Organic components of plasma. General properties of blood. Formed elements of blood

The main component that forms the internal environment of the human body is blood. Among all the tissues of the body, it is the only one that has liquid foundation, its volume is from 4 to 6 liters. In newborn babies, the amount of blood is approximately 200 - 350 ml. Blood circulation is carried out by closed system It does not have direct communication with blood vessels under the influence of rhythmic contractions of the heart and with other tissues (histohematological barriers are responsible for this). In the human body, blood is formed from special stem cells (their number reaches 30,000), which are located mainly in the bone marrow, but also some of them are found in the small intestine, lymph nodes, thymus and spleen.

Blood is a rapidly renewing tissue. Physiological regeneration her constituent elements occurs as a result of the breakdown of old cells and the formation of new ones in the hematopoietic organs. IN human body the main such organ is the bone marrow, which is located in large tubular and pelvic bones. The main filtering organ for blood is the spleen, which is also responsible for the immunological control of the blood.

Components blood:

• plasma is a liquid system;
• blood cells - platelets, erythrocytes, leukocytes.

Main functions of blood:

1. Respiratory - transportation of molecules throughout the body carbon dioxide and oxygen.
2. Supporting the balance of the internal environment (homeostasis).
3. Transfer of nutritional compounds, vitamins, hormones and minerals.
4. Picking up products metabolic processes from tissues and moving them to the lungs and kidneys for subsequent excretion.
5. Protection of the body from foreign elements (in combination with lymph).
6. Thermoregulation - blood controls body temperature.
7. Mechanical – creation of turgor tension due to the flow of blood to the organs.

Types of Blood Cells

The following main types of blood cells are distinguished:

1. Red blood cells

Red blood cells have a biconcave shape and an elastic membrane. These features, as well as the absence of a nucleus, allow them to easily pass through small vessels (capillaries), the lumen of which is narrower than the diameter of the cell itself.

The formation of red blood cells in the bone marrow occurs quite slowly; after certain stages, reticulocytes (immature cells) appear first, having remnants of the nucleus and a small amount of hemoglobin. After 2 days they mature into full-fledged red cells. In the fetus, red blood cells begin to form from the 4th week in the liver and spleen, and some time before the birth of the child, this function passes to the bone marrow.

Red blood cells have a lifespan of 110 to 120 days, after which they are removed from the bloodstream as they pass through the spleen, liver, and bone marrow.

2. Leukocytes

Leukocytes are white blood cells with a nucleus.

They protect the body from harmful viruses and bacteria. The blood contains much less of them than red blood cells (from 4 to 10 thousand per 1 microliter). Leukocytes may contain granules, depending on the presence or absence of which they are divided into granulocytes and agranulocytes.

These cells are very actively involved in various processes in the body, and the granules contain a large number of enzymes.

The quantitative content of leukocytes in the blood is expressed as a percentage, since the absolute digital designation is not indicative. Ratio various types white cells is called the leukocyte formula.

Granulocytes are divided into:

• Neutrophils - among all leukocytes, they make up the majority. Their nuclei include from 2 to 5 segments. In the peripheral bloodstream, these cells live for about 7 hours, after which they rush into the tissues to perform a protective function.
• Eosinophilic - occupy about 4% of the total number of leukocytes. Their core consists of 2 segments. The granules of these cells include the main protein and peroxidase, which are involved in the release of histamine from the structures of basophils, that is, they take part in the formation of the allergic response.
• Basophils - they occupy about 1% of the total composition of white blood cells. They have specific granules that contain histamine, chondroitin sulfate, and heparin. The release of heparin initiates a cascade during the development of an allergic response.

Agranulocytes are divided into:

• Lymphocytes - they are needed to protect the body from viruses, tumor cells, and autoimmune agents. There are T and B lymphocytes. The former are responsible for cellular immunity and act as transmitters in the immune response system. The latter are needed for the synthesis of antibodies against pathogens various diseases. All lymphocytes have memory, so if they encounter the microbe again, they begin to fight it faster.
• Monocytes are the largest blood cells, constituting about 8% of the total number of leukocytes. Their life time in the bloodstream is no more than 12 hours, after which they turn into macrophages in the tissues. The main purpose of these cells is to resist any foreign agents.

3.Platelets

In another way, these particles are called blood platelets; they are the smallest elements of blood. These cells are disc-shaped and have no nuclei. U healthy people the number of platelets in the bloodstream ranges from 150 to 450 thousand per 1 microliter. Lifespan blood platelets is equal to 9–12 days, during which they do not change in any way, but their population is continuously renewed, and the excess is utilized by the spleen.

Platelets are fragments of a large red bone marrow cell - a megakaryocyte. They perform their functions in regulating the process of hemocoagulation (blood clotting) due to special factors contained in alpha granules. These cells are also involved in stopping bleeding (hemostasis). If damage occurs blood vessel, then at the rupture site a blood clot, then a crust forms and the bleeding stops. Without platelet recruitment, any small wound or nosebleed, for example, can cause large blood loss.

Plasma composition and functions

Plasma is a solution consisting of 90% water, and the dry residue includes inorganic and organic compounds. The plasma pH value (acidity level) is a fairly stable value and is equal to 7.36 in arterial blood and 7.4 in venous blood. In the body of an adult, approximately 2.8 to 3.5 liters of plasma circulates, which is about 5% of the total body weight.

The composition of blood plasma is quite rich. Some elements of plasma are unique to blood and are not found in any other environment or tissue of the body. The liquid part of blood includes the following inorganic compounds:

1. Sodium - its amount ranges from 138 to 142 mmol/l. This element is the main cation of fluid outside cells, it is necessary to maintain pH levels and constant volume, as well as to regulate osmotic pressure.
2. Potassium - plasma contains from 3.8 to 5.1 mmol/l. It serves to activate large quantity enzymes are the main elements of fluid inside cells and maintain the excitability of muscles and nerve fibers at the desired level.
3. Calcium - its concentration ranges from 2.26 to 2.75 mmol/l. This element is needed to form bone tissue, transmission of neuromuscular excitation and muscle contraction, as well as to ensure blood clotting and heart function.
4. Magnesium – normally it should be from 0.7 to 1.3 mmol/l. It is involved in the processes of inhibition in nervous system and activates some enzymes.
5. Chlorides – their amount is 97 – 106 mmol/l. In combination with sodium, they are needed to stabilize plasma osmolarity, maintain a stable volume and pH level. In addition, chlorine ions play a vital role in the digestion of food in the stomach.
6. Bicarbonate - its concentration ranges from 24 to 35 mmol/l. It is involved in the transfer of carbon dioxide molecules and maintaining blood pH, which makes it possible for many enzymes to work actively.
7. Phosphorus – normal amount from 0.7 to 1.6 mmol/l. It is needed to maintain normal pH and bone tissue formation.

Organic plasma components

The first place among all compounds is occupied by proteins, or, in other words, blood plasma proteins. Their quantity ranges from 60 to 80 g/l, that is, the entire volume of plasma contains about 200 g.

There are three types of proteins:

1. Albumin - normally in the blood of an adult, their concentration should be 40 g/l.
2. Globulins are in turn divided into alpha, beta and gamma globulins. In total, there should be 26 g/l in the blood plasma, while approximately 15 g/l are immunoglobulins (gamma-series compounds), which protect the body from the influence of viruses and bacteria.
3. Fibrinogen - its amount is 4 g/l.

The functions of blood plasma proteins are as follows:

• maintaining a constant volume of blood fluid;
• movement of enzymes various products exchange and other organic compounds V various points body, for example, from the brain to the heart, or from the liver to the kidneys;
• pH level regulation (so-called protein buffer);
• protecting the body from tumor cells, bacteria and viruses, as well as from its own antibodies (forming tolerance to its cells);
• participation in the process of blood clotting (the ability to form clots and close gaps in blood vessels) and maintaining it in a liquid state.

Plasma organic substances also include:

1. Nitrogen compounds - amino acids, ammonia, urea, transformation products of purine and pyrimidine bases, creatinine.
2. Nitrogen-free substances - glucose, fatty acid, phospholipids, lactate, pyruvate, cholesterol, triacylglycerols.
3. Biologically active compounds – vitamins, mediators, hormones, enzymes.

In addition, blood plasma contains gases - oxygen and carbon dioxide.

Blood plasma facilitates the transfer of any organic substances “from point A to point B,” that is, from the point of their penetration into the body to the place where they carry out their tasks. For example, glucose (the most important substance - a source of energy) is delivered from the site of absorption in the intestine to the cells in the brain using plasma. Or vitamin D, which begins to form in the skin, and thanks to the blood is transported to the bones.

Blood refers to the fluids of the internal environment of the body, more precisely - to the extracellular fluid, even more precisely - to the blood plasma circulating in the vascular system and cells suspended (suspended) in the plasma. Clotted (coagulated) blood consists of a clot (thrombus), which includes cellular elements and some plasma proteins, and a clear liquid similar to plasma, but devoid of fibrinogen (serum). The blood system includes hematopoietic organs (hematopoiesis) and peripheral blood, both its circulating and deposited (reserved) fractions in organs and tissues. Blood is one of the integrating systems of the body. Various deviations in the state of the body and individual organs lead to changes in the blood system, and vice versa. That is why, when assessing a person’s state of health or illness, they carefully examine the parameters characterizing the blood (hematological parameters).

Blood functions

The numerous functions of blood are determined not only by the inherent properties of the blood itself (plasma and cellular elements), but also by the fact that the blood circulates in the vascular system that penetrates all tissues and organs, and is in constant exchange with the interstitial fluid that washes all the cells of the body. In the very general view blood functions include transport, homeostatic, protective and hemocoagulation. As part of the internal environment of the body, blood is an integral part of almost any functional activity (for example, blood participation in respiration, nutrition and metabolism, excretion, hormonal and temperature regulation, regulation acid-base balance and volume of fluids, the implementation of immune reactions).

Blood volumes

Total blood volume It is customary to calculate based on body weight (excluding fat), which is approximately 7% (6-8%, for newborns - 8.5%). So, in an adult man weighing 70 kg, the blood volume is about 5600 ml. In this case, 3.5-4 liters usually circulate in the vascular bed and cavities of the heart (circulating blood fraction, or BCC- circulating blood volume) and 1.5-2 liters are deposited in the vessels of organs abdominal cavity, lungs, subcutaneous tissue and other tissues (deposited fraction). Plasma volume is approximately 55% total volume blood, cellular elements- 45% (36-48%) of the total blood volume.

Hematocrit(Ht, or hematocrit number) - the ratio of the volume of cellular elements of the blood (99% is erythrocytes) to the volume of plasma - is normally 0.41-0.50 for men, 0.36-0.44 for women. Blood volume is determined directly (by labeling red blood cells with 51 Cr) or indirectly (by labeling plasma albumin with 131 I or determining hematocrit).

Rheological properties

Rheological (including viscous) properties of blood are important when it is necessary to assess the movement of blood in vessels and the suspension stability of red blood cells.

Viscosity- property of a liquid that affects the speed of its movement. Blood viscosity is determined 99% by red blood cells. Resistance to blood flow (according to Poiseuille's law) is directly proportional to viscosity, and viscosity is directly proportional to hematocrit. Thus, an increase in hematocrit means an increase in the load on the heart(i.e., there is an increase in the volume of filling and ejection of the heart).

Suspension stability of erythrocytes. Red blood cells repel each other because they have a negative charge on their surface. A decrease in the surface negative charge of erythrocytes causes their aggregation; such aggregates are less stable in the gravitational field, since their effective density is increased. Erythrocyte sedimentation rate(ESR) is a measure of the suspension stability of red blood cells. The ESR value is measured using graduated capillary pipettes, and to prevent blood clotting, trisodium citrate (so-called citrated blood) is added to it.

Within an hour, a light column of plasma appears in the upper part of the capillary tube, the height of which in millimeters is the ESR value (in healthy individuals 2-15 mm/h). Most common reason increasing ESR- inflammation of various origins (bacterial, autoimmune), pregnancy, tumor diseases, which leads to changes in the protein composition of the blood plasma (ESR is especially “accelerated” by an increase in the content of fibrinogen and partly γ-globulins).

PLASMA

The supernatant formed after centrifugation of clotted blood is blood serum. Supernatant after centrifugation of whole blood with anticoagulants added to it (citrated blood, heparinized blood) - plasma blood. Unlike plasma, serum does not contain a number of plasma blood coagulation factors (I - fibrinogen, II - prothrombin, V - proaccelerin and VIII - antihemophilic factor). Plasma is a pale amber liquid containing proteins, carbohydrates, lipids, lipoproteins, electrolytes, hormones and others. chemical compounds. The volume of plasma is about 5% of body weight (with a weight of 70 kg - 3500 ml) and 7.5% of all body water. Blood plasma consists of water (90%) and substances dissolved in it (10%, organic - 9%, inorganic - 1%; in the solid residue, proteins account for approximately 2/3, and 1/3 are low molecular weight substances and electrolytes) . Chemical composition plasma is similar to interstitial fluid (the predominant cation is Na +, the predominant anions are Cl -, HCO 3 -), but the protein concentration in plasma is higher (70 g/l).

Squirrels

Plasma contains several hundred different proteins, coming mainly from the liver, but also from cellular elements circulating in the blood and from many extravascular sources. The functions of plasma proteins are extremely diverse.

Classifications.Plasma proteins are classified according to physicochemical characteristics (more precisely, according to their mobility in an electric field), as well as depending on the functions they perform.

Electrophoretic mobility. Five electrophoretic fractions of plasma proteins were isolated: albumins and globulins (α 1 - and α 2 -, β- and γ-).

Φ Albumin(40 g/l, M r ~ 60-65 kD) largely determine oncotic (colloid-osmotic) pressure(25 mmHg, or 3.3 kPa) blood (5 times the oncotic pressure intercellular fluid. That is why, with massive loss of albumin (hypoalbuminemia), “renal” edema develops through the kidneys, and during fasting, “hungry” edema develops.

Φ Globulins(30 g/l), including (examples):

♦ a^globulins: a 1 -antitrypsin, a 1 -lipoproteins ( high density), prothrombin;

♦ a 2 -globulins: a 2 -macroglobulin, a 2 -antithrombin III, a 2 -haptoglobulin, plasminogen;

♦ β-globulins: β-lipoproteins (low density), apoferritin, hemopexin, fibrinogen, C-reactive protein;

♦ γ-globulins: immunoglobulins (IgA, IgD, IgE, IgG, IgM). Functional classification. There are three main groups: 1) proteins of the blood coagulation system; 2) proteins involved in immune reactions; 3) transport proteins.

