STRESS

From Big Medical Encyclopedia

STRESS (English. stress). Understand the state arising at action extraordinary or patol as S. irritants and leading to tension of nonspecific adaptable mechanisms of an organism. The term «stress» is entered into medical literature in 1936. The Selye, to-ry defines a stress as the condition of an organism arising at presentation to it any requirements.

The wedge which is observed at S., a syndrome — the general adaptation syndrome , (see) can have three stages of development: a stage of alarm, at a cut there is a mobilization of initial forces of an organism; stage of resistance; it is noted a stage of exhaustion, edge at influence of an intensive irritant or at long influence of a weak irritant, and also at functional weakness of adaptive mechanisms of an organism; at the same time the syndrome gains pathogenic character. In this regard G. Selye distinguished eustress — the syndrome promoting preservation of health and a distress — the syndrome getting a role of a pathogenic factor. Considered G. Selye's disturbances arising in the latter case as an adaptation disease. S.'s development is connected with mechanisms homeostasis (see), to-rye provide relative constancy of internal environment of an organism.

On the Selye, treat the hormones taking the greatest part in S.'s implementation: kortikoliberin (see. Hypothalamic neurohormones ), AKTG (see. Adrenocorticotropic hormone ), somatotropic hormone (see), corticosteroids (see), adrenaline (see) and, perhaps, thyroid hormones (see. Thyroid gland ).

Stressful reaction can arise under the influence of an injury, a burn, action on an organism various patol. irritants, and also at emotional influences — emotional stress (see). According to Raab (W. Raab, 1968), at infant rats, the long time contained one by one, arises stressful reaction, edges is followed by change of electrolytic structure (reduction of contents in a myocardium of potassium ions and magnesium, increase in quantity of ions of sodium) and sharp sensitization of animals to cardiotoxic action catecholamines (see). Emotional S. at the person was widely studied by the Swedish researchers, to-rye showed that both surplus, and full switching off of emotional influences can bring to Page.

Emergence and S.'s character are defined also reactivity of an organism (see), edges, in turn, depends on hereditary properties of an organism, earlier postponed influences, on age and other factors. These «conditioning factors» (on the Selye) are explained, e.g., why the same stress factor, or a stress factor (the irritant causing S.) can cause various manifestations and effects in different persons. An outcome the stress reaction can be return to an initial condition of an organism or developing of a disease.

Various irritants give to S. the features caused by emergence of specific reactions to qualitatively various influences.

The initial (afferent) impulse causing S. is unknown. Its emergence can be caused by contagious excitation, disturbance of a homeostasis, influence of any metabolic factor, etc. Irrespective of the nature of an irritant and the arising «first mediator» (on the Selye) crucial importance in effector implementation a stress reaction activation of system has a hypothalamus — a hypophysis — bark of adrenal glands and excitement of a sympathetic nervous system, as a result to-rogo catecholamines are allocated. Secretion of corticosteroids is noted not only at S. Tak, AKTG can cause allocation of corticosteroids without emergence of any symptoms of a stress. On the other hand, separate manifestations a stress reaction can be observed also at adrenal-zktomirovannykh of animals.

Excitement of a sympathetic nervous system (see. Autonomic nervous system ) and allocation of catecholamines, first of all adrenaline. the stress reaction is considered as one of the most important releasers. At emotional influence increase in level of catecholamines in blood and urine is the most sensitive test a stress reaction. At the same time inclusion of system a hypophysis — bark of adrenal glands can sometimes not happen. Value of a sympathetic nervous system in adaptation of an organism as it showed L. A. Orbeli, U. Kenion, etc., is much wider and is not limited to activation of mechanisms a stress reaction.

Works of. A Selye (1979) and its followers it is established that the mechanism of implementation a stress reactions is started in hypothalamus (see) under the influence of the nervous impulses arriving from a cerebral cortex, a reticular formation, limbic system. Neurosecretory cells of a hypothalamus perceive afferent signals from other parts of the nervous system and emit neurohormones in blood. Neurosecretory cells of a hypothalamus develop not only liberina, but also statines, to-rye inhibit gormonopoetichesky functions hypophysis (see).

Development of the general adaptation syndrome is connected with the changes of an organism caused by adaptive hormones. The typical and the most expressed manifestation of a stage of alarm of G. Selye considered the shock (see) proceeding in two phases — a phase of shock and a phase of a countercurrent.

The most expressed initial biochemical and structural changes happening in cortical substance adrenal glands (see), lead to the fact that under the influence of endogenous AKTG the maintenance of corticosteroids in blood already in a few minutes increases. At the same time in adrenal glands contents ascorbic to - you falls. The amount of cholesterol and its ethers decreases in several hours after heavy and long S., cells of cortical substance of adrenal glands are exposed to a hyperplasia and a hypertrophy that demonstrates acquisition of a certain degree of resistance of an organism (see). Increase in resistance to one agent causes protection of an organism against different stress factors (cross resistance). However also sensitization to other agents (a nonspecific sensitization) can take place.

