Physicochemical properties of blood. Blood buffer systems

Bloodis a liquid connective tissue that circulates in humans and mammals through a closed circulatory system. Its volume normally amounts to 8-10% of a person’s body weight (from 3.5 to 5.5 l ). Being in continuous movement along the vascular bed, blood transfers certain substances from one tissue to another, performing a transport function that predetermines a number of others:

(C) Ø (C) respiratory, consisting of the transport of O 2 from the lungs to the tissues and CO 2 in the opposite direction;

(C) Ø (C) nutritious(trophic), which consists in the transfer of nutrients (amino acids, glucose, fatty acids, etc.) by blood from the gastrointestinal tract, fat depots, liver to all tissues of the body;

(C) Ø (C) excretory(excretory), consisting in the transfer by blood of the final products of metabolism from tissues, where they are constantly formed, to organs excretory system, through which they are eliminated from the body;

(C) Ø (C) humoral regulation (from lat. humor - liquid), which consists in the transport of biologically active substances by blood from the organs where they are synthesized to the tissues on which they have a specific effect;

(C) Ø (C) homeostatic , due to constant blood circulation and interaction with all organs of the body, as a result of which the constancy of both the physicochemical properties of the blood itself and other components is maintained internal environment body;

(C) Ø (C) protective, which is provided in the blood by antibodies, some proteins that have nonspecific bactericidal and antiviral effect(lysozyme, properdin, interferon, complement system), and some leukocytes capable of neutralizing genetically foreign substances that enter the body.

The constant movement of blood is ensured by the activity of the heart - the pump in the cardiovascular system.

Bloodlike other connective tissues, it is composed of cells and intercellular substance. Blood cells are called shaped elements (they account for 40-45% of the total blood volume), and the intercellular substance - plasma (accounts for 55-60% of the total blood volume).

Plasmaconsists of water (90-92%) and dry residue (8-10%), represented by organic and inorganic substances. Moreover, 6-8% of the total plasma volume is proteins, 0.12% is glucose, 0.7-0.8% is fats, less than 0.1% is end products of organic metabolism (creatinine, urea) and 0.9% for mineral salts. Each plasma component performs specific functions. Thus, glucose, amino acids and fats can be used by all cells of the body for construction (plastic) and energy purposes. Blood plasma proteins are presented in three fractions:

(C) Ø (C) albumins(4.5%, globular proteins, differing from others in their smallest size and molecular weight);

(C) Ø (C) globulins(2-3%, globular proteins, larger than albumins);

(C) Ø (C) fibrinogen(0.2-0.4%, fibrillar large molecular protein).

Albumins and globulins perform trophic(nutritional) function: under the influence of plasma enzymes, they are able to partially break down and the resulting amino acids are consumed by tissue cells. At the same time, albumins and globulins bind and deliver to certain tissues biologically active substances, microelements, fats, etc. ( transport function). A subfraction of globulins calledg -globulins and representing antibodies, provides protective function blood. Some globulins take part in blood clotting, and fibrinogen is a precursor of fibrin, which is the basis of a fibrin thrombus formed as a result of blood clotting. In addition, all plasma proteins determine colloid osmotic blood pressure (the proportion of blood osmotic pressure created by proteins and some other colloids is called oncotic pressure ), on which the normal implementation of water-salt exchange between blood and tissues largely depends.

Mineral salts (mainly ions Na + , Cl - , Ca 2+ , K + , HCO 3 - etc.) create blood osmotic pressure (osmotic pressure is the force that determines the movement of a solvent through a semi-permeable membrane from a solution with a lower concentration to a solution with a higher concentration).

Blood cells, called its formed elements, are classified into three groups: red blood cells, white blood cells and blood platelets (platelets) . Red blood cells- these are the most numerous formed elements of blood, which are non-nuclear cells, having the shape of a biconcave disk, diameter 7.4-7.6 microns, thickness from 1.4 to 2 microns. Their number in 1 mm 3 of blood of an adult is from 4 to 5.5 million, and in men this indicator higher than that of women. Red blood cells are formed in the hematopoietic organ - red bone marrow (fills cavities in spongy bones) - from their nuclear precursors, erythroblasts. The lifespan of red blood cells in the blood ranges from 80 to 120 days; they are destroyed in the spleen and liver. The cytoplasm of erythrocytes contains the protein hemoglobin (also called respiratory pigment, it accounts for 90% of the dry residue of the erythrocyte cytoplasm), consisting of a protein part (globin) and a non-protein part (heme). Hemoglobin heme contains an iron atom (in the form Fe 2+ ) and has the ability to bind oxygen at the level of the capillaries of the lungs, turning into oxyhemoglobin, and release oxygen in the capillaries of tissues. The protein part of hemoglobin chemically binds a small amount of CO 2 in the tissues, releasing it in the capillaries of the lungs. Most carbon dioxide is transported by blood plasma in the form of bicarbonates (HCO 3 - ions). Consequently, red blood cells perform their main function - respiratory , being in the bloodstream.

Erotrocyte

Leukocytes- these are white blood cells that differ from red blood cells in the presence of a nucleus, larger size and the ability to amoeboid movement. The latter makes it possible for leukocytes to penetrate the vascular wall into surrounding tissues, where they perform their functions. The number of leukocytes in 1 mm 3 of peripheral blood of an adult is 6-9 thousand and is subject to significant fluctuations depending on the time of day, the state of the body, and the conditions in which it resides. Dimensions various forms leukocytes range from 7 to 15 µm. The duration of stay of leukocytes in the vascular bed is from 3 to 8 days, after which they leave it, moving into the surrounding tissues. Moreover, leukocytes are only transported by blood, and their main functions are protective and trophic - performed in fabrics. Trophic function of leukocytes lies in their ability to synthesize a number of proteins, including enzyme proteins, which are used by tissue cells for construction (plastic) purposes. In addition, some proteins released as a result of the death of leukocytes can also serve to carry out synthetic processes in other cells of the body.

Protective function of leukocytes lies in their ability to free the body from genetically foreign substances (viruses, bacteria, their toxins, mutant cells of one’s own body, etc.), preserving and maintaining the genetic constancy of the body’s internal environment. Protective function of white cells blood can be carried out either

Ø (C) by phagocytosis(“devouring” genetically alien structures),

Ø (C) by damage to the membranes of genetically foreign cells(which is provided by T-lymphocytes and leads to the death of foreign cells),

Ø (C) antibody production (substances of a protein nature that are produced by B-lymphocytes and their descendants - plasma cells and are capable of specifically interacting with foreign substances (antigens) and leading to their elimination (death))

Ø (C) production of a number of substances (for example, interferon, lysozyme, components of the complement system), which capable of exerting nonspecific antiviral or antibacterial effects.

Blood plates (platelets) are fragments of large red bone marrow cells - megakaryocytes. They are nuclear-free, oval-round in shape (in the inactive state they are disc-shaped, and in the active state they are spherical) and differ from other blood cells the smallest sizes(0.5 to 4 µm). Quantity blood platelets in 1 mm 3 of blood is 250-450 thousand. The central part of the blood platelets is granular (granulomere), and the peripheral part does not contain granules (hyalomer). They perform two functions: trophic in relation to the cells of the vascular walls (angiotrophic function: as a result of the destruction of blood platelets, substances are released that are used by the cells for their own needs) and participate in blood clotting. The latter is their main function and is determined by the ability of platelets to crowd and stick together into a single mass at the site of damage to the vascular wall, forming a platelet plug (thrombus), which temporarily plugs a hole in the vessel wall. In addition, according to some researchers, blood platelets are able to phagocytose foreign bodies from the blood and, like other formed elements, fix antibodies on their surface.

Bibliography.

1. Agadzhanyan A.N. Fundamentals of general physiology. M., 2001

Blood is a type of connective tissue consisting of a liquid intercellular substance of complex composition and cells suspended in it - blood cells: erythrocytes (red blood cells), leukocytes (white blood cells) and platelets (blood platelets) (Fig.). 1 mm 3 of blood contains 4.5-5 million red blood cells, 5-8 thousand leukocytes, 200-400 thousand platelets.

When blood cells precipitate in the presence of anticoagulants, a supernatant called plasma is produced. Plasma is an opalescent liquid containing all the extracellular components of blood [show] .

Most of the plasma contains sodium and chloride ions, therefore, in case of large blood losses, an isotonic solution containing 0.85% sodium chloride is injected into the veins to maintain heart function.

The red color of blood is given by red blood cells containing red respiratory pigment - hemoglobin, which absorbs oxygen in the lungs and releases it to the tissues. Blood saturated with oxygen is called arterial, and blood depleted of oxygen is called venous.

Normal blood volume averages 5200 ml in men and 3900 ml in women, or 7-8% of body weight. Plasma makes up 55% of blood volume and formed elements make up 44% of total blood volume, while other cells account for only about 1%.

If blood is allowed to clot and then the clot is separated, blood serum is obtained. Serum is the same plasma, devoid of fibrinogen, which is part of the blood clot.

According to its physicochemical properties, blood is a viscous liquid. The viscosity and density of blood depend on the relative content of blood cells and plasma proteins. Normally, the relative density of whole blood is 1.050-1.064, plasma - 1.024-1.030, cells - 1.080-1.097. The viscosity of blood is 4-5 times higher than the viscosity of water. Viscosity is important in maintaining blood pressure at a constant level.

Blood, carrying out the transport of chemical substances in the body, combines biochemical processes occurring in different cells and intercellular spaces into a single system. Such a close relationship between blood and all tissues of the body makes it possible to maintain a relatively constant chemical composition of the blood due to powerful regulatory mechanisms (CNS, hormonal system, etc.) that ensure a clear relationship in the work of such important organs and tissues as the liver, kidneys, lungs and heart. -vascular system. All random fluctuations in the composition of the blood in a healthy body quickly level out.

In many pathological processes, more or less sharp changes are observed in the chemical composition of the blood, which signal disturbances in the state of human health, make it possible to monitor the development of the pathological process and judge the effectiveness of therapeutic measures.

Erythrocytes, or red blood cells, are small (7-8 microns in diameter) anucleate cells, shaped like a biconcave disk. The absence of a nucleus allows the red blood cell to accommodate a large amount of hemoglobin, and its shape helps to increase its surface area. There are 4-5 million red blood cells in 1 mm 3 of blood. The number of red blood cells in the blood is not constant. It increases with increasing altitude, large losses of water, etc.

