, neutrophils, erythrocytes and platelets.

At different stages of hematopoiesis, as a result of pathological influences, disturbances in the maturation of hematopoietic cells can occur and blood diseases develop. In addition, the blood system responds to many pathological processes that occur in the body by changing its cellular composition and other parameters.

CIRCULATING BLOOD VOLUME DISORDERS

Rice. 42. Scheme of hematopoiesis (according to I. L. Chertkov and A. I. Vorobyov).

In various diseases and pathological processes, the total volume of blood, as well as the ratio of its formed elements and plasma, may change. Highlight 2 main groups of blood volume disorders:

• hypervolemia - conditions characterized by an increase in total blood volume and. usually, a change in hematocrit;
• hypovolemia - conditions characterized by a decrease in total blood volume and combined with a decrease or increase in hematocrit.

HYPERVOLEMIA

Kinds:

• Normocythemic hypervolemia - a condition manifested by an equivalent increase in the volume of formed elements and the liquid part of the circulating blood. Hematocrit remains within normal limits. This condition occurs, for example. when transfusing a large amount (at least 2 liters) of blood.
• Oligocythemic hypervolemia - a condition characterized by an increase in total blood volume due to an increase mainly in plasma volume. The hematocrit indicator is below normal. Such hypervolemia occurs when a large amount of saline or blood substitutes is administered, as well as when the excretory function of the kidneys is insufficient.
• Polycythaemic hypervolemia - a condition manifested by an increase in the total volume of blood due to a predominant increase in the number of its formed elements, primarily erythrocytes. In this case, the hematocrit becomes higher than normal. Most often, this phenomenon is observed during prolonged hypoxia, which stimulates the release of red blood cells from the bone marrow into the blood, for example in residents of high mountains, at certain stages of the pathogenesis of a number of diseases of the lungs and heart.

HYPOVOLEMIA

Kinds:

• Normocythemic hypovolemia - a condition manifested by a decrease in total blood volume while maintaining hematocrit within normal limits, which is observed immediately after blood loss.
• Oligocythaemic hypovolemia characterized by a decrease in total blood volume with a predominant decrease in the number of its formed elements. The hematocrit is below normal. It is also observed after blood loss, but at a later date, when tissue fluid enters the vessels from the intercellular space. In this case, the volume of circulating blood begins to increase, but the number of red blood cells remains low.
• Polycythaemic hypovolemia - a condition in which a decrease in total blood volume is due mainly to a decrease in plasma volume. The hematocrit indicator is higher than normal. Such blood thickening is observed with loss of fluid after extensive burns, with hyperthermia with massive sweating, cholera, characterized by uncontrollable vomiting and diarrhea. Blood thickening also contributes to the formation of blood clots, and a decrease in total blood volume often leads to heart failure.

PATHOLOGY OF THE RED CYTE SYSTEM

Anemia, or anemia, - a decrease in the total amount of hemoglobin in the body and, as a rule, hematocrit. In most cases, anemia is accompanied by erythropenia - a decrease in the number of red blood cells per unit volume of blood below normal (less than 3 10 9 / l in women and 4 10 9 / l in men). The exceptions are iron deficiency anemia and thalassemia, in which the number of red blood cells may be normal or even increased.

The significance of anemia for the body is determined primarily by a decrease in the oxygen capacity of the blood and the development of hypoxia, which is associated with the main symptoms of life disorders in these patients.

Types of anemia:

• due to blood loss - posthemorrhagic;
• due to impaired blood formation - deficient;
• due to increased blood destruction - hemolytic.

Anemia can be acute or chronic.

Based on changes in the structure of erythrocytes in anemia, the following are distinguished:

• anisocytosis, which is characterized by different shapes of red blood cells;
• Poikilocytosis - characterized by different sizes of red blood cells.

With anemia it changes color indicator - hemoglobin content in red blood cells, which is normally equal to I. In anemia, it can be:

• more than 1 (hyperchromic anemia);
• less than 1 (hypochromic anemia).

ANEMIA DUE TO BLOOD LOSS (POSTHEMORRHAGIC)

These anemias are always secondary, as they arise as a result of illness or injury.