Φ 1. Proteins of the blood coagulation system(see details below). There are coagulants and anticoagulants. Both groups of proteins provide balance between the processes of clot formation and destruction.

♦ Coagulants(primarily plasma coagulation factors) are involved in the formation of a blood clot, for example fibrinogen (synthesized in the liver and turns into fibrin during hemocoagulation).

♦ Anticoagulants- components of the fibrinolytic system (prevent clotting).

Φ 2. Proteins involved in immune reactions. This group includes Ig (for more details, see Chapter 29) and proteins of the complement system.

Φ 3. Transport proteins- albumins (fatty acids), apolipoproteins (cholesterol), transferrin (iron), haptoglobin (Hb), ceruloplasmin (copper), transcortin (cortisol), transcobalamins (vitamin B 12) and many others

Lipoproteins

In blood plasma, cholesterol and triglycerides form complexes with proteins. So different in size and other signs the complexes are called lipoproteins (LP). Cholesterol transport is carried out by low-density lipoproteins (LDL), very low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), high-density lipoproteins (HDL), and chylomicrons. From a clinical point of view (the likelihood of developing arteriosclerotic lesions - atherosclerosis), the content of cholesterol in the blood and the ability of the drug to be fixed in the arterial wall (atherogenicity) are of significant importance.

HDL - the smallest LP in size (5-12 nm) - easily penetrates the arterial wall and leaves it just as easily, i.e. HDL is not atherogenic.

LDL (18-25 nm), intermediate density LDL (25-35 nm) and a few VLDL (about 50 nm in size) are too small to penetrate the arterial wall. After oxidation, these drugs are easily retained in the arterial wall. It is these categories of drugs that are atherogenic.

Large LPs - chylomicrons (75-1200 nm) and VLDL of significant size (80 nm) - are too large to penetrate into the arteries and are not regarded as atherogenic.

Osmotic and oncotic pressure

Osmolytes contained in plasma (osmotically active substances), i.e. electrolytes of low molecular weight (inorganic salts, ions) and high molecular weight substances (colloidal compounds, mainly proteins) determine the most important properties of blood - osmotic and oncotic pressure. IN medical practice these parameters are important not only in relation to blood per se(for example, the idea that solutions are isotonic), but also for a real situation in vivo(for example, to understand the mechanisms of water transfer through the capillary wall between blood and intercellular fluid, in particular the mechanisms of the development of edema, separated by the equivalent of a semi-permeable membrane - the capillary wall). In this context for clinical practice Parameters such as effective hydrostatic and central venous pressure.

Φ Osmotic pressure(π, see more in Chapter 3, including Fig. 2-9) - excess hydrostatic pressure on a solution separated from the solvent (water) by a semi-permeable membrane, at which diffusion of the solvent through the membrane stops (under conditions in vivo it is the vascular wall). Blood osmotic pressure can be determined by its freezing point (i.e., cryoscopically); normally it is 7.5 atm (5800 mmHg, 770 kPa, 290 mOsmol/kg water).

Φ Oncotic pressure(colloid osmotic pressure - COP) - pressure that arises due to the retention of water in the vascular bed by blood plasma proteins. With a normal plasma protein content (70 g/l), the plasma CODE is 25 mm Hg. (3.3 kPa), while the COD of the interstitial fluid is much lower (5 mm Hg, or 0.7 kPa).

Φ Effective hydrostatic pressure- the difference between the hydrostatic pressure of the intercellular fluid (7 mm Hg) and the hydrostatic pressure of blood in the microvessels. Normally, the effective hydrostatic pressure in the arterial part of the microvessels is 36-38 mm Hg, and in the venous part - 14-16 mm Hg.

Φ Central venous pressure- blood pressure inside venous system(in the superior and inferior vena cava), normally 4-10 cm of water column. Central venous pressure decreases with a decrease in blood volume and increases with heart failure and stagnation in the circulatory system. Infusion solutions

Saline infusion solutions for intravenous administration must have the same osmotic pressure as plasma, i.e. be isosmotic (isotonic, for example the so-called saline- 0.85% sodium chloride solution).

Acid-base balance, including buffer systems blood, discussed in Chapter 28.

CELL ELEMENTS OF BLOOD

To blood cells (obsolete name - shaped elements) include red blood cells, white blood cells and platelets, or blood platelets (Fig. 24-1). Blood cells are studied microscopically

Rice. 24-1. Blood cells. Blood contains three types of cells: erythrocytes (non-nucleated cells shaped like a biconcave disk), leukocytes (nuclear spherical cells containing various types of granules) and platelets (fragments of the cytoplasm of giant cells located in the bone marrow - megakaryocytes). A - erythrocyte; B - neutrophil; B - eosinophil; G - basophil; D - lymphocytes (small and large); E - monocyte; F - platelets.

on smears stained according to Romanovsky-Giemsa, Wright, etc. Contents in peripheral blood adult human red blood cells in men - 4.5-5.7 x 10 12 / l (in women - 3.9-5 x 10 12 / l), leukocytes - 3.8-9.8 x 10 9 / l (lymphocytes - 1.2-3 .3x10 9 /l, monocytes - 0.2-0.7x10 9 /l, granular leukocytes - 1.8-6.6x10 9 /l), platelets - 190-405x10 9 /l. Definitive forms of cells circulate in the peripheral blood, the formation of which (hematopoiesis, or hematopoiesis) occurs in the red bone marrow and organs of the lymphoid system (thymus, spleen, The lymph nodes and lymphoid follicles). From the hematopoietic stem cell in the red bone marrow, erythroid cells are formed (red blood cells and reticulocytes enter the blood), myeloid cells (granular leukocytes, rod- and segmented neutrophil leukocytes, mature basophilic and eosinophilic leukocytes enter the blood), monocytes, blood platelets and some lymphocytes , in the organs of the lymphoid system - T- and B-lymphocytes.

Hematopoiesis

Hematopoiesis is the formation from a hematopoietic stem cell of precursor cells of specific hematopoiesis, their production

proliferation and differentiation, as well as maturation of blood cellular elements under specific microenvironment conditions and under the influence of hematopoietic factors. In the prenatal period, hematopoiesis occurs in several developing organs (see Chapter 20). Hematopoiesis after birth, in children, adolescents and adults, occurs in the bone marrow of flat bones (skull, ribs, sternum, vertebrae, pelvic bones) and epiphyses of tubular bones, and hematopoietic organs for lymphocytes are the spleen, thymus, lymph nodes, lymphoid follicles in various organs.

Mature peripheral blood cells develop from precursors that mature in the red bone marrow. The unitary theory of hematopoiesis (Fig. 24-2) provides that the ancestor of all cellular elements of the blood is hematopoietic stem cell. Her descendants are pluripotent progenitor cells lymphocytopoiesis (CFU-Ly) and myelopoiesis (CFU-GEMM). As a result of the division of CFU-Ly and CFU-GEMM, their descendants remain

Rice. 24-2. Scheme of hematopoiesis. CFU-GEMM - pluripotent myelopoiesis progenitor cell; CFU-Ly - pluripotent lymphocytopoiesis progenitor cell; CFU-GM - pluripotent cell precursor of granulocytes and monocytes; CFU-G is a pluripotent progenitor cell of neutrophils and basophils. BFU-E and CFU-E are unipotent erythrocyte precursors; CFU-Eo - eosinophils; CFU-M - monocytes; CFU-Meg - megakaryocytes. CFU (Colony Forming Unit) - colony-forming unit (CFU), BFU - Burst Forming Unit - explosion-forming unit.

pluripotent or turn into committed (predetermined by fate) unipotent progenitor cells, also capable of dividing, but differentiating (developing) only in one direction. Proliferation of unipotent progenitor cells is stimulated colony-stimulating factors And interleukins(especially interleukin-3).

Erythropoiesis. Beginning of the erythroid series - stem cell erythropoiesis, or burst-forming unit (BFU-E), from which the unipotent precursor of erythrocytes (CFU-E) is formed. The latter gives rise to the proerythroblast. As a result of further differentiation, the Hb content increases and the nucleus is lost. From the proerythroblast, erythroblasts successively develop through proliferation and differentiation: basophilic- polychromatophilic- oxyphilic (normoblast) and then non-dividing forms - reticulocyte and erythrocyte. From BFU-E to normoblast is 12 cell generations, and from CFU-E to late normoblast is 6 or fewer cell divisions. The duration of erythropoiesis (from its BFU-E stem cell to an erythrocyte) is 2 weeks. The intensity of erythropoiesis is controlled by erythropoietin. The main stimulus for the production of erythropoietin is a decrease in the oxygen content in the blood (pO 2) - hypoxia (Fig. 24-3).

Granulocytopoiesis(Fig. 24-4). Granulocytes are formed in the bone marrow. Neutrophils and basophils are derived from the pluripotent neutrophil and basophil precursor cell (CFU-G), and eosinophils are derived from the unipotent eosinophil precursor (CFU-Eo). CFU-G and CFU-Eo are descendants of the pluripotent granulocyte-monocyte progenitor cell (CFU-GM). During the development of granulocytes, the following stages can be distinguished: myeloblasts- promyelocytes - myelocytes - metamyelocytes - band and segmented granulocytes. Specific granules appear at the myelocyte stage; from this point on, the cells are named according to the type of mature granulocytes they produce. Cell division stops at the metamyelocyte stage. The proliferation and differentiation of progenitor cells is controlled by colony-stimulating factors (granulocytes and macrophages - GM-CSF, granulocytes - G-CSF), IL-3 and IL-5 (eosinophil precursors).

Rice. 24-3. Regulation of erythropoiesis . Proliferation of the burst-forming unit of erythropoiesis (BFU-E) is stimulated by interleukin-3. The unipotent erythrocyte precursor CFU-E is sensitive to erythropoietin. The most important stimulus for the formation of red blood cells is hypoxia, which triggers the synthesis of erythropoietin in the kidney, and in the fetus, in the liver. Erythropoietin is released into the blood and enters the bone marrow, where it stimulates the proliferation and differentiation of unipotent erythrocyte precursor (CFU-E) and the differentiation of subsequent erythroid cells. As a result, the number of red blood cells in the blood increases. Accordingly, the amount of oxygen entering the kidney increases, which inhibits the formation of erythropoietin.

Monocytopoiesis. Monocytes and granulocytes share a common progenitor cell, the colony-forming unit of granulocytes and monocytes (CFU-GM), which is derived from a pluripotent myelopoiesis progenitor cell (CFUGEMM). There are two stages in the development of monocytes - monoblast and promonocyte.

Thrombocytopoiesis. The largest (30-100 µm) bone marrow cells, megakaryocytes, develop from megakaryoblasts. During differentiation, the megakaryocyte increases in size and its nucleus becomes lobulated. A developed system of demarcation membranes is formed, along which platelets are separated (“unlaced”) (Fig. 24-5). The proliferation of megakaryocyte precursors - megakaryoblasts - is stimulated by thrombopoietin synthesized in the liver.

Lymphopoiesis. From a hematopoietic stem cell (CFU-blast) comes a pluripotent lymphatic precursor cell.

Rice. 24-4. Granulocytopoiesis. During the differentiation of granulocyte precursors, myeloblast, promyelocyte, myelocyte, metamyelocyte, band and segmented granulocytes are isolated.

Rice. 24-5. Platelet formation . The megakaryocyte located in the bone marrow forms a proplatelet pseudopodia. The latter penetrates through the capillary wall into its lumen. Platelets are separated from the pseudopodia and enter the bloodstream.

poetry (CFU-Ly), which subsequently gives rise to B-lymphopoiesis progenitor cells, T-lymphopoiesis and (partially) NK cell progenitors. The early precursors of B lymphocytes are formed in the bone marrow, and T lymphocytes in the thymus. Further differentiation includes levels of pro-B(T) cells, pre-B(T) cells, immature B(T) cells, mature (“naive”) B(T) cells and (after exposure to Ag ) - mature B(T) cells in the final stages of differentiation. IL-7 produced by bone marrow stromal cells promotes the formation of T and B lymphocytes by acting on their precursor cells. Unlike other blood cells, lymphocytes can proliferate outside the bone marrow. It occurs in immune system tissues in response to stimulation.

Red blood cells

From the red bone marrow, predominantly immature red blood cells enter the blood - reticulocytes. They (unlike mature red blood cells) contain ribosomes, mitochondria and the Golgi complex. Final differentiation into erythrocytes occurs within 24-48 hours after the release of reticulocytes into the bloodstream. The number of reticulocytes entering the bloodstream is normally equal to the number of red blood cells removed. Reticulocytes make up about 1% of all circulating red blood cells. Red blood cells(see Fig. 24-1, A) - anucleate cells with a diameter of 7-8 microns (normocytes). The number of red blood cells in women is 3.9-4.9x10 12 /l, in men - 4.0-5.2x10 12 /l. The higher content of red blood cells in men is due to the erythropoiesis-stimulating effect of androgens. Lifespan(blood circulation time) 100-120 days.

Shape and dimensions.An erythrocyte in the blood has the shape of a biconcave disk with a diameter of 7-8 microns. It is believed that it is this configuration that creates the largest surface area in relation to volume, which ensures maximum gas exchange between blood plasma and red blood cells. With any other form of red blood cells, they speak of poikilocytosis. Dispersion of erythrocyte sizes is anisocytosis, cells with a diameter of more than 9 microns are macrocytes, less than 6 microns are microcytes. In a number of blood diseases, the size and shape of red blood cells change, and their osmotic resistance decreases, which leads to the destruction (hemolysis) of red blood cells.

Age-related changes in red blood cells. At birth and in the first hours of life, the number of red blood cells in the blood is increased and amounts to 6.0-7.0x10 12 / l. In newborns, anisocytosis with a predominance of macrocytes is observed, as well as increased content reticulocytes. During the first day of the postnatal period, the number of red blood cells decreases, by the 10-14th day it reaches the adult level and continues to decrease. The minimum indicator is observed in the 3-6th month of life (physiological anemia), when the level of erythropoietin is reduced. This is due to a decrease in the synthesis of erythropoietin in the liver and the beginning of its production in the kidney. At the 3-4th year of life, the number of red blood cells is reduced (lower than in an adult), i.e. 1 liter contains less than 4.5x10 12.