Throughout a person's life, red blood cells are formed from nucleated cells in the red bone marrow of the spongy bone. During the process of maturation, they lose their nucleus and enter the blood. The lifespan of human red blood cells is about 120 days, then they are destroyed in the liver and spleen and bile pigment is formed from hemoglobin.

The function of red blood cells is to transport oxygen and partially carbon dioxide. Red blood cells perform this function due to the presence of hemoglobin in them.

Hemoglobin is a red iron-containing pigment consisting of an iron porphyrin group (heme) and globin protein. 100 ml of human blood contains an average of 14 g of hemoglobin. In the pulmonary capillaries, hemoglobin, combining with oxygen, forms a fragile compound - oxidized hemoglobin (oxyhemoglobin) due to divalent heme iron. In the capillaries of tissues, hemoglobin gives up its oxygen and turns into reduced hemoglobin of a darker color, so venous blood flowing from tissues is dark red, and arterial blood, rich in oxygen, is scarlet.

Hemoglobin carries carbon dioxide from tissue capillaries to the lungs [show] .

Carbon dioxide formed in tissues enters red blood cells and, interacting with hemoglobin, is converted into carbonic acid salts - bicarbonates. This transformation occurs in several stages. Oxyhemoglobin in arterial blood erythrocytes is in the form of potassium salt - KHbO 2. In tissue capillaries, oxyhemoglobin gives up its oxygen and loses its acid properties; At the same time, carbon dioxide diffuses into the erythrocyte from the tissues through the blood plasma and, with the help of the enzyme present there - carbonic anhydrase - combines with water, forming carbonic acid - H 2 CO 3. The latter, as an acid stronger than reduced hemoglobin, reacts with its potassium salt, exchanging cations with it:

KHbO 2 → KHb + O 2; CO 2 + H 2 O → H + · NSO - 3;
KHb + H + · НСО — 3 → Н · Нb + K + · НСО — 3 ;

The potassium bicarbonate formed as a result of the reaction dissociates and its anion, due to its high concentration in the erythrocyte and the permeability of the erythrocyte membrane to it, diffuses from the cell into the plasma. The resulting lack of anions in the erythrocyte is compensated by chlorine ions, which diffuse from the plasma into the erythrocytes. In this case, a dissociated sodium salt of bicarbonate is formed in the plasma, and the same dissociated potassium chloride salt is formed in the erythrocyte:

Note that the erythrocyte membrane is impermeable to K and Na cations and that the diffusion of HCO - 3 from the erythrocyte occurs only until its concentration in the erythrocyte and plasma is equalized.

In the capillaries of the lungs, these processes go in the opposite direction:

H Hb + O 2 → H Hb0 2;
H HbO 2 + K HCO 3 → H HCO 3 + K HbO 2.

The resulting carbonic acid is broken down by the same enzyme to H 2 O and CO 2, but as the HCO 3 content in the erythrocyte decreases, these anions from the plasma diffuse into it, and the corresponding amount of Cl anions leaves the erythrocyte into the plasma. Consequently, oxygen in the blood is bound to hemoglobin, and carbon dioxide exists in the form of bicarbonate salts.

100 ml of arterial blood contains 20 ml of oxygen and 40-50 ml of carbon dioxide, venous blood contains 12 ml of oxygen and 45-55 ml of carbon dioxide. Only a very small proportion of these gases are directly dissolved in blood plasma. The bulk of blood gases, as can be seen from the above, are in a chemically bound form. With a reduced number of red blood cells in the blood or hemoglobin in red blood cells, a person develops anemia: the blood is poorly saturated with oxygen, so organs and tissues receive insufficient amounts of it (hypoxia).

Leukocytes, or white blood cells, - colorless blood cells with a diameter of 8-30 microns, of variable shape, having a nucleus; The normal number of leukocytes in the blood is 6-8 thousand per 1 mm3. Leukocytes are formed in the red bone marrow, liver, spleen, lymph nodes; their lifespan can vary from several hours (neutrophils) to 100-200 or more days (lymphocytes). They are also destroyed in the spleen.

Based on their structure, leukocytes are divided into several [the link is available to registered users who have 15 messages on the forum], each of which performs specific functions. The percentage of these groups of leukocytes in the blood is called the leukocyte formula.

The main function of leukocytes is to protect the body from bacteria, foreign proteins, and foreign bodies. [show] .

By modern views body protection, i.e. its immunity to various factors that carry genetically foreign information is ensured by immunity, represented by a variety of cells: leukocytes, lymphocytes, macrophages, etc., thanks to which foreign cells or complex organic substances that enter the body, different from the cells and substances of the body, are destroyed and eliminated .

Immunity maintains the genetic constancy of the organism in ontogenesis. When cells divide as a result of mutations in the body, cells with an altered genome are often formed. To ensure that these mutant cells during further division do not lead to disturbances in the development of organs and tissues, they are destroyed by the body’s immune systems. In addition, immunity is manifested in the body's immunity to transplanted organs and tissues from other organisms.

The first scientific explanation of the nature of immunity was given by I. I. Mechnikov, who came to the conclusion that immunity is provided due to the phagocytic properties of leukocytes. Later it was found that, in addition to phagocytosis (cellular immunity), the ability of leukocytes to produce protective substances - antibodies, which are soluble protein substances - immunoglobulins (humoral immunity), produced in response to the appearance of foreign proteins in the body, is of great importance for immunity. In blood plasma, antibodies glue foreign proteins together or break them down. Antibodies that neutralize microbial poisons (toxins) are called antitoxins.

All antibodies are specific: they are active only against certain microbes or their toxins. If a person’s body has specific antibodies, it becomes immune to certain infectious diseases.

There are innate and acquired immunity. The first provides immunity to a particular infectious disease from the moment of birth and is inherited from parents, and immune bodies can penetrate through the placenta from the vessels of the mother’s body into the vessels of the embryo or newborns receive them with mother’s milk.

Acquired immunity appears after suffering an infectious disease, when antibodies are formed in the blood plasma in response to foreign proteins of a given microorganism. In this case, natural, acquired immunity occurs.

Immunity can be developed artificially by introducing weakened or killed pathogens of a disease into the human body (for example, smallpox vaccination). This immunity does not occur immediately. For its manifestation, time is required for the body to produce antibodies against the introduced weakened microorganism. Such immunity usually lasts for years and is called active.

The world's first vaccination against smallpox was carried out by the English doctor E. Jenner.

Immunity acquired by introducing immune serum from the blood of animals or humans into the body is called passive (for example, anti-measles serum). It appears immediately after the administration of the serum, persists for 4-6 weeks, and then the antibodies are gradually destroyed, immunity weakens, and repeated administration of the immune serum is necessary to maintain it.

The ability of leukocytes to move independently with the help of pseudopods allows them, making amoeboid movements, to penetrate through the walls of capillaries into the intercellular spaces. They are sensitive to the chemical composition of substances secreted by microbes or decayed cells of the body, and move towards these substances or decayed cells. Having come into contact with them, leukocytes envelop them with their pseudopods and pull them into the cell, where they are broken down with the participation of enzymes (intracellular digestion). In the process of interaction with foreign bodies many leukocytes die. In this case, decay products accumulate around the foreign body and pus is formed.

This phenomenon was discovered by I.I. Mechnikov. I. I. Mechnikov called leukocytes that capture various microorganisms and digest them phagocytes, and the phenomenon of absorption and digestion itself was called phagocytosis. Phagocytosis is a protective reaction of the body.

The phagocytic ability of leukocytes is extremely important because it protects the body from infection. But in certain cases, this property of white blood cells can be harmful, for example during organ transplantation. Leukocytes react to transplanted organs in the same way as to pathogenic microorganisms - they phagocytose and destroy them. To avoid an undesirable reaction of leukocytes, phagocytosis is inhibited with special substances.

Platelets, or blood platelets, - colorless cells 2-4 microns in size, the number of which is 200-400 thousand in 1 mm 3 of blood. They are formed in the bone marrow. Platelets are very fragile and are easily destroyed when blood vessels are damaged or when blood comes into contact with air. At the same time, a special substance thromboplastin is released from them, which promotes blood clotting.

Blood plasma proteins

Of the 9-10% of the dry residue of blood plasma, proteins account for 6.5-8.5%. Using the method of salting out with neutral salts, blood plasma proteins can be divided into three groups: albumins, globulins, fibrinogen. The normal content of albumin in blood plasma is 40-50 g/l, globulin - 20-30 g/l, fibrinogen - 2-4 g/l. Blood plasma devoid of fibrinogen is called serum.

The synthesis of blood plasma proteins occurs primarily in the cells of the liver and reticuloendothelial system. The physiological role of blood plasma proteins is multifaceted.

1. Proteins maintain colloid osmotic (oncotic) pressure and thereby maintain a constant blood volume. The protein content in plasma is significantly higher than in tissue fluid. Proteins, being colloids, bind water and retain it, preventing it from leaving the bloodstream. Despite the fact that oncotic pressure makes up only a small part (about 0.5%) of the total osmotic pressure, it determines the predominance of the osmotic pressure of the blood over the osmotic pressure of the tissue fluid. It is known that in the arterial part of the capillaries, as a result of hydrostatic pressure, protein-free blood fluid penetrates into the tissue space. This occurs up to a certain point - the “turning point”, when the falling hydrostatic pressure becomes equal to the colloid-osmotic pressure. After the “turning” moment, a reverse flow of fluid from the tissue occurs in the venous part of the capillaries, since now the hydrostatic pressure is less than the colloid osmotic pressure. Under other conditions, hydrostatic pressure in the circulatory system would cause water to seep into the tissue, causing swelling various organs and subcutaneous tissue.
2. Plasma proteins take an active part in blood clotting. A number of plasma proteins, including fibrinogen, are the main components of the blood coagulation system.
3. Plasma proteins to a certain extent determine the viscosity of the blood, which, as already noted, is 4-5 times higher than the viscosity of water and plays an important role in maintaining hemodynamic relations in the circulatory system.
4. Plasma proteins take part in maintaining a constant blood pH, as they constitute one of the most important buffer systems in the blood.
5. The transport function of blood plasma proteins is also important: combining with a number of substances (cholesterol, bilirubin, etc.), as well as with drugs (penicillin, salicylates, etc.), they transport them into the tissue.
6. Blood plasma proteins play an important role in immune processes (especially immunoglobulins).
7. As a result of the formation of non-dialyzable compounds with plasma proteins, the level of cations in the blood is maintained. For example, 40-50% of serum calcium is bound to proteins, and a significant portion of iron, magnesium, copper and other elements are also bound to whey proteins.
8. Finally, blood plasma proteins can serve as a reserve of amino acids.

