Chapter 7. Blood gases and acid-base balance Blood gases: oxygen (02) and carbon dioxide (CO2) Oxygen transport To survive, a person must be able to absorb oxygen from the atmosphere and transport it to cells, where it is used in metabolism. Some

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

Volume and physicochemical 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 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 and the functional state of the bloodstream. At a relatively low flow rate, blood particles are located parallel to each other. This flow is laminar, while the blood flow is layered. If the linear speed of blood increases 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 laminar flow becomes turbulent is approximately 1160. Data indicate that turbulence of blood flow is possible in the large branches and at the beginning of the aorta. Most vessels are characterized by laminar blood flow. The movement of blood through the vessels is also determined by other important parameters: “shear stress” and “shear rate”.

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

Shear stress is the force acting on a unit surface area of ​​a container 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 value. It is measured in pascal seconds and is defined as the ratio of shear stress to shear rate.

How are blood properties assessed?

The main factor influencing 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.

The task of developing rheology analysis methods that would objectively reflect the properties of blood still remains relevant.

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

For quotation: 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 // RMZh. 2008. No. 4. S. 200

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

Diabetes, as a component of MS, in its prevalence ranks immediately after cardiovascular diseases and cancer, and according to WHO experts, its prevalence will reach 215 million people by 2010.
Diabetes is dangerous due to its complications, since vascular damage in diabetes is the cause of the development of hypertension, myocardial infarction, cerebral stroke, renal 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 occurs, 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 the rheological parameters of blood belongs to the formed elements of blood, primarily erythrocytes, which make up 98% of the total volume of formed elements of blood.
The progression of any disease is accompanied by functional and structural changes in certain blood cells. Of particular interest are changes in erythrocytes, the membranes of which 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 blood pressure regulation and organ perfusion is reflected in Poiseuille’s law:

