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. CHANGE !N THE T"TA# $"#%&E "' THE (#"") $arious forms of increased and decreased total volume of the blood are observed in pathology. An e*cess of the total volume of blood in the budy is called polyemia, hypervolemia or plethora. )epending on the ratio of plasma to erythrocytes, three+ forms of hypervolemia are distinguished, -. hypervolemia plasma/erythrocyte ratio, 0. hypervolemia 1ith an e*cess of erythrocytes2 3. hypervolemia 1ith an e*cess of plasma. The first form / simple hypervolemia 1ith a normal plasma 4erythrocyte ratio / occurs very rarely. !t may arise for short time follo1ing transfusion of large amounts of blood from the blood depots in the beginning of strenuous 1or5, or under high e*ternal temperature. 6epeated e*periments have been made to produce hypervolemic, in animals by transfusion of homogenous blood. Ho1ever, thest7 attempts 1ere for the most part accompanied only by a brief increase in the blood volume and a slight, and also brief, rise in blood pressure.. 8rocesses of compensation follo1 immediately. The blood plasma very soon passes into the tissues., 1hile the transfused erythrocytes are gradually destroyed, 1hich is attested by e*cessive formation of bile pigments from the hemoglobin. 8lethora 1ith a -9: per cent or higher increase in the mass of blood artificially produced in animals imperils their life. ;, disturbs the regulation of the volume of circulating blood, reduces vascular tone, e*cessively dilates the vessels and/causes circulatory disorders2 these disturbances are soon follo1ed by hemoconcentration <as a result of increased transudation o^: plasma into the tissues and serous cavities., considerable disintegration of erythrocytes and cardiac failure. The second form is polyc=theroic hypervolemia, i.e., 1ith an increased number of erythrg>cytes, the increase in the amount of hemoglobin lagging behind the increase in the number ?of erythrocytes. The erythrocytes may number from -: million to -3 million per - mm3 of blood. This disease ig also 5n?o1n@?a$b/utp plethora or true polyemia and is characterised bv increased hematopoiesis v&hose signs are usually easily observed in the marro1, spleen Aad ot h er h emaifbp BCDC;EABF gahs ;A ! t Gis supposed that the increased hematopoietic function of the bone marro1 HI2IJ stimulated by some substance formed in the process of disturbed metabolism. !n 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@eg#ementary @hypereinia, elevated blood ressure, hypertrophy of the left ventricle 1hich 1ith /each systole drives more blood into the aorta. The third form is oligocythemic hypervolemia or hydremic pletora 1ith an e*ecess of plasma. !t may be due to retention of 1ater in the blood stream as a result of certain diseases of the 5idneys or the hematopoietic system, or disturbances in 1ater metabolism. Attempts have been made to produce oligocythemic hypervolemia e*perimentylly by intravenous inKections of physiologic saline solution in the dog or rabbit. As a rule, these attempts have failed because the e*cess of fluid rapidly passed from

