A.P. Yastrebov, A.V. Osipenko, A.I. Volozhin, G.V. Poryadin, G.P. Shchelkunov

Chapter 2. Pathophysiology of the blood system.

Blood is the most important component of the body, providing its homeostasis. It carries oxygen from the lungs to tissues and removes carbon dioxide from tissues (respiratory function), delivers various substances necessary for life to cells (transport function), participates in thermoregulation, in maintaining water balance and excretion toxic substances(detoxification function), in the regulation of the acid-base state. The amount of blood depends on the amount blood pressure and the work of the heart, the function of the kidneys and other organs and systems. Leukocytes provide cellular and humoral immunity. Platelets, together with plasma clotting factors, stop bleeding.

Blood consists of plasma and formed elements - erythrocytes, leukocytes and platelets. In 1 liter of blood, the proportion of formed elements (mainly erythrocytes) in men is 0.41 - 0.53 liters (hematocrit = 41 - 53%), and in women - 0.36 - 0.48 liters (hematocrit = 36 - 48%. The amount of blood in a person is 7 - 8% of his body weight, i.e. in a person weighing about 70 kg - about 5 liters.

With any anemia, the number of erythrocytes in the blood decreases (hematocrit-Ht is below normal), but the volume of circulating blood (CBV) remains normal due to plasma. Such a state is called oligocythemic normovolemia. In this case, due to a deficiency of hemoglobin (Hb), the oxygen capacity of the blood decreases and hypoxia of the hemic (blood) type develops.

With an increase in the number of erythrocytes in the blood (erythrocytosis), against the background of normal BCC, a polycythemic normovolemia(Ht above normal). In most cases, erythrocytosis, with the exception of some pathological forms(see below), compensates for hypoxia of various origins due to an increase in the oxygen capacity of the blood. With significant increases in hematocrit, blood viscosity may increase and be accompanied by microcirculation disorders.

Changes in circulating blood volume (CBV)

The decrease in BCC is called hypovolemia. There are 3 forms of hypovolemia:

Simple hypovolemia occurs in the first minutes (hours) after massive acute blood loss, when, against the background of a decrease in BCC, the hematocrit remains normal (hidden anemia). At the same time, depending on the degree of reduction in BCC, there may be a drop in blood pressure (BP), a decrease in cardiac output (COS, MOS), tachycardia, redistribution of blood flow, release of deposited blood, a decrease in diuresis, disorders cerebral circulation up to loss of consciousness and other consequences. Due to the weakening of microcirculation and a decrease in the total amount of Hb, circulatory and hemic hypoxia develops.

Oligocythemic hypovolemia characterized by a decrease in BCC and a decrease in hematocrit. This condition can develop in patients suffering from severe anemia complicated by acute bleeding or dehydration, for example, with leukemia, aplastic anemia, radiation sickness, malignant tumors, some kidney diseases, etc. In this case, very severe hypoxia develops. mixed type, due to both Hb deficiency and violation of the central and peripheral circulation.

the best way correction of simple and oligocythemic hypovolemia is a blood transfusion or blood substitutes.

Polycythemic hypovolemia characterized by a decrease in BCC and an increase in Ht. Its main cause is hypohydration, when, due to a lack of water in the body, the volume of blood plasma decreases. And although the oxygen capacity of the blood remains normal (Hb is normal), circulatory type hypoxia develops, since, depending on the degree of dehydration (see pathophysiology of water-electrolyte metabolism), a decrease in BCC leads to a drop in blood pressure, a decrease in cardiac output, a violation of the central and peripheral circulation, reduced filtration in the glomeruli of the kidneys, the development of acidosis. An important consequence is an increase in blood viscosity, impeding the already weakened microcirculation, increasing the risk of blood clots.

To restore the BCC, it is necessary to infuse fluids, administer drugs that reduce blood viscosity and improve its rheological properties, antiplatelet agents, anticoagulants.

An increase in BCC is called hypervolemia. There are also 3 forms of hypervolemia: simple, oligocythemic and polycythemic.

Simple hypervolemia can be observed after massive blood transfusions and be accompanied by an increase in blood pressure and MOS. Usually it is temporary, because, due to the inclusion of regulatory mechanisms, the BCC returns to normal.

Oligocythemic hypervolemia characterized by an increase in BCC and a decrease in hematocrit. It usually develops against the background of hyperhydration, when an increase in water in the body is accompanied by an increase in blood plasma volume. This condition is especially dangerous in patients with renal insufficiency and chronic, congestive heart failure, because. at the same time, blood pressure rises, overload of the heart and its hypertrophy develop, edema occurs, including life-threatening. Hypervolemia and hyperhydration in these patients is usually supported by activation of the RAAS and the development of secondary aldosteronism.

To restore BCC, diuretics, RAAS blockers (mainly ACE blockers - see pathophysiology of water and electrolyte metabolism) should be used.

On the background kidney failure patients usually develop anemia, which in turn further reduces the hematocrit, and the patient's condition is aggravated by the development of hemic-type hypoxia.

Polycythemic hypervolemia characterized by an increase in BCC and an increase in hematocrit. A classic example of such a condition is the chronic myeloproliferative disorder (see below) erythremia (Wakez's disease). In patients, the content of all formed elements in the blood is sharply increased - especially erythrocytes, as well as platelets and leukocytes. The disease is accompanied by arterial hypertension, overload of the heart and its hypertrophy, microcirculation disorders and a high risk of thrombosis. Patients often die from heart attacks and strokes. See the principles of therapy below.

Regulation of hematopoiesis

There are specific and non-specific mechanisms for regulating hematopoiesis. Specific - include short- and long-range regulatory mechanisms.

short range(local) mechanisms of regulation of hematopoiesis work in the system of hematopoiesis-inducing microenvironment (HIM) and extend mainly to classes I and II of hematopoietic bone marrow cells. Morphologically, GIM includes three components.

1. Tissue - represented by cellular elements: bone marrow, fibroblasts, reticular, stromal mechanocytes, fat, macrophages, endothelial cells; fibers and the main substance of the connective tissue (collagen, glycosaminoglycans, etc.). Connective tissue cells are actively involved in various intercellular interactions and carry out the transport of metabolites. Fibroblasts produce a large number of biologically active substances: colony-stimulating factor, growth factors, factors regulating osteogenesis, etc. Monocytes-macrophages play an important role in the regulation of hematopoiesis. The bone marrow is characterized by the presence of erythroblastic islets - structural and functional formations with a centrally located macrophage surrounded by a layer of erythroid cells, one of the functions of which is the transfer of iron to developing erythroblasts. The existence of islets for granulocytopoiesis was also shown. Along with this, macrophages produce CSF, interleukins, growth factors and other biologically active substances, and also have a morphogenetic function.

