Chapter 7. Blood Gases and Acid-Base Balance Blood Gases: Oxygen (O2) and Carbon Dioxide (CO2) Oxygen Transport To survive, a person must be able to absorb oxygen from the atmosphere and transport it to the cells where it is used in metabolism. Some

Blood. What element walks through the veins? How to determine the character of a person by blood group. Astrological correspondence by blood group. There are four blood groups: I, II, III, IV. According to scientists, blood can determine not only the state of human health and

Volume and physico-chemical properties of blood Blood volume - the total amount of blood in the body of an adult is on average 6 - 8% of body weight, which corresponds to 5-6 liters. An increase in the total blood volume is called hypervolemia, a decrease is called hypovolemia. Relative

It moves at different speeds, which depends on the contractility of the heart, the functional state of the bloodstream. At a relatively low flow velocity, blood particles are parallel to each other. This flow is laminar, with the blood flow being layered. If the linear velocity of the blood rises and becomes greater than a certain value, its flow becomes erratic (the so-called "turbulent" flow).

The speed of blood flow is determined using the Reynolds number, its value at which the laminar flow becomes turbulent is approximately 1160. The data indicate that turbulence of the blood flow is possible in the branches of large and at the beginning of the aorta. Most blood vessels are characterized by laminar blood flow. The movement of blood through the vessels is also other important parameters: "shear stress" and "shear rate".

The viscosity of the blood will depend on the shear rate (in the range of 0.1-120 s-1). If the shear rate is greater than 100 s-1, the changes in blood viscosity are not pronounced, after the shear rate reaches 200 s-1, the viscosity does not change.

Shear stress is the force acting per unit area of ​​the vessel and is measured in pascals (Pa). Shear rate is measured in reciprocal seconds (s-1), this parameter indicates the speed at which layers of fluid moving in parallel move relative to each other. Blood is characterized by its viscosity. It is measured in pascal seconds and is defined as the ratio of shear stress to shear rate.

How are the properties of blood evaluated?

The main factor affecting blood viscosity is the concentration of red blood cells, which is called hematocrit. Hematocrit is determined from a blood sample using centrifugation. Blood viscosity also depends on temperature, and is also determined by the composition of proteins. Fibrinogen and globulins have the greatest influence on blood viscosity.

Until now, the task of developing methods for analyzing rheology that would objectively reflect the properties of blood remains relevant.

The main value for assessing the properties of blood is its aggregation state. The main methods for measuring the properties of blood are carried out using various types of viscometers: devices are used that work according to the Stokes method, as well as according to the principle of recording electrical, mechanical, acoustic vibrations; rotational rheometers, capillary viscometers. The use of rheological techniques makes it possible to study the biochemical and biophysical properties of blood in order to control microregulation in metabolic and hemodynamic disorders.

For citation: Shilov A.M., Avshalumov A.S., Sinitsina E.N., Markovsky V.B., Poleshchuk O.I. Changes in the rheological properties of blood in patients with metabolic syndrome // RMJ. 2008. No. 4. S. 200

Metabolic syndrome (MS) is a complex of metabolic disorders and cardiovascular diseases that are pathogenetically interconnected through insulin resistance (IR) and include impaired glucose tolerance (IGT), diabetes mellitus (DM), arterial hypertension (AH), combined with abdominal obesity and atherogenic dyslipidemia (increase in triglycerides - TG, low density lipoprotein - LDL, decrease in high density lipoprotein - HDL).

DM, as a component of MS, in its prevalence takes place immediately after cardiovascular and oncological diseases, and according to WHO experts, its prevalence by 2010 will reach 215 million people.
DM is dangerous for its complications, since vascular damage in diabetes is the cause of the development of hypertension, myocardial infarction, cerebral stroke, kidney failure, loss of vision and amputation of limbs.
From the standpoint of classical biorheology, blood can be considered as a suspension consisting of formed elements in a colloidal solution of electrolytes, proteins and lipids. The microcirculatory section of the vascular system is the place where the greatest resistance to blood flow is manifested, which is associated with the architectonics of the vascular bed and the rheological behavior of blood components.
Blood rheology (from the Greek word rhe'os - flow, flow) - blood fluidity, determined by the totality of the functional state of blood cells (mobility, deformability, aggregation activity of erythrocytes, leukocytes and platelets), blood viscosity (concentration of proteins and lipids), blood osmolarity (glucose concentration). The key role in the formation of rheological parameters of blood belongs to blood cells, primarily erythrocytes, which make up 98% of the total volume of blood cells.
The progression of any disease is accompanied by functional and structural changes in certain blood cells. Of particular interest are changes in erythrocytes, whose membranes are a model of the molecular organization of plasma membranes. Their aggregation activity and deformability, which are the most important components in microcirculation, largely depend on the structural organization of red blood cell membranes.
Blood viscosity is one of the integral characteristics of microcirculation that significantly affects hemodynamic parameters. The share of blood viscosity in the mechanisms of regulation of blood pressure and organ perfusion is reflected in Poiseuille's law:

