Chapter 2. Physiology

Physiology in numbers Newton managed to express the movement of celestial bodies in mathematical equations. Mathematical thought has the power to transform biology, pathology and medicine. In its most basic application it can facilitate the discovery of new possibilities for

Muscle physiology There are three types of muscles: striated skeletal muscles, striated cardiac muscle and smooth muscles. Muscles have the following physiological properties: 1. excitability, i.e. the ability to be excited by the action of stimuli; 2.

Physiology of synapses The term “synapse” was introduced by C. Sherrington. A synapse is a functional connection between nerve cell and other cells. Synapses are those areas where nerve impulses can influence the activity of a postsynaptic cell, exciting or

Physiology of the heart

Physiology of sleep Sleep is a physiological state that is characterized by the loss of active mental connections of the subject with the world around him. Sleep is vital for higher animals and humans. Long time believed that sleep represents rest,

During phase I, lysokinase, entering the blood, brings the plasminogen proactivator into an active state. This reaction occurs as a result of the cleavage of a number of amino acids from the proactivator.

Phase II – conversion of plasminogen to plasmin due to the cleavage of the lipid inhibitor under the influence of the activator.

During phase III, under the influence of plasmin, fibrin is broken down into polypeptides and amino acids. These enzymes are called fibrinogen/fibrin degradation products and have a pronounced anticoagulant effect. They inhibit thrombin and inhibit the formation of prothrombinase, suppress the process of fibrin polymerization, platelet adhesion and aggregation, enhance the effect of bradykinin, histamine, angeotensin on the vascular wall, which promotes the release of fibrinolysis activators from the vascular endothelium.

Distinguish two types of fibrinolysis– enzymatic and non-enzymatic.

Enzymatic fibrinolysis carried out with the participation of the proteolytic enzyme plasmin. Fibrin is broken down into degradation products.

Non-enzymatic fibrinolysis carried out by complex compounds of heparin with thrombogenic proteins, biogenic amines, hormones, conformational changes occur in the fibrin-S molecule.

The process of fibrinolysis occurs through two mechanisms - external and internal.

Along the external pathway, activation of fibrinolysis occurs due to tissue lysokinases and tissue plasminogen activators.

Proactivators and activators of fibrinolysis take part in the internal activation pathway, capable of converting proactivators into plasminogen activators or acting directly on the proenzyme and converting it into plasmin.

Leukocytes play a significant role in the process of fibrin clot dissolution due to their phagocytic activity. Leukocytes capture fibrin, lyse it and release its degradation products into the environment.

The process of fibrinolysis is considered in close connection with the process of blood coagulation. Their relationships occur at the level of common pathways of activation in the reaction of the enzyme cascade, as well as through neurohumoral regulatory mechanisms.

Factors that accelerate and slow down blood clotting.

Factors that accelerate the blood clotting process:

Destruction of blood cells and tissue cells (increases the output of factors involved in blood clotting):

Calcium ions (participate in all main phases of blood clotting);

Thrombin;

Vitamin K (participates in the synthesis of prothrombin);

Heat (blood clotting is an enzymatic process);

Adrenalin.

Factors that slow down blood clotting

Elimination mechanical damage blood cells (waxing of cannulas and containers for collecting donor blood);

Sodium citrate (precipitates calcium ions);

Heparin;

Hirudin;

Decrease in temperature;

Plasmin.

Anticoagulant mechanisms. Under normal conditions, the blood in the vessels is always in a liquid state, although conditions for the formation of intravascular blood clots constantly exist. Maintaining the liquid state of blood is ensured by the principle of self-regulation with the formation of appropriate functional system. The main reaction apparatuses of this functional system are the coagulation and anticoagulation systems. Currently, it is customary to distinguish two anticoagulant systems - the first and the second.

The first anticoagulant system (PAC) neutralizes thrombin in the circulating blood provided that it is formed slowly and in small quantities. Neutralization of thrombin is carried out by those anticoagulants that are constantly in the blood and therefore the PPS functions constantly. Such substances include:

Fibrin, which adsorbs part of thrombin;

Antithrombins (4 types of antithrombins are known), they prevent the conversion of prothrombin to thrombin;

Heparin - blocks the transition phase of prothrombin to thrombin and fibrinogen to fibrin, and also inhibits the first phase of blood coagulation;

Lysis products (destruction of fibrin), which have antithrombin activity, inhibit the formation of prothrombinase;

Cells of the reticuloendothelial system absorb thrombin from blood plasma.