Modern physicochemical research methods have made it possible to discover and describe about 100 different protein components of blood plasma. At the same time, the electrophoretic separation of blood plasma (serum) proteins has acquired particular importance. [show] .

In the blood serum of a healthy person, electrophoresis on paper can detect five fractions: albumin, α 1, α 2, β- and γ-globulins (Fig. 125). By electrophoresis in agar gel, up to 7-8 fractions are detected in blood serum, and by electrophoresis in starch or polyacrylamide gel - up to 16-17 fractions.

It should be remembered that the terminology of protein fractions obtained by various types of electrophoresis has not yet been completely established. When changing electrophoresis conditions, as well as during electrophoresis in different media (for example, in starch or polyacrylamide gel), the migration rate and, consequently, the order of protein zones can change.

An even larger number of protein fractions (about 30) can be obtained using the immunoelectrophoresis method. Immunoelectrophoresis is a unique combination of electrophoretic and immunological methods for analyzing proteins. In other words, the term “immunoelectrophoresis” means carrying out electrophoresis and precipitation reactions in the same medium, i.e. directly on the gel block. At this method Using the serological precipitation reaction, a significant increase in the analytical sensitivity of the electrophoretic method is achieved. In Fig. 126 shows a typical immunoelectropherogram of human serum proteins.

Characteristics of the main protein fractions

• Albumin [show] .

  Albumin accounts for more than half (55-60%) of human blood plasma proteins. The molecular weight of albumin is about 70,000. Serum albumin is renewed relatively quickly (the half-life of human albumin is 7 days).

  Due to their high hydrophilicity, especially due to the relatively small size of the molecules and significant concentration in the serum, albumins play an important role in maintaining the colloid osmotic pressure of the blood. It is known that serum albumin concentrations below 30 g/l cause significant changes in blood oncotic pressure, which leads to edema. Albumin perform important function for the transport of many biologically active substances (in particular, hormones). They are able to bind to cholesterol and bile pigments. A significant portion of serum calcium is also bound to albumin.

  When electrophoresis in starch gel, the albumin fraction in some people is sometimes divided into two (albumin A and albumin B), i.e., such people have two independent genetic loci that control albumin synthesis. The additional fraction (albumin B) differs from regular serum albumin in that the molecules of this protein contain two or more dicarboxylic amino acid residues that replace tyrosine or cystine residues in the polypeptide chain of regular albumin. There are other rare variants of albumin (Reading albumin, Gent albumin, Maki albumin). Inheritance of albumin polymorphism occurs in an autosomal codominant manner and is observed over several generations.

  In addition to hereditary albumin polymorphism, transient bisalbuminemia occurs, which in some cases can be mistaken for congenital. The appearance of a fast component of albumin in patients receiving large doses of penicillin has been described. After discontinuation of penicillin, this fast component of albumin soon disappeared from the blood. There is an assumption that an increase in the electrophoretic mobility of the albumin - antibiotic fraction is associated with an increase negative charge complex due to the COOH groups of penicillin.

• Globulins [show] .

  When salted out with neutral salts, serum globulins can be divided into two fractions - euglobulins and pseudoglobulins. It is believed that the euglobulin fraction mainly consists of γ-globulins, and the pseudoglobulin fraction includes α-, β- and γ-globulins.

  α-, β- and γ-globulins are heterogeneous fractions that, during electrophoresis, especially in starch or polyacrylamide gels, can be separated into a number of subfractions. It is known that α- and β-globulin fractions contain lipoproteins and glycoproteins. Among the components of α- and β-globulins there are also metal-bound proteins. Most of the antibodies contained in serum are in the γ-globulin fraction. Reducing the protein content of this fraction sharply reduces protective forces body.

In clinical practice, there are conditions characterized by changes in both the total amount of blood plasma proteins and the percentage of individual protein fractions.

As noted, α- and β-globulin fractions of serum proteins contain lipoproteins and glycoproteins. The carbohydrate part of blood glycoproteins mainly includes the following monosaccharides and their derivatives: galactose, mannose, fucose, rhamnose, glucosamine, galactosamine, neuraminic acid and its derivatives (sialic acids). The ratio of these carbohydrate components in individual serum glycoproteins is different.

Most often, aspartic acid (its carboxyl) and glucosamine take part in the connection between the protein and carbohydrate parts of the glycoprotein molecule. Somewhat less common is the connection between the hydroxyl of threonine or serine and hexosamines or hexoses.

Neuramic acid and its derivatives (sialic acids) are the most labile and active ingredients glycoproteins. They occupy the final position in the carbohydrate chain of the glycoprotein molecule and largely determine the properties of this glycoprotein.

Glycoproteins are present in almost all protein fractions of blood serum. When electrophoresis on paper, glycoproteins are detected in greater quantities in the α 1 - and α 2 -fractions of globulins. Glycoproteins associated with α-globulin fractions contain little fucose; at the same time, glycoproteins detected in the β- and especially γ-globulin fractions contain significant amounts of fucose.

An increased content of glycoproteins in plasma or serum is observed in tuberculosis, pleurisy, pneumonia, acute rheumatism, glomerulonephritis, nephrotic syndrome, diabetes, myocardial infarction, gout, as well as in acute and chronic leukemia, myeloma, lymphosarcoma and some other diseases. In patients with rheumatism, an increase in the content of glycoproteins in the serum corresponds to the severity of the disease. This is explained, according to a number of researchers, by depolymerization of the main substance of connective tissue during rheumatism, which leads to the entry of glycoproteins into the blood.

Plasma lipoproteins- these are complex complex compounds with a characteristic structure: inside the lipoprotein particle there is a fat drop (core) containing non-polar lipids (triglycerides, esterified cholesterol). The fat droplet is surrounded by a membrane that contains phospholipids, protein and free cholesterol. The main function of plasma lipoproteins is the transport of lipids in the body.

Several classes of lipoproteins have been found in human blood plasma.

• α-lipoproteins, or high-density lipoproteins (HDL). During electrophoresis on paper, they migrate together with α-globulins. HDL is rich in protein and phospholipids, and is constantly found in the blood plasma of healthy people at a concentration of 1.25-4.25 g/l in men and 2.5-6.5 g/l in women.
• β-lipoproteins, or low-density lipoproteins (LDL). They correspond in electrophoretic mobility to β-globulins. They are the most cholesterol-rich class of lipoproteins. LDL level in the blood plasma of healthy people is 3.0-4.5 g/l.
• pre-β-lipoproteins, or very low density lipoproteins (VLDL). Located on the lipoproteinogram between α- and β-lipoproteins (electrophoresis on paper), they serve as the main transport form of endogenous triglycerides.
• Chylomicrons (CM). They do not move during electrophoresis either to the cathode or to the anode and remain at the start (the place where the test plasma or serum sample is applied). They are formed in the intestinal wall during the absorption of exogenous triglycerides and cholesterol. First, chemical substances enter the thoracic lymphatic duct, and from it into the bloodstream. ChMs are the main transport form of exogenous triglycerides. The blood plasma of healthy people who have not eaten for 12-14 hours does not contain CM.

It is believed that the main place of formation of plasma pre-β-lipoproteins and α-lipoproteins is the liver, and β-lipoproteins are formed from pre-β-lipoproteins in the blood plasma under the action of lipoprotein lipase.

It should be noted that electrophoresis of lipoproteins can be carried out both on paper and in agar, starch and polyacrylamide gels, cellulose acetate. When choosing an electrophoresis method, the main criterion is to clearly obtain four types of lipoproteins. Electrophoresis of lipoproteins in polyacrylamide gel is currently the most promising. In this case, the fraction of pre-β-lipoproteins is detected between CM and β-lipoproteins.

In a number of diseases, the lipoprotein spectrum of blood serum may change.

According to the existing classification of hyperlipoproteinemia, the following five types of deviation of the lipoprotein spectrum from the norm have been established [show] .

• Type I - hyperchylomicronemia. The main changes in the lipoproteinogram are as follows: high content of CM, normal or slightly increased content pre-β-lipoproteins. Sharp increase serum triglyceride levels. Clinically, this condition manifests itself as xanthomatosis.
• Type II - hyper-β-lipoproteinemia. This type is divided into two subtypes:
  • IIa, characterized by a high level of p-lipoproteins (LDL) in the blood,
  • IIb, characterized by a high content of two classes of lipoproteins simultaneously - β-lipoproteins (LDL) and pre-β-lipoproteins (VLDL).

  In type II, there is a high, and in some cases very high, cholesterol content in the blood plasma. The content of triglycerides in the blood can be either normal (type IIa) or elevated (type IIb). Type II is clinically manifested by atherosclerotic disorders, and coronary heart disease often develops.

• Type III - “floating” hyperlipoproteinemia or dys-β-lipoproteinemia. Lipoproteins with an unusually high cholesterol content and high electrophoretic mobility (“pathological” or “floating” β-lipoproteins) appear in the blood serum. They accumulate in the blood due to a violation of the conversion of pre-β-lipoproteins into β-lipoproteins. This type of hyperlipoproteinemia is often combined with various manifestations atherosclerosis, including coronary heart disease and damage to the blood vessels of the legs.
• Type IV - hyperpre-β-lipoproteinemia. Increased levels of pre-β-lipoproteins, normal levels of β-lipoproteins, absence of CM. Increased triglyceride levels with normal or slightly elevated cholesterol levels. Clinically, this type is combined with diabetes, obesity, and coronary heart disease.
• Type V - hyperpre-β-lipoproteinemia and chylomicronemia. There is an increase in the level of pre-β-lipoproteins and the presence of CM. Clinically manifested by xanthomatosis, sometimes combined with latent diabetes. Coronary heart disease is not observed with this type of hyperlipoproteinemia.

Some of the most studied and clinically interesting plasma proteins

• Haptoglobin [show] .

  Haptoglobin is part of the α 2 -globulin fraction. This protein has the ability to bind to hemoglobin. The resulting haptoglobin-hemoglobin complex can be absorbed by the reticuloendothelial system, thereby preventing the loss of iron, which is part of hemoglobin, both during physiological and pathological release from erythrocytes.

