Physiological functions of blood plasma proteins. Blood plasma proteins and their significance. Age characteristics. Increase and decrease in total protein volume

Meaning blood plasma proteins diverse:

1. Proteins give rise to oncotic pressure (see below), the magnitude of which is important for regulating water exchange between blood and tissues.
2. Proteins, having buffering properties, maintain the acid-base balance of the blood.
3. Proteins provide the blood plasma with a certain viscosity, which is important in maintaining blood pressure levels.
4. Plasma proteins help stabilize the blood, creating conditions that prevent red blood cell sedimentation.
5. Plasma proteins play an important role in blood clotting.
6. Blood plasma proteins are important factors in immunity, i.e., immunity to infectious diseases.

Blood plasma contains several dozen different proteins, which make up three main groups: albumins, globulins and fibrinogen. Since 1937, the electrophoresis method has been used to separate plasma proteins, based on the fact that different proteins have different mobility in an electric field. Using electrophoresis, globulins are divided into several fractions: α1-, α2-, β and γ - globulins.

Electrophoretic diagram blood plasma proteins shown on rice. 1. Gamma globulins are important in protecting the body from viruses, bacteria and their toxins.

This is due to the fact that the so-called antibodies are mainly γ-globulins. Their administration to patients increases the body's resistance to infections. Recently, a protein complex has been found in blood plasma that plays a similar role - properdin.

Osmotic pressure of blood plasma proteins

is created not only by crystalloids dissolved in the blood plasma, but also by colloids - plasma proteins. The osmotic pressure caused by them is called oncotic.

Although the absolute amount of plasma proteins is 7-8% and almost 10 times greater than the amount of dissolved salts, the oncotic pressure they create is only about 1/200 of the osmotic pressure of plasma (equal to 7.6-8.1 atm), t i.e. 0.03-0.04 atm. (25-30 mmHg). This is due to the fact that protein molecules are very large in size and their number in plasma is many times less than the number of crystalloid molecules.

Despite its small value, oncotic pressure plays an extremely important role in the exchange of water between blood and tissues. Oncotic pressure affects those physiological processes that are based on filtration phenomena (formation of interstitial fluid, lymph, urine, absorption of water in the intestines). Large molecules of plasma proteins, as a rule, do not pass through the endothelial wall of the capillaries. Remaining inside the bloodstream, they retain a certain amount of water in the blood (in accordance with the value of their osmotic pressure). By doing this, they help maintain the relative constancy of water content in the blood and tissues.

The ability of blood proteins to retain water in the vascular bed can be proven by the following experiment. If you perform repeated bloodletting on a dog and, using centrifugation, separate the plasma of the taken blood from the red blood cells, and the latter are injected back into the blood in a saline solution, then in this way you can greatly reduce the amount of proteins in the blood. In this case, the animal experiences significant swelling. In an experiment with isolated organs, when Ringer's or Ringer-Locke solution is passed through them for a long time, tissue edema occurs. If you replace the saline solution with blood serum, then the swelling that has begun can be destroyed. This explains the need to introduce colloidal substances into blood replacement solutions. In this case, the oncotic pressure and viscosity of such solutions are selected so that they are equal to the viscosity and oncotic pressure of the blood.

Human blood plasma contains more than 100 different proteins. Most plasma proteins are synthesized in the liver, with the exception of immunoglobulins and protein-peptide hormones. The functions of blood plasma proteins are very diverse. Proteins create oncotic pressure and thereby maintain a constant blood volume, i.e. bind water and hold it in the bloodstream. Proteins provide blood viscosity. The speed of blood flow, arterial and venous pressure and other indicators of the cardiovascular system depend on viscosity. Proteins, together with the bicarbonate and phosphate buffer systems, maintain the acid-basic acid reaction (pH 7.34–7.36). Plasma contains proteins of the coagulation (fibrinogen) and anticoagulation systems (antithrombin). Plasma contains transport proteins: nonspecific (albumin) and specific (transferrin). Plasma contains antiproteases that protect blood cells and blood vessels from destruction. Immunoglobulins, the complement system, and other immune system proteins provide humoral immunity. Plasma proteins are components of the kinin and angiotensin systems. Bradykinin dilates blood vessels and lowers blood pressure, angiotensin narrows them and increases blood pressure. The nutritional function of plasma proteins is important during fasting and certain diseases.

Proteins can be divided into fractions in several ways. For example, according to their mobility during electrophoresis, they can be roughly divided into 5 fractions: albumin, a 1 -, a 2 -, b- and g-globulins. Each fraction is a mixture of individual proteins with the same charge.

Albumins are synthesized by liver hepatocytes. Among plasma proteins, quantitatively this is the largest fraction (42 g/l). These are simple proteins that perform most of the common functions of blood plasma proteins. They provide blood viscosity and oncotic pressure, since they have a lower M and there are many of them, and they participate in the regulation of ACR, since they contain more charged amino acids. Albumins perform a transport function for lipophilic substances, transport long-chain fatty acids (FFA), bilirubin, some hormones, vitamins, and medications. In addition, albumin binds Ca 2+ and Mg 2+ ions. Albumins are a reserve of amino acids for gluconeogenesis and perform a nutritional function during fasting.

a 1 -, a 2 -, b-globulins are synthesized by RES cells, g-globulins are synthesized by B-lymphocytes - 90%, Kupffer cells - 10%.

a 1 -globulins are a fraction that includes transport proteins (thyroxine-binding), acute phase proteins (a 1 -antipeptidases), HDL apoproteins, prothrombin, etc.

a 2 -globulins are a fraction that also contains transport protein (ceruloplasmin), acute phase protein a 2 -macroglobulin, antithrombin, etc.

b-globulins are a fraction that contains LDL apoproteins, fibrinogen, transcobalamin, etc.

g-globulins are a fraction that contains antibodies (immunoglobulins).

Normally, the concentration of total protein in blood plasma is 63–83 g/l. Hyperproteinemia - increased protein concentration is often relative when the body is dehydrated (diarrhea, vomiting, burns). Absolute hyperproteinemia occurs in chronic inflammatory diseases (g-globulinemia). Hyperproteinemia is usually hyperglobulinemia. Hypoproteinemia – reduced protein concentration, most often hypoalbuminemia . Dysproteinemias occur when the ratio between fractions is disturbed while the total amount of protein is normal. Using the protein spectrum of blood plasma, it is possible, for example, to differentiate between acute and chronic inflammation. In acute inflammation, albumin is reduced and a 1 and a 2 globulins are increased. With chronic inflammation, g-globulins also increase. In liver pathology, albumin is reduced and b- and g-globulins are increased.

Individual blood plasma proteins represent 4 main groups: 1) immunoglobulins, 2) transport proteins, 3) enzymes, 4) acute phase proteins.

Transport proteins, such as ceruloplasmin, transport copper ions. A hereditary defect in this protein leads to the disease hepatolenticular degeneration (Wilson-Konovalov disease). For treatment, complexones (EDTA) are prescribed, which bind copper ions. Transferrin serves to transport iron ions, retinol-binding protein transports vitamin A, thyroxine-binding protein for transporting iodothyronines and others necessary for the transfer of hydrophobic compounds.

Plasma enzymes can be divided into functional and non-functional. Functional enzymes are synthesized in the liver, enter the plasma and perform various functions. These are cholinesterase, enzymes of the coagulation and anticoagulant systems, enzymes of the kinin system (kallikrein), enzymes of the angiotensin system (angiotensin-converting enzyme - ACE). Non-functional or cellular enzymes are normally found in trace amounts in plasma and appear as a result of normal cell turnover. Nonfunctional enzymes enter the plasma when cells are destroyed as a result of inflammation or necrosis. Such enzymes are called indicator enzymes, since if they are tissue specific, they are used in enzyme diagnostics. For the enzymatic diagnosis of myocardial infarction, determination of the activity of AST > ALT, LDH 1, creatine kinase (especially the MB isoenzyme) is useful. In liver diseases, plasma levels increase: ALT > AST, LDH 5, OCT (ornithine carbamoyltransferase), arginase. In acute pancreatitis, the activity of other enzymes in the plasma is increased - pancreatic a-amylase and lipase.

Acute phase proteins (glycoproteins) are so called because they are normally absent from the blood or are present in trace amounts. In pathology, their concentration increases many times over. For example, C-reactive protein forms precipitates with C-polysaccharides of pneumococci, appears during pneumonia and other inflammatory diseases, acute infections. Acid 1-glycoprotein (orosomucoid) is increased in chronic and acute diseases and is characterized by a high carbohydrate content (42%). a 1 -antitrypsin, a 2 -macroglobulin, these are peptidase inhibitors that protect plasma and vascular proteins from peptidases that enter the blood during cell lysis. The level of a 2 -macroglobulin increases during pregnancy and estrogen intake. Hereditary deficiency of these peptidases contributes to the development of certain diseases (emphysema, cirrhosis). Haptoglobin – This is a protein that forms complexes with hemoglobin and prevents iron loss during hemolysis of red blood cells. Cryoglobulin differs in that it can gel when the temperature decreases. Cryoglobulin is not detected in healthy people; it appears in nephrosis, leukemia, myeloma, etc.

Determination of the total protein content of blood plasma (serum) is an element of a complex of diagnostic measures already at the initial stage of medical care.

Most blood plasma proteins are synthesized in hepatocytes. The catabolism of many blood plasma proteins occurs in the endothelial cells of the capillaries and the system of functional phagocytes - monocytes and macrophages - after the absorption of proteins by pinocytosis. Low molecular weight proteins pass through the filtration barrier of the renal corpuscles into the primary urine, from which they are reabsorbed by proximal tubular epithelial cells and catabolized to amino acids.