MOorgan \u003d (Rart - Rven) / Rlok, where Rlok. \u003d 8Lh / pr4,

Where L is the length of the vessel, h is the viscosity of the blood, r is the diameter of the vessel (Fig. 1).
A large number of clinical studies on blood hemorheology in DM and MS have revealed a decrease in the parameters characterizing the deformability of erythrocytes. In patients with diabetes, the reduced ability of erythrocytes to deform and their increased viscosity are the result of an increase in the amount of glycated hemoglobin (HbA1c). It has been suggested that the associated difficulty in blood circulation in the capillaries and the change in pressure in them stimulates the thickening of the basement membrane, leads to a decrease in the coefficient of diffusion oxygen delivery to tissues, that is, abnormal erythrocytes play a trigger role in the development of diabetic angiopathy.
HbA1c is a glycated hemoglobin in which glucose molecules are fused to the b-terminal valine of the b-chain of the HbA molecule. More than 90% of hemoglobin in a healthy person is represented by HbAO, which has 2β- and 2b-polypeptide chains. Glycated forms of hemoglobin make up? HbA = HbA1a + HbA1b + HbA1c. Not all intermediate labile compounds of glucose with HbA are converted into stable ketone forms, since their concentration depends on the duration of contact of the erythrocyte and the amount of glucose in the blood at a particular moment (Fig. 2). At first, this connection between glucose and HbA is “weak” (i.e., reversible), then, with a stable elevated blood sugar level, this connection becomes “strong” and persists until the erythrocytes are destroyed in the spleen. On average, the life span of erythrocytes is 120 days, so the level of sugar-bound hemoglobin (HbA1c) reflects the state of metabolism in a diabetic patient over a period of 3-4 months. The percentage of Hb bound to the glucose molecule gives an idea of ​​the degree of increase in blood sugar; it is the higher, the longer and higher the blood sugar level and vice versa.
Today it is postulated that high blood sugar is one of the main causes of the development of adverse effects of diabetes, the so-called late complications (micro- and macroangiopathies). Therefore, high levels of HbA1c are a marker of the possible development of late complications of DM.
HbA1c, according to various authors, is 4-6% of the total amount of Hb in the blood of healthy people, while in patients with diabetes, the level of HbA1c is 2-3 times higher.
A normal erythrocyte under normal conditions has a biconcave disk shape, due to which its surface area is 20% larger compared to a sphere of the same volume.
Normal erythrocytes are able to significantly deform when passing through the capillaries, while not changing their volume and surface area, which maintains the diffusion of gases at a high level throughout the entire microvasculature of various organs. It has been shown that with a high deformability of erythrocytes, the maximum transfer of oxygen to the cells occurs, and with a deterioration in deformability (increase in rigidity), the supply of oxygen to the cells decreases sharply, and tissue pO2 drops.
Deformability is the most important property of erythrocytes, which determines their ability to perform a transport function. This ability of erythrocytes to change their shape at a constant volume and surface area allows them to adapt to the conditions of blood flow in the microcirculation system. The deformability of erythrocytes is due to factors such as intrinsic viscosity (concentration of intracellular hemoglobin), cellular geometry (maintaining the shape of a biconcave disk, volume, surface to volume ratio), and membrane properties that provide the shape and elasticity of erythrocytes.
Deformability largely depends on the degree of compressibility of the lipid bilayer and the constancy of its relationship with the protein structures of the cell membrane.
The elastic and viscous properties of the erythrocyte membrane are determined by the state and interaction of cytoskeletal proteins, integral proteins, the optimal content of ATP, Ca2+, Mg2+ ions and hemoglobin concentration, which determine the internal fluidity of the erythrocyte. The factors that increase the rigidity of erythrocyte membranes include: the formation of stable hemoglobin compounds with glucose, an increase in the concentration of cholesterol in them and an increase in the concentration of free Ca2 + and ATP in the erythrocyte.
Deterioration of the deformability of erythrocytes occurs when the lipid spectrum of membranes changes, and first of all, when the cholesterol/phospholipids ratio is disturbed, as well as in the presence of products of membrane damage as a result of lipid peroxidation (LPO). LPO products have a destabilizing effect on the structural and functional state of erythrocytes and contribute to their modification. This is expressed in a violation of the physicochemical properties of erythrocyte membranes, a quantitative and qualitative change in membrane lipids, an increase in the passive permeability of the lipid bilayer for K+, H+, Ca2+. In recent studies, using electron spin resonance spectroscopy, a significant correlation was noted between the deterioration of erythrocyte deformability and MS markers (BMI, BP, glucose level after an oral glucose tolerance test, atherogenic dyslipidemia).