the blood into the tissues and 1as gradually eliminated mainly through the 5idneys. The changes occurring in connection 1ith intravenous administration of physiologic saline solution are observed in the follo1ing e*periment, a :.L per cent sodium chloride solution is slo1ly introduced through a cannula into the frog@s abdominal. vein. Mhile this is done the circulatory changes are observed in the stretched 1eb. The circulation of the blood in the vessels is N noticeably accelerated, the blood is diluted, the volume of the fluid part increases and the mass of corpuscles relat i?O7iy diminishes. $ascular permeability appreciably increase. These phenomena are soon follo1ed by increased e*cretion of fluid into the lymph sac, ur*nary bladder and abdominal cavity. All i,h.@Pe phenomena must be considered compensatory sin?ce the/y /QDF?/=P t.o restore the normal volume of blood. 6apid administration of large amounts of fluid leads to the animalRs death due to e*tensive disturbances in blood circulation, congestion in pulmonary circulation, hemorrhages and affection7 of the myocardium. Hydremic plethora should be distinguished from hydremia 1hose characteristic feature is a decrease in the dense residue 1ithout a general increase in the total volume of blood 7rrv <oliigocythemic normovolemia.. uch phenomena often occur in cache*ias, 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 freSuently accompanied by a decrease in the number and changes in the Suality of erythrocytes. Analogously 1ith hypenyplemia three forms of hypovolemia may also be distinguished according to the ratio of the plasma to the ereythrocytes, -. hypovolemia 1ith a normal plasma/erythrocyte .ratio2 0. ? hypovolemia 1ith a decreased amount of plasma, or hemoconcentration2 3. hypovolemia 1ith a / decreased number of erythrocytes. The first form 4 hypovolemia 1ith a normal plasma/erythrocyte ratio / is observed directly after acute hemorrhages 1hich may be due to inKuries 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 flo1, the mass of blood, lost and the general condition of the organism. 'or a healthy organism a single loss of 9:/T: 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 o*ygen@ in the blood <hypo*emia., o*ygen deficiency <hypo*ia., disorders @of hemodynamics and respiration, shoc5 and phenomena of asphy*ia result. The condition is also accompanied by a drop in arterial pressure2 acute cerebral anemia, e*treme pallor, increasing depression of the functions of the respiratory and vasomotor centres, and cardiac failure2 the pulse becomes thready. The diminution in the mass of the circulating blood and the o*ygen deficiency give rise to e*citation of the motor Uone of the cerebral corte* and convulsions. These phenomena are the more strongly pronounced the more rapid the hemorrhage. The organism may die e*hibiting a considerable drop in blood pressure, a fall of the body temperature and paralysis of the respiratory centre. 6epeated minor hemorrhages cause a slo1 development of hypovolemia. imultaneously 1ith the disorders of a number of vitally in@tartant functions hemorrhages lead to mobilisation of the adaptive physiological defence mechanisms by means of 1hich it is possible to restore the blood pressure, as 1ell as the volumeG and function of the blood. The lo1ered blood pressure is compensated by the follo1ing processes, -. refle* stimulation of the vasomotor centre 1ith a resultant increase in vascular tone and spasm of the peripheral vessels2/0. increase in the mass of the circulating blood through an inflo1 of blood from the blood depots and tissue fluid2 3. increased blood clotting 1hich lead to arrest of the hemorrhage, and N. subseSuent hyperfunction of the hematopoietic apparatus stimulated by the hemorrhage and insufficiency of available o*ygen <hypo*ia. .

6estoration of the blood pressure after a hamorrhage is noticeably accelerated by protective inhibition in the cerebral corte*. !t is therefore facilitated by means of Gartificial sTeepG, 1hich 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 - mrllion per - mm . and in intensified blood clotting. Mithin a fe1 days the number of leu5ocytes increases a@ a result of their discharge from the intensely functioning bone m?arro1. The number of erythrocytes at first decreases o1ing to dilution of the blood by tissue lymph and then gradually increases as a result of increased hematopoiesis in the bone marro1. Voung forms of red blood cells / normoblasts, reticulccytes and polychromatophilic erythrocytes appear in the blood. The e*tent of restoration of the blood elements varies andO depends on the amount of blood lost, the rate of bleeding, and regenerative capacity of the organism and its hematopoietic system. ince the principal cause of death after a massive 7c,ute hemorrhage is a drop in blood pressure, transfusion of blood or blood substitutes, 1hich is usually resorted to in operations or in cases, of inKuries 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 1hich diffuse in the tissues slo1ly and are longer retained in the blood stream. !n addition to blood,