With a rapid avalanche-like increase in the amount of thrombin in the blood, PPS cannot prevent the formation of intravascular thrombi. In this case, the second anticoagulant system (ACS) comes into play, which ensures the maintenance of the liquid state of blood in the vessels by a reflex-humoral way according to the following scheme. Sharp increase concentration of thrombin in the circulating blood leads to irritation of vascular chemoreceptors. Impulses from them enter the giant cell nucleus reticular formation medulla oblongata, and then along the efferent pathways to the reticuloendothelial system (liver, lungs, etc.). Heparin and substances that carry out and stimulate fibrinolysis (for example, plasminogen activators) are released into the blood in large quantities.

Heparin inhibits the first three phases of blood coagulation and interacts with substances that take part in blood coagulation. The resulting complexes with thrombin, fibrinogen, adrenaline, serotonin, factor XIII, etc. have anticoagulant activity and a lytic effect on unstabilized fibrin.

Consequently, the maintenance of blood in a liquid state is carried out due to the action of PPS and IPS.

Regulation of blood clotting. Regulation of blood coagulation is carried out using neuro-humoral mechanisms. Excitation of the sympathetic department of the autonomic nervous system, which occurs during fear, pain, and stressful conditions, leads to a significant acceleration of blood clotting, which is called hypercoagulation. The main role in this mechanism belongs to adrenaline and norepinephrine. Adrenaline triggers a number of plasma and tissue reactions.

First, release from vascular wall thromboplastin, which quickly turns into tissue prothrombinase.

Secondly, adrenaline activates factor XII, which initiates the formation of blood prothrombinase.

Thirdly, adrenaline activates tissue lipases, which break down fats and thereby increase the content fatty acids in the blood with thromboplastic activity.

Fourthly, adrenaline enhances the release of phospholipids from blood cells, especially from red blood cells.

Irritation vagus nerve or the administration of acetylcholine leads to the release from the walls of blood vessels of substances similar to those released under the action of adrenaline. Consequently, in the process of evolution, only one protective-adaptive reaction was formed in the hemocoagulation system - hypercoagulemia, aimed at urgently stopping bleeding. The identity of hemocoagulation shifts upon stimulation of the sympathetic and parasympathetic parts of the autonomic nervous system indicates that primary hypocoagulation does not exist, it is always secondary and develops after primary hypercoagulation as a result (consequence) of the consumption of part of the blood coagulation factors.

Acceleration of hemocoagulation causes increased fibrinolysis, which ensures the breakdown of excess fibrin. Activation of fibrinolysis is observed during physical work, emotions, and painful stimulation.

Blood coagulation is influenced by the higher parts of the central nervous system, including the cortex cerebral hemispheres brain, which is confirmed by the possibility of changing hemocoagulation conditionally reflexively. It exerts its influence through the autonomic nervous system and endocrine glands, the hormones of which have a vasoactive effect. Impulses from the central nervous system arrive to the hematopoietic organs, to the organs that store blood and cause an increase in blood output from the liver, spleen, and activation of plasma factors. This leads to the rapid formation of prothrombinase. Then humoral mechanisms are turned on, which support and continue the activation of the coagulation system and at the same time reduce the effects of the anticoagulation system. The significance of conditioned reflex hypercoagulation appears to be in preparing the body to protect itself from blood loss.

The blood coagulation system is part of a larger system - the system for regulating the state of aggregation of blood and colloids (PACK), which maintains the constant internal environment the body and its state of aggregation at a level that is necessary for normal life by ensuring the maintenance of the liquid state of the blood, restoring the properties of the walls of blood vessels, which change even during their normal functioning.

Used Books:

Study of the blood system in clinical practice. / Ed. G. I. Kozints and V. A. Makarov. - M.: Triada-X, 1997.

Panteleev M. A., Vasiliev S. A., Sinauridze E. I., Vorobyov A. I., Ataullakhanov F. I. Practical coagulology / Ed. A. I. Vorobyova. - M.: Practical Medicine, 2011.

