The changes in the blood occurring in disease in some measure reflect the dysfunctions of various organs and tissues. The changes originally arising in the blood itself and especially, in the organs of hematopoiesis are of particular interest. These diseases have long been classified in a special group designated a«, diseases of the blood and hematopoiesis. Changes in the total volume or mass of the blood, its formed elements, and its biochemical and physicochemical composition are distinguished according to the character of the phenomena observed. CHANGES IN THE TOTAL VOLUME OF THE BLOOD Various forms of increased and decreased total volume of the blood are observed in pathology. An excess of the total volume of blood in the budy is called polyemia, hypervolemia or plethora. Depending on the ratio of plasma to erythrocytes, three? forms of hypervolemia are distinguished: 1) hypervolemia plasma-erythrocyte ratio: 2) hypervolemia with an excess of erythrocytes; 3) hypervolemia with an excess of plasma. The first form - simple hypervolemia with a normal plasma –erythrocyte ratio - occurs very rarely. It may arise for short time following transfusion of large amounts of blood from the blood depots in the beginning of strenuous work, or under high external temperature. Repeated experiments have been made to produce hypervolemic, in animals by transfusion of homogenous blood. However, thest* attempts were for the most part accompanied only by a brief increase in the blood volume and a slight, and also brief, rise in blood pressure.. Processes of compensation follow immediately. The blood plasma very soon passes into the tissues., while the transfused erythrocytes are gradually destroyed, which is attested by excessive formation of bile pigments from the hemoglobin. Plethora with a 150 per cent or higher increase in the mass of blood artificially produced in animals imperils their life. Г: disturbs the regulation of the volume of circulating blood, reduces vascular tone, excessively dilates the vessels and-causes circulatory disorders; these disturbances are soon followed by hemoconcentration (as a result of increased transudation o^: plasma into the tissues and serous cavities), considerable disintegration of erythrocytes and cardiac failure. The second form is polycуtheroic hypervolemia, i.e., with an increased number of erythrg_cytes, the increase in the amount of hemoglobin lagging behind the increase in the number 'of erythrocytes. The erythrocytes may number from 10 million to 13 million per 1 mm3 of blood. This disease ig also kn'own^'aVb-utp plethora or true polyemia and is characterised bv increased hematopoiesis vMhose signs are usually easily observed in the marrow, spleen ~ad ot h er h emaifbp оТеТГс~ог gahs Г~ I t "is supposed that the increased hematopoietic function of the bone marrow !•;•> stimulated by some substance formed in the process of disturbed metabolism. In addition to the increased number of ery throcytes, true plethora is, as a result of the increase in the volume of blood, often characterised by t^egLementary ^hypereinia, elevated blood ressure, hypertrophy of the left ventricle which with -each systole drives more blood into the aorta. The third form is oligocythemic hypervolemia or hydremic pletora with an execess of plasma. It may be due to retention of water in the blood stream as a result of certain diseases of the kidneys or the hematopoietic system, or disturbances in water metabolism. Attempts have been made to produce oligocythemic hypervolemia experimentylly by intravenous injections of physiologic saline solution in the dog or rabbit. As a rule, these attempts have failed because the excess of fluid rapidly passed from the blood into the tissues and was gradually eliminated mainly through the kidneys. The changes occurring in connection with intravenous administration of physiologic saline solution are observed in the following experiment: a 0.7 per cent sodium chloride solution is slowly introduced through a cannula into the frog^s abdominal. vein. While this is done the circulatory changes are observed in the stretched web. The circulation of the blood in the vessels is «4 noticeably accelerated, the blood is diluted, the volume of the fluid part increases and the mass of corpuscles relat i'/*iy diminishes. Vascular permeability appreciably increase. These phenomena are soon followed by increased excretion of fluid into the lymph sac, urxnary bladder and abdominal cavity. All i:h.