Acute posthemorrhagic anemia occurs during acute blood loss. for example, from the vessels of the bottom of a stomach ulcer, from a rupture of the fallopian tube in the case of tubal pregnancy, from pulmonary cavities in tuberculosis, etc. (internal bleeding) or from damaged vessels in case of injuries to the limbs, neck and other parts of the body (external bleeding).

Mechanisms of development of acute posthemorrhagic conditions. At the initial stage of blood loss, the volume of circulating blood decreases to a greater or lesser extent and hypovolemia develops. In this regard, the flow of venous blood to the heart decreases. its shock and minute release. This causes a drop in blood pressure and weakening of cardiac activity. As a result, the transport of oxygen and metabolic substrates from the blood to the cells, and from the latter - carbon dioxide and waste metabolic products, decreases. Hypoxia develops, which largely determines the outcome of blood loss. The extreme degree of these disorders in the body is designated as posthemorrhagic shock.

Morphology.

Manifestations of acute anemia are pallor of the skin and anemia of internal organs. Due to a sharp decrease in tissue oxygenation, the production of erythropoietin, which stimulates erythropoiesis, increases. In the bone marrow, a significant increase in the number of erythroid cells occurs and the bone marrow acquires a crimson color. Foci of extramedullary, or extramedullary, hematopoiesis appear in the spleen, lymph nodes, and perivascular tissue. Normalization of peripheral blood parameters after replenishment of blood loss occurs in approximately 48-72 hours.

Impaired hemodynamics and a decrease in the intensity of biological oxidation in cells determine the inclusion adaptive mechanisms :

• activation of thrombus formation;
• reactions of cardiovascular compensation for blood loss in the form of narrowing of the lumen of small vessels and the release of blood from the depot;
• increased cardiac output;
• maintaining the volume of circulating blood due to the flow of fluid from the interstitium into the vessels.

Chronic posthemorrhagic anemia occurs with significant blood loss due to repeated bleeding, for example from hemorrhoidal veins, uterine bleeding, etc. Such blood loss leads to chronic tissue hypoxia and metabolic disorders in them.

Morphology.

Chronic hypoxia contributes to the development of fatty degeneration of parenchymal organs. Yellow bone marrow transforms into red as erythro- and myelopoiesis increases. Foci of extramedullary hematopoiesis may appear in the liver, spleen, and lymph nodes. However, with long-term repeated and severe cololosses, hypo- and aplasia of hematopoietic tissue may occur, which indicates depletion of hematopoiesis.

ANEMIA DUE TO IMPAIRED BLOOD FORMATION (DEFECTIVE)

These anemias are a consequence of a lack of a number of substances necessary for normal hematopoiesis - iron, vitamin B 12, folic acid, etc. Among them, Addison-Birmer's pernicious anemia is of greatest importance. which is based on a deficiency of vitamin B 12 and folic acid.

At 12 - deficiency, or folate deficiency, anemia. The etiology of anemia is associated with a deficiency of vitamin B 12 and folic acid, which regulates normal hematopoiesis in the bone marrow. However, to activate folic acid, it is necessary that the vitamin supplied with food B 12 (external factor) combines with a protein formed in the stomach - gastromucoprotein(internal factor), which is produced by accessory cells of the glands of the gastric mucosa. Together they form a complex called antianemic factor . This complex then enters the liver and activates folic acid, which in turn stimulates erythropoiesis of the erythroblastic type. If autoimmune gastritis develops and antibodies appear to additional cells or gastromucoprotein, which destroy these cells or internal factor, then vitamin B 12 is not absorbed in the gastric mucosa and gastromucoprotein is not formed. The same situation occurs with high gastric resection for a tumor or ulcerative process.

Pathogenesis.

As a result of atrophy of the gastric mucosa of an autoimmune nature, a deficiency of folic acid and vitamin B 12 occurs. Erythropoiesis is disrupted and instead of red blood cells, their precursors are formed - large megaloblasts, which appear in the peripheral blood. However, megaloblasts are quickly destroyed, anemia and general hemosiderosis develop. In addition, with a deficiency of vitamin B 12, the formation of myelin in the membranes of nerve trunks is disrupted, which impairs their function.

Pathological anatomy.