Rice. 24-6. Perimembrane cytoskeleton of the erythrocyte . Band 3 protein is a major transmembrane protein. The spectrin-actin complex forms a network-like structure of the perimembrane cytoskeleton. Band 4.1 protein is associated with the spectrin-actin complex, stabilizing it. Ankyrin, through band 3 protein, connects the spectrin-actin complex to the cell membrane. The names of protein bands characterize their electrophoretic mobility.

Plasmolemma and perimembrane cytoskeleton. The cell membrane of an erythrocyte is quite plastic, which allows the cell to deform and easily pass through narrow capillaries (their diameter is 3-4 microns). The main transmembrane proteins of the erythrocyte are band 3 protein and glycophorins. Protein stripe 3(Fig. 24-6) together with the proteins of the near-membrane cytoskeleton (spectrin, ankyrin, fibrillar actin, band 4.1 protein) ensures the maintenance of the shape of the erythrocyte in the form of a biconcave disk. Glycophorins- membrane glycoproteins, their polysaccharide chains contain Ag determinants (for example, agglutinogens A and B of the AB0 blood group system).

Hemoglobin

Almost the entire volume of the red blood cell is filled with respiratory protein - hemoglobin(Hb). The Hb molecule is a tetramer, consisting

consisting of four subunits - polypeptide chains of globin (two chains α and two chains β, γ, δ, ε, θ, ζ in different combinations), each of which is covalently linked to one heme molecule. Heme built of four pyrrole molecules forming a porphyrin ring, in the center of which there is an iron atom (Fe 2 +). The main function of Hb is the transport of O 2. There are several types of Hb produced by different dates development of the organism, differing in the structure of globin chains and affinity for oxygen. Fetal Hb(ζ- and ε-chains) appear in a 19-day embryo and are contained in erythroid cells in the first 3-6 months of pregnancy. Fetal Hb(HbF - α 2 γ 2) appears in the 8-36th week of pregnancy and makes up 90-95% of the total Hb of the fetus. After birth, its amount gradually decreases and by 8 months it is 1%. Definitive Hb- the main Hb of adult human erythrocytes (96-98% - HbA (A 1,) - α 2 β 2, 1.5-3% - HbA 2 - α 2 δ 2). More than 1000 mutations of different globins are known, significantly changing the properties of Hb, primarily the ability to transport O 2.

Forms of hemoglobin. In erythrocytes, Hb is found in reduced (HbH) and/or oxidized (HbO 2) forms, as well as in the form of glycosylated Hb. In some cases, the presence of carboxyhemoglobin and methemoglobin is possible.

F Oxyhemoglobin. In the lungs, with increased pO 2, Hb binds (associates) O 2, forming oxyhemoglobin (HbO 2). In this form, HbO 2 carries O 2 from the lungs to the tissues, where the O 2 is easily released (dissociated) and the HbO 2 becomes deoxygenated by Hb (referred to as HbH). For the association and dissociation of O 2, it is necessary that the heme iron atom be in a reduced state (Fe 2 +). When ferric iron (Fe 3 +) is included in heme, methemoglobin is formed - a very poor transporter of O 2. F Methemoglobin(MetHb) - Hb containing Fe heme in trivalent form (Fe 3 +) does not tolerate O 2; strongly binds O 2, so the dissociation of the latter is difficult. This leads to methemoglobinemia and inevitable gas exchange disorders. MetHb formation can be hereditary or acquired. IN the latter case this is the result of exposure of red blood cells to strong oxidizing agents. These include nitrates and inorganic nitrites, sulfonamides and local anesthetics (for example, lidocaine).

Φ Carboxyhemoglobin- poor oxygen carrier. Hb binds more easily (about 200 times) than with O2 to carbon monoxide CO ( carbon monoxide), forming carboxyhemoglobin (O 2 is replaced by CO).

Φ Glycosylated Hb(HbA 1C) - HbA (A1:), modified by the covalent addition of glucose to it (normal HbA 1C 5.8-6.2%). One of the first signs of diabetes mellitus is an increase in the amount of HbA 1C by 2-3 times. This Hb has a worse affinity for oxygen than regular Hb.

Oxygen transport. Blood transports about 600 liters of O2 from the lungs to the tissues every day. The main volume of O 2 is transported by HbO 2 (O 2 is reversibly associated with Fe 2 + heme; this is the so-called chemically bound O 2 - an essentially incorrect, but, unfortunately, well-established term). A small part of O 2 is dissolved in the blood (physically dissolved O 2). The O2 content in the blood depending on the partial pressure of O2 (Po2) is shown in Fig. 24-7.

A gas physically dissolved in the blood. According to Henry's law, the amount of O 2 (any gas) dissolved in the blood is proportional to Po 2 (the partial pressure of any gas) and the solubility coefficient of the particular gas. The physical solubility of O 2 in the blood is approximately 20 times less than the solubility of CO 2, but for both gases it is insignificant. At the same time, the gas physically dissolved in the blood is necessary stage transport of any gas (for example, when O 2 moves into an erythrocyte from the cavity of the alveoli).

Oxygen capacity blood- the maximum possible amount associated with HbO 2 is theoretically 0.062 mmol O 2 (1.39 ml O 2) per 1 g of Hb (the real value is slightly less - 1.34 ml O 2 per 1 g of Hb). The measured values ​​are for men 9.4 mmol/l (210 ml O 2 /l), for women 8.7 mmol/l (195 ml O 2 /l).

Saturation(saturation, S) Hb() 2(So ​​2) depends on the partial pressure of oxygen (Po 2) and actually reflects the content of oxygenated Hb (HbO 2, see curve A in Fig. 24-7). So 2 can take values ​​from 0 ( Hb() 2 no) to 1 (no HbH). At half saturation (S 05) Po 2 is equal to 3.6 kPa (27 mm Hg), at S 075 - 5.4 kPa, at S 0 98 1 3, 3 kPa. In other words-

Oxygen partial pressure (mmHg)

Rice. 24-7. Blood oxygen content . A - associated with HbO 2. B - O 2 physically dissolved in the blood. Please note that curve A (unlike curve B) is not linear; it is a so-called S-shaped (sigmoid) curve; This shape of the curve reflects the fact that the four Hb subunits bind to O 2 cooperatively. This circumstance has important physiological significance: at specific and different (!) values ​​of Po 2 in arterial and mixed (venous) blood, the most favorable conditions for the association of Hb and O 2 in the lung capillaries and for the dissociation of Hb and O 2 in tissue capillaries. At the same time, only a small part of O 2 is physically dissolved in the blood plasma (maximum 6%); the physical solubility of O 2 is described by Henry's law: with an increase in Po 2, the O 2 content increases linearly.

mi (see curve A in Fig. 24-7), the relationship between So 2 and Po 2 is not linear (characteristic S-shaped curve), which favors not only the binding of O 2 in the lungs (arterial blood) and the transport of O 2, but also the release of O 2 in blood capillaries organs and tissues, since the saturation of arterial blood with oxygen (S a o 2) is approximately 97.5%, and the saturation venous blood(S v o 2) - 75%. Affinity of Hb to O2, those. saturation Hb() 2 for a specific

Po 2 changes a number of factors (temperature, pH and Pco 2, 2,3-biphos-

foglycerate; rice. 24-8).

pH, Pwith 2 and the Bohr effect. The influence of pH is especially significant: decrease pH value (shift to the acidic side)

Rice. 24-8. Dissociation of oxyhemoglobin in the blood depending on Po 2 . Depending on changes (indicated by arrows) in blood temperature, pH, Pco 2 and red blood cell 2,3-bisphosphoglycerate concentration, the hemoglobin O 2 saturation curve shifts to the right (meaning less oxygen saturation) or left (meaning more oxygen saturation). The position corresponding to half saturation (S 05) is marked with a circle on the curve.

well - into the acidosis zone) shifts the Hb dissociation curve to the right (which promotes the dissociation of O 2), whereas increase pH (shift to the alkaline side - to the zone of alkalosis) shifts the Hb dissociation curve to the left (which increases the O2 affinity). The effect of Pco 2 on the dissociation curve of oxyhemoglobin is carried out primarily through a change in the pH values: when Co 2 enters the blood, the pH decreases, which promotes the dissociation of O 2 and its diffusion from the blood into the tissues. On the contrary, in the lungs CO 2 diffuses from the blood into the alveoli, which causes an increase in pH, i.e. promotes the binding of O 2 to Hb. This effect of CO 2 and H+ on the affinity of O 2 for Hb is known as Christian Bohr effect(father of the great physicist Niels Bohr). Thus, the Bohr effect is primarily due to changes in pH with increasing Co 2 content and only partially due to the binding of Co 2 to Hb (see below). The physiological consequence of the Bohr effect is facilitating the diffusion of o 2 from the blood into tissues and the binding of o 2 arterial blood in the lungs.

Temperature. The effect of temperature on the affinity of Hb for O2 in homeothermic animals is theoretically unimportant, but may be important in a number of situations. Thus, with intense muscle load, body temperature rises, as a result of which the dissociation curve shifts to the right (the intake of O 2 into the tissue increases). As the temperature decreases (especially of the fingers, lips, and ear), the dissociation curve shifts to the left, i.e. O 2 affinity increases; therefore, the supply of O 2 to the tissues does not increase.

2,3-Bisphosphoglycerate(BPG), an intermediate product of glycolysis, is found in erythrocytes in approximately the same molar concentration as Hb. BPG binds to Hb (mainly due to interaction with the β-subunit, i.e. with definitive Hb, but not with fetal Hb, which does not contain the β-subunit). The binding of BPG to Hb shifts the Hb dissociation curve to the right (see Fig. 24-8), which promotes the dissociation of O 2 at moderate Po 2 values ​​(for example, in tissue capillaries), but has virtually no effect on the dissociation curve at high Po 2 values ​​( in the capillaries of the lung). It is significant that with increased glycolysis (anaerobic oxidation), the concentration of BPG in erythrocytes increases, playing

the role of a mechanism that adapts the body to hypoxia, which is observed in lung diseases, anemia, and elevation. Thus, during the period of adaptation to high altitudes (more than 4 km above sea level), the concentration of BPG increases almost 2 times after 2 days (from 4.5 to 7.0 mM). It is clear that this reduces the affinity of Hb for O 2 and increases the amount of O 2 released from the capillaries into the tissue. T transport CO2. Like O 2, CO 2 is transported by the blood both in a physically dissolved and chemically bound state (in the composition of bicarbonates and in combination with proteins, i.e. in the form of carbamates, including in connection with Hb - carbohemoglobin). In all three states (dissolved, bicarbonate, carbamates), CO 2 is contained in both erythrocytes (89%) and blood plasma (11%). The chemical bonding of CO 2 produces a significant amount of protons (H+).

Approximately 2/3 of CO 2 (68%, including 63% in red blood cells) is transported in the blood in the form of bicarbonate (HCO 3 -). A fifth of CO 2 (22%, including in the form of carbohemoglobin - 21%) is transferred by carbamates (CO 2 is reversibly attached to the non-ionized terminal α-amino groups of proteins, forming the R-NH-COO - group). 10% of CO 2 is in a dissolved state (equally in plasma and erythrocytes). It is extremely important that in reactions of chemical binding of CO 2 H+ ions are formed:

CO 2 + H 2 O ↔ H 2 CO 3 ↔ H++ HCO 3 - , R-NH 2 + CO 2 ↔ R-NH-COO - + H+.

Φ From both equilibrium reactions it follows that the chemical binding of CO 2 occurs with the formation of H+ ions. Thus, for chemical binding of CO 2 it is necessary to neutralize H+. This problem is solved by the hemoglobin buffer system.

Hemoglobin buffer system (binding of H+ ions) is important for the transport of CO 2 in the blood.

In the capillaries of the systemic circulation HbO 2 releases oxygen, and CO 2 enters the blood. In erythrocytes, under the influence of carbonic anhydrase, CO 2 interacts with H 2 O, forming carbonic acid (H 2 CO 3), which dissociates into HCO 3 - and H +. The H+ ion binds to Hb (reduced Hb - HHb is formed), and HCO 3 - from the erythrocytes enters the blood plasma; in return, an equivalent amount enters the red blood cells

Rice. 24-9. Transfer of O 2 and CO 2 with blood . A - influence of CO 2 and H+ on the release of O 2 from the complex with hemoglobin in tissues (Bohr effect); B - oxygenation of deoxyhemoglobin in the lungs, formation and release of CO 2.

Rice. 24-10. Mechanisms of CO 2 transport in blood .

Cl - . At the same time, part of the CO 2 binds to Hb (carbohemoglobin is formed). In the capillaries of the lungs(i.e., under conditions of low pCO 2 and high pO 2) Hb adds O 2 and oxyhemoglobin (HbO 2) is formed. At the same time, CO 2 is released as a result of the rupture of carbamine bonds. In this case, HCO 3 - from the blood plasma enters the erythrocytes (in exchange for Cl - ions) and interacts with H +, split off from Hb at the time of its oxygenation. The resulting carbonic acid (H 2 CO 3) under the influence of carbonic anhydrase is split into CO 2 and H 2 O. CO 2 diffuses into the alveoli and is excreted from the body. CO 2 dissociation curve shows the relationship between blood CO 2 and pCO 2 levels. Unlike the dissociation curve of Hb and O 2 (see Fig. 24-7), the dissociation curve of CO 2 at physiological values ROD 2 (arterial blood - 40 mm Hg, venous blood - 46 mm Hg) is linear. Moreover, at any pCO 2 value, the CO 2 content in the blood is inversely proportional to pO 2 (Hb0 2 saturation). This inverse relationship between CO 2 content and oxygen partial pressure ^O 2) is known as Haldane effect. Like the Bohr effect, the Haldane effect has important physiological significance. Thus, in the capillaries of the systemic circulation, as O 2 diffuses from the capillaries increases the ability of the blood to absorb CO 2, as a result, CO 2 enters the blood. On the contrary, in the capillaries of the lung, when the blood is oxygenated, its ability to absorb CO 2 decreases, as a result, CO 2 is “dumped” into the alveoli.

HEMOGLOBIN METABOLISM

Removing red blood cells from the bloodstream occurs in three ways: 1) by phagocytosis, 2) as a result of hemolysis and 3) during thrombus formation.