^»e phenomena must be considered compensatory sin'ce the-y -эег'-у» t.o restore the normal volume of blood. Rapid administration of large amounts of fluid leads to the animal’s death due to extensive disturbances in blood circulation, congestion in pulmonary circulation, hemorrhages and affection* of the myocardium. Hydremic plethora should be distinguished from hydremia whose characteristic feature is a decrease in the dense residue without a general increase in the total volume of blood *rrv (oliigocythemic normovolemia). Such phenomena often occur in cachexias, anemias and avitaminoses. A decrease in the total volume of blood - oligemia or hypavoleraia - may be very brief in its pure form. Hypovolemia is most frequently accompanied by a decrease in the number and changes in the quality of erythrocytes. Analogously with hypenyplemia three forms of hypovolemia may also be distinguished according to the ratio of the plasma to the ereythrocytes: 1) hypovolemia with a normal plasma-erythrocyte .ratio; 2) ' hypovolemia with a decreased amount of plasma, or hemoconcentration; 3) hypovolemia with a - decreased number of erythrocytes. The first form – hypovolemia with a normal plasma-erythrocyte ratio - is observed directly after acute hemorrhages which may be due to injuries of large vessels, ulcers, active forms of pulmonary tuberculosis or rupture of the fallopian tubes. The results of acute hemorrhages vary greatly. They depend on the rate of the blood flow, the mass of blood, lost and the general condition of the organism. For a healthy organism a single loss of 50-60 per cent of the total amount of blood is fatal. After such a hemorrhage restoration of the mass of blood by natural means becomes impossible and insufficiency of oxygen^ in the blood (hypoxemia), oxygen deficiency (hypoxia), disorders ^of hemodynamics and respiration, shock and phenomena of asphyxia result. The condition is also accompanied by a drop in arterial pressure; acute cerebral anemia, extreme pallor, increasing depression of the functions of the respiratory and vasomotor centres, and cardiac failure; the pulse becomes thready. The diminution in the mass of the circulating blood and the oxygen deficiency give rise to excitation of the motor zone of the cerebral cortex and convulsions. These phenomena are the more strongly pronounced the more rapid the hemorrhage. The organism may die exhibiting a considerable drop in blood pressure, a fall of the body temperature and paralysis of the respiratory centre. Repeated minor hemorrhages cause a slow development of hypovolemia. Simultaneously with the disorders of a number of vitally in^tartant functions hemorrhages lead to mobilisation of the adaptive physiological defence mechanisms by means of which it is possible to restore the blood pressure, as well as the volume" and function of the blood. The lowered blood pressure is compensated by the following processes: 1) reflex stimulation of the vasomotor centre with a resultant increase in vascular tone and spasm of the peripheral vessels;-2) increase in the mass of the circulating blood through an inflow of blood from the blood depots and tissue fluid; 3) increased blood clotting which lead to arrest of the hemorrhage, and 4) subsequent hyperfunction of the hematopoietic apparatus stimulated by the hemorrhage and insufficiency of available oxygen (hypoxia) . Restoration of the blood pressure after a hamorrhage is noticeably accelerated by protective inhibition in the cerebral cortex. It is therefore facilitated by means of "artificial sTeep", which closely resembles natural sleep, but is retarded by deep narcotic sleep. This denotes participation of the higher parts of the nervous system in the restoration of the blood. The resultf of hemorrhage consist not only in the , changed volume of the blood, . but also in its altered composition. The first result is an increase in the number of blood platelets (sometimes to 1 mrllion per 1 mm ) and in intensified blood clotting. Within a few days the number of leukocytes increases a^ a result of their discharge from the intensely functioning bone m'arrow. The number of erythrocytes at first decreases owing to dilution of the blood by tissue lymph and then gradually increases as a result of increased hematopoiesis in the bone marrow. Young forms of red blood cells - normoblasts, reticulccytes and polychromatophilic erythrocytes appear in the blood. The extent of restoration of the blood elements varies and/ depends on the amount of blood lost, the rate of bleeding, and regenerative capacity of the organism and its hematopoietic system. Since the principal cause of death after a massive *c:ute hemorrhage is a drop in blood pressure, transfusion of blood or blood substitutes, which is usually resorted to in operations or in cases: of injuries to vessels, is the most effective measure. The pathogenic role of the diminution in the mass of blood and of the drop in blood pressure during hemorrhage is evidenced by the favourable effect produced by blood- and plasma-substituting solutions which diffuse in the tissues slowly and are longer retained in the blood stream. In addition to blood, especially treated foreign proteins have been proposed and are successfully used <N.A.Fyodorov). Plasma or serum containing hypnotics and anodynes are used for the same purposes. , In hemorrhages» anemia, shock, etc., blood transfusion produces a very favourable effect. Firstly, the blood is for some time restored quantitatively. Secondly, by stimulating the interoceptors of the vessels the transfused blood and the physiologically active products of partial disintegration of erythrocytes reflexly stimulate the function of the hemotopoietic: apparatus/ improve the process of blood clotting and raise the general immunobiological stability of the? organism, The second form of hypovolemia, i.e., with * decreased amount of plasma - polycythemic hypovolemia or anhydremia - j.s characterised by appreciable concentration and increased viscosity of the blood. Anhydremia is observed in connection with considerable losa" of water by the organism, as in cholera, dysentery, infantile Diarrhea, intractable vomiting, and extensive burns involving loss of a great deal of fluid with the exudate and evaporation from burned surfaces. The third form of oligemia is oligocythemic hypovolemia – a diminished volume of blood mainly because of a decreased number of erythrcfcytes. It is observed after hemorrhages in cases of increased passage of fluid from tissues into the vascular syflftem and in certain forms of anemia, for example, pernicious anemia. IN ADDITION TO THE LECTURE «ANEMIAS» Anemias of diminished erythropoiesis (diserythropoietic anemias)' impairec Ted cell production. Classification (according to Robins' textbook). A. Disturbance of proliferation and differentiation of stem cells: aplastic anemias, pure red cell aplasia, anemia of renal failure, anemia of endocrine disorders. B. Disturbance of proliferation and maturation of erythroblasts: 1. Defective DNA synthesis: deficiency or impaired utilization of vit В12 and filic acid (megaloblastic anemias). 2. Defective hemoglobin synthesis. a. Deficient heme synthesis: iron deficiency b. Deficient globin synthesis: Thalassemias 3. Unknown or multiple mechanisms: sideroblastic anemia, anemia of chronic infections, myelophthisic anemias due to marrow infiltrations. MEGALOBLASTIC ANEMIAS. Megaloblastic anemias develop as the result of vit В and folic acid deficiency. The daily requirement is of the order of 2 to 3 g, and the normal balanced diet contains significantly larger amounts. The main steps of vit В absorption. I. In the stomach: (Vit В12 + salivary binding protein) - complex forms. II. In the duodenum: (vit В12 + salivary binding protein) - complex is broken by pancreatic proteases action. (vit В12 + Intrinsic factor) - complex forms. Intrinsic factor (iFO is secreted by the parietal cells of the fundic mucosa along with HCL. III. In the ileum: (vit В12 + Intrinsic factor) - complex adheres to Intrinsic factor - receptors on the ileal cells. Vit В12 then transverse the plasma membrane to enter the mucosal cell. It is picked up from the cell by a plasma protein, transcobalamin, which is capable to deliver it to the liver and other cells, particularly in the bone marrow. IV. In the blood: (vit В12 + transcobalamin II) - complex is transported. The causes of vit В12 deficiency: I. Impaired utilization: 1. Achlorhydria and loss of pepsin secretion (vit В is not readily released from its protein - bound form); 2. Gastrectomy and atrophic gastritis: the deficiency of intrinsic factor formation and disturbance in vit В transport of the ileum; 3. Loss of exocrine pancreatic function: vit В cannot be released from vit В12 + salivary binding protein complexes. 4. Ileal diseases can disturb vit В + intrinsic factor complex absorption. II. Increased requirements: relative deficiency under some circumstances (pregnancy, hyperthyroidism, etc). III. Food deficiency, or decreased intake. Biochemical functions of vitamin В Vitamin В (methylcobalamin), the synthetic form of it is a stable cyanocobalamin. It has two pathways of biochemical effects. 1. Methylcobalamin is an essential cofactor for the enzyme ensuring transmethylatipn reaction. It is involved in the DNA synthesis. The tetrahydrofolic acid (FH) is required for the formation of immediate precursor of DNA. The fundamental cause of impaired DNA synthesis in vitamin В deficiency is the reduced availability of tetrahydrofolic acid. The internal folate deficiency results from the lack of vitamin В12. 