The content of proteins in the intravascular space at each moment of time is the result of a constant equilibrium between the synthesis and secretion of proteins into the blood, their absorption by cells, catabolic processes and excretion of low molecular weight proteins in the urine. In addition, a constant exchange of proteins occurs between the intravascular and extravascular pools of extracellular fluid. Maintaining a constant intravascular blood volume is carried out by the colloid osmotic system. The constancy of the oncotic component of osmotic pressure in the blood is ensured by albumin.

Functions of blood plasma proteins

1. Proteins cause oncotic pressure (see below), the value of which is important for regulating water exchange between blood and tissues. 2. Proteins, having buffering properties, maintain the acid-base balance of the blood. 3. Proteins provide the blood plasma with a certain viscosity, which is important in maintaining blood pressure levels. 4. Plasma proteins help stabilize the blood, creating conditions that prevent red blood cell sedimentation. 5. Plasma proteins play an important role in blood clotting. 6. Blood plasma proteins are important factors in immunity, i.e., immunity to infectious diseases.

Blood plasma protein groups

Blood plasma contains a mixture of proteins that are different both in origin and in their function. For many proteins, their functions have not yet been established. Several dozen individual proteins of diagnostic value have been identified in blood serum. In pathological situations, it is not the total protein content that changes mainly, but its individual components significantly increase or decrease, with the appearance in some cases of proteins that are not contained under normal conditions.

The components of the blood coagulation system and many peptide hormones are functionally well characterized. Only a few of the enzymes circulating in the blood have a real physiological function here, most of them enter the bloodstream as a result of cell destruction. All proteins of the complement system are functionally significant, as is a large group of acute phase proteins, the content of which increases by 2 orders of magnitude during the inflammatory process.

Main protein fractions:

Albumin is a protein with a molecular weight of about 70,000 Da. Due to their hydrophilicity and high content in plasma, they play an important role in maintaining colloid-osmotic (oncotic) blood pressure and regulating the exchange of fluids between blood and tissues. They perform a transport function: they transport free fatty acids, bile pigments, steroid hormones, Ca2+ ions, and many drugs. Albumins also serve as a rich and quickly available reserve of amino acids.

b1-Globulins:

Acid b1-glycoprotein (orosomucoid) - contains up to 40% carbohydrates, its isoelectric point is in an acidic environment (2.7). The function of this protein is not fully established; it is known that in the early stages of the inflammatory process, orosomucoid promotes the formation of collagen fibers at the site of inflammation (Ya. Musil, 1985).

b1-Antitrypsin - inhibitor of a number of proteases (trypsin, chymotrypsin, kallikrein, plasmin). A congenital decrease in the content of β1-antitrypsin in the blood may be a predisposition factor to bronchopulmonary diseases, since the elastic fibers of the lung tissue are especially sensitive to the action of proteolytic enzymes.

Retinol binding protein transports fat-soluble vitamin A.

Thyroxine binding protein - binds and transports iodine-containing thyroid hormones.

Transcortin - binds and transports glucocorticoid hormones (cortisol, corticosterone).

b2-Globulins:

Haptoglobins (25% b2-globulins) - form a stable complex with hemoglobin that appears in the plasma as a result of intravascular hemolysis of red blood cells. Haptoglobin-hemoglobin complexes are taken up by RES cells, where heme and protein chains undergo breakdown and iron is reused for hemoglobin synthesis. This prevents the body from losing iron and causing hemoglobin damage to the kidneys.

Ceruloplasmin - a protein containing copper ions (one ceruloplasmin molecule contains 6-8 Cu2+ ions), which give it a blue color. It is a transport form of copper ions in the body. It has oxidase activity: it oxidizes Fe2+ to Fe3+, which ensures the binding of iron by transferrin. Capable of oxidizing aromatic amines, participates in the metabolism of adrenaline, norepinephrine, and serotonin.

β-Globulins:

Transferrin - the main protein of the β-globulin fraction, is involved in the binding and transport of ferric iron into various tissues, especially hematopoietic tissues. Transferrin regulates Fe3+ levels in the blood and prevents excess accumulation and loss in urine.

Hemopexin - binds heme and prevents its loss by the kidneys. The heme-hemopexin complex is taken up from the blood by the liver.

C-reactive protein (CRP) - a protein capable of precipitating (in the presence of Ca2+) C-polysaccharide of the pneumococcal cell wall. Its biological role is determined by its ability to activate phagocytosis and inhibit the process of platelet aggregation. In healthy people, the concentration of CRP in plasma is negligible and cannot be determined by standard methods. During an acute inflammatory process, it increases more than 20 times; in this case, CRP is detected in the blood. The study of CRP has an advantage over other markers of the inflammatory process: determination of ESR and counting the number of leukocytes. This indicator is more sensitive, its increase occurs earlier and after recovery it returns to normal faster.

g-Globulins:

Immunoglobulins (IgA, IgG, IgM, IgD, IgE) are antibodies produced by the body in response to the introduction of foreign substances with antigenic activity. For more information about these proteins, see 1.2.5.

Immunoglobulins(antibodies) - a group of proteins produced in response to foreign structures (antigens) entering the body. They are synthesized in the lymph nodes and spleen by B lymphocytes. There are 5 classes immunoglobulins- IgA, IgG, IgM, IgD, IgE.

Figure 3 Scheme of the structure of immunoglobulins (the variable region is shown in gray, the constant region is not shaded)

Immunoglobulin molecules have a single structure plan. The structural unit of immunoglobulin (monomer) is formed by four polypeptide chains connected to each other by disulfide bonds: two heavy (H chains) and two light (L chains) (see Figure 3). IgG, IgD and IgE are, as a rule, monomers in their structure, IgM molecules are built from five monomers, IgA consist of two or more structural units, or are monomers.

The protein chains that make up immunoglobulins can be divided into specific domains, or areas that have certain structural and functional features.

The N-terminal regions of both the L and H chains are called the variable region (V), since their structure is characterized by significant differences between different classes of antibodies. Within the variable domain there are 3 hypervariable regions, characterized by the greatest diversity of amino acid sequences. It is the variable region of antibodies that is responsible for the binding of antigens according to the principle of complementarity; the primary structure of the protein chains in this region determines the specificity of antibodies.

The C-terminal domains of the H and L chains have a relatively constant primary structure within each class of antibodies and are called the constant region (C). The constant region determines the properties of various classes of immunoglobulins, their distribution in the body, and can take part in triggering mechanisms that cause the destruction of antigens.

Interferons- a family of proteins synthesized by body cells in response to a viral infection and having an antiviral effect. There are several types of interferons that have a specific spectrum of action: leukocyte (b-interferon), fibroblast (b-interferon) and immune (g-interferon). Interferons are synthesized and secreted by some cells and exert their effect by affecting other cells, in this respect they are similar to hormones. The mechanism of action of interferons is shown in Figure 4.

Figure 4

By binding to cellular receptors, interferons induce the synthesis of two enzymes - 2,5"-oligoadenylate synthetase and protein kinase, probably due to the initiation of transcription of the corresponding genes. Both resulting enzymes exhibit their activity in the presence of double-stranded RNA, and it is these RNAs that are the replication products of many viruses or are contained in their virions. The first enzyme synthesizes 2",5"-oligoadenylates (from ATP), which activate cellular ribonuclease I; the second enzyme phosphorylates the translation initiation factor IF2. The end result of these processes is the inhibition of protein biosynthesis and virus reproduction in the infected cell (Yu.A. Ovchinnikov, 1987).

Lipoproteins are complex compounds that transport lipids in the blood. They include: hydrophobic core containing triacylglycerols and cholesterol esters, and amphiphilic shell, formed by phospholipids, free cholesterol and apoproteins (Figure 2). Human blood plasma contains the following fractions of lipoproteins:

Figure 2 Scheme of the structure of blood plasma lipoprotein

High density lipoproteins or b-lipoproteins , since during electrophoresis on paper they move along with b-globulins. They contain many proteins and phospholipids and transport cholesterol from peripheral tissues to the liver.

Low density lipoproteins or β-lipoproteins , since during electrophoresis on paper they move along with β-globulins. Rich in cholesterol; transport it from the liver to peripheral tissues.

Very low density lipoproteins or pre-b-lipoproteins (located on the electropherogram between b- and b-globulins). They serve as a transport form of endogenous triacylglycerols and are precursors of low-density lipoproteins.

Chylomicrons - electrophoretically immobile; are absent in blood taken on an empty stomach. They are a transport form of exogenous (food) triacylglycerols.

Fibrinogen (factor I) is a soluble plasma glycoprotein with a molecular weight of about 340,000. It is synthesized in the liver. The fibrinogen molecule consists of six polypeptide chains: two A b-chains, two B b-chains, and two g-chains (see Figure 9). The ends of fibrinogen polypeptide chains carry a negative charge. This is due to the presence of a large number of glutamate and aspartate residues in the N-terminal regions of the Aa and Bb chains. In addition, the B-regions of the Bb chains contain residues of the rare amino acid tyrosine-O-sulfate, which are also negatively charged:

This promotes the solubility of the protein in water and prevents the aggregation of its molecules.

Figure 9 Diagram of the structure of fibrinogen; arrows indicate bonds hydrolyzed by thrombin. R. Murray et al., 1993)

The conversion of fibrinogen to fibrin is catalyzed by thrombin(factor IIa). Thrombin hydrolyzes four peptide bonds in fibrinogen: two bonds in the A b chains and two bonds in the B c chains. Fibrinopeptides A and B are split off from the fibrinogen molecule and fibrin monomer is formed (its composition is b2 b2 r2). Fibrin monomers are insoluble in water and easily associate with each other, forming a fibrin clot.

Stabilization of the fibrin clot occurs under the action of an enzyme transglutaminase(factor XIIIa). This factor is also activated by thrombin. Transglutaminase cross-links fibrin monomers using covalent isopeptide bonds.