Human physiology edited by V.M. Pokrovsky, G.F. Korotko.

Fibrinolytic syndrome- a hemorrhagic syndrome caused by excessive fibrinolytic activity, which can appear in a variety of clinical variants. In the past it was included in the category of plasmatic hemorrhagic diathesis, but in 1959 Sherry individualized it as an independent nosological entity.

Clinic of fibrinolytic syndrome. From a clinical point of view, hemorrhagic syndrome can take various aspects: epistaxis, large ecchymoses with a contour geographical map, gastrointestinal bleeding, hemorrhages at injection or puncture sites, hemorrhages after surgical interventions. At first these phenomena are of a moderate nature; over time, they become more and more severe, as they are accompanied by various deficiencies in hemostasis caused by the very development of the fibrinolytic process; eventually the hemorrhagic syndrome becomes so severe that it puts the patient's life in danger.

Pathophysiology of fibrinolytic syndrome. Normal action The fibrinolysis mechanism is ensured by a dynamic balance between activators and inhibitors. Whenever activators predominate, the imbalance manifests clinically as fibrinolytic syndrome; the greater the discrepancy, the more severe the clinical aspect.

Fibrinolysis can act as an independent disorder (primary) or as a consequence of simple or disseminated intravascular coagulation (secondary). Primary fibrinolysis can occur due to the growth of plasminogen activators (spontaneous) or the introduction into circulation of plasminogen activators to lyse known blood clots (therapeutic).

In all cases result is the release of plasmin, which, due to its lytic effect on fibrin, fibrinogen, F. V, F. VIII causes hemorrhagic syndrome, described in the symptomatology section.

Primary fibrinolysis happens extremely rarely (5%); secondary is much more common.

Laboratory research for the diagnosis of fibrinolytic syndrome. The results of laboratory tests are very variable depending on the moment when they are performed and on the type of fibrinolysis of the patient (primary or secondary). Below we will focus on tests of primary fibrinolysis, since secondary fibrinolysis will be presented in connection with DIC syndrome.

T.N., RTT and T.Q. may be slightly elongated (F.D.P. interferes with platelet function and thrombin activity, and plasma lyses F. V and VIII). Sample clots are small (little fibrinogen). TLCE has been significantly reduced; the shorter it is, the more severe the syndrome. The Astrup test (with fibrin plates) allows you to isolate the causal agent of fibrinolysis: lysokinase, activator, plasmin. TEG presents a characteristic track, like a tennis racquet. The FDP detection test is positive (with grades from + to + + + +).

Dosage fibrinogen gives lower numbers, the stronger the fibrinolysis. Other tests for hemostasis and coagulation give normal results.

Positive clinical diagnosis of fibrinolytic syndrome is based on the following: late appearance of bleeding, map-shaped contour of ecchymosis, bleeding at the injection and puncture sites, a small and fragile clot that releases a large number of red blood cells (when the syndrome is severe, the blood loses its ability to coagulate!).

Laboratory research show almost normal coagulation tests along with positive fibrinolysis tests, allowing a definitive diagnosis. Differential diagnosis produced in relation to other hemorrhagic diathesis. The circumstances under which bleeding occurs and laboratory results provide an indisputable diagnosis.

Course and complications of fibrinolytic syndrome. Fibrinolytic syndrome can have a very diverse evolution. Within this evolution, chronic and acute fibrinolytic syndromes are at two extremes.

Chronic syndrome has a benign evolution and without complications. It may worsen due to surgical intervention, produced without antifibrinolytic protection.

Acute or fulminant syndrome has a dramatic evolution. Death may occur before diagnosis and treatment. In those diagnosed and treated for modern methods In some cases, favorable results are obtained within the first 12 hours.