2. Another derivative of cobalamin - desoxyadenosyl cobalamin is a prosthetic group on the enzyme that is necessary for the metabolism of methylmalonic acid. This disorder is followed by increased levels of methylmalonate and its precursor propionate. It leads to the formation of abnormal fatty acids incorporated into neuronal lipids that results in myelin breakdown and development of neurologic complications. Thus, lack of either vit В or folic acid causes diminished DNA and consequently failure of nuclear maturation and division. Furthermore, the erythorblastic cells of the bone marrow, in normal, developing into so - called megaloblasts, and the adult erythrocytes have a flimsy membrane and is often irregular, large, and oval instead of the usual beconcave disc. This altered type of erythoropoieses resembles embryonal type and is called megaloblastic. The cause of the abnormal cells seems to be as follows: The inability of the cells to synthesize adequate quantities of DNA leads to slow reproduction of the cells but does not prevent formation of RNA by the DNA that is already available in each presently existing cell. Therefore the quantity of RNA in each cell becomes much greater than normal, leading to excess production of cytoplasmic hemoglobin and other constituents which causes the cells to enlargement because of abnormalities of some of the genes (the DNA), the structural components of the L :11 membrane and cytoskeleton are malformed wuich leads to abnormal cell shapes and especially greatly increased cell membrane fragility. Pernicious anemia (Addison's or Biermer's anemia) is a megaloblastic anemia in which there is atrophy of the gastric mucosa with consequent failure of intrinsic factor production and vit В melabsorption. Pernicious anemia is believed to result from immunologically mediated, possibly autoimmune, destruction of gastric mucosa. The resultant chronic gastritis is marked by a loss of parietal cells. Three types of antibodies are present in many, but not all, patients with pernicious anemia: 1. Blocking В12 - IF binding (Ig G); 2. Binding antibodies reacts with both IF and (vit В +IF) - complex; 3. Parietal antibodies. Autoantibodies cause gastric mucosal injury. The major specific changes in pernicious anemia are found in the bone marrow, alimentary tract and CNS. The principal alterations involve the spinal cord, where there is myelin degeneration of the dorsal and lateral tracts (sensory ataxia, severe parethesias). Blood picture. Certain morphologic features are common to all forms of megaloblastic anemia. The peripheral blood reveals. 1. Marked variation in the size and shape of red cells - anisocytosis. 2. They are nonetheless normochromic. 3. Many erythrocytes are macrocytic and oval shaped (macro- ovalocytes). 4. They are thicker than normal and well filled with hemoglobin; most macrocytes lack the central pallor of normal cells and may even appear "hyperchromic". 5. The reticulocyte ',ount is lower than normal and occasionally with severe anemia, nucleated red cells appear in the circulating blood. 6. Neutrophils are larger than normal (macropolymorphonuclear) and are hypersegmented. They may have five to six or more nuclear lobules. The bone marrow. • r-m The megaloblastic change is detected in all stages of red cell development (the - embryonal type of hemopoiesis). Because DNA synthesis is impaired in all proliferating cells nuclear - cytoplasmic asynchrony becomes apparent in all cells. The cells are large, the nuclei are large. Ineffective erymropoiesis occurs: premature destructfon of all cells in marrow. Folate deficiency. A deficiency of folic acid, more properly pteroylmonoglutamic acid, results in a megaloblastic anemia having the same characteristics as those encountered in vitamin В deficiency. However, the neurologic changes seen in vit В deficiency do not occur. FH derivatives acts as an acceptor of one - carbon fragments for the synthesis of biologically active molecules. Supressed synthesis of DNA, the common denominator of folic acid and vit В12 deficiency, is the immediate cause of megaloblastosis. There are three major causes of folic acid deficiency: (1) decreased intake; (2) increased requirements (pregnancy, infancy) (3) impaired utilization (manifestations: cheilosis, glossitis, dermatitis). In addition to Addison's or Biermer's pernicious anemia, there are also secondary pernicious anemias, as in cases of infestation with tapewarms (Diphyllobothrium latum), and certain severe affections of the stomach (syphilis, cancer, pellagra). In all these cases a pathogenetic role is also played by the antianemia factor deficiency due to its diminished absorption or utilization in the organism. Anemias due to marrow aplasia. 