Hemoglobin breakdown. With any type of destruction of red blood cells, Hb breaks down into heme and globins (Fig. 24-11). Globins, like other proteins, are broken down into amino acids, and when heme is destroyed, iron ions, carbon monoxide (CO) and protoporphyrin (verdoglobin, from which biliverdin is formed, which is reduced to bilirubin), are released. Bilirubin in combination with albumin, it is transported to the liver, from where it enters the intestine as part of bile, where it is converted into urobiol.

Rice. 24-11. Exchange of hemoglobin and bilirubin .

linogens. The conversion of heme to bilirubin can be observed in a hematoma: the purple color caused by heme slowly passes through the green colors of verdoglobin into yellow bilirubin.

Hematins.Under certain conditions, hydrolysis of Hb causes the formation of hematins (hemomelanin, or malarial pigment, and hydrochloric acid hematin).

IRON METABOLISM

Iron is involved in the functioning of all body systems. The daily requirement for iron is 10 mg for men, 18 mg for women (during pregnancy and lactation - 38 and 33 mg, respectively). The total amount of iron (mainly in combination with

Rice. 24-12. Diagram of iron (Fe) metabolism in the body healthy man with a body weight of 70 kg .

heme Hb) in the body - about 3.5 g (in women - 3 g). Iron is absolutely necessary for erythropoiesis. There are cellular, extracellular iron and iron stores (Fig. 24-12).

The bulk of the body's iron is part of heme (Hb, myoglobin, cytochromes). Some iron is stored in the form of ferritin (in hepatocytes, bone marrow and spleen macrophages) and hemosiderin (in von Kupffer cells of the liver and bone marrow macrophages). A certain amount is in a labile state due to transferrin. Iron, necessary for heme synthesis, is extracted mainly from destroyed red blood cells. Sources of iron- intake from food and destroyed red blood cells.

Iron from food absorbed in the intestines duodenum and the initial section of the jejunum. Iron is absorbed predominantly in divalent form (Fe 2 +). The absorption of Fe 2 + in the gastrointestinal tract is limited and controlled by its concentration in the blood plasma (the ratio of proteins - iron-free apoferritin and ferritin). Absorption is enhanced by ascorbic, succinic, pyruvic acid, sorbitol, and alcohol; suppress - oxalates, calcium supplements and calcium-containing foods (for example, cottage cheese, milk, etc.). On average, 10 mg of iron is absorbed per day. In the gastrointestinal tract, iron accumulates in the epithelial cells of the mucous membrane small intestine. From here transferrin transfers iron to the red bone marrow (for erythropoiesis, this is only 5% of absorbed Fe 2 +), to the liver, spleen, muscles and other organs (for storage).

Iron of dead red blood cells with the help of transferrin, it enters the erythroblasts of the red bone marrow (about 90%), part of this iron (10%) is stored in the composition of ferritin and hemosiderin.

Physiological iron loss occurs in feces. A small portion of iron is lost through sweat and epidermal cells. Total iron loss is 1 mg/day. Physiological is also considered iron loss with menstrual blood and breast milk.

Iron deficiency occurs when its losses exceed 2 mg/day. With iron deficiency, the most common anemia develops - iron deficiency, i.e. anemia due to an absolute decrease in iron resources in the body.

Red blood cell antigens and blood groups

As part of glycoproteins and glycolipids on the surface of erythrocytes, there are hundreds of antigenic determinants, or antigens (Ags), many of which determine group affiliation blood (blood groups). These Ags could potentially interact with their corresponding antibodies (Abs), if such Abs were contained in the blood serum. However, such an interaction does not occur in the blood of a particular person, since the immune system has already removed the clones of plasma cells secreting these ATs (see Chapter 29 for more details). However, if

the corresponding antibodies enter the blood (for example, during transfusion of someone else’s blood or its components), an interaction reaction between erythrocyte Ags and serum antibodies develops, with often catastrophic consequences (blood type incompatibility). In particular, agglutination (gluing) of red blood cells and their subsequent hemolysis occurs. It is for these reasons that it is so important to determine the group affiliation of the transfused blood (donor blood) and the blood of the person to whom the blood is transfused (recipient), as well as strict compliance with all rules and procedures for transfusion of blood or its components (in the Russian Federation, the procedure for blood transfusion is regulated by order of the Ministry of Health of the Russian Federation and instructions for the use of blood components attached to the order).

Of the hundreds of erythrocyte Ags, the International Society of Blood Transfusion (ISBT) classified the following in alphabetical order as ABO as blood group systems [in the English-language literature the name ABO (the letter “O” is accepted), in the Russian-language literature - AB0 (digit “0”)]. In the practice of blood transfusion (hemotransfusion) and its components, it is mandatory to check for compatibility with the Ag systems A0 (four groups) and Rh (two groups), for a total of eight groups. The remaining systems (they are known as rare) are much less likely to cause blood group incompatibility, but they should also be taken into account when carrying out blood transfusions and determining the likelihood of developing a hemolytic disease in a newborn (see below “Rh-system”).

AB0-SYSTEM

Erythrocyte Ag AB0 systems: A, B and 0 - belong to the class of glycophorins. Their polysaccharide chains contain Ag determinants - agglutinogens A and B. The formation of agglutinogens A and B occurs under the influence of glycosyltransferases encoded by alleles of the gene AB0. This gene encodes three polypeptides (A, B, 0), two of them (glycosyltransferases A and B) modify the polysaccharide chains of glycophorins; polypeptide 0 is functionally inactive. As a result, the surface of red blood cells different persons may contain either agglutinogen A, or agglutinogen B, or both agglutinogens (A and B), or contain neither agglutinogen A nor agglutinogen B. In accordance with the type of expression of agglutinogens A and B on the surface of erythrocytes

In the AB0 system, there are four blood groups, designated by Roman numerals I, II, III and IV. Erythrocytes of blood group I do not contain either agglutinogen A or agglutinogen B, its abbreviated name is 0(I). Red blood cells of blood group IV contain both agglutinogens - AB(IV), group II - A(II), group III - B(III). The first three blood groups were discovered in 1900 by Karl Landsteiner, and the fourth group a little later by Decastrello and Sturli.

Agglutinins.Blood plasma may contain antibodies to agglutinogens A and B (α- and β-agglutinins, respectively). Blood plasma of group 0(I) contains α- and β-agglutinins; group A(II) - β-agglutinins, B(III) - α-agglutinins, blood plasma of group AB(IV) does not contain agglutinins.

Table 24-1.Content in blood different groups(AB0 system) agglutinogens (Ag) and agglutinins (AT)

Thus, in the blood of a particular person, antibodies to erythrocyte Ags of the AB0 system are not simultaneously present (Table 24-1), but when blood is transfused from a donor with one group to a recipient with another group, a situation may arise when both are present in the recipient’s blood at the same time. Ag, and AT is precisely for this Ag, i.e. a situation of incompatibility will arise. In addition, such incompatibility may occur in other blood group systems. That is why it has become a rule that Only blood of the same type can be transfused. More precisely, it is not whole blood that is transfused, but components, since “the indications for transfusion of whole canned blood are donated blood no, with the exception of cases of acute massive blood loss, when there are no blood substitutes or fresh frozen plasma, red blood cells or their suspension” (from the order of the Ministry of Health of the Russian Federation). And that is why the theoretical idea of ​​“ universal donor» with blood group 0(I) is left in practice.

Rh-SYSTEM

Each person can be Rh-positive or Rh-negative, which is determined by his genotype and the expressed Ags of the Rh system.

Φ Antigens. Six alleles of three genes of the Rh system encode Ags: c, C, d, D, e, E. Taking into account the extremely rare Ags of the Rh system, 47 phenotypes of this system are possible. Φ Antibodies Rh systems belong to the IgG class (antibodies only to Ag d were not detected). Rh positive And Rh negative individuals. If the genotype of a particular person encodes at least one of Ags C, D and E, such persons Rh positive(in practice, individuals who have Ag D, a strong immunogen, on the surface of their red blood cells are considered Rh positive). Thus, AT are formed not only against “strong” Ag D, but can also be formed against “weak” Ag c, C, e and E. Rh negative only individuals with the cde/cde (rr) phenotype.

Φ Rhesus conflict(incompatibility) occurs during transfusion Rh positive blood donor to an Rh-negative recipient or in the fetus during a second pregnancy of an Rh-negative mother with an Rh-positive fetus (first pregnancy and/or birth of an Rh-positive fetus). In this case, hemolytic disease of the newborn develops.

Leukocytes

Leukocytes are spherical nuclear cells (see Fig. 24-1). There are granules in the cytoplasm of leukocytes. Depending on the type of granules, leukocytes are divided into granulocytes (granular) and agranulocytes (non-granular).

Φ Granulocytes(neutrophils, eosinophils, basophils) contain specific (secondary) and azurophilic (lysosomes) granules.

Φ Agranulocytes(monocytes, lymphocytes) contain only

azurophilic granules. Φ Core. Granulocytes have a lobed nucleus of varied

forms, hence their common name - polymorphonuclear

leukocytes.Lymphocytes and monocytes have non-lobed

the core is mononuclear leukocytes.

Physiological leukocytosis - a condition characterized by an increase in the number of leukocytes per unit volume of blood above normal (>9x10 9 /l). Among physiological leukocytosis There are functional and protective-adaptive ones.

Φ Functional leukocytosis due to the fact that the body performs certain functions (for example, leukocytosis during pregnancy, an increase in the number of leukocytes in the blood after eating or after prolonged physical work).

Φ Protective-adaptive leukocytosis develops during inflammatory processes, damage to cells and tissues (for example, after heart attacks or strokes, soft tissue injuries), stress reactions.

Leukopenia- a condition in which the number of white blood cells per unit volume of blood decreases below normal (<4х10 9 /л). Различают первичные (врождённые или наследственные) и

secondary (acquired as a result of radiation damage, poisoning, drug use) leukopenia. Leukocyte formula- percentage of certain forms of leukocytes in peripheral blood. Calculation of the leukocyte formula is extremely important for clinical practice, since it is leukocytes that react earlier and faster than other blood elements to external and internal changes (in particular, inflammation).

Relative and absolute changes in the leukocyte formula. When changes relative(percentage) content of one or another type of leukocytes in the leukocyte formula speaks either of relative neutropenia, eosinopenia, lymphopenia, monocytopenia (with a decrease in the percentage of leukocytes of the corresponding type), or about relative neutrophilia, eozonophilia, relative monocytosis, lymphocytosis (with an increase in their relative content).

Changes in absolute leukocyte count per unit volume of blood is denoted as absolute neutropenia, eosinopenia, lymphopenia, monocytopenia (if their absolute number per unit volume of blood decreases) or absolute neutrophilia, eosinophilia, absolute monocytosis or lymphocytosis (if the number of corresponding types of leukocytes increases).

When characterizing changes in the composition of leukocytes, it is necessary to evaluate both relative and absolute (required!) their content. This is determined by the fact that absolute values ​​reflect the true content of certain types of leukocytes in the blood, while relative values ​​characterize only the ratio of different cells to each other in a unit volume of blood.

In many cases, the direction of relative and absolute changes coincides. Often there is, for example, relative and absolute neutrophilia or neutropenia.

The deviation in the relative (percentage) content of cells per unit volume of blood does not always reflect a change in their true, absolute number. Thus, relative neutrophilia can be combined with absolute neutropenia (a similar situation arises if relative neutrophilia is observed in conditions of significant leukopenia: for example, the neutrophil content is 80%, and the total number of leukocytes is only 1.0x10 9 /l).

To determine the absolute number of a particular type of leukocyte in the blood, it is necessary to calculate this value based on the total number of leukocytes and the percentage of corresponding cells(in the example given, 80% of 1.0x10 9 /l will be 0.8x10 9 /l. This is more than two times less than 2.0x10 9 /l - the lower limit of the normal absolute neutrophil content).

Age-related changes in blood cells

Red blood cells. At birth and in the first hours of life, the number of red blood cells in the blood is increased and amounts to 6.0-7.0x10 12 / l. In newborns, anisocytosis with a predominance of macrocytes, as well as an increased content of reticulocytes, is observed. During the first day of the postnatal period, the number of red blood cells decreases, by the 10-14th day it reaches the adult level and continues to decline. The minimum indicator is observed in the 3-6th month of life (physiological anemia), when the level of erythropoietin is reduced. This is due to a decrease in the synthesis of erythropoietin in the liver and the beginning of its production in the kidney. At the 3-4th year of life, the number of red blood cells is reduced (lower than in an adult), i.e. 1 liter contains less than 4.5x10 12. The content of red blood cells reaches the adult norm during puberty.

Leukocytes. The number of leukocytes in newborns is increased and equals 10-30x10 9 /l. The number of neutrophils is 60.5%, eosinophils - 2%, basophils - 0.2%, monocytes - 1.8%, lymphocytes - 24%. During the first 2 weeks, the number of leukocytes decreases to 9-15x10 9 /l, by 4 years it decreases to 7-13x10 9 /l, and by 14 years it reaches the level characteristic of an adult. The ratio of neutrophils and lymphocytes changes, which causes the occurrence of so-called physiological crossovers.

Φ First cross. In a newborn, the ratio of the content of these cells is the same as in an adult. Subsequently, the content of neutrophils decreases, and lymphocytes increase, so that on the 3-4th day their number equalizes. Subsequently, the number of neutrophils continues to decrease and reaches 25% by 1-2 years. At the same age, the number of lymphocytes is 65%.

Φ Second cross. Over the following years, the number of neutrophils gradually increases, and lymphocytes decrease, so that in four-year-old children these indicators are equalized again and constitute 35% of the total number of leukocytes. The number of neutrophils continues to increase, and the number of lymphocytes continues to decrease, and by the age of 14 these indicators correspond to those of an adult.

Lifespan of leukocytes

Granulocytes live in circulating blood for 4-5 hours, and in tissues for 4-5 days. In cases of serious tissue infection, the lifespan of granulocytes is shortened to several hours, since they very quickly enter the site of infection, perform their functions and are destroyed.

Monocytes after 10-12 hours in the bloodstream they enter the tissues. Once in the tissue, they increase in size and become tissue macrophages. In this form, they can live for months until they are destroyed, performing the function of phagocytosis.

Lymphocytes enter the circulatory system constantly in the process of draining lymph from the lymph nodes. A few hours later, they return to the tissues through diapedesis and then return again and again with lymph into the blood. This ensures constant circulation of lymphocytes through the tissue. The lifespan of lymphocytes is months and even years, depending on the body's needs for these cells.