Long before G. Selye's works is the Soviet pathophysiologist A. A. The pilgrim (1905) for the first time showed that under intense conditions for an organism (the strengthened muscular work, pregnancy, intoxication) there is strengthening of function of cortical substance of adrenal glands.

In a wedge, conditions and in an experiment it is established that insufficiency of cortical substance of adrenal glands sharply lowers body resistance. So, Filkins (J. P. Filkins, 1972) showed that sensitivity of rats to Salmonella enteritidis endotoxin after removal of both adrenal glands increases in several thousands of times.

Increase in nonspecific body resistance in a stage of resistance is defined by increase in secretion cortical substance of adrenal glands of the glucocorticoid hormones (see) possessing antiinflammatory action.

G. Selye distinguished I sintoksiche-will hold down also katatoksichesky a stress reaction. The syntactic reaction caused first of all by glucocorticoids creates a condition of passive tolerance in relation to a disturbing factor. Katato-ksichesky reaction accelerates metabolic destructions of a pathogenic factor by strengthening of formation of mikrosomny enzymes of hepatocytes. As a result resistance of an organism to a certain factor increases.

Along with the general adaptation syndrome of G. Selye allocated also local adaptation syndrome — local nonspecific reaction, at a cut action of an irritant is limited generally to limits of the damaged fabric. As a typical example of such reaction he offered a pilot model of an acute inflammation in the form of a so-called granulemny pocket (abscess). For this purpose under skin of a back of a rat the syringe enter air along with a small amount of any strong irritant into friable connecting fabric (croton oil, formalin, mustard oil, etc.). In development of a local adaptation syndrome of G. Selye also established three stages: local stage of alarm, local stage of resistance and local stage of exhaustion. The local stage of alarm develops immediately after introduction of an irritant and is that cells and fibers of connecting fabric are exposed to the dystrophic changes leading to development of a necrosis. This process is considered as an equivalent of a phase of shock of the general adaptation syndrome. Further dedifferentiation of mature fibroblasts in roundish cells of embryonal type is observed (polyblasts), to-rye are capable to be transformed in several directions. This process, apparently, is an equivalent of a phase of a countercurrent of the general adaptation syndrome.

The local stage of resistance is shown by differentiation of cells in fibroblasts, lymphoid cells, macrophages, colossal cells and others depending on specific properties of an irritant. E.g., the most fine particles of a kaolin to a stim lirut formation of macrophages, mustard powder — colossal cells, croton oil — proliferation of fibroblasts, etc. Functionally this stage is characterized by high local resilience to further influence even of higher necrotizing doses of this irritant (specific resistance). In similar experiments an opportunity and cross resistance, i.e. increase in resilience to other irritants was shown.

The local stage of exhaustion begins cicatricial reduction of a granulemny pocket and comes to an end with perforation of skin and an exit of contents from abscess. A local adaptation syndrome as well as the general adaptation syndrome, is unusually sensitive to adaptive hormones. At the general adaptation syndrome systemic inflammatory lesions (e.g., a nodular periarteritis, polyarthritis) can be caused by so-called pro-inflammatory hormones (cortexone, dezoksikorti-zoly, somatotropic hormone) while antiinflammatory hormones (AKTG, a cortisone, a hydrocortisone) have opposite effect, reducing a wedge, manifestations of an inflammation (see). Antiinflammatory hormones not necessarily oppress an inflammation to the same extent in all sites of an organism. Selectivity of their action can depend on blood supply: where it is weaker, inflammatory reaction decreases, the centers of a necrosis increase. At a local adaptation syndrome somatotropic hormone possesses the expressed antinekrotiche-sky action.

The general and local adaptation syndromes mutually influence at each other. Any local process can be the cause of development of the general adaptation syndrome.

The leading role in regulation of intensity of synthesis and disintegration of enzymes, i.e. their activities, belongs to hormones. It is important at extreme states, or in the conditions of S. when there is a need for increase in amount of any enzyme or for change of its quality (adaptive change of a metabolism). It is established that corticosteroids can influence all stages of synthesis and disintegration of enzymes, providing thereby corresponding «setup» of exchange processes of an organism.

At S. under the influence of catecholamines easily available energy sources are quickly formed. Catecholamines work through phosphorylase system of a liver, edges are activated by a glycogenolysis and an exit of glucose in blood. To development hyperglycemia (see) increase in concentration of the glucocorticoids stimulating glyconeogenesis, i.e. formation of carbohydrates from not carbohydrate sources promotes (see. Carbohydrate metabolism ).