Lymphocytes have a significant effect on hematopoietic cells, which produce substances that act on the proliferation of hematopoietic stem cells, interleukins that provide cytokine control of proliferation, intercellular interactions in the GIM, and much more.

The main substance of the connective tissue of the bone marrow is represented by collagen, reticulin, elastin, which form a network in which hematopoietic cells are located. The composition of the main substance includes glycosaminoglycans (GAGs), which play an important role in the regulation of hematopoiesis. They affect hematopoiesis in different ways: acidic GAGs support granulocytopoiesis, while neutral ones support erythropoiesis.

The extracellular fluid of the bone marrow contains a variety of highly active enzymes that are practically absent in the blood plasma.

2. microvascular - represented by arterioles, capillaries, venules. This component provides oxygenation, as well as the regulation of the entry and exit of cells into the bloodstream.

3. Nervous - communicates between blood vessels and stromal elements. The main mass of nerve fibers and endings maintains a topographic connection with blood vessels, thereby regulating cell trophism and vasomotor reactions.

In general, local control of hematopoiesis is carried out through the interaction of its three components.

Starting from committed cells, the mechanisms long distance regulation having specific factors for each germ.

Long distance regulation erythropoiesis is carried out mainly by two systems: 1) erythropoietin and an erythropoiesis inhibitor; 2) keylon and anti-keylon.

Central to the regulation of erythropoiesis is erythropoietin, the production of which increases under the action of extreme factors on the body ( different kinds hypoxia), requiring the mobilization of red blood cells. Erythropoietin is a glycoprotein by its chemical nature. The main place of formation is the kidneys. Erythropoietin acts mainly on erythropoietin-sensitive cells, stimulating them to proliferate and differentiate. Its action is realized through a system of cyclic nucleotides (mainly through cAMP). Along with the stimulant, the regulation of erythropoiesis is also involved inhibitor erythropoiesis. It is produced in the kidneys, possibly in lymphatic system and spleen with polycythemia (an increase in the number of red blood cells in the blood), with an increase in the partial pressure of oxygen in the inhaled air. The chemical nature is close to albumins.

The action is associated with inhibition of differentiation and proliferation of erythroid cells, or neutralization of erythropoietin, or a violation of its synthesis.

The next system is "keylon-anti-keylon". They are usually secreted by mature cells and are specific to each cell type. Keylon - biologically active substance, which inhibits the proliferation of the same cell that produced it. On the contrary, erythrocyte antikeylon stimulates the entry of dividing cells into the phase of DNA synthesis. It is assumed that this system regulates the proliferative activity of erythroblasts, and under the action of extreme factors, erythropoietin comes into action.

Long-range regulation of leukopoiesis extends its action to committed cells, proliferating and maturing bone marrow cells and is carried out by various mechanisms. Great importance in the regulation of leukopoiesis belongs to colony stimulating factor(CSF), which acts on committed progenitor cells of myelopoiesis and on more differentiated cells of granulocytopoiesis, activating DNA synthesis in them. It is formed in the bone marrow, lymphocytes, macrophages, vascular walls, and a number of other cells and tissues. Serum CSF levels are regulated by the kidneys. CSF is heterogeneous. There is evidence that CSF can regulate granulocytomonocytopoiesis (GM-CSF), monocytopoiesis (M-CSF), and eosinophil production (EO-CSF).

An equally important role in the regulation of leukopoiesis is played by leukopoetins. Depending on the type of cells whose proliferation is stimulated by leukopoetins, several of their varieties are distinguished: neutrophilopoietin, monocytopoetin, eosinophilopoeitin, lymphocytopoetins. Leukopoetins are formed by various organs: liver, spleen, kidneys, leukocytes. Leukocytosis inducing factor (LIF) occupies a special place among leukopoetins, which promotes the transfer of deposited granulocytes from the bone marrow into the circulating blood.

To humoral regulators leukopoiesis include thermostable and thermolabile factors of leukocytosis, isolated by Menkin biochemically from the focus of inflammation.

Currently, as regulators of leukopoiesis are considered interleukins(cytokines) - waste products of lymphocytes and macrophages, which are one of the most important mechanisms of communication between immunocompetent cells and regenerating tissues. Their main property is the ability to regulate the growth and differentiation of hematopoietic and immunocompetent cells. They are included in the complex network of cytokine control of proliferation and differentiation of not only hematopoietic, but also bone tissues. There are several types of interleukins. Thus, IL-2 is a specific inducer of the formation of T-lymphocytes. IL-3 - stimulates the proliferative activity of various hematopoietic germs. IL-4 is a product of activated T-lymphocytes, stimulates the production of B-lymphocytes. At the same time, IL-1 is one of the most important systemic regulators of osteogenesis, has an activating effect on the proliferation and synthesis of proteins by fibroblasts, and regulates the growth and functional state of osteoblasts.

Along with stimulants, leukopoiesis is also regulated by inhibitors. In addition to the thermostable and thermolabile factors of Menkin's leukopenia, there is evidence of the existence of an inhibitor of granulocytopoiesis. Its main source is granulocytes and bone marrow cells. Granulocyte caylon and antikeylon have been isolated.

Control over hematopoiesis is also carried out at the level of mature, specialized cells that have lost their differentiation capabilities and is accompanied by the active destruction of such cells. In this case, the resulting decay products of blood cells have a stimulating effect on hematopoiesis. Thus, the destruction products of erythrocytes are able to activate erythropoiesis, and the decay products of neutrophils - neutrophilopoiesis. The mechanism of action of such regulators is associated: with a direct effect on the bone marrow, mediated through the formation of hematopoietins, as well as by changing the hematopoietic microenvironment.

This mechanism of regulation of hematopoiesis is also found in physiological conditions. It is associated with intramedullary destruction of blood cells and implies the destruction of low-viable cells of the erythroid and granulocytic series in it - the concept of "ineffective" erythro- and leukopoiesis.