  Electrophoresis revealed three groups of haptoglobins, which were designated as Hp 1-1, Hp 2-1 and Hp 2-2. It has been established that there is a connection between the inheritance of haptoglobin types and Rh antibodies.

• Trypsin inhibitors [show] .

  It is known that during electrophoresis of blood plasma proteins, proteins capable of inhibiting trypsin and other proteolytic enzymes move in the zone of α 1 and α 2 globulins. Normally, the content of these proteins is 2.0-2.5 g/l, but during inflammatory processes in the body, during pregnancy and a number of other conditions, the content of proteins - inhibitors of proteolytic enzymes increases.

• Transferrin [show] .

  Transferrin belongs to β-globulins and has the ability to combine with iron. Its complex with iron is orange. In the iron transferrin complex, iron is in the trivalent form. The concentration of transferrin in the blood serum is about 2.9 g/l. Normally, only 1/3 of transferrin is saturated with iron. Consequently, there is a certain reserve of transferrin capable of binding iron. Transferrin different people may belong to different types. 19 types of transferrin have been identified, differing in the charge of the protein molecule, its amino acid composition and the number of sialic acid molecules associated with the protein. The detection of different types of transferrins is associated with heredity.

• Ceruloplasmin [show] .

  This protein has a bluish color due to the presence of 0.32% copper in its composition. Ceruloplasmin is an oxidase of ascorbic acid, adrenaline, dioxyphenylalanine and some other compounds. In hepatolenticular degeneration (Wilson-Konovalov disease), the content of ceruloplasmin in the blood serum is significantly reduced, which is an important diagnostic test.

  Using enzyme electrophoresis, the presence of four isoenzymes of ceruloplasmin was established. Normally, two isoenzymes are found in the blood serum of adults, which differ markedly in their mobility when electrophoresed in acetate buffer at pH 5.5. Two fractions were also found in the serum of newborn children, but these fractions have a higher electrophoretic mobility than adult ceruloplasmin isoenzymes. It should be noted that in terms of its electrophoretic mobility, the isoenzyme spectrum of ceruloplasmin in blood serum in Wilson-Konovalov disease is similar to the isoenzyme spectrum of newborn children.

• C-reactive protein [show] .

  This protein received its name as a result of its ability to undergo a precipitation reaction with the C-polysaccharide of pneumococci. C-reactive protein is absent in the blood serum of a healthy body, but is found in many pathological conditions accompanied by inflammation and tissue necrosis.

  C-reactive protein appears during the acute period of the disease, so it is sometimes called the “acute phase” protein. With the transition to the chronic phase of the disease, C-reactive protein disappears from the blood and appears again when the process worsens. During electrophoresis, the protein moves together with α 2 globulins.

• Cryoglobulin [show] .

  Cryoglobulin is also absent in the blood serum of healthy people and appears in it under pathological conditions. A distinctive property of this protein is the ability to precipitate or gel when the temperature drops below 37°C. During electrophoresis, cryoglobulin most often moves together with γ-globulins. Cryoglobulin can be detected in blood serum in cases of myeloma, nephrosis, liver cirrhosis, rheumatism, lymphosarcoma, leukemia and other diseases.

• Interferon [show] .

  Interferon- a specific protein synthesized in the cells of the body as a result of exposure to viruses. In turn, this protein has the ability to inhibit the reproduction of the virus in cells, but does not destroy existing viral particles. The interferon formed in the cells easily enters the bloodstream and from there re-enters the tissues and cells. Interferon is species specific, although not absolute. For example, monkey interferon inhibits the reproduction of the virus in human cell culture. The protective effect of interferon depends largely on the relationship between the rates of spread of the virus and interferon in the blood and tissues.

• Immunoglobulins [show] .

  Until recently, four main classes of immunoglobulins included in the γ-globulin fraction were known: IgG, IgM, IgA and IgD. In recent years, a fifth class of immunoglobulins, IgE, has been discovered. Immunoglobulins practically have a single structure plan; they consist of two heavy polypeptide chains H (mol. wt 50,000-75,000) and two light chains L (mol. wt ~ 23,000), connected by three disulfide bridges. In this case, human immunoglobulins can contain two types of L chains (K or λ). In addition, each class of immunoglobulins has its own type heavy chains H: IgG - γ-chain, IgA - α-chain, IgM - μ-chain, IgD - σ-chain and IgE - ε-chain, which differ in amino acid composition. IgA and IgM are oligomers, i.e. the four-chain structure in them is repeated several times.

  
  

  Each type of immunoglobulin can specifically interact with a specific antigen. The term "immunoglobulins" refers not only to normal classes of antibodies, but also to more so-called pathological proteins, for example myeloma proteins, the increased synthesis of which occurs when multiple myeloma. As already noted, in the blood of this disease, myeloma proteins accumulate in relatively high concentrations, and Bence-Jones protein is found in the urine. It turned out that Bence-Jones protein consists of L-chains, which are apparently synthesized in the patient's body in excess quantities compared to H-chains and are therefore excreted in the urine. The C-terminal half of the polypeptide chain of Bence-Jones protein molecules (actually L-chains) in all patients with multiple myeloma has the same sequence, and the N-terminal half (107 amino acid residues) of the L-chains has a different primary structure. A study of the N-chains of myeloma blood plasma proteins also revealed an important pattern: the N-terminal fragments of these chains in different patients have different primary structures, while the rest of the chain remains unchanged. It was concluded that the variable regions of the L- and H-chains of immunoglobulins are the site of specific binding of antigens.

  In many pathological processes, the content of immunoglobulins in blood serum changes significantly. Thus, with chronic aggressive hepatitis there is an increase in IgG, with alcoholic cirrhosis - IgA and with primary biliary cirrhosis - IgM. It has been shown that the concentration of IgE in blood serum increases in bronchial asthma, nonspecific eczema, ascariasis and some other diseases. It is important to note that children who have IgA deficiency are more likely to have infectious diseases. It can be assumed that this is a consequence of insufficient synthesis of a certain part of the antibodies.

  Complement system

  The complement system of human blood serum includes 11 proteins with a molecular weight from 79,000 to 400,000. The cascade mechanism of their activation is triggered during the reaction (interaction) of an antigen with an antibody:

  

  As a result of the action of complement, the destruction of cells through their lysis, as well as the activation of leukocytes and their absorption of foreign cells as a result of phagocytosis are observed.

  According to the sequence of functioning, proteins of the human serum complement system can be divided into three groups:

  1. “recognition group”, which includes three proteins and binds the antibody on the surface of the target cell (this process is accompanied by the release of two peptides);
  2. both peptides on another part of the surface of the target cell interact with three proteins of the “activating group” of the complement system, and two peptides are also formed;
  3. newly isolated peptides contribute to the formation of a group of “membrane attack” proteins, consisting of 5 proteins of the complement system, cooperatively interacting with each other on the third area of ​​the surface of the target cell. The binding of membrane attack proteins to the cell surface destroys it by forming end-to-end channels in the membrane.

  Blood plasma (serum) enzymes

  Enzymes that are normally found in plasma or serum can, however somewhat arbitrarily, be divided into three groups:

  • Secretory - synthesized in the liver, they are normally released into the blood plasma, where they play a certain physiological role. Typical representatives of this group are enzymes involved in the process of blood clotting (see p. 639). Serum cholinesterase belongs to this group.
  • Indicator (cellular) enzymes perform certain intracellular functions in tissues. Some of them are concentrated mainly in the cytoplasm of the cell (lactate dehydrogenase, aldolase), others - in mitochondria (glutamate dehydrogenase), others - in lysosomes (β-glucuronidase, acid phosphatase), etc. Most of the indicator enzymes in blood serum are determined only in trace amounts. When certain tissues are damaged, the activity of many indicator enzymes increases sharply in the blood serum.
  • Excretory enzymes are synthesized mainly in the liver (leucine aminopeptidase, alkaline phosphatase, etc.). Under physiological conditions, these enzymes are mainly excreted in bile. The mechanisms regulating the entry of these enzymes into bile capillaries have not yet been fully elucidated. In many pathological processes, the release of these enzymes with bile is disrupted and the activity of excretory enzymes in the blood plasma increases.

  Of particular clinical interest is the study of the activity of indicator enzymes in blood serum, since the appearance of a number of tissue enzymes in unusual quantities in plasma or serum can indicate functional state and diseases of various organs (for example, liver, cardiac and skeletal muscles).

  Thus, from the point of view of diagnostic value, studies of enzyme activity in blood serum during acute myocardial infarction can be compared with the electrocardiographic diagnostic method introduced several decades ago. Determination of enzyme activity during myocardial infarction is advisable in cases where the course of the disease and electrocardiographic data are atypical. In acute myocardial infarction, it is especially important to study the activity of creatine kinase, aspartate aminotransferase, lactate dehydrogenase and hydroxybutyrate dehydrogenase.

  In case of liver diseases, in particular with viral hepatitis (Botkin's disease), the activity of alanine and aspartate aminotransferases, sorbitol dehydrogenase, glutamate dehydrogenase and some other enzymes in the blood serum changes significantly, and the activity of histidase and urocaninase appears. Most of the enzymes contained in the liver are also present in other organs and tissues. However, there are enzymes that are more or less specific to liver tissue. Organ-specific enzymes for the liver are: histidase, urocaninase, ketose-1-phosphate aldolase, sorbitol dehydrogenase; ornithine carbamoyltransferase and, to a slightly lesser extent, glutamate dehydrogenase. Changes in the activity of these enzymes in the blood serum indicate damage to the liver tissue.

  In the last decade, the study of isoenzyme activity in blood serum, in particular lactate dehydrogenase isoenzymes, has become a particularly important laboratory test.

  It is known that in the heart muscle the isoenzymes LDH 1 and LDH 2 are most active, and in the liver tissue - LDH 4 and LDH 5. It has been established that in patients with acute myocardial infarction, the activity of isoenzymes LDH 1 and partly LDH 2 sharply increases in the blood serum. The isoenzyme spectrum of lactate dehydrogenase in blood serum during myocardial infarction resembles the isoenzyme spectrum of the heart muscle. On the contrary, with parenchymal hepatitis in the blood serum the activity of the isoenzymes LDH 5 and LDH 4 increases significantly and the activity of LDH 1 and LDH 2 decreases.

  The study of the activity of creatine kinase isoenzymes in blood serum is also of diagnostic importance. There are at least three creatine kinase isoenzymes: BB, MM and MB. The BB isoenzyme is mainly present in brain tissue, and the MM form is present in skeletal muscles. The heart contains predominantly the MM form, as well as the MV form.