Glucocorticoids stimulate mobilization and the proteolysis, formation of carbohydrates from nitrogen-free products of dezaminirovanny amino acids that results in negative nitrogenous balance (see. Nitrogen metabolism ). An energy source are also free fat to - you, to-rye are formed of triglycerides under the influence of a glucagon. Mobilization of energy resources is followed by their redistribution (see. Lipometabolism ).

Corticosteroids influence exchange of various mediators (see) and modulators of synoptic transfers, to-rykh catecholamines, piperidic to - that, serotonin, etc. are among.

The weight loss (mass) of a body is caused by dominance of a catabolism (dissimilation), strengthening to-rogo is usually attributed to action of corticosteroids. However influence of glucocorticoids is not always unambiguous. They can stimulate synthetic processes and work anabolic, napr, in a liver, or at insufficiency of function of adrenal glands.

At S. there is an activation of peroxide oxidation of lipids and in this regard disturbance of membrane structures of cells. The lipemia and oxidates of lipids can promote development atherosclerosis (see).

The role of corticosteroids in maintenance of a tone of vessels and cardiac performances is noted in the conditions of clinic and an experiment long ago. It is established that glucocorticoids strengthen pressor impacts of a nervous system on vessels and increase force of cordial reductions. Hypotension is observed at an addisonovy disease, and also in an experiment after removal of adrenal glands.

In G. Selye's works it is shown that S.'s influence or administration of steroid drugs in combination with effect of various electrolytes can promote emergence of a cardiopathy or warn her. The pathology of heart arising at the same time, on the Selye, generally has two forms. One of them is designated by it as an electrolytic and steroid cardiopathy with a hyalinosis, another — as an electrolytic and steroid cardiopathy with a necrosis of muscular tissue of heart.

As a rule, surplus in a diet of sodium of chloride promotes that endogenous corticosteroids can exert pathogenic impact. At the same time excess of sodium of chloride in combination with action of mineralokorti-koid, napr, cortexone, leads to development of an elektrolitnosteroidny cardiopathy with a hyalinosis. This form of pathology is observed at myocarditis, a nodular periarteritis and is followed by development of a nephrosclerosis and hypertensia. The electrolytic and steroid cardiopathy with a necrosis easily is reproduced at rats by injections of an active synthetic kortikoid of 2-a-methyl-9-a-chlorcortisol and introduction through a mouth of Na2HP04, Na2S04 or NaC104. However the listed electrolytes, as well as other impacts on animals (cold bathtubs, an immobilization, section of a spinal cord, bloodletting, administration of adrenaline, etc.) lead to emergence of the centers of a necrosis in a myocardium if these influences are carried out against the background of preliminary introduction of corticosteroids. On the Selye, necroses of a myocardium — result of action not of any one factor, but a consequence of joint influence of a number of factors in the form of «nonspecific humoral conditionality». Experiments showed that in similar conditions simultaneous introduction of MgCl2 or KC1 protects a myocardium from emergence of necroses.

Thus, one factors (corticosteroids, sodium salts) sensibilize an organism, others (salts of magnesium, potassium) — desensibilize it. The page can act not only as sensibilizing, but also a protective factor in development of necrotic changes of a myocardium.

T. 3. Meerson (1981) investigated mechanisms of prevention of stressful injuries of heart in an experiment. Mediators and modulators take part in these mechanisms, to-rye limit excitement of adrenergic and pituitary and adrenal systems (piperidic to - that, gamma and hydroxy-butyric to - that).

In particular, it was revealed that at intact animals gamma and hydroxy-butyric to - that increases the speed of reduction and relaxation of papillary muscles of heart. At S. these indicators decrease by 30 — 50% and are recovered after introduction gamma and hydroxy-butyric to - you.

In addition to the central mechanisms, in cells under the influence of catecholamines there are exchange shifts playing an adaptive role and preventing injuries of a myocardium. Strengthening of synthesis and release of prostaglandins of group E concern to them (see Prostaglandins). At S. antioxidant substances (alpha tocopherol and its synthetic analogs) can play a protective role, to-rye weaken processes of peroxide oxidation of lipids in an organism.

Damages of a mucous membrane went. - kish. a path can be rather easily reproduced at experimental animals (mice, rats, Guinea pigs and dogs) by such stressful influences as an immobilization, cold (immersion in a bathtub at a temperature of 23 °), bandaging of a pylorus, etc. Process develops quickly, on a mucous membrane erosion and ulcers are formed, to-rye can get into a muscular coat and even to cause perforation of a wall. Developing of ulcers at S. at experimental animals is followed by increase in acidity and the digesting force of a gastric juice, reduction of quantity and change of quality of slime, increase in frequency and volume of the return flowings of juice of a duodenum, strengthening in serum and a blood plasma of a histamine, catecholamines and glucocorticoids. A protective role is played by strengthening of blood supply of fabrics, cellular regeneration and products of slime. Major importance in damage of a mucous membrane went. - kish. a path belongs to increase in secretion salt to - you; the quantity of the arising ulcers directly correlates with acid value of a gastric juice. Increase in secretion salt to - you a mucous membrane of a stomach happens owing to stimulation by a front and back share of a hypothalamus and increase in a tone of a vagus nerve (see). The role of a vagus nerve is confirmed by the fact that reception of atropine or vagisection before S. increases blood supply of a mucous membrane, and damages went. - kish. the path does not arise. However process of formation of ulcers is more difficult. It in many respects depends on biologically active agents (a histamine, serotonin, heparin) which are emitted at S. from granules of mast cells. Therefore medicamentous prevention is not limited only to reception of atropine; experiments showed efficiency at the same time of an eskulamin, heparin. In a crust, time the role of neuropeptids in treatment of experimental ulcers of a duodenum is established that allows to assume an essential role of opiate receptors in a pathogeny of a peptic ulcer.