Transferrins-- blood plasma proteins that transport iron ions. Transferrins are glycosylated proteins that bind iron ions tightly but reversibly. About 0.1% of all iron ions in the body are bound to transferrins (which is about 4 mg), but the iron ions bound to transferrins are of great importance for metabolism. Transferrins have a molecular weight of about 80 kDa and have two Fe 3+ binding sites. The affinity of transferrin is very high (10 23 M ?1 at pH 7.4), but it progressively decreases as the pH decreases below the neutral point. When transferrin is not bound to iron, it is apoprotein.

In humans, transferrin is a polypeptide chain consisting of 679 amino acids. It is a complex consisting of alpha helices and beta sheets that form 2 domains (the first is located at the N-terminus and the second at the C-terminus). The N- and C-terminal sequences are represented by spherical lobes, between which there is an iron binding site. The amino acids that bind iron ions to transferrin are identical for both lobes: 2 tyrosines, 1 histidine, 1 aspartic acid. To bind the iron ion, an anion is required, preferably a carbonate ion (CO 3 2?). Transferrin also has a transferrin receptor: it is a disulfide-linked homodimer. In humans, each monomer consists of 760 amino acids. Each monomer consists of 3 domains: apical domain, helical domain, protease domain.

When transferrin is bound to iron ions, the transferrin receptor on the surface of the cell (for example, red blood cell precursors in red bone marrow) attaches to it and, as a result, enters the cell in a vesicle. The pH inside the vesicle is then lowered by proton ion pumps, causing transferrin to release iron ions. The receptor moves back to the cell surface, once again ready to bind transferrin. Each transferrin molecule can transport 2 iron ions Fe 3+ at once.

The gene encoding transferrin in humans is located on chromosome 3q21. Studies conducted on king snakes in 1981 showed that transferrin is inherited through a codominant mechanism.

Total protein

Blood plasma, exudates and transudates can be used as biological material. They all give comparable results, although due to the presence of fibrinogen, the level of total protein in the blood plasma is 2-4 g/l higher than in the serum. The protein is stable in serum and plasma for a week at room temperature, at least up to 2 months at -20 °C. Hemolysis gives a false-positive increase in total protein of 3% for every 1 g of free hemoglobin in 1 liter of blood serum.

Physiological fluctuations in the content of total protein in blood serum depend in most cases on changes in the volume of the liquid part of the blood and are to a lesser extent associated with the synthesis or loss of protein. Normally, the protein content in blood serum is the same in both vegetarians and people with a normal diet, although protein loading can increase the total protein content in the blood. High physical activity contributes only to a slight increase in the content of total protein in the blood.

Nutrition (3 liters of plasma contains 200 g of protein) is an adequate supply of nutrients.

Transport - due to the presence of hydrophilic and hydrophobic regions, proteins are able to bind to molecules and fat-like substances and carry them through the bloodstream. Plasma proteins bind 2/3 of plasma calcium.

The oncotic pressure of plasma to a greater extent (80%) depends on albumins (lower molecular weight, but larger amounts in plasma than globulins). A decrease in albumin concentration leads to the retention of H 2 O in the intercellular space (interstitial edema).

Buffer function - maintains a constant blood pH by binding H + or OH -, due to amphoteric properties.

Prevention of blood loss is due to the presence of fibrinogen in the blood plasma. The high viscosity of fibrinogen solutions is due to the property of its molecules to form clots in the form of “strings of beads”. The chain of hemostasis reactions in which plasma proteins participate ends with the transformation of fibrinogen dissolved in plasma into a network of fibrin molecules, forming a clot (thrombus). The fibrin molecule has an elongated shape (length/width ratio – 17:1).

Properties and functions of individual protein fractions.

Plasma albumin determines 80% of the colloid-osmotic (oncotic) pressure of plasma. It accounts for 60% of total plasma protein (35-45 g/l).

Albumin is a low molecular weight compound and is therefore well suited to serve as a carrier for many substances transported in the blood. Albumin binds: bilirubin, urobilin, fatty acids, bile salts, penicillin, sulfamedin, mercury.

During inflammatory processes and damage to the liver and kidneys, the amount of albumin decreases.

Globulins.

a 1 – globulins, otherwise they are called glycoproteins. 2/3 of the total amount of plasma glucose is present in bound form as part of glycoproteins. The subfraction of glycoproteins includes a group of carbohydrate-containing proteins - proteoglycans (mucoproteins).

a 2 - globulins are a proteoglycan or otherwise a copper-containing protein ceruloplasmin, which binds 90% of all copper contained in plasma.

b-globulin is a protein carrier of lipids and polysaccharides. They hold water-insoluble fats and lipids in solution and thereby ensure their transport in the blood.

g - globulins. This is a heterogeneous group of proteins that perform protective and neutralizing functions, otherwise called immunoglobulins. The size and composition of g - globulins varies significantly. In all diseases, especially inflammatory ones, the content of g-globulins in plasma increases. G-globulins include blood agglutinins: Anti-A and Anti-B.

erythrocytes

The most numerous formed elements of blood are red blood cells (erythrocytes). In men – 4 - 5 million in 1 µl; in women, as a rule, it does not exceed 4.5 million in 1 μl. During pregnancy, the number of red blood cells can decrease to 3.5 and even 3 million per 1 μl.

Normally, the number of red blood cells is subject to slight fluctuations.

In various diseases, the number of red blood cells may decrease (“erythropenia”). This often accompanies anemia or anemia.

An increase in the number of red blood cells is referred to as “erythrocytosis.”

Human red blood cells are anucleate, flat cells shaped like biconcave discs. Their thickness at the edges is 2 µm.

The surface of the disk is 1.7 times larger than the surface of a body of the same volume, but spherical in shape. Consequently, this form ensures the transport of a large number of different substances. This shape allows red blood cells to be attached to the fibrin network during the formation of a blood clot. But the main advantage is that this form ensures the passage of red blood cells through the capillaries. In this case, the red blood cell twists in the middle narrow part, the contents from the wider end flow to the center, due to which the red blood cell enters the narrow capillary.

The cytoskeleton in the form of tubes and microfilaments passing through the cell is absent in the erythrocyte, which gives it elasticity and deformability (necessary properties for passing through capillaries).

Price-Jones curve– This is the distribution of red blood cells by diameter. The distribution of erythrocyte diameters normally corresponds to the normal distribution curve.

Normocyte - the average diameter of a red blood cell in an adult is 7.5 microns. (7.5 – 8.3 µm).

Macrocytes - the diameter of a red blood cell is from 8 to 12 microns. Macrocytosis is observed when the curve shifts to the right.

Microcytes - red blood cell diameter less than 6 microns - shift of the curve to the left. Dwarf red blood cells with a shortened life span are detected.

The flat shape of the Price-Jones curve indicates an increase in the number of both microcytes and macrocytes. This phenomenon is called anisocytosis.

Red blood cells have reversible deformation, that is, they have plasticity.

As we age, the plasticity of red blood cells decreases.

The most well-known pathologically altered forms of red blood cells are spherocytes (round-shaped red blood cells) and sickle-shaped red blood cells (SCR).

Poikilocytosis- a condition in which red blood cells of various unusual shapes occur.

Functions of erythrocytes: transport, protective, regulatory.

Transport function: transport O 2 and CO 2, amino acids, polypeptides, proteins, carbohydrates, enzymes, hormones, fats, cholesterol, biologically active substances, trace elements, etc.

Protective function: play a role in specific and nonspecific immunity, take part in vascular-platelet hemostasis, blood coagulation and fibrinolysis.

Regulatory function: thanks to hemoglobin, they regulate blood pH, ionic composition of plasma and water metabolism.

Penetrating into the arterial end of the capillary, the erythrocyte gives up water and O2 dissolved in it and decreases in volume, and when moving to the venous end of the capillary, it takes up water, CO2 and metabolic products coming from the tissues and increases in volume.

Help maintain the relative constancy of blood plasma. For example, if the concentration of proteins in the plasma increases, red blood cells actively adsorb them. If the protein content in plasma decreases, red blood cells release them into the plasma.

Erythrocytes are regulators of erythropoiesis, because. they contain erythropoietic factors, which, when red blood cells are destroyed, enter the bone marrow and promote the formation of red blood cells.

Erythropoiesis is the process of formation of red blood cells.

Red blood cells are formed in hematopoietic tissues:

In the yolk sac of the embryo

In the liver and spleen of the fetus

In the red bone marrow of flat bones in an adult.

The common precursors of all blood cells are pluripotent (pluripotent) stem cells, which are found in all hematopoietic organs.

At the next stage of erythropoiesis, committed precursors are formed, from which only one type of blood cell can develop: erythrocytes, monocytes, granulocytes, platelets or lymphocytes.

Table cell → Basophilic proerythrblast → Erythroblast (macroblast) → Normoblast → Reticulocytes II, III, IV → Erythrocytes.

Anucleate young red blood cells leave the bone marrow in the form of so-called reticulocytes. Unlike red blood cells, reticulocytes retain elements of cellular structures. The number of reticulocytes is important information about the state of erythropoiesis. Normally, the number of reticulocytes is 0.5 - 2% of the total number of red blood cells. When erythropoiesis accelerates, the number of reticulocytes increases, and when erythropoiesis slows down, it decreases. With increased destruction of red blood cells, the number of reticulocytes can exceed 50%. The transformation of a reticulocyte into a young erythrocyte (normocyte) occurs in 35-45 hours.

Mature erythrocytes circulate in the blood for 80-120 days, after which they are phagocytosed primarily by cells of the reticuloendothelial system of the bone marrow, macrophages (“erythrophagocytosis”). The resulting destruction products, and primarily iron, are used to build new red blood cells. Castle introduced the concept of “erythron” to refer to the entire mass of red blood cells in the circulating blood, in the blood depots and in the bone marrow.

Any tissue in the body can also destroy red blood cells (disappearance of “bruises”).

Every 24 hours, approximately 0.8% of the total number of red blood cells (25 · 10 12 pcs.) is renewed. In 1 minute, 60 · 10 6 red blood cells are formed.