Patients have pallor of the skin, watery blood, pinpoint hemorrhages, and due to atrophy of the mucous membrane of the tongue, it acquires a crimson color ( Gunter's glossitis), characterized by atrophic gastritis, thickening and enlargement of the liver due to fatty degeneration and hemosiderosis associated with hypoxia and increased destruction of megaloblasts. In the spinal cord - disintegration of the axial cylinders in the posterior and lateral columns and foci of softening of brain tissue ( funicular myelosis), which is accompanied by severe neurological symptoms. The bone marrow of flat and tubular bones is red and resembles raspberry jelly. In the spleen and lymph nodes there are foci of extramedullary hematopoiesis.

The course of the disease is progressive, with periods of remission and exacerbation. Treatment of anemia with folic acid and vitamin B 12 preparations led to the fact that patients stopped dying from this disease.

ANEMIA DUE TO INCREASED BLOOD DESTRUCTION - HEMOLYTIC

These anemias are characterized by a predominance of the process of destruction of red blood cells (hemolysis) over their formation. The lifespan of red blood cells is reduced and does not exceed 90-100 days.

Types of hemolytic anemias

Based on their origin, hemolytic anemia is divided into acquired (secondary) and congenital or hereditary.

Acquired hemolytic anemias can be caused by numerous factors. The etiology of these anemias is associated with the action of physical, chemical and biological factors, including autoimmune ones, especially with a deficiency of substances that stabilize erythrocyte membranes, such as α-tocopherol. The most important are the so-called hemolytic poisons of chemical (compounds of arsenic, lead, phosphorus, etc.) and biological origin. Among the latter are mushroom poisons, various toxic substances formed in the body during severe burns, infectious diseases (for example, malaria, relapsing fever), blood transfusions that are incompatible by group or Rh factor.

Pathogenesis.

Hemolysis of red blood cells can occur inside and outside blood vessels. In this case, hemoglobin breaks down and two pigments are synthesized from heme - hemosiderin and bilirubin. Therefore, hemolytic anemia is usually accompanied by the development of general hemosiderosis and jaundice. In addition, erythropenia and the breakdown of hemoglobin lead to severe hypoxia, accompanied by fatty degeneration of parenchymal organs.

Morphology hemolytic anemia is characterized by the development of hyperplastic processes in the bone marrow, due to which it acquires a crimson color, the appearance of foci of extramedullary hematopoiesis, severe jaundice of the skin and internal organs, hemosiderosis and fatty degeneration of the liver, heart and kidneys.

Hemolytic disease of the newborn is an example of acquired hemolytic anemia and is of great importance in obstetric and pediatric practice. It is based on an immune conflict between mother and fetus due to the Rh factor, which has antigenic properties. This factor was first discovered in the red blood cells of rhesus monkeys and is present in 80-85% of people. If the mother is Rh-negative, i.e., does not have an Rh factor, and the fetus is Rh-positive, then the mother’s body produces antibodies against the fetus’s red blood cells and intravascular hemolysis of the red blood cells occurs.

Rice. 43. Sickle cell anemia. Red blood cells are sickle-shaped. Electron diffraction pattern.

In this case, the fetus may die in the 5-7th month of pregnancy, and newborns develop hemolytic anemia, accompanied by anemia and fatty degeneration of internal organs, severe jaundice and hemosiderosis.

Hereditary, or congenital, hemolytic anemia is associated with some genetic defect in the structure of membranes, enzymes or hemoglobin. This defect is inherited.

Types: congenital hemolytic anemia, depending on the genetic defect, can be caused by membranopathies, fermentopathy, hemoglobinopathies.

Pathogenesis All congenital hemolytic anemias are basically similar - as a result of one or another genetic defect, either the erythrocyte membrane is destroyed, and the erythrocytes themselves decrease in size and can take on a spherical shape ( microspherocytosis), either the permeability of the membrane increases and red blood cells increase in size due to the intake of excess fluid, or hemoglobin synthesis is disrupted ( hemoglobinoses) and irregularly shaped red blood cells are formed, containing rapidly decaying hemoglobin, which retains oxygen (thalassemia, sickle cell anemia, etc.)(Fig. 43).