MOorgana = (Rart - Rven) / Rlok, where Rlok. = 8Lh / pr4,

Where L is the length of the vessel, h is the blood viscosity, r is the diameter of the vessel (Fig. 1).
A large number of clinical studies devoted to blood hemorheology in diabetes and MS have revealed a decrease in parameters characterizing the deformability of erythrocytes. In patients with diabetes, the reduced ability of red blood cells to deform and their increased viscosity are a consequence 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 changes in pressure in them stimulate the thickening of the basement membrane, leading to a decrease in the coefficient of diffusion oxygen delivery to the tissues, that is, abnormal red blood cells play a trigger role in the development of diabetic angiopathy.
HbA1c is a glycated hemoglobin in which glucose molecules are condensed with the b-terminal valine of the b-chain of the HbA molecule. More than 90% of the hemoglobin of a healthy person is represented by HbAO, which has 2?- and 2b-polypeptide chains. Glycated forms of hemoglobin together constitute?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 steadily increased level of sugar in the blood, this connection becomes “strong” and persists until the red blood cells are destroyed in the spleen. On average, the lifespan of red blood cells is 120 days, so the level of sugar-bound hemoglobin (HbA1c) reflects the metabolic state of a patient with diabetes over a period of 3-4 months. The percentage of Hb bound to a glucose molecule gives an idea of ​​the degree of increase in blood sugar; the longer and higher the blood sugar level, the higher it is and vice versa.
Today it is postulated that high blood sugar is one of the main causes of the development of adverse consequences of diabetes, the so-called late complications (micro- and macroangiopathy). Therefore, high HbA1c levels are a marker of the possible development of late complications of diabetes.
HbA1c, according to various authors, makes up 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 red blood cell 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 red blood cells are capable of being significantly deformed when passing through capillaries, without changing their volume and surface area, which maintains gas diffusion processes at a high level throughout the entire microvasculature of various organs. It has been shown that with high deformability of erythrocytes, maximum oxygen transfer into the cells occurs, and with deterioration of deformability (increased rigidity), the supply of oxygen to the cells sharply decreases, tissue pO2 falls.
Deformability is the most important property of red blood cells, determining their ability to perform a transport function. It is the ability of red blood cells to change their shape at a constant volume and surface area that allows them to adapt to the conditions of blood flow in the microcirculatory system. The deformability of erythrocytes is determined by factors such as internal viscosity (concentration of intracellular hemoglobin), cellular geometry (maintaining the shape of a biconcave disc, 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. 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 Ca2+ and ATP in the erythrocyte.
Deterioration in the deformability of erythrocytes occurs when the lipid spectrum of membranes changes, and primarily when the cholesterol/phospholipids ratio is disrupted, as well as in the presence of membrane damage products 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, quantitative and qualitative changes in membrane lipids, and an increase in the passive permeability of the lipid bilayer for K+, H+, Ca2+. Recent studies using electron spin resonance spectroscopy have noted a significant correlation between the deterioration of erythrocyte deformability and MS markers (BMI, blood pressure, 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, changes in the shape of erythrocytes and changes in plasma (concentration of proteins, lipid spectrum, levels of total cholesterol, fibrinogen, heparin). Increased aggregation of erythrocytes leads to disruption of transcapillary exchange, release of biologically active substances, and stimulates platelet adhesion and aggregation.
Deterioration in the deformability of erythrocytes accompanies the activation of lipid peroxidation processes and a decrease in the concentration of components of the antioxidant system during various stress situations or diseases (in particular, diabetes and CVD). Intracellular accumulation of lipid peroxides arising from the autoxidation of membrane polyunsaturated fatty acids 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 indicators of the oxygen transport function of the blood and oxygen transport to 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, significant and ongoing activation of lipid peroxidation 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 the activation of LPO, first by increasing the deformability of erythrocytes, and then, as LPO products accumulate and antioxidant protection is depleted, by increasing membrane rigidity 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 balance between the processes of free radical oxidation and antioxidant protection in the body. The indicated properties of blood determine the nature and magnitude of the diffusion of oxygen to tissues, depending on the need for it and the efficiency of its use, contributes to the pro-oxidant-antioxidant state, exhibiting either anti-oxidant 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 influences the effectiveness of the functioning of antioxidant defense and, ultimately, the entire organization of maintaining the prooxidant-antioxidant balance of the body.