Irrespective of G. Selye's works, the standard pathology arising at dogs after mechanical impact on the vegetative centers at the placement to areas of a gray hillock of a glass ball was described by A. D. Speransky (1935). At the same time dogs had a number of changes in a type of bleeding of gums, a keratitis, hemorrhages in lungs, etc. Changes were the most constant went. - kish. a path, to-rye arose in 5 — 15 hours originally in the form of intestinal bleedings, and then erosion and ulcers developed. A. D. Speransky treated such pathology as result of disturbance of trophic influences.

The stress influences immune system of an organism. According to Yu. I. Zimin (1979), the experimental animals subjected to various stressful influences become more sensitive to the herpes simplex viruses, poliomyelitis, Kok Saky In, polioma, and also to causative agents of other infections. The reactions of hypersensitivity of the slowed-down type estimated by in vitro and in vivo decrease; also resistance to tumoral growth decreases. Duration and degree of an immunosuppression (see Immuio-depressions) depend at most and duration of action of a stress factor. In most cases the immunosuppression at S. is connected with increase in concentration of glucocorticoids in blood serum, redistribution of lymphocytes, dissociation of cells in an immune response and activation of T lymphocytes (suppressors). The period of suppression of function of immune system can be replaced by the period of recovery or even increase immunol. indicators. Mobilization of lymphocytes, their interaction with gemotyuetichesky stem cells of marrow and the subsequent stimulation of immunity represent adaptive reaction of an organism. At influence of a stress factor of big intensity the period of recovery is swept a little up or is absent.

In the first works devoted to S. changes in blood (a neutrocytosis, an eosinopenia and a lymphopenia) and in lymphoid bodies were established (reduction of quantity of cells as then believed, owing to the lyseing action of corticosteroids on lymphocytes). Further it was established that heterogeneous population of lymphoid cells reacts not unambiguously (there are kortizonchuvstvitelny and korti-zonrezistentny lymphoid cells). Detailed studying at the same time of all departments of system of blood (blood, marrow, a thymus, a spleen) revealed a number of patterns of reaction of various cell populations at Page. Their migration is the main reason for reduction of quantity of lymphoid cells in blood.

In marrow in 3 — 6 hours after influence of an irritant the number of mature granulocytes decreases owing to their exit in blood. At the same time there is a short-term increase in quantity of the lymphoid cells migrating from blood in marrow that, apparently, has essential value for activation of a hemopoiesis. It was shown in experiences with post-radiation recovery (see) cellular structure of marrow and spleen. Value of migration of stem cells in post-radiation recovery of marrow is proved in an experiment.

On adrenalectomized and gi-pofizektomirovanny animals it was established that a neutrophylic leukosis, reduction of number of mature granulocytes and increase in lymphoid cells in marrow do not depend on anterior pituitary hormones and cortical substance of adrenal glands. Dependent on stressful hormones of reaction of system of blood in a stage of mobilization are among: a lymphopenia and an eosinopenia in blood, increase in number of stem gemonoetichesky cells and activation of a granulocytopoiesis in marrow, reduction of cellular structure in a thymus.

In a stage of resistance occur recovery of lymphoid bodies (in a thymus sometimes partial), a passing hyperplasia of marrow; in a stage of exhaustion secondary involution of lymphoid bodies and a hypoplasia of marrow is noted.

Reduction of quantity of cells in a spleen depends on excitement and - adrenergic receptors. Receipt in marrow of T - and V-lymphocytes during the first hours after S. is regulated R-adrenoretsepto-rami. In reaction of system of blood at S. play a role and other mechanisms.

Value of system of blood in specific and nonspecific resistance of an organism is big. In nonspecific adaptive reactions, except polynuclear cells, an essential role is played by lymphoid cells and processes of cellular cooperation. Lymphoid cells produce humoral factors — lymphokines (see Mediators of cellular immunity), to-rye activate cellular proliferation, promote posttraumatic cellular regeneration in a liver, kidneys and other bodies. At destruction of lymphocytes corticosteroids promote synthesis of protein and carbohydrates in a liver and a reutilization of metabolites.