  Creatine kinase isoenzymes are especially important to study in acute myocardial infarction, since the MB form is found in significant quantities almost only in the heart muscle. Therefore, an increase in the activity of the MB form in the blood serum indicates damage to the heart muscle. Apparently, the increase in enzyme activity in the blood serum in many pathological processes is explained by at least two reasons: 1) the release of enzymes into the bloodstream from damaged areas of organs or tissues against the background of their ongoing biosynthesis in damaged tissues and 2) a simultaneous sharp increase in catalytic activity tissue enzymes that pass into the blood.

  It is possible that a sharp increase in enzyme activity when the mechanisms of intracellular regulation of metabolism break down is associated with the cessation of the action of the corresponding enzyme inhibitors, a change under the influence of various factors in the secondary, tertiary and quaternary structures of enzyme macromolecules, which determine their catalytic activity.

  Non-protein nitrogenous components of blood

  The content of non-protein nitrogen in whole blood and plasma is almost the same and is 15-25 mmol/l in the blood. Non-protein nitrogen in the blood includes urea nitrogen (50% of the total amount of non-protein nitrogen), amino acids (25%), ergothioneine - a compound found in red blood cells (8%), uric acid (4%), creatine (5%), creatinine ( 2.5%), ammonia and indican (0.5%) and other non-protein substances containing nitrogen (polypeptides, nucleotides, nucleosides, glutathione, bilirubin, choline, histamine, etc.). Thus, the composition of non-protein nitrogen in the blood consists mainly of nitrogen from the end products of metabolism of simple and complex proteins.

  Non-protein nitrogen in the blood is also called residual nitrogen, that is, remaining in the filtrate after precipitation of proteins. In a healthy person, fluctuations in the content of non-protein, or residual, blood nitrogen are insignificant and mainly depend on the amount of protein ingested from food. In a number of pathological conditions, the level of non-protein nitrogen in the blood increases. This condition is called azotemia. Azotemia, depending on the reasons that caused it, is divided into retention and production. Retention azotemia occurs as a result of insufficient excretion of nitrogen-containing products in the urine during their normal entry into the bloodstream. It, in turn, can be renal or extrarenal.

  With renal retention azotemia, the concentration of residual nitrogen in the blood increases due to a weakening of the cleansing (excretory) function of the kidneys. A sharp increase in the content of residual nitrogen during retention renal azotemia occurs mainly due to urea. In these cases, urea nitrogen accounts for 90% of the non-protein nitrogen in the blood instead of 50% normally. Extrarenal retention azotemia may result from severe circulatory failure, decreased blood pressure, and decreased renal blood flow. Often, extrarenal retention azotemia is the result of an obstruction to the outflow of urine after its formation in the kidney.

  Table 46. Content of free amino acids in human blood plasma
  Amino acids	Content, µmol/l
  Alanin	360-630
  Arginine	92-172
  Asparagine	50-150
  Aspartic acid	150-400
  Valin	188-274
  Glutamic acid	54-175
  Glutamine	514-568
  Glycine	100-400
  Histidine	110-135
  Isoleucine	122-153
  Leucine	130-252
  Lysine	144-363
  Methionine	20-34
  Ornithine	30-100
  Proline	50-200
  Serin	110
  Threonine	160-176
  Tryptophan	49
  Tyrosine	78-83
  Phenylalanine	85-115
  Citrulline	10-50
  Cystine	84-125

  Productive azotemia observed when there is an excessive intake of nitrogen-containing products into the blood, as a result of increased breakdown of tissue proteins. Mixed azotemia is often observed.

  As already noted, in terms of quantity, the main end product of protein metabolism in the body is urea. It is generally accepted that urea is 18 times less toxic than other nitrogenous substances. In acute renal failure, the concentration of urea in the blood reaches 50-83 mmol/l (normal 3.3-6.6 mmol/l). An increase in the urea content in the blood to 16.6-20.0 mmol/l (calculated on urea nitrogen [The value of the urea nitrogen content is approximately 2 times, or more precisely 2.14 times less than the number expressing the concentration of urea.]) is a sign renal dysfunction moderate severity, up to 33.3 mmol/l - severe and over 50 mmol/l - very severe disorder with a poor prognosis. Sometimes a special coefficient is determined or, more precisely, the ratio of blood urea nitrogen to residual blood nitrogen, expressed as a percentage: (Urea Nitrogen / Residual Nitrogen) X 100

  Normally the ratio is below 48%. With renal failure, this figure increases and can reach 90%, and if the urea-forming function of the liver is impaired, the coefficient decreases (below 45%).

  Uric acid is also an important protein-free nitrogenous substance in the blood. Let us recall that in humans, uric acid is the end product of the metabolism of purine bases. Normally, the concentration of uric acid in whole blood is 0.18-0.24 mmol/l (in serum - about 0.29 mmol/l). An increase in uric acid in the blood (hyperuricemia) is the main symptom of gout. With gout, the level of uric acid in the blood serum increases to 0.47-0.89 mmol/l and even to 1.1 mmol/l; The residual nitrogen also includes nitrogen from amino acids and polypeptides.

  The blood always contains a certain amount of free amino acids. Some of them are of exogenous origin, that is, they enter the blood from the gastrointestinal tract, while the other part of the amino acids is formed as a result of the breakdown of tissue proteins. Almost a fifth of the amino acids contained in plasma are glutamic acid and glutamine (Table 46). Naturally, the blood contains aspartic acid, asparagine, cysteine, and many other amino acids that are part of natural proteins. The content of free amino acids in serum and blood plasma is almost the same, but differs from their level in erythrocytes. Normally, the ratio of the amino acid nitrogen concentration in erythrocytes to the amino acid nitrogen content in plasma ranges from 1.52 to 1.82. This ratio (coefficient) is characterized by great constancy, and only in some diseases is its deviation from the norm observed.

  Total determination of the level of polypeptides in the blood is performed relatively rarely. However, it should be remembered that many of the blood polypeptides are biologically active compounds and their determination is of great clinical interest. Such compounds, in particular, include kinins.

  Kinins and blood kinin system

  Kinins are sometimes called kinin hormones, or local hormones. They are not produced in specific endocrine glands, but are released from inactive precursors that are constantly present in the interstitial fluid of a number of tissues and in the blood plasma. Kinins are characterized by a wide range of biological effects. This action is mainly aimed at the smooth muscles of blood vessels and the capillary membrane; hypotensive effect is one of the main manifestations of the biological activity of kinins.

  

  The most important plasma kinins are bradykinin, kallidin and methionyl-lysyl-bradykinin. In fact, they form a kinin system, which ensures the regulation of local and general blood flow and the permeability of the vascular wall.

  The structure of these kinins has been fully established. Bradykinin is a polypeptide of 9 amino acids, kallidin (lysyl-bradykinin) is a polypeptide of 10 amino acids.

  In blood plasma, the content of kinins is usually very low (for example, bradykinin 1-18 nmol/l). The substrate from which kinins are released is called kininogen. There are several kininogens in the blood plasma (at least three). Kininogens are proteins associated in the blood plasma with the α 2 -globulin fraction. The site of kininogen synthesis is the liver.

  The formation (cleavage) of kinins from kininogens occurs with the participation of specific enzymes - kininogenases, which are called kallikreins (see diagram). Kallikreins are trypsin-type proteinases; they break peptide bonds in the formation of which the NOOS groups of arginine or lysine are involved; Proteolysis of proteins in a broad sense is not characteristic of these enzymes.

  There are blood plasma kallikreins and tissue kallikreins. One of the kallikrein inhibitors is a polyvalent inhibitor isolated from the lungs and salivary gland of a bovine, known as trasylol. It is also a trypsin inhibitor and is used therapeutically for acute pancreatitis.

  Part of bradykinin can be formed from kallidin as a result of cleavage of lysine with the participation of aminopeptidases.

  In blood plasma and tissues, kallikreins are found mainly in the form of their precursors - kallikreinogens. It has been proven that in blood plasma the direct activator of kallikreinogen is the Hageman factor (see p. 641).

  Kinins have a short-term effect in the body; they are quickly inactivated. This is explained by the high activity of kininases - enzymes that inactivate kinins. Kininases are found in blood plasma and almost all tissues. It is the high activity of kininases in blood plasma and tissues that determines the local nature of the action of kinins.

  As already noted, physiological role The kinin system is reduced mainly to the regulation of hemodynamics. Bradykinin is the most powerful vasodilator. Kinins act directly on vascular smooth muscle, causing it to relax. They also actively influence capillary permeability. Bradykinin in this regard is 10-15 times more active than histamine.

  There is evidence that bradykinin, by increasing vascular permeability, promotes the development of atherosclerosis. A close connection between the kinin system and the pathogenesis of inflammation has been established. It is possible that the kinin system plays an important role in the pathogenesis of rheumatism, and the therapeutic effect of salicylates is explained by inhibition of bradykinin formation. Vascular abnormalities characteristic of shock are also likely associated with shifts in the kinin system. The participation of kinins in the pathogenesis of acute pancreatitis is also known.

  An interesting feature of kinins is their bronchoconstrictor effect. It has been shown that the activity of kininases in the blood of asthma sufferers is sharply reduced, which creates favorable conditions for the manifestation of the action of bradykinin. There is no doubt that research into the role of the kinin system in bronchial asthma is very promising.

  Nitrogen-free organic blood components

  The group of nitrogen-free organic substances in the blood includes carbohydrates, fats, lipoids, organic acids and some other substances. All these compounds are either products of intermediate metabolism of carbohydrates and fats, or play the role of nutrients. Basic data characterizing the content of various nitrogen-free organic substances in the blood are presented in table. 43. In the clinic, great importance is attached to the quantitative determination of these components in the blood.

  Electrolyte composition of blood plasma

  It is known that the total water content in the human body is 60-65% of body weight, i.e. approximately 40-45 l (if body weight is 70 kg); 2/3 of the total amount of water is intracellular fluid, 1/3 is extracellular fluid. Part of the extracellular water is in the vascular bed (5% of body weight), while the majority is outside the vascular bed - this is interstitial, or tissue, fluid (15% of body weight). In addition, a distinction is made between “free water”, which forms the basis of intra- and extracellular fluids, and water associated with colloids (“bound water”).

  The distribution of electrolytes in body fluids is very specific in its quantitative and qualitative composition.

