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Practical hematology of children's age

Table of contents
Practical hematology of children's age
Embryonal hemopoiesis
Morfofunktsionalny characteristic of cells of marrow and peripheral blood
Marrow parenchyma cells
Peripheral blood of children of different age
The system of a hemostasis is normal
Etiology and pathogeny of leukoses
Acute leukoses
Acute leukoses - a preleukosis
Possibilities of a predictive assessment of a course of an acute lymphoblastoid leukosis at children
General principles of treatment of an acute leukosis
Chemotherapeutic drugs
Treatment of an acute lymphoblastoid leukosis
Treatment of myeloid forms of an acute leukosis
Infectious complications and symptomatic therapy of an acute leukosis
Consolidation and maintenance therapy of an acute leukosis
Remission and recurrence of an acute leukosis
Inborn leukosis
Macrofollicular lymphoma
Angioimmunoblastny lymphadenopathy
Leukemoid tests
Infectious lymphocytosis
Infectious mononucleosis
Leukemoid tests of different types
Dysfunctions of granulocytes
Histiocytoses - an eosinophilic granuloma
Malignant histiocytosis
Family erythrophagocytal histiocytosis
Accumulation diseases
Nimann's illness — Peak
Hemorrhagic vasculitis (Shenleyn's illness — Genokh)
Mayokki's purpura
Ataxy teleangiectasia
Entsefalotrigeminalny angiomatosis
Kortiko-meningealny diffusion angiomatosis
Cerebroretinal angiomatosis
Hypertrophic gemangiektaziya
Multiple and huge hemangiomas
Elastic fibrodisplaziya
Hereditary coagulopathies
Hemophilia And
Clinic of hemophilia
Treatment of hemophilia
Cristmas disease (Kristmas's illness)
Hereditary deficit of factors of XI, XII, XIII and I
Hereditary deficit of factors of VII, X, V and II
Deficit K-vitaminozavisimykh of factors of coagulation
Syndrome of the disseminated intravascular coagulation
Clinic and diagnosis of the IDCS
Treatment of the IDCS
Idiopathic Werlhof's disease
Clinic and diagnosis of an idiopathic Werlhof's disease
Treatment of an idiopathic Werlhof's disease
Isoimmune Werlhof's disease
Transimmune Werlhof's disease of newborns
Trombogemolitichesky Werlhof's disease (syndrome Moshkovich)
Hereditary Werlhof's diseases
The anemias connected with blood loss
Chronic posthemorrhagic anemia
Iron deficiency anemias
Clinic and diagnosis of an iron deficiency anemia
Treatment of iron deficiency anemias
Sideroakhrestichesky, sideroblastny anemias
Megaloblastny anemias
Foliyevodefitsitny anemia
Hereditary forms of megaloblastny anemias
Hereditary dizeritropoetichesky anemias
The anemias connected with oppression of proliferation of cells of marrow
Hereditary hypoplastic anemias
Hemolitic anemias
Hemolitic anemias - an ovalocytosis, a hereditary stomatocytosis
Acanthocytosis, piknotsitoz
The hereditary hemolitic anemias connected with disturbance of activity of enzymes of erythrocytes
The hereditary hemolitic anemias connected with disturbance of structure or synthesis of hemoglobin
The acquired immune hemolitic anemias
Isoimmune hemolitic anemias
Treatment of a hemolitic illness of newborns
Autoimmune hemolitic anemias
List of references

Reznik B. Ya. — doctor of medical sciences, head of the department of pediatrics of the Odessa medical institute;
Zubarenko A. V. is the candidate of medical sciences, the assistant to the same department.
In a grant the main questions of hematology of children's age are taken up. From positions of achievements of modern medicine the doctrine about a hemopoiesis is considered, the morfofunktsionalny characteristic of haemo cytopoetic cells, features of composition of blood at children is given.
In the heads devoted to private questions of hematology the modern concept of an etiology and pathogeny of tumoral pathology, feature of a clinical picture, the principles of cytostatic therapy are provided; pathology of leukocytes, accumulation diseases, histiocytoses, clinical options of anemias are described.
The special attention is paid to methods of research and treatment.
For pediatricians and hematologists.
Production edition
Reznik Boris Yakovlevich Zubarenko Alexander Vsevolodovich
The hematology was considerably enriched with basic researches and practical developments in recent years.
At the same time, it is impossible to forget that diagnosis and treatment of hematologic diseases at children begin at the first stages of their inspection by the pediatrician. In this regard the knowledge of fundamentals of hematology is extremely necessary for the pediatrician working in policlinic and a hospital of the general profile. Absence of this knowledge leads to the fact that the doctor cannot independently comprehend and compare clinical displays of a disease with hematologic changes and is forced in all cases to resort to consultation of the hematologist. For the solution of this task we considered it expedient to generalize experiment of pediatric clinic on diagnosis and treatment of the most widespread diseases of system of a hemopoiesis. At the same time, naturally, we stated a number of theoretical fundamental provisions in abbreviated form, giving preference to almost significant questions of diagnosis and treatment of diseases of system of a hemopoiesis at children. We hope that the book will help pediatricians to expand and deepen the knowledge in the field of hematology, to improve clinical work on early diagnosis, rational treatment and dispensary observation of hematologic diseases at children.

In the course of formation and the subsequent development of hematology as sciences one of the main places always occupied the doctrine about a hemopoiesis. The theory of a hemopoiesis arose at the same time and developed in parallel with the doctrine about blood. In historical aspect studying of a hemopoiesis began in the XVI—XVII century and had generally descriptive character. In the middle of the XIX century scientists considered blood as the independent body tissue consisting of specific cells. P. Virchov (1989) noted that the only way of formation of cells is their division. By the end of the 19th century of P. Erlich formulated the first theory of an origin of blood cells. According to this hypothesis, in an organism two isolated systems of a hemopoiesis — myeloid (marrow) and lymphoid function (lymph nodes, a spleen). Each of the described P. Erlich of classes of leukocytes (five types of granular and three types of not granular cells) has the independent parent cellular forms which are not capable to pass one into another. The Polifiletichesky theory of a hemopoiesis of P. Erlich served further for development of some other hypotheses of an origin of blood cells — dualistic, trialistichesky etc. A common feature of these theories is the isolated allocation of two and more hemopoietic systems functioning independently from each other and which are not connected among themselves.
A specific place in the doctrine about a hemopoiesis was held by the unitary theory created by A. A. Maximov. According to this theory, all elements of blood have the general parent cell — a lymphocyte (an indifferent mezenkhimny aletocyte).
In experiences of J. E. Till and E. A. McCulloch (1961), fatally irradiated mice who applied a marrow cloning method in a spleen, proved existence of a uniform parent hemopoietic cell. After radiation to mice intravenously entered marrow of healthy animals and repeatedly irradiated to a total lethal dose. Further in a spleen the visible centers of a hemopoiesis provided by a set of colonies were found. By means of a method of chromosomal markers it is shown that in one colony the cells having identical chromosomal anomalies contain, that is such colony develops from one cell as a result of proliferation and differentiation and is its posterity — a clone. In a spleen of fatally irradiated mice define various types of colonies — erythrocyte, granulotsitarny, megakariotsitarny and mixed. However irrespective of an orientation among unilaterally the differentiated cells undifferentiated cellular elements with potential developmental potency in any direction remain. The cell capable to form colonies in a spleen received the name — colony-forming unit of a spleen (KOEs).
In the most recognized modern scheme of a hemopoiesis offered by I. L. Chertkov and A. I. Vorobyov (1973, 1981) the uniform parent cell of a haemo cytopoiesis — a stem cell, originative is allocated to all sprouts of a hemopoiesis (fig. 1). Depending on degree of a differentiation and ability to proliferation in the scheme of a haemo cytopoiesis distinguish 6 classes of cells that finally gives a complete idea of an ontogenetic ladder of a hemopoiesis, consecutive steps of development of blood cells. The I class of polipotentny cells predecessors is provided by stem hemopoietic cells. They make insignificant part of all hemopoietic fabric, their concentration is equal in marrow of mice to 0,1 — 0,2%. However and it is quite enough for maintenance of a normal hemopoiesis. The main property of stem hemopoietic cells is ability to self-maintenance, proliferation and a differentiation. It is established that self-maintenance of a stem cell is limited very big, but final number of divisions. Unlike them, malignant KOEs possess unlimited ability to self-maintenance which does not decrease also after several passages. Proliferative activity of stem cells is under normal conditions small, but can increase considerably at influence of the factors menacing to a haemo cytopoiesis. So, at balance in a haemo cytopoiesis the majority of cellular elements is in a stage of rest (Go) of a cellular cycle and only 10% from them proliferate. At blood loss and other extreme situations the quantity of the proliferating cells can increase up to 50%.
Stem cells of a polipotentna can be also differentiated in any direction of a hemopoiesis on all sprouts of a haemo cytopoiesis. The stroma of the hemopoietic bodies is under construction irrespective of hemopoietic cells. Stromal cells — fibroblasts, endothelial cells and others are not directly involved in a hemopoiesis, and make hemopoietic microenvironment. Reticular elements have an independent stem cell which gistogenetichesk differs from a stem hemopoietic cell. However despite gistogenetichesky distinctions, the hemopoietic and stromal cells are in close interrelation. It is shown that the stroma of the hemopoietic bodies is the specific microenvironment inducing proliferation of stem hemopoietic cells. The further differentiation of a stem cell of a hemogenesis goes in two main directions — the lymphocytopoiesis and a miyelotsitopoez making the following link of a hemopoiesis.

  1. class it is limited polipotentny cells predecessors it is provided by two types of cells — predecessors of a miyelotsitopoez and lymphocytopoiesis. It should be noted that if existence of a cell-predshestvenni: tsy a miyelotsitopoeza it is proved now, that existence of a cell predecessor of a lymphocytopoiesis is hypothetical. The cell predecessor on the properties is close to a stem cell, it possesses limited self-maintenance and differentiation potency. However further transformations are connected with two opportunities — or a lymphocytopoiesis, or miyelotsitopoez. The cell differentiation - predecessors of a miyelotsitopoez goes in three directions — granulo-cytomonocytic, erythroblastic and megakariotsitarny ranks. Hypothetically the cell predecessor of a lymphocytopoiesis is differentiated in two directions — T - and the V-lymphocytopoiesis. The listed above cells make the following step of development of a hemopoiesis.

Fig. 1. Scheme of a hemopoiesis (I. L. Chertkov, A. I. Vorobyov, 1981)

The III class of unipotent cells predecessors is provided by several types of cells which further differentiation assumes strictly certain type of cells. Unipotent cells predecessors still keep ability to self-maintenance which decreases in process of a maturity. If stem hemopoietic cells are capable to make to 100 mitoses, then unipotent cells predecessors — only 10 — 15, and more mature — to 6 mitoses. Proliferative activity of elements III of a class high, quantity of the sharing cells in normal conditions makes 50 — 70%.
Two subclasses are distinguished from unipotent cells predecessors of a miyelotsitopoez: a) the earliest cells which are capable to development in the direction of two sprouts of a hemopoiesis and b) more mature which are differentiated already only in one direction. Existence of most of these predecessors is proved now and methods of their definition are developed. At a stage of unipotent cells predecessors regulation of a hemopoiesis is carried out by humoral factors — erythropoetin, leykopoetiny, trombopoetiny. Early unipotent cells predecessors of a miyelotsitopoez are provided by the granulotsitarno-monocytic, granulotsitarno-erythrocyte and megakariotsitarno-erythrocyte cells predecessors which are differentiated in two corresponding sprouts of a hemopoiesis. Cells, and also cell predecessor of eosinophilic granulocytes belong to more mature unipotent cells predecessors of a miyelotsitopoez of the III class independent granulotsitarny and separate monocytic. By analogy with eozinofilotsitopoezy existence of a separate cell predecessor for basphilic granulocytes is allowed. Also assume that there is a cell predecessor of a mast cell.
Now several cells predecessors of the second subclass of a red row — burstobrazuyushchy and colony-forming erythroidal units are known. Quantitative regulation in this direction of a hemopoiesis is carried out by erythropoetin which is studied in detail now. Dependence on erythropoetin grows in process of a cell predecessor maturity. The differentiation of a megakariotsitarny sprout is carried out from a separate cell predecessor of megacaryocytes. There are bases to assume participation in regulation of a thrombocytopoiesis at this stage of special hormone — a trombopoetina.
Unlike a miyelotsitopoez, data on a lymphocytopoiesis at an early stage have hypothetical character. It concerns both cells of II, and the III class. However it is proved that T cells predecessors - and the V-lymphopoiesis have a marrowy origin. They are descendants of a stem polipotentny cell. Regulation of T - and the V-lymphocytopoiesis is carried out by a number of factors. So, the differentiation of T-cells occurs under the influence of a humoral factor of a thymus gland and a microenvironment. The differentiation of V-cells is connected with analogs of a bursa of Fabricius of birds — lymphoid follicles of intestines.
Still important addition in the doctrine about a hemopoiesis is an existence of a shuntovy hemopoiesis. Therefore, not only the rectilinear differentiation of the above-located forms in more mature elements can be carried out, but also emergence morphologically and functionally identical mature cells, as a result of a differentiation of different cells predecessors is possible (A. I. Vorobyov and soavt., 1979, 1981).
Shuntovy hemopoiesis joins when there is a need for the increased requirement of these or those blood cells. And these situations can be both acute, and long on time. The most fully shuntovy hemopoiesis is studied in the conditions of an intense erythrogenesis (see the scheme).
Important feature of modern ideas of a hemopoiesis is the proof of the hemopoietic origin of macrophagic elements which are descendants of monocytes and have the general cell predecessor of a monocytopoiesis. Earlier these cells were considered as derivatives of reticuloendothelial system. Also mast cells have the hemopoietic origin. That is all system of the englobing mononuklear has no gistogenetichesky community neither with reticular macrophages, nor with an endothelium, and is posterity of the hemopoietic cells.
The IV class of morphologically recognizable proliferating cells is provided by the imperious elements having already cytochemical and morphological recognizable features specific to the row. High proliferative activity which decreases in process of a differentiation of cells is characteristic of cells of this class. Imperious elements — myeloblasts (neutrophylic, eosinophilic, basphilic), monoblasts, erythroblasts, megakaryoblasts, lymphoblasts (T - and V-type) normal begin separate corresponding ranks of a hemopoiesis. Making several mitoses, (4 — cells of a granulotsitarny row, 5 — 6 erythrocyte rows), blast elements move ahead on the way of a differentiation. Vklass of cells is provided by the various cellular forms having morphological and cytochemical characteristics. In more detail cells of this class will be considered at the description of a marrowy hemopoiesis.
In the course of a differentiation ability to division decreases. The last forms capable to proliferation among a granulotsitarny row, are myelocytes, and among erythrocyte — polychromatophilous normocytes. Division of kernels without division of all cell is characteristic of cells of a megakariotsitarny row, since a megakaryoblast.
According to the proposal of authors of this scheme of a hemopoiesis of I. L. Chertkov and A. I. Vorobyov, in an erythrocyte number of a haemo cytopoiesis at the forms following an erythroblast, the termination "blast" is replaced on "tsit". So, earlier designated cells "pro-normoblast", "normoblast" have the name "pro-normocyte", "normocyte" now, that is the termination "blast" remains only behind the cells beginning separate ranks of a hemopoiesis.

  1. class of the ripening cells. The differentiated cells which did not reach a final stage of maturing yet enter it, but already lost ability to proliferation.
  2. the class of mature cells with a limited life cycle is provided morphologically and functionally mature cellular elements which usually are present at peripheral blood. As it was already noted, distinctive feature of this scheme of a hemopoiesis is reference of the englobing mononuklear to derivatives of the hemopoietic cells. Functionally mature form — a macrophage — these cells reach in various body tissues. Characteristics of cells of a lymphoid row from which two lines T - and the V-lymphocytes having various final morfofunktsionalny forms are distinguished are also specified. It is established that plasmocytes develop from V-lymphocytes.

There is no total kinetic characteristic of cytochemical changes in the hemopoietic cells of various sprouts of a haemo cytopoiesis today. The cytochemical characteristic is well traced, since a stage of morphologically recognizable proliferating cells (an erythroblast, a monoblast, a myeloblast etc.) . In a myeloblast all cytochemical signs characteristic of this row are found. In particular, reveal a moderate sudanofiliya and diffusion weak coloring of cytoplasm at CHIC reaction. In cytoplasm of cells activity of acid phosphatase and p-glucuronidase comes to light, activity of nucleases, especially alkaline DNA-ases and RNK-az is found. In cytoplasm of some myeloblasts activity of peroxidase and a hloratsetatesteraza already appears. In process of maturing of cells the content of polysaccharides, phospholipids, activity of peroxidase, a hloratsetatesteraza, nucleases increase. The alkaline phosphatase (a marker of secondary granules) begins to come to light at a myelocyte stage, and in process of maturing the percent of the cells containing enzyme increases. It should be noted that activity of a number of enzymes (acid phosphatase, p-glucuronidase, nespstsifichesky esterase) is much higher in neutrophylic promyelocytes, than in neutrophylic band and segmentoyaderny granulocytes.
For a monocytic number of the most characteristic reaction to nonspecific esterase with use is and-naftilatsetata. Higher activity of peroxidase and acid phosphatase in marrow monocytes, in comparison with monocytes of peripheral blood is established.
Recognizable elements of an erythroidal row youngest morphologically — erythroblasts, possess moderate activity RNK-az that distinguishes them from other blast cells. The expressed activity of dehydrogenases is noted in erythroblasts, and then in process of a cellular differentiation it decreases. Functionally full-fledged erythroidal predecessors do not contain CHIC-positive material, it appears in a small amount of cells (to 10%) at late stages of maturing.

Fig. 2. Phases of a cellular cycle

In a megakariotsitarny row CHIC-positive material comes to light in 100% of cells. In pro-megacaryocytes it is found in the form of dense granules, in process of a cellular differentiation decides in a diffusion form, and in megacaryocytes, on the beginning formation of thrombocytes, in the form of small powdered granules. In process of maturing of cells of a megakariotsitarny row activity of esterases — a hloratsetatesteraza and nonspecific esterase increases. Activity of lizosomalny enzymes small and in process of maturing decreases.
Cells of a lymphoid row are characterized by availability of hydrolytic enzymes (the acid phosphatase, p-glucuronidase, nonspecific esterase, acid nonspecific esterase) defined to a granular form. Increase in hydrolytic enzymes is characteristic of T lymphocytes, in V-population the content of polysaccharides is higher (G. I. Kozinets and soavt., 1982).
The hemopoietic fabric is constantly renewed system of an organism in which processes of dying and products of cells are in a dynamic equilibrium. Modern ideas of a hemopoiesis are substantially expanded by studying of kinetic aspects of a haemo cytopoiesis, that is a life cycle of the hemopoietic cells. The main way of reproduction of cells is mitotic division after which cells or stop sharing, are differentiated and carry out the specific function, or begin preparation for a new mitosis. The mitotic cycle is divided into 4 periods designated by Gi, S, G2, M (fig. 2).
Gi — presinteticheskiya (or post-mitotic) the period during which there are biochemical processes preparing synthesis of DNA. In this period, the following ambassador of a mitosis, daughter cells contain a diploid set of chromosomes and the corresponding quantity of DNA (2 c). Then the cell enters a S-phase (the synthetic period) where there is an intensive synthesis and doubling of quantity of DNA. By the end of the period the kernel contains a tetraploid set of chromosomes (4 c). G2 — post-synthetic (or premitotic) the period when there is a preparation for mitotic division. The m — a mitosis, is characterized by hypodispersion of hereditary material between daughter cells. Duration of the periods fluctuates over a wide range and can change under the influence of various influences. In a cellular cycle also allocate Go period — a phase of temporary rest. According to modern representations, after the manager? the mitosis rsheniya a cell can leave a mitotic cycle and a certain period to be in a condition of "rest", and then again to enter a division cycle. Transition to a resting phase from the period of Gi and back is, as a rule, characteristic of the hemopoietic cells. At a final exit of a cell from a mitotic cycle there is its differentiation and further performance of specific function up to death of a cell.
What mechanisms regulate proliferation and a differentiation of the hemopoietic cells? There are no accurate facts testimonial of existence of uniform specific system of regulation now. It was already mentioned influence of a microenvironment which broad understanding included set of conditions in a hemopoiesis microsite (cellular factors, a surrounding hemopoietic stroma, blood supply). Does not raise doubts that proliferation and a differentiation of a stem cell happen only in the hemopoietic fabric, on a stroma of the hemopoietic bodies. In the absence of such stroma stem cells do not function and perish, that is they are sensitive to change of local conditions. Thus, the hemopoietic stroma creating a certain microenvironment is a necessary factor for regulation of a normal haemo cytopoiesis (L. Coulombel, 1987). But hemopoietic microenvironment is not capable to implementation of some functions necessary for thin regulation of a haemo cytopoiesis (O. A. Gurevich, I. L. Chertkov, 1982).
According to the stochastic (accidental) theory, the differentiation of stem hemopoietic cells is carried out by the sum of stochastic processes, but their probability is not accidental and depends on a microenvironment (I. L. Chertkov, 1976: M of Ogawa, 1983). The question of how stem hemopoietic cells directly function is not solved. It is known that each stem hemopoietic cell is capable to make about 100 mitoses that considerably exceeds needs of an organism for the hemopoietic elements. In experiences on mice it is shown that one clone, that is posterity of one stem cell suffices to recover a normal haemo cytopoiesis. Therefore, one stem hemopoietic cell can provide all process of a hemopoiesis whereas other cells remain in a reserve.
However, according to many authors, the model of a hemopoiesis has several other appearance — the bent hemopoiesis model (I. L. Chertkov, 1976; A. I. Vorobyov, M. D. Brilliant, 1977; D. Metcalf, M. of A. Moore, 1971). According to the available representations, over all life there is a continuous change of cellular clones, on a trope, change of cellular "layers", replacement of one "layer" of cells with another, carrying out essentially identical functions (A. I. Vorobyov, I. L. Chertkov, 1979). The sharing stem hemopoietic cell proliferates several mitoses, and then passes into a condition of rest. On change the following stem hemopoietic cell etc. enters. The cellular clone which began to proliferate actively blocks and forces out clones which already slowed down proliferation (I. L. Chertkov). Thus, in the hemopoietic system the dynamic equilibrium providing the stable maintenance of mature elements of blood remains.
Now regulation of a hemopoiesis and kinetics of a haemo cytopoiesis of separate sprouts are studied in detail, each of which is characterized by the expressed behavior autonomy.
In marrow allocate three stages of development of granulocytes: 1) stage of morphologically unrecognizable cells predecessors; 2) a stage of morphologically recognizable predecessors of a granulocytopoiesis — myeloblasts, promyelocytes and myelocytes; 3) a stage of the ripening not sharing cells — metamyelocytes and mature granulocytes.
Out of marrow distinguish two pools of granulocytes — a pool of the circulating granulocytes and a pool of pristenochny, regional, or capillary granulocytes (E. B. Vladimirskaya, 1976). Total number of neutrocytes in marrow of healthy people makes (7,70±1,20Х109) cells/kg of weight (J. Dancey and soavt., 1976). Daily products of neutrocytes are equal (0,85X109) cells/kg of weight. In a circulatory bed the total quantity of neutrocytes makes (0,61X109) cells/kg of weight (L. Boggs, 1975). Kinetic researches showed that all way from a myeloblast to an exit in blood of a segmentoyaderny neutrocyte lasts 238 — 285 h. The half-cycle of circulation of segmentoyaderny neutrocytes is equal in peripheral blood to 7,6 h, and average, or transit, time of circulation makes 10,8 h, that is less than per day the structure of the circulating neutrocytes is updated twice (G. I. Kozinets and soavt. 1982). The rest of the time (about 1 — 2 day) granulocytes are in fabrics (D. W. Bainton and soavt., 1975). There they carry out the main functions and perish, completing a life cycle. Not numerous data on   kinetics of eosinophilic granulocytes demonstrate that it differs from kinetics of neutrocytes a little.
According to modern representations, regulation of a granulocytopoiesis is carried out in the humoral way in which it is possible to allocate two mechanisms: the mechanism of the return negative communication — granulocytopoiesis inhibitors take part in it; the positive feedback mechanism which is carried out by means of granulocytopoiesis stimulators. The colony stimulating factor (KSF) is considered one of activators. KSF is produced by cells of many bodies, including marrow. It represents the glycoprotein having various molecular weight at the person — 25 000 — 45 000 dalton. It is shown that KSF is necessary for maintenance of proliferation and maturing of KOE-K and its descendants in colonies on semisolid environments. Except KSF, the granulocytopoiesis at experimental animals is stimulated by other agents: androgens, lithium.
The special part in regulation of a granulocytopoiesis is assigned to chalones. Chalones are the endogenous tkanespetsifichesky inhibitors of proliferation which are not possessing toxicity. They are produced in the same fabrics on which make impact, and regulate cellular proliferation by the principle of negative feedback. Now chalones of the hemopoietic fabric, including granulotsitarny chalone are emitted (V. J. Lord and soavt., 1974). Many researchers consider that chalone inhibits proliferation, affecting cellular membranes. A number of authors offered a kontsenpiya according to which efficiency of regulation is defined not only existence of negative feedback (chalone), but also positive feedback (antnkeylon). Any mechanism connecting chalone can have effect of anti-chalone (S. Jversen, 1973; N. Aardal and soavt., 1977). Now we emitted granulotsitarny chalone and granulotsitarny anti-chalone (V. N. Nemykh, Yu. M. Ball, 1977).
Erythroidal cells of the person consist of the following classes: parent, proliferating, ripening, mature and specifically functioning. Cells also subdivide on synthesizing and not synthesizing hemoglobin.
The kinetics of erythron consists of several ways. The general erythrocytopoiesis — education in marrow of necessary number of erythroidal predecessors. The effective erythrocytopoiesis is quantity of the erythroidal cells ripening to an erythrocyte stage, an inefficient erythrogenesis — quantity of erythroidal cells which did not finish a cycle of a differentiation and collapsed in marrow. Erythroidal cells breed intensively, in marrow during a day of them about 2Х1011 is formed. In peripheral blood of the adult circulates 25 — ZOH1012 of erythrocytes. Average life expectancy of an erythrocyte of 120 days. The main stimulator of an erythrocytopoiesis is erythropoetin (A. J. Sytkowski, 1985). It is a glycoprotein which is generally formed in kidneys. As the regulator for production of erythropoetin serves oxygen tension degree in fabrics. Kidneys produce an inactive erythrogene which in serum turns into erythropoetin. Erythropoetin is capable to accelerate proliferation of cells, but its main function consists in regulation of differentiation of stem cells towards an erythrocytopoiesis. At the same time it affects only part of the stem cells which received the name of eritropoetinchuvstvitelny. A point of application of erythropoetin are also the ripening cells. It promotes ripening of cells, increase in synthesis of hemoglobin, activates an exit of reticulocytes from marrow in a peripheral bed. The regulating impact on an erythrocytopoiesis is exerted also by hormones, vitamins, microelements. Erythrocytopoiesis inhibitors — the erythrocyte chalone emitted from mature erythrocytes participate in specific regulation. Erythrocyte chalone prevents the introduction of cells in a generative cycle, thereby reducing proliferative activity of erythron. In erythrocytes the substance operating by the principle of the return positive communication, stimulating an erythrocytopoiesis — erythrocyte anti-chalone is also revealed.
Among population of megacaryocytes distinguish three types: 1) megarioblasta, the most unripe, the making 10% of all population: 2) pro-megacaryocytes — an intermediate stage, make 15%; and 3) the mature megacaryocytes passing a final endomitosis and a trombotsitootdeleniye; make 75% of population (G. I. Kozinets and soavt., 1982). Process of transformation of a megakaryoblast into a megacaryocyte lasts 43 — 45 h (S. Ebbe, 1974). Each megacaryocyte depending on its size gives from 2000 to 8000 thrombocytes. Average life expectancy of thrombocytes is estimated for 4 — 6 days. About 40% of the circulating thrombocytes daily perish (N. A. Torubarova, 1976).
Speed of formation of progenitors of a megakariotsitopoez is carried out by the principle of feedback, to the general for all granular cells — surplus of thrombocytes in peripheral blood normal is braked by a thrombocytopoiesis, thrombocytopenia — stimulates. Existence of humoral stimulators of a thrombocytopoiesis — trombopoetin is proved. Existence of inhibitors of a thrombocytopoiesis is established; though these substances are purely not emitted.
In marrow of healthy people one of predecessors of monocytes — a promonocyte is allocated now. According to G. Meuret and coauthors (1975), the absolute maintenance of promonocytes makes (6X108) cells/kg of weight. The mitotic cycle of a promonocyte proceeds 30 h, the speed of a circulation of monocytes is equal (7x10e) cells / kg-ch that is 120 times lower, than at neutrocytes. The minimum time of stay of monocytes in marrow of 9 h, an average — about 3 days. All pool of monocytes makes (80HYu6) of weight cells/kg, a pool of the circulating monocytes much less —(18X10®) weight cells/kg. Time of circulation of monocytes in blood of 12 — 32 h (R. Van Furth and soavt., 1979). From blood monocytes get into fabrics where macrophages turn in fabric. Macrophages in limited scales keep ability to division in pathological conditions (an acute and chronic inflammation).
The lymphocytopoiesis represents the complex system of forming of functionally heterogeneous cell populations which is carried out step by step by different bodies. In marrow parent lymphoid cells, the general both for T - and for V-lymphocytes are formed. The predecessor of T lymphocytes migrate in a thymus gland where under the influence of humoral factors ("timichesky hormone") are differentiated and become immunocompetent T lymphocytes. The part of cells makes a recirculating pool. Other part of cells comes to blood and occupies peripheral lymphoid bodies where the second stage of a differentiation is carried out. Geterogenna T lymphocytes also develop independently, providing to generation of cells with various functions.
The place of the first stage of a differentiation of V-lymphocytes at mammals is unknown, it is established only at birds (bursa of Fabricius). At the first stage of a differentiation of V-lymphocytes of a cell already have immunoglobin superficial receptors, but are still independent of effect of antigen. The second stage of a differentiation of V-lymphocytes passes in a peripheral adenoid tissue. V-lymphocytes at this stage under the influence of antigenic incentive are differentiated in antibody producers.
The lymphocytopoiesis in many respects depends on age and is exposed to involution what changes of an adenoid tissue at elderly people testify to. This system is also imperfect and children of the first months have lives. On average at the person in day about 20X109 lymphocytes are formed that for seventy-year life makes about 275 kg. Life expectancy of lymphocytes varies over a wide range — from several days to 10 flyings. Long and short-lived cells are available in both lines. Constantly there is a recirculation of lymphocytes from lymphatic bodies in blood and back. The quantity of lymphocytes in peripheral blood are 40 times less than their total number in an organism (G. I. Kozinets, 1980).

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