Implementation of action of lymphoid cells at a stress reactions takes place with the participation of mononuclear monocytes. Resistance of an organism and adaptive role a stress reaction in many respects depends on function of mononuclear monocytes and neutrophils.

Recognizing a big role of G. Selye in development of a problem C., it should be noted that nek-ry provisions of his doctrine did not find positive assessment abroad and in the USSR. First of all it seemed unclear how uniform nonspecific neuroendocrinal reaction is protective in relation to the factors demanding opposite processes of exchange, napr at action of heat and cold. It was the main cause of revaluation of the concept of not specificity. So, Mason (J. W. Mason, 1971) on the basis of experiments came to a conclusion that the nonspecific response of an organism to influence of an irritant shall be considered only as behavioural reaction, qualitative features a cut depend on emotional perception of action of any stress factor. Therefore at further development of the concept the Selye it is necessary to pay more attention to identification of receptors and a role of afferent ways, to-rye lead to change of endocrine activity.

G. Selye's attempt to transfer biol. patterns of response of an organism to social relationship of people, its theological approaches to S.'s phenomena and other provisions are methodologically wrong. It is unlikely it is possible to recognize successful the concept «adaptation diseases». Insufficiently accurately G. Selye treats essence of a plyurikauzalnost of various diseases.

Despite an illegibility in terminology and an inaccuracy of nek-ry concepts, the doctrine about S. played a big role in modern medicine and continues to draw attention of clinical physicians and experimenters. An undoubted merit of G. Selye is clarification of an adaptive role of neuroendocrinal system at S., opening of a pathogeny nek-ry patol. processes and possible ways of their prevention and treatment. Its feature patofiziol. researches it is characterized by studying of reactions of a complete organism that is important in a crust, time when the cellular and molecular biology violently develops. Their association — one of the main tasks of medical science.

A stress at extreme states. If at action on an organism of stress factors of moderate force and duration of disturbance of a homeostasis disappear in process of formation of adaptation, then at extreme influences when processes of adaptation and compensation are insufficiently effective, shifts of key parameters of a homeostasis it is long remain and even progress. These shifts, strengthening and prolonging effect of primary influence, play a role of powerful incentives of S. and cause its features at extreme states (see).

The general patterns of development of S. at action on an organism of extreme factors are connected with features of reaction in these situations gipotalamo - pituitary nadpo-chechnikovoy systems at various levels. Under the influence of extreme influences first of all the condition of structures of c changes. N of the page regulating adrenocorticotropic function of a hypophysis. It is established that in extreme states first of all and it is most expressed activity of a cerebral cortex is oppressed (see) and those departments of limbic system (see), to-rye in fiziol. conditions exert preferential brake impacts on products of a kortikoliberin. Permanent excitement (disinhibition) of structures of a hypothalamus (see) can be result of it that is a proximate cause of duration of Page.

The important mechanism of maintenance of steadily high activity gi - potalamo - pituitary nadpochechniko-howl systems — accumulation in blood and fabrics, including in structures of a hypothalamus, catecholamines (see), serotonin (see), a histamine (see), vasopressin (see), kinin (see), prostaglandins (see) and other biologically active agents (see), capable to stimulate activity of the central and peripheral links gipotalamo - pituitary and adrenal system. The effect of a negative feed-back at the same time turns out insufficiently expressed that it is connected with decrease in sensitivity of reactive zones of a hypothalamus to brake action of corticosteroids, and also, apparently, with switching of a feedback mechanism to recently found «detained» type, to-ry is shown only at high concentration of corticosteroids and has long stage of latency, during to-rogo a feed-back in gipotalamo-hypo-fizarno-adrenal system is absent. Moreover, in the specified conditions the positive feed-backs realized through a hippocampus and also through nek-ry predecessors of biosynthesis and the metabolites of corticosteroids collecting at S. and capable to stimulate hypothat-lamo - pituitary and adrenal system can form.

Thus, intensity, duration and weight of manifestations of S. at extreme states is caused by dominance of the stimulating and exponential influences on hypothat-lamo - pituitary and adrenal system that leads to its hyper activation. The phenomena of hyper activation are expressed in synchronous and extremely sharp increase in level of functioning of the central, peripheral, transport and reserve and effector links of system, simultaneous activation of processes of synthesis, secretion and metabolism of hormones, strengthening of reactivity concerning the stimulating factors at suppression or even loss of sensitivity to the inhibiting influences. Such reorganization of functions gipotalamo - pituitary and adrenal system at extreme influences is very dangerous since reserve mechanisms, and also fermental systems of synthesis and metabolism of its hormones can be exhausted quickly enough. At the same time at extreme states so accurate correlation between processes of synthesis and an inkretion of a kortikoliberin, AKTG and corticosteroids, as is not observed at other views of the Village. Activation of cortical substance of adrenal glands happens to a lesser extent, than increase in level of a kortikoliberin and AKTG. It gives the grounds to conclude that the central links gipotalamo - pituitary nadpochechni-kovoy systems have higher lability and reactivity.