especially treated foreign proteins have been proposed and are successfully used WN.A.'yodorov.. 8lasma or serum containing hypnotics and anodynes are used for the same purposes. , !n hemorrhagesP anemia, shoc5, etc., blood transfusion produces a very favourable effect. 'irstly, the blood is for some time restored Suantitatively. econdly, by stimulating the interoceptors of the vessels the transfused blood and the physiologically active products of partial disintegration of erythrocytes refle*ly stimulate the function of the hemotopoietic, apparatusO improve the process of blood clotting and raise the general immunobiological stability of the+ organism, The second form of hypovolemia, i.e., 1ith 7 decreased amount of plasma / polycythemic hypovolemia or anhydremia / K.s characterised by appreciable concentration and increased viscosity of the blood. Anhydremia is observed in connection 1ith considerable losaG of 1ater by the organism, as in cholera, dysentery, infantile )iarrhea, intractable vomiting, and e*tensive burns involving loss of a great deal of fluid 1ith the e*udate and evaporation from burned surfaces. The third form of oligemia is oligocythemic hypovolemia 4 a diminished volume of blood mainly because of a decreased number of erythrcfcytes. !t is observed after hemorrhages in cases of increased passage of fluid from tissues into the vascular syflftem and in certain forms of anemia, for e*ample, pernicious anemia.

IN ADDITION TO THE LECTURE ANE&!A P Anemias of diminished erythropoiesis <diserythropoietic anemias.? impairec Ted cell production. Classification <according to 6obins? te*tboo5.. A. )isturbance of proliferation and differentiation of stem cells, aplastic anemias, pure red cell aplasia, anemia of renal failure, anemia of endocrine disorders. (. )isturbance of proliferation and maturation of erythroblasts, -. )efective )NA synthesis, deficiency or impaired utiliUation of vit X-0 and filic acid <megaloblastic anemias.. 0. )efective hemoglobin synthesis. a. )eficient heme synthesis, iron deficiency b. )eficient globin synthesis, Thalassemias 3. %n5no1n or multiple mechanisms, sideroblastic anemia, anemia of chronic infections, myelophthisic anemias due to marro1 infiltrations. &EGA#"(#A T!C ANE&!A . &egaloblastic anemias develop as the result of vit X and folic acid deficiency. The daily reSuirement is of the order of 0 to 3 g, and the normal balanced diet contains significantly larger amounts. The main steps of vit X absorption. !. !n the stomach, <$it X-0 Y salivary binding protein. / comple* forms. !!. !n the duodenum, <vit X-0 Y salivary binding protein. / comple* is bro5en by pancreatic proteases action.

<vit X-0 Y !ntrinsic factor. / comple* forms. !ntrinsic factor <i'" is secreted by the parietal cells of the fundic mucosa along 1ith HC#. !!!. !n the ileum, <vit X-0 Y !ntrinsic factor. / comple* adheres to !ntrinsic factor / receptors on the ileal cells. $it X-0 then transverse the plasma membrane to enter the mucosal cell. !t is pic5ed up from the cell by a plasma protein, transcobalamin, 1hich is capable to deliver it to the liver and other cells, particularly in the bone marro1. !$. !n the blood, <vit X-0 Y transcobalamin !!. / comple* is transported. The causes of vit X-0 deficiency, !. !mpaired utiliUation, -. Achlorhydria and loss of pepsin secretion <vit X is not readily released from its protein / bound form.2 0. Gastrectomy and atrophic gastritis, the deficiency of intrinsic factor formation and disturbance in vit X transport of the ileum2 3. #oss of e*ocrine pancreatic function, vit X cannot be released from vit X12 + salivary binding protein comple*es. N. !leal diseases can disturb vit X Y intrinsic factor comple* absorption. !!. !ncreased reSuirements, relative deficiency under some circumstances <pregnancy, hyperthyroidism, etc.. !!!. 'ood deficiency, or decreased inta5e.

(iochemical functions of vitamin X $itamin X <methylcobalamin., the synthetic form of it is a stable cyanocobalamin. !t has t1o path1ays of biochemical effects.