The deformability of erythrocytes decreases due to the absorption of plasma proteins, primarily fibrinogen, on the surface of erythrocyte membranes. This includes changes in the membranes of the erythrocytes themselves, a decrease in the surface charge of the erythrocyte membrane, a change in the shape of the erythrocytes and changes in the plasma (protein concentration, lipid spectrum, total cholesterol, fibrinogen, heparin). Increased aggregation of erythrocytes leads to disruption of transcapillary metabolism, release of biologically active substances, stimulates platelet adhesion and aggregation.
Deterioration of erythrocyte deformability accompanies the activation of lipid peroxidation processes and a decrease in the concentration of antioxidant system components in various stressful situations or diseases (in particular, in diabetes and CVD). Intracellular accumulation of lipid peroxides arising from the autoxidation of polyunsaturated fatty acids of membranes is a factor that reduces the deformability of erythrocytes.
Activation of free radical processes causes disturbances in hemorheological properties realized through damage to circulating erythrocytes (oxidation of membrane lipids, increased rigidity of the bilipid layer, glycosylation and aggregation of membrane proteins), having an indirect effect on other parameters of the oxygen transport function of the blood and oxygen transport in tissues. Blood serum with moderately activated LPO, confirmed by a decrease in the level of malondialdehyde (MDA), leads to an increase in the deformability of erythrocytes and a decrease in erythrocyte aggregation. At the same time, a significant and ongoing activation of LPO in serum leads to a decrease in the deformability of erythrocytes and an increase in their aggregation. Thus, erythrocytes are among the first to respond to LPO activation, first by increasing the deformability of erythrocytes, and then, as LPO products accumulate and antioxidant protection is depleted, by an increase in membrane stiffness and aggregation activity, which, accordingly, leads to changes in blood viscosity.
The oxygen-binding properties of blood play an important role in the physiological mechanisms of maintaining a balance between the processes of free radical oxidation and antioxidant protection in the body. These properties of blood determine the nature and magnitude of oxygen diffusion to tissues, depending on the need for it and the effectiveness of its use, contribute to the prooxidant-antioxidant state, showing either antioxidant or prooxidant qualities in various situations.
Thus, the deformability of erythrocytes is not only a determining factor in the transport of oxygen to peripheral tissues and ensuring their need for it, but also a mechanism that affects the effectiveness of the antioxidant defense and, ultimately, the entire organization of maintaining the prooxidant-antioxidant balance of the body.
With IR, an increase in the number of erythrocytes in the peripheral blood was noted. In this case, an increase in erythrocyte aggregation occurs due to an increase in the number of adhesion macromolecules and a decrease in the deformability of erythrocytes is noted, despite the fact that insulin at physiological concentrations significantly improves the rheological properties of blood. In IR accompanied by an increase in blood pressure, a decrease in the density of insulin receptors and a decrease in the activity of tyrosine protein kinase (an intracellular insulin signal transmitter for GLUT) were found, while the number of Na + / H + channels on the erythrocyte membrane increased.
At present, the theory that considers membrane disorders as the leading causes of organ manifestations of various diseases, in particular, hypertension in MS, has become widespread. Membrane disorders are understood as a change in the activity of ion-transporting systems of plasma membranes, manifested in the activation of Na + / H + exchange, an increase in the sensitivity of K + channels to intracellular calcium. The main role in the formation of membrane disorders is assigned to the lipid framework and cytoskeleton as regulators of the structural state of the membrane and intracellular signaling systems (cAMP, polyphosphoinositides, intracellular calcium).
Cellular disorders are based on an excess concentration of free (ionized) calcium in the cytosol (absolute or relative due to the loss of intracellular magnesium, a physiological calcium antagonist). This leads to increased contractility of smooth vascular myocytes, initiates DNA synthesis, increasing growth effects on cells with their subsequent hyperplasia. Similar changes occur in various types of blood cells: erythrocytes, platelets, lymphocytes.
Intracellular redistribution of calcium in platelets and erythrocytes entails damage to microtubules, activation of the contractile system, reaction of the release of biologically active substances (BAS) from platelets, triggering their adhesion, aggregation, local and systemic vasoconstriction (thromboxane A2).