The rate of erythropoiesis increases several times

For blood loss

When the partial pressure of O 2 decreases

Under the influence of substances that accelerate erythropoiesis - erythropoietins.

The place of synthesis of erythropoietins is the kidneys, liver, tear, bone marrow. Erythropoietin stimulates differentiation and accelerates the proliferation of red blood cell precursors in the bone marrow.

The effect of erythropoietin is enhanced by androgens, thyroxine, and growth hormones.

Androgens enhance erythropoiesis, and estrogens inhibit erythropoiesis.

Osmotic properties of erythrocytes.

When red blood cells are placed in a hypotonic solution, hemolysis develops - this is the rupture of the red blood cell membrane and the release of hemoglobin into the plasma, due to which the blood acquires a varnish color. The minimum limit of hemolysis for healthy people corresponds to a solution containing 0.42 - 0.48% NaCl. The maximum resistance limit is 0.28 - 0.34% NaCl.

The causes of hemolysis can also be chemical agents (chloroform, ether, etc.), venoms of some snakes (biological hemolysis), exposure to low and high temperatures (thermal hemolysis), incompatibility of transfused blood (immune hemolysis), and mechanical effects.

Erythrocyte sedimentation rate(ESR).

Blood provides a suspension or suspension of red blood cells. The suspension of red blood cells in plasma is maintained by the hydrophilic nature of their surface, as well as the negative charge that causes them to repel each other. With a decrease, negative red blood cells collide with each other, forming so-called “coin columns”.

Farreus - placing blood in a test tube, after adding Na citrate (which prevents blood clotting), discovered that the blood was divided into two layers. The bottom layer represents the formed elements.

The main reasons affecting the erythrocyte sedimentation rate:

The amount of negative charge on the surface of red blood cells

The magnitude of the positive charge of plasma proteins and their properties

Infectious, inflammatory and oncological diseases.

The value of ESR depends to a greater extent on the properties of plasma than on the properties of erythrocytes. For example, if normal red blood cells of men are placed in the blood plasma of a pregnant woman, then the red blood cells of men will settle at the same rate as those of women during pregnancy.

ESR – in newborns – 1-2 mm/h; for men – 6-12 mm/h; for women – 8-15 mm/h; in older people – 15-20 mm/h.

ESR increases with increasing fibrinogen concentration, for example during pregnancy; for inflammatory, infectious and oncological diseases; as well as with a decrease in the number of red blood cells. A decrease in ESR in children over 1 year of age is considered an unfavorable sign.

Hemoglobin and its compounds.

The main functions of red blood cells are determined by the presence of hemoglobin in their composition. Its molecular weight is 68800. Hemoglobin consists of a protein part (globin) and iron-containing parts (heme) 1: 4 (there are 4 heme molecules per globin molecule).

Heme consists of a porphyrin molecule, in the center of which there is an Fe 2+ ion capable of attaching O 2.

The structure of the protein part of hemoglobin is not the same, i.e. the protein part of hemoglobin can be divided into a number of fractions: A fraction - 95-98% for an adult; And fraction 2 – 2-3%; F fraction – 1-2%.

Fraction F is fetal hemoglobin, which is contained in the fetus. Fetal hemoglobin has a greater affinity for O 2 than hemoglobin A. By the time the child is born, it accounts for 70-90%. This allows the fetal tissues not to experience hypoxia at a relatively low O 2 voltage.

Hemoglobin has the ability to form compounds with O 2, CO 2 and CO:

hemoglobin with O 2 (gives the light red color of blood) - called oxyhemoglobin (HHbO 2);

hemoglobin that has given up O 2 is called reduced or reduced (HHb);

hemoglobin with CO 2 is called carbohemoglobin (HHbCO 2) (dark blood) 10-20% of all CO 2 transported by blood;

hemoglobin forms a strong carboxyhemoglobin (HhbCO) bond with CO; the affinity of hemoglobin for CO is higher than for O2.

The rate of breakdown of carboxyhemoglobin increases when pure O 2 is inhaled.

Strong oxidizing agents (ferrocyanide, berthollet salt, hydrogen peroxide) change the charge of Fe 2+ to Fe 3+ - oxidized hemoglobin METHHEMOGLOBIN appears, a strong compound with O 2; O2 transport is disrupted, which leads to severe consequences for humans and death.

When red blood cells are destroyed, bilirubin is formed from the released hemoglobin, which is one of the components of bile.

Color index(farb index Fi).

A relative value characterizing the saturation of an average of 1 red blood cell with hemoglobin. A value equal to 166.7 g/l is taken as 100% hemoglobin, and 5 * 10 12 as 100% erythrocytes. If a person has 100% hemoglobin and red blood cells, then the color index is 1.

It is calculated by the formula: CP = Hb (g/l) * 3 / (the first three digits of the number of red blood cells).

Normal range is from 0.85 to 1.15 (normochromic red blood cells). If less than 0.85 – hypochromic erythrocytes. If more than 1.15 - hyperchromic. In this case, the volume of the red blood cell increases, which allows it to contain a higher concentration of hemoglobin. This gives the false impression that the red blood cells are oversaturated with hemoglobin.

Hypo- and hyperchromia occur in anemia.

Anemia.

Anemia (bloodlessness) is a decrease in the ability to carry oxygen, associated either with a decrease in the number of red blood cells, or with a decrease in the hemoglobin content of red blood cells, or both.

Iron deficiency anemia occurs with a lack of iron in food (in children), with impaired absorption of iron in the digestive tract, with chronic blood loss (peptic ulcer, tumors, colitis, helminthic infestations, etc.). Small red blood cells with a reduced hemoglobin content are formed in the blood.

Megablastic anemia is the presence in the blood and bone marrow of enlarged red blood cells (megalocytes) and immature precursors of megalocytes (megablasts). Occurs when there is a lack of substances that promote the maturation of red blood cells (vitamin B 12), i.e. with delayed maturation of red blood cells.

Hemolytic anemia is associated with increased fragility of red blood cells, which leads to increased hemolysis. The cause is congenital forms of spherocytosis, sickle cell anemia and thalassemia. This category also includes anemia that occurs due to malaria and Rh incompatibility.

Aplastic anemia and pancytopenia are inhibition of bone marrow hematopoiesis. Erythropoiesis is suppressed. The cause is a hereditary form and/or damage to the bone marrow by ionizing radiation.

6.3. LEUCOCYTES

White blood cells (leukocytes) are formations of various shapes and sizes. They are divided into two large groups:

granular (granulocytes): neutrophils, eosinophils, basophils

non-granular (agranulocytes): lymphocytes, monocytes.

Granulocytes get their name from their ability to stain with dyes: eosinophils are stained with eosin (acid dye), basophils with hematoxylin (alkaline dye), and neutrophils with both.

Normally, the number of leukocytes in adults ranges from 4.5 to 8.5 thousand per 1 mm3. An increased number of white blood cells is called – leukocytosis. Reduced – leukopenia.

Leukopenia occurs only in pathology. Particularly severe in case of bone marrow damage (acute leukemia, radiation sickness). At the same time, not only the number of leukocytes decreases, but their functional activity also changes. There are disturbances in specific and nonspecific protection, and associated diseases (often of an infectious nature).

Leukocytosis can be physiological and pathological. Physiological leukocytosis: food; myogenic; emotional; during pregnancy.

Dietary leukocytosis. Occurs after eating (increase by 1-3 thousand in 1 μl), rarely goes beyond the physiological norm. A large number of leukocytes accumulate in the submucosa of the small intestine. Here they perform a protective function, preventing foreign agents from entering the blood and lymph.

It is redistributive in nature. It is ensured by the entry of leukocytes into the bloodstream from the blood depot.

Myogenic leukocytosis. Observed after performing heavy muscular work. The number of leukocytes can increase 3-5 times. White blood cells accumulate in the muscles. It is both redistributive and true in nature, because with this leukocytosis, bone marrow hematopoiesis increases.

Emotional leukocytosis (as with painful stimulation) is redistributive in nature. Rarely achieves high levels.

Leukocytosis during pregnancy. Accumulate in the submucosa of the uterus. This leukocytosis is mainly local in nature. This leukocytosis prevents infections and stimulates the contractile function of the uterus.

Leukocyte formula (leukogram).

Mature and young forms of leukocytes can be found in the blood. Normally, they are easiest to detect in the largest group, i.e. in neutrophils. Young neutrophils (myelocytes) have a rather large bean-shaped nucleus. Band nuclear - a nucleus that is not divided into separate segments. Mature, or segmented, have a nucleus divided into 2-3 segments. The more segments, the older the neutrophil.

An increase in the number of young and band neutrophils indicates rejuvenation of the blood - this is a shift in the leukocyte formula to the left (leukemia, leukemia, infections, inflammation). A decrease in the number of these cells indicates aging of the blood - this is a shift in the leukocyte formula to the right.

Neutrophils.

They mature in the bone marrow and remain there for 3-5 days, forming a bone marrow reserve of granulocytes. They enter the vascular bed due to amoeboid movement and the release of proteolytic enzymes that can dissolve bone marrow and capillary proteins.

Neutrophils live in circulating blood from 8 hours to 2 days. Conventionally divided into: 1) freely circulating; and 2) occupying a marginal position in the vessels. There is a dynamic balance and constant exchange between these groups. That. there are approximately 2 times more neutrophils in the vascular bed than are detected in the flowing blood.

It is assumed that the destruction of neutrophils occurs outside the vascular bed. All leukocytes go into the tissues, where they die. They have a phagocytic function. Absorb bacteria and tissue destruction products.

In 1968, the cytotoxic effect, or killing, was discovered. In the presence of IgG and in the presence of complement, they approach the target cell, but do not phagocytose, but damage at a distance, due to the release of reactive oxygen species - hydrogen peroxide, hypochloric acid, etc.