  Of the plasma cations, sodium occupies a leading place and makes up 93% of their total quantity. Among the anions, chlorine should be distinguished first, followed by bicarbonate. The sum of anions and cations is almost the same, i.e. the entire system is electrically neutral.

  Tab. 47. Ratios of concentrations of hydrogen and hydroxyl ions and pH values ​​(according to Mitchell, 1975)
  H+	pH value	OH-
  10 0 or 1.0	0,0	10 -14 or 0.00000000000001
  10 -1 or 0.1	1,0	10 -13 or 0.0000000000001
  10 -2 or 0.01	2,0	10 -12 or 0.000000000001
  10 -3 or 0.001	3,0	10 -11 or 0.00000000001
  10 -4 or 0.0001	4,0	10 -10 or 0.0000000001
  10 -5 or 0.00001	5,0	10 -9 or 0.000000001
  10 -6 or 0.000001	6,0	10 -8 or 0.00000001
  10 -7 or 0.0000001	7,0	10 -7 or 0.0000001
  10 -8 or 0.00000001	8,0	10 -6 or 0.000001
  10 -9 or 0.000000001	9,0	10 -5 or 0.00001
  10 -10 or 0.0000000001	10,0	10 -4 or 0.0001
  10 -11 or 0.00000000001	11,0	10 -3 or 0.001
  10 -12 or 0.000000000001	12,0	10 -2 or 0.01
  10 -13 or 0.0000000000001	13,0	10 -1 or 0.1
  10 -14 or 0.00000000000001	14,0	10 0 or 1.0

  • Sodium [show] .

    Sodium is the main osmotically active ion in the extracellular space. In blood plasma, the concentration of Na + is approximately 8 times higher (132-150 mmol/l) than in erythrocytes (17-20 mmol/l).

    With hypernatremia, as a rule, a syndrome associated with overhydration of the body develops. The accumulation of sodium in the blood plasma is observed in a special kidney disease, the so-called parenchymal nephritis, in patients with congenital heart failure, in primary and secondary hyperaldosteronism.

    Hyponatremia is accompanied by dehydration of the body. Correction of sodium metabolism is carried out by introducing sodium chloride solutions with the calculation of its deficiency in the extracellular space and cell.

  • Potassium [show] .

    Plasma K+ concentration ranges from 3.8 to 5.4 mmol/L; in erythrocytes it is approximately 20 times more (up to 115 mmol/l). The level of potassium in cells is much higher than in the extracellular space, therefore, in diseases accompanied by increased cellular breakdown or hemolysis, the potassium content in the blood serum increases.

    Hyperkalemia is observed in acute renal failure and hypofunction of the adrenal cortex. Lack of aldosterone leads to increased urinary excretion of sodium and water and retention of potassium in the body.

    On the contrary, with increased production of aldosterone by the adrenal cortex, hypokalemia occurs. At the same time, the excretion of potassium in the urine increases, which is combined with sodium retention in the tissues. Developing hypokalemia causes severe disturbances in the functioning of the heart, as evidenced by ECG data. A decrease in serum potassium is sometimes observed when large doses of adrenal hormones are administered for therapeutic purposes.

  • Calcium [show] .

    Traces of calcium are found in erythrocytes, while in plasma its content is 2.25-2.80 mmol/l.

    There are several fractions of calcium: ionized calcium, non-ionized calcium, but capable of dialysis, and non-dialyzable (non-diffusing) protein-bound calcium.

    Calcium takes an active part in the processes of neuromuscular excitability as an antagonist of K +, muscle contraction, blood clotting, forms the structural basis of the bone skeleton, affects the permeability of cell membranes, etc.

    A distinct increase in the level of calcium in the blood plasma is observed with the development of tumors in the bones, hyperplasia or adenoma of the parathyroid glands. In these cases, calcium comes into the plasma from the bones, which become brittle.

    The determination of calcium in hypocalcemia is of great diagnostic importance. The state of hypocalcemia is observed in hypoparathyroidism. Loss of function of the parathyroid glands leads to sharp decline the content of ionized calcium in the blood, which may be accompanied by convulsive attacks (tetany). A decrease in plasma calcium concentration is also noted in rickets, sprue, obstructive jaundice, nephrosis and glomerulonephritis.

  • Magnesium [show] .

    This is mainly an intracellular divalent ion contained in the body in an amount of 15 mmol per 1 kg of body weight; the concentration of magnesium in plasma is 0.8-1.5 mmol/l, in erythrocytes 2.4-2.8 mmol/l. There is 10 times more magnesium in muscle tissue than in blood plasma. The level of magnesium in plasma, even with significant losses, can remain stable for a long time, replenished from the muscle depot.

  • Phosphorus [show] .

    In the clinic, when testing blood, the following fractions of phosphorus are distinguished: total phosphate, acid-soluble phosphate, lipoid phosphate and inorganic phosphate. For clinical purposes, the determination of inorganic phosphate in blood plasma (serum) is often used.

    Hypophosphatemia (decreased plasma phosphorus levels) is especially characteristic of rickets. It is very important that a decrease in the level of inorganic phosphate in the blood plasma is observed in the early stages of the development of rickets, when clinical symptoms are not sufficiently pronounced. Hypophosphatemia is also observed with insulin administration, hyperparathyroidism, osteomalacia, sprue and some other diseases.

  • Iron [show] .

    In whole blood, iron is contained mainly in erythrocytes (- 18.5 mmol/l), in plasma its concentration averages 0.02 mmol/l. Every day, during the breakdown of hemoglobin in erythrocytes in the spleen and liver, about 25 mg of iron is released and the same amount is consumed during the synthesis of hemoglobin in the cells of hematopoietic tissues. The bone marrow (the main erythropoietic tissue of humans) contains a labile supply of iron that exceeds 5 times the daily requirement for iron. The supply of iron in the liver and spleen is significantly greater (about 1000 mg, i.e. a 40-day supply). An increase in iron content in blood plasma is observed with weakened hemoglobin synthesis or increased breakdown of red blood cells.

    With anemia of various origins, the need for iron and its absorption in the intestine increase sharply. It is known that in the intestines iron is absorbed into duodenum in the form of ferrous iron (Fe 2+). In the cells of the intestinal mucosa, iron combines with the protein apoferritin to form ferritin. It is assumed that the amount of iron entering the blood from the intestines depends on the content of apoferritin in the intestinal walls. Further transport of iron from the intestine to the hematopoietic organs occurs in the form of a complex with the blood plasma protein transferrin. Iron in this complex is in trivalent form. In the bone marrow, liver and spleen, iron is deposited in the form of ferritin - a kind of reserve of easily mobilized iron. In addition, excess iron can be deposited in tissues in the form of metabolically inert hemosiderin, well known to morphologists.

    Lack of iron in the body can cause disruption of the last stage of heme synthesis - the conversion of protoporphyrin IX into heme. As a result of this, anemia develops, accompanied by an increase in the content of porphyrins, in particular protoporphyrin IX, in erythrocytes.

    Mineral substances found in tissues, including in the blood, in very small quantities (10 -6 -10 -12%) are called microelements. These include iodine, copper, zinc, cobalt, selenium, etc. It is believed that most trace elements in the blood are in a protein-bound state. Thus, plasma copper is part of ceruloplasmin, erythrocyte zinc belongs entirely to carbonic anhydrase, 65-76% of blood iodine is in organically bound form - in the form of thyroxine. Thyroxine is found in the blood mainly in protein-bound form. It complexes predominantly with the globulin that specifically binds it, which is located during electrophoresis of serum proteins between two fractions of α-globulin. Therefore, thyroxine-binding protein is called interalphaglobulin. Cobalt found in the blood is also found in protein-bound form and only partially as a structural component of vitamin B12. A significant portion of selenium in the blood is part of the active site of the enzyme glutathione peroxidase and is also associated with other proteins.

  Acid-base state

  The acid-base state is the ratio of the concentrations of hydrogen and hydroxyl ions in biological media.

  Considering the difficulty of using in practical calculations values ​​of the order of 0.0000001, which approximately reflect the concentration of hydrogen ions, Zörenson (1909) proposed the use of negative decimal logarithms of the concentration of hydrogen ions. This indicator is named pH after the first letters of the Latin words puissance (potenz, power) hygrogen - “hydrogen power”. The ratios of the concentrations of acidic and basic ions corresponding to different pH values ​​are given in table. 47.

  It has been established that only a certain range of fluctuations in blood pH corresponds to the normal state - from 7.37 to 7.44 with an average value of 7.40. (In other biological fluids and in cells, the pH may differ from the pH of blood. For example, in red blood cells the pH is 7.19 ± 0.02, differing from the pH of blood by 0.2.)

  No matter how small the limits of physiological pH fluctuations seem to us, nevertheless, if they are expressed in millimoles per 1 liter (mmol/l), it turns out that these fluctuations are relatively significant - from 36 to 44 ppm millimoles per 1 liter, i.e. e. constitute approximately 12% of the average concentration. More significant changes in blood pH towards increasing or decreasing the concentration of hydrogen ions are associated with pathological conditions.

  Regulatory systems that directly ensure the constancy of blood pH are buffer blood systems and tissues, lung activity and kidney excretory function.

  Blood buffer systems

  Buffer properties, i.e. the ability to counteract changes in pH when acids or bases are added to the system, are possessed by mixtures consisting of a weak acid and its salt with a strong base or a weak base with a salt of a strong acid.

  The most important blood buffer systems are:

  • [show] .

    Bicarbonate buffer system- a powerful and, perhaps, the most controllable system of extracellular fluid and blood. The bicarbonate buffer accounts for about 10% of the total buffer capacity of the blood. The bicarbonate system consists of carbon dioxide (H 2 CO 3) and bicarbonates (NaHCO 3 - in extracellular fluids and KHCO 3 - inside cells). The concentration of hydrogen ions in a solution can be expressed through the dissociation constant of carbonic acid and the logarithm of the concentration of undissociated H 2 CO 3 molecules and HCO 3 - ions. This formula is known as the Henderson-Hesselbach equation:

    

    Since the true concentration of H 2 CO 3 is insignificant and is directly dependent on the concentration of dissolved CO 2, it is more convenient to use a version of the Henderson-Hesselbach equation containing the “apparent” dissociation constant of H 2 CO 3 (K 1), which takes into account the total concentration of CO 2 in solution. (The molar concentration of H 2 CO 3 compared to the concentration of CO 2 in the blood plasma is very low. At PCO 2 = 53.3 hPa (40 mm Hg), there are approximately 500 molecules of CO 2 per 1 molecule of H 2 CO 3.)