In case of IR, an increase in the number of erythrocytes in the peripheral blood was noted. In this case, there is an increase in erythrocyte aggregation 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 in physiological concentrations significantly improves the rheological properties of blood. In case of 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 (intracellular transmitter of the insulin signal for GLUT) was found; at the same time, an increase in the number of Na+/H+ channels on the erythrocyte membrane occurs.
Currently, a 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 mean a change in the activity of ion transport systems of plasma membranes, manifested in the activation of Na+/H+ exchange and an increase in the sensitivity of K+ channels to intracellular calcium. The main role in the formation of membrane disorders is given to the lipid framework and cytoskeleton, as regulators of the structural state of the membrane and intracellular signaling systems (cAMP, polyphosphoinositides, intracellular calcium).
The basis of cellular disorders is the excessive 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 vascular smooth myocytes, initiates DNA synthesis, increasing germinal effects on the cells with their subsequent hyperplasia. Similar changes occur in various types of blood cells: red blood cells, platelets, lymphocytes.
Intracellular redistribution of calcium in platelets and erythrocytes entails damage to microtubules, activation of the contractile system, the reaction of the release of biologically active substances (BAS) from platelets, triggering their adhesion, aggregation, local and systemic vasoconstriction (tromboxane A2).
In patients with hypertension, changes in the elastic properties of erythrocyte membranes are accompanied by a decrease in their surface charge with the subsequent formation of erythrocyte aggregates. The maximum rate of spontaneous aggregation with the formation of persistent erythrocyte aggregates was observed in patients with stage III hypertension with a complicated course of the disease. Spontaneous aggregation of erythrocytes increases the release of intraerythrocyte ADP with subsequent hemolysis, which causes associated platelet aggregation. Hemolysis of erythrocytes in the microcirculatory system may also be associated with a violation of the deformability of erythrocytes, as a limiting factor in their life expectancy.
The most significant changes in the shape of red blood cells are observed in the microvasculature, some capillaries of which have a diameter of less than 2 microns. Intravital microscopy shows that red blood cells moving in the capillary undergo significant deformation, acquiring various shapes.
In patients with hypertension combined with diabetes, an increase in the number of abnormal forms of erythrocytes was detected: echinocytes, stomatocytes, spherocytes and old erythrocytes in the vascular bed.
Leukocytes make a major 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 cell-humoral interaction of hemostasis systems. Literature data indicate a violation of the functional activity of platelets already at the early stage of hypertension, which is manifested by an increase in their aggregation activity and increased 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, expressed by increased expression of adhesive glycoproteins on the platelet surface (GpIIb/IIIa, P-selectin), increased density and sensitivity to platelet a-2-adrenergic agonists. noreceptors, 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-thrombo-modulin) , increasing the processes of free radical oxidation of lipids of platelet membranes.
Researchers have 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 value of systolic and diastolic blood pressure. Electron microscopic examination of platelets from patients with hypertension revealed the presence of different morphological forms of platelets, the result of their increased activation. The most typical shape changes are pseudopodial and hyaline type. There was a high correlation between an increase in the number of platelets with their altered shape and the frequency of thrombotic complications. In MS patients with hypertension, an increase in platelet aggregates circulating in the blood is detected.
Dyslipidemia makes a significant contribution to functional platelet hyperactivity. An increase in the content of total cholesterol, LDL and VLDL during 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 lipoprotein receptors apo-B and apo-E 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 level>8%. Among the examined patients there were 34 women (34.7%) and 64 men (65.3%); in the group as a whole, the average age of patients was 54.6±6.5 years.
Standard indicators of blood rheology were determined in normotensive patients (20 patients) undergoing regular routine dispensary examination.
Electrophoretic mobility of erythrocytes (EMME) was determined on an “Opton” cytophotometer 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 using the formula: B=I/t.E, where I is the path of red blood cells 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 speed of 20-30 erythrocytes was calculated (N EFPE = 1.128 ± 0.018 μm/cm/sec-1/B-1). At the same time, hemoscanning of capillary blood was carried out using a Nikon Eklips 80i microscope.
Platelet hemostasis - platelet aggregation activity (AATr) was assessed using a laser aggregometer - Aggregation Analyzer - Biola Ltd (Unimed, Moscow) according to the Born method modified by O’Brien. ADP (Serva, France) was used as an aggregation inducer at a final concentration of 0.1 µM (N AATp = 44.2±3.6%).
The level of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) was determined by the enzymatic method on an FM-901 autoanalyzer (Labsystems - Finland) using reagents from Randox (France).
The concentrations of very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) were sequentially calculated using the Friedewald W.T. formula. (1972):