In patients with hypertension, changes in the elastic properties of erythrocyte membranes are accompanied by a decrease in their surface charge, followed by the formation of erythrocyte aggregates. The maximum rate of spontaneous aggregation with the formation of persistent erythrocyte aggregates was noted in patients with grade III AH with a complicated course of the disease. Spontaneous aggregation of erythrocytes enhances the release of intra-erythrocyte ADP, followed by hemolysis, which causes conjugated platelet aggregation. Hemolysis of erythrocytes in the microcirculation system can also be associated with a violation of the deformability of erythrocytes, as a limiting factor in their lifespan.
The most significant changes in the shape of erythrocytes are observed in the microvasculature, some of the capillaries of which have a diameter of less than 2 microns. Vital microscopy shows that erythrocytes moving in the capillary undergo significant deformation, while acquiring various shapes.
In patients with hypertension, combined with diabetes, an increase in the number of abnormal forms of erythrocytes was revealed: echinocytes, stomatocytes, spherocytes and old erythrocytes in the vascular bed.
Leukocytes make a great contribution to hemorheology. Due to their low ability to deform, leukocytes can be deposited at the level of the microvasculature and significantly affect the peripheral vascular resistance.
Platelets occupy an important place in the cellular-humoral interaction of hemostasis systems. Literature data indicate a violation of the functional activity of platelets already at an early stage of AH, which is manifested by an increase in their aggregation activity, an increase in sensitivity to aggregation inducers.
A number of studies have demonstrated the presence of changes in the structure and functional state of platelets in arterial hypertension, which is expressed by an increase in the expression of adhesive glycoproteins on the surface of platelets (GpIIb / IIIa, P-selectin), an increase in density and sensitivity to platelet α-2-adrenergic agonists. no-receptors, an increase in the basal and thrombin-stimulated concentration of Ca2+ ions in platelets, an increase in the plasma concentration of platelet activation markers (soluble P-selectin, b-throm-bo-modulin) , an increase in the processes of free-radical lipid oxidation of platelet membranes.
The researchers noted a qualitative change in platelets in patients with hypertension under the influence of an increase in free calcium in the blood plasma, which correlates with the magnitude of systolic and diastolic blood pressure. An electron microscopic study of platelets in patients with hypertension revealed the presence of various morphological forms of platelets, the result of their increased activation. The most characteristic are such changes in shape as the pseudopodial and hyaline type. A high correlation was noted between an increase in the number of platelets with their altered shape and the frequency of thrombotic complications. In MS patients with AH, an increase in platelet aggregates circulating in the blood is revealed.
Dyslipidemia contributes significantly to functional platelet hyperactivity. An increase in the content of total cholesterol, LDL and VLDL in hypercholesterolemia causes a pathological increase in the release of thromboxane A2 with an increase in platelet aggregation activity. This is due to the presence of apo-B and apo-E lipoprotein receptors on the surface of platelets. On the other hand, HDL reduces thromboxane production by inhibiting platelet aggregation by binding to specific receptors.
In order to assess the state of blood hemorheology in MS, we examined 98 patients with BMI>30 kg/m2, with IGT and HbA1c>8%. Among the examined patients there were 34 women (34.7%) and 64 men (65.3%); in the whole group, the average age of patients was 54.6±6.5 years.
Normative indicators of blood rheology were determined in normotonic patients (20 patients) undergoing a regular, routine dispensary examination.
The electrophoretic mobility of erythrocytes (EPME) was determined on the cytophotometer "Opton" in the mode: I=5 mA, V=100 V, t=25°. The movement of erythrocytes was recorded in a phase-contrast microscope at a magnification of 800 times. EFPE was calculated by the formula: B=I/t.E, where I is the path of erythrocytes in the microscope eyepiece grid in one direction (cm), t is the transit time (sec), E is the electric field strength (V/cm). In each case, the migration rate of 20-30 erythrocytes was calculated (N EPME=1.128±0.018 µm/cm/sec-1/B-1). At the same time, hemoscanning of capillary blood was performed using a Nikon Eklips 80i microscope.
Platelet hemostasis - platelet aggregation activity (AATP) was assessed on a laser aggregometer - Aggregation Analyzer - Biola Ltd (Unimed, Moscow) according to the Born method modified by O'Brien. ADP (Serva, France) at a final concentration of 0.1 µm (N AATP = 44.2±3.6%) was used as an aggregation inducer.
The levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were determined by the enzymatic method on an FM-901 autoanalyzer (Labsystems, Finland) using reagents from Randox (France).
The concentration of very-low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) was successively calculated using the formula of Friedewald W.T. (1972):