-. &ethylcobalamin is an essential cofactor for the enUyme ensuring transmethylatipn reaction. !t is involved in the )NA synthesis. The tetrahydrofolic acid <'H. is reSuired for the formation of immediate precursor of )NA. The fundamental cause of impaired )NA synthesis in vitamin X deficiency is the reduced availability of tetrahydrofolic acid. The internal folate deficiency results from the lac5 of vitamin X-0. 0. Another derivative of cobalamin / deso*yadenosyl cobalamin is a prosthetic group on the enUyme that is necessary for the metabolism of methylmalonic acid. This disorder is follo1ed by increased levels of methylmalonate and its precursor propionate. !t leads to the formation of abnormal fatty acids incorporated into neuronal lipids that results in myelin brea5do1n and development of neurologic complications. Thus, lac5 of either vit X or folic acid causes diminished )NA and conseSuently failure of nuclear maturation and division. 'urthermore, the erythorblastic cells of the bone marro1, 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 follo1s, The inability of the cells to synthesiUe adeSuate Suantities of )NA leads to slo1 reproduction of the cells but does not prevent formation of 6NA by the )NA that is already available in each presently e*isting cell. Therefore the Suantity of 6NA in each cell becomes much greater than normal, leading to e*cess production of cytoplasmic hemoglobin and other constituents 1hich causes the cells to enlargement because of abnormalities of some of the genes <the )NA., the structural components of the # ,-- membrane and cytos5eleton are malformed 1uich leads to abnormal cell shapes and especially greatly increased cell membrane fragility.

8ernicious anemia (Addison?s or (iermer?s anemia. is a megaloblastic anemia in 1hich there is atrophy of the gastric mucosa 1ith conseSuent failure of intrinsic factor production and vit X melabsorption. 8ernicious anemia is believed to result from immunologically mediated, possibly autoimmune, destruction of gastric mucosa. The resultant chronic gastritis is mar5ed by a loss of parietal cells. Three types of antibodies are present in many, but not all, patients 1ith pernicious anemia, -. (loc5ing X-0 / !' binding <!g G.2 0. (inding antibodies reacts 1ith both !' and <vit X Y!'. / comple*2 3. 8arietal antibodies. Autoantibodies cause gastric mucosal inKury. The maKor specific changes in pernicious anemia are found in the bone marro1, alimentary tract and CN . The principal alterations involve the spinal cord, 1here there is myelin degeneration of the dorsal and lateral tracts <sensory ata*ia, severe parethesias.. (lood picture. Certain morphologic features are common to all forms of megaloblastic anemia. The peripheral blood reveals. -. &ar5ed variation in the siUe and shape of red cells / anisocytosis. 0. They are nonetheless normochromic. 3. &any erythrocytes are macrocytic and oval shaped <macro/ ovalocytes.. N. They are thic5er than normal and 1ell filled 1ith hemoglobin2 most macrocytes lac5 the central pallor of normal cells and may even appear GhyperchromicG. 9. The reticulocyte ?,ount is lo1er than normal and occasionally 1ith severe anemia, nucleated red cells appear in the circulating blood. T. Neutrophils are larger than normal <macropolymorphonuclear. and are hypersegmented. They may have five to si* or more nuclear lobules.