Morphology Congenital hemolytic anemia differs little from changes in secondary hemolytic anemia, with the exception of the size and shape of red blood cells. Also characteristic are pronounced intravascular hemolysis, hypoxia, hemosiderosis, fatty degeneration of parenchymal organs, hyperplasia of hematopoietic tissue, possible foci of extramedullary hematopoiesis, hepato- and splenomegaly.

PATHOLOGY OF THE LEUKOCYTE SYSTEM

The blood of a healthy person under resting conditions on an empty stomach contains 4 10 9 /l leukocytes. Many leukocytes are found in tissues, where they participate in immune control.

Typical changes in the number of leukocytes per unit volume of blood are characterized by either a decrease - leukopenia, or an increase - leukocytosis, which, as a rule, is a reaction of the leukocyte system that develops in diseases and pathological conditions. Therefore, cure of the disease leads to normalization of the leukocyte formula.

Leukopenia is a decrease in the number of leukocytes per unit volume of blood below normal, usually less than 4 10 9 / l. It occurs as a result of inhibition of the white sprout of the hematopoietic system, with increased destruction of leukocytes or with the redistribution of blood between the bloodstream and the blood depot, which is observed, for example, in shock.

The significance of leukopenia lies in weakening the body's defenses and increasing its susceptibility to various infectious pathogens.

Types of leukopenia by origin:

• primary leukopenias(congenital or hereditary) are associated with various genetic defects in the hematopoietic system at different stages of leukopoiesis;
• secondary leukopenias occur when the body is exposed to various factors - physical (ionizing radiation, etc.), chemical (benzene, insecticides, cytostatics, sulfonamides, barbiturates, etc.), metabolic products or components of various pathogens.

Leukocyte formula- the ratio of different types of circulating leukocytes.

If the number of young forms of neutrophils (bands, metamyelocytes, myelocytes, promyelocytes) located on the left side of the leukocyte formula increases, they speak of a shift of the formula to the left, which indicates increased proliferation of cells of the myelocytic series. On the right side of the formula are the mature forms of these cells. Curing the disease leads to normalization of the leukocyte formula. A decrease in the normal number of leukocytes in the leukocyte formula indicates a decrease in the regenerative capabilities of myeloid tissue.

Pathogenesis of leukopenia reflects a violation or inhibition of the process of leukopoiesis, as well as excessive destruction of leukocytes in the circulating blood or in hematopoietic organs, redistribution of leukocytes in the vascular bed, and loss of leukocytes by the body is also possible. Moreover, due to the inhibition of regeneration of leukopoietic tissue in the initial stages of leukopenia, the number of young forms of neutrophils decreases, and an increase in their young forms (i.e., a shift in the leukocyte formula to the left) indicates the cessation of the damaging effect and activation of leukopoiesis. Anisocytosis and poikilocytosis of leukocytes are also possible.

Leukocytosis- an increase in the number of leukocytes per unit volume of blood above 4 10 9 / l. It can be physiological, adaptive, pathological, or take the form of a pakemoid reaction.

• Physiological leukocytosis occurs in healthy people due to the redistribution of blood during digestion and during physical work.
• Adaptive leukocytosis develops in diseases, especially those characterized by inflammation. In this case, the number of leukocytes can increase to 40 10 9 / l.
• Pathological leukocytosis reflects the tumor nature of leukocytosis and characterizes leukemia.

Leukemoid reaction- an increase in the total purity of peripheral blood leukocytes more than 40 10 9 / l with the appearance of their immature forms (promyelocytes, myeloblasts), which makes leukocytosis similar to leukemia.

Types of leukocytosis are associated with an increase in certain forms of leukocytes:

Agranulocytosis- absence or significant decrease in the absolute number of all types of granular granulocytes (leukocytes) - neutrophils, eosinophils, basophils. Agranulocytosis is usually combined with leukopenia.

TUMORS OF THE BLOOD SYSTEM, OR HEMOBLASTOSES

Hemoblastoses - tumor diseases of hematopoietic and lymphatic tissue. They are divided into systemic diseases - leukemia , and regional - malignant lymphomas, or hematosarcomas . In leukemia, the bone marrow is primarily affected and tumor cells are found in the blood (leukemia), and in terminal lymphomas, extensive metastasis occurs with secondary damage to the bone marrow. In terms of prevalence, hemoblastosis ranks 5th among all human tumors. In children during the first 5 years of life, they account for 30% of cancer cases.