VLDL cholesterol = TG/2.2
LDL cholesterol = TC - (VLDL cholesterol + HDL cholesterol)

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

AI = (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 determining normal fasting blood glucose levels -<5,6 ммоль/л.
The main goals of pharmacotherapy (metformin - 1 g 1-2 times a day, fenofibrate - 145 mg 1-2 times a day; bisoprolol - 5-10 mg per day) in the study group of patients with MS were: normalization of glycemic and lipidemic blood profiles, achieving target blood pressure level - 130/85 mm Hg. The examination results before and after treatment are presented in Table 1.
Microscopic examination of whole blood in MS patients 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 results obtained revealed a close statistically significant inverse correlation between the dynamics of EFPE and HbA1c - rEFPE-HbA1c=-0.76; a similar relationship was obtained between the functional state of erythrocytes, blood pressure and AI levels: rEFPE-SBP = -0.56, rEFPE - DBP = -0.78, rEFPE - AI = -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).
Hypertension in MS is determined by many interacting metabolic, neurohumoral, hemodynamic factors and the functional state of blood cells. The normalization of blood pressure levels may be due to overall positive changes in the biochemical and rheological parameters of the blood.
The hemodynamic basis of hypertension in MS is a violation of the relationship between cardiac output and peripheral vascular resistance. First, functional changes in blood vessels occur, 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, OPSS changes to a greater extent than under physiological conditions. If the reserve for dilatation of the vascular bed is exhausted, then the rheological parameters become of particular importance, since high blood viscosity and reduced deformability of erythrocytes contribute to the growth of peripheral vascular resistance, 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 by a high content of HbA1c), disturbances in the rheological parameters of the blood occur: a decrease in the elasticity and mobility of erythrocytes, an increase in platelet aggregation activity and blood viscosity due to hyperglycemia and dyslipidemia . Changed rheological properties of blood contribute to an increase in general peripheral resistance at the level of microcirculation and, in combination with sympathicotonia that occurs in MS, underlie the genesis of hypertension. Pharmaco-logical (biguanides, fibrates, statins, selective b-blockers) correction of glycemic and lipid blood profiles helps normalize blood pressure. An objective criterion for the effectiveness of therapy for 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.

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Blood rheology(from the Greek word rheos– flow, flow) – fluidity of blood, 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 the rheological parameters of blood belongs to the formed elements of blood, primarily erythrocytes, which make up 98% of the total volume of formed elements of blood. .

The progression of any disease is accompanied by functional and structural changes in certain blood cells. Of particular interest are changes in erythrocytes, the membranes of which 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 blood pressure regulation and organ perfusion is reflected by Poiseuille’s law: MOorgana = (Rart – Rven) / Rlok, where Rloc = 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 devoted to blood hemorheology in diabetes mellitus (DM) and metabolic syndrome (MS) have revealed a decrease in parameters characterizing the deformability of erythrocytes. In patients with diabetes, the reduced ability of red blood cells to deform and their increased viscosity are a consequence of an increase in the amount of glycosylated hemoglobin (HbA1c). It has been suggested that the associated difficulty in blood circulation in the capillaries and changes in pressure in them stimulate the thickening of the basement membrane, leading to a decrease in the coefficient of oxygen delivery to the tissues, i.e. abnormal red blood cells play a trigger role in the development of diabetic angiopathy.

A normal red blood cell under normal conditions has a biconcave disk shape, due to which its surface area is 20% greater than a sphere of the same volume. Normal red blood cells are capable of being significantly deformed when passing through capillaries, without changing their volume and surface area, which maintains gas diffusion processes at a high level throughout the entire microvasculature of various organs. It has been shown that with high deformability of erythrocytes, maximum oxygen transfer into the cells occurs, and with deterioration of deformability (increased rigidity), the supply of oxygen to the cells sharply decreases, tissue pO2 falls.

Deformability is the most important property of red blood cells, determining their ability to perform a transport function. It is the ability of red blood cells to change their shape at a constant volume and surface area that allows them to adapt to the conditions of blood flow in the microcirculatory system. The deformability of red blood cells is determined by factors such as intrinsic viscosity (concentration of intracellular hemoglobin), cellular geometry (maintaining the shape of a biconcave disc, volume, surface-to-volume ratio) and membrane properties that provide the shape and elasticity of red blood cells.
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. 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.

Disturbances in the deformability of erythrocytes occur when the lipid spectrum of membranes changes and, above all, when the ratio of cholesterol/phospholipids is disrupted, as well as when there are 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, changes in the shape of erythrocytes and changes in plasma (concentration of proteins, lipid spectrum, levels of total cholesterol, fibrinogen, heparin). Increased aggregation of erythrocytes leads to disruption of transcapillary exchange, release of biologically active substances, and stimulates platelet adhesion and aggregation.