The bone marro1. I r-m The megaloblastic change is detected in all stages of red cell development <the / embryonal type of hemopoiesis.. (ecause )NA synthesis is impaired in all proliferating cells nuclear / cytoplasmic asynchrony becomes apparent in all cells. The cells are large, the nuclei are large. !neffective erymropoiesis occurs, premature destructfon of all cells in marro1. 'olate deficiency. A deficiency of folic acid, more properly pteroylmonoglutamic acid, results in a megaloblastic anemia having the same characteristics as those encountered in vitamin X deficiency. Ho1ever, the neurologic changes seen in vit X deficiency do not occur. 'H derivatives acts as an acceptor of one / carbon fragments for the synthesis of biologically active molecules. upressed synthesis of )NA, the common denominator of folic acid and vit X-0 deficiency, is the immediate cause of megaloblastosis. There are three maKor causes of folic acid deficiency, <-. decreased inta5e2 <0. increased reSuirements <pregnancy, infancy. <3. impaired utiliUation <manifestations, cheilosis, glossitis, dermatitis.. !n addition to Addison?s or (iermer?s pernicious anemia, there are also secondary pernicious anemias, as in cases of infestation 1ith tape1arms <)iphyllobothrium latum., and certain severe affections of the stomach <syphilis, cancer, pellagra.. !n all these cases a pathogenetic role is also played by the antianemia factor deficiency due to its diminished absorption or utiliUation in the organism. Anemias due to marro1 aplasia. -. !nciting or causative agents may be radiation, drug <especially benUene derivatives., certain antibiotics, viruses. Not only the marro1 but also other sites of

hematopoiesis reflect inKury to the stem cells. The marro1 spaces are occupied only by fat. 0. ome cases of aplasia involve only one hematopoietic line, as in )iamond /(lac5fan syndrome, a congenital defect involving erymroid hypoplasia, Certain tumors, such as thymomas, are associated 1ith pure red cell aplasia. &yelophthisic anemias. !n this conditions, the marro1 is replaced by foreign GinvadersG <e.g. carcinomas, leu5emias, granulomas.. E*tramedullary hematopoiesis, particularly in the spleen <as in the fetal period., is found. 8rimary bone marro1 myofibrosis also induces this types of anemia by replacing marro1 in fibrosis of un5no1n causes.

Anemias due to systemic disorders. Endocrine diseases, such as hypothyroidism, hypopituitarism are associated 1ith lo1 blood counts. 8oor marro1 function and anemia can be seen in uremia and malignancy. !ron deficiency anemias. !ron distribution in healthy young adults, -. 'unctional compartments, hemoglobin <Z:[., myoglobin, iron / containing enUymes <catalase, cytochromes.2 0. torage compartments, ferritin, hemosiderin <-9/0:[ of total body iron.. 'erritin is essentially a protein / iron comple* that can be found in all tissues but particularly in liver, spleen, bone marro1 and s5eletal muscles. !n the liver, most of the ferritin is stored 1ithin the parenchymal cells, 1hereas in other tissues, such as spleen, a bone marro1, it is mainly in the mononuclear phagocytic cells. Ths iron 1ithin the hepatocytes is derived from plasma transferrin, in the mononuclear phagocytic cells is obtained from the brea5do1n of red blood cells.. !ron from ferritin is aggregated into hemosiderin granules <in