VLDL cholesterol \u003d TG / 2.2
LDL cholesterol = total cholesterol - (VLDL cholesterol + HDL cholesterol)

The atherogenic index (AI) was calculated using the formula A.I. Klimova (1977):

IA \u003d (OXC - HDL cholesterol) / HDL cholesterol.

The concentration of fibrinogen in blood plasma was determined photometrically with the turbodimetric registration method "Fibrintimer" (Germany), using commercial kits "Multifibrin Test-Kit" (Behring AG).
In 2005, the International Diabetes Foundation (IDF) introduced some more stringent criteria for defining a normal fasting glucose level -<5,6 ммоль/л.
The main goal of pharmacotherapy (metformin - 1 g 1-2 times a day, fenofibrate - 145 mg 1-2 times a day; bisoprolol - 5-10 mg per day) of the study group of patients with MS were: normalization of glycemic and lipidemic blood profiles, achievement target level of blood pressure - 130/85 mm Hg. The results of the examination before and after treatment are presented in Table 1.
Microscopic examination of whole blood in patients with MS reveals an increase in the number of deformed erythrocytes (echinocytes, ovalocytes, poikilocytes, acanthocytes) and erythrocyte-platelet aggregates circulating in the blood. The severity of changes in the morphology of capillary blood during microscopic hemoscanning is in direct proportion to the level of HbA1c% (Fig. 3).
As can be seen from the table, by the end of the control treatment, there was a statistically significant decrease in SBP and DBP, respectively, by 18.8 and 13.6% (p<0,05). В целом по группе, на фоне статистически достоверного снижения концентрации глюкозы в крови на 36,7% (p<0,01), получено значительное снижения уровня HbA1c - на 43% (p<0,001). При этом одновременно документирована выраженная статистически достоверная положительная динамика со стороны функционального состояния форменных элементов крови: скорость ЭФПЭ увеличилась на 38,3% (р<0,001), ААТр уменьшилась на 29,1% (p<0,01) (рис. 4). В целом по группе к концу лечения получена статистически достоверная динамика со стороны биохимических показателей крови: ИА уменьшился на 24,1%, концентрация ФГ снизилась на 21,5% (p<0,05).
A multivariate analysis of the obtained results revealed a close statistically significant inverse correlation between the dynamics of EPPE and HbA1c - rEPPE-HbA1c=-0.76; a similar relationship was obtained between the functional state of erythrocytes, BP and IA levels: rEPPE-SBP = -0.56, rEPPE - DBP = -0.78, rEPPE - IA = -0.74 (p<0,01). В свою очередь, функциональное состояние тромбоцитов (ААТр) находится в прямой корреляционной связи с уровнями АД: rААТр - САД = 0,67 и rААТр - ДАД = 0,72 (р<0,01).
AH in MS is determined by a variety of interacting metabolic, neurohumoral, hemodynamic factors and the functional state of blood cells. Normalization of blood pressure levels may be due to total positive changes in biochemical and rheological blood parameters.
The hemodynamic basis of hypertension in MS is a violation of the relationship between cardiac output and TPVR. First, there are functional changes in blood vessels associated with changes in blood rheology, transmural pressure and vasoconstrictor reactions in response to neurohumoral stimulation, then morphological changes in microcirculation vessels are formed, which underlie their remodeling. With an increase in blood pressure, the dilatation reserve of arterioles decreases, therefore, with an increase in blood viscosity, the peripheral vascular resistance changes to a greater extent than under physiological conditions. If the reserve of dilatation of the vascular bed is exhausted, then the rheological parameters become of particular importance, since the high blood viscosity and the reduced deformability of erythrocytes contribute to the growth of OPSS, preventing the optimal delivery of oxygen to the tissues.
Thus, in MS, as a result of protein glycation (in particular, erythrocytes, which is documented by a high content of HbA1c), there are violations of blood rheological parameters: a decrease in elasticity and mobility of erythrocytes, an increase in platelet aggregation activity and blood viscosity due to hyperglycemia and dyslipidemia . Altered rheological properties of blood contribute to the growth of total peripheral resistance at the level of microcirculation and, in combination with sympathicotonia, which occurs with MS, underlie the genesis of AH. Pharma-co-lo-gi-che-sky (biguanides, fibrates, statins, selective b-blockers) correction of the glycemic and lipid profiles of the blood contributes to the normalization of blood pressure. An objective criterion for the effectiveness of ongoing therapy in MS and DM is the dynamics of HbA1c, a decrease in which by 1% is accompanied by a statistically significant decrease in the risk of developing vascular complications (MI, cerebral stroke, etc.) by 20% or more.

Literature
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Blood rheology(from the Greek word rheos- flow, flow) - blood fluidity, determined by the totality of the functional state of blood cells (mobility, deformability, aggregation activity of erythrocytes, leukocytes and platelets), blood viscosity (concentration of proteins and lipids), blood osmolarity (glucose concentration). The key role in the formation of rheological parameters of blood belongs to blood cells, primarily erythrocytes, which make up 98% of the total volume of blood cells. .

The progression of any disease is accompanied by functional and structural changes in certain blood cells. Of particular interest are changes in erythrocytes, whose membranes are a model of the molecular organization of plasma membranes. Their aggregation activity and deformability, which are the most important components in microcirculation, largely depend on the structural organization of red blood cell membranes. Blood viscosity is one of the integral characteristics of microcirculation that significantly affects hemodynamic parameters. The share of blood viscosity in the mechanisms of regulation of blood pressure and organ perfusion is reflected by the Poiseuille law: MOorgana = (Rart - Rven) / Rlok, where Rlok= 8Lh / pr4, L is the length of the vessel, h is the viscosity of the blood, r is the diameter of the vessel. (Fig.1).

A large number of clinical studies on blood hemorheology in diabetes mellitus (DM) and metabolic syndrome (MS) have revealed a decrease in the parameters characterizing the deformability of erythrocytes. In patients with diabetes, the reduced ability of erythrocytes to deform and their increased viscosity are the result of an increase in the amount of glycated hemoglobin (HbA1c). It has been suggested that the resulting difficulty in blood circulation in the capillaries and the change in pressure in them stimulates the thickening of the basement membrane and leads to a decrease in the coefficient of oxygen delivery to the tissues, i.e. abnormal red blood cells play a triggering role in the development of diabetic angiopathy.

A normal erythrocyte under normal conditions has a biconcave disk shape, due to which its surface area is 20% larger compared to a sphere of the same volume. Normal erythrocytes are able to significantly deform when passing through the capillaries, while not changing their volume and surface area, which maintains the diffusion of gases at a high level throughout the entire microvasculature of various organs. It has been shown that with a high deformability of erythrocytes, the maximum transfer of oxygen to cells occurs, and with a deterioration in deformability (increased rigidity), the supply of oxygen to cells sharply decreases, and tissue pO2 drops.

Deformability is the most important property of erythrocytes, which determines their ability to perform a transport function. This ability of erythrocytes to change their shape at a constant volume and surface area allows them to adapt to the conditions of blood flow in the microcirculation system. The deformability of erythrocytes is due to factors such as intrinsic viscosity (concentration of intracellular hemoglobin), cellular geometry (maintaining the shape of a biconcave disk, volume, surface to volume ratio) and membrane properties that provide the shape and elasticity of erythrocytes.
Deformability largely depends on the degree of compressibility of the lipid bilayer and the constancy of its relationship with the protein structures of the cell membrane.