Products are isolated that enhance the mitotic activity of cells, accelerate repair processes, stimulate hematopoiesis and dissolution of the fibrin clot.

In clinical practice, it is necessary to study not only the quantity, but also the functional activity of neutrophils. Hypofunction of neutrophils is a variant of immunodeficiency. Manifests itself in a decrease in the migration ability and bactericidal activity of neutrophils.

Basophils.

There are few basophils in the blood (40-60 in 1 μl), but various tissues, including the vascular wall, contain “tissue basophils” or mast cells.

Absorption, synthesis, accumulation and release of biologically active substances.

Histamine – increases tissue permeability, dilates blood vessels, enhances hemocoagulation, and in high concentrations causes inflammation.

Heparin is a histamine antagonist. Anticoagulant (prevents blood clotting). Inhibits fibrinolysis (destruction of fibrin), many lysosomal enzymes, histaminase (destroying histamine).

Hyaluronic acid (affects the permeability of the vascular wall).

Platelet activating factor.

Thromboxanes (promote platelet aggregation).

Arachidonic acid derivatives play an important role in allergic reactions (bronchial asthma, urticaria, drug disease).

The number of basophils increases during leukemia, stressful situations and slightly during inflammation.

In connection with the isolation of various forms of basophils and the identification of various biologically active substances in them, there are synonyms - heparinocyte, histaminocyte, mast cell, etc.

The antagonists of basophils are eosinophils and macrophages.

Eosinophils.

The duration of stay of eosinophils in the bloodstream does not exceed several hours, after which they penetrate into tissues, where they are destroyed.

In tissues, eosinophils accumulate in those organs where histamine is contained - in the mucous membrane and submucosa of the stomach, small intestine, and lungs. Eosinophils take up and destroy histamine using the enzyme histaminase. They are also able to inactivate heparin and phagocytose granules secreted by basophils. These properties are associated with the participation of eosinophils in reducing immediate hypersensitivity reactions.

Phagocytic activity is pronounced. Cocci are especially intensively phagocytosed.

The role of eosinophils in the fight against helminths, their eggs and larvae (anthelminthic immunity) is extremely important. When an activated eosinophil comes into contact with larvae, it degranulates, followed by the release of a large amount of protein and enzymes (for example, peroxidases) onto the surface of the larva, which leads to the destruction of the latter.

Eosinophils are able to bind antigens, preventing them from entering the vascular bed.

Eosinophils contain cationic proteins that activate components of the kallekrein-kinin system and affect blood clotting.

In severe infections, the number of eosinophils decreases. Sometimes they are not detected at all (aneosinopenia).

Monocytes:

They circulate in the blood for up to 70 hours, then migrate into tissues, forming an extensive family of tissue macrophages.

They are extremely active phagocytes and have cytotoxic effects. The apparatus of lysosomes containing important enzymes has been developed.

The outer plasma membrane contains numerous receptors, including those that allow “recognition” of immunoglobulins, a fragment of complement, and lymphocyte mediators - lymphokines. Due to this, macrophages play a role not only in cellular nonspecific immunity, but also participate in the regulation of specific immunity. They recognize the antigen, convert it into an immunogenic form, and form biologically active compounds - monokines that act on lymphocytes.

Lymphocytes.

Like other leukocytes, lymphocytes are formed in the bone marrow and then enter the vascular bed. Some lymphocytes receive “specialization” in the thymus gland where they turn into T-lymphocytes (thymus-dependent).

Another population is B lymphocytes (bursa - in birds). In humans and mammals, their formation occurs in the bone marrow, or in the system of lymphoid-epithelial formations located along the small intestine (lymphoid or Peyer's patches).

T lymphocytes:

Killer T cells (killers) - carry out lysis (destruction) of target cells.

T-helpers (helpers) – enhance cellular immunity.

T-T - helpers - enhance cellular immunity.

T-B - helpers - strengthen humoral immunity.

T-amplifiers – enhance the functional activity of lymphocytes.

Suppressor T cells – interfere with the immune response.

T-T suppressors – suppress cellular immunity.

T-B suppressors – suppress humoral immunity.

T - countersuppressors - interfere with the action of T-suppressors and thereby enhance the immune response.

T - immune memory cells that store information about previously active antigens and regulate the secondary immune response, which develops in a shorter time.

Td lymphocytes (differentiating). They regulate the function of hematopoietic stem cells, the ratio of erythrocyte, platelet, and leukocyte sprouts of the bone marrow.

B lymphocytes.

Most B lymphocytes, in response to the action of antigens and cytokines, turn into plasma cells and produce antibodies (antibody producers).

In addition, among B-lymphocytes there are:

Killer B cells (same function as killer T cells).

B-helpers – enhance the effect of Td-lymphocytes and T-suppressors.

B-suppressors – inhibit the proliferation of antibody producers.

There are neither T- nor B-lymphocytes - 0-lymphocytes (precursors of T- and B-lymphocytes).

Some researchers include NK lymphocytes (natural killer cells) as 0-lymphocytes.

There are cells that carry markers of both T- and B-lymphocytes (double cells) and are capable of replacing both.

Cytotoxic effects:

They secrete proteins that can drill holes in the membranes of foreign cells. They contain proteolytic enzymes (cytolysins), which penetrate into a foreign cell through the formed pores and destroy it.

IMMUNITY

Immunity is a way of protecting the body from living bodies and substances that carry signs of foreign genetic information.

Immunological regulation, on the one hand, is an integral part of humoral regulation, since most processes are carried out with the direct participation of humoral intermediaries. However, immune regulation is often targeted in nature, and thus resembles nervous regulation. Lymphocytes and monocytes, as well as other cells participating in the immune response, give the humoral messenger directly to the target organ. Hence immunological regulation is called cellular-humoral.

The immune system is represented by all types of leukocytes, as well as organs in which leukocytes develop: bone marrow, thymus, spleen, lymph nodes.

There are nonspecific and specific immunity:

1. Nonspecific – directed against any foreign substance (antigen). Manifests itself in the form of humoral - production of bactericidal substances; and cellular – phagocytosis, cytotoxic effect (1968...)

Phagocytosis is inherent in: neutrophils, eosinophils, monocytes, macrophages. The cytotoxic effect also affects lymphocytes.

2. Specific – directed against a specific foreign substance. Also in 2 forms: humoral - production of antibodies by B lymphocytes and plasma cells and cellular - with the participation of T lymphocytes.

During an immune response, the mechanisms of both humoral and cellular immunity usually operate, but to varying degrees (in measles, the humoral response predominates, in contact allergies, the cellular response predominates).

Topic: “BLOOD BIOCHEMISTRY. BLOOD PLASMA: COMPONENTS AND THEIR FUNCTIONS. METABOLISM OF ERYTHROCYTES. THE IMPORTANCE OF BIOCHEMICAL BLOOD ANALYSIS IN THE CLINIC"

1. Blood plasma proteins: biological role. Content of protein fractions in plasma. Changes in the protein composition of plasma under pathological conditions (hyperproteinemia, hypoproteinemia, dysproteinemia, paraproteinemia).
2. Proteins of the acute phase of inflammation: biological role, examples of proteins.
3. Lipoprotein fractions of blood plasma: compositional features, role in the body.
4. Blood plasma immunoglobulins: main classes, structure diagram, biological functions. Interferons: biological role, mechanism of action (scheme).
5. Blood plasma enzymes (secretory, excretory, indicator): diagnostic value of studying the activity of aminotransferases (ALT and AST), alkaline phosphatase, amylase, lipase, trypsin, lactate dehydrogenase isoenzymes, creatine kinase.
6. Non-protein nitrogen-containing blood components (urea, amino acids, uric acid, creatinine, indican, direct and indirect bilirubin): structure, biological role, diagnostic value of their determination in the blood. Concept of azotemia.
7. Nitrogen-free organic blood components (glucose, cholesterol, free fatty acids, ketone bodies, pyruvate, lactate), the diagnostic value of their determination in the blood.
8. Features of the structure and function of hemoglobin. Regulators of hemoglobin affinity for O2. Molecular forms of hemoglobin. Hemoglobin derivatives. Clinical and diagnostic value of determining hemoglobin in the blood.
9. Erythrocyte metabolism: the role of glycolysis and the pentose phosphate pathway in mature erythrocytes. Glutathione: role in red blood cells. Enzyme systems involved in the neutralization of reactive oxygen species.
10. Blood coagulation as a cascade of activation of proenzymes. Internal and external coagulation pathways. The general pathway of blood coagulation: activation of prothrombin, conversion of fibrinogen to fibrin, formation of fibrin polymer.
11. Participation of vitamin K in post-translational modification of blood coagulation factors. Dicumarol as antivitamin K.

30.1. Composition and functions of blood.

Blood- liquid mobile tissue circulating in a closed system of blood vessels, transporting various chemicals to organs and tissues, and integrating metabolic processes occurring in various cells.

Blood is made up of plasma And shaped elements (erythrocytes, leukocytes and platelets). Blood serum differs from plasma in the absence of fibrinogen. 90% of blood plasma is water, 10% is a dry residue, which includes proteins, non-protein nitrogenous components (residual nitrogen), nitrogen-free organic components and minerals.

30.2. Blood plasma proteins.

Blood plasma contains a complex multicomponent (more than 100) mixture of proteins that differ in origin and function. Most plasma proteins are synthesized in the liver. Immunoglobulins and a number of other protective proteins by immunocompetent cells.

30.2.1. Protein fractions. By salting out plasma proteins, albumin and globulin fractions can be isolated. Normally, the ratio of these fractions is 1.5 - 2.5. Using the paper electrophoresis method makes it possible to identify 5 protein fractions (in descending order of migration speed): albumins, α1 -, α2 -, β- and γ-globulins. When using finer fractionation methods, a whole range of proteins can be isolated in each fraction, except albumin (the content and composition of protein fractions of blood serum, see Figure 1).