$ery small amounts of ferritin normally circulate in the plasma <a good indicator of the adeSuacy of body iron stores.. !ron is transported in the plasma by an iron / binding glycoprotein called @ transferrin, 1hich is synthesiUed in the liver. The maKor function of plasma transferrin is to deliver iron to the cells including erythroid precursors. !mmature red cells posses high / affinity receptors for transferrin, and iron is transported into erythroblasts by receptor / mediated endocytosis. The fi* daily losses of iron rangers bet1een - and -,9 mg. (ecause only -: to -9 [ of the ingested iron is absorbed, the daily iron reSuirement for adult males is 9 to -: mg and for adults females L to 0: mg. Ascorbic acid, citric acid, aminoacids, and sugars in the diet enhance absorption of inorganic iron, but tannates <as in tea., carbonates, o*alates, and phosphates inhibit its absorption. An iron deficiency may result from <-. dietary lac5 <diets a predominantly vegetarian.2 <0. impaired absorption2 <3. increased reSuirement, or gro1ing infants and children, adolescent\?, pregnancy2 <N. chronic blood loss. Mhatever the basis, iron deficiency induces a hypochromic microcytic anemia. imultaneously, depletion of essential iron / containing enUymes in cells throughout the body may cause other changes including brittle nails, coilonychia, alopecia, atrophic changes in the tonSue and gastric mucosa, and intestinal malabsorption, hypotension, fatiSubility. HE&"#VT!C ANE&!A <!NC6EA E) 6ATE "' 6E) CE## )E T6%CT!"N.. Classification <according to 6obins? te*tboo5.. A. Intrinsic (intracorpuscular) abnormalities of red cells Hereditary, -. )isorders of red cell membrane cytos5eleton <spherocytosis, elliptocytosis.. 0. 6ed cell enUyme deficiencies a. Glycolytic enUymes, pyruvate 5inase he*o5inase b. Glutathione synthetase 3. )isorders of hemoglobin synthesis, a.Thalassemia syndromes / deficient globin synthesis, b. tructurally abnormal globin <hemoglobinopathies., ic5le cell anemia. AcSuired, -. &embrane defect, paro*ysmal nocturnal hemoglobinuria. !" E#trinsic (e#tracorpuscular) abnormalities" -. Antibody mediated. a. !sohemagglutinins, transfusion reations b. Autoantibodies, idiopathic <primary. drug / associated 0. &echanical trauma to red cells. a. &icroangiopathic hemolytic anemias b. Cardiac traumatic hemolytic anemia 3. !nfections, &alaria N. Chemical inKury, lead poisoning 9. eSuestration in mononuclear phagocyte system, hypersplenism The hemolytic anemias all are characteriUed by <-. shortening of the normal red cell life span, that is, premature destruction of red cells2 <0. accumulation of the products of hemoglobin catabolism, and <3. a mar5ed increase in erythropoiesis 1ithin the bone marro1, in an attempt

synthesis

to compensate for the loss of red cells. !ntravascular hemolysis is manifested by, <-. hemoglobinemia, <0. hemoglobinuria, ~ <3. methemalbuminemia,

<N. Kaundice, and <9. hemosiderinuria. Mhen hemoglobin escapes into the plasma, it is promptly bound by an alpha globin <haptoglobin. to produce a comple* that prevents e*cretion into the urine, since the comple*es are rapidly cleared by the reticuloendothelial system. A decrease in serum haptoglobin level is characteristically seen in all cases intravascular hemolysis. Mhen the haptoglobin is depleted, the unbound or free hemoglobin is in part rapidly o*idiUed to methemoglobin, and both hemoglobin and methemoglobin are e*creted through the 5idneys <hemoglobinuria, methemoglobinuria.. E*travascular hemolysis ta5es place 1henever red cells are inKured, are rendered GforeignG, or become less deformable. 'or e*ample, in hereditary spherocytosis an abnormal membrane cytos5eleton decreases the deformability of the red cell. AnaloSuously, in sic5le cell anemia, the abnormal hemoglobin gelsP or crystalliUesP 1ithin the erythrocyte, deforming it and reducing its platicity. Mith e*travascular hemolysis it is obvious that hemoglinemia, hemoglobinuria, and the relatide intravascular changes do not appear. Ho1ever, the catabolism of erythrocytes in the phagocytic cells induces anemia and Kaundice. Erythrophagocytosis may lead to hypertrophy of the mononuclear phagocyte system and splenomegaly. (lood 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. 8"#VCVTHE&!A 8olycythemia is defined as an increase in red cell count in blood volume unit and also increase in hemoglobin content and hematocrit. !t can?t be divided into

<-. an absolute erythrocytosis 1here there is a true increase in red cell volume or <0. relative erythrocytosis 1here red blood cell volume is normal but there is a . decrease in the plasma volume <dehydration, burns, etc... Absolute erythrocytosis may be due to <-. primary polycythemia or <0. secondary polycythemia. 8rimary polycythemia <polycvthemia vera. ervthremia is a clonal stem cell disorder in 1hich there is an alteration in the pluripotent progenitor cell leading to e*cessive proliferation of erythroid, myeloid and mega5aryocytic elements. The main clinical problems are due to the increased volume and viscosity of the blood and to the bone marro1 overactivity. 6ed blood cell count may be as high as L to Z millionOmm and hematocrit as high as T: to L: [. The total blood volume also increases, rarely to almost t1ice normal. The entire vascular system becomes intensely engoged. &any of the capillaries become plugged by the viscous blood. The bone marro1 sho1s erythroid hyperplasia and increased number of mega5aryocytes. !t is a myeloproliferative disorder, ho1ever, in polycythemia very the erythroid precursors dominate. econdary polvcvthemia may be physiologic condition in response to hypo*ia and due to an appropriate increase in erythropoietin production. 8hysiologic polycythemia occurs in natives 1ho live at altitude of -N, ::: to -L, ::: feet. econdary polycythemia may be caused by a variety of hypo*ic conditions, such as impaired pulmonary ventilation and heart diseases. !n such disorders, erythropoietin is elevatide and stimulated marro1 cells to produce erythrocytes. "ther marro1 element are normal in number, function and morphology.

In addition to lecture $Leu%oc&tosis Leu%openia$ Neural mec'anisms of leu%oc&tosis de(elopment. !t is 5no1n that tissue inKury and also their antigenic and biochemical changes cause the refle* activation of CN . !f the sympathetic/adrenal system activation is predominant t1o follo1ing mechanisms of neutrophilia development are involved, <-. the stimulation of the bone marro1 activity and acceleration of leu5ocyte eKection into the peripheral blood <0. adrenergic vasoconstriction and the mobilisation of leu5ocytes from the marginal pool2 <3. the accumulation of lymphocytes in the bone marro1. !f the parasympathetic nervous activity is predominant the elevated counts of lymphocytes and eosinophils in the peripheral blood are arised, i.e. lymphocytosis develops. T'e c'aracter and e#pression of leu%oc&tosis depend on <-. the strength and character of pathogenic action2 <0. organises reactivity <3. the localiUation of pathologic processes !t is 5no1n that pathology of respiratory system and the thora* is follo1ed by the sympathetic activation and development of neutrophilia and lyrnphocytopenia. "n the contrary the pathology of the gastrointestiral tract often is follo1ed by the parasympathetic activation and the development of lymphocytesis and eosinophilia. The distinct mechanisms of leu5ocytosis development may be activated in the certain seSuence. There is the evidence of the certain seSuential induction induction of the different mechanism controlling leu5ocytosis development in particular in aciite different infectious diseases !n these cases three follo1ing phases of leu5ocytosis development 1ere found, <-. neutrophilia2 <0.monocytosis2 <3.lymphocytosis. Neutrophilia corresponds to the beggining of an acute infectious disease. The main mechanisms of its development are as follo1s <-. adrenergic activation causing neutrophilia cells mobi-iUation from the bone marro1 and marginal reserves <0. hypothalamo/pituitary system and target/gland activation promoting to netrophillia and lymphopenia2 <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. )onoc&tosis phase corresponds to the mar5ed period of the disease and to the onset of recoveryO This period is characteriUed by the enhance of macrophage system activity. The principal mechanism of this system activation is formation of antigen antibody comple*. Limp'oc&tosis phase corresponds to the recovery. !t is observed as result of antigen elimination stopping of the antigen activation of T/ cells come bac5 in the blood from tissue. The recurrence of T/cells in the blood from the tissue is thought the important mechanism of limphocytosis development. Leu%emoid reactions #eu5omoid reactions are the pathologic reactions of the blood system resembling leu5emia because of the appearance of immature 1hite blood cells and very high leu5ocyte count. The principal difference leu5emoid reaction in comparison 1ith leu5emias it completely disappears after stopping of it arises in severe infectious diseases and completely dissappears after infection elimination. T1o forms of leu5emoid reactions are 5no1n <-. myeloid and <0. monocytic/lymphocytic. #ymphatic myeloid reaction may be observed in infectious mononucleousi A leu5emoid reaction is an overproduction of 1hite cells 1ith many immature cells. !t may occur in severe infections, tuberculosis, and occasionally after hemorrage or hemolysis. T'e principal differences from leu%emia <-. in etiology leu5emoid reaction arises as the result of certain causative action2