Microphages and macrophages. The main function of neutrophils and monocytes is phagocytosis and subsequent intracellular destruction of bacteria, viruses, damaged cells that have completed their life cycle, and foreign agents. Neutrophils (and to some extent eosinophils) are mature cells that phagocytose various materials (another name for phagocytic neutrophils is microphages). Blood monocytes are immature cells. Only after entering tissues do monocytes mature into tissue macrophages and acquire the ability to fight pathogens. Neutrophils and macrophages move through tissues through amoeboid movements stimulated by substances that are formed in the inflamed area. This attraction of neutrophils and macrophages to the area of ​​inflammation is called chemotaxis.

Neutrophils

Neutrophils are the most numerous type of leukocytes. They make up 40-75% of the total number of leukocytes. The size of a neutrophil in a blood smear is 12 microns; the diameter of a neutrophil migrating in tissues increases to almost 20 microns. Neutrophils are formed in the bone marrow within 7 days, after 4 days they enter the bloodstream and remain in it for 8-12 hours. Life expectancy is about 8 days. Old cells are phagocytosed by macrophages.

Neutrophil pools. There are three pools of neutrophils: circulating, border and reserve.

Φ Circulating- passively transported blood cells. When a bacterial infection of the body occurs, their number increases several (up to 10) times within 24-48 hours due to the border pool, as well as due to the accelerated release of reserve cells from the bone marrow.

Φ Border the pool consists of neutrophils associated with endothelial cells of small vessels of many organs, especially the lungs and spleen. The circulating and boundary pools are in dynamic equilibrium.

Φ Spare pool - mature bone marrow neutrophils.

Core. Depending on the degree of differentiation, they distinguish rod and segmented(see Fig. 24-1, B) neutrophils. In neutrophils in women, one of the nuclear segments contains a drumstick-shaped outgrowth - Barr's body or sex chromatin (this inactivated X chromosome is visible in 3% of neutrophils in a woman's blood smear).

♦ Band neutrophils- immature forms of cells with a horseshoe-shaped nucleus. Normally, their number is 3-6% of the total number of leukocytes.

♦ Segmented neutrophils- mature cells with a nucleus, which consists of 3-5 segments connected by thin bridges.

Φ Nuclear shifts of the leukocyte formula. Since during microscopy of a blood smear the main criterion for identifying different forms of maturity of granular leukocytes is the nature of the nucleus (shape, size, color intensity), shifts in the leukocyte formula are designated as “nuclear”.

Φ Shift left characterized by an increase in the number of young and immature forms of neutrophils (see Fig. 24-4). In acute purulent-inflammatory diseases, in addition to leukocytosis, the content of young forms of neutrophils, usually band neutrophils, less often young neutrophils (metamyelocytes and myelocytes), increases, which indicates a serious inflammatory process.

Φ Shift right manifested by an increased number of segmented nuclear forms of neutrophils.

Φ Nuclear shift index reflects the ratio of the percentage of the sum of all young forms of neutrophils (bands, metamyelocytes, myelocytes, promyelocytes, see Fig. 24-4) to their mature forms. In healthy adults, the nuclear shift index ranges from 0.05 to 0.10. An increase in it indicates a nuclear shift of neutrophils to the left, a decrease indicates a shift to the right.

Neutrophil granules

Φ Azurophilic granules neutrophils contain various proteins that destroy components of the extracellular matrix and have antibacterial activity. The granules contain cathepsins, elastase, proteinase-3 (myeloblastin), azurocidin, defensins, cationic proteins, lysozyme, arylsulfatase. The main enzyme of azurophilic granules is myeloperoxidase. This protein makes up 2-4% of the neutrophil's mass and catalyzes the formation of hypochlorous acid and other toxic agents that significantly enhance the bactericidal activity of the neutrophil.

Φ Specific granules much smaller, but twice as numerous as azurophiles. The granules contain proteins with bacteriostatic properties: lactoferrin, vitamin B 12-binding proteins. In addition, the granules contain lysozyme, collagenase, alkaline phosphatase, and cationic proteins.

Receptors. Receptors for adhesion molecules, cytokines, colony-stimulating factors, opsonins, chemoattractants, and inflammatory mediators are built into the plasmolemma of neutrophils. Binding of their ligands to these receptors leads to activation of neutrophils (exit from the vascular bed, migration

into the site of inflammation, degranulation of neutrophils, formation of superoxides).

Function of neutrophils. Neutrophils remain in the blood for only a few hours (in transit from the bone marrow to tissues), and their inherent functions are performed outside the vascular bed (exit from the vascular bed occurs as a result of chemotaxis) and only after activation of neutrophils. The main function is phagocytosis of tissue debris and destruction of opsonized microorganisms. Phagocytosis and subsequent digestion of the material occurs in parallel with the formation of arachidonic acid metabolites and respiratory burst. Phagocytosis occurs in several stages. After preliminary specific recognition of the material to be phagocytosed, invagination of the neutrophil membrane around the particle occurs and the formation of a phagosome. Next, as a result of the fusion of the phagosome with lysosomes, a phagolysosome is formed, after which the bacteria are destroyed and the captured material is destroyed. For this, lysozyme, cathepsin, elastase, lactoferrin, defensins, and cationic proteins enter the phagolysosome; myeloperoxidase; superoxide O 2 - and hydroxyl radical OH - formed (along with H 2 O 2) during a respiratory explosion. After a single burst of activity, the neutrophil dies. Such neutrophils constitute the main component of pus (“pus” cells).

Φ Activation. Biologically active compounds of various origins: for example, the contents of platelet granules, arachidonic acid metabolites (lipid mediators), acting on neutrophils, stimulate their activity (many of these substances are at the same time chemoattractants, along the concentration gradient of which neutrophils migrate).

Φ Lipid mediators produce activated neutrophils, as well as basophils and mast cells, eosinophils, monocytes and macrophages, platelets. In an activated cell, arachidonic acid is released from membrane phospholipids, from which prostaglandins, thromboxanes, leukotrienes and a number of other biologically active substances are formed.

Φ Respiratory explosion. During the first seconds after stimulation, neutrophils sharply increase oxygen uptake and quickly consume a significant amount of it. This phenomenon is known as respiratory (oxygen) explosion. In this case, H 2 O 2, superoxide O 2 - and hydroxyl radical OH -, which are toxic to microorganisms, are formed.

Φ Chemotaxis. Neutrophils migrate to the site of infection along a concentration gradient of many chemical factors. Important among them are N-formylmethionyl peptides (for example, the chemoattractant f-Met-Leu-Phe), which are formed during the breakdown of bacterial proteins or mitochondrial proteins during cell damage.

Φ Adhesion. The activated neutrophil attaches to the vascular endothelium. Adhesion to the endothelium is stimulated by many agents: anaphylatoxins, IL-I, thrombin, platelet activating factor PAF, leukotrienes LTC 4 and LTB 4, tumor necrosis factor α, etc.

Φ Migration. After attaching to the endothelium and leaving the vessel, neutrophils increase in size, elongate and become polarized, forming a broad head end (lamellipodia) and a narrowed posterior part. The neutrophil, moving the lamellipodia forward, migrates to the source of the chemoattractant. In this case, the granules move to the head end, their membranes merge with the plasmalemma, and the contents of the granules (including proteases) are released from the cell - degranulation.

Eosinophils

but 8-14 days. Eosinophils on their surface have membrane receptors for the Fc fragments of IgG, IgM and IgE, complement components C1s, C3a, C3b, C4 and C5a, the chemokine eotaxin, and interleukins. The migration of eosinophils in tissues is stimulated by eotaxin, histamine, eosinophil chemotaxis factor ECF, interleukin-5, etc. After performing their functions (after degranulation) or in the absence of activation factors (for example, IL-5), eosinophils die.

Metabolic activity. Like neutrophils, eosinophils synthesize arachidonic acid metabolites (lipid mediators), including leukotriene LTC 4 and platelet activating factor PAF.

Chemotaxis. Activated eosinophils move along a gradient of chemotaxis factors - bacterial products and complement elements. Particularly effective as chemoattractants are substances secreted by basophils and mast cells - histamine and eosinophil chemotaxis factor ECF.

Φ Participation in allergic reactions. The contents of eosinophil granules inactivate histamine and leukotriene LTC 4. Eosinophils produce an inhibitor that blocks mast cell degranulation. Slow reacting factor anaphylaxis (SRS-A), released by basophils and mast cells, is also inhibited by activated eosinophils.

Φ Side effects of eosinophils. Substances secreted by the eosinophil can damage normal tissue. Thus, with a constant high content of eosinophils in the blood, chronic secretion of the contents of eosinophil granules causes thromboembolic damage, tissue necrosis (especially the endocardium) and the formation of fibrous tissue. IgE stimulation of eosinophils can cause reversible changes in vascular permeability. Secretion products of eosinophils damage the bronchial epithelium and activate complement and the blood coagulation system.

Basophils

Basophils make up 0-1% of the total number of leukocytes in circulating blood. Basophils with a diameter of 10-12 microns remain in the blood for 1-2 days. Like other granular leukocytes, they can leave the bloodstream when stimulated, but their ability for amoeboid movement is limited. Lifespan and tissue fate are unknown.

Specific granules quite large (0.5-1.2 microns), colored metachromatically (in a different color than the dye, from

reddish-violet to intense violet). The granules contain various enzymes and mediators. The most significant of them include heparin sulfate (heparin), histamine, inflammatory mediators (for example, slow-reacting anaphylaxis factor SRS-A, eosinophil chemotaxis factor ECF).

Metabolic activity. When activated, basophils produce lipid mediators. Unlike mast cells, they do not have PGD 2 synthetase activity and oxidize arachidonic acid predominantly to leukotriene

LTC 4.

Function. Activated basophils leave the bloodstream and participate in allergic reactions in tissues. Basophils have high-affinity surface receptors for the Fc fragments of IgE, and IgE is synthesized by plasma cells when Ag (allergen) enters the body. Basophil degranulation is mediated by IgE molecules. In this case, cross-linking of two or more IgE molecules occurs. The release of histamine and other vasoactive factors during degranulation and the oxidation of arachidonic acid cause the development of an immediate allergic reaction (such reactions are characteristic of allergic rhinitis, some forms of bronchial asthma, anaphylactic shock).

Monocytes

Monocytes (see Fig. 24-1, E) are the largest leukocytes (diameter in a blood smear is about 15 microns), their number is 2-9% of all leukocytes in circulating blood. They are formed in the bone marrow, enter the bloodstream and circulate for about 2-4 days. Blood monocytes are actually immature cells on their way from the bone marrow to the tissues. In tissues, monocytes differentiate into macrophages; a collection of monocytes and macrophages - mononuclear phagocyte system.

Activation of monocytes. Various substances formed at sites of inflammation and tissue destruction are agents of chemotaxis and activation of monocytes. As a result of activation, cell size increases, metabolism increases, monocytes secrete biologically active substances (IL-1, colony-stimulating factors M-CSF and GM-CSF, Pg, interferons, neutrophil chemotaxis factors, etc.).

Function. The main function of monocytes and macrophages formed from them is phagocytosis. Lysosomal enzymes, as well as intracellularly formed H 2 O 2, OH -, O 2 -, participate in the digestion of phagocytosed material. Activated monocytes/macrophages also produce endogenous pyrogens.

Φ Pyrogens. Monocytes/macrophages produce endogenous pyrogens(IL-1, IL-6, IL-8, tumor necrosis factor TNF-α, α-interferon) - polypeptides that trigger metabolic changes in the thermoregulation center (hypothalamus), which leads to an increase in body temperature. The formation of prostaglandin PGE 2 plays a critical role. The formation of endogenous pyrogens by monocytes/macrophages (as well as a number of other cells) is caused by exogenous pyrogens- proteins of microorganisms, bacterial toxins. The most common exogenous pyrogens are endotoxins (lipopolysaccharides of gram-negative bacteria).

Macrophage- differentiated form of monocytes - large (about 20 microns), mobile cell of the mononuclear phagocyte system. Macrophages- professional phagocytes, they are found in all tissues and organs; it is a mobile population of cells. The lifespan of macrophages is months. Macrophages are divided into resident and mobile. Resident macrophages are normally found in tissues in the absence of inflammation. Among them, there are free, round-shaped, and fixed macrophages - star-shaped cells, attached with their processes to the extracellular matrix or to other cells.

Properties of a macrophage depend on their activity and location. Lysosomes of macrophages contain bactericidal agents: myeloperoxidase, lysozyme, proteinases, acid hydrolases, cationic proteins, lactoferrin, superoxide dismutase - an enzyme that promotes the formation of H 2 O 2, OH -, O 2 -. Under the plasma membrane there are large numbers of actin microfilaments, microtubules, and intermediate filaments necessary for migration and phagocytosis. Macrophages migrate along a concentration gradient of many substances coming from various sources. Activated macrophages

form irregularly shaped cytoplasmic pseudopodia involved in amoeboid movement and phagocytosis. Functions. Macrophages capture denatured proteins and aged red blood cells from the blood (fixed macrophages of the liver, spleen, bone marrow). Macrophages phagocytose cell debris and tissue matrix. Nonspecific phagocytosis characteristic of alveolar macrophages that capture dust particles of various natures, soot, etc. Specific phagocytosis occurs when macrophages interact with an opsonized bacterium. An activated macrophage secretes more than 60 factors. Macrophages exhibit antibacterial activity by releasing lysozyme, acid hydrolases, cationic proteins, lactoferrin, H 2 O 2, OH -, O 2 -. Antitumor activity consists of the direct cytotoxic effect of H 2 O 2, arginase, cytolytic proteinase, tumor necrosis factor from macrophages. A macrophage is an antigen-presenting cell: it processes Ag and presents it to lymphocytes, which leads to stimulation of lymphocytes and the launch of immune reactions (see more in Chapter 29). Interleukin-1 from macrophages activates T-lymphocytes and, to a lesser extent, B-lymphocytes. Macrophages produce lipid mediators: PgE 2 and leukotrienes, platelet activating factor PAF. The cell also secretes α-interferon, which blocks viral replication. An activated macrophage secretes enzymes that destroy the extracellular matrix (elastase, hyaluronidase, collagenase). On the other hand, growth factors synthesized by the macrophage effectively stimulate the proliferation of epithelial cells (transforming growth factor TGFα, bFGF), proliferation and activation of fibroblasts (platelet-derived growth factor PDGF), collagen synthesis by fibroblasts (transforming growth factor TGFp), the formation of new blood vessels - angiogenesis (fibroblast growth factor bFGF). Thus, the main processes underlying wound healing (re-epithelialization, formation of extracellular matrix, restoration of damaged vessels) are mediated by growth factors produced by macrophages. By producing a number of colony-stimulating factors (macrophages - M-CSF, granulocytes - G-CSF), macrophages influence the differentiation of blood cells.