1. Inciting or causative agents may be radiation, drug (especially benzene derivatives), certain antibiotics, viruses. Not only the marrow but also other sites of hematopoiesis reflect injury to the stem cells. The marrow spaces are occupied only by fat. 2. Some cases of aplasia involve only one hematopoietic line, as in Diamond - Blackfan syndrome, a congenital defect involving erymroid hypoplasia, Certain tumors, such as thymomas, are associated with pure red cell aplasia. Myelophthisic anemias. In this conditions, the marrow is replaced by foreign "invaders" (e.g. carcinomas, leukemias, granulomas). Extramedullary hematopoiesis, particularly in the spleen (as in the fetal period), is found. Primary bone marrow myofibrosis also induces this types of anemia by replacing marrow in fibrosis of unknown causes. Anemias due to systemic disorders. Endocrine diseases, such as hypothyroidism, hypopituitarism are associated with low blood counts. Poor marrow function and anemia can be seen in uremia and malignancy. Iron deficiency anemias. Iron distribution in healthy young adults: 1. Functional compartments: hemoglobin (80%), myoglobin, iron - containing enzymes (catalase, cytochromes); 2. Storage compartments: ferritin, hemosiderin (15-20% of total body iron). Ferritin is essentially a protein - iron complex that can be found in all tissues but particularly in liver, spleen, bone marrow and skeletal muscles. In the liver, most of the ferritin is stored within the parenchymal cells, whereas in other tissues, such as spleen, a bone marrow, it is mainly in the mononuclear phagocytic cells. Ths iron within the hepatocytes is derived from plasma transferrin, in the mononuclear phagocytic cells is obtained from the breakdown of red blood cells). Iron from ferritin is aggregated into hemosiderin granules (in Very small amounts of ferritin normally circulate in the plasma (a good indicator of the adequacy of body iron stores). Iron is transported in the plasma by an iron - binding glycoprotein called ^ transferrin, which is synthesized in the liver. The major function of plasma transferrin is to deliver iron to the cells including erythroid precursors. Immature red cells posses high - affinity receptors for transferrin, and iron is transported into erythroblasts by receptor - mediated endocytosis. The fix daily losses of iron rangers between 1 and 1,5 mg. Because only 10 to 15 % of the ingested iron is absorbed, the daily iron requirement for adult males is 5 to 10 mg and for adults females 7 to 20 mg. Ascorbic acid, citric acid, aminoacids, and sugars in the diet enhance absorption of inorganic iron, but tannates (as in tea), carbonates, oxalates, and phosphates inhibit its absorption. An iron deficiency may result from (1) dietary lack (diets a predominantly vegetarian); (2) impaired absorption; (3) increased requirement, or growing infants and children, adolescent}', pregnancy; (4) chronic blood loss. Whatever the basis, iron deficiency induces a hypochromic microcytic anemia. Simultaneously, depletion of essential iron - containing enzymes in cells throughout the body may cause other changes including brittle nails, coilonychia, alopecia, atrophic changes in the tonque and gastric mucosa, and intestinal malabsorption, hypotension, fatiqubility. HEMOLYTIC ANEMIAS (INCREASED RATE OF RED CELL DESTRUCTION). Classification (according to Robins' textbook). A. Intrinsic (intracorpuscular) abnormalities of red cells: Hereditary: 1. Disorders of red cell membrane cytoskeleton (spherocytosis, elliptocytosis). 2. Red cell enzyme deficiencies a) Glycolytic enzymes: pyruvate kinase hexokinase b) Glutathione synthetase 3. Disorders of hemoglobin synthesis: a)Thalassemia syndromes - deficient globin synthesis, b) Structurally abnormal globin synthesis (hemoglobinopathies): Sickle cell anemia. Acquired: 1. Membrane defect: paroxysmal nocturnal hemoglobinuria. B. Extrinsic (extracorpuscular) abnormalities. 1. Antibody mediated. a) Isohemagglutinins: transfusion reations b) Autoantibodies: idiopathic (primary) drug - associated 2. Mechanical trauma to red cells. a) Microangiopathic hemolytic anemias b) Cardiac traumatic hemolytic anemia 3. Infections: Malaria 4. Chemical injury: lead poisoning 5. Sequestration in mononuclear phagocyte system: hypersplenism The hemolytic anemias all are characterized by (1) shortening of the normal red cell life span, that is, premature destruction of red cells; (2) accumulation of the products of hemoglobin catabolism, and (3) a marked increase in erythropoiesis within the bone marrow, in an attempt to compensate for the loss of red cells. Intravascular hemolysis is manifested by: (1) hemoglobinemia, (2) hemoglobinuria, ~ (3) methemalbuminemia, (4) jaundice, and (5) hemosiderinuria. When hemoglobin escapes into the plasma, it is promptly bound by an alpha globin (haptoglobin) to produce a complex that prevents excretion into the urine, since the complexes are rapidly cleared by the reticuloendothelial system. A decrease in serum haptoglobin level is characteristically seen in all cases intravascular hemolysis. When the haptoglobin is depleted, the unbound or free hemoglobin is in part rapidly oxidized to methemoglobin, and both hemoglobin and methemoglobin are excreted through the kidneys (hemoglobinuria, methemoglobinuria). Extravascular hemolysis takes place whenever red cells are injured, are rendered "foreign", or become less deformable. For example, in hereditary spherocytosis an abnormal