Picture 1. Electropherogram of blood serum proteins and composition of protein fractions.

Albumin- proteins with a molecular weight of about 70,000 Da. Due to their hydrophilicity and high content in plasma, they play an important role in maintaining colloid-osmotic (oncotic) blood pressure and regulating the exchange of fluids between blood and tissues. They perform a transport function: they transport free fatty acids, bile pigments, steroid hormones, Ca2 + ions, and many drugs. Albumins also serve as a rich and quickly available reserve of amino acids.

α 1 -Globulins:

• Sour α 1-glycoprotein (orosomucoid) - contains up to 40% carbohydrates, its isoelectric point is in an acidic environment (2.7). The function of this protein is not fully established; it is known that in the early stages of the inflammatory process, orosomucoid promotes the formation of collagen fibers at the site of inflammation (Ya. Musil, 1985).
• α 1 - Antitrypsin - inhibitor of a number of proteases (trypsin, chymotrypsin, kallikrein, plasmin). A congenital decrease in the content of α1-antitrypsin in the blood may be a predisposition factor to bronchopulmonary diseases, since the elastic fibers of the lung tissue are especially sensitive to the action of proteolytic enzymes.
• Retinol binding protein transports fat-soluble vitamin A.
• Thyroxine binding protein - binds and transports iodine-containing thyroid hormones.
• Transcortin - binds and transports glucocorticoid hormones (cortisol, corticosterone).

α 2 -Globulins:

• Haptoglobins (25% α2-globulins) - form a stable complex with hemoglobin that appears in the plasma as a result of intravascular hemolysis of erythrocytes. Haptoglobin-hemoglobin complexes are taken up by RES cells, where heme and protein chains undergo breakdown and iron is reused for hemoglobin synthesis. This prevents the body from losing iron and causing hemoglobin damage to the kidneys.
• Ceruloplasmin - a protein containing copper ions (one ceruloplasmin molecule contains 6-8 Cu2+ ions), which give it a blue color. It is a transport form of copper ions in the body. It has oxidase activity: it oxidizes Fe2+ to Fe3+, which ensures the binding of iron by transferrin. Capable of oxidizing aromatic amines, participates in the metabolism of adrenaline, norepinephrine, and serotonin.

β-Globulins:

• Transferrin - the main protein of the β-globulin fraction, is involved in the binding and transport of ferric iron into various tissues, especially hematopoietic tissues. Transferrin regulates Fe3+ levels in the blood and prevents excess accumulation and loss in urine.
• Hemopexin - binds heme and prevents its loss by the kidneys. The heme-hemopexin complex is taken up from the blood by the liver.
• C-reactive protein (CRP) - a protein capable of precipitating (in the presence of Ca2+) C-polysaccharide of the pneumococcal cell wall. Its biological role is determined by its ability to activate phagocytosis and inhibit the process of platelet aggregation. In healthy people, the concentration of CRP in plasma is negligible and cannot be determined by standard methods. During an acute inflammatory process, it increases more than 20 times; in this case, CRP is detected in the blood. The study of CRP has an advantage over other markers of the inflammatory process: determination of ESR and counting the number of leukocytes. This indicator is more sensitive, its increase occurs earlier and after recovery it returns to normal faster.

γ-Globulins:

• Immunoglobulins (IgA, IgG, IgM, IgD, IgE) are antibodies produced by the body in response to the introduction of foreign substances with antigenic activity. For more information about these proteins, see 1.2.5.

30.2.2. Quantitative and qualitative changes in the protein composition of blood plasma. Under various pathological conditions, the protein composition of blood plasma may change. The main types of changes are:

• Hyperproteinemia - increase in the content of total plasma protein. Causes: loss of large amounts of water (vomiting, diarrhea, extensive burns), infectious diseases (due to an increase in the amount of γ-globulins).
• Hypoproteinemia - decrease in the content of total protein in plasma. It is observed in liver diseases (due to impaired protein synthesis), kidney diseases (due to loss of proteins in the urine), and during fasting (due to a lack of amino acids for protein synthesis).
• Dysproteinemia - change in the percentage of protein fractions with a normal content of total protein in the blood plasma, for example, a decrease in albumin content and an increase in the content of one or more globulin fractions in various inflammatory diseases.
• Paraproteinemia - the appearance in the blood plasma of pathological immunoglobulins - paraproteins that differ from normal proteins in physicochemical properties and biological activity. Such proteins include, for example, cryoglobulins, forming precipitates with each other at temperatures below 37 ° C. Paraproteins are found in the blood with Waldenström's macroglobulinemia, with multiple myeloma (in the latter case they can overcome the renal barrier and are found in the urine as Bence-Jones proteins). Paraproteinemia is usually accompanied by hyperproteinemia.

30.2.3. Lipoprotein fractions of blood plasma. Lipoproteins are complex compounds that transport lipids in the blood. They include: hydrophobic core containing triacylglycerols and cholesterol esters, and amphiphilic shell, formed by phospholipids, free cholesterol and apoproteins (Figure 2). Human blood plasma contains the following fractions of lipoproteins:

Figure 2. Scheme of the structure of blood plasma lipoprotein.

• High density lipoproteins or α-lipoproteins , since during electrophoresis on paper they move along with α-globulins. They contain many proteins and phospholipids and transport cholesterol from peripheral tissues to the liver.
• Low density lipoproteins or β-lipoproteins , since during electrophoresis on paper they move along with β-globulins. Rich in cholesterol; transport it from the liver to peripheral tissues.
• Very low density lipoproteins or pre-β-lipoproteins (located on the electropherogram between α- and β-globulins). They serve as a transport form of endogenous triacylglycerols and are precursors of low-density lipoproteins.
• Chylomicrons - electrophoretically immobile; are absent in blood taken on an empty stomach. They are a transport form of exogenous (food) triacylglycerols.

30.2.4. Proteins of the acute phase of inflammation. These are proteins whose content increases in the blood plasma during an acute inflammatory process. These include, for example, the following proteins:

1. haptoglobin ;
2. ceruloplasmin ;
3. C-reactive protein ;
4. α 1 -antitrypsin ;
5. fibrinogen (component of the blood coagulation system; see 30.7.2).

The rate of synthesis of these proteins increases primarily due to a decrease in the formation of albumin, transferrin and albumin (a small fraction of plasma proteins that has the greatest mobility during disk electrophoresis, and which corresponds to the band on the electropherogram in front of albumin), the concentration of which decreases during acute inflammation.

The biological role of acute phase proteins: a) all these proteins are inhibitors of enzymes released during cell destruction and prevent secondary tissue damage; b) these proteins have an immunosuppressive effect (V.L. Dotsenko, 1985).

30.2.5. Protective proteins in blood plasma. Proteins that perform a protective function include immunoglobulins and interferons.

Immunoglobulins (antibodies) - a group of proteins produced in response to foreign structures (antigens) entering the body. They are synthesized in the lymph nodes and spleen by B lymphocytes. There are 5 classes immunoglobulins- IgA, IgG, IgM, IgD, IgE.

Figure 3. Diagram of the structure of immunoglobulins (the variable region is shown in gray, the constant region is not shaded).

Immunoglobulin molecules have a single structure plan. The structural unit of immunoglobulin (monomer) is formed by four polypeptide chains connected to each other by disulfide bonds: two heavy (H chains) and two light (L chains) (see Figure 3). IgG, IgD and IgE are, as a rule, monomers in their structure, IgM molecules are built from five monomers, IgA consist of two or more structural units, or are monomers.

The protein chains that make up immunoglobulins can be divided into specific domains, or areas that have certain structural and functional features.

The N-terminal regions of both the L and H chains are called the variable region (V), since their structure is characterized by significant differences between different classes of antibodies. Within the variable domain there are 3 hypervariable regions, characterized by the greatest diversity of amino acid sequences. It is the variable region of antibodies that is responsible for the binding of antigens according to the principle of complementarity; the primary structure of the protein chains in this region determines the specificity of antibodies.

The C-terminal domains of the H and L chains have a relatively constant primary structure within each class of antibodies and are called the constant region (C). The constant region determines the properties of various classes of immunoglobulins, their distribution in the body, and can take part in triggering mechanisms that cause the destruction of antigens.

Interferons - a family of proteins synthesized by body cells in response to a viral infection and having an antiviral effect. There are several types of interferons that have a specific spectrum of action: leukocyte (α-interferon), fibroblast (β-interferon) and immune (γ-interferon). Interferons are synthesized and secreted by some cells and exert their effect by affecting other cells, in this respect they are similar to hormones. The mechanism of action of interferons is shown in Figure 4.

Figure 4. The mechanism of action of interferons (Yu.A. Ovchinnikov, 1987).

By binding to cellular receptors, interferons induce the synthesis of two enzymes - 2",5"-oligoadenylate synthetase and protein kinase, probably due to the initiation of transcription of the corresponding genes. Both resulting enzymes exhibit their activity in the presence of double-stranded RNA, and it is these RNAs that are the replication products of many viruses or are contained in their virions. The first enzyme synthesizes 2",5"-oligoadenylates (from ATP), which activate cellular ribonuclease I; the second enzyme phosphorylates the translation initiation factor IF2. The end result of these processes is the inhibition of protein biosynthesis and virus reproduction in the infected cell (Yu.A. Ovchinnikov, 1987).

30.2.6. Blood plasma enzymes. All enzymes contained in blood plasma can be divided into three groups:

1. secretory enzymes - synthesized in the liver and released into the blood, where they perform their function (for example, blood clotting factors);
2. excretory enzymes - synthesized in the liver, normally excreted in bile (for example, alkaline phosphatase), their content and activity in the blood plasma increases when the outflow of bile is impaired;
3. indicator enzymes - are synthesized in various tissues and enter the bloodstream when the cells of these tissues are destroyed. Different enzymes predominate in different cells, so when a particular organ is damaged, enzymes characteristic of it appear in the blood. This can be used in diagnosing diseases.