Lymphocytes

Lymphocytes (see Fig. 24-1, E) make up 20-45% of the total number of blood leukocytes. Blood is the medium in which lymphocytes circulate between the organs of the lymphoid system and other tissues. Lymphocytes can exit the vessels into the connective tissue, and also migrate through the basement membrane and penetrate the epithelium (for example, in the intestinal mucosa). The lifespan of lymphocytes ranges from several months to several years. Lymphocytes are immunocompetent cells that are of great importance for the body’s immune defense reactions (see Chapter 29 for more details). From a functional point of view, B-, T-lymphocytes and NK cells are distinguished.

B lymphocytes(pronounced “bae”) are formed in the bone marrow and make up less than 10% of blood lymphocytes. Some B lymphocytes in tissues differentiate into clones of plasma cells. Each clone synthesizes and secretes antibodies against only one Ag. In other words, plasma cells and the antibodies they synthesize provide humoral immunity.

T-lymphocytes. T-lymphocyte precursor cells enter the thymus from the bone marrow. Differentiation of T lymphocytes occurs in the thymus. Mature T lymphocytes leave the thymus and are found in the peripheral blood (80% or more of all lymphocytes) and lymphoid organs. T-lymphocytes, like B-lymphocytes, react (i.e., recognize, multiply and differentiate) to specific Ags, but unlike B-lymphocytes, the participation of T-lymphocytes in immune reactions is associated with the need to recognize the main proteins in the membrane of other cells. MHC histocompatibility complex. The main functions of T-lymphocytes are participation in cellular and humoral immunity (thus, T-lymphocytes destroy abnormal cells of their body, participate in allergic reactions and in the rejection of foreign transplants). Among T-lymphocytes, CD4+- and CD8+-lymphocytes are distinguished. CD4+ lymphocyte I(T-helpers) support the proliferation and differentiation of B lymphocytes and stimulate the formation of cytotoxic T lymphocytes, and also promote the proliferation and differentiation of suppressor T lymphocytes.

NK cells- lymphocytes lacking the surface cell determinants characteristic of T- and B-cells. These cells make up about 5-10% of all circulating lymphocytes, contain cytolytic granules with perforin, and destroy transformed (tumor) and virus-infected cells, as well as foreign cells.

Blood plates

Platelets, or blood platelets (Fig. 24-13), are fragments of megakaryocytes located in the red bone marrow. The size of blood platelets in a blood smear is 3-5 microns. The number of platelets in the circulating blood is 190-405x10 9 /l. Two thirds of the blood platelets are in the blood, the rest are deposited in the spleen. The lifespan of platelets is 8 days. Old platelets are phagocytosed in the spleen, liver and bone marrow. Platelets circulating in the blood can be activated under a number of circumstances; activated platelets participate in blood clotting and restoration of the integrity of the vessel wall. One of the most important properties of activated blood platelets is their ability to mutual adhesion and aggregation, as well as adhesion to the wall of blood vessels.

Glycocalyx. The protruding parts of the molecules that make up the integral proteins of the plasma membrane, rich in polysaccharide side chains (glycoproteins), create the outer covering of the lipid bilayer - the glycocalyx. Coagulation factors and immunoglobulins are also adsorbed here. Receptor sites are located on the outer parts of glycoprotein molecules. After their combination with agonists, an activation signal is induced, transmitted to the internal parts of the peripheral platelet zone.

Plasma membrane contains glycoproteins that act as receptors for platelet adhesion and aggregation. Thus, glycoprotein Ib (GP Ib, Ib-IX) is important for platelet adhesion; it binds to von Willebrand factor and subendothelial connective tissue. Glycoprotein IV (GP IIIb) is a thrombospondin receptor. Glycoprotein IIb-IIIa (GP IIb-IIIa) - receptor for fibrinogen, fibronectin, thrombospondin, vitronectin, von Willebrand factor; these factors promote adhesion and aggregation of thrombosis

Rice. 24-13. The platelet has the shape of an oval or round disk. Small accumulations of glycogen and large granules of several types are visible in the cytoplasm. The peripheral part contains circular bundles of microtubules (necessary for maintaining the oval shape of the platelet), as well as actin, myosin, gelsolin and other contractile proteins necessary for changing the shape of platelets, their mutual adhesion and aggregation, as well as for retraction of the blood clot formed during platelet aggregation . Along the periphery of the platelet there are also anastomosing membrane tubules that open into the extracellular environment and are necessary for the secretion of the contents of α-granules. Scattered in the cytoplasm are narrow, irregularly shaped membrane tubes that make up a dense tubular system. The tubules contain cyclooxygenase (necessary for the oxidation of arachidonic acid and the formation of thromboxane TXA 2. Acetylsalicylic acid (aspirin) irreversibly acetylates cyclooxygenase localized in the tubules of the dense tubular system, which blocks the formation of thromboxane, necessary for platelet aggregation; as a result, platelet function is impaired and bleeding time is prolonged ) .

cytes, mediating the formation of fibrinogen “bridges” between them.

Granules. Platelets contain three types of granules (α-, δ-, λ-) and microperoxisomes.

Φ α-Granules contain various glycoproteins (fibronectin, fibrinogen, von Willebrand factor), heparin binding proteins (eg platelet factor 4), platelet-derived growth factor PDGF and transforming growth factor β, plasma coagulation factors VIII and V, and thrombospondin (promotes platelet adhesion and aggregation) and cell adhesion receptor GMP-140. Φ Other granules.δ-Granules accumulate inorganic phosphate P., ADP, ATP, Ca 2 +, serotonin and histamine (serotonin and histamine are not synthesized in platelets, but come from plasma). λ-Granules contain lysosomal enzymes and may be involved in clot dissolution. Microperoxisomes have peroxidase activity. Functions of platelets. Under physiological conditions, platelets are in an inactive state, i.e. circulate freely in the blood, do not adhere to each other and are not attached to the endothelium of the vessel (this is partly due to the fact that endothelial cells produce prostacyclin PGI 2, which prevents platelet adhesion to the vessel wall). However, when a blood vessel is damaged, platelets, together with plasma clotting factors, form a blood clot - a thrombus, which prevents bleeding.

Stop bleeding occurs in three stages. 1. First, the lumen of the blood vessel contracts. 2. Next, in the damaged area of ​​the vessel, platelets attach to the vessel wall and, layering on top of each other, form a platelet hemostatic plug (white thrombus). These processes (changes in the shape of blood platelets, their adhesion and aggregation) are reversible, so that weakly aggregated platelets can be separated from hemostatic platelet plugs and returned to the bloodstream. 3. Finally, soluble fibrinogen is converted into insoluble fibrin, which forms a strong three-dimensional network, in the loops of which blood cells, including red blood cells, are located. Is it fibrin, or red, thrombus.

Φ The formation of a fibrin thrombus is preceded by a cascade of proteolytic reactions, leading to the activation of the enzyme thrombin, which converts fibrinogen into fibrin. Thus, at one of the stages of thrombus formation, blood clotting (hemocoagulation) occurs - part of the hemostasis system, to which platelets are most directly related.

Hemostasis

In the applied sense, the term “hemostasis” (from gr. haima- blood, stasis- stop) is used to denote the actual process of stopping bleeding. The hemostatic system includes factors and mechanisms of three categories: coagulation, anticoagulation and fibrinolytic.

Φ Coagulation system namely, plasma coagulation factors (procoagulants), forming a complex hemocoagulation cascade, ensures fibrinogen coagulation and thrombus formation (Fig. 24-14). The cascade of reactions leading to the formation of thrombin can occur in two ways - external (in the figure on the left and above) and internal (in the figure on the right and above). To initiate reactions of the extrinsic pathway, the appearance of tissue factor on the outer surface of the plasma membrane of platelets, monocytes and endothelium is necessary. The intrinsic pathway begins with the activation of factor XII upon its contact with the damaged endothelial surface. The concept of internal and external coagulation pathways is very arbitrary, since the cascade of blood coagulation reactions occurs primarily along the external route, and not along two relatively independent pathways.

Φ Anticoagulant system physiological anticoagulants cause inhibition or blockade of blood coagulation.

Φ Fibrinolytic system carries out lysis of fibrin thrombus.

Plasma coagulation factors - various plasma components responsible for the formation of a blood clot. Coagulation factors are designated by Roman numerals (a lowercase letter “a” is added to the number of the activated form of the factor).

Rice. 24-14. Hemocoagulation cascade . Activation of factor XII triggers the internal (contact) mechanism, the release of tissue factor, and activation of factor VII triggers the external coagulation mechanism. Both pathways lead to the activation of factor X. In rectangles with rounded corners are the numbers of plasma coagulation factors. Enzyme complexes are adjacent rectangles with solid and intermittent boundaries.

♦ I- soluble fibrinogen, which is converted into insoluble fibrin under the influence of thrombin (factor Ha).

♦ II- prothrombin (proenzyme), converted into thrombin protease (factor IIa) under the influence of the factor Xa complex, phospholipids of platelet and other cell membranes, Ca 2 + and factor Va.

♦ III- tissue factor. Complex of tissue factor, phospholipids, factor VIIa and Ca 2+ triggers the external coagulation mechanism.

♦ IV- Ca 2+.

♦ V- proaccelerin is a precursor of accelerin (Va), an activator protein of the Xa-Va-Ca 2+ membrane complex.

♦ VII- proconvertin (proenzyme), VIIa - protease that activates factors X and IX.

♦ VIII- inactive antihemophilic globulin A - a precursor of factor VIIIa (active antihemophilic globulin) - an activator protein of the membrane complex IXa-VIIIa-Ca 2+. Factor VIII deficiency causes the development of classical hemophilia A, which is observed only in men.

♦ IX- inactive antihemophilic globulin B (proenzyme, inactive Christmas factor) - a precursor of active antihemophilic factor B (active Christmas factor) - a protease that activates factor X. Factor IX deficiency leads to the development of hemophilia B (Christmas disease).

♦ X- inactive Stewart-Prower factor (active form - factor Xa - protease that activates factor II), deficiency of Stewart factor leads to coagulation defects.

♦ XI- proenzyme of the contact pathway of blood coagulation - an inactive plasma precursor of thromboplastin (the active form is factor XIa - a serine protease that converts factor IX into factor IXa). Factor XI deficiency causes bleeding.

♦ XII- inactive Hageman factor - proenzyme of the contact pathway of blood coagulation, active form - factor XIIa (active Hageman factor) - activates factor XI, prekallikrein (proenzyme of the contact pathway of blood coagulation), plasminogen.

♦ XIII- fibrin-stabilizing factor (Lucky-Laurent factor) - thrombin-activated factor XIII (factor XIIIa), forms insoluble fibrin, catalyzing the formation of amide bonds between fibrin monomer molecules, fibrin and fibronectin.

External path plays a central role in blood clotting. Enzyme membrane complexes (see below) are formed only in the presence of platelets, tissue factor endothelial cells and negatively charged phospholipids on the outer surface of the plasma membrane, i.e. during the formation of negatively charged (thrombogenic) areas and exposure to tissue factor apoprotein. In this case, tissue factor and the surface of the cell membrane become accessible to plasma factors. F Enzyme activation. Circulating blood contains proenzymes (factors II, VII, IX, X). Cofactor proteins (factors Va, VIIIa, as well as tissue factor - factor III) contribute to the conversion of proenzymes into enzymes (serine proteases). F Enzyme membrane complexes. When the cascade mechanism of enzyme activation is activated, three enzyme complexes associated with phospholipids of the cell membrane are sequentially formed. Each complex consists of a proteolytic enzyme, a cofactor protein and Ca 2+ ions: VIIa-tissue factor-phospholipid-Ca 2+, Ka-VIIIa-phospholipid-Ca2+ (tenase complex, factor X activator); Xa-Va-phospholipid-Ca 2+ (prothrombinase complex, prothrombin activator). The cascade of enzymatic reactions ends with the formation of fibrin monomers and the subsequent formation of a blood clot. F Ca 2+ ions. The interaction of enzyme complexes with cell membranes occurs with the participation of Ca 2 + ions. The γ-carboxyglutamic acid residues in factors \VIIIa, Ka, Xa and prothrombin ensure the interaction of these factors through Ca 2 + with negatively charged phospholipids of cell membranes. Without Ca 2+ ions, blood does not clot. That is why, in order to prevent blood clotting, the Ca 2 + concentration is reduced by deionization of calcium citrate (citrate blood) or precipitation of calcium in the form of oxalates (oxalate blood). F Vitamin K Carboxylation of glutamic acid residues in the proenzymes of the procoagulant pathway is catalyzed by carboxylase, the coenzyme of which is the reduced form of vitamin K (naphthoquinone). That's why

Vitamin K deficiency inhibits blood clotting and is accompanied by bleeding, subcutaneous and internal hemorrhages, and structural analogues of vitamin K (for example, warfarin) are used in clinical practice to prevent thrombosis.

Contact path Blood coagulation begins with the interaction of the proenzyme (factor XII) with the damaged endothelial surface of the vascular wall. This interaction leads to the activation of factor XII and initiates the formation of membrane enzyme complexes of the contact phase of coagulation. These complexes contain the enzymes kallikrein, factors XIa (plasma precursor of thromboplastin) and XIIa (Hageman factor), as well as a cofactor protein - high molecular weight kininogen.

Anticoagulant blood system. Physiological inhibitors play an important role in maintaining blood in a liquid state and preventing the spread of a blood clot beyond the damaged area of ​​the vessel. Thrombin, which is formed as a result of blood coagulation reactions and ensures the formation of a blood clot, is washed out of the blood clot by the blood flow; Thrombin is subsequently inactivated when interacting with inhibitors of blood clotting enzymes and at the same time activates the anticoagulant phase, which inhibits the formation of a blood clot.

F Anticoagulant phase. This phase is triggered by thrombin (factor II), causing the formation of enzyme complexes of the anticoagulant phase on the intact vascular endothelium. In addition to thrombin, the reactions of the anticoagulant phase involve endothelial cell thrombomodulin, vitamin K-dependent serine protease - protein C, activating protein S and plasma coagulation factors Va and

VIIIa.