Treatment of fibrinolytic syndrome refers to acute syndrome and pursues the goal of stopping hemorrhagic syndrome. As effective means can be used:
a) Antifibrinolytic, which suppress the mechanism of fibrinolysis; this can be achieved in two ways:
1) Antiplasmin action: blocking of plasmin, which is carried out by antiplasmins or protease inhibitors, of two types: the Kunitz inhibitor, made from the pancreas and marketed under the name Iniprol, and the Frey inhibitor, made from the parotid salivary gland and marketed under the name Trasylol (the former is ten times more active than the latter).
2) Anti-activating effect: blocking the activation of plasminogen into plasmin, which is carried out by synthetic substances of two types: with a linear molecule (EACA) and a cyclic molecule (AMCNA) (the latter is 7 times more active than the first).

b) Substitution: injected fibrinogen and lyophilized antihemophilic plasma, both containing coagulation factors that were lysed in the patient's plasma during the process of hyperfibrinolysis and which we replace using perfusion.

Treatment regimen for fibrinolytic syndrome: We start with Trasylol 1,000,000 units as a slow perfusion over 24 hours. An hour after the start of perfusion with Trasylol, it is injected slowly i.v. EACA at a dose of 0.3 g/kg body weight/day, divided into 4 doses (1 every 6 hours).

2 hours after the first injection of EACA, injected i.v. fibrinogen 2 g and perfusion of one vial of lyophilized antihemophilic plasma continues. Usually within 24 hours the effect of treatment is favorable, so it should be interrupted; if the patient's condition requires it, we repeat the same treatment the next day. (Attention! for secondary fibrinolysis, all of the above treatment should be preceded by the administration of heparin: 40,000 U/day, 10,000 U IV, every 6 hours for 2-3 days).

Fibrinolysis is an integral part of the hemostasis system, always accompanies the process of blood coagulation and is activated by factors involved in this process. As an important protective reaction, fibrinolysis prevents blockage blood vessels fibrin clots. In addition, fibrinolysis leads to vascular recanalization after bleeding has stopped.

The enzyme that destroys fibrin is plasmin (sometimes called “fibrinolysin”), which is in an inactive state in the circulation as the proenzyme plasminogen.

Fibrinolysis, like the process of blood coagulation, can occur through an external and internal mechanism (pathway). The external mechanism of activation of fibrinolysis is carried out with the participation of tissue activators, which are synthesized mainly in the vascular endothelium. These include tissue plasminogen activator (tPA) and urokinase. The latter is also formed in the juxtaglomerular complex (apparatus) of the kidney. The internal mechanism of activation of fibrinolysis is carried out by plasma activators, as well as activators of blood cells - leukocytes, platelets and erythrocytes and is divided into Hageman-dependent and Hageman-independent. Hagemai-dependent fibrinolysis occurs under the influence of factors XIIa, kallikrein and BMC, which convert plasminogen into plasmin. Hageman-independent fibrinolysis occurs most quickly and is urgent. Its main purpose is to cleanse the vascular bed of unstabilized fibrin formed during the process of intravascular blood coagulation.

Plasmin formed as a result of activation causes the breakdown of fibrin. In this case, early (large molecular) and late (low molecular) PDFs appear.

Fibrinolysis inhibitors are also found in plasma. The most important of them are a²-antiplasmin, which binds plasmin, trypsin, kallikrein, urokinase, tPA and, therefore, interferes with the process of fibrinolysis both in the early and early stages. late stages. Ai-protease inhibitor is a strong inhibitor of plasmin. In addition, fibrinolysis is inhibited by da-macroglobulin, a Ci-protease inhibitor, as well as a number of plasminogen activator inhibitors synthesized by endothelium, macrophages, monocytes and fibroblasts.

Fibrinolytic activity of blood is largely determined by the ratio of activators and inhibitors of fibrinolysis.

By accelerating blood clotting and simultaneous inhibition of fibrinolysis, favorable conditions are created for the development of thrombosis, embolism and disseminated intravascular coagulation syndrome.

Along with enzymatic fibrinolysis, according to Professor B.A. Kudryashov, there is so-called non-enzymatic fibrinolysis, which is caused by complex compounds of the natural anticoagulant heparin with enzymes and hormones. Non-enzymatic fibrinolysis leads to the breakdown of unstabilized fibrin, clearing the vascular bed of fibrin monomers and fibrin s.