<0. it has in its basis the reactive hyperplasia of the bone marro1 but not neoplasin <3. it is a temporary disorder and stops after the cessation of primary disease. Leu%openia #eu5openia is a decrease in the leu5ocyte count in the volume unit of the circulatory blood belo1 N.:7 -: cell !n the most cases e*tent the total leu5ocyte blood count is ensured by decrease in absolute neutrophil count. Three main mechanisms are <underlied. based the basis of the -en5openia pathoSenesis. They are <-. decrease in leu5ocyte production in the bone marro12 <0. disturbances in leu5ocyte eKection from the bone marro12 <3. inorease in leu5bcyte distruction. <N. the redistribution of leu5ocytes 1ithin blood vascular system2 THE disturbances in leukocyte production <-. the internal deficiency of stem cells to proliferate and differentiate <0. the autoimmune inKury of bone marro1 progenitor cells /the conseSuence of it, the distinct forms of aplastic and hypoplastic anemias, panleu5openia, acute agranulocytasis2 <3. the damage of the precursors of granulopoiesis <leu5opoisis. by T/cells2 <N. the direct action of myeloto*ic agents <some drugs, benUene radiation.2 <9. the viral damage of hemopoiesis2 <T. the deficiency of hemopoietic agents v.(-0 folic acid. <L. the to*ic action of neoplastic cell in leu5emia2 <Z. the ousting of leucopoiesis cells by neoplastic metastasis tissue <]. the deficiency of leu5opoietic factor format ion <for e*ample the deficiency of the monocyte secretion of the g/C ' <granulocyte colony stimulating factor... These deficiencies may occur in immune deficiency diseases. Disturbances in leukocyte ejection from the bone marrow <-. the disorders of leu5ocyte motile activity as the result of memranopathy /. the syndrome of GleasyG leu5ocytes. These disorders are divided into hereditary and acSuired ones <as the result of some drug action.. Decrease in the duration of leukocyte circulation in the blood. <-. the autoimmune damage of circulating <neutrophils. leu5ocytes via agglutinins2 <0. the autoimmune damage of circulating <neutrophils. leu5ocytes via opsonins 1ith the follo1ing phagocytosis2 <3. the autoimmune damage of circulating <neutrophils. leu5ocytes via T/cells <N. the destruction of leu5ocytes by to*ins2 <9. the elevated destruction of leu5ocytes in liver and spleen, <T. the elevated destruction of leu5ocytes as the result of memfaranopattiy <for e*ample, in magaloblastic anemia. . T'e redistribution of leu%oc&tes *it'in blood (ascular s&stem (s'oc%+ c'ills+ strenuous muscle *or%)" ASranulocytosis is the disorder characterised by complete or about complete disappearance blood neutrophils the neutrophil count is less L9: eel !sO limn T1o main forms of agranulocytosis are distinguished according to the etiology into <-. acSuired and <0. idiopathic Acquired agranulocytosis is often caused b& some dru, application+ namel& cytostatic drugs, sulfonilamides, antibiotics, antithyroid drugs and some others. According to the mechanisms of development the drug caused agranulocytoses are divided into myeloto*ic and immune ones. Myelotoxic agranloucytosis arises as a result of to*ic inhibition action of drugs on the proliferative activity of granulopoiesis. !t is usually combined 1ith anemia and thrombocytopetvia involvement has the follo1ing e*planations drug substance serves as hapten, produces formation of complete antigen, causes the antibody production. 'ormed antibodies act on the leu5ocytes and destroy them.