Etiology of hemoblastomas is not fundamentally different from the causes of other tumors (see Chapter 10) - these are various mutagenic factors of exo- and endogenous origin acting on stem and semi-stem progenitor cells. The hereditary factor is of great importance in the occurrence of hemoblastoses.

Pathogenesis.

Many etiological factors affect the genome of stem and semi-stem cells, leading to their malignant transformation. Therefore, the genome is a so-called bottleneck through which mutagens act on proto-oncogenes and antioncogenes, turning them into cellular oncogenes, which leads to the appearance of a tumor. The development of hemoblastoses begins with the malignancy of one stem or semi-stem cell, which produces a pool of tumor cells. Consequently, all hemoblastoses are of monoclonal origin, and all subsequent tumor cells develop from the initially mutated cell and belong to the same clone. In addition to malignancy at the level of stem and semi-stem progenitor cells, a block of differentiation also develops in the pool of tumor cells and they lose the ability to mature.

LEUKEMIA

Leukemia- systemic tumor diseases arising from hematopoietic cells with damage to the bone marrow.

The incidence of leukemia ranges from 3 to 10 per 100,000 population. Men get sick 1.5 times more often than women. Acute leukemia is most often observed between the ages of 10 and 18 years, and chronic leukemia occurs in people over 40 years of age.

Morphogenesis.

In leukemia, tumor tissue initially grows in the bone marrow and gradually suppresses and displaces normal hematopoiesis. Therefore, patients with leukemia develop anemia, platelet-, lymphocyte-, and granulocytopenia, which leads to increased bleeding, hemorrhages, decreased immunity and the addition of infectious diseases. Metastasis in leukemia consists of the appearance of leukemic infiltrates in the liver, spleen, lymph nodes, vessel walls, etc. Obstruction of blood vessels by tumor cells leads to the development of organ infarctions and ulcerative-necrotic complications.

Classification of leukemia based on 5 signs of these diseases.

1. According to the degree of differentiation of tumor cells distinguish undifferentiated, powerful and cytic leukemias. At a high level of differentiation block, tumor cells resemble undifferentiated and blast forms of hematopoiesis. Such leukemias are acute and very malignant.
   When differentiation stops at the level of procytic and cytic progenitor cells, leukemias are chronic and less malignant.
2. According to cytogenetic characteristics Acute leukemias are divided into lymphoblastic, myeloblastic, monoblastic, erythromyeloblastic, megakaryoblastic, and undifferentiated. Хронические лейкозы делят на лейкозы миелоцитарного происхождения (хронический миелоцитарный, хронический нейтрофильный, хронический эозинофильный и др.), лимфоцитарного (хронический лимфолейкоз и парапротеинемические лейкозы - миеломная болезнь, первичная макроглобулинемия Вальденстрема и др.) и моноцитарного - хронический моноцитарный лейкоз, гистиоцитоз X.
3. By immune phenotype tumor cells: based on identifying markers of their antigens.
4. Based on the total number of leukocytes in peripheral blood leukemias are isolated:
   • leukemic- tens and hundreds of thousands of leukocytes in 1 μl of blood, including blasts;
   • subleukemic- the number of blood leukocytes is 25-50 10 9 /l, including blast forms;
   • leukopenic- the number of leukocytes in peripheral blood is below normal, but there are blasts;
   • aleukemic- the number of leukocytes in the blood is less than normal and there are no blast forms.
5. According to the nature of the flow, they are distinguished:
   1. acute leukemia (also known as undifferentiated and blastic);
   2. chronic leukemia (cytic).

Acute leukemias develop from all lineages of morphologically undifferentiated hematopoietic progenitor cells. The duration of the disease is 2-18 months; with successful treatment, remission can last up to 5-8 years.

Morphogenesis.