One of the general mechanisms C. in extreme conditions is inozrastany roles of a naragipofizarny way of regulation of activity of bark of adrenal glands, to-rogo, apparently, strengthening of direct neuroconduction and humoral influences owing to accumulation of biologically active agents is the cornerstone.

Synthesis and secretion of corticosteroids at extreme states change not only quantitatively, but also is qualitative. Most often the shift of a steroidogenesis progressing together with weight of a state towards stimulation of synthesis and secretion of corticosterone which is combined with relative or absolute hydrocortisone insufficiency is found.

Changes of the transport and reserve mechanism consist in braking of process a kompleksirova-niya of corticosteroids with kortiko-steroidsvyazyvayushchy globulin. It promotes bystry accumulation in blood of a significant amount of free biologically active forms of hormones and facilitates their receipt in a cell.

Typical feature of S. at extreme states is formation of corticosteroid insufficiency. On the mechanism of development it has several forms: the adrenal form connected with disturbance of synthesis and secretion of hormones cortical substance of adrenal glands; the extraadrenal form which is observed at critical conditions and caused by increase in linkng of corticosteroids with blood proteins and erythrocytes or decline in the ability of fabrics to elimination, and, apparently, utilization of corticosteroids that leads to suppression of their effects; the relative form, a cut is the cornerstone discrepancy between sharply increased needs of an organism for corticosteroids and ability gi - potalamo - pituitary nadpochechniko-howl systems to satisfy these requirements; the combined form, edges at extreme states meets most often.

The stress reaction at extreme states has nek-ry specific features. First of all it is unequal degree of manifestation of changes of functions hypothat - la mo - pituitary and adrenal system at With. caused by various factors, and qualitative distinctions in the nature of shifts at its various levels. So, at traumatic and burn shock forms quicker and is longer high activity of hypo-t and l and m about - pituitary and adrenal system remains, than at such processes as hypo - and a hyperthermia, a hemorrhagic and acute anaphylaxis. Accurate distinctions are found in a range of the adrenal glands of hormones cosecreted by cortical substance. At traumatic shock the shift of a steroidogenesis towards hypersecretion of corticosterone early comes to light and quickly progresses what data of clinic and an experiment confirm. At burn shock such shift is observed only in the terminal period, and at hemorrhagic shock and an immobilization — meets very seldom. At different types of S. monkeys have not only unequally expressed, but also opposite directed changes of synthesis and secretion of a hydrocortisone, Aldosteronum, a pregne-nolon, progesterone, 17a-oxy-irogesterona, a 11-dezoksikortizona.

Certain features are found also in the transport and reserve mechanism. At depressed cases (see Shock), in particular, significant increase in maintenance of corticosteroids in erythrocytes is observed; reservation of hormones due to increase in a kompleksirovaniye with kortikostero-idsvyazyvayushchy globulin is characteristic of a deep hypothermia. Also intensity of elimination of corticosteroids fabrics and processes of their metabolism depends on a type of extreme influence.

The role a stress reaction at action of extreme factors considerably is defined by effects of corticosteroids and catecholamines. The main direction of effect of these hormones consists in urgent mobilization of power and functional reserves of an organism. Ideas that at S. not only mobilization of energy and plastic resources, but also their redistribution towards preferential providing the systems functioning with a maximum load is observed develop in a crust, time.

Thus, it is possible to consider fixed that the stress reaction plays an important role in processes of adaptation and compensation at extreme states. Preliminary weakening of functions of gipotalamo-gi-pofizarno-adrenal system leads to sharp weighting of a current and the result of process whereas introduction of AKTG or corticosteroids yields positive preventive and therapeutic take.

However excessive intensity and S.'s duration at extreme influences leads to manifestation of biologically negative sides of this reaction. The excess quantity of catecholamines can cause centralization of blood circulation, dangerous to parenchymatous bodies, (see), disturbances of microcirculation (see), a hypoxia (see) a metabolic acidosis (see), activation of peroxide oxidation of lipids, damage of cellular membranes. High concentration of glucocorticoids at heavy S. sharply stimulates catabolic processes, especially in protein metabolism, breaks activity of immune system, causes disintegration and migration of lymphoid cells. Thus, the phenomena of overcompensation in development lead a stress reaction at action of extreme factors to the fact that this reaction can turn from a link of adaptation into the link of a pathogeny playing an important role in progressing of disturbances of a homeostasis.