membrane cytoskeleton decreases the deformability of the red cell. Analoquously, in sickle cell anemia, the abnormal hemoglobin «gels» or «crystallizes» within the erythrocyte, deforming it and reducing its platicity. With extravascular hemolysis it is obvious that hemoglinemia, hemoglobinuria, and the relatide intravascular changes do not appear. However, the catabolism of erythrocytes in the phagocytic cells induces anemia and jaundice. Erythrophagocytosis may lead to hypertrophy of the mononuclear phagocyte system and splenomegaly. Blood picture. The accelerate compensatory erythropoiesis leads to a prominent reticulcytosis in the peripheral blood. The elevated level of billirubin promote the formation of pigment gallstones. POLYCYTHEMIA Polycythemia is defined as an increase in red cell count in blood volume unit and also increase in hemoglobin content and hematocrit. It can't be divided into (1) an absolute erythrocytosis where there is a true increase in red cell volume or (2) relative erythrocytosis where red blood cell volume is normal but there is a . decrease in the plasma volume (dehydration, burns, etc.). Absolute erythrocytosis may be due to (1) primary polycythemia or (2) secondary polycythemia. Primary polycythemia (polycvthemia vera) ervthremia is a clonal stem cell disorder in which there is an alteration in the pluripotent progenitor cell leading to excessive proliferation of erythroid, myeloid and megakaryocytic elements. The main clinical problems are due to the increased volume and viscosity of the blood and to the bone marrow overactivity. Red blood cell count may be as high as 7 to 8 million/mm and hematocrit as high as 60 to 70 %. The total blood volume also increases, rarely to almost twice normal. The entire vascular system becomes intensely engoged. Many of the capillaries become plugged by the viscous blood. The bone marrow shows erythroid hyperplasia and increased number of megakaryocytes. It is a myeloproliferative disorder, however, in polycythemia very the erythroid precursors dominate. Secondary polvcvthemia may be physiologic condition in response to hypoxia and due to an appropriate increase in erythropoietin production. Physiologic polycythemia occurs in natives who live at altitude of 14, 000 to 17, 000 feet. Secondary polycythemia may be caused by a variety of hypoxic conditions, such as impaired pulmonary ventilation and heart diseases. In such disorders, erythropoietin is elevatide and stimulated marrow cells to produce erythrocytes. Other marrow element are normal in number, function and morphology. In addition to lecture "Leukocytosis Leukopenia" Neural mechanisms of leukocytosis development. It is known that tissue injury and also their antigenic and biochemical changes cause the reflex activation of CNS. If the sympathetic-adrenal system activation is predominant two following mechanisms of neutrophilia development are involved: (1) the stimulation of the bone marrow activity and acceleration of leukocyte ejection into the peripheral blood (2) adrenergic vasoconstriction and the mobilisation of leukocytes from the marginal pool; (3) the accumulation of lymphocytes in the bone marrow. If the parasympathetic nervous activity is predominant the elevated counts of lymphocytes and eosinophils in the peripheral blood are arised, i.e. lymphocytosis develops. The character and expression of leukocytosis depend on (1) the strength and character of pathogenic action; (2) organises reactivity (3) the localization of pathologic processes It is known that pathology of respiratory system and the thorax is followed by the sympathetic activation and development of neutrophilia and lyrnphocytopenia. On the contrary the pathology of the gastrointestiral tract often is followed by the parasympathetic activation and the development of lymphocytesis and eosinophilia. The distinct mechanisms of leukocytosis development may be activated in the certain sequence. There is the evidence of the certain sequential induction induction of the different mechanism controlling leukocytosis development in particular in aciite different infectious diseases In these cases three following phases of leukocytosis development were found: (1) neutrophilia; (2)monocytosis; (3)lymphocytosis. Neutrophilia corresponds to the beggining of an acute infectious disease. The main mechanisms of its development are as follows (1) adrenergic activation causing neutrophilia cells mobi1ization from the bone marrow and marginal reserves (2) hypothalamo-pituitary system and target-gland activation promoting to netrophillia and lymphopenia; (3) the humoral activation of the bone marro via colony stimulating factors. The emigration of T-cells from blood to the damaged tissue and lymphatic node also ensures lymphonia development. Monocytosis phase corresponds to the marked period of the disease and to the onset