Regulation of blood coagulation and fibrinolysis

Coagulation of blood in contact with injured tissues occurs within 5-10 minutes. The main time in this process is spent on the formation of prothrombinase, while the transition of prothrombin to thrombin and fibrinogen to fibrin occurs quite quickly. Under natural conditions, blood clotting time can decrease (hypercoagulation develops) or lengthen (hypocoagulation occurs).

A significant contribution to the study of the regulation of blood coagulation and fibrinolysis was made by domestic scientists E.S. Ivanitsky-Vasilenko, A.A. Markosyan, B.A. Kudryashov, S.A. Georgieva and others.

It has been established that when acute blood loss, hypoxia, intense muscular work, painful irritation, stress, blood clotting is significantly accelerated, which can lead to the appearance of fibrin monomers and even fibrin s in the vascular bed. However, due to the simultaneous activation of fibrinolysis, which is protective in nature, emerging fibrin clots quickly dissolve and do not harm a healthy body.

Acceleration of blood coagulation and increased fibrinolysis in all of these conditions is due to an increase in the tone of the sympathetic nervous system and the entry of adrenaline and norepinephrine into the bloodstream. In this case, the Hageman factor is activated, which leads to the launch of the external and internal mechanism of prothrombinase formation, as well as the stimulation of Hageman-dependent fibrinolysis. In addition, under the influence of adrenaline, the formation of apoprotein III, a component of thromboplastin, is enhanced, and the separation of cell membranes from the endothelium, which has the properties of thromboplastin, is observed, which contributes to a sharp acceleration of blood clotting. TPA and urokinase are also released from the endothelium, leading to stimulation of fibrinolysis.

In case of increased tone of the parasympathetic nervous system (irritation of the vagus nerve, administration of ACh, pilocarpine), acceleration of blood coagulation and stimulation of fibrinolysis are also observed. Under these conditions, thromboplastin and plasminogen activators are released from the endothelium of the heart and blood vessels. Consequently, the main efferent regulator of blood coagulation and fibrinolysis is the vascular wall. Let us also recall that Pgb is synthesized in the vascular endothelium, which prevents platelet adhesion and aggregation in the bloodstream. At the same time, developing hypercoagulation can be replaced by hypocoagulation, which in natural conditions is secondary in nature and is caused by the consumption (consumption) of platelets and plasma coagulation factors, the formation of secondary anticoagulants, as well as a reflex release into the vascular bed in response to the appearance of factor Na, heparin and antithrombin III (see Diagram 6.4).

In many diseases accompanied by the destruction of erythrocytes, leukocytes, platelets and tissues and or hyperproduction of apoprotein III by stimulated endothelial cells, monocytes and macrophages (this reaction is mediated by the action of antigens and interleukins), DIC syndrome develops, significantly aggravating the course of the pathological process and even leading to death sick. Currently, DIC syndrome is detected in more than 100 various diseases. It occurs especially often during transfusion of incompatible blood, extensive injuries, frostbite, burns, long-term surgical interventions on the lungs, liver, heart, prostate gland, all types of shock, as well as in obstetric practice when amniotic fluid saturated with thromboplastin of placental origin enters the mother’s bloodstream . In this case, hypercoagulation occurs, which, due to the intensive consumption of platelets, fibrinogen, factors V, VIII, XIII, etc. as a result of intense intravascular coagulation, is replaced by secondary hypocoagulation up to the complete inability of the blood to form fibrin clots, which leads to bleeding that is difficult to treat .

Knowledge of the basic physiology of hemostasis allows the clinician to choose the best options for dealing with diseases accompanied by thrombosis, embolism, disseminated intravascular coagulation syndrome and increased bleeding.

Fibrinolysis is the process of dissolving blood clots, including the breakdown of the insoluble fibrin protein by the enzyme plasmin. Simultaneously with retraction, fibrinolysis begins - the breakdown of fibrin.

Fibrinolysis also promotes recanalization of blood vessels after bleeding has stopped. Hageman-dependent fibrinolysis occurs under the influence of blood coagulation factor XIIa, kallikrein, which causes the conversion of plasminogen to plasmin. Hageman-dependent fibrinolysis occurs most quickly and is urgent.

Increased fibrinolysis is due to an increase in the tone of the sympathetic nervous system and the entry of adrenaline and norepinephrine into the blood. This causes activation of the Hageman factor, which triggers the external and internal mechanisms of prothrombinase production, and also stimulates Hageman-dependent fibrinolysis.