For example, if liver cells are damaged ( hepatitis) the activity of alanine aminotransferase (ALT), aspartate aminotransferase (ACT), lactate dehydrogenase isoenzyme LDH5, glutamate dehydrogenase, and ornithine carbamoyltransferase increases in the blood.

When myocardial cells are damaged ( heart attack) in the blood, the activity of aspartate aminotransferase (ACT), the lactate dehydrogenase LDH1 isoenzyme, and the creatine kinase MB isoenzyme increases.

When pancreatic cells are damaged ( pancreatitis) the activity of trypsin, α-amylase, and lipase increases in the blood.

30.3. Non-protein nitrogenous components of blood (residual nitrogen).

This group of substances includes: urea, uric acid, amino acids, creatine, creatinine, ammonia, indican, bilirubin and other compounds (see Figure 5). The content of residual nitrogen in the blood plasma of healthy people is 15-25 mmol/l. An increase in the level of residual nitrogen in the blood is called azotemia . Depending on the cause, azotemia is divided into retention and production.

Retention azotemia occurs when there is a violation of the excretion of nitrogen metabolism products (primarily urea) in the urine and is characteristic of insufficiency of renal function. In this case, up to 90% of the non-protein nitrogen in the blood is urea nitrogen instead of 50% normally.

Productive azotemia develops when there is an excessive intake of nitrogenous substances into the blood due to increased breakdown of tissue proteins (prolonged fasting, diabetes mellitus, severe wounds and burns, infectious diseases).

Determination of residual nitrogen is carried out in protein-free blood serum filtrate. As a result of mineralization of the protein-free filtrate when heated with concentrated H2 SO4, the nitrogen of all non-protein compounds is converted into the form (NH4)2 SO4. NH4 + ions are determined using Nessler's reagent.

• Urea - the main end product of protein metabolism in the human body. It is formed as a result of the neutralization of ammonia in the liver and is excreted from the body by the kidneys. Therefore, the urea content in the blood decreases in liver diseases and increases in renal failure.
• Amino acids- enter the bloodstream when absorbed from the gastrointestinal tract or are products of the breakdown of tissue proteins. In the blood of healthy people, alanine and glutamine predominate among the amino acids, which, along with their participation in protein biosynthesis, are transport forms of ammonia.
• Uric acid- the end product of the catabolism of purine nucleotides. Its content in the blood increases with gout (as a result of increased formation) and with impaired renal function (due to insufficient excretion).
• Creatine- synthesized in the kidneys and liver, in the muscles it is converted into creatine phosphate - a source of energy for the processes of muscle contraction. In diseases of the muscular system, the content of creatine in the blood increases significantly.
• Creatinine- the end product of nitrogen metabolism, formed as a result of dephosphorylation of creatine phosphate in muscles, excreted from the body by the kidneys. The content of creatinine in the blood decreases with diseases of the muscular system, and increases with renal failure.
• Indican - a product of indole neutralization, formed in the liver and excreted by the kidneys. Its content in the blood decreases with liver diseases, and increases with increased processes of protein putrefaction in the intestines, and with kidney diseases.
• Bilirubin (direct and indirect)- products of hemoglobin catabolism. The content of bilirubin in the blood increases with jaundice: hemolytic (due to indirect bilirubin), obstructive (due to direct bilirubin), parenchymal (due to both fractions).

Figure 5. Non-protein nitrogenous compounds of blood plasma.

30.4. Nitrogen-free organic components of blood.

This group of substances includes nutrients (carbohydrates, lipids) and the products of their metabolism (organic acids). Of greatest clinical importance is the determination of blood glucose, cholesterol, free fatty acids, ketone bodies and lactic acid. The formulas of these substances are presented in Figure 6.

• Glucose- the main energy substrate of the body. Its content in healthy people in the blood on an empty stomach is 3.3 - 5.5 mmol/l. Increased blood glucose levels (hyperglycemia) observed after meals, during emotional stress, in patients with diabetes mellitus, hyperthyroidism, Itsenko-Cushing's disease. Reduced blood glucose levels (hypoglycemia) observed during fasting, intense physical activity, acute alcohol poisoning, and insulin overdose.
• Cholesterol- an obligatory lipid component of biological membranes, a precursor of steroid hormones, vitamin D3, bile acids. Its content in the blood plasma of healthy people is 3.9 - 6.5 mmol/l. Increased cholesterol levels in the blood ( hypercholesterolemia) is observed in atherosclerosis, diabetes mellitus, myxedema, gallstone disease. Reducing cholesterol levels in the blood ( hypocholesterolemia) is found in hyperthyroidism, liver cirrhosis, intestinal diseases, fasting, and when taking choleretic drugs.
• Free fatty acids (FFA) used by tissues and organs as energy material. The content of FFA in the blood increases during fasting, diabetes, after the administration of adrenaline and glucocorticoids; decreases in hypothyroidism after insulin administration.
• Ketone bodies. Ketone bodies include acetoacetate, β-hydroxybutyrate, acetone- products of incomplete oxidation of fatty acids. The content of ketone bodies in the blood increases ( hyperketonemia) during fasting, fever, diabetes.
• Lactic acid (lactate)- the end product of anaerobic oxidation of carbohydrates. Its content in the blood increases during hypoxia (physical activity, diseases of the lungs, heart, blood).
• Pyruvic acid (pyruvate)- an intermediate product of the catabolism of carbohydrates and some amino acids. The most dramatic increase in the content of pyruvic acid in the blood is observed during muscular work and vitamin B1 deficiency.

Figure 6. Nitrogen-free organic substances of blood plasma.

30.5. Mineral components of blood plasma.

Minerals are essential components of blood plasma. The most important cations are sodium, potassium, calcium and magnesium ions. They correspond to anions: chlorides, bicarbonates, phosphates, sulfates. Some cations in the blood plasma are associated with organic anions and proteins. The sum of all cations is equal to the sum of anions, since blood plasma is electrically neutral.

• Sodium- the main cation of extracellular fluid. Its content in blood plasma is 135 - 150 mmol/l. Sodium ions are involved in maintaining the osmotic pressure of the extracellular fluid. Hypernatremia is observed with hyperfunction of the adrenal cortex when a hypertonic solution of sodium chloride is administered parenterally. Hyponatremia may be caused by a salt-free diet, adrenal insufficiency, or diabetic acidosis.
• Potassium is the main intracellular cation. In blood plasma it is contained in an amount of 3.9 mmol/l, and in erythrocytes - 73.5 - 112 mmol/l. Like sodium, potassium maintains osmotic and acid-base homeostasis in the cell. Hyperkalemia is observed with increased cell destruction (hemolytic anemia, long-term crush syndrome), with impaired potassium excretion by the kidneys, and with dehydration. Hypokalemia is observed with hyperfunction of the adrenal cortex, with diabetic acidosis.
• Calcium in the blood plasma is contained in the form of forms. Performing various functions: protein-bound (0.9 mmol/l), ionized (1.25 mmol/l) and non-ionized (0.35 mmol/l). Only ionized calcium is biologically active. Hypercalcemia is observed with hyperparathyroidism, hypervitaminosis D, Itsenko-Cushing syndrome, and destructive processes in bone tissue. Hypocalcemia occurs in rickets, hypoparathyroidism, and kidney diseases.
• Chlorides Contained in blood plasma in an amount of 95 - 110 mmol/l, they participate in maintaining osmotic pressure and the acid-base state of extracellular fluid. Hyperchloremia is observed with heart failure, arterial hypertension, hypochloremia - with vomiting, kidney disease.
• Phosphates in blood plasma they are components of the buffer system, their concentration is 1 - 1.5 mmol/l. Hyperphosphatemia is observed in kidney diseases, hypoparathyroidism, hypervitaminosis D. Hypophosphatemia is observed in hyperparathyroidism, myxedema, and rickets.

0.6. Acid-base state and its regulation.

Acid-base state (ABS) is the ratio of the concentrations of hydrogen (H+) and hydroxyl (OH-) ions in body fluids. A healthy person is characterized by relative constancy of CBS indicators, due to the combined action of blood buffer systems and physiological control (respiratory and excretory organs).

30.6.1. Blood buffer systems. The body's buffer systems consist of weak acids and their salts with strong bases. Each buffer system is characterized by two indicators:

• pH buffer(depends on the ratio of buffer components);
• buffer tank, that is, the amount of strong base or acid that must be added to the buffer solution to change the pH by one (depending on the absolute concentrations of the buffer components).

The following blood buffer systems are distinguished:

• bicarbonate(H2 CO3 /NaHCO3);
• phosphate(NaH2PO4 /Na2HPO4);
• hemoglobin(deoxyhemoglobin as a weak acid/potassium salt of oxyhemoglobin);
• protein(its effect is due to the amphoteric nature of proteins). The bicarbonate and closely related hemoglobin buffer systems together account for more than 80% of the buffer capacity of the blood.

30.6.2. Respiratory regulation of CBS carried out by changing the intensity of external respiration. When CO2 and H+ accumulate in the blood, pulmonary ventilation increases, which leads to normalization of the blood gas composition. A decrease in the concentration of carbon dioxide and H+ causes a decrease in pulmonary ventilation and normalization of these indicators.

30.6.3. Renal regulation CBS carried out mainly through three mechanisms:

• reabsorption of bicarbonates (in the cells of the renal tubules, carbonic acid H2 CO3 is formed from H2 O and CO2; it dissociates, H+ is released into the urine, HCO3 is reabsorbed into the blood);
• reabsorption of Na+ from the glomerular filtrate in exchange for H+ (in this case, Na2 HPO4 in the filtrate turns into NaH2 PO4 and the acidity of urine increases) ;
• NH secretion 4 + (during the hydrolysis of glutamine in the tubular cells, NH3 is formed; it interacts with H +, NH4 + ions are formed, which are excreted in the urine.