    Then, instead of the concentration of H 2 CO 3, the concentration of CO 2 can be substituted:

    

    

    In other words, at pH 7.4, the ratio between carbon dioxide physically dissolved in the blood plasma and the amount of carbon dioxide bound in the form of sodium bicarbonate is 1:20.

    The mechanism of the buffering action of this system is that when large quantities of acidic products are released into the blood, hydrogen ions combine with bicarbonate anions, which leads to the formation of weakly dissociating carbonic acid.

    In addition, excess carbon dioxide immediately decomposes into water and carbon dioxide, which is removed through the lungs as a result of their hyperventilation. Thus, despite a slight decrease in the concentration of bicarbonate in the blood, the normal ratio between the concentration of H 2 CO 3 and bicarbonate (1:20) is maintained. This ensures that the blood pH is kept within normal limits.

    If the number of basic ions in the blood increases, they combine with weak carbonic acid to form bicarbonate anions and water. To maintain the normal ratio of the main components of the buffer system, in this case, physiological mechanisms for regulating the acid-base state are activated: a certain amount of CO 2 is retained in the blood plasma as a result of hypoventilation of the lungs, and the kidneys begin to secrete basic salts in larger quantities than usual (for example, Na 2 HP0 4). All this helps maintain a normal ratio between the concentration of free carbon dioxide and bicarbonate in the blood.

  • Phosphate buffer system [show] .

    Phosphate buffer system constitutes only 1% of the buffer capacity of the blood. However, in tissues this system is one of the main ones. The role of acid in this system is played by monobasic phosphate (NaH 2 PO 4):

    NaH 2 PO 4 -> Na + + H 2 PO 4 - (H 2 PO 4 - -> H + + HPO 4 2-),

    
    and the role of the salt is dibasic phosphate (Na 2 HP0 4):

    Na 2 HP0 4 -> 2Na + + HPO 4 2- (HPO 4 2- + H + -> H 2 PO 4 -).

    For a phosphate buffer system, the following equation holds:

    

    At pH 7.4, the ratio of the molar concentrations of monobasic and dibasic phosphates is 1:4.

    The buffering effect of the phosphate system is based on the possibility of binding hydrogen ions with HPO 4 2- ions to form H 2 PO 4 - (H + + HPO 4 2- -> H 2 PO 4 -), as well as on the interaction of OH - ions with H 2 ions PO 4 - (OH - + H 4 PO 4 - -> HPO 4 2- + H 2 O).

    The phosphate buffer in the blood is in close connection with the bicarbonate buffer system.

  • Protein buffer system [show] .

    Protein buffer system- a fairly powerful buffer system of blood plasma. Since blood plasma proteins contain a sufficient amount of acidic and basic radicals, the buffering properties are associated mainly with the content of actively ionized amino acid residues—monoaminodicarboxylic and diaminomonocarboxylic acids—in the polypeptide chains. When the pH shifts to the alkaline side (remember the isoelectric point of the protein), the dissociation of basic groups is inhibited and the protein behaves like an acid (HPr). By binding with a base, this acid produces a salt (NaPr). For a given buffer system, the following equation can be written:

    

    As pH increases, the amount of proteins in the form of salt increases, and as pH decreases, the amount of plasma proteins in the form of acid increases.

  • [show] .

    Hemoglobin buffer system- the most powerful blood system. It is 9 times more powerful than bicarbonate: it accounts for 75% of the total buffer capacity of the blood. The participation of hemoglobin in the regulation of blood pH is associated with its role in the transport of oxygen and carbon dioxide. The dissociation constant of the acid groups of hemoglobin changes depending on its oxygen saturation. When hemoglobin is saturated with oxygen, it becomes a stronger acid (HHbO 2) and increases the release of hydrogen ions into the solution. If hemoglobin gives up oxygen, it becomes a very weak organic acid (HHb). The dependence of blood pH on the concentrations of HHb and KHb (or, respectively, HHbO 2 and KHb0 2) can be expressed by the following comparisons:

    The hemoglobin and oxyhemoglobin systems are interconvertible systems and exist as a single whole; the buffering properties of hemoglobin are primarily due to the possibility of interaction of acid-reactive compounds with the potassium salt of hemoglobin to form an equivalent amount of the corresponding potassium salt of the acid and free hemoglobin:

    KHb + H 2 CO 3 -> KHCO 3 + HHb.

    It is in this way that the conversion of the potassium salt of hemoglobin of erythrocytes into free HHb with the formation of an equivalent amount of bicarbonate ensures that the pH of the blood remains within physiologically acceptable values, despite the entry into the venous blood of a huge amount of carbon dioxide and other acid-reactive metabolic products.

    Once in the capillaries of the lungs, hemoglobin (HHb) is converted into oxyhemoglobin (HHbO 2), which leads to some acidification of the blood, displacement of some H 2 CO 3 from bicarbonates and a decrease in the alkaline reserve of the blood.

    The alkaline reserve of the blood - the ability of the blood to bind CO 2 - is studied in the same way as total CO 2, but under conditions of balancing the blood plasma at PCO 2 = 53.3 hPa (40 mm Hg); determine the total amount of CO 2 and the amount of physically dissolved CO 2 in the test plasma. By subtracting the second from the first digit, we get a value called reserve blood alkalinity. It is expressed in volume percent CO 2 (volume of CO 2 in milliliters per 100 ml of plasma). Normally, a person's reserve alkalinity is 50-65 vol.% CO 2.

  So, the listed blood buffer systems play an important role in the regulation of acid-base status. As noted, in this process, in addition to the blood buffer systems, the respiratory system and the urinary system also take an active part.

  Acid-base disorders

  In a condition where the body's compensatory mechanisms are unable to prevent changes in the concentration of hydrogen ions, a disorder of the acid-base state occurs. In this case, two opposite conditions are observed - acidosis and alkalosis.

  Acidosis is characterized by a concentration of hydrogen ions above normal limits. In this case, naturally, the pH decreases. A decrease in pH value below 6.8 causes death.

  In cases where the concentration of hydrogen ions decreases (accordingly, the pH increases), a state of alkalosis occurs. The limit of compatibility with life is pH 8.0. In clinics, pH values ​​such as 6.8 and 8.0 are practically not found.

  Depending on the mechanism, the development of acid-base disorders, respiratory (gas) and non-respiratory (metabolic) acidosis or alkalosis are distinguished.

  • acidosis [show] .

    Respiratory (gas) acidosis may occur as a result of a decrease in minute breathing volume (for example, with bronchitis, bronchial asthma, emphysema, mechanical asphyxia, etc.). All these diseases lead to hypoventilation of the lungs and hypercapnia, i.e., an increase in arterial blood PCO 2. Naturally, the development of acidosis is prevented by blood buffer systems, in particular the bicarbonate buffer. The bicarbonate content increases, i.e. the alkaline reserve of the blood increases. At the same time, the excretion in urine of free and bound ammonium salts of acids increases.

    Non-respiratory (metabolic) acidosis caused by the accumulation of organic acids in tissues and blood. This type of acidosis is associated with metabolic disorders. Non-respiratory acidosis is possible with diabetes (accumulation of ketone bodies), fasting, fever and other diseases. Excessive accumulation of hydrogen ions in these cases is initially compensated by reducing the alkaline reserve of the blood. The CO 2 content in the alveolar air is also reduced, and pulmonary ventilation is accelerated. The acidity of urine and the concentration of ammonia in the urine are increased.

  • alkalosis [show] .

    Respiratory (gas) alkalosis occurs with a sharp increase respiratory function lungs (hyperventilation). For example, when inhaling pure oxygen, compensatory shortness of breath that accompanies a number of diseases, when being in a rarefied atmosphere and other conditions, respiratory alkalosis can be observed.

    Due to a decrease in the content of carbonic acid in the blood, a shift occurs in the bicarbonate buffer system: part of the bicarbonates is converted into carbonic acid, i.e., the reserve alkalinity of the blood decreases. It should also be noted that PCO 2 in the alveolar air is reduced, pulmonary ventilation is accelerated, urine has low acidity and the ammonia content in urine is reduced.

    Non-respiratory (metabolic) alkalosis develops with the loss of a large number of acid equivalents (for example, uncontrollable vomiting, etc.) and the absorption of alkaline equivalents of intestinal juice, which have not been neutralized by acidic gastric juice, as well as with the accumulation of alkaline equivalents in tissues (for example, with tetany) and in the case of unreasonable correction metabolic acidosis. At the same time, the alkaline reserve of the blood and PCO 2 in the avelveolar air increase. Pulmonary ventilation is slowed down, the acidity of urine and the ammonia content in it are reduced (Table 48).

    Table 48. The simplest indicators for assessing acid-base status
    Shifts (changes) in acid-base state	Urine, pH	Plasma, HCO 2 -, mmol/l	Plasma, HCO 2 -, mmol/l
    Norm	6-7	25	0,625
    Respiratory acidosis	reduced	increased	increased
    Respiratory alkalosis	increased	reduced	reduced
    Metabolic acidosis	reduced	reduced	reduced
    Metabolic alkalosis	increased	increased	increased

  In practice, isolated forms of respiratory or non-respiratory disorders are extremely rare. Determining a set of indicators of acid-base status helps to clarify the nature of the disorders and the degree of compensation. Over the past decades, sensitive electrodes for direct measurement of pH and PCO 2 of blood have become widespread to study indicators of acid-base status. In clinical settings, it is convenient to use devices such as "Astrup" or domestic devices - AZIV, AKOR. Using these instruments and corresponding nomograms, the following basic indicators of acid-base status can be determined:

  1. actual blood pH is the negative logarithm of the concentration of hydrogen ions in the blood under physiological conditions;
  2. actual PCO 2 of whole blood - partial pressure of carbon dioxide (H 2 CO 3 + CO 2) in the blood under physiological conditions;
  3. actual bicarbonate (AB) - the concentration of bicarbonate in blood plasma under physiological conditions;
  4. standard blood plasma bicarbonate (SB) - the concentration of bicarbonate in blood plasma, balanced by alveolar air and at full saturation with oxygen;
  5. buffer bases of whole blood or plasma (BB) - an indicator of the power of the entire buffer system of blood or plasma;
  6. normal whole blood buffer bases (NBB) - whole blood buffer bases at physiological pH and PCO 2 values ​​of alveolar air;
  7. base excess (BE) is an indicator of excess or lack of buffer capacity (BB - NBB).