Fibrinolysis - (from Fibrin and Greek lýsis - decomposition, dissolution) dissolution of intravascular blood clots and extravascular fibrin deposits under the action of the enzyme Fibrinolysin. This transformation is balanced by continuous fibrinolysis, which normally prevents the formation of a clot in an intact vessel. The most important stimulator of the external mechanism of fibrinolysis are protein plasminogen activators, which are synthesized in the wall.

The high efficiency of fibrinolysis is due to the fact that during blood clotting, fibrin adsorbs plasminogen. During phase III, under the influence of plasmin, fibrin is broken down into polypeptides and amino acids.

There are two types of fibrinolysis - enzymatic and non-enzymatic. Enzymatic fibrinolysis is carried out with the participation of the proteolytic enzyme plasmin. Along the external pathway, activation of fibrinolysis occurs due to tissue lysokinases and tissue plasminogen activators. Principle: The method is based on the precipitation in an acidic environment and at low temperatures of the euglobulin fraction containing coagulation and fibrinolysis factors.

Euglobulin lysis can be significantly accelerated by adding fibrinolysis activators (streptokinase, urokinase, etc.) to the system or by pre-treating the plasma with kaolin. Blood coagulation is a chain enzymatic process in which the activation of coagulation factors and the formation of their complexes sequentially occur.

See what “FIBRINOLYSIS” is in other dictionaries:

High molecular weight kininogen (f XV) and kallikrein (f XIV) are also involved in the activation and action of factor XII. Factor XII then activates factor XI, forming a complex with it. Second phase. During this phase, under the influence of prothrombinase, prothrombin transforms into the active enzyme thrombin. Under the influence of fibrin-stabilizing factor XIII, the formation of an insoluble fibrin polymer (fibrin “I”, insoluble), resistant to fibrinolysis, occurs.

Hemostasis system

It is an important protective reaction of the body and prevents blockage of blood vessels by fibrin clots. The external activation pathway is carried out with the integral participation of tissue activators, synthesized mainly in the vascular endothelium.

The internal activation mechanism is carried out thanks to plasma activators and activators of blood cells - leukocytes, platelets and erythrocytes. The internal activation mechanism is divided into Hageman-dependent and Hageman-independent.

Description and interpretation of laboratory parameters online

Tissue plasminogen activator and urokinase are also released from the endothelium, stimulating the process of fibrinolysis. It is believed that transformation processes constantly occur in the blood small quantity fibrinogen to fibrin.

During the breakdown of fibrin, the proteolytic enzyme plasmin is formed. Therefore, it acts locally (in blood clots). An intense release of vascular activators into the blood occurs when vascular patency is impaired, physical activity under the influence of substances that constrict blood vessels.

As a result, plasmin appears directly in the blood clot, which begins to break down immediately after formation. Potent plasminogen activators are found in all blood cells, especially leukocytes.

A unified method for determining fibrinolytic activity by lysis of plasma euglobulins (according to E. Kowalski et al., 1959).

There are two groups of activators: direct action and indirect action. Direct-acting activators directly convert plasminogen into its active form - plasmin. Indirect-acting activators are in the blood plasma in an inactive state in the form of a proactivator. During phase I, lysokinase, entering the blood, brings the plasminogen proactivator into an active state.

Phase II – conversion of plasminogen to plasmin due to the cleavage of the lipid inhibitor under the influence of the activator. Leukocytes play a significant role in the process of fibrin clot dissolution due to their phagocytic activity. Leukocytes capture fibrin, lyse it and release its degradation products into the environment. The time of lysis of a euglobulin clot is the time from the moment of formation of a blood clot to the moment of its dissolution in the blood plasma. Thrombin is added to the precipitated plasma fraction to form a clot.

A balance is maintained between the processes of blood coagulation and fibrinolysis in the body. This mechanism also provides cadaveric fibrinolysis. Fibrinolysis, like the process of blood coagulation, occurs via an external or internal mechanism. The fibrinolysis system is an enzymatic system that breaks down fibrin strands that are formed during blood clotting into soluble complexes.