30.6.4. Laboratory parameters of blood CBS. The following indicators are used to characterize the WWTP:

• blood pH;
• CO2 partial pressure (pCO2) blood;
• O2 partial pressure (pO2) blood;
• bicarbonate content in the blood at given pH and pCO2 values ​​( topical or true bicarbonate, AB );
• the content of bicarbonates in the patient’s blood under standard conditions, i.e. at рСО2 =40 mm Hg. ( standard bicarbonate, S.B. );
• sum of grounds all blood buffer systems ( BB );
• excess or foundation deficiency blood compared to the normal value for a given patient ( BE , from English base excess).

The first three indicators are determined directly in the blood using special electrodes; based on the data obtained, the remaining indicators are calculated using nomograms or formulas.

30.6.5. Blood CBS disorders. There are four main forms of acid-base disorders:

• metabolic acidosis - occurs with diabetes and fasting (due to the accumulation of ketone bodies in the blood), with hypoxia (due to the accumulation of lactate). With this disorder, pCO2 and [HCO3 - ] blood decrease, NH4 + excretion in the urine increases;
• respiratory acidosis - occurs with bronchitis, pneumonia, bronchial asthma (as a result of carbon dioxide retention in the blood). With this disorder, pCO2 and blood levels increase, NH4 + excretion in the urine increases;
• metabolic alkalosis - develops with loss of acids, for example, with uncontrollable vomiting. With this disorder, pCO2 and blood levels increase, HCO3 excretion in the urine increases, and urine acidity decreases.
• respiratory alkalosis - observed with increased ventilation of the lungs, for example, in climbers at high altitudes. With this disorder, pCO2 and [HCO3 - ] blood decrease, and urine acidity decreases.

To treat metabolic acidosis, administration of sodium bicarbonate solution is used; for the treatment of metabolic alkalosis - administration of a solution of glutamic acid.

30.7. Some molecular mechanisms of blood coagulation.

30.7.1. Blood clotting- a set of molecular processes leading to the cessation of bleeding from a damaged vessel as a result of the formation of a blood clot (thrombus). A general diagram of the blood coagulation process is presented in Figure 7.

Figure 7. General diagram of blood coagulation.

Most coagulation factors are present in the blood in the form of inactive precursors - proenzymes, the activation of which is carried out by partial proteolysis. A number of blood coagulation factors are vitamin K-dependent: prothrombin (factor II), proconvertin (factor VII), Christmas factors (IX) and Stewart-Prower (X). The role of vitamin K is determined by its participation in the carboxylation of glutamate residues in the N-terminal region of these proteins with the formation of γ-carboxyglutamate.

Blood clotting is a cascade of reactions in which the activated form of one clotting factor catalyzes the activation of the next until the final factor, which is the structural basis of the clot, is activated.

Features of the cascade mechanism are as follows:

1) in the absence of a factor initiating the thrombus formation process, the reaction cannot occur. Therefore, the process of blood clotting will be limited only to that part of the bloodstream where such an initiator appears;

2) factors acting in the initial stages of blood coagulation are required in very small quantities. At each link of the cascade, their effect is multiplied ( amplified), which ultimately ensures a quick response to damage.

Under normal conditions, there are internal and external pathways of blood clotting. Inner path is initiated by contact with an atypical surface, which leads to the activation of factors initially present in the blood. External path coagulation is initiated by compounds that are not normally present in the blood, but enter there as a result of tissue damage. For the normal course of the blood clotting process, both of these mechanisms are necessary; they differ only at the initial stages, and then combine into common path , leading to the formation of a fibrin clot.

30.7.2. Mechanism of activation of prothrombin. Inactive thrombin precursor - prothrombin - synthesized in the liver. Vitamin K is involved in its synthesis. Prothrombin contains residues of a rare amino acid - γ-carboxyglutamate (abbreviated name - Gla). The process of activation of prothrombin involves platelet phospholipids, Ca2+ ions and coagulation factors Va and Xa. The activation mechanism is presented as follows (Figure 8).

Figure 8. Scheme of activation of prothrombin on platelets (R. Murray et al., 1993).

Damage to a blood vessel leads to the interaction of blood platelets with collagen fibers of the vascular wall. This causes platelet destruction and promotes the release of negatively charged phospholipid molecules from the inner side of the platelet plasma membrane. Negatively charged phospholipid groups bind Ca2+ ions. Ca2+ ions, in turn, interact with γ-carboxyglutamate residues in the prothrombin molecule. This molecule is fixed on the platelet membrane in the desired orientation.

The platelet membrane also contains receptors for factor Va. This factor binds to the membrane and attaches factor Xa. Factor Xa is a protease; it cleaves the prothrombin molecule in certain places, resulting in the formation of active thrombin.

30.7.3. Conversion of fibrinogen to fibrin. Fibrinogen (factor I) is a soluble plasma glycoprotein with a molecular weight of about 340,000. It is synthesized in the liver. The fibrinogen molecule consists of six polypeptide chains: two A α chains, two B β chains, and two γ chains (see Figure 9). The ends of fibrinogen polypeptide chains carry a negative charge. This is due to the presence of a large number of glutamate and aspartate residues in the N-terminal regions of the Aa and Bb chains. In addition, the B-regions of the Bb chains contain residues of the rare amino acid tyrosine-O-sulfate, which are also negatively charged:

This promotes the solubility of the protein in water and prevents the aggregation of its molecules.

Figure 9. Scheme of the structure of fibrinogen; arrows indicate bonds hydrolyzed by thrombin. R. Murray et al., 1993).

The conversion of fibrinogen to fibrin is catalyzed by thrombin (factor IIa). Thrombin hydrolyzes four peptide bonds in fibrinogen: two bonds in the A α chains and two bonds in the B β chains. Fibrinopeptides A and B are split off from the fibrinogen molecule and fibrin monomer is formed (its composition is α2 β2 γ2). Fibrin monomers are insoluble in water and easily associate with each other, forming a fibrin clot.

Stabilization of the fibrin clot occurs under the action of an enzyme transglutaminase (factor XIIIa). This factor is also activated by thrombin. Transglutaminase cross-links fibrin monomers using covalent isopeptide bonds.

30.8. Features of erythrocyte metabolism.

30.8.1. Red blood cells - highly specialized cells whose main function is to transport oxygen from the lungs to the tissues. The lifespan of red blood cells averages 120 days; their destruction occurs in the cells of the reticuloendothelial system. Unlike most cells in the body, the red blood cell lacks a cell nucleus, ribosomes and mitochondria.

30.8.2. Energy exchange. The main energy substrate of the erythrocyte is glucose, which comes from the blood plasma through facilitated diffusion. About 90% of the glucose used by the red blood cell undergoes glycolysis(anaerobic oxidation) with the formation of the final product - lactic acid (lactate). Remember the functions that glycolysis performs in mature red blood cells:

1) in glycolysis reactions it is formed ATP by substrate phosphorylation . The main direction of ATP use in erythrocytes is to ensure the functioning of Na+,K+-ATPase. This enzyme transports Na+ ions from erythrocytes to the blood plasma, prevents the accumulation of Na+ in erythrocytes and helps maintain the geometric shape of these blood cells (biconcave disc).

2) in the dehydrogenation reaction glyceraldehyde-3-phosphate is formed in glycolysis NADH. This coenzyme is a cofactor of the enzyme methemoglobin reductase , involved in the restoration of methemoglobin to hemoglobin according to the following scheme:

This reaction prevents the accumulation of methemoglobin in red blood cells.

3) metabolite of glycolysis 1, 3-diphosphoglycerate capable with the participation of an enzyme diphosphoglycerate mutase in the presence of 3-phosphoglycerate transform into 2, 3-diphosphoglycerate:

2,3-Diphosphoglycerate is involved in the regulation of hemoglobin's affinity for oxygen. Its content in erythrocytes increases during hypoxia. The hydrolysis of 2,3-diphosphoglycerate is catalyzed by the enzyme diphosphoglycerate phosphatase.

Approximately 10% of the glucose consumed by the red blood cell is used in the pentose phosphate oxidation pathway. Reactions in this pathway serve as the main source of NADPH for the erythrocyte. This coenzyme is necessary to convert oxidized glutathione (see 30.8.3) into a reduced form. Deficiency of a key enzyme of the pentose phosphate pathway - glucose-6-phosphate dehydrogenase - accompanied by a decrease in the NADPH/NADP+ ratio in erythrocytes, an increase in the content of the oxidized form of glutathione and a decrease in cell resistance (hemolytic anemia).

30.8.3. Mechanisms of neutralization of reactive oxygen species in erythrocytes. Under certain conditions, molecular oxygen can be converted into active forms, which include superoxide anion O2 -, hydrogen peroxide H2 O2, and hydroxyl radical OH. and singlet oxygen 1 O2. These forms of oxygen are highly reactive and can have a damaging effect on proteins and lipids of biological membranes and cause cell destruction. The higher the O2 content, the more its active forms are formed. Therefore, red blood cells, constantly interacting with oxygen, contain effective antioxidant systems that can neutralize active oxygen metabolites.

An important component of antioxidant systems is the tripeptide glutathione, formed in erythrocytes as a result of the interaction of γ-glutamylcysteine ​​and glycine:

The reduced form of glutathione (abbreviated G-SH) is involved in the detoxification reactions of hydrogen peroxide and organic peroxides (R-O-OH). This produces water and oxidized glutathione (abbreviated G-S-S-G).

The conversion of oxidized glutathione to reduced glutathione is catalyzed by the enzyme glutathione reductase. Hydrogen source - NADPH (from the pentose phosphate pathway, see 30.8.2):

Red blood cells also contain enzymes superoxide dismutase And catalase , carrying out the following transformations:

Antioxidant systems are of particular importance for erythrocytes, since protein renewal does not occur in erythrocytes through synthesis.