Circulation management. Changes in the rheological properties of blood in patients with metabolic syndrome Three options are possible here

Blood rheology(from the Greek word rheos- flow, flow) - blood fluidity, determined by the totality of functional state 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. From structural organization membranes of red blood cells largely depend on their aggregation activity and deformability, which are the most important components in microcirculation. 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 blood pressure and organ perfusion is reflected by Poiseuille's 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 works on blood hemorheology in patients with diabetes(DM) and metabolic syndrome (MS), revealed a decrease in the parameters characterizing the deformability of erythrocytes. In patients with diabetes, a reduced ability of erythrocytes to deform and 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.

Normal erythrocyte in normal conditions It 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 supports the diffusion of gases on high level throughout the 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 oxygen supply to the cells decreases sharply, and tissue pO2 drops.

Deformability is the most important property 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, 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 hemoglobin compounds 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 changing lipid spectrum membranes and, above all, in violation of the ratio of cholesterol / phospholipids, 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, level 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 one of the first to respond to the activation of LPO, first by increasing the deformability of erythrocytes, and then as the accumulation of LPO products and depletion antioxidant protection 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 important role in physiological mechanisms 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, manifesting in different situations either antioxidant or prooxidant qualities.

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 has become widespread. various diseases, in particular in the pathogenesis arterial hypertension with MS.

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, and a biological release reaction. 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. Max Speed 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 red blood cells 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 early stage AG, 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 microcirculation vessels underlying 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 in 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 glycation of proteins, in particular erythrocytes, which is documented high content HbAc1, there are violations of the rheological parameters of the blood: a decrease in the 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 the total peripheral resistance at the level of microcirculation and in combination with sympathicotonia, which occurs with MS, underlie the genesis of AH. Pharmacological (biguanides, fibrates, statins, selective beta-blockers) correction of glycemic and lipid profiles 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(THEM, 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

The rheological properties of blood as a heterogeneous liquid are of particular importance when it flows through microvessels, the lumen of which is comparable to the size of its formed elements. When moving in the lumen of capillaries and the smallest arteries and veins adjacent to them, erythrocytes and leukocytes change their shape - they bend, stretch in length, etc. Normal blood flow through microvessels is possible only under conditions if: a) shaped elements can be easily deformed; b) they do not stick together and do not form aggregates that could impede blood flow and even completely clog the lumen of microvessels, and c) the concentration of blood cells is not excessive. All these properties are important primarily in erythrocytes, since their number in human blood is about a thousand times greater than the number of leukocytes.

The most accessible and widely used in the clinic method for determining the rheological properties of blood in patients is its viscometry. However, the conditions of blood flow in any currently known viscometers are significantly different from those that take place in a living microvasculature. In view of this, the data obtained by viscometry reflect only some of the general rheological properties of blood, which can promote or hinder its flow through microvessels in the body. The viscosity of blood, which is detected in viscometers, is called relative viscosity, comparing it with the viscosity of water, which is taken as a unit.

Violations of the rheological properties of blood in microvessels are mainly associated with changes in the properties of erythrocytes in the blood flowing through them. Such blood changes can occur not only throughout vascular system organism, but also locally in any organs or their parts, as, for example, it always takes place in the foci of inflammation. Below are the main factors that determine the violation of the rheological properties of blood in the microvessels of the body.

8.4.1. Violation of the deformability of erythrocytes

Erythrocytes change their shape during the flow of blood, not only through the capillaries, but also in the wider arteries and veins, where they are usually elongated in length. The ability to deform (deformability) in erythrocytes is associated mainly with the properties of their outer membrane, as well as with the high fluidity of their contents. In the blood flow, the membrane rotates around the content of red blood cells, which also moves.

The deformability of erythrocytes is extremely variable with vivo. It gradually decreases with the age of erythrocytes, as a result of which an obstacle is created for their passage through the narrowest (3 μm in diameter) capillaries of the reticuloendothelial system. It is assumed that due to this there is a "recognition" of old red blood cells and their elimination from the circulatory system.

