HYPOXIA (hypoxia; grech, hypo-+ lat. oxy[genium] oxygen; synonym: oxygen insufficiency, air hunger) — the state arising at poor supply of body tissues oxygen or disturbance of its utilization in process biol, oxidations.
It is observed very often and forms a pathogenetic basis various patol, processes; insufficient power ensuring processes of life activity is the cornerstone of it. Is one of the central problems of pathology.
In normal conditions efficiency biol, the oxidation which is the main source of the high-energy phosphoric connections necessary for function and updating of structures corresponds to functional activity of bodies and fabrics (see. biological oxidation ). At disturbance of this compliance there is a condition of power deficit bringing to various functional and morfol, to disturbances up to death of fabric.
Depending on etiol, a factor, rate of increase and duration of a hypoxemic state, G.'s degree, reactivity of an organism, etc. G.'s manifestations can vary considerably. The changes arising in an organism represent set of direct effects of influence of a hypoxemic factor, the disturbances for the second time arising, and also the developing compensatory and adaptive reactions. These phenomena are in close connection among themselves and not always give in to accurate differentiation.
the Big role in studying of problem G * was played by domestic scientists. The foundation of development of a problem G. was laid by I. M. Sechenov fundamental works on physiology of breath and gas exchange function of blood in the conditions of the normal, lowered and increased atmospheric pressure. V. V. Pashutin for the first time created the general doctrine about air hunger as one of the main problems of the general pathology and considerably defined further development of this problem in Russia. In «Lectures of the general pathology» Pashutin (1881) gave close to modern classification of hypoxemic states. P. M. Albitsky (1853 — 1922) established value of a time factor in G.'s development, studied compensatory reactions of an organism at a lack of oxygen and described G. arising at primary disturbances of fabric exchange. The problem G. was developed by E. A. Kartashevsky, N. V. Veselkin, H. N. Sirotinin, I. R. Petrov, paying roles of a nervous system at development of hypoxemic states special attention.
Abroad Bør (P. Bert) studied influence of fluctuations of barometric pressure upon live organisms; researches high-rise and some other forms G. belong to Tsunttsu and Levi (N. Zuntz, A. Loewy, 1906), Van-Lear (E. Van Liere, 1942); mechanisms of disturbances of system of external respiration and their role in G.'s development were described by J. Haldane, J. Priestley. Value of blood for transport of oxygen in an organism was studied by J. Barkroft (1925). A role of fabric respiratory enzymes in G.'s development O. in detail explored Warburg (1948).
was widely adopted classification of Barkroft (1925) distinguishing three types G. (anoxias): 1) an anoxic anoxia, at a cut the partial pressure of oxygen in inhaled air and the oxygen content in an arterial blood is lowered; 2) the anemic anoxia, a cut is the cornerstone reduction of oxygen capacity of blood with a standard partial pressure of oxygen in alveoluses and its tension in blood; 3) the congestive anoxia arising owing to a circulatory unefficiency at the normal oxygen content in an arterial blood. Peters and Van-Slayk (J. P. Peters, D. D. Van Slyke, 1932) suggested to distinguish also the fourth type — a gistotoksichesky anoxia, edges arises at some poisonings as a result of inability of fabrics in a due measure to use oxygen. The term «anoxia» applied by these authors and meaning total absence of oxygen or complete cessation of oxidizing processes is unsuccessful and gradually goes out of use since total absence of oxygen, as well as the termination of oxidation, in an organism practically never meets during lifetime.
The following classification was recommended for conferences on a problem G. in Kiev (1949). 1. Hypoxemic G.: a) from decrease in partial pressure of oxygen in inhaled air; b) as a result of difficulty of penetration of oxygen into blood through respiratory tracts; c) owing to disorders of breath. 2. Gemicheskaya G.: a) anemic type; b) as a result of an inactivation of hemoglobin. 3. Circulator G.: a) congestive form; b) ischemic form. 4. Fabric
G. V is extended by the USSR also the classification offered by I. R. Petrov (1949); the reasons and
mechanisms G. 1 are its basis. A hypoxia owing to decrease in partial pressure of oxygen in inhaled air (exogenous G.).
2. At patol, the processes breaking supply of fabrics with oxygen at normal contents it in the environment or utilization of oxygen from blood at its normal oxygenation; here the following types belong: 1) respiratory (pulmonary); 2) cardiovascular (circulator); 3) blood (gemicheskiya); 4) fabric (gistotoksicheskiya) and 5) mixed.
Besides, I. R. Petrov considered it expedient to differentiate the general and local hypoxemic state.
According to modern representations, G. (usually short-term) can arise also without existence in an organism any patol, the processes breaking transport of oxygen or its utilization in fabrics. It is observed when functional reserves of systems of transport and utilization of oxygen even at their maximum mobilization appear incapable to satisfy the need of an organism for energy which sharply increased in connection with extreme intensity of its functional activity. There can also be in the conditions of normal or raised, in comparison with norm, a consumption fabrics of oxygen as a result of reduction of power efficiency biol, oxidations and decrease in synthesis of makroergichesky connections, first of all ATP, on unit of absorbed oxygen.
In addition to classification of G. based on the reasons and mechanisms of its emergence it is accepted to distinguish acute and hron. G.; sometimes allocate subacute and fulminant forms. Exact criteria for G.'s differentiation on rate of development and duration of a current do not exist yet; however in a wedge, practice can carry to a fulminant form G., developed during several tens seconds, to acute within several minutes or tens of minutes, subacute — within several hours or tens of hours; to hron, to forms carry G. proceeding for weeks, months and years.
The etiology and a pathogeny
the Hypoxia owing to decrease in partial pressure of oxygen in inhaled air (exogenous type) arises hl. obr. at rise on height (see. Hypobaropathy , Mountain disease ). At very bystry decrease in barometric pressure (e.g., at disturbance of tightness of high-rise aircraft) there is a symptom complex differing on a pathogeny and manifestations from a hