Features of the hematopoietic organs in children. The formation of hematopoiesis in the antenatal and postnatal periods. Features of the hemogram and coagulogram of a newborn child. Features of hematopoiesis in children. Blood parameters in different age periods. BUT

In the human embryo, hematopoiesis includes 4 periods. During 1st period(3-4th week of intrauterine development) there is the emergence of hematopoietic cells in the extraembryonic mesenchyme and the formation of initial hematopoiesis in the yolk sac, chorion and umbilical cord where Wolf's blood islands are formed. This process proceeds in parallel with the formation of the vascular network, which creates conditions for the migration of hematopoietic cells into the embryo. Hemopoietic stem cells are formed in the blood islands and erythropoiesis begins - "primitive" erythroblasts (megaloblasts of the 1st generation) are formed, synthesizing the "primitive" Hb - HvP. From the yolk sac, hematopoiesis is transferred to the liver, where from the 5th to the 22nd week 2nd period hematopoiesis - hepatic, during which megaloblasts of the 2nd generation are formed, synthesizing, along with primitive Hb, fetal Hb - HbF. By the 3rd month of fetal development, primitive (megaloblastic) erythropoiesis is replaced by normal - normoblastic. In addition to erythropoiesis, granulocytes, megakaryocytes, monocytes and a small amount of lymphocytes are formed in the embryonic liver, there is also a small percentage (3-5%) of stem cells. Despite such a long stay of the liver in hematopoiesis, the highest intensity of hepatic hematopoiesis occurs at 8-9 weeks of embryonic development. During the same period, the thymus is populated by lymphoid cells. At the same time, from the 8-11th week of development, the formation 3rd period hematopoiesis - KM-th. At first, the CM is inactive, but, starting from the 15th week, it becomes the main hematopoietic organ. At the 12th week of development, it is also initiated 4th period- period splenic hematopoiesis. First, islets of erythroid cells and granulocytes appear in the spleen, from the 15th week lymphocytes begin to be produced. A little later, lymph nodes are included in lymphopoiesis.

After birth in humans, the following organs are involved in hematopoiesis:

    Red bone marrow (CM) - the central organ of hematopoiesis, which communicates with the bloodstream through a capillary network. In an adult, CM is approximately 4.5% of the total body weight, it is located in the tubular bones, ribs, sternum, vertebrae, bones of the skull, and pelvis. All types of blood cells are formed in the BM - leukocytes (including immune B-lymphocytes), erythrocytes and platelets.

    thymus - organ of formation and differentiation of T-lymphocytes.

    Spleen and lymphatic tissue(lymph nodes and lymphoid formations in the skin, mucous membranes of the pharynx, bronchi and intestines) are the site of formation of only lymphocytes.

    Extramedullary hematopoiesis - the phenomenon of the formation of leukocytes and erythrocytes outside the bone marrow: in the spleen, lymph nodes, liver, kidneys, adrenal glands, lungs, in the tissue of various organs (normal in the embryonic period and in pathology).

Organs of hemorrhage

RES (mononuclear phagocyte system) - macrophages KM, spleen, lymph glands, lungs, Kupffer cells of the liver, connective tissue histiocytes.

Features of the blood of laboratory animals

In general, the cellular composition of the blood of humans and laboratory animals (dogs, rabbits, guinea pigs, rats, mice) is similar. However, there are also some differences. So, for example, if in humans the OKL is 4-8 * 10 9 / l (G / l), then in animals it fluctuates in a wider range - from 5 to 18 G / l. In addition, in rats and mice, the formation of the nucleus of polymorphonuclear leukocytes occurs according to the annular type. As a result, the nuclei of maturing granulocytes in these animals do not look like "rods" (as in humans), but "rings". In rabbits and guinea pigs, granulocyte granularity has a higher affinity for acidic dyes compared to human leukocytes. Such cells are called "pseudo-eosinophils", since only eosinophilic leukocytes have this property in humans. In guinea pigs, in the cytoplasm of lymphocytes and monocytes, protein-polysaccharide grains - Kurlov's bodies (a sign of cell aging) can be found, in humans they are not.

TO THE PRACTICE

IV year specialty "Pediatrics"

Discipline:"Propaedeutics of childhood diseases with healthy child courses and general child care"

ANATOMO-PHYSIOLOGICAL FEATURES

OF HEMATOPOISING ORGANS IN CHILDREN AND ADOLESCENTS.

Lesson duration __ _hours

Class type- practical lesson.

PURPOSE OF THE LESSON: To study the anatomical and physiological features of the hematopoietic system in children.

MAIN QUESTIONS OF THE TOPIC:

1. Stages of embryonic hematopoiesis and their role in understanding the occurrence of foci of extramedullary hematopoiesis in pathology of hematopoietic organs in children and adolescents.

2. Pluripotent stem cell and stages of its differentiation.

3. Patterns of changes in the leukocyte formula with the age of children.

4. Erythrocyte germ and its changes in the postnatal period.

5. Granular hematopoietic system.

6. Lymphoid system of hematopoiesis.

7. Hemostasis system in children and adolescents

Questions for independent study by students.

1. Modern scheme of hematopoiesis.

  1. Examination of the patient, evaluation of data from the study of peripheral blood in a patient with a norm.

LESSON EQUIPMENT: tables, diagrams, case histories.

METHODOLOGICAL INSTRUCTIONS.

Blood is one of the most labile fluid systems of the body, constantly coming into contact with organs and tissues, providing them with oxygen and nutrients, carrying waste products of metabolism to the excretory organs, participating in the regulatory processes of maintaining homeostasis.

The blood system includes organs of hematopoiesis and blood destruction (red bone marrow, liver, spleen, lymph nodes, other lymphoid formations) and peripheral blood, neurohumoral and physico-chemical regulatory factors.

The components of blood are the formed elements (erythrocytes, leukocytes, platelets) and the liquid part - plasma.

The total amount of blood in the body of an adult is 7% of body weight and is equal to 5 liters, or 70 ml per 1 kg of body weight. The amount of blood in a newborn is 14% of body weight or 93-147 ml per 1 kg of body weight, in children of the first three years of life - 8%, 4-7 years - 7-8%, 12-14 years 7-9% of body weight .

Embryonic hematopoiesis.

Hematopoiesis in the prenatal period of development begins early. As the embryo and fetus grow, the localization of hematopoiesis consistently changes in various organs.

Tab. 1. Development of the human hematopoietic system (according to N.S. Kislyak, R.V. Lenskaya, 1978).

Hematopoiesis begins in the yolk sac at the 3rd week of development of the human embryo. In the beginning, it comes down mainly to erythropoiesis. The formation of primary erythroblasts (megaloblasts) occurs inside the vessels of the yolk sac.

On the 4th week, hematopoiesis appears in the organs of the embryo. From the yolk sac, hematopoiesis moves to the liver, which by the 5th week of gestation becomes the center of hematopoiesis. Since that time, along with erythroid cells, the first granulocytes and megakaryocytes begin to form, while the megaloblastic type of hematopoiesis is replaced by normoblastic. By the 18-20th week of development of the human fetus, hematopoietic activity in the liver is sharply reduced, and by the end of intrauterine life, as a rule, it completely stops.

In the spleen, hematopoiesis begins from the 12th week, erythrocytes, granulocytes, megakaryocytes are formed. From the 20th week, myelopoiesis in the spleen is replaced by intense lymphopoiesis.

The first lymphoid elements appear at 9-10 weeks in the stroma of the thymus; in the process of their differentiation, immunocompetent cells, T-lymphocytes, are formed. By the 20th week, the thymus in terms of the ratio of small and medium lymphocytes is similar to the thymus of a full-term baby; by this time, immunoglobulins M and G begin to be detected in the fetal blood serum.

The bone marrow is formed at the end of the 3rd month of embryonic development due to mesenchymal perivascular elements penetrating together with blood vessels from the periosteum into the medullary cavity. Hematopoietic foci in the bone marrow appear from 13-14 weeks of fetal development in the diaphysis of the femur and humerus. By the 15th week, these loci show an abundance of young forms of granulo-, erythro-, and megakaryocytes. Bone marrow hematopoiesis becomes the main one by the end of fetal development and throughout the entire postnatal period. Bone marrow in the prenatal period is red. Its volume increases by 2.5 times with the age of the fetus and by birth is about 40 ml. and it is present in all bones. By the end of gestation, fat cells begin to appear in the bone marrow of the extremities. After birth, during the growth of a child, the mass of the bone marrow increases and by the age of 20 it averages 3000 g, but the share of red bone marrow will be about 1200 g, and it will be localized mainly in flat bones and vertebral bodies, the rest will be replaced by yellow bone marrow.

The main difference in the composition of the formed elements of the fetal blood is a constant increase in the number of red blood cells, hemoglobin content, and the number of leukocytes. If in the first half of fetal development (up to 6 months) many immature elements (erythroblasts, myeloblasts, promyelocytes and myelocytes) are found in the blood, then in the following months, predominantly mature elements are contained in the peripheral blood of the fetus.

The composition of hemoglobin also changes. Initially (9-12 weeks) in megaloblasts there is primitive hemoglobin (HbP), which will be replaced by fetal hemoglobin (HbF). It becomes the main form in the prenatal period. Although erythrocytes with adult-type hemoglobin (HbA) begin to appear from the 10th week, its proportion before the 30th week is only 10%. By the birth of a child, fetal hemoglobin is approximately 60%, and an adult - 40% of the total hemoglobin of peripheral blood erythrocytes. An important physiological property of primitive and fetal hemoglobins is their higher affinity for oxygen, which is important in the prenatal period for providing the fetus with oxygen, when the oxygenation of the fetal blood in the placenta is relatively limited compared to the oxygenation of the blood after birth due to the establishment of pulmonary respiration.


Similar information.


Hematopoiesis begins shortly after implantation. The first foci of hematopoiesis are formed in the walls of the yolk sac, where megaloblasts and megalocysts are formed. From the 5th - 6th week, hematopoiesis begins in the liver (yolk hematopoiesis stops). The liver is the main organ of hematopoiesis for the II-III months of the prenatal period; hematopoiesis in it begins to fade from the 20th week of pregnancy. The predominant elements formed in the liver are red blood cells; a small number of cells of the myeloid series are found. From the end of the third month of pregnancy, the hematopoietic function of the bone marrow begins. It produces red blood cells and myeloid elements. Gradually, the bone marrow becomes the main organ of hematopoiesis, and hematopoiesis in the liver decreases and fades. From the fourth month of pregnancy, hematopoiesis begins in the spleen: lymphocytes, myeloid cells and erythrocytes are formed in it. The process of production of lymphocytes prevails. In the peripheral blood of the fetus, erythrocytes appear on the 7-8th week, myeloid cells - on the 12th, lymphocytes - on the 16th week of the prenatal period. In the early stages of development, the blood is poor in formed elements and hemoglobin; there are many nucleated cells among the erythrocytes. With the development of the fetus, the number of erythrocytes, hemoglobin, leukocytes and lymphocytes increases. There is more hemoglobin and red blood cells in the blood of a mature fetus than in an adult (hemoglobin 105-125%, red blood cells 5-7 million), which contributes to the delivery of the required amount of oxygen and other substances to the tissues of a rapidly growing organism. Fetal hemoglobin has a pronounced affinity for oxygen. Fetal hemoglobin is characterized by an increased ability to absorb oxygen from the mother's blood; this ability of fetal hemoglobin is important in providing oxygen to all its tissues and organs. Fetal ("embryonic") hemoglobin is gradually replaced by hemoglobin of the usual type. Proteins in the blood serum appear in the early stages of development. At the third month of pregnancy, 5-7 fractions of proteins of the albumin and globulin series are determined, with albumins predominating. At 12-13 weeks, gamma globulin, which is involved in immunogenesis, first appears. By the 20th week, the composition of blood serum proteins is enriched (8-12 fractions), at the end of the intrauterine period, it becomes even more complicated. However, the composition of the fractions of proteins in the blood serum of a newborn is incomplete compared to adults. In addition to the fractions of albumin and globulin, the fetus produces proteins that are inherent only in the prenatal period of development - stage-specific proteins. The alpha-fetoprotein was found in the fetus, the amount of which increases until the 20th week and gradually decreases, disappearing by the 36th week. It is believed that this protein affects the growth and development of fetal tissues. A second stage-specific protein, beta-fetoprotein, has been discovered, the physiological significance of which has not yet been clarified. The fetal blood coagulation system develops mainly in the second half of the prenatal period. In the first months, the fetal blood's ability to clot is extremely low, and no blood clot is formed. Factor V appears at the fifth month of pregnancy, but its activity is extremely low; in the same period, fibrinogen begins to be determined in a small amount. At the beginning of the sixth month of pregnancy, prothrombin appears and the content of other blood procoagulants increases, tests characterizing the general coagulation activity (recalcification, plasma tolerance to heparin) become positive. Free heparin is determined from the end of the sixth month of fetal development. At the end of the 6th month of pregnancy, all procoagulants are found in the blood of the fetus; in the following months of intrauterine life, only a quantitative change in their content is noted.

LESSON #6

TOPIC:Features of hematopoiesis in children. Blood parameters in different age periods. Anemia in children. The concept of immunity. hemorrhagic syndrome. Vasopathy, thrombocytopathy, thrombocytopenia, coagulopathy. medical tactics.

Hematopoiesis during fetal development

Embryonic hematopoiesis begins very early: by the end of the 2nd - the beginning of the 3rd week of gestation, it passes with varying intensity, with a change in the predominant localization of hematopoiesis at different gestational periods. Its characteristic features are as follows:

- a consistent change in tissues and organs that are the main springboards for the formation of blood elements - the yolk sac, liver, spleen, thymus, l / y and, finally, the bone marrow;

- a change in the type of hematopoiesis and produced cells - from megaloblastic to normoblastic.

During the period of intrauterine development, topographically, 4 stages of hematopoiesis can be distinguished:

1) mesoblastic (extraembryonic)

2) hepatic (extramedullary)

3) splenic (extramedullary)

4) bone marrow

mesoblastic stage type of hematopoiesis megaloblastic. Hematopoiesis occurs in the yolk sac, chorion stalk by the end of the 2nd beginning - the 3rd week of gestation. Vessels are formed from the peripheral cells of the yolk sac, and hematopoietic cells are formed from the central cells, which are oval in shape, large in size (up to 30 microns), basophilic cytoplasm, and a nucleus with nucleoli. They are called primitive erythroblasts (outwardly similar to megaloblasts). These cells gradually accumulate Hb. From the 6th week of gestation, cells without nuclei, megalocytes, are found in the blood of the embryo. During this period, predominantly erythropoiesis occurs, but it is already possible to detect precursor cells of all hematopoietic germs, including polypeptone stem cells (they are distinguished by an increased ability to reproduce themselves). That. in the yolk sac there are cells capable of differentiating in various hematopoietic directions, and it is from it that the precursor cells of hematopoiesis migrate to other organs.

Starting from the 8th week of gestation, the hematopoietic islets in the yolk sac begin to regress, and by the 12-15th week megaloblasts disappear from the blood.

Hepatic stage(6-27 weeks) hematopoiesis occurs from the 5th week of gestation, and in the period of 3-6 months. (peak at 12-20 weeks) of gestation, the liver is the main hematopoietic organ and the site of erythropoietin (EP) formation. type of hematopoiesis macro-normoblastic.

EP - humoral regulator of hematopoiesis (erythropoiesis). The main, but not the only place of production are the kidneys. The main producers of extrarenal EN are monocyte macrophages. Probably, in an inactive state, it enters the plasma, where, under the influence of a specific enzyme, erythrogenin, it is converted into an active EP. The main regulator of the production of EP is the content of O2 in the blood, or rather its availability to tissues. The metabolism of EP is slow. About 10% of EP is excreted from the body in the urine.

Initially, intense erythrogenesis occurs in the liver - by the 9-10th week of gestation, up to 93.4% of nuclear cells are primitive erythroblasts (primary), which are gradually replaced by secondary erythroblasts, and by the 32nd week, erythroid cells account for 40%.

In terms of 6-7 weeks of gestation, eosinophils (E), basophils (B), monocytes (M), macrophages and megakaryocytes are found in the embryonic liver. By 8-9-12 weeks. megaloblasts disappear from the liver and hematopoiesis acquires a macro-normoblastic character.

Leckopoiesis. Starting from 8-9 weeks, lymphocytes (L) (0.14%) are detected, increasing to 10% by 22-27 weeks. At 8 weeks of gestation, up to 90% of L belong to pre-B cells, V-L carrying surface Ig M are determined, at 11.5 weeks cells appear, on the surface of which Ig G and Ig A are determined.

Starting from the 18-20th week of gestation, the hematopoietic activity of the liver gradually decreases and stops by the time of birth.

Splenic stage starts from the 12th week of gestation. Initially, granulo-, erythro- and megakaryocytopoiesis (partially) are determined. From the 15th week, VL appears.

At the age of 19-25 weeks of gestation, 85% of spleen cells are lymphoid in nature. L appear with intracellular content of Ig M and Ig G. Intensive lymphopoiesis continues in the spleen throughout a person's life.

Hemopoiesis in the spleen reaches its maximum by the 4th month of gestation, then declines and stops at the age of 6.5 months. in / uterine development.

The decrease in extramedullary hematopoiesis coincides with the appearance of the first signs of bone marrow hematopoiesis.

In an adult human spleen:

foothold of immunogenesis, responsible for the humoral, B-cell link of immunity, here, including IgG and M, antibodies, autoantibodies are produced.

- takes part in the regulation of maturation and exit from the bone marrow of erythropoiesis and granulopoiesis cells, platelets and lymphocytes.

- is an organ of blood destruction (in the reticuloendothelium of the pulp and sinuses, the destruction of aging erythrocytes (Er) and thrombocytosis (Tr) occurs)

- participates in the interstitial exchange of iron (Fe), the organ of Fe deposition.

- an important blood depot (accommodates 20% of circulating blood).

– humorally affects the process of Er denucleation; after splenectomy, Er with Jolly bodies appear.

Bone marrow hematopoiesis starts from the 3rd month of gestation and reaches a maximum by 30 weeks. from 20 weeks it is the main organ of hematopoiesis and remains so until the end of a person's life. type of hematopoiesis macro-normoblastic.

In the last 10 weeks of intrauterine development, the volume of the brain does not change significantly. Initially, the bone marrow arises in the bodies of vertebrae 95 mm long. At 11-14 weeks of gestation, immature hematopoietic cells and erythrocytes are determined in the ilium; after 23-27 weeks, elements of all 3 hematopoietic sprouts are detected at all stages of development.

At the age of 13-14 weeks in utero, the first foci of hematopoiesis appear in the diaphysis of the humerus and femur. As the skeleton grows, the role of bone marrow hematopoiesis increases, after 30 weeks the bone marrow is represented by all hematopoietic cells, it becomes the main source of blood cell formation.

In the prenatal period, the entire bone marrow is red, i.e., hematopoietic. From 32 weeks of age, all spaces of bone tissue (i.e., all cavities of flat and tubular bones) are filled with hematopoietic tissue, i.e., the volume of the bone marrow is equal to the volume of hematopoietic cells. By the time of the birth of a child, hematopoiesis is almost completely represented by the bone marrow. In a newborn child, the bone marrow averages 1.4% of the child's weight (in an adult - 4.6%)

Starting from the first year of life, fat cells appear in the diaphyses of long tubular bones (bone marrow lipolization), which gradually increase and at 12-14 years old, red bone. the brain disappears from the diaphyses, and by the age of 20-25 - from the epiphyses of tubular bones, and at 16-18 years old, the red bone marrow is preserved only in the vertebral bodies, ribs, sternum, pelvic bones, and skull. The most active areas of hematopoiesis are determined in bones with a high content of spongy substance.

Fatty degeneration of the bone marrow continues throughout life, but should not exceed 50-75%. If it is more than 75%, we are talking about a pathological hypoplastic state of hematopoiesis. % fatty degeneration of the bone marrow is specified by trepanobiopsy. Blood cells in the bone marrow are formed outside the vessels (extravascular), having reached maturity, they enter the general blood flow through the wall of the endothelial sinuses.

In the bone marrow, the processes of leukopoiesis, erythropoiesis and thrombocytopoiesis occur. In the bone marrow, there are erythroid, granulocytic-monocytic and megakaryocytic hematopoietic sprouts that produce the corresponding cells.

Myelogram

Puncture the sternum, the ilium closer to the spine, in newborns - the calcaneus. Do 5 strokes

Blasts - 0-5%

Total cells of the neutrophilic series - 36-66%

Total cells of the eosinophilic series - 0.5-12.6%

Total cells of the basophilic series - 0-1.8%

Lymphocytes - 11.8-33.4%

Monocytes - 0-7.8%

Total erythroid cells - 10-26%

Nuclear myelokaryocytes - 60-400´109/l

Megakaryocytes – 40-200´109/l

With age, the ratio changes: L is more than erythroid cells;

Lecco-ritroblastic ratio - 3-4: 1

Erythroblast maturation index - 0.8-0.9

Maturation index L - 0.6-0.9

The development of the lymphoid tissue of the thymus occurs at the 6-7th week of gestation. The first l / y appear on the 10th week, and the lymphoid apparatus of the intestine - on the 14-16th week. Initially, myelopoiesis is determined in l / y, which is soon replaced by lymphocytopoiesis. By the time of birth, the child has 220 l / y. However, the final formation of the sinuses and l / y stroma occurs in the postnatal period.

Hb is found in primitive erythrokaryocytes at the early stages of ontogenesis. In the embryo up to 5-6 weeks of gestation, HbP (primitive) predominates, which dominates up to 12 weeks. Then it quickly changes to HbF (fetal) and after 12 weeks of gestation is the main one. HbA (adult) begins to be synthesized from the 3rd week of gestation, increases slowly, and by the time of birth does not exceed 10-15%.

Blood parameters in different age periods

Main differences in the composition of blood cells of the fetus is a constant increase in the number of Er, the content of Hb, the amount of L. If up to 6 months of intravenous development, many immature elements (erythroblasts, myeloblasts, pro- and myelocytes) are found in the blood, then in the following months, predominantly mature elements are found in the peripheral blood of the fetus .

Red blood. Immediately after birth, the child's blood contains an increased content of Hb and the number of Er.

By birth, HbF is 60-80% (it has a high affinity for O2)

On the 1st day Hb–180-240g/l and Er–6-8*1012/l

From the 2nd day, the Hb and Er indicators decrease, and at the age of 9-15 days they average 188 g/l (134-198 g/l) and 5.41´1012/l, respectively. The maximum decrease in Hb is observed by the 10th day, Er - by 5-7.

At 1 month of life Hb 107-171 g/l, Er 3.3-5.3´1012/l

The content of Rt is increased within 1 day after birth (5-6%), then gradually decreases and by the 5-7th day reaches the minimum values. After a year, the amount Rt =1%. All this testifies to intensive erythropoiesis. Transient reticulocytosis also occurs at 5-6 months, which is explained by the low content of copper and iron in the diet before the introduction of complementary foods.

After birth, hypoxia is replaced by hyperoxia, which leads to a decrease in the production of erythropoietin, erythropoiesis is suppressed + a shortened life of Er (12 days) + a tendency of Er containing HbF to hemolysis. As a result, after the neonatal period, the number of Er and Hb continues to decrease, and the amount of Hb decreases to a greater extent. These indicators reach their minimum values ​​by 2-4 months (Hb up to 116-90 g / l, Er up to 3.0 * 1012 / l) - "physiological anemia", there is a tendency to hypochromia, a decrease in Er hemoglobinization .

The physiological anemic state is due to:

The transition from HbF to HbA, followed by hemolysis of Er

Immaturity of the erythrocyte germ of the bone marrow

Lack of erythropoietins and weak sensitivity of progenitor cells to them

Depletion of Fe reserves, intensive decay of Er containing HbF.

The life span Er of a healthy adult is 120 days.

The minimum osmotic resistance Er is reduced.

Then, due to an increase in the production of erythropoietin, first the numbers of Rt, and then Er and Hb begin to recover. By the middle of the 1st year of life, the number of Er exceeds 4´10 12/l, and Hb - 110-120 g/l. Subsequently, during the 1st year of life, these indicators do not change and differ little from their level in adults.

Anemia in the first weeks of life is diagnosed at the level of Hb<145 г/л Er < 4,5´10 12/л, гематокрита (Ht) < 0,4; на 3-4 нед жизни – при уровне Hb <120 г/л Er < 4,0´10 12/л

Indicators of red blood in newborns are characterized not only quantitatively, but also qualitatively. Anisocytosis (5-7 days), macrocytosis, polychromasia, a decrease in osmotic resistance of Er, a higher content of Hb in them, many young formed elements, nucleated Er (active hematopoiesis) are noted.

White blood: The number L in the first hours of life varies widely - from 10 to 30´109 / l. During the 1st, sometimes the 2nd day of life, their number increases somewhat, and then decreases, averaging 11´10 9/l. In subsequent years, the decrease in L continues and normally amounts to 6.7 - 8.9´10 9/l.

With age, the L-formula changes significantly. After the birth of neutrophils (N) = 60-70%, L–25-30%, i.e., the luukocyte formula (L-formula) is shifted to the left (to p / o, megamyelocytes, young). Starting from the 2nd day of life, the content decreases H and the number of L increases. In 5-6 days, their content levels off, amounting to 40-44% (1st crossover). In premature babies a little earlier (on the 3rd day). The minimum content of s / I H and the maximum number of L is determined at 5-6 months (in preterm infants at 1-2 months). After a year, the number of H increases, and L decreases, and at the age of 4-5 years, their content levels off again (2nd cross). From 5 to 12 years old, H increases by 2% every year. At the age of 14-15, the content of these elements is the same as in adults. Life expectancy L averages about 2 weeks.

Physiological processes of death of all formed elements occur in the spleen. ESR - 2-8 mm / h

Features of the coagulation system

The blood coagulation system is a physiological system that maintains the blood in a liquid state due to the dynamic balance of coagulation and anticoagulation factors.

The process of homeostasis is provided by 3 main links: vascular, plasma and platelet.

Vascular link of homeostasis basically completes its development by birth. However, there is an increased fragility and permeability of capillaries, as well as a decrease in the contractile function of precapillaries, which maintains a high level of metabolism in-in, characteristic of children in the first days of life. By the end of the neonatal period, the vascular link of homeostasis = adults.

Plasma link of homeostasis :

Proaccellirin (factor V), antihemophilic globulin A (factor VIII), fibrin-stabilizing factor (XIII) by childbirth = adult

Vitamin K-dependent factor, prothrombin (II), proconvertin (VII), antihemophilic globulin B (IX), Stuart-Power factor (X) and contact factors (XI and XII) are relatively low in the first hours of life, especially on the 3rd day of life . Then their activity increases, which is explained both by the sufficient intake of vitamin K and the maturation of the protein-synthetic function of the liver.

Platelet link homeostasis:-reduced functional activity (ability to aggregate) Tr, although their number=adults.

The activity of the anticoagulant system has not been studied enough. It is known that newborns have a high level heparin during the first 10 days.

fibrinolytic activity immediately after birth is increased and within a few days decreases to the level of an adult.

Reduced level plasminogen= adults by 3-6 months.

Low activity of clotting factors protects newborns from thrombosis, which can occur when tissues are damaged during childbirth.

By the end of the 1st year of life, the indicators of the coagulation and anticoagulation systems = adults. Large fluctuations are noted in the pre - and puberty periods.

Hemogram of a premature baby

The level of Er and Hb = the level of full-term children with a slight tendency to decrease, erythroblasts are detected.

Anemia on the 1st week life is diagnosed at the level of Hb< 150 г/л

on the 2nd week–Hb< 130 г/л

on the 3rd week - Hb< 116 г/л

leiocytosis diagnosed at L level >35.0´10 9/l

Leukopenia-L<3,6´10 9/л

In preterm infants, the L number is somewhat less than in full-term ones; I crossover in the leukocyte formula is observed on the 3rd day of life, the shift of the formula to the left.

There may be a downward trend in Tr, a large percentage of giant cells.

ESR - 2-8 mm / h

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Hemogram of a child under 1 year old

After the neonatal period, the Er number and the Hb content continue to decrease. Hb decreases as much as possible in 2-4 months (physiological anemia), there is a tendency to hypochromia, a decrease in Er hemoglobinization.

After 3-4 months, Hb rises, reaching 110-140 g/l by 6 months, and 113-141 g/l by 1 year.

In children from the age of 1 month to 5-6 years anemia diagnosed with Hb level< 110 г/л. колебания Er – 3,5-5,5´1012/л, отмечается анизоцитоз, полихроматофилия менее выражена, макроцитов практически нет.

Reticulocytes (Rt) - 0.2-2.1%.

Fluctuations of L are 6.0-12.0´10 9/l (average - 9.0´10 9/l). Leukocytosis is diagnosed at the level L> 15.0-17.0 ´10 9/l, leukopenia– at level L<6,0 ´10 9/л). В L - формуле преобладают Л (60-70%), М – 7-8%.

Hemogram of children older than 1 year

Hb gradually increases: up to 5-6 years old it is 110-140 g / l, over 5 years old - 120-160 g / l. Anemia in children older than 5-6 years are diagnosed with Hb level<120 г/л.

Fluctuations of L are 4.0-9.0´109/l. Leukocytosis is diagnosed at the level L > 12.0´10 9/l, leukopenia– at level L<4,0 ´10 9/л).

In the L-formula at 4-5 years, the number of H and L equalizes (2 crosses), after 5 years the amount of L decreases, the final content of H 60-65% and L - 25-30% is established in the prepubertal or pubertal period.

Fluctuations Tr 150-400 ´10 9/l (average 200-300 ´10 9/l). Thrombocytopenia observed with a decrease in the amount of Tr< 150´10 9/л.

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Types of normal hemoglobin

Hb is a respiratory pigment contained in Er, which transports molecular O2 from the lungs to the tissues. The Hb molecule consists of 2 parts - heme (4%) and globin (96%).

Hb P (9-18 weeks of gestation) corresponds to the period of yolk hematopoiesis.

Hb F (8-13 weeks) at birth is 75-80%, from 5 to 12 months. decreases to 1-2%, typical for the period of the hepatic-splenic stage of hematopoiesis.

Hb A consists of Hb A1 (96-98%), Hb A2 (2-5%) and Hb A3 (0.5-1%). Characteristic for the period of bone marrow hematopoiesis.

MCV is the average volume of Er in cubic micrometers or femtoliters. MCV less than 80 fl is regarded as microcytosis. More than 95 fl – macrocytosis (fl=10–5/l)

MCH - reflects the absolute content of Hb in Er in picograms, this indicator is more reliable than the CPU calculation. (N=27-32 pg/erythrocyte)

MCHC is the average saturation of Er with hemoglobin and is determined by dividing the concentration of Hb by the value of Ht (N=32-36 g%). A decrease in MCHC of less than 31% reflects absolute hypochromia.

RDW – index of Er anisocytosis (indicator of Er distribution by volume) (N=11.5-14.5%).

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The life expectancy of Er is 80-120 days, L - 1-3 weeks (average 2 weeks), Tr - 8-11 days.

Features of immunity in children

Immunity (IT) is a way of protecting the body from living bodies and substances that carry signs of foreign information (status), leads to a weakening of anti-infective resistance, a decrease in antitumor protection, and an increase in the risk of autoimmune disorders and diseases.

– have species specificity and low antigenic activity

- their formation goes in parallel with the penetration of the virus and the onset of a febrile reaction

- they are produced by cells that are primarily affected by viruses

– most intensively produced L

- show their effect at the intracellular stage of virus reproduction (block the formation of DNA necessary for virus replication)

– have antitoxin action against exo- and endotoxins

- low doses of I promote antibody formation, as well as, to some extent, activation of the cellular link I-ta

- enhance phagocytosis

- modify the reactions of specific I-that.

The ability to educate I immediately after birth is high, then decreases in children of the 1st year of life, and, gradually increasing, reaches a maximum by the age of 12-18.

Complement system(SC) is a complex system of blood serum proteins, includes 9 components and 3 inhibitors, consists of 2 parallel systems: classical and alternative (properdin subsystem). The first is activated by C-reactive protein and trypsin-like enzymes (its participants are designated as "components" of the system by the letter "C"), the second - by endotoxins and fungal antigens (its participants are called "factors").

Activated SC components enhance phagocytosis and lysis of bacterial cells. As a result of the activation of the entire SC, its cytolytic effect is manifested. SC has a protective function, but can contribute to damage to the body's own tissues (with glomerulonephritis, SLE, myocarditis, etc.).

Components C2 and C4 are synthesized by macrophages, C3 and C4 - in the liver, lungs and peritoneal cells, C1 and C5 - in the intestine, C-inhibitor - in the liver.

The SC is formed between the 8th and 15th week of gestation, but by the time of birth the level and activity in = ½ of the level of the mother. In the first week of life, the level of SC increases rapidly, and at the age of 1 month = the level of adults.

Phagocytosis(F) the most ancient defensive reaction of the organism. It is an early defense mechanism of the fetus. The system of nonspecific immunity is represented by circulating phagocytes (polymorphonuclear L, M, E), as well as phagocytes fixed in tissues (macrophages, spleen cells, stellate reticuloendotheliocytes (Kupffer cells) of the liver, alveolar macrophages of the lungs, macrophages of the lymph glands, microglial cells of the brain). There are microphages (H) and macrophages (M and mononuclear cells).

The cells of this system appear between the 6th and 12th week of gestation.

The absorptive capacity of phagocytes in newborns is sufficiently developed, but the completed phase F is not yet perfect and is formed after 2-6 months (incomplete F), because the level of non-enzymatic cationic proteins (lysozyme, lactoferrin, myeloperoxidase, etc.) involved in the final stage of F low. The F level, starting from the 1st month of life and throughout life, is 40%. Pneumococcus Klebsiella pneumoniae, Haemophilus influenzae are not exposed to F Þ higher incidence of pneumonia in young children. Staphylococcus and gonococcus even retain the ability to multiply in the protoplasm of phagocytes.

specific immunity. The ability to produce a / t by own cells of the B-system in the fetus begins from 11-12 weeks of gestation. In general, intravenous Ig synthesis is limited and increases only with IUI. There are 5 classes of Ig (A, M, G, E, D)

IgG (70-75%) are synthesized from the 5th month of intravenous development

- they include a / t, which play a leading role in protecting against many viruses (measles, smallpox, rabies) and bacteria, mainly gram (+), as well as against tetanus, malaria, anti-rhesus hemolysins, antitoxins (diphthyria, staphylococcal)

- have a virus-neutralizing effect

- are able to pass through the placenta, starting from the 12th week of gestation, this ability increases with the increase in its terms

- possible reverse transfer of IgG from the fetus to the mother

- crossing of own and maternal IgG is noted at 5-6 months of life (during the first 4-6 months maternal IgG are destroyed and synthesis of own begins)

- maternal IgG completely disappear by 1 year

- are not absorbed through the intestinal mucosa

- synthesis is slow, reaches the level of an adult by 5-6 years

IgM (10%) protect the body from infections. It consists of a / t against gram (-) bacteria (shigella, typhoid fever), viruses, as well as hemolysins of the ABO system, rheumatoid factor, antiorganic a / t

– have a high agglutinating activity and are able to activate SC along the classical pathway

- in the body of the fetus are synthesized first from 3 months of intravenous development

- enter the blood of the child only with increased permeability of the placenta in gynecological diseases of the mother (endomnitis)

- synthesized V-L

- reach adult level by 4-5 years

IgA (20%) is formed by lymphoid cells of the mucous membrane of the gastrointestinal tract and the respiratory system

- begin to be synthesized from 7 months of development

– serum IgA are involved in the activation of SC, in the lysis of bacteria and cells (Er)

- serum IgA is a source for the synthesis of secretory

– secretory IgA up to 1 month is practically absent, traces appear from the 1st week of life

– secretory IgA is produced by lymphoid cells of the mucous membrane of the gastrointestinal tract and the respiratory system Þ participate in the local immune system

are the first line of defense against infections

- in the secrets of the nasal mucosa at the 1st month of life is absent and grows very slowly up to 2 years Þ frequent SARS

- have an anti-absorption effect

- supplied with mother's milk

- reaches adult level by 10-12 years

- a lot in colostrum, which compensates for the immaturity of local intestinal immunity

IgD (0.001 g / l) little is known about their function, it is found in the tissue of the tonsils, adenoids Þ is responsible for local immunity

- has antiviral activity

– activates SC by alternative type

– timing of intravenous synthesis is not well understood

- increases after 6 weeks of life

- reaches adult level by 5-10 years

IgE (reagins) level is low (in the blood serum it has a concentration of 0.0033 g / l), however, many L carrying IgE are found in the umbilical cord blood

- from 11 weeks in / in development is synthesized in the liver and lungs, and from 21 weeks - in the spleen

- with IgE, the presence of reagins involved in allergic reactions of the immediate type is associated

– activate macrophages and E, which may enhance phagocytosis or macrophage activity (N)

- IgE levels increase with age, reflecting an increase in the incidence of allergic diseases after 1 year.

Immunodeficiency states (IDS) - a violation of the normal immune status, which is caused by a deficiency of one or more mechanisms of the immune response.

Their deficiency may be hereditary(or primary) (i.e. genetically determined), transitory(due to a slowdown in the maturation of them, more often the humoral link) and acquired(or secondary) (due to, for example, long-term use of drugs, especially cytostatics).

It can also be distinguished cellular, humoral, complementary immunodeficiency and failure of phagocytic function.

1) Primary IDS in the B-cell system is characterized by:

- repeated and severe purulent diseases caused by streptococci, pneumococci and Haemophilus influenzae;

- fungal and viral lesions are relatively rare (except for enteroviruses and poiomyelitis);

- diarrheal diseases and disorders associated with giardiasis;

- moderate growth retardation;

2) Primary IDS of the T-cell system is characterized by:

- repeated severe infections caused by viruses, fungal complications and diseases, protozoan invasions, persistent helminthiases;

- severe complications from immunization with live virus vaccines or BCG vaccine;

- frequent diarrheal disorders;

- exhaustion, lag in growth and development;

- the concentration of tumor diseases in the family.

3) Primary phagocytic disorders are characterized by:

- repeated skin infections and fungal skin lesions. The most likely pathogens are: staphylococcus aureus, pseudomonas, E. coli, from fungi - aspergillium;

4) Complementary deficiency is characterized by:

- repeated bacterial infections caused by pyogenic pathogens such as pneumococcus or Haemophilus influenzae;

- unusual sensitivity and frequency of gonococcal and meningococcal infections;

- repeated severe diseases of the respiratory tract and skin;

- the concentration in the family of cases of SLE, rheumatoid arthritis or glomerulonephritis.

Examples of primary insufficiency of cellular im-that (T-L):

1. SyndromeDi George(hypoplasia of the thymus) - an anomaly in which there is hypoplasia of the thymus, parathyroid glands and many other malformations, including CHD. Associated with hypocalcemia. Usually not inherited. Occurs as a result of embryopathy with damage to the III and IV parapharyngeal gill pockets.

Clinically manifested immediately after birth, tetany, facial malformations (“fish-shaped mouth”, cleft lip and palate, low-set ears, auricle recess, hypertelorism, micrognathia, antimongoloid slit of the eyes), CCC, cataracts, recurrent infections of the lungs and intestines.

Paraclinic: hypocalcemia, hyperphosphatemia, low T-cell count, normal or high levels of V-L and Ig.

In surviving children (possibly spontaneous recovery), the number of T-cells is restored by 5 years.

The prognosis depends on the timeliness of diagnosis, the ability to correct CHD and the T-system defect (thymus transplantation).

2. Deficiency of purine nucleoside phosphorylase. It is inherited in an autosomal recessive manner, the mutation was determined on the 14th chromosome. In homozygotes, it leads to the accumulation of a large amount of guanosine triphosphate, which inhibits ribonucleotid reductase, and, consequently, DNA synthesis. Manifested at the age of 6 months to 7 years (in the first years of life).

Clinic: developmental delay, phenomena of spastic paresis and paralysis, anemia (megaloblastic, autoimmune or hypoplastic), recurring DNA viral infections (herpes, CMV), otitis media, diarrhea, convulsive tendencies, ataxia.

Paraclinic: lymphocytopenia, low level of urinary to-you in the blood and urine, low number of T-cells with normal levels of V-L and Ig.

3. Syndrome of short-legged dwarfs.

4. Chronic mucocutaneous candidiasis.

Examples of primary insufficiency of humoral im-that (V-L):

1. Agammaglobulinemia (Bruton's disease) X-linked

2. Autosomal recessive agammaglobulinemia

3. Bloom syndrome inherited in an autosomal recessive manner and is characterized by dwarf growth, photosensitivity, chromosomal abnormalities, and a high incidence of malignant neoplasms.

4. Transient hypoglobulinemia

5. selective scarcityIgA

6. Deficiency of the secretory component of IgA

7. selective scarcityIgM

8. Hypogammaglobulinemia with elevated IgG levels

9. selective scarcityIgG

10. Dysgammaglobulinemia

Combined insufficiency of humoral and cellular im-that.

1. Wiskott-Aldrich Syndrome inherited by a recessive type linked to the X chromosome and is characterized by a triad of symptoms: recurrent purulent infections (otitis media, skin lesions, lungs), hemorrhagic syndrome (purpura, melena, epistaxis) due to thrombocytopenia and eczema.

2. Ataxia-telangiectasia (Louis-Barr syndrome) It is inherited in an autosomal recessive manner. Clinically manifested in the 1st and 3rd years of life: progressive cerebellar ataxia, combined with increasing expansion of the lymphatic vessels in limited areas (telangiectasia), starting from the vessels of the conjunctiva, then on the oral mucosa and by 5 years on the skin.

Causes leading to secondary immunodeficiencies:

Viral infections:

- human herpes virus

- Epstein-Barr virus

- HIV infection

Metabolic diseases:

- diabetes

- malnutrition

– uremia

- sickle cell anemia

- zinc deficiency

– multiple cocarboxylase deficiency

Conditions with severe protein loss:

- nephrotic syndrome

protein-losing enteropathy

Other states:

- underweight and/or prematurity

- treatment with immunosuppressive drugs

– malignant neoplastic diseases (OLL, LGM, cancerous neoplasms outside the lymphoid system)