Deterioration in the deformability of erythrocytes accompanies the activation of lipid peroxidation processes and a decrease in the concentration of components of the antioxidant system 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 red blood cells (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 to tissues. Significant and ongoing activation of lipid peroxidation in serum leads to a decrease in the deformability of erythrocytes and an increase in their aggregation. Thus, erythrocytes are one of the first to respond to the activation of LPO, first by increasing the deformability of erythrocytes, and then, as LPO products accumulate and antioxidant protection is depleted, by an increase in the rigidity of erythrocyte membranes, their aggregation activity and, accordingly, changes in blood viscosity.

The oxygen-binding properties of blood play an important role in the physiological mechanisms of maintaining balance between the processes of free radical oxidation and antioxidant protection in the body. The indicated properties of blood determine the nature and magnitude of oxygen diffusion to tissues, depending on the need for it and the efficiency of its use, contributes to the pro-oxidant-antioxidant state, exhibiting 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 influences the effectiveness of the functioning of antioxidant defense and, ultimately, the entire organization of maintaining the pro-oxidant-antioxidant balance of the whole organism.

With insulin resistance (IR), an increase in the number of erythrocytes in the peripheral blood is 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 in physiological concentrations significantly improves the rheological properties of blood.

Currently, a 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: red blood cells, platelets, lymphocytes. .

Intracellular redistribution of calcium in platelets and erythrocytes entails damage to microtubules, activation of the contractile system, and 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 with the subsequent formation of erythrocyte aggregates. The maximum rate of spontaneous aggregation with the formation of persistent erythrocyte aggregates was observed in patients with stage III hypertension with a complicated course of the disease. Spontaneous aggregation of erythrocytes increases the release of intraerythrocyte ADP with subsequent hemolysis, which causes associated platelet aggregation. Hemolysis of erythrocytes in the microcirculatory system may 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 red blood cells are observed in the microvasculature, some capillaries of which have a diameter of less than 2 microns. Intravital microscopy of blood (approx. native blood) shows that red blood cells moving in the capillary undergo significant deformation, acquiring various shapes.

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

Leukocytes make a major contribution to hemorheology. Due to their low ability to deform, leukocytes can be deposited at the level of the microvasculature and significantly influence 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 the early stage of hypertension, which is manifested by an increase in their aggregation activity and increased sensitivity to aggregation inducers.

Researchers have 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 value of systolic and diastolic blood pressure. Electron microscopic examination of platelets from patients with hypertension revealed the presence of various morphological forms of platelets caused by their increased activation. The most typical shape changes are pseudopodial and hyaline type. There was a high correlation between an increase in the number of platelets with their altered shape and the frequency of thrombotic complications. In MS patients with hypertension, an increase in platelet aggregates circulating in the blood is detected. .

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

Arterial hypertension in MS is determined by many interacting metabolic, neurohumoral, hemodynamic factors and the functional state of blood cells. Normalization of blood pressure levels may be due to overall 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 peripheral vascular resistance. First, functional changes in blood vessels occur, 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, peripheral resistance changes to a greater extent than under physiological conditions. If the reserve for dilatation of the vascular bed is exhausted, then the rheological parameters become of particular importance, since high blood viscosity and reduced deformability of erythrocytes contribute to the growth of peripheral vascular resistance, 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 by a high content of HbAc1, disturbances in the rheological parameters of the blood occur: 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 an increase in total peripheral resistance at the level of microcirculation and, in combination with sympathicotonia that occurs in MS, underlie the genesis of hypertension. Pharmacological (biguanides, fibrates, statins, selective beta blockers) correction of glycemic and lipid profiles of the blood contribute to the normalization of blood pressure. An objective criterion for the effectiveness of therapy for MS and DM is the dynamics of HbAc1, a decrease of 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 an article by A.M. Shilov, A.Sh. Avshalumov, E.N. Sinitsina, V.B. Markovsky, Poleshchuk O.I. MMA im. I.M.Sechenova

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

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Violation of blood rheology

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

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

Violations of rheology manifest themselves in the form of changes in the viscosity and stability of the suspension. They can be local (with inflammation or venous stagnation), as well as general – with shock or weakness of the heart. The supply of oxygen and nutrients to the cells depends on the rheological properties.