  Blood functions Blood ensures the vital functions of the body and performs the following important functions: respiratory - supplies cells with oxygen from the respiratory organs and removes carbon dioxide (carbon dioxide) from them; nutritious - carries nutrients throughout the body that, during digestion, enter the blood vessels from the intestines; excretory - removes from organs decay products formed in cells as a result of their vital activity; regulatory - transports hormones that regulate metabolism and the functioning of various organs, carries out humoral communication between organs; protective - microorganisms that enter the blood are absorbed and neutralized by leukocytes, and the toxic waste products of microorganisms are neutralized with the participation of special blood proteins - antibodies. All these functions are often combined under a common name - the transport function of blood. In addition, blood maintains the constancy of the internal environment of the body - temperature, salt composition, environmental reaction, etc. Nutrients from the intestines, oxygen from the lungs, and metabolic products from tissues enter the blood. However, blood plasma remains relatively constant in composition and physicochemical properties. The constancy of the internal environment of the body - homeostasis is maintained by the continuous work of the digestive, respiratory, and excretory organs. The activity of these organs is regulated by the nervous system, which responds to changes in the external environment and ensures the equalization of shifts or disturbances in the body. In the kidneys, the blood is freed from excess mineral salts, water and metabolic products, in the lungs - from carbon dioxide. If the concentration of any substance in the blood changes, then neurohormonal mechanisms, regulating the activity of a number of systems, reduce or increase its release from the body.

  Some blood plasma proteins play an important role in blood coagulation and anticoagulation systems.

  Blood clotting- a protective reaction of the body that protects it from blood loss. People whose blood is unable to clot suffer serious illness- hemophilia.

  The mechanism of blood clotting is very complex. Its essence is the formation of a blood clot - a thrombus that clogs the wound area and stops bleeding. A blood clot is formed from the soluble protein fibrinogen, which during the blood clotting process turns into the insoluble protein fibrin. The conversion of soluble fibrinogen into insoluble fibrin occurs under the influence of thrombin, an active enzyme protein, as well as a number of substances, including those released during the destruction of platelets.

  The blood clotting mechanism is triggered by a cut, puncture, or injury, leading to damage to the platelet membrane. The process takes place in several stages.

  When platelets are destroyed, the enzyme protein thromboplastin is formed, which, when combined with calcium ions present in the blood plasma, converts the inactive plasma protein enzyme prothrombin into active thrombin.

  In addition to calcium, other factors also take part in the blood clotting process, such as vitamin K, without which the formation of prothrombin is disrupted.

  Thrombin is also an enzyme. It completes the formation of fibrin. The soluble protein fibrinogen turns into insoluble fibrin and precipitates in the form of long threads. From the network of these threads and blood cells that linger in the network, an insoluble clot is formed - a thrombus.

  These processes occur only in the presence of calcium salts. Therefore, if calcium is removed from the blood by binding it chemically (for example, with sodium citrate), then such blood loses its ability to clot. This method is used to prevent blood clotting during preservation and transfusion.

  Internal environment of the body

  Blood capillaries do not approach every cell, so the exchange of substances between cells and blood, communication between the organs of digestion, respiration, excretion, etc. carried out through the internal environment of the body, which consists of blood, tissue fluid and lymph.

  Internal environment	Compound	Location	Source and place of formation	Functions
  Blood	Plasma (50-60% of blood volume): water 90-92%, proteins 7%, fats 0.8%, glucose 0.12%, urea 0.05%, mineral salts 0.9%	Blood vessels: arteries, veins, capillaries	Due to the absorption of proteins, fats and carbohydrates, as well as mineral salts of food and water	The relationship of all organs of the body as a whole with the external environment; nutritional (delivery of nutrients), excretory (removal of dissimilation products, CO 2 from the body); protective (immunity, coagulation); regulatory (humoral)
  	Formed elements (40-50% of blood volume): red blood cells, leukocytes, platelets	Blood plasma	Red bone marrow, spleen, lymph nodes, lymphoid tissue	Transport (respiratory) - red blood cells transport O 2 and partially CO 2; protective - leukocytes (phagocytes) neutralize pathogens; platelets provide blood clotting
  Tissue fluid	Water, nutrient organic and inorganic substances dissolved in it, O 2, CO 2, dissimilation products released from cells	The spaces between the cells of all tissues. Volume 20 l (for an adult)	Due to blood plasma and end products of dissimilation	It is an intermediate medium between blood and body cells. Transfers O2, nutrients, mineral salts, and hormones from the blood to the cells of organs. Returns water and dissimilation products to the bloodstream through lymph. Transfers CO2 released from cells into the bloodstream
  Lymph	Water, decay products of organic substances dissolved in it	Lymphatic system, consisting of lymphatic capillaries ending in sacs and vessels merging into two ducts that empty into the vena cava of the circulatory system in the neck	Due to tissue fluid absorbed through sacs at the ends of lymphatic capillaries	Return of tissue fluid to the bloodstream. Filtration and disinfection of tissue fluid, which is carried out in the lymph nodes where lymphocytes are produced

  The liquid part of the blood - plasma - passes through the walls of the thinnest blood vessels - capillaries - and forms intercellular, or tissue, fluid. This fluid washes all the cells of the body, gives them nutrients and takes away metabolic products. In the human body there is up to 20 liters of tissue fluid; it forms the internal environment of the body. Most of this fluid returns to the blood capillaries, and a smaller part, penetrating into the lymphatic capillaries closed at one end, forms lymph.

  The color of the lymph is yellowish-straw. It is 95% water and contains proteins, mineral salts, fats, glucose, and lymphocytes (a type of white blood cell). The composition of lymph resembles that of plasma, but there are fewer proteins, and it has its own characteristics in different parts of the body. For example, in the intestinal area there are a lot of fat droplets, which gives it a whitish color. Lymph by lymphatic vessels going to thoracic duct and through it enters the blood.

  Nutrients and oxygen from the capillaries, according to the laws of diffusion, first enter tissue fluid, and from it are absorbed by cells. This is how the connection between capillaries and cells occurs. Carbon dioxide, water and other metabolic products formed in cells are also released from the cells first into the tissue fluid due to the difference in concentrations, and then enter the capillaries. Arterial blood becomes venous and delivers waste products to the kidneys, lungs, and skin, through which they are removed from the body.

The main component that forms the internal environment of the human body is blood. Among all body tissues, it is the only one with a liquid base; its volume is from 4 to 6 liters. In newborn babies, the amount of blood is approximately 200 - 350 ml. Blood circulation occurs through a closed system of vessels under the influence of rhythmic contractions of the heart and does not have direct communication 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 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 the 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 carbon dioxide and oxygen molecules throughout the body.
2. Supporting the balance of the internal environment (homeostasis).
3. Transfer of nutritional compounds, vitamins, hormones and minerals.
4. Taking metabolic products 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) first appear, 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. The ratio of different types of 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 an 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 serve as transmitters in the immune response system. The latter are needed for the synthesis of antibodies against pathogens of 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, making up about 8% of the total number of white blood cells. 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. In healthy people, the number of platelets in the bloodstream ranges from 150 to 450 thousand per 1 microliter. The lifespan of blood platelets is 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 a blood vessel is damaged, a blood clot gradually forms at the site of the rupture, 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 a large number of enzymes, is the main element of fluid inside cells and maintains 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 for the formation of bone tissue, the 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 inhibition processes in the 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 is 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 metabolic products and other organic compounds to various points in the 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 acids, 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 most general terms, the functions of blood 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 of acid-base balance and volume of fluids, 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 fabrics (deposited fraction). Plasma volume makes up approximately 55% of the total blood volume, 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). The most typical reason for an increase in ESR is 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 other 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) . The chemical composition of 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 mm Hg, or 3.3 kPa) of blood (5 times more than the oncotic pressure of the intercellular fluid. This is why, with massive loss of albumin (hypoalbuminemia) through the kidneys, “renal” edema develops, and during fasting, “hungry” edema .

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 (osmotically active substances) contained in plasma, 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, 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 the 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 blood buffer systems, discussed in Chapter 28.

CELL ELEMENTS OF BLOOD

Blood cells (outdated name - formed elements) include red blood cells, leukocytes 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. The content of erythrocytes in the peripheral blood of an adult in men is 4.5-5.7x10 12 / l (in women - 3.9-5x10 12 / l), leukocytes - 3 .8-9.8x10 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, 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 the 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. The beginning of the erythroid series is the stem cell of 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, 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 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 from four molecules pyrrole, 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, formed at different stages of organism development, 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, gas physically dissolved in the blood is a necessary stage in the transport of any gas (for example, when moving O 2 into an erythrocyte from the cavity of the alveoli).

Blood oxygen capacity- 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 are created for the association of Hb and O 2 in the capillaries of the lung 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 of venous blood (S v o 2) is 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 the facilitation of the diffusion of o 2 from the blood into tissues and the binding of o 2 by 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. In contrast to the dissociation curve of Hb and O 2 (see Fig. 24-7), the dissociation curve of CO 2 at physiological values ​​of pOD 2 (arterial blood - 40 mm Hg, venous blood - 46 mm Hg) is linear character. 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 partial pressure of oxygen (^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 the destruction of heme releases iron ions, carbon monoxide (CO) and protoporphyrin (verdoglobin, from which biliverdin is formed, which is reduced to bilirubin). 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 color of verdoglobin into the yellow color of 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 of a healthy man weighing 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 primarily from destroyed red blood cells. Sources of iron- intake from food and destroyed red blood cells.

Iron from food absorbed in the intestine in the duodenum and the initial part 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 small intestinal mucosa. 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 antibodies (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 erythrocytes of different individuals 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 on the surface of erythrocytes of agglutinogens A and B

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.Contents of agglutinogens (Ag) and agglutinins (AT) in the blood of different groups (AB0 system)

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 “there are no indications for the transfusion of whole canned donor blood, 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 RF). And that is why the theoretical concept of a “universal donor” with blood of group 0 (I) has been abandoned 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 IgG class(ATs 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 when Rh-positive blood is transfused from a donor to an Rh-negative recipient or in a fetus during a repeat 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 lobulated 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 leukocytoses, functional and protective-adaptive are distinguished.

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 with 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 total number 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.