- conditions after splenectomy

– periodontitis

- repeated blood transfusions

- neutropenia of any nature

- bone marrow transplantation

The role of the yolk sac. Some time after fertilization of the egg (2-3 weeks), embryonic hematopoiesis occurs. The first stages of this process take place in the yolk sac, where undifferentiated cells called mesoblasts are found that migrate into it from the primitive streak of the embryo. Mesoblasts have a high mitotic activity and subsequently differentiate into cells called primary erythroblasts, undoubtedly related to mature adult blood cells, as well as to primary endothelial cells that form the vascular system of the yolk sac. Within a few hours after migration, the mesoblasts of the yolk sac divide and differentiate into primary erythrocytes. Most of these cells are nucleated, while some do not have nuclei. But they all synthesize hemoglobin, which causes the reddish color of the well-defined blood islands of the yolk sac.
Also found in the blood islands are precursors of platelets, megakaryocytes, which also originate from mesoblasts. Other mesoblasts appear to differentiate into cells called hemocytoblasts.
In some mammalian embryos, a second stage of hematopoiesis has been described in the yolk sac. It also exists in human embryos, but it does not proceed as vigorously as, for example, in a rabbit, the embryogenesis of blood cells of which is most studied. At the second stage of hematopoiesis in the yolk sac, hemocytoblasts differentiate into final erythroblasts, which subsequently synthesize hemoglobin and become final, or secondary, normoblasts. The latter may lose their nuclei and become the final erythrocytes. Vascular channels form in the blood islands, eventually uniting into a network of blood vessels. This network of primitive blood vessels contains primary erythroblasts and hemocytoblasts in the early stages, and mature erythroblasts and erythrocytes in later stages. By the end of the third week of embryonic development of the rabbit, the hematopoietic activity of the blood islands decreases, and the process of hematopoiesis moves to the liver.
Embryonic mesenchyme. An additional role in early embryonic hematopoiesis directly in the body cavity is played by primary mesenchymal cells, especially in the region of the anterior precordial mesenchyme. A small proportion of mesenchymal cells develop into erythroblasts, megakaryocytes, granulocytes, and phagocytic cells similar to the corresponding adult cells. The number of these cells is small, and large growths of blood cells, similar to the hematopoietic islets of the yolk sac, do not form in the mesenchyme of the body cavity. Stem cells located among these hematopoietic cells (outside the yolk sac) probably play a major role in the generation of subsequent generations of hematopoietic cells in the fetus and in the postnatal period, although the relative contribution of primary stem cells located in and outside the yolk sac in the later hematopoiesis is not yet clear.
Hepatic period of embryonic hematopoiesis. In humans, starting at about the 12 mm embryo stage (6 weeks of age), hematopoiesis gradually moves to the liver. The liver soon becomes the main site of hematopoiesis and is active in this regard until birth. As the liver endodermal bands form into transverse septa, they collide with wandering mesenchymal cells with lymphocyte morphology. These small round lymphoid cells, called lymphocytoid vagus cells, are subsequently trapped between the primary hepatic endodermal cords and the endothelial cells of the ingrowing capillaries. They form hemocytoblasts similar to those in the yolk sac. These hemocytoblasts soon form foci of hematopoiesis, similar to the blood islands of the yolk sac, where secondary erythroblasts form in large numbers. Secondary erythroblasts subsequently divide and differentiate into mature erythrocytes, with activation of hemoglobin synthesis and loss of the cell nucleus. Although mature erythrocytes are found in the liver of the embryo already at the age of 6 weeks, they appear in the circulation in significant quantities much later. Thus, by the fourth month of fetal life, the majority of circulating erythrocytes are represented by secondary mature forms. Megakaryocytes are also probably formed from hemocytoblasts in the liver of the embryo and fetus. In the embryonic liver, granulocytic cells are found, but they apparently develop not from hemocytoblasts, but directly from wandering lymphocytoid cells.
Embryonic bone marrow and myelopoiesis. Different bones in the embryo are not formed simultaneously. Before others - the long bones of the additional skeleton. Initially, a cartilaginous model of each bone is formed. The central nucleus of the diaphysis subsequently ossifies, and soon after the ingrowth of mesenchymal cells, an area of ​​bone resorption develops from the periosteum. The process of movement of mesenchymal cells is accompanied by ingrowth into capillaries. The number of mesenchymal cells continues to increase due to the continuous influx of new cells, as well as the division of those that are already inside the newly formed medullary cavity. They produce non-cellular material, or matrix, that fills the developing bone cavity. From these early bone marrow mesenchymal cells, cells are formed that are morphologically similar to hemocytoblasts of the liver and yolk sac. Like the latter, they give rise to megakaryocytes and erythroid cells, as well as myeloid cells, including neutrophils, basophils, and eosinophils. The embryonic bone marrow differs markedly from the centers of the earlier development of hematopoiesis in that the formation of myeloid cells is especially vigorous here and dominates in hematopoiesis. The process of early myeloid cell formation, or myelopoiesis, begins in the central part of the medullary cavity and spreads from there to eventually invade the entire bone cavity. Erythropoiesis in the embryonic bone marrow develops a little later and is mainly mixed with the process of myelopoiesis, so that among the majority of maturing cells of the myeloid line, small foci of erythropoiesis can be observed. After birth in humans, hematopoiesis ceases in the liver, but continues in the bone marrow for the rest of life.
Hematopoiesis in the spleen of the embryo and fetus. The last important focus of hematopoiesis, which is formed in the embryonic period, is the spleen. Although the spleen itself forms much earlier in humans, circulating hematopoietic progenitors begin to fill it around the fourth month of pregnancy. Probably as a result of the accumulation of a large volume of blood, the fetal spleen becomes the center of hematopoiesis until the moment of birth, when splenic erythropoiesis gradually ceases. In general, the myelopoietic activity of the spleen of the embryo and fetus is relatively low. Later, during the fifth month of embryonic development, the white pulp of the spleen is formed. This process is associated with the differentiation of mesenchymal cells, which are grouped around the splenic arterioles. The formation of splenic lymphocytes in the embryo is completely spatially separated from the centers of erythropoiesis in this organ.
Other sites of hematopoiesis in the embryo and fetus. The embryonic thymus develops as a derivative of the third gill pocket. The thymic epithelium is filled with wandering mesenchymal cells, which begin to multiply rapidly and differentiate into lymphocytes. At the same time, a small number of erythroid and myeloid cells are formed in the thymus, but the process of lymphopoiesis predominates. Lymphocytes formed in this organ represent a special class of lymphocytes with a special function - participation in cellular immunity. Lymph nodes develop as outgrowths of primitive lymphatic vessels, which are soon surrounded by a large number of mesenchymal cells. Subsequently, these cells round and become similar in appearance to adult lymphocytes. Some of the mesenchymal cells give rise to other cell lines, such as erythrocytes, granulocytes, megakaryocytes, but this phenomenon is transient, since the main process in the thymus is lymphopoiesis.
Conclusion. In all hematopoietic organs of the embryo and fetus, identical processes occur. Circulating primary hematopoietic stem cells settle in a specific tissue niche in a manner that is not yet fully understood. There they differentiate into cells recognizable as hematopoietic progenitors. These embryonic hematopoietic progenitors are likely capable of multilineage differentiation, but at each specific site, the process of hematopoiesis may be targeted to form a specific cell lineage, possibly under the influence of the local microenvironment. Different foci of embryonic hematopoiesis are active only at the corresponding stages of development. This activation is followed by a programmed involution. The exception is the bone marrow, which is preserved as the main center of hematopoiesis in adults. Lymph nodes, spleen, thymus and other lymphoid tissues continue to perform a lymphopoietic function in an adult.

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