F Physiological inhibitors blood clotting enzymes (antithrombin III, heparin, a 2-macroglobulin, anticonvertin, a j -antitrypsin) limit the spread of a blood clot to the site of vessel damage.

Fibrinolytic system. The clot may dissolve within a few days after formation. With fibrinolysis - enzymatic breakdown of fibrin fibers -

Soluble peptides are produced. Fibrinolysis occurs under the action of the serine protease plasmin, more precisely, through the interaction of fibrin, plasminogen and tissue plasminogen activator.

Laboratory parameters of the hemostasis system. Blood of a healthy person in vitro coagulates in 5-10 minutes. In this case, the formation of the prothrombinase complex takes 5-8 minutes, the activation of prothrombin - 2-5 s, and the conversion of fibrinogen to fibrin - 2-5 s. In clinical practice, to assess hemostasis, the content of various components of the coagulation system, anticoagulants and fibrinolysis are assessed. The simplest laboratory methods include determining bleeding time, thrombin and prothrombin time, activated partial thromboplastin time and prothrombin index.

Chapter Summary

Blood is a liquid connective tissue circulating in the vascular system, which has the most important functions: transport, immune, blood clotting and maintaining homeostasis of the body.

The average adult contains approximately 5 liters of whole blood, which contains about 45% formed elements, suspended in 55% plasma and solutions.

Plasma contains proteins (albumin, globulins, fibrinogen, enzymes, hormones, etc.), lipids (cholesterol, triglycerides) and carbohydrates (glucose).

Red blood cells are anucleate disc-like cells that deliver oxygen to all cells of the body through hemoglobin.

Changes in the number of red blood cells, their shape, size, color and maturity are a valuable indicator for the diagnosis of various diseases.

At the end of the 4th month of life, old red blood cells are absorbed by macrophages. Their hemoglobin, including iron, is processed into a diagnostically important substance - bilirubin.

Leukocytes are morphologically divided into granulocytes (eosinophils, basophils and neutrophils) and agranulocytes (monocytes and lymphocytes). Lymphocytes are functionally divided into T and B cells with different subsets.

Leukocytes protect the body from infection using phagocytosis and various antimicrobial agents, releasing mediators that control inflammation and thereby promoting healing.

Hematopoiesis is the development of blood cells from neutral multipotent stem cells of the bone marrow. Immature cells differentiate into mature cells under the influence of hematopoietins and other cytokines.

Platelets (blood platelets) are small, irregularly shaped, nuclear-free structures that, together with plasma proteins, control blood clotting.

During blood transfusion, the donor and recipient must avoid agglutination between the red blood cell-associated antigens A, B and Rh and the anti-A, anti-B and anti-Rh antibodies found in the plasma.

Let us consider in more detail the composition of plasma and cellular elements of blood.

Plasma. After the separation of cellular elements suspended in the blood, an aqueous solution of complex composition remains, called plasma. As a rule, plasma is a clear or slightly opalescent liquid, the yellowish color of which is determined by the presence of small amounts of bile pigment and other colored organic substances.

However, after consuming fatty foods, many fat droplets (chylomicrons) enter the bloodstream, causing the plasma to become cloudy and oily.

Plasma is involved in many vital processes of the body. It transports blood cells, nutrients and metabolic products and serves as a link between all extravascular (i.e., located outside the blood vessels) fluids; the latter include, in particular, the intercellular fluid, and through it communication with the cells and their contents occurs. Thus, the plasma comes into contact with the kidneys, liver and other organs and thereby maintains the constancy of the internal environment of the body, i.e. homeostasis.

The main components of plasma and their concentrations are given in table. 1. Among the substances dissolved in plasma are low molecular weight organic compounds (urea, uric acid, amino acids, etc.); large and very complex protein molecules; partially ionized inorganic salts. The most important cations (positively charged ions) include sodium (Na +), potassium (K +), calcium (Ca 2+) and magnesium (Mg 2+) cations; The most important anions (negatively charged ions) are chloride anions (Cl –), bicarbonate (HCO 3 –) and phosphate (HPO 4 2– or H 2 PO 4 –). The main protein components of plasma are albumin, globulins and fibrinogen.

Plasma proteins

Of all proteins, albumin, synthesized in the liver, is present in the highest concentration in plasma. It is necessary to maintain osmotic balance, which ensures normal distribution of fluid between blood vessels and the extravascular space. During fasting or insufficient protein intake from food, the albumin content in plasma decreases, which can lead to increased accumulation of water in tissues (edema). This condition, associated with protein deficiency, is called starvation edema.

Plasma contains globulins of several types, or classes, the most important of which are designated by the Greek letters a (alpha), b (beta) and g (gamma), and the corresponding proteins are a 1, a 2, b, g 1 and g 2. After separation of globulins (by electrophoresis), antibodies are detected only in fractions g 1, g 2 and b. Although antibodies are often called gamma globulins, the fact that some of them are also present in the b-fraction led to the introduction of the term “immunoglobulin”. The a- and b-fractions contain many different proteins that ensure the transport of iron, vitamin B12, steroids and other hormones in the blood. This same group of proteins also includes coagulation factors, which, along with fibrinogen, are involved in the process of blood clotting.

The main function of fibrinogen is to form blood clots (thrombi). During the process of blood clotting, whether in vivo (in a living body) or in vitro (outside the body), fibrinogen is converted into fibrin, which forms the basis of a blood clot; Plasma that does not contain fibrinogen, usually in the form of a clear, pale yellow liquid, is called blood serum.

Red blood cells.

Red blood cells, or erythrocytes, are round discs with a diameter of 7.2–7.9 µm and an average thickness of 2 µm (µm = micron = 1/10 6 m). 1 mm 3 of blood contains 5–6 million red blood cells. They make up 44–48% of the total blood volume.

Red blood cells have the shape of a biconcave disc, i.e. The flat sides of the disk are compressed, making it look like a donut without a hole. Mature red blood cells do not have nuclei. They contain mainly hemoglobin, the concentration of which in the intracellular aqueous medium is approx. 34%. [In terms of dry weight, the hemoglobin content in erythrocytes is 95%; per 100 ml of blood, the hemoglobin content is normally 12–16 g (12–16 g%), and in men it is slightly higher than in women.] In addition to hemoglobin, red blood cells contain dissolved inorganic ions (mainly K +) and various enzymes . The two concave sides provide the red blood cell with optimal surface area through which gases can be exchanged: carbon dioxide and oxygen. Thus, the shape of cells largely determines the efficiency of physiological processes. In humans, the area of ​​surfaces through which gas exchange occurs averages 3820 m2, which is 2000 times the surface of the body.

In the fetus, primitive red blood cells are first formed in the liver, spleen and thymus. From the fifth month of intrauterine development, erythropoiesis gradually begins in the bone marrow - the formation of full-fledged red blood cells. In exceptional circumstances (for example, when normal bone marrow is replaced by cancerous tissue), the adult body can switch back to producing red blood cells in the liver and spleen. However, under normal conditions, erythropoiesis in an adult occurs only in flat bones (ribs, sternum, pelvic bones, skull and spine).

Red blood cells develop from precursor cells, the source of which is the so-called. stem cells. In the early stages of red blood cell formation (in cells still in the bone marrow), the cell nucleus is clearly visible. As the cell matures, hemoglobin accumulates, formed during enzymatic reactions. Before entering the bloodstream, the cell loses its nucleus - due to extrusion (squeezing out) or destruction by cellular enzymes. With significant blood loss, red blood cells are formed faster than normal, and in this case, immature forms containing a nucleus may enter the bloodstream; This apparently occurs because the cells leave the bone marrow too quickly. The period of maturation of erythrocytes in the bone marrow - from the moment the youngest cell appears, recognizable as the precursor of an erythrocyte, until its full maturation - is 4-5 days. The lifespan of a mature erythrocyte in peripheral blood is on average 120 days. However, with certain abnormalities of the cells themselves, a number of diseases, or under the influence of certain medications, the lifespan of red blood cells can be shortened.

Most of the red blood cells are destroyed in the liver and spleen; in this case, hemoglobin is released and breaks down into its components heme and globin. The further fate of globin was not traced; As for heme, iron ions are released from it (and returned to the bone marrow). Losing iron, heme turns into bilirubin, a red-brown bile pigment. After minor modifications occurring in the liver, bilirubin in bile is excreted through the gallbladder into the digestive tract. Based on the content of the final product of its transformations in feces, the rate of destruction of red blood cells can be calculated. On average, in an adult body, 200 billion red blood cells are destroyed and re-formed every day, which is approximately 0.8% of their total number (25 trillion).

Hemoglobin.

The main function of the red blood cell is to transport oxygen from the lungs to the tissues of the body. A key role in this process is played by hemoglobin, an organic red pigment consisting of heme (a porphyrin compound with iron) and globin protein. Hemoglobin has a high affinity for oxygen, due to which the blood is able to carry much more oxygen than a regular aqueous solution.

The degree of binding of oxygen to hemoglobin depends primarily on the concentration of oxygen dissolved in the plasma. In the lungs, where there is a lot of oxygen, it diffuses from the pulmonary alveoli through the walls of blood vessels and the aqueous medium of the plasma and enters the red blood cells; There it binds to hemoglobin - oxyhemoglobin is formed. In tissues where the oxygen concentration is low, oxygen molecules are separated from hemoglobin and penetrate into the tissue due to diffusion. Insufficiency of red blood cells or hemoglobin leads to a decrease in oxygen transport and thereby to disruption of biological processes in tissues.

In humans, a distinction is made between fetal hemoglobin (type F, from fetus) and adult hemoglobin (type A, from adult). There are many known genetic variants of hemoglobin, the formation of which leads to abnormalities of red blood cells or their function. Among them, the most famous is hemoglobin S, which causes sickle cell anemia.

Leukocytes.

White peripheral blood cells, or leukocytes, are divided into two classes depending on the presence or absence of special granules in their cytoplasm. Cells that do not contain granules (agranulocytes) are lymphocytes and monocytes; their kernels have a predominantly regular round shape. Cells with specific granules (granulocytes) are usually characterized by the presence of irregularly shaped nuclei with many lobes and are therefore called polymorphonuclear leukocytes. They are divided into three types: neutrophils, basophils and eosinophils. They differ from each other in the pattern of granules stained with various dyes.

In a healthy person, 1 mm 3 of blood contains from 4,000 to 10,000 leukocytes (on average about 6,000), which is 0.5–1% of blood volume. The proportion of individual types of cells in the composition of white blood cells can vary significantly between different people and even within the same person at different times. Typical values ​​are given in table. 2.

Polymorphonuclear leukocytes (neutrophils, eosinophils and basophils) are formed in the bone marrow from progenitor cells, which give rise to stem cells, probably the same ones that give rise to red blood cell precursors. As the nucleus matures, the cells develop granules that are typical for each cell type. In the bloodstream, these cells move along the walls of the capillaries primarily due to amoeboid movements. Neutrophils are able to leave the internal space of the vessel and accumulate at the site of infection. The lifespan of granulocytes appears to be approx. 10 days, after which they are destroyed in the spleen.

The diameter of neutrophils is 12–14 µm. Most dyes color their core purple; the nucleus of peripheral blood neutrophils can have from one to five lobes. The cytoplasm is stained pinkish; under a microscope, many intense pink granules can be distinguished in it. In women, approximately 1% of neutrophils carry sex chromatin (formed by one of the two X chromosomes), a drumstick-shaped body attached to one of the nuclear lobes. These so-called Barr bodies allow sex to be determined by examining blood samples.

Eosinophils are similar in size to neutrophils. Their nucleus rarely has more than three lobes, and the cytoplasm contains many large granules, which clearly stain bright red with eosin dye.

Unlike eosinophils, basophils have cytoplasmic granules stained blue with basic dyes.

Monocytes. The diameter of these non-granular leukocytes is 15–20 µm. The nucleus is oval or bean-shaped, and only in a small part of the cells is it divided into large lobes that overlap each other. When stained, the cytoplasm is bluish-gray and contains a small number of inclusions that are stained blue-violet with azure dye. Monocytes are formed both in the bone marrow and in the spleen and lymph nodes. Their main function is phagocytosis.

Lymphocytes. These are small mononuclear cells. Most peripheral blood lymphocytes have a diameter of less than 10 µm, but lymphocytes with a larger diameter (16 µm) are sometimes found. The cell nuclei are dense and round, the cytoplasm is bluish in color, with very sparse granules.

Although lymphocytes appear morphologically uniform, they differ clearly in their functions and cell membrane properties. They are divided into three broad categories: B cells, T cells, and O cells (null cells, or neither B nor T).

B lymphocytes mature in the human bone marrow and then migrate to the lymphoid organs. They serve as precursors to cells that form antibodies, the so-called. plasmatic. In order for B cells to transform into plasma cells, the presence of T cells is necessary.

T cell maturation begins in the bone marrow, where prothymocytes are formed, which then migrate to the thymus gland, an organ located in the chest behind the breastbone. There they differentiate into T lymphocytes, a highly heterogeneous population of immune system cells that perform various functions. Thus, they synthesize macrophage activation factors, B-cell growth factors and interferons. Among T cells there are inducer (helper) cells that stimulate the formation of antibodies by B cells. There are also suppressor cells that suppress the functions of B cells and synthesize the growth factor of T cells - interleukin-2 (one of the lymphokines).

O cells differ from B and T cells in that they do not have surface antigens. Some of them serve as “natural killers”, i.e. kill cancer cells and cells infected with a virus. However, the overall role of O cells is unclear.

Hematopoiesis (lat. haemopoiesis), hematopoiesis is the process of formation, development and maturation of blood cells - leukocytes, erythrocytes, platelets in vertebrates.

Highlight:

• -embryonic (intrauterine) hematopoiesis;
• - postembryonic hematopoiesis.

The precursors of all blood cells are hematopoietic stem cells of the bone marrow, which can differentiate in two ways: into the precursors of myeloid cells (myelopoiesis) and into the precursors of lymphoid cells (lymphopoiesis).

Red blood cells circulate for 120 days and are destroyed in the liver and spleen.

The average lifespan of platelets is about one week. The lifespan of most leukocytes is from several hours to several months. Neutrophilic leukocytes (neutrophils) make up 95% of granular leukocytes. They circulate in the blood for no more than 8-12 hours, and then migrate into the tissues.