The membranes of erythrocytes become more rigid under the influence of various pathogenic factors, for example, their loss of ATP, hyperosmolarity, etc. As a result, the rheological properties of blood change in such a way that its flow through microvessels becomes more difficult. This occurs in heart disease, diabetes insipidus, cancer, stress, etc., in which the fluidity of blood in microvessels is significantly reduced.

8.4.2. Violation of the structure of blood flow in microvessels

In the lumen of blood vessels, the flow of blood is characterized by complex structure associated with: a) uneven distribution of non-aggregated erythrocytes in the blood stream across the vessel; b) with a peculiar orientation of erythrocytes in the flow, which can vary from longitudinal to transverse; c) with the trajectory of the movement of erythrocytes inside the vascular lumen; d) with a velocity profile of individual blood layers, which can vary from parabolic to blunt varying degrees. All this can have a significant impact on the fluidity of blood in the vessels.

From the point of view of violations of the rheological properties of blood, changes in the structure of the blood flow in microvessels with a diameter of 15-80 microns, i.e., somewhat wider than capillaries, are of particular importance. So, with the primary slowing of blood flow, the longitudinal orientation of erythrocytes often changes to transverse, the velocity profile in the vascular lumen becomes dull, and the trajectory of erythrocytes becomes chaotic. All this leads to such changes in the rheological properties of blood, when the resistance to blood flow increases significantly, causing an even greater slowdown in the flow of blood in the capillaries and disrupting microcirculation.

8.4.3. Increased intravascular aggregation of red blood cells causing blood stasis

In microvessels

The ability of erythrocytes to aggregate, i.e., to stick together and form “coin columns”, which then stick together, is their normal property. However, aggregation can be significantly enhanced under the influence of various factors that change both the surface properties of erythrocytes and the environment surrounding them. With increased aggregation, the blood turns from a suspension of erythrocytes with high fluidity into a mesh suspension, completely devoid of this ability. In general, erythrocyte aggregation disrupts the normal pattern of blood flow in microvessels and is probably the most important factor altering the normal rheological properties of the blood. With direct observations of blood flow in microvessels, one can sometimes see intravascular aggregation of red blood cells, called "granular blood flow". With increased intravascular aggregation of erythrocytes in the entire circulatory system, aggregates can clog the smallest precapillary arterioles, causing blood flow disturbances in the corresponding capillaries. Increased erythrocyte aggregation can also occur locally, in microvessels, and disrupt the microrheological properties of the blood flowing in them to such an extent that the blood flow in the capillaries slows down and stops completely - stasis occurs, despite the fact that the ar-geriovenous blood pressure difference throughout these microvessels saved. However, in the capillaries small arteries and veins accumulate erythrocytes, which are in close contact with each other, so that their boundaries cease to be visible (“blood homogenization”). However, in the beginning, with blood stasis, neither hemolysis nor blood clotting occurs. For some time, the stasis is reversible - the movement of erythrocytes can be resumed and the patency of microvessels is restored again.

The occurrence of intracapillary aggregation of erythrocytes is influenced by a number of factors:

1. Damage to the walls of the capillaries, causing increased filtration of fluid, electrolytes and low molecular weight proteins (albumins) into the surrounding tissues. As a result, the concentration of high-molecular proteins - globulins and fibrinogen - increases in the blood plasma, which, in turn, is the most important factor in enhancing erythrocyte aggregation. It is assumed that the absorption of these proteins on erythrocyte membranes reduces their surface potential and promotes their aggregation.

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The main characteristic of blood is its viscosity, which is divided into apparent and Caisson (dynamic):

Apparent blood viscosity. It is determined by the ratio of shear force and shear rate, measured in centipoise (cps) and characterizes the non-Newtonian behavior of blood. Depends on the state, mainly erythrocytes and platelets.
Caisson (dynamic) blood viscosity. It is determined under conditions of complete blood dispersion and depends on the protein composition of the plasma. It is measured in centipoise (cps).

Factors that most affect blood viscosity include:

temperature and ,
hematocrit,
the amount of high molecular weight proteins in plasma,
the degree of erythrocyte aggregation and its reversibility,
shear characteristics.