Along with the specific regulation of hematopoiesis, there are a number of nonspecific mechanisms that affect the metabolism of many body cells, including hematopoietic ones.

Endocrine regulation of hematopoiesis. Significant effect on blood and hematopoiesis pituitary. In animal experiments, it has been established that hypophysectomy causes the development of microcytic anemia, reticulocytopenia, and a decrease in bone marrow cellularity.

The anterior pituitary hormone ACTH increases the content of erythrocytes and hemoglobin in the peripheral blood, inhibits the migration of hematopoietic stem cells and reduces endogenous colony formation, while simultaneously inhibiting lymphoid tissue. STH - potentiates the reaction of erythropoietin-sensitive cells to erythropoietin and does not affect progenitor cells of granulocytes and macrophages. The middle and posterior lobes of the pituitary gland do not have a noticeable effect on hematopoiesis.

adrenal glands. With adrenalectomy, the cellularity of the bone marrow decreases. Glucocorticoids stimulate bone marrow hematopoiesis, accelerating the maturation and release of granulocytes into the blood, with a simultaneous decrease in the number of eosinophils and lymphocytes.

gonads. Male and female sex hormones affect hematopoiesis in different ways. Estrogens have the ability to inhibit bone marrow hematopoiesis. In the experiment, the introduction of estrone leads to the development of osteosclerosis and bone marrow replacement bone tissue with a decrease in the number of hematopoietic stem cells. Androgens- stimulate erythropoiesis. Testosterone, when administered to animals, stimulates all links in the formation of granulocytes.

In general, hormones have a direct effect on the proliferation and differentiation of hematopoietic cells, change their sensitivity to specific regulators, and form hematological changes characteristic of the stress response.

Nervous regulation of hematopoiesis. Cortex has a regulatory effect on hematopoiesis. At experimental neuroses anemia and reticulocytopenia develop. Various departments hypothalamus may affect the blood in different ways. Thus, stimulation of the posterior hypothalamus stimulates erythropoiesis, while the anterior hypothalamus inhibits erythropoiesis. When removed cerebellum macrocytic anemia may develop.

The influence of the nervous system on hematopoiesis is also realized through a change in hemodynamics. The sympathetic and parasympathetic parts of the nervous system play a role in changing the composition of the blood: irritation of the sympathetic part and its mediators increases the number of blood cells, while the parasympathetic part decreases.

Along with the indicated specific and nonspecific regulation, there are mechanisms of immunological and metabolic regulation of hematopoiesis. So, the regulatory influence immune system on hematopoiesis is based on the commonality of these systems and the crucial role of lymphocytes in hematopoiesis, as well as the presence of a morphogenetic function in lymphocytes, which ensures constancy cellular composition organism.

metabolic control is carried out by direct (metabolites act as inducers of cell proliferation) and indirect (metabolites change cell metabolism and thereby act on proliferation - cyclic nucleotides) influence on hematopoiesis.

Pathophysiology of erythron.

Erythron is a collection of mature and immature red blood cells - erythrocytes. Red blood cells are born in the red bone marrow from a stem cell, like all other formed elements. Monopotent cells from which only erythrocytes can develop are BFUer (erythroid burst-forming units), which, under the influence of renal erythropoietins (EPO), interleukin-3 (IL-3) and colony-stimulating factors (CSF), are converted into CFUer (erythroid colony-forming units), also responsive to EPO, and then to erythroblasts. Erythroblasts, simultaneously proliferating, differentiate into pronormocytes, further - basophilic normocytes, polychromatophilic normocytes and oxyphilic normocytes. Normocytes (the old name for normoblasts) are a class of maturing nuclear precursors of red blood cells. The last cell capable of division is the polychromatophilic normocyte. At the stage of normocytes, hemoglobin synthesis occurs. Oxyphilic normocytes, losing nuclei, turn into mature non-nuclear oxyphilic erythrocytes through the reticulocyte stage. 10 - 15% of erythrocyte precursors die in the bone marrow, which is called " ineffective erythropoiesis».

In the peripheral blood of a healthy person, there should be no nuclear precursors of erythrocytes. Of the immature cells of the red germ in the blood, only reticulocytes (or polychromatophilic erythrocytes) are normally found from two to ten per thousand (2-10% o or 0.2 - 1%). Reticulocytes (cells containing reticular granularity in the cytoplasm - the remnants of polyribosomes) are detected only with a special supravital staining with brilliantcresylblue dye. The same cells, when stained according to Wright or according to Romanovsky-Giemsa, perceiving both acidic and basic dyes, have purple colour cytoplasm without granularity.

The bulk of peripheral blood cells are mature non-nuclear oxyphilic erythrocytes. Their number in men is 4–5 ´ 10 12 /l, in women - 3.7–4.7 ´ 10 12 /l. Therefore, the hematocrit in men is 41-53%, and in women - 36-48%. The total hemoglobin content (Hb) is 130–160 g/l in men and 120–140 g/l in women. The average content of hemoglobin (SSG = Hb g/l:number Er/l) - 25.4 - 34.6 pg/cell. Average concentration of hemoglobin (SKG = Нb g/l:Нt l/l) – 310 – 360 g/l of erythrocyte concentrate. The average concentration of cellular hemoglobin (MCCH) = 32 - 36%. The average diameter of erythrocytes is 6-8 µm, and the average cell volume (SOC or MCV) is 80-95 µm 3 . The erythrocyte sedimentation rate (ESR) in men is 1 - 10 mm / hour, and in women - 2 - 15 mm / hour. Osmotic resistance of erythrocytes (ORE), i.e. their resistance to hypotonic solutions NaCl: minimum - 0.48 - 0.44%, and maximum - 0.32 - 0.28% NaCl. Due to its biconcave shape normal red blood cells have a margin of safety when entering a hypotonic environment. Their hemolysis is preceded by the movement of water into the cells and their transformation into easily collapsing spherocytes.

The maximum lifespan of erythrocytes in the blood is 100-120 days. Obsolete erythrocytes are destroyed in the reticuloendothelial system, mainly in the spleen (“erythrocyte graveyard”). When erythrocytes are destroyed by successive transformations, the pigment bilirubin is formed.

Erythron pathology can be expressed both in a change in the number of erythrocytes and in a change in their morphological and functional properties. Violations can occur at the stage of their birth in the bone marrow, at the stage of their circulation in the peripheral blood and at the stage of their death in the RES.