Regulation of hematopoiesis - hematopoiesis or hematopoiesis occurs under the influence of various growth factors, which ensure the division and differentiation of blood cells in the red bone marrow. There are two forms of regulation: humoral and nervous. Nervous regulation is carried out when adrenergic neurons are excited, and hematopoiesis is activated, and when cholinergic neurons are excited, hematopoiesis is inhibited.

Humoral regulation occurs under the influence of factors of exo- and endogenous origin. Endogenous factors include: hematopoietins (products of the destruction of formed elements), erythropoietins (formed in the kidneys when the oxygen concentration in the blood decreases), leukopoietins (formed in the liver), thrombocytopoietins: K (in plasma), C (in the spleen). Exogenous vitamins: B3 - formation of erythrocyte stroma, B12 - formation of globin; trace elements (Fe, Cu...); Castle's external factor. And also such growth factors as: interleukins, colony-stimulating factors CSF, transcription factors - special proteins that regulate the expression of genes of hematopoietic cells. In addition, the bone marrow stroma plays an important role, which creates the hematopoietic microenvironment necessary for the development, differentiation and maturation of cells.

Thus, the regulation of hematopoiesis is a single system consisting of several interconnected links of the cascade mechanism, which responds to changing conditions of the external and internal environment and various pathological conditions (with severe anemia - a decrease in the content of erythrocytes, a decrease in the content of leukocytes, platelets, blood clotting factors, acute blood loss, etc.). Inhibition of hematopoiesis occurs under the influence of inhibitory factors. These include products formed by cells in the last stages of maturation

Blood, sanguis is a special tissue consisting of formed elements (40-45%) and liquid intercellular substance - plasma (55-60% of blood volume).

Blood circulates in blood vessels and is separated from other tissues by the vascular wall, but formed elements, as well as blood plasma, can pass into the connective tissue surrounding the blood vessels. Thanks to this, blood ensures the constancy of the composition of the internal environment of the body.

Blood functions:

1. Transport

Respiratory (transport of oxygen and carbon dioxide)

Excretory (transport of metabolic products - uric acid, bilirubin, etc. to the excretory organs - kidneys, intestines, skin, etc.)

Nutritional (transport of glucose, amino acids, etc.)

Homeostatic (uniform distribution of blood between organs and tissues, maintaining constant osmotic pressure and pH with the help of blood plasma proteins, etc.)

2. Protective (neutralization of microorganisms, toxins, tissue breakdown products, formation of antibodies, blood clot formation)

3. Regulatory

Regulatory (hormone transport)

Thermoregulatory (transfer of heat outward from deep-lying organs to the vessels of the skin, uniform distribution of heat in the body due to the high heat capacity and thermal conductivity of the blood)

In humans, blood mass is 6-8% of body weight (4.5-5 l). At rest, 40-50% of all blood circulates, the rest is in the depot (liver, spleen, skin). The pulmonary circulation contains 20-25% of the blood volume, and the large circulation contains 75-80%. 15-20% of the blood circulates in the arterial system, 70-75% in the venous system, and 5-7% in the capillaries.

Blood composition:

1. formed elements – 40-45% of blood volume

2. blood plasma (intercellular substance) – 55-60% of blood volume (approx. 3 l)

Plasma can be obtained by centrifuging blood - this is a liquid, light yellow part of the blood, without formed elements.

Blood plasma 90% consists of water, in which salts and low molecular weight organic substances are dissolved, and also contains lipids, proteins and their complexes. Proteins (7-8%) are presented:

Fibrinogen, involved in the blood clotting process

Albumin (60% proteins), low molecular weight proteins that transport poorly soluble substances, incl. medicinal

Antibody-forming globulin (high molecular weight protein)

Plasma ensures a constant volume of intravascular fluid and acid-base balance (ABC), and participates in the transfer of active substances and metabolic products.

Blood plasma devoid of fibrinogen is called serum . The whey does not coagulate. The serum remains after blood clotting (when the clot is removed).

Formed elements of blood are divided into:

1. red blood cells,

2. leukocytes and

3. platelets.

All formed elements of blood are formed in the bone marrow from a stem cell, from there they enter the venous blood. All cells perform specific functions, but at the same time, they all participate in the transport of various substances and perform protective and regulatory functions.

The number of formed elements per unit volume of blood is called hemogram- This is a clinical blood test. Includes data on the number of all blood cells, their morphological features, ESR, hemoglobin content, the ratio of different types of leukocytes, etc.

Red blood cells – were first discovered in the blood of a frog by Malpighius (1661), and Leeuwenhoek showed that they are also present in human blood (1673). These are highly specialized anucleate cells with a diameter of 7-8 microns, shaped like a biconcave disk (the surface area of ​​such a disk is 1.7 times greater than spheres of the same diameter). Red blood cells are highly elastic; they easily pass through capillaries, which have half the diameter of the cell itself.

The lifespan of an erythrocyte is about 3 months. Red blood cells are formed in the red bone marrow from precursor cells that lose their nucleus before entering the bloodstream, and die (destroyed) in the spleen and liver.

Functions of red blood cells:

1. Respiratory - hemoglobin is able to bind 70 times more oxygen than dissolved in plasma

2. Nutrient – ​​amino acids are adsorbed on the surface

3. Protective – capable of binding toxins due to antibodies on the surface, and also participate in blood clotting

4. Enzymatic – they are carriers of enzymes.

The cytoplasm of the erythrocyte contains a special protein chromoprotein - hemoglobin, which consists of a protein (globin) and iron-containing (hem) part. Occupies 25% of the erythrocyte volume. For every 1 globin molecule there are 4 heme molecules. A Hb molecule can be associated with 4 oxygen molecules. Fe(II) atoms give individual red blood cells in fresh blood a yellow color, and the blood itself (many red blood cells) a red color. Normally, the blood contains 140 g/l of hemoglobin (women 135-140 g/l, men 135-155 g/l). The content of hemoglobin in erythrocytes is judged by the color indicator (percentage ratio of hemoglobin and erythrocytes), which is normally 0.75-1.0. The main purpose of hemoglobin is the transport of oxygen and carbon dioxide; in addition, it has buffering properties and is able to bind toxic substances.

After the destruction of red blood cells in the spleen, iron atoms are used mainly for the needs of the body; part of the heme is converted into bile pigments (bilirubin and biliverdin), which determine the color of urine and feces.

Types of hemoglobin:

§ Hemoglobin that has added oxygen is called oxyhemoglobin,

§ giving up oxygen – reduced or reduced hemoglobin.

Oxyhemoglobin predominates in arterial blood, which gives it a scarlet color. In venous blood up to 35% of reduced hemoglobin.

§ In addition, part of the hemoglobin binds with carbon dioxide, forming carbohemoglobin, due to which 10 to 20% of all CO 2 transported in the blood is transferred.

§ Carboxyhemoglobin is a compound of hemoglobin and carbon monoxide, which is 300 times easier to attach to hemoglobin than oxygen. Therefore, hemoglobin, which has attached CO, is not able to bind to O2. In case of carbon monoxide poisoning, vomiting, headache, and loss of consciousness are observed; it is necessary to give pure oxygen to breathe, which accelerates the breakdown of carboxyhemoglobin. Normally - about 1% carboxyhemoglobin, in smokers - 3-10%.

§ Strong oxidizing agents (ferrocyanide, hydrogen peroxide, etc.) change the charge of iron from 2+ to 3+, resulting in the formation of oxidized hemoglobin - methemoglobin, which very firmly retains oxygen, while oxygen transport is disrupted. Has a brown color. It is more common among people employed in hazardous chemicals. Production, as well as with excessive consumption of drugs with oxidizing properties.

§ Myoglobin is a respiratory pigment found in muscles; its structure is similar to hemoglobin; is able to bind a much larger amount of oxygen and therefore performs a storage function (oxygen reserve in the muscles)

The blood contains 4-4.5 million red blood cells/ml in women and 4.5-5 million red blood cells/ml in men. An increased number of red blood cells (erythrocytosis) in residents of high mountains, in athletes, in children, with hypoxia, congenital heart defects, cardiovascular failure. A decrease in the amount of hemoglobin in red blood cells is called anemia. The destruction of red blood cells, in which hemoglobin is released into the plasma, is called hemolysis. In this case, the blood takes on a lacquered color. Hemolysis can be caused by chemical agents that destroy the red blood cell membrane (acetic acid poisoning, some snake bites); mechanical hemolysis - when shaking an ampoule with blood, in patients with cardiac valve prostheses, during prolonged walking; immune hemolysis - due to transfusion of incompatible blood.

The specific density of erythrocytes is higher than the density of plasma (1.096 and 1.027), therefore, erythrocyte sedimentation occurs in a vertical test tube (sodium citrate must be added to the blood to prevent blood clotting). The erythrocyte sedimentation rate (ESR) characterizes some physicochemical properties of blood. The greatest influence on the ESR value is exerted by the fibrinogen content (more than 4 g/l ESR increases), therefore ESR depends more on the properties of plasma than erythrocytes. ESR in men is normal 5-7 mm/h, in women 8-12 to 15 mm/h. Increased ESR is typical for pregnant women - up to 30 mm/h, patients with infectious and inflammatory diseases, as well as with malignant tumors - up to 50 mm/h or more.

Hemoglobin is a chromoprotein and contains protein - globin. A solution of such a substance in plasma would increase blood viscosity several times. This would lead to increased blood pressure and the heart would have to pay the price.

Leukocytes – spherical cells, unlike red blood cells, have a nucleus. The size of a leukocyte is up to 20 microns. The lifespan of a leukocyte is several days. 1 ml of blood contains 4-9 thousand leukocytes. The number of leukocytes changes throughout the day, least of all in the morning on an empty stomach. An increase in the number of leukocytes in the blood is leukocytosis, a decrease is leukopenia.

They are formed in the red bone marrow from stem cells, in the spleen, thymus, and lymph nodes. They are destroyed in the spleen and liver.

The lifespan of leukocytes averages from several. Day to several days Tens of days. More than 50% of leukocytes are located outside the vascular cortex - in various tissues.

Leukocytes are capable of active movement (like amoebas), they can penetrate through the capillary wall into the surrounding connective and epithelial tissue and participate in the body’s defense reactions (digestion of foreign bodies, microorganisms, formation of antibodies).

Leukocytes may have granularity (granules) in the cytoplasm - g ranulocytes, which are non-granular - agranulocytes. The granules can be painted in various colors. Depending on the color of the granules, granulocytes are divided into:

- eosinophils(painted pink with acidic dyes) - capable of neutralizing foreign proteins and proteins of dead tissue. The number of eosinophils increases during allergic reactions.

- basophils(colored blue with basic dyes) - take part in blood clotting and regulation of vascular permeability for formed elements. Basophils produce heparin and histamine.

- neutrophils(colored with neutral dyes in pink-violet color) - are able to penetrate into intercellular spaces and capture and digest microorganisms, stimulate cell reproduction. Dead neutrophils, together with the remains of cells and tissues, form pus.

Agranulocytes are leukocytes that consist of a rounded nucleus and non-granular cytoplasm. They are divided into lymphocytes and monocytes.

Lymphocytes– spherical, with a diameter of 7-10 microns. They consist of two populations: lymphocytes formed in the thymus gland (thymus) - T-lymphocytes (responsible for the cellular immunity system and, with the help of enzymes, independently destroy foreign cells, including mutated ones, counteract pathogenic viruses, fungi - T-killers, strengthening cellular immunity or facilitating the course of humoral immunity T-helpers, interfering with immunity during recovery T-suppressors, memory T-cells - store information about previously active antigens, i.e. accelerate the secondary immune response) and B-lymphocytes formed from stem lymphoid cells cells of the bone marrow and spleen, lymphoid accumulations of the wall of the small intestine, tonsils, lymph nodes (they are responsible for the humoral immune system and protect the body from bacteria and viruses by producing special proteins - antibodies). The lifespan of lymphocytes is from 3 days to 6 months, and some – up to 5 years.

Monocytes– the largest blood cells, size up to 20 microns. Formed in the bone marrow. They actively penetrate into areas of inflammation and absorb (phagocytose) bacteria.

The ratio of blood cells is called a hemogram (blood formula), the percentage of different types of leukocytes is called leukocyte formula:

Leukocytes 4-9 *10 9 /l

Eosinophils 1-5%

Basophils 0-0.5%

Neutrophils 60-70%: young 0-1%, band 2-5%,

segmented 55-68%

Lymphocytes 25-30%

Monocytes 5-8%

In the blood of a healthy person, mature and young forms of leukocytes can be found, but normally they can be detected only in the largest group - neutrophils. These include young and band neutrophils. An increase in the number of young and band neutrophils indicates rejuvenation of the blood and is called shift of the leukocyte formula to the left, often observed in leukemia, infectious and inflammatory diseases. In a number of diseases, the number of certain types of leukocytes increases. For whooping cough, typhoid fever - lymphocytes, for malaria - monocytes, for bacterial infections - neutrophils, for allergic reactions - eosinophils.

Platelets– colorless polymorphic anucleate bodies 1-4 microns in size, contain a large number of granules. Platelets are formed in bone marrow cells called megakaryocytes. Their lifespan is 5-11 days. 1 ml of blood contains 180-320 to 400 thousand platelets. During muscular work, stress, eating, pregnancy, the number of platelets increases (thrombocytosis). The main purpose of platelets is to participate in the process of hemostasis (help stop bleeding). When the integrity of the vessel wall is violated, platelets are destroyed and release a specific substance that promotes blood clotting.

When activated, platelets acquire a spherical shape and form special outgrowths (pseudopodia), with the help of which they can connect with each other (aggregate) and adhere to the damaged vessel wall. Platelets contain fibrinogen, as well as the contractile protein thrombastenin. They are rich in glycogen, serotonin (constricts blood vessels), histamine, and contain inactive thromboplastin (triggers coagulation).

Lymph- fluid returned to the bloodstream from tissue spaces through the lymphatic system. Lymph is formed from tissue fluid that accumulates in the intercellular space. The most important function of lymph is to return proteins, electrolytes and water from the interstitial space to the blood. More than 100g is returned per day. squirrel. The lymphatic system acts as a transport system to remove red blood cells remaining in the tissues after bleeding, as well as to remove and neutralize bacteria trapped in the tissues. It consists of plasma and formed elements. Lymphoplasm, unlike blood, contains more metabolic products coming from tissues. Of the formed elements in lymph, lymphocytes predominate (up to 20,000/ml); monocytes and eosinophils are found in small quantities.