The elastic and viscous properties of the erythrocyte membrane are determined by the state and interaction of cytoskeleton proteins, integral proteins, the optimal content of ATP, Ca ++, Mg ++ ions and hemoglobin concentration, which determine the internal fluidity of the erythrocyte. The factors that increase the rigidity of erythrocyte membranes include: the formation of stable compounds of hemoglobin with glucose, an increase in the concentration of cholesterol in them and an increase in the concentration of free Ca ++ and ATP in the erythrocyte.

Violation of the deformability of erythrocytes occurs when the lipid spectrum of membranes changes and, first of all, when the ratio of cholesterol / phospholipids is disturbed, as well as in the presence of products of membrane damage as a result of lipid peroxidation (LPO). LPO products have a destabilizing effect on the structural and functional state of erythrocytes and contribute to their modification.
The deformability of erythrocytes decreases due to the absorption of plasma proteins, primarily fibrinogen, on the surface of erythrocyte membranes. This includes changes in the membranes of the erythrocytes themselves, a decrease in the surface charge of the erythrocyte membrane, a change in the shape of the erythrocytes and changes in the plasma (protein concentration, lipid spectrum, total cholesterol, fibrinogen, heparin). Increased aggregation of erythrocytes leads to disruption of transcapillary metabolism, release of biologically active substances, stimulates platelet adhesion and aggregation.

Deterioration of erythrocyte deformability accompanies the activation of lipid peroxidation processes and a decrease in the concentration of antioxidant system components in various stressful situations or diseases, in particular, in diabetes and cardiovascular diseases.
Activation of free radical processes causes disturbances in hemorheological properties, realized through damage to circulating erythrocytes (oxidation of membrane lipids, increased rigidity of the bilipid layer, glycosylation and aggregation of membrane proteins), having an indirect effect on other indicators of the oxygen transport function of the blood and oxygen transport in tissues. Significant and ongoing activation of lipid peroxidation in serum leads to a decrease in the deformability of erythrocytes and an increase in their aregation. Thus, erythrocytes are among the first to respond to LPO activation, first by increasing the deformability of erythrocytes, and then, as LPO products accumulate and antioxidant protection is depleted, to an increase in the rigidity of erythrocyte membranes, their aggregation activity and, accordingly, to changes in blood viscosity.

The oxygen-binding properties of blood play an important role in the physiological mechanisms of maintaining a balance between the processes of free radical oxidation and antioxidant protection in the body. These properties of blood determine the nature and magnitude of oxygen diffusion to tissues, depending on the need for it and the effectiveness of its use, contribute to the pro-oxidant-antioxidant state, showing either antioxidant or pro-oxidant qualities in various situations.

Thus, the deformability of erythrocytes is not only a determining factor in the transport of oxygen to peripheral tissues and ensuring their need for it, but also a mechanism that affects the effectiveness of the antioxidant defense and, ultimately, the entire organization of maintaining the prooxidant-antioxidant balance of the whole organism.

With insulin resistance (IR), an increase in the number of erythrocytes in the peripheral blood was noted. In this case, increased aggregation of erythrocytes occurs due to an increase in the number of adhesion macromolecules and a decrease in the deformability of erythrocytes is noted, despite the fact that insulin at physiological concentrations significantly improves the rheological properties of blood.

At present, the theory that considers membrane disorders as the leading causes of organ manifestations of various diseases, in particular, in the pathogenesis of arterial hypertension in MS, has become widespread.

These changes also occur in various types of blood cells: erythrocytes, platelets, lymphocytes. .

Intracellular redistribution of calcium in platelets and erythrocytes entails damage to microtubules, activation of the contractile system, release of biologically active substances (BAS) from platelets, triggering their adhesion, aggregation, local and systemic vasoconstriction (thromboxane A2).

In patients with hypertension, changes in the elastic properties of erythrocyte membranes are accompanied by a decrease in their surface charge, followed by the formation of erythrocyte aggregates. The maximum rate of spontaneous aggregation with the formation of persistent erythrocyte aggregates was noted in patients with grade III AH with a complicated course of the disease. Spontaneous aggregation of erythrocytes enhances the release of intra-erythrocyte ADP, followed by hemolysis, which causes conjugated platelet aggregation. Hemolysis of erythrocytes in the microcirculation system can also be associated with a violation of the deformability of erythrocytes, as a limiting factor in their life expectancy.

Particularly significant changes in the shape of erythrocytes are observed in the microvasculature, some of the capillaries of which have a diameter of less than 2 microns. Vital microscopy of blood (approx. native blood) shows that erythrocytes moving in the capillary undergo significant deformation, while acquiring various shapes.

In patients with hypertension combined with diabetes, an increase in the number of abnormal forms of erythrocytes was revealed: echinocytes, stomatocytes, spherocytes and old erythrocytes in the vascular bed.

Leukocytes make a great contribution to hemorheology. Due to their low ability to deform, leukocytes can be deposited at the level of the microvasculature and significantly affect the peripheral vascular resistance.

Platelets occupy an important place in the cellular-humoral interaction of hemostasis systems. Literature data indicate a violation of the functional activity of platelets already at an early stage of AH, which is manifested by an increase in their aggregation activity, an increase in sensitivity to aggregation inducers.

The researchers noted a qualitative change in platelets in patients with hypertension under the influence of an increase in free calcium in the blood plasma, which correlates with the magnitude of systolic and diastolic blood pressure. Electron - microscopic examination of platelets in patients with hypertension revealed the presence of various morphological forms of platelets caused by their increased activation. The most characteristic are such changes in shape as the pseudopodial and hyaline type. A high correlation was noted between an increase in the number of platelets with their altered shape and the frequency of thrombotic complications. In MS patients with AH, an increase in platelet aggregates circulating in the blood is detected. .

Dyslipidemia contributes significantly to functional platelet hyperactivity. An increase in the content of total cholesterol, LDL and VLDL in hypercholesterolemia causes a pathological increase in the release of thromboxane A2 with an increase in platelet aggregability. This is due to the presence of apo-B and apo-E lipoprotein receptors on the surface of platelets. On the other hand, HDL reduces the production of thromboxane, inhibiting platelet aggregation, by binding to specific receptors.

Arterial hypertension in MS is determined by a variety of interacting metabolic, neurohumoral, hemodynamic factors and the functional state of blood cells. Normalization of blood pressure levels may be due to total positive changes in biochemical and rheological blood parameters.

The hemodynamic basis of AH in MS is a violation of the relationship between cardiac output and TPVR. First, there are functional changes in blood vessels associated with changes in blood rheology, transmural pressure and vasoconstrictor reactions in response to neurohumoral stimulation, then morphological changes in microcirculation vessels are formed that underlie their remodeling. With an increase in blood pressure, the dilatation reserve of arterioles decreases, therefore, with an increase in blood viscosity, OPSS change to a greater extent than under physiological conditions. If the reserve of dilatation of the vascular bed is exhausted, then the rheological parameters become of particular importance, since the high blood viscosity and the reduced deformability of erythrocytes contribute to the growth of OPSS, preventing the optimal delivery of oxygen to the tissues.

Thus, in MS, as a result of protein glycation, in particular erythrocytes, which is documented by a high content of HbAc1, there are violations of blood rheological parameters: a decrease in elasticity and mobility of erythrocytes, an increase in platelet aggregation activity and blood viscosity, due to hyperglycemia and dyslipidemia. Altered rheological properties of blood contribute to the growth of total peripheral resistance at the level of microcirculation and, in combination with sympathicotonia that occurs with MS, underlie the genesis of AH. Pharmacological (biguanides, fibrates, statins, selective beta-blockers) correction of the glycemic and lipid profiles of the blood, contribute to the normalization of blood pressure. An objective criterion for the effectiveness of ongoing therapy in MS and DM is the dynamics of HbAc1, a decrease in which by 1% is accompanied by a statistically significant decrease in the risk of developing vascular complications (MI, cerebral stroke, etc.) by 20% or more.

Fragment of the article by A.M. Shilov, A.Sh. Avshalumov, E.N. Sinitsina, V.B. Markovsky, Poleshchuk O.I. MMA them. I.M. Sechenov

Blood is a suspension (suspension) of cells that are in plasma, consisting of protein and fat molecules. Rheological properties include viscosity and suspension stability. They determine the ease of its movement - fluidity. To improve microcirculation, infusion therapy is used, drugs that reduce clotting and cell aggregation into clots.

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Violation of blood rheology

The properties of blood that determine its passage through the circulatory system depend on such factors:

• the ratio of the liquid (plasma) part and cells (mainly erythrocytes);
• protein composition of plasma;
• cell shapes;
• movement speed;
• temperature.

Rheological disturbances manifest themselves in the form of a change in viscosity and stability of the state of the suspension. They are local (with inflammation or venous congestion), as well as general - with shock or weakness of cardiac activity. The flow of oxygen and nutrients to the cells depends on the rheological properties.

Blood viscosity

When blood flow slows down, erythrocytes are located not along the vessel (as is normal), but in different planes, which reduces blood flow. In this case, the vessels and the heart require increased efforts to move it forward. To measure viscosity, an indicator such as is determined. It is calculated by dividing the volume of blood cells by the total volume. In a normal state of viscosity, 45% of cells and 55% of plasma are in the blood. The hematocrit of a healthy person is 0.45.

The higher this indicator, the worse the rheological characteristics of the blood, since its viscosity is higher.

The hematocrit level can be affected by bleeding, dehydration, or, conversely, excessive blood dilution (for example, during intensive fluid therapy). Cooling increases hematocrit by more than 1.5 times.

The Sludge Phenomenon

If suspension stability is disturbed, that is, the suspended state of red blood cells, then the blood can be divided into a liquid part (plasma) and a clot of red blood cells, platelets and white blood cells. This becomes possible due to the association, adhesion, gluing of cells. This phenomenon is called sludge, which means silt or thick mud. Sludge of blood cells leads to severe disruption of microcirculation.

Causes of the phenomenon of separation (separation) of blood:

• circulatory failure due to weakness of the heart;
• stagnation of blood in the veins;
• spasm of the arteries or blockage of their lumen;
• blood diseases with excessive cell formation;
• dehydration with vomiting, diarrhea, taking diuretics;
• inflammation of the vessel wall;
• allergic reactions;
• tumor processes;
• violation of the cellular charge with an imbalance of electrolytes;
• elevated plasma protein.

The sludge phenomenon leads to a decrease in the speed of blood movement, up to its complete stop. The rectilinear direction changes to turbulent, that is, flow turbulence occurs. Due to the large number of accumulations of blood cells, there is a discharge from arterial to venous vessels (shunts open), blood clots form.

At the tissue level, the processes of transport of oxygen and nutrients are disrupted, metabolism and cell recovery in case of damage slow down.

Watch the video about blood rheology and vascular quality:

Methods for measuring blood rheology

To study the viscosity of blood, devices called viscometers or rheometers are used. Two types are currently common:

• rotational - blood rotates in a centrifuge, its shear flow is calculated using hemodynamic formulas;
• capillary - blood flows through a tube of a given diameter under the influence of a known pressure difference at the ends, that is, the physiological regime of blood flow is reproduced.

Rotational viscometers consist of two cylinders of different diameters, one nested within the other. The inner one is connected to a dynamometer, while the outer one rotates. There is blood between them, it begins to move due to its viscosity. A modification of the rotational rheometer is a device with a cylinder that floats freely in a liquid (Zakharchenko's apparatus).

Why you need to know about hemodynamics

Since the state of blood flow is greatly influenced by such mechanical factors as pressure in the vessels and the speed of the flow, the basic laws of hemodynamics are applicable for their study. With their help, it is possible to establish a relationship between the main parameters of blood circulation and the properties of blood.

The movement of blood through the vascular system is carried out due to the pressure difference, it moves from a high to a low zone. This process is influenced by viscosity, suspension stability and arterial wall resistance. The latter indicator is the highest in arterioles, since they have the greatest length with a small diameter. The main force of heart contractions is spent on the movement of blood into these vessels.

The resistance of arterioles, in turn, strongly depends on their lumen, which is affected by various environmental factors and stimuli of the autonomic nervous system. These vessels are called the taps of the human body.

The length may change during the period of growth, as well as during the work of the skeletal muscles (regional arteries).

In all other cases, the length is considered a constant factor, and the lumen of the vessel and blood viscosity are variable values, they determine the state of blood flow.

Evaluation of indicators

The main characteristics of hemodynamics in the body are:

• Stroke volume is the amount of blood that enters the vessels during heart contraction, its norm is 70 ml.
• Ejection fraction - the ratio of systolic ejection in ml to the residual volume of blood at the end of diastole. It is about 60%, if it drops to 45, then this is a sign of systolic dysfunction (heart failure). If it falls below 40%, the condition is assessed as critical.
• Blood pressure - systolic from 100 to 140, diastolic from 60 to 90 mm Hg. Art. All values ​​below this range are a sign of hypotension, and higher ones indicate arterial hypertension.
• Total peripheral resistance is calculated as the ratio of mean arterial pressure (diastolic and one-third of pulse rate) to blood ejection per minute. Measured in dyne x s x cm-5, it ranges from 700 to 1500 units in the norm.

To assess the rheological indicators determine:

• Content of erythrocytes. Normally 3.9 - 5.3 million / μl, it is lowered with anemia, tumors. High rates are with leukemia, chronic oxygen deficiency, blood clots.
• Hematocrit. In healthy people, it ranges from 0.4 to 0.5. Increased with respiratory disorders, tumors or cysts of the kidneys, dehydration. Decreases with anemia, excessive infusion of fluids.
• Viscosity. The norm is considered to be about 23 MPa × s. It increases with atherosclerosis, diabetes mellitus, diseases of the respiratory, digestive systems, pathology of the kidneys, liver, taking diuretics, alcohol. Decreases with anemia, intensive fluid intake.

Drugs that improve blood rheology

To facilitate the movement of blood with increased viscosity, use:

• Hemodilution - dilution of blood by transfusion of plasma substitutes (Reopoliglyukin, Gelofusin, Voluven, Refortan, Stabizol, Poliglukin);
• anticoagulant therapy -, Fraxiparin, Fragmin, Fenilin, Sinkumar, Wessel Due F, Cibor, Pentasan;
• antiplatelet agents - Plavix, Ipaton, Cardiomagnyl, Aspirin, Curantil, Ilomedin, Brilinta.

In addition to drugs, plasmapheresis is used to remove excess protein from plasma and improve the suspension stability of red blood cells, as well as or ultraviolet light.

The rheological and hemodynamic properties of blood determine the delivery of oxygen and nutrients to the tissues. The former depend on the ratio of the number of blood cells and the volume of the liquid part, as well as the stability of the cell suspension in plasma. Indicators of blood rheology are viscosity, hematocrit, erythrocyte content.

Hemodynamic parameters of blood flow are determined by measuring pressure, cardiac output and peripheral resistance. Violations of the rate of blood flow leads to a slowdown in metabolism in tissues. To improve fluidity, medicines are used - plasma substitutes, anticoagulants, antiaggregants.

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