Blood viscosity

When blood flow slows down, red blood cells are not located along the vessel (as is normal), but in different planes, which reduces blood fluidity. In this case, the blood vessels and heart require increased efforts to move it. To measure viscosity, an indicator such as . It is calculated by dividing the volume of blood cells by the entire volume. At normal viscosity, the blood contains 45% cells and 55% plasma. 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 dilution of the blood (for example, during intensive infusion therapy). Cooling increases the hematocrit by more than 1.5 times.

Sludge phenomenon

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

Reasons for the phenomenon of blood separation:

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

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

At the tissue level, the processes of transport of oxygen and nutrients are disrupted, metabolism and cell restoration slow down when damaged.

Watch the video about blood rheology and the quality of blood vessels:

Methods for measuring blood rheology

To study blood viscosity, instruments called viscometers or rheometers are used. There are currently two common types:

• 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 of which is nested inside the other. The inner one is connected to the dynamometer, and the outer one rotates. Between them there is blood, 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 apparatus).

Why you need to know about hemodynamics

Since the state of blood flow is greatly influenced by mechanical factors such as pressure in the vessels and the speed of flow, the basic laws of hemodynamics are applicable to their study. With their help, it is possible to establish a connection 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 the high to 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 precisely on moving 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 can change during growth, as well as during the work of skeletal muscles (regional arteries).

In all other cases, 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 when the heart contracts; its norm is 70 ml.
• Ejection fraction is the ratio of systolic ejection in ml to the residual blood volume at the end of diastole. It is about 60%, if it decreases to 45, then this is a sign of systolic dysfunction (heart failure). If it falls below 40%, the condition is considered critical.
• Blood pressure – systolic from 100 to 140, diastolic from 60 to 90 mm Hg. Art. Any reading below this range is a sign of hypotension, while anything higher is indicative of hypertension.
• Total peripheral resistance is calculated as the ratio of mean arterial pressure (diastolic and one third of pulse) to blood output per minute. Measured in din x s x cm-5, the normal range is from 700 to 1500 units.

To assess rheological parameters, determine:

• Red blood cell content. Normally 3.9 - 5.3 million/µl, it is reduced in case of anemia and tumors. High levels occur with leukemia, chronic oxygen deficiency, and blood thickening.
• Hematocrit In healthy people it ranges from 0.4 to 0.5. Increased with breathing problems, kidney tumors or cysts, and dehydration. Decreases with anemia and excessive fluid infusion.
• Viscosity. About 23 mPa×s is considered normal. It increases with atherosclerosis, diabetes mellitus, diseases of the respiratory and digestive systems, kidney and liver pathologies, taking diuretics and alcohol. Decreases with anemia and intense fluid intake.

Drugs that improve blood rheology

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

• Hemodilution - dilution of blood using transfusion of plasma substitutes (Reopoliglyukin, Gelofusin, Voluven, Refortan, Stabizol, Poliglyukin);
• anticoagulant therapy - Fraxiparine, Fragmin, Phenilin, Sinkumar, Wessel Due F, Tsibor, Pentasan;
• antiplatelet agents - Plavix, Ipaton, Cardiomagnil, 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 ultraviolet light.

The rheological and hemodynamic properties of blood determine the delivery of oxygen and nutrients to 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 the plasma. Indicators of blood rheology are viscosity, hematocrit, and erythrocyte content.

Hemodynamic parameters of blood flow are determined by measuring pressure, cardiac output and peripheral resistance. Impaired blood flow speed leads to a slowdown in tissue metabolism. To improve fluidity, medications are used - plasma expanders, anticoagulants, antiplatelet agents.

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