Erythrocytosis

Erythrocytosis- a condition characterized by an increase in the content of erythrocytes and hemoglobin per unit volume of blood and an increase in hematocrit, without signs of systemic hyperplasia of the bone marrow tissue. Erythrocytosis can be relative and absolute, acquired and hereditary.

Relative erythrocytosis is a consequence of a decrease in blood plasma volume, mainly against the background of hypohydration (see above, polycythemic hypovolemia). Due to the decrease in plasma volume per unit volume of blood, the content of erythrocytes, hemoglobin increases and Ht increases, blood viscosity increases and microcirculation is disturbed. And although the oxygen capacity of the blood does not change, tissues may experience oxygen starvation due to circulatory disorders.

Absolute erythrocytosis acquired (secondary) are usually an adequate response of the body to tissue hypoxia. With a lack of oxygen in the air (for example, among residents of high mountains), with chronic respiratory and heart failure, with an increase in the affinity of Hb for O 2 and a weakening of the dissociation of oxyhemoglobin in tissues, with oppression of tissue respiration, etc. the universal compensatory mechanism is switched on: in the kidneys (mainly) erythropoietins (EPO) are produced, under the influence of which cells sensitive to them (see above) increase their proliferation and enter the blood from the bone marrow more erythrocytes (called physiological, hypoxic, compensatory erythrocytosis). This is accompanied by an increase in the oxygen capacity of the blood and an increase in its respiratory function.

Absolute erythrocytosis hereditary (primary) may be of several types:

· An autosomal recessive defect in the amino acid regions of Hb responsible for its deoxygenation leads to an increase in the affinity of Hb for oxygen and makes it difficult for oxyhemoglobin to dissociate in tissues that receive less oxygen. In response to hypoxia, erythrocytosis develops.

· A decrease in 2,3-diphosphoglycerate in erythrocytes (may decrease by 70%) also leads to an increase in the affinity of Hb for oxygen and difficulty in the dissociation of oxyhemoglobin. The result is similar - in response to hypoxia, EPO are produced and erythropoiesis is enhanced.

· Constant increased production of erythropoietins by the kidneys, which, due to an autosomal recessive genetic defect, no longer adequately respond to the level of tissue oxygenation.

Genetically determined increased proliferation of erythroid cells in the bone marrow without an increase in EPO.

Hereditary erythrocytoses are pathological, are characterized by an increase in Ht, blood viscosity and impaired microcirculation, tissue hypoxia (especially with an increase in the affinity of Hb to O 2), an increase in the spleen (working hypertrophy), may be accompanied by headaches, increased fatigue, varicose veins vessels, thrombosis and other complications.

anemia

Anemia(verbatim - anemia, or general anemia) – this is a clinical and hematological syndrome characterized by a decrease in hemoglobin content and (with rare exceptions) the number of red blood cells per unit volume of blood.

As a result of a decrease in the number of red blood cells, the hematocrit also decreases.

Since all anemias are characterized low level hemoglobin, which means that the oxygen capacity of the blood is reduced and its respiratory function is impaired, then All anemic patients develop hemic hypoxic syndrome. His clinical manifestations: pallor skin and mucous membranes, weakness, fatigue, dizziness, there may be a headache, shortness of breath, palpitations with tachycardia or arrhythmia, pain in the heart, sometimes changes in the ECG. Since blood viscosity decreases against the background of low hematocrit, the consequence of this is usually an acceleration of ESR (the fewer erythrocytes, the faster they settle), as well as symptoms such as tinnitus, systolic murmur at the apex of the heart and a "top" noise on the jugular veins.

Anemia classifications.

There are several approaches to the classification of anemia: by pathogenesis, by type of erythropoiesis, by color index (CI), by MCCG (see above), by the diameter of erythrocytes and by SOC (see above), by the functional state of the bone marrow (its regenerative ability ).

According to the pathogenesis, all anemias are divided into three groups:

Anemia due to impaired blood formation (hematopoiesis). This group includes all deficiency anemia: iron deficiency (IDA), B 12 - and folate deficiency anemia, sideroblastic anemia (SBA), anemia with a deficiency of protein, trace elements and other vitamins, as well as anemia caused by disorders of the bone marrow itself - hypo- and aplastic anemia. In recent years, anemia in chronic diseases (ACD) has been considered separately.

Analysis of equity capital according to the statement of changes in equity.

Hypovolemia - pathological condition, manifested by a decrease in the volume of circulating blood, in some cases accompanied by a violation of the ratio between plasma and formed elements (erythrocytes, platelets, leukocytes).

For information, in normal adult women, the total blood volume is 58-64 ml per 1 kg of body weight, in men - 65-75 ml / kg.

The reasons

Lead to the development of hypovolemia:

acute blood loss;
significant loss of fluid by the body (with burns of a large area, diarrhea, indomitable vomiting, polyuria);
vasodilatory collapse (a sharp expansion of blood vessels, as a result of which their volume ceases to correspond to the volume of circulating blood);
shock conditions;
insufficient intake of fluid into the body with increased losses (for example, with high temperature environment).

Against the background of a decrease in the volume of circulating blood, functional insufficiency of a number of internal organs(brain, kidney, liver).

Kinds

Depending on the hematocrit (an indicator of the ratio of blood cells and plasma), the following types of hypovolemia are distinguished:

Normocythemic. It is characterized by a general decrease in blood volume while maintaining the ratio of plasma and formed elements (hematocrit within the normal range).
Oligocythemic. The content of blood cells is predominantly reduced (the value of hematocrit decreases).
Polycythemic. To a greater extent, there is a decrease in plasma volume (hematocrit above normal).

The most severe manifestation of hypovolemia is called hypovolemic shock.

signs

Clinical manifestations of hypovolemia are determined by its type.

The main symptoms of normocythemic hypovolemia:

weakness;
dizziness;
lowering blood pressure;
tachycardia;
weak pulse impulse;
decrease in diuresis;
cyanosis of mucous membranes and skin;
decrease in body temperature;
fainting;
cramps in the muscles of the lower extremities.

Oligocythemic hypovolemia is characterized by signs of impaired blood supply to organs and tissues, a decrease in the oxygen capacity of the blood, and increasing hypoxia.

Signs of polycythemic hypovolemia:

a significant increase in blood viscosity;
severe disorders of microcirculatory circulation;
disseminated microthrombosis; and etc.

Hypovolemic shock is manifested by a pronounced clinical picture with rapid onset of symptoms.

Diagnostics

The diagnosis and degree of hypovolemia is based on clinical symptoms.

Normally, in adult women, the total blood volume is 58-64 ml per 1 kg of body weight, in men - 65-75 ml / kg.

The volume of laboratory and instrumental studies depends on the nature of the pathology that led to a decrease in the volume of circulating blood. The required minimum includes:

determination of hematocrit;
general blood analysis;
blood biochemistry;
general urine analysis;
determination of blood group and Rh factor.

If hypovolemia is suspected due to bleeding in abdominal cavity perform diagnostic laparoscopy.

Treatment

The goal of therapy is to restore normal circulating blood volume as soon as possible. For this, infusion of dextrose solutions is carried out, physiological saline and polyionic solutions. In the absence of a lasting effect, intravenous administration of artificial plasma substitutes (solutions of hydroxyethyl starch, gelatin, dextran) is indicated.

In parallel, the underlying pathology is treated to prevent an increase in the severity of hypovolemia. So, in the presence of a source of bleeding, surgical hemostasis is performed. If the decrease in circulating blood volume is due to state of shock appropriate antishock therapy is prescribed.

In a serious condition of the patient and the appearance of signs of respiratory failure, the question of the advisability of tracheal intubation and the transfer of the patient to artificial lung ventilation is being decided.

In the absence of emergency therapy, severe hypovolemia ends with the development of hypovolemic shock - life threatening states.

Prevention

Prevention of hypovolemia includes:

injury prevention;
timely treatment of acute intestinal infections;
sufficient intake of water into the body, correction of the water regime under changing environmental conditions;
Refusal to self-medicate with diuretics.

Consequences and complications

In the absence of emergency treatment, severe hypovolemia ends with the development of hypovolemic shock, a life-threatening condition. In addition, against the background of a decrease in the volume of circulating blood, functional insufficiency of a number of internal organs (brain, kidneys, liver) may occur.

Volume of circulating blood (VCC)

The oxygen transport capabilities of the body depend on the volume of blood and the content of hemoglobin in it.

The volume of circulating blood at rest in young women averages 4.3 liters, in men - 5.7 liters. With a load, the BCC first increases, and then decreases by 0.2-0.3 l due to the outflow of part of the plasma from the dilated capillaries into the intercellular space of the working muscles. During prolonged exercise, the average value of the BCC in women is 4 liters, in men - 5.2 liters . Endurance training leads to an increase in BCC. With a load of maximum aerobic power, the BCC in trained men is on average 6.42 liters

BCC and its components: the volume of circulating plasma (CV) and the volume of circulating erythrocytes (VCE) increase during sports. The increase in BCC is a specific effect of endurance training. It is not observed in representatives of speed-strength sports. Taking into account the size (weight) of the body, the difference between the BCC in endurance athletes, on the one hand, and untrained people and athletes training others physical qualities On the other hand, the average is more than 20%. If the BCC of an athlete training endurance is 6.4 liters (95.4 ml per 1 kg of body weight), then for untrained athletes it is 5.5 liters (76.3 ml / kg of body weight).

Table 9 shows the indicators of BCC, BCC, BCP and the amount of hemoglobin per 1 kg of body weight in athletes with different orientations of the training process.

Table 9

Indicators of BCC, BCC, BCP and the amount of hemoglobin in athletes with different orientations of the training process

From table 9 it follows that with an increase in BCC in endurance athletes, the total number of erythrocytes and blood hemoglobin proportionally increases. This significantly increases the total oxygen capacity of the blood and contributes to an increase in aerobic endurance.

Due to the increase in BCC, the central blood volume and venous return to the heart increase, which provides a large CO2 in the blood. The blood filling of the alveolar capillaries increases, which increases the diffuse capacity of the lungs. An increase in circulating blood volume allows more blood to be directed to the skin network and thus increases the body's ability to transfer heat during prolonged work.

During the period of working out, blood pressure, CO, SV, AVR-O2 grow more slowly than heart rate. The reason for this is a slow increase (2-3 min) in the volume of circulating blood due to the slow release of blood from the depot. The rapid growth of BCC can have a traumatic load on the vascular bed.

During loads of high aerobic capacity, a large amount of blood is pumped through the heart at high speed. The excess plasma provides a reserve to avoid hemoconcentration and increase in viscosity. That is, in athletes, an increase in BCC, due more to an increase in plasma volume than to erythrocyte volume, leads to a decrease in hematocrit (blood viscosity) compared to non-athletes (42.8 vs. 44.6).

Due to the large volume of plasma, the concentration in the blood of tissue metabolism products, such as lactic acid, decreases. Therefore, the concentration of lactate during anaerobic exercise increases more slowly.

The mechanism of BCC growth is as follows: working muscle hypertrophy => an increase in the body's demand for proteins => an increase in protein production by the liver => an increase in the release of proteins by the liver into the blood => an increase in colloid osmotic pressure and blood viscosity => an increase in the absorption of water from the tissue fluid inside blood vessels and also there is a retention of water entering the body => an increase in plasma volume (plasma is based on proteins and water) => an increase in BCC.

"The volume of circulating blood is the dominant factor in a well-balanced circulation." The decrease in BCC, the accumulation of blood in the depot (in the liver, in the spleen, in the portal vein network) is accompanied by a decrease in the volume of blood that arrives at the heart and is ejected with each systole. A sudden decrease in BCC leads to acute heart failure. A decrease in blood volume is, of course, always followed by severe tissue and cellular hypoxia.

BCC (in relation to body weight) depends on age: in children under 1 year old - 11%, in adults - 7%. For 1 kg of body weight in children 7-12 years old - 70 ml, in adults - 50-60 ml.

Physiology distinguishes between two types of hemodynamic load on the ventricles of the heart: preload and afterload.

This is the load with the volume of blood that fills the cavity of the ventricle before the start of exile. AT clinical practice a measure of preload is the end-diastolic pressure (EDP) in the cavity of the ventricle (right - KDDp, left - KDDl). This pressure is determined only by an invasive method. Normal KDDp = 4-7 mm Hg, KDDl = 5-12 mm Hg.

For the right ventricle, an indirect indicator may be the value of central venous pressure (CVP). For the left ventricle, a very informative indicator can be the filling pressure of the left ventricle (LVF), which can be determined by a non-invasive (rheographic) method.

Increased preload

To an increase in preload (right or left) of any origin, the ventricle adapts to new working conditions according to the law of O. Frank and E. Starling. E. Starling described this pattern as follows: "stroke volume is proportional to the final diastolic volume":

The essence of the law is that the more the muscle fibers of the ventricle stretch when it is overfilled, the greater the force of their contraction in the subsequent systole.

The validity of this law has been confirmed by numerous studies, even at the cellular level (the force of cardiomyocyte contraction is a function of the length of the sarcomere before it begins to contract). Main question in the law of O. Frank and E. Starling in why the supernormal increase in the length of the muscle fiber increases the force of its contraction?

Here it is appropriate to cite the answer of FZ Meyerson (1968). The force of muscle fiber contraction is determined by the number of actin-myosion bonds that can occur in the muscle fiber at the same time. Elongation of the fiber to a certain limit changes the mutual arrangement of actin and myosin filaments in such a way that during contraction either the number of actin-myosin bonds increases (more precisely, the rate of their formation), or the contractile force that each such bond develops.

Up to what limit (limit) does adaptive reaction O. Frank and E. Starling, when changing the length of the fiber changes the voltage, and it changes the force of contraction?

This law is valid as long as the length of the muscle fiber increases by 45% above the usual length with normal filling of the ventricle (i.e., approximately 1.5 times). A further increase in diastolic pressure in the ventricle increases the length of the muscle fiber to a small extent, because. the fibers become difficult to stretch because the process involves the difficult to stretch connective tissue elastic skeleton of the fibers themselves.

A clinically controlled reference point for the right ventricle may be an increase in CVP of more than 120 mm H 2 O (normal 50-120). This is an indirect reference. The immediate guideline is to increase the KDDp to 12 mm Hg. The reference point for the left ventricle is an increase in EDDL (LVL) up to 18 mm Hg. In other words, when KDDp is in the range from 7 to 12 or KDDl is in the range from 12 to 18 mm Hg, then the right or left ventricle is already working according to the law of O. Frank and E. Starling.

With the adaptive reaction of O. Frank and E. Starling, the VR of the left ventricle does not depend on the diastolic blood pressure (DBP) in the aorta, and the systolic blood pressure (SBP) and DBP in the aorta do not change. S. Sarnoff called this adaptive reaction of the heart heterometric regulation (heteros in Greek - another; in relation to the topic of the section - regulation by means of a different fiber length).

It should be noted that back in 1882, Fick and in 1895 Blix noted that “the law of the heart is the same as the law of skeletal muscle, namely, that the mechanical energy released during the transition from a state of rest to a state of contraction depends on the area "chemically contracting surfaces", i.e. from the length of the muscle fiber.

In the ventricles, as well as in the entire vascular system, some part of the blood volume is filling and some part is stretching, which creates the KDD.

Since the adaptive reaction of the heart, which obeys the law, has a certain limit, beyond which this law of O. Frank and E. Starling is no longer valid, the question arises: is it possible to strengthen the effect of this law? The answer to this question is very important for anesthetists and intensivists. In the studies of E.H. Sonnenblick (1962-1965), it was found that with excessive preload, the myocardium is able to significantly increase the force of contraction under the influence of positive inotropic agents. changing functional states myocardium through the action of inotropic agents (Ca, glycosides, norepinephrine, dopamine) with the same blood flow (the same stretching of the fibers), he received a whole family of "E. Starling curves" with an upward shift from the original curve (without the action of inotropic ).

Figure 4. Graph of the change in the stress curve without and with an inotropic agent for the same length of the muscle fiber

Figure 4 shows that:

1. An increase in tension (T2) when using an inotropic agent and an unchanged initial length of the muscle fiber (L1) over the same period of time (t1) is associated with an acceleration in the formation of actinomyosin bonds (V2> V1);

2. With an inotropic agent, the same effect of the T1 value is obtained, as well as without it, in a shorter period of time - t2 (3).

3. With an inotropic agent, the resulting effect of the T1 value is achieved, as it were, with a shorter fiber length L2 (3).

Reduced preload.

It is due to a decrease in blood flow to the ventricular cavity. This may be due to a decrease in BCC, vasoconstriction in the ICC, vascular insufficiency, organic changes in the heart (stenosis of the AV valves on the right or left).

Initially, the following adaptive elements are included:

1. The expulsion of blood from the atrium to the ventricle increases.

2. The rate of relaxation of the ventricle increases, which contributes to its filling, because. the bulk of the blood enters the phase of rapid filling.

3. The rate of contraction of muscle fibers and increase in tension increases, due to which the ejection fraction is maintained and the residual volume of blood in the ventricular cavity decreases.

4. The rate of expulsion of blood from the ventricles increases, which contributes to maintaining the duration of diastole and filling the ventricle with blood.

If the combination of these adaptive elements is insufficient, then tachycardia develops, aimed at maintaining CO.

This is a load of resistance to blood flow when it is expelled from the cavity of the ventricle. In clinical practice, a measure of afterload is the value of total pulmonary resistance (RLR) for ICC, which is normally 150-350 dyn*s*cm-5, and total peripheral vascular resistance (OPVR) for BCC, which is normally 1200-1700 dyn*s *cm-5. An indirect sign of a change in afterload for the left ventricle may be the value of BPmean, which is normally equal to 80-95 mm Hg.

However, in physiology, the classical concept of afterload is the pressure over the semilunar valves before expulsion of blood by the ventricles. In other words, this is the end-diastolic pressure over the semilunar valves in pulmonary artery and aorta. Naturally, the greater the peripheral vascular resistance, the greater the end-diastolic pressure over the semilunar valves.

Increased afterload.

This situation occurs with a functional narrowing of arterial peripheral vessels, even in the ICC, even in the BCC. It may be due to organic changes in the vessels (primary pulmonary hypertension or hypertonic disease). This may be due to narrowing of the outlet section from the right or left ventricle (subvalvular, valvular stenosis).

The law according to which the ventricle adapts to the resistance load was first discovered by G. Anrep (1912, E. Starling's laboratory).

Further studies of this law were continued by E. Starling himself and further by many well-known physiologists. The results of each study were the support and impetus for the next.

G. Anrep found that with an increase in resistance in the aorta, at first, the volume of the heart increases for a short time (similar to the adaptive reaction of O. Frank and E. Starling). However, then the volume of the heart gradually decreases to a new, larger than the initial value, and then remains stable. At the same time, despite the increase in resistance in the aorta, SV remains the same.

The adaptive reaction of the heart according to the law of G. Anrep and A. Hill with an increase in resistance load FZ Meyerson explains as follows (1968): as the resistance load increases, the number of actinomyosin bonds increases. And the number of free centers capable of reacting with each other in actin and myosin fibers decreases. Therefore, with each increasing load, the number of newly formed actinomyosin bonds decreases per unit time.

At the same time, both the rate of contraction and the amount of mechanical and thermal energy released during the disintegration of actinomyosin bonds decrease, gradually approaching zero.

It is very important that the number of actinomyosin bonds increases, and their decay decreases. This means that with an increase in the load, overcontraction of actinomyosin fibers occurs, which limits the efficiency of the heart.

So, when the resistance load increases by 40-50%, the power and strength of muscle contraction adequately increases. With a greater increase in load, the effectiveness of this adaptive reaction is lost due to the loss of the muscle's ability to relax.

Another factor that eventually limits this adaptive reaction is, as was established by F.Z. Meyerson and his colleagues (1968), a decrease in the conjugation of oxidation and phosphorylation by 27-28% in the area - "cytochrome c" - "oxygen" , while the amount of ATP and especially creatine phosphate (CP) decreases in the myocardium.

This means that the law of G. Anrep and A. Hill ensures the adaptation of the heart muscle to resistance load by increasing the power of the ventricle, which leads to an increase in the force of contraction without changing the initial length of the muscle fiber.

S. Sarnoff called the adaptive reaction of G. Anrep and A. Hill homeometric regulation (homoios in Greek - similar; in relation to the topic of the section - regulation by means of the same fiber length).

The question is also important here: is it possible to enhance the effect of the law of G. Anrep and A. Hill? Research by E.H. Sonnenblick (1962-1965) showed that under excessive afterload, the myocardium is able to increase the power, speed and force of contraction under the influence of positive inotropic agents.

Reduced afterload.

It is associated with a decrease in pressure over the semilunar valves. With normal bcc, a decrease in afterload becomes possible only under the only circumstance - with an increase in the volume of the vascular bed, i.e. with vascular insufficiency.

A decrease in pressure over the semilunar valves shortens the period of intraventricular pressure increase and reduces the very value of this pressure before the start of blood expulsion. This reduces myocardial oxygen demand and its energy consumption for tension.

However, all this reduces the linear and volumetric blood flow velocity. In this regard, the venous return also decreases, which worsens the filling of the ventricles. Under such conditions, the only possible adaptive response is an increase in heart rate aimed at maintaining CO. As soon as tachycardia becomes accompanied by a decrease in CO, this adaptive reaction becomes pathological.

The totality of all studies performed by O. Frank, E. Starling, G. Anrep, A. Hill and other physiologists of that period made it possible to distinguish two options for contraction of the heart fiber: isotonic and isometric contractions.

In accordance with this, two variants of the work of the ventricles of the heart are distinguished.

1. When the ventricle works predominantly with a volume load, it works according to the isotonic contraction variant. At the same time, muscle tone changes to a lesser extent (isotony), mainly the length and cross section of the muscle change.

2. When the ventricle works predominantly with a resistance load, it works according to the isometric contraction variant. In this case, the muscle tension (tone) mainly changes, and its length and cross section change to a lesser extent or almost do not change (isometry).

When the ventricle is working with a resistance load (even with a functional change in the RLS or OPSS), the myocardial oxygen demand increases many times over. Therefore, it is extremely important to provide such a patient in the first place with oxygen.

Doctors often have to increase the work of the heart with inotropic agents. In circulatory physiology (including clinical) inotropism is understood (F.Z. Meyerson, 1968) to regulate the rate of contraction and relaxation, and therefore the power and efficiency of the heart with the same size of the ventricle.

Inotropism is not aimed at an abnormal increase in the force of contractions of the heart, but at maintaining the force of contractions, in best case close to normal.

Inotropism differs from the law of O. Frank and E. Starling in that the initial length of myocardial fibers does not change. It differs from the law of G. Anrep and A. Hill in that it increases not only the rate of contraction, but also (most importantly!) The rate of relaxation of myocardial fibers (which prevents overcontraction, or contracture, of the myocardium).

However, with artificial inotropic regulation of the work of the heart by norepinephrine, etc. similar means could be a serious hazard. If the introduction of an inotropic agent is sharply and significantly reduced or its administration is stopped, then myocardial tone may sharply decrease.

There is an acute tonogenic dilatation of the ventricle. Its cavity increases, intraventricular pressure sharply decreases. Under these conditions, in order to achieve the previous voltage value, a large amount of energy is required.

The process of building tension is the most important consumer of energy in the cardiac cycle. Besides, he goes first. There is a law in physiology that the first process always tries to use the available energy as fully as possible in order to complete it completely and completely. The rest of the energy is spent on the next process, and so on. (i.e., each previous process is like Louis XV: "after us, even a flood").

The process of increasing tension is followed by the work of moving blood from the ventricles to the vessels. Due to the fact that almost all available energy is spent on tension, and it is not enough to expel it, the work of the ventricles to move blood begins to lag behind tension. As a result, the overall efficiency of the heart decreases. With each such defective contraction, the residual volume of blood in the cavity of the ventricle progressively increases and, in the end, asystole occurs.

The volume of circulating blood (VCC) is 2.4 liters per 1 m 2 of body surface in women and 2.8 liters per 1 m 2 of body surface in men, which corresponds to 6.5% of women's body weight and 7.5% of men's body weight [Shuster X. P. et al., 1981].

The BCC value can be calculated in milliliters per kilogram of body weight. In healthy men, the BCC averages 70 ml / kg, in healthy women— 65 ml/kg. G. A. Ryabov (1982) recommends using the calculation table compiled by Moore to determine the proper value of the BCC.

For practical work, especially in emergency cases, in the treatment of acute blood loss, it is more convenient to calculate the amount of blood loss in relation to the BCC. So, the average BCC of an adult with a body weight of 70 kg is 5 liters, of which 2 liters are cellular elements- erythrocytes, leukocytes, platelets (globular volume) and 3 l - for plasma (plasma volume). Thus, on average, BCC is 5-6 liters, or 7% of body weight Klimansky V.A., Rudaev Ya.A., 1984].

Volume of circulating blood in healthy people (in milliliters)

Weight body, kg	Men				Women
Weight body, kg	normosthenics (7.0)*	hypersthenics (6.0)	hyposthenics (6.5)	with developed muscles (7.5)	normosthenics (6.5)	hypersthenics (5.5)	hyposthenics (6.0)	with advanced muscles (7.0)
40	2800	2400	2600	3000	2600	2200	2400	2800
45	3150	2700	2920	3370	2920	2470	2700	3150
50	3500	3000	3250	3750	3250	2750	3000	3500
55	3850	3300	3570	4120	3570	3020	3300	3850
60	4200	3600	3900	4500	3900	3300	3600	4200
65	4550	3900	4220	4870	4220	3570	3900	4550
70	4900	4200	4550	5250	4550	3850	4200	4900
75	5250	4500	4870	5620	4870	4120	4500	5250
80	5600	4800	5200	6000	5200	4400	4800	5600
85	5950	5100	5520	6380	5520	4670	5100	5950
90	6300	5400	5850	6750	5850	4950	5400	6300
95	6650	5700	6170	7120	6170	5220	5700	6650

70-80% of the blood circulates in the veins, 15-20% in the arteries and 5-7.5% in the capillaries [Malyshev V.D., 1985]. In general, in cardiovascular system circulates 80%, in parenchymal organs - 20% of the BCC.

BCC is characterized by relative constancy. This is provided by mechanisms of self-regulation. The regulation of BCC is a complex and multi-stage process, but ultimately it comes down to the movement of fluid between the blood and the extravascular space and to changes in the excretion of fluid from the body [Levite E. M. et al., 1975; Seleznev S. A. et al., 1976; Kletskin S. 3., 1983].

At the same time, BCC is a value that is very variable even for one person, depending on his physical status and the state of homeostasis. People who systematically go in for sports have a large BCC. The value of BCC is influenced by age, gender, profession, ambient temperature, atmospheric pressure and other factors.

In response to acute blood loss, pathophysiological changes develop in the body, which are first of a compensatory-protective nature and ensure the preservation of life. We will consider some of them below.

"Infusion-transfusion therapy of acute blood loss",
E.A. Wagner, V.S. corners

The venomotor effect compensates for the loss of 10-15% of the BCC (500-700 ml) in an adult, if he does not suffer from any chronic disease and he has no evidence of hypovolemic shock or circulating volume deficiency. Such a "centralization" of blood circulation is biologically expedient, because for some time the blood supply to the vital important organs(brain, heart, lungs). However, in itself, it can cause the development of severe ...

Systemic blood flow response acute blood loss and hemorrhagic shock initially give a protective effect. However, prolonged vasoconstriction due to the development of acidosis and the accumulation of elevated concentrations of tissue metabolites - vasodilators leads to changes that are considered responsible for the development of decompensated reversible and irreversible shock. Thus, the contraction of arterioles leads to a decrease in tissue blood flow and oxygenation, causing a decrease in pH ...

Reactions that develop in response to a decrease in BCC lead to a decrease in volumetric blood flow in tissues and the development of compensatory mechanisms aimed at correcting reduced blood flow. One of these compensatory mechanisms is hemodilution - the entry of extravascular, extracellular fluid into the vascular bed. In hemorrhagic shock, there is progressive hemodilution that increases with the severity of the shock. The hematocrit is an indicator of the level of hemodilution. AT…

Compensation for the deficiency of plasma proteins occurs due to the mobilization of lymph from all lymphatic vessels. Under the influence of increased concentrations of adrenaline and excitation of the sympathetic nervous system, a spasm of small lymphatic vessels develops. The lymph contained in them is pushed into the venous collectors, which is facilitated by reduced venous pressure. The volume of lymph in the chest lymphatic duct increases rapidly after bleeding. This contributes to an increase in BCC ...

Peripheral blood flow depends not only on perfusion blood pressure, bcc and vascular tone. An important role belongs to the rheological properties of blood and, first of all, its viscosity. Sympathetic-adrenal stimulation leads to pre- and post-capillary vasoconstriction, resulting in a significant decrease in tissue perfusion. Tissue blood flow in the capillaries slows down, which creates conditions for the aggregation of erythrocytes and platelets and the development ...

Circulatory disorders in acute blood loss and hemorrhagic shock and massive infusion therapy can cause respiratory failure, which increases several hours after the operation. It is manifested by a violation of pulmonary capillary membrane permeability - interstitial pulmonary edema, i.e., one of the variants of the "shock lung". Trauma and acute blood loss cause hyperventilation. In hemorrhagic shock, minute ventilation is usually 1 1/2-2 ...

Experimental and clinical researches showed that in acute blood loss there is a decrease in renal blood flow by 50-70% with a selective decrease in cortical blood flow. Cortical blood flow is approximately 93% of renal blood flow. Selective reduction of renal β-flow due to preglomerular arterial vasoconstriction reduces glomerular pressure to a level at which glomerular filtration decreases or stops, oliguria or anuria develops. Hemodynamic…

Acute blood loss, especially massive, often causes liver dysfunction. They are primarily due to a decrease in hepatic blood flow, mainly arterial. The emerging liver ischemia leads to the development of centrilobular necrosis (IRauber, Floguet, 1971). Liver function is impaired: the content of transaminase increases, the amount of prothrombin decreases, hypoalbuminemia and hyperlaccidemia are observed. Due to resorption of a hematoma or as a result of a massive ...

An indicator of a change in metabolism is the formation of lactic acid as an end product instead of the normal end product of aerobic metabolism, CO2. As a result, metabolic acidosis develops. The number of buffer bases progressively decreases, and although respiratory compensation develops early, it is often inadequate in hemorrhagic shock. Studying the changes in metabolism in patients with blood loss and shock, A. Labori (1980) found that ...

Acute blood loss as a result of reduced venous age (absolute or relative hypovolemia) leads to a decrease in cardiac output. In connection with the release of catecholamines in the endings of the postganglionic sympathetic nerves of the precapillary and postcapillary parts vascular system there is a maximum stimulation of adrenocortical secretion. The reactions of the body to acute blood loss "Infusion-transfusion therapy of acute blood loss", E.A. Wagner, V.S. corners