of recovery/ This period is characterized by the enhance of macrophage system activity. The principal mechanism of this system activation is formation of antigen antibody complex. Limphocytosis phase corresponds to the recovery. It is observed as result of antigen elimination stopping of the antigen activation of T-cells come back in the blood from tissue. The recurrence of T-cells in the blood from the tissue is thought the important mechanism of limphocytosis development. Leukemoid reactions Leukomoid reactions are the pathologic reactions of the blood system resembling leukemia because of the appearance of immature white blood cells and very high leukocyte count. The principal difference leukemoid reaction in comparison with leukemias it completely disappears after stopping of it arises in severe infectious diseases and completely dissappears after infection elimination. Two forms of leukemoid reactions are known (1) myeloid and (2) monocytic-lymphocytic. Lymphatic myeloid reaction may be observed in infectious mononucleousi A leukemoid reaction is an overproduction of white cells with many immature cells. It may occur in severe infections, tuberculosis, and occasionally after hemorrage or hemolysis. The principal differences from leukemia (1) in etiology leukemoid reaction arises as the result of certain causative action; (2) it has in its basis the reactive hyperplasia of the bone marrow but not neoplasin (3) it is a temporary disorder and stops after the cessation of primary disease. Leukopenia Leukopenia is a decrease in the leukocyte count in the volume unit of the circulatory blood below 4.0* 10 cell In the most cases extent the total leukocyte blood count is ensured by decrease in absolute neutrophil count. Three main mechanisms are (underlied) based the basis of the 1enkopenia pathoqenesis. They are (1) decrease in leukocyte production in the bone marrow; (2) disturbances in leukocyte ejection from the bone marrow; (3) inorease in leukbcyte distruction. (4) the redistribution of leukocytes within blood vascular system; THE disturbances in leukocyte production (1) the internal deficiency of stem cells to proliferate and differentiate (2) the autoimmune injury of bone marrow progenitor cells -the consequence of it: the distinct forms of aplastic and hypoplastic anemias, panleukopenia, acute agranulocytasis; (3) the damage of the precursors of granulopoiesis (leukopoisis) by T-cells; (4) the direct action of myelotoxic agents (some drugs, benzene radiation); (5) the viral damage of hemopoiesis; (6) the deficiency of hemopoietic agents v.B12 folic acid) (7) the toxic action of neoplastic cell in leukemia; (8) the ousting of leucopoiesis cells by neoplastic metastasis tissue (9) the deficiency of leukopoietic factor format ion (for example the deficiency of the monocyte secretion of the g-CSF (granulocyte colony stimulating factor)). These deficiencies may occur in immune deficiency diseases. Disturbances in leukocyte ejection from the bone marrow (1) the disorders of leukocyte motile activity as the result of memranopathy -. the syndrome of "leasy" leukocytes. These disorders are divided into hereditary and acquired ones (as the result of some drug action). Decrease in the duration of leukocyte circulation in the blood. (1) the autoimmune damage of circulating (neutrophils) leukocytes via agglutinins; (2) the autoimmune damage of circulating (neutrophils) leukocytes via opsonins with the following phagocytosis; (3) the autoimmune damage of circulating (neutrophils) leukocytes via T-cells (4) the destruction of leukocytes by toxins; (5) the elevated destruction of leukocytes in liver and spleen, (6) the elevated destruction of leukocytes as the result of memfaranopattiy (for example, in magaloblastic anemia) . The redistribution of leukocytes within blood vascular system (shock, chills, strenuous muscle work). Aqranulocytosis is the disorder characterised by complete or about complete disappearance blood neutrophils the neutrophil count is less 750 eel Is/ limn Two main forms of agranulocytosis are distinguished according to the etiology into (1) acquired and (2) idiopathic Acquired agranulocytosis is often caused by some drug application, namely cytostatic drugs, sulfonilamides, antibiotics, antithyroid drugs and some others. According to the mechanisms of development the drug caused agranulocytoses are divided into myelotoxic and immune ones. Myelotoxic agranloucytosis arises as a result of toxic inhibition action of drugs on the proliferative activity of granulopoiesis. It is usually combined with anemia and thrombocytopetvia involvement has the following explanations drug substance serves as hapten, produces formation of complete antigen, causes the antibody production. Formed antibodies act on the leukocytes and destroy them.
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