Stress and mental diseases. S.'s concept found broad reflection in psychiatry. It drew to itself attention of psychiatrists first of all with the fact that allowed to understand many displays of psychoses, first of all acute symptomatic, at to-rykh an important place occupy somatic manifestations of Page. At symptomatic psychoses (see) and febrile schizophrenia (see) are observed fiziol. shifts similar to phases of an adaptation syndrome (phase of shock and phase of a countercurrent). Depending on a stage of a disease multidirectional changes of permeability of vessels (see Permeability), hypochlorine an emiya (see) or a hyperchloremia (see), a lymphopenia and an eosinopenia, decrease or increase in maintenance of corticosteroids and other adaptive hormones in blood and urine and corresponding changes of level of their metabolites can be noted.

At schizophrenia features of function of pituitary and adrenal system depending on type of a course of a disease were established. At periodic schizophrenia the expressed fluctuations of function of cortical substance of adrenal glands and changes of activity of other closed glands interfaced to them were noted, to-rye characterize development of each attack of disease. The corresponding hormonal and biochemical shifts especially clearly act at a periodic catatonia (see. Catatonic syndrome). At continuously current schizophrenia at most of patients decrease in adaptation ability and the phenomenon of dysfunction of separate glands and endocrine system in general takes place. Dysfunction of cortical substance of adrenal glands is shown by insufficient synthesis of hormones of group of a cortisone and dominance of androgens, with to-rymi connect the phenomena of a hirsutism which are found at patients with schizophrenia of women (see). Also ability of blood serum of patients with schizophrenia to influence a condition of pituitary and adrenal system at experimental animals is established. Blood serum of patients with periodic schizophrenia activates pituitary and adrenal system while blood serum of patients with the most malignant option of continuously current schizophrenia is capable to cause blockade a stress reactions and to have the damaging effect on fabrics. At gistokhy. braking of process of neurosecretion was established to assessment of neurosecretion of a hypothalamus in these cases.

The expressed disturbances of reactivity of pituitary and adrenal system at schizophrenia formed the basis for reference of this disease to adaptation diseases. Increase in toxicity biol is noted. liquids of patients with schizophrenia at Page.

Stressful influences at the corresponding predisposition are capable to provoke emergence or an aggravation of a mental disease. There is an assumption that a number of factors (psychogenic influences, childbirth, somatopathies, etc.) it is capable to provoke displays of schizophrenia, maniac-depressive psychosis, neurosises and other mental diseases. Connect with stressful mechanisms also development of a number of somatopathies — an idiopathic hypertensia (see), a peptic ulcer (see), bronchial asthma (see), to-rye in foreign literature received the name of psychosomatic diseases. In a crust, time it is established that at S. (including mental) neyrotransmitterny and neyropep-tidny systems of a brain suffer. It allows to study from new positions fiziol. bases of interaction of external and internal (genetic) factors at psychoses that gives the chance more precisely to define S.'s role in a pathogeny of individual diseases.

From positions of the theory of S. attempts to consider mechanisms of action of nek-ry therapeutic means were made. So, insulin therapy, electroconvulsive therapy were considered as the strong stress factors leading to activation of protective forces of an organism, and neuroleptics, tranquilizers — as antistress means.

In psychiatric literature acute S.'s problems and not enough feature hron are widely covered. actions of stressful factors on the person — a local stress. Understand the conditions of mental tension of different expressiveness caused in the modern person by a complex of daily operating various negative factors as the last (the family and production conflicts, impact of noise and vibration, and also environmental pollution, threat of unemployment in the capitalist countries, dangers of nuclear weapons, threat of war, etc.). Local S. extends to big groups of people, the whole populations. Its effects in most cases a long time remain hidden (subclinical). Usually judge them retrospectively after manifestation of this or that pathology (mental, psychosomatic). Detection of such pathology can be provoked by acute Page. At acute and chronic S.'s interaction their manifestations can be aggravated.

In a crust, time allocate also accident a lny stress — the state caused by the superstrong influences (wars, accidents, natural disasters, etc.) covering various groups of people on number.

Such important medico-social problem as the increasing use of antistress means, in particular drugs of a benzodiazepine row is connected with a problem C. in modern psychiatry.

Stress-protective influence of biologically active and pharmacological agents. The stress reaction is an important link the activation of simpatsadrenalovy system (see) at all levels leading to change of balance of mediators in c. N of page and to inclusion in it the brake systems which are implemented with participation piperidic to - you are (GAMK). An essential role is played by also mediator activation of kernels of a hypothalamus leading to allocation of a proopiokortin with the subsequent formation from it of AKTG, r-lipotropina and endorphine.

If stressful influence intensively is also long or repeats through the time slices insufficient for full normalization of the functional and metabolic disturbances caused by the previous influence there are disturbances, the connected many catecholamines, the corticosteroids and endorphines (see Opiates endogenous) having the central and peripheral toxic effect and creating a basis for disturbances of energy balance and pathology of membranes in various bodies, in particular in c. N of page, for development of neurotic states, ulcer and an idiopathic hypertensia.