Various forms of acute leukemia have stereotypical morphological manifestations. They are involved in the development of leukemic infiltration of the bone marrow by atypical cells of the early stages of hematopoiesis (Fig. 44). Due to the lack of differentiation of these cells, their cytogenetic affiliation can only be determined using cytochemical and immunohistochemical methods. The bone marrow of tubular bones becomes red; in some acute leukemias, it acquires a greenish color, characteristic of pus, - pioid bone marrow. In this case, normal hematopoietic cells are replaced by tumor cells. In the peripheral blood and bone marrow there are only blast and mature forms of cells, but their intermediate forms are absent. This blood pattern is called " leukemic failure ".

Leukemic infiltrates are found in the lymph nodes, spleen and liver, which leads to increased inflammation of the oral cavity and tonsil tissue, complicated by necrotizing gingivitis, tonsillitis, necrotizing tonsillitis, and with infiltration of the meninges, leukemic meningitis develops. Suppression of erythrocyte growth leads to increasing hypoxia and fatty degeneration of parenchymal organs.

Rice. 44. Bone marrow in acute lymphoblastic leukemia. Brain tissue consists mainly of lymphoblasts (a), the lumens of blood vessels are filled with the same cells (b).

As a result of thrombocytopenia, damage to the liver and vascular walls, patients develop hemorrhagic syndrome, including cerebral hemorrhages and fatal gastrointestinal bleeding. Against this background, sepsis sometimes occurs, leading patients to death (Fig. 45). Most often, especially in children, it occurs acute lymphoblastic leukemia, associated with tumor transformation of T- and B-lymphocyte precursors, and acute myeloblastic leukemia,

which most often affects adults, caused by tumor proliferation of myeloid progenitor cells.

Rice. 45. Acute leukemia, a - leukemic infiltration of the liver (shown by arrows); b - necrosis of the tonsil (necrotizing tonsillitis); c - leukemic infiltration of the kidneys; d - multiple hemorrhages in the epicardium and endocardium; e - leukemic infiltration of the bone marrow (pioid bone marrow), thinning of the cortical layer of the femur (shown by the arrow). Rice. 46.

Liver in chronic myeloid leukemia. Proliferation of myeloid cells (a) along the sinusoids. Chronic leukemia

• lasts for more than 4 years; with successful treatment, remission of the disease can last 20 years or more. Chronic leukemias differ from acute leukemias by the cytic differentiation of tumor cells and a longer course, which has certain stages:
• the monoclonal stage is characterized by the presence of only one clone of tumor cells, lasts for years, and is relatively benign; polyclonal stage, or power crisis

Morphogenesis.

Leukemic infiltrates grow in the bone marrow, liver, spleen, kidneys, lymph nodes, intestinal mesentery, and often in the mediastinum, due to which these organs and tissues sharply increase in size and can compress neighboring organs (Fig. 46). Splenomegaly (spleen weight reaches 6-8 kg) and hepatomegaly (liver weight 5-6 kg) are especially pronounced. Leukemic blood clots form in the vessels, which can lead to the development of ischemic infarctions, most often in the spleen and kidneys. The number of neutrophilic leukocytes or lymphocytes and many transitional cellular forms increases in the blood. There is anemia, thrombocytopenia, significant immunosuppression and a predisposition to infectious complications, from which patients often die. Bone marrow is gray-red. Fatty degeneration of parenchymal organs gives them a gray-yellow color.

The benign course is replaced by a blast crisis. At the same time, the number of blast forms in the blood quickly increases - myelo-, erythro-, lympho-, megakaryoblasts, etc. The total number of peripheral blood leukocytes can reach several million in 1 μl. The power crisis causes the death of patients.

PARAPROTENEMIC LEUKEMIA

Paraproteinemic leukemias are characterized by the ability of tumor cells to synthesize homogeneous immunoglobulins or their fragments - paraproteins.

In this case, tumor cells are atypical plasmacytes and therefore retain the ability to synthesize atypical immunoglobulins in a distorted form. Myeloma (plasmocytoma)

- chronic leukemia, the most common among paraproteinemic hemoblastoses. It occurs mainly in adults and with modern treatment methods can last 4-5 years. The disease is based on tumor growth in the bone marrow of atypical plasma cells, called myeloma cells.