Liquid limit of blood. It shows what minimum force must be applied to move one layer of blood relative to another (measured in days / cm 2).

Aggregation factor. It indicates the strength of the adhesion of blood cells, that is, the strength of aggregates and (measured in days / cm 2).

All of the above parameters of blood viscosity are determined using a coaxial-cylindrical viscometer with a freely floating internal cylinder of the V.N. Zakharchenko, which makes it possible to make a model and plot a blood flow curve in a wide range of shear stresses.

Indirect indicators of blood viscosity is the value of hematocrit, the number of erythrocytes, the level of fibrinogen and globulin protein fractions, the level total lipids and their spectrum in plasma, as well as blood sugar levels. With certain diseases, for example, with varicose veins in men, as a rule, these indicators are enough to assess the viscosity and set indications for the appointment.

The degree of erythrocyte aggregation- is determined using a calorimeter - nephelometer and is expressed in units of optical density (or in percent).

Degree of platelet aggregation- (induced ADP) is determined using an aggregometer type "Elvi-840" (England), expressed in units of optical density (or in percent).

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 viscometers various types: devices are used that work according to the Stokes method, as well as on the principle of registering 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.

The rheological properties of blood (which determine its fluidity) can change significantly in different parts of the bloodstream, which is significantly influenced by hydrodynamic factors and the geometry of the vascular bed.

The fluidity of blood is determined mainly by the dynamic viscosity of the blood. Blood plasma has a higher viscosity than water (about 1.8 times) due to the content of proteins in it, mainly globulin and fibrinogen. The viscosity of whole blood is about 3 times that of plasma and increases as the number of red blood cells increases. At the same time, in some cases, the viscosity of blood with a lower hematocrit may exceed the viscosity of blood with a higher hematocrit, but with a lower content of proteins in it (Dintenfass L., 1962).

The blood flow is heterogeneous and consists of layers of erythrocytes, leukocytes, platelets, protein molecules, as well as water molecules, electrolytes, etc. The friction between the individual layers is different, which determines the different viscosity of the blood when its composition changes. Blood is characterized by greater viscosity at low speeds, low pressure, and also under conditions of hypothermia. The viscosity of the blood decreases with a decrease in the diameter of the vessels, but in the capillaries it increases. Nevertheless, the erythrocyte is deformed and, under physiological conditions, easily passes through the capillary, even if its diameter exceeds the diameter of the capillary. At the same time, acting as a piston, the erythrocyte contributes to the renewal of fluid and other diffusing substances located along the walls of the capillaries. Viscosity in capillaries increases when passing through them as granulocytes, the stiffness and diameter of which is greater than that of erythrocytes (Adel R.

Et al., 1970) and more rigid and viscous macrophages (Roser B., Dintenfass L., 1966).

With a decrease in the rate of blood flow in the microcirculation system at the level of venules and small veins, the formation of erythrocytes occurs.

I and M III I . 11 111 Ml.1 ІОН l|surface contacts) and the increase in blood viscosity. Under physiological conditions, aggregates easily disintegrate with an increase in blood flow velocity. The decrease in blood flow velocity in the microcirculation system during shock is more pronounced, prolonged, and the formation of erythrocyte aggregates becomes generalized, which is also facilitated by a change in the properties of erythrocytes (volume, shape, internal environment, metabolism) and their environment (Seleznev S. A., Vashetina S. M., Mazurkevich G. S., 1976). RBC aggregation may contribute to the development of disseminated intravascular coagulation, but may also be a consequence of it.

Violations of the rheological properties of blood in victims with shock (traumatic, hemorrhagic, septic and cardiogenic) are characterized by phase development: the initial increase in blood viscosity as shock develops is replaced by its decrease. A pronounced decrease in blood viscosity indicates deep and persistent disorders in the microcirculatory bed (stasis and sequestration of blood, development of plasma flow) and is most characteristic of terminal conditions refractory to resuscitation (Radzivil G. G., Minsker G. D., 1985).

Circulation management. Changes in the rheological properties of blood in patients with metabolic syndrome Three options are possible here

How are the properties of blood evaluated?

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