For prevention and therapy of the central and vegetative disturbances at S. use generally three groups of pharmaceuticals: 1) the drugs influencing processes of transformation of an afferent impulsation and increasing activity of anti-nociceptive or brake mediator systems of a brain; 2) the means interfering implementation of a superactivity of sympathoadrenal and peptidergichesky systems by blockade of specific receptors through to-rye toxic action of catecholamines and endorphines is mediated; 3) the means influencing neurochemical processes in c. N page and peripheral bodies, preventing disturbances of a power and chemical homeostasis.

Tranquilizers and drugs piperidic to - you concern to the first group of connections. From tranquilizers (see) diazepam is most effective, to-ry removes emotionally caused hyperactivity, suppresses an affective component of pain. It is applied at the psychoneurological frustration resulting from conflict situations. Unlike Phenazepamum, to-ry possesses more expressed tranquilizing and smaller sedation, diazepam does not weaken attention and assessment of the alarm importance of an incentive and does not change quality of performance of a task. The specified properties of diazepam allow to use it for prevention of the disturbances connected with emotional pressure and parallel influence of stressful factors. A basis of antistress effect of diazepam is the ability shown in an experiment it at preventive introduction completely to prevent activation of mezokortikal-ny dofaminergichesky neurons in a ventral part of a tire of a mesencephalon that it leads to decrease in content of dopamine in a frontal zone of bark. In effect of diazepam the large role is played by the its intervention in exchange of GAMK (the main brake mediator in c. N of page) leading to increase in its concentration in various departments of a brain.

Antistressorny effect also nek-ry antidepressants (see), napr, nomifenzin, capable to inhibit capture of noradrenaline synaptosomes of a hypothalamus have.

Increase in maintenance of GAMK in various departments of a brain and activation of inhibitory GAMK-ergichesky neurons is noted also at preventive administration of hydroxybutyrate of sodium. Ability of hydroxybutyrate of sodium to warn patol is shown. shifts (ulcerations of a mucous membrane of a stomach, exhaustion of fund of catecholamines in most bodies, neurochemical shifts in the GAMK system of peripheral bodies and c. N of page), characteristic of emotional and painful Page. From other derivative GAMK efficiency of the Phenibutum having tranquilizing effect and which found ability to warn situational hypertensive states in an experiment and clinic is proved.

Considerable doses of corticosteroids at single introduction due to oppression of allocation of proopio-Cortinum are also capable to render to lay down. effect at the expressed degrees emotional or painful S. Otmechen antistress effect of Pyrroxanum — central and - adre-noblokatora, effective at treatment of the hypertensive states connected with emotional influence.

From drugs of the second group are most studied in a wedge, conditions beta-blockers (propranolol, etc.), to-rye prevent the disturbances of a heart rhythm connected with emotional and painful incentives and also developing of stomach ulcer at animals in an experiment.

Considerable interest in a crust, time is caused by data on a role of endorphines in a pathogeny of vegetative disturbances at S. of various etiology. Is shown to lay down. effect of stereoisomer of Naloxonum in small doses at different types of S.; this effect is not shown in an experiment during removal of a hypophysis. It is established that Naloxonum prevents cardio-depressor effect of morphine, and stereoisomer of Naloxonum does not possess similar action.

It is possible to carry to the third group of antistress connections, first of all, antioxidants (see). Use in an experiment of an ionol allowed to show that peripheral disturbances in development of S., and in particular process of a peroksidation of lipids of membranes of cells, are an obligatory link in a pathogenetic chain of stressful disturbances.

Treats this group of connections etimizol, to-ry normalizes the broken energy balance in c. N page and peripheral bodies at various stressful influences. In the mechanism of its action a part is played by influence on exchange of mediators as against the background of treatment etimizoly decrease in content of serotonin in a hypothalamus and safety of catecholamines in a myocardium and a mucous membrane of a stomach is noted.

The extensive group also treats the substances having antistress effect at the level of cellular exchange adaptogens, presented by generally plant substances (a rhodiola, a ginseng, levzeya, eleuterokokk, etc.). The antistress effect concerning different influences, including at the asthenic decompensation developing at intense cerebration is noted at course use of such drugs (extract of a rhodiola is most in detail investigated).

In a number of works of the experimental and clinical plan quite long current of S. after the termination of stressful influence is shown. It is explained by change of hemodynamic indicators, lag of recovery of fund of catecholamines in bodies, quite long normalization of level of enzymes in blood and contents of oxidates. Apply to acceleration of these processes various pharmakol. means.

The obligatory requirement for all means offered for S.'s prevention is the possibility of performance of professional activity against the background of their reception.



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P. D. Gorizontov; Yu. G. Bobkov (a stress - protective influence of biologically active and pharmacological agents), M. E. Vartanyan (a stress and mental diseases), B. A. Saakov, S. A. Eremina (a stress at extreme states).

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