They synthesize paraproteins, which are found in the blood and urine of patients. Based on the nature and extent of the tumor infiltrate in the bone marrow, nodular and diffuse forms of the disease are distinguished. in the bone marrow, usually flat bones (cranial vault, ribs, pelvis) and vertebrae. Leukemic infiltration is accompanied by liquefaction of the bone or its axillary resorption (osteolysis and osteoporosis) with the formation of a regular shape of round defects, which on an x-ray look like smooth-walled holes. Axillary resorption causes the release of calcium from the bones and the development of hypercalcemia with the appearance of multiple calcareous metastases in the muscles and parenchymal organs. In addition, pathological bone fractures occur.

In the generalized form of myeloma The proliferation of myeloma cells occurs, in addition to the bone marrow, in the spleen, lymph nodes, liver, kidneys and other internal organs.

Morphogenesis.

Abnormal immune proteins (paraproteins) are found in the peripheral blood, including finely dispersed Bence Jones protein, which easily passes through the kidney filter and is detected in the urine. Due to the high concentration of Bence Jones protein, paraproteinemic nephrosis develops. In addition, due to disturbances in the normal synthesis of immunoproteins, plasmacytoma is often complicated by the development of amyloidosis with kidney damage. Therefore, the cause of death in these patients is often uremia. Due to a sharp suppression of the function of the immune system, a secondary infection may be added to the underlying disease, which also causes death in patients with myeloma.

MALIGNANT LYMPHOMA (HAEMATOSARCOMA)

Malignant lymphomas (hematosarcomas)- regional malignant tumors of lymphoid tissue of monoclonal origin.

Lymphomas develop from immature forms of lymphocytes and affect the lymphatic tissue of any one area, however, in the terminal stage of the disease, generalization of the tumor process with the development of metastases to the bone marrow is possible.

Etiology.

The causes of malignant lymphomas are, in principle, no different from the causes of tumors of other origins. At the same time, it has been proven that some lymphomas. like some other leukemias, it is of viral origin. A hereditary predisposition to the disease cannot be ruled out. The transformation of normal hematopoietic cells into tumor cells occurs as a result of changes in the genome, as a result of which the normal genetic program of hematopoiesis changes in the direction of tumor atypia.

Classification of lymphomas.

1. According to clinical and morphological features:
   • lymphogranulomatosis, or Hodgkin's disease;
   • non-Hodgkin's lymphomas.
2. According to the source of growth (cytogenesis):
   • B lymphocytes;
   • T-lymphocyte.
3. According to the degree of differentiation of tumor cells:
   • low malignancy;
   • moderate malignancy;
   • high malignancy.

Lymphogranulomatosis (Hodgkin's disease) described in 1832 by the English physician T. Hodgkin. The incidence of the disease is 3 cases per 100,000 population, or 1% of all malignant neoplasms. The tumor usually affects the lymph nodes of one area - cervical, mediastinal, retroperitoneal, less often axillary or inguinal.

Morphogenesis.

The affected lymph nodes increase in size, merge with each other and form large bags. At the beginning of the disease, the lymph nodes are soft and pink when cut. As lymphoma progresses, necrotic and then sclerotic changes develop in them, due to which the lymph nodes become denser and look dry and mottled when cut. In its development, lymphogranulomatosis goes through several stages - from isolated damage to a group of lymph nodes to generalized damage to internal organs with suppression of lymphoid tissue and its replacement by fields of sclerosis.

On microscopic examination, the tumor consists of polymorphic tumor cells of the lymphocytic series, among which there are characteristic giant cells with a lobed nucleus and a narrow rim of cytoplasm - Berezovsky-Sternberg cells. These cells serve as a diagnostic sign of lymphogranulomatosis. In addition, it is characteristic Hodgkin cells - large cells with a large light nucleus and a dark nucleolus.

Often, at the end of the disease, it becomes generalized, affecting many internal organs - the stomach, lungs, liver, skin. During the autopsy of those who died from lymphogranulomatosis, the spleen looks especially demonstrative - it is enlarged in size, dense, red in section with multiple white-yellow foci of necrosis and sclerosis, which gives it a resemblance to a special type of granite - porphyry(porphyritic spleen).

Non-Hodgkin's lymphomas.

This is a group of malignant tumors from undifferentiated and blast forms of B and T cells of lymphatic tissue. The diagnosis of these diseases requires mandatory morphological and immunohistochemical examination of lymph node biopsies.

Anemia is a group of diseases characterized by a decrease in the total amount of hemoglobin. In the peripheral blood, red blood cells of various sizes (poikilocytosis), shape (anisocytosis), varying degrees of color (hypochromia, hyperchromia), inclusions (basophilic grains, or Jolly bodies, basophilic rings, or Cabot rings) may appear. And according to bone puncture, the form of anemia is judged by the state of erythropoiesis (hyper- or hyporegeneration) and by the type of erythropoiesis (erythroblastic, normoblastic and megaloblastic).

The causes of anemia are various: blood loss, increased blood destruction, insufficient erythropoietic function.

Classification of anemia

By etiology: post-hemorrhagic, hemolytic and due to impaired blood formation. According to the nature of the course: chronic and acute. According to the state of the bone marrow: regenerative, hyporegenerative, hypoplastic, aplastic and dysplastic.

Anemia due to blood loss can be chronic or acute. The pathological anatomy of acute posthemorrhagic anemia is as follows. Bone marrow cells of flat bones and epiphyses of long bones intensively proliferate, the bone marrow becomes juicy and bright. The adipose (yellow) bone marrow of long bones also becomes red, rich in erythropoietic and myeloid cells. Foci of extramedullary (extramedullary) hematopoiesis appear in the spleen, lymph nodes, thymus, perivascular tissue, fiber of the renal hilum, mucous and serous membranes, and skin. In chronic posthemorrhagic anemia, the skin and internal organs are pale. Bone marrow of flat bones of normal appearance. In the bone marrow of tubular bones, regeneration phenomena expressed to varying degrees and the transformation of fatty bone marrow into red are observed. Chronic hypoxia of tissues and organs occurs, which explains the development of fatty degeneration of the myocardium, liver, kidneys, and dystrophic changes in brain cells. Multiple pinpoint hemorrhages appear in the serous and mucous membranes and in the internal organs.

Deficiency anemia (due to impaired blood formation) occurs as a result of lack of iron (iron deficiency), vitamin B 12 and folic acid (B 12 – deficiency anemia), hypo- and aplastic anemia. Iron deficiency anemia is hypochromic. IN 12 – deficiency anemia megaloblastic hyperchromic. The skin is pale with a lemon-yellow tint, the sclera is yellow. Hemorrhages form on the skin, mucous and serous membranes. Hemosiderosis of internal organs, especially the spleen, liver, and kidneys, is noted. The gastric mucosa is thinned, sclerotic, smooth and devoid of folds. The glands are reduced, their epithelium is atrophic, only the main cells are preserved. Lymphoid follicles are atrophic. Atrophic processes are also present in the intestinal mucosa. The bone marrow of flat bones is crimson-red and juicy. In long bones, the bone marrow has the appearance of raspberry jelly. In hyperplastic bone marrow, immature forms of erythropoiesis predominate - erythroblasts, which are also found in the peripheral blood. In the spinal cord, the breakdown of myelin and axial cylinders is visualized. Sometimes areas of ischemia and softening appear in the spinal cord.

Hypo- and aplastic anemia are a consequence of profound changes in hematopoiesis, especially in young elements of hematopoiesis. Oppression occurs up to the suppression of hematopoiesis. If only suppression occurs, then in the punctate from the sternum one can find young cell forms of the erythro- and myelopoietic series. When hematopoiesis is suppressed, the bone marrow is emptied and replaced by fatty marrow, thus developing panmyelophthisis. Multiple hemorrhages occur in the mucous and serous membranes, phenomena of general hemosiderosis, fatty degeneration of the myocardium, liver, kidneys, and ulcerative-necrotic processes in the gastrointestinal tract. Hemolytic anemia occurs as a result of the predominance of blood destruction processes over blood formation. They are classified into anemia with intravascular and extravascular hemolysis. Anemias with extravascular hemolysis are divided into erythrocytopathies, erythrocytoenzymepathies and hemioglobinopathies.

The pathological picture is as follows. General hemosiderosis and suprahepatic jaundice, as well as hemoglobinuric nephrosis, occur. The bone marrow is hyperplastic, pink-red, juicy. Foci of extramedullary hematopoiesis appear in the spleen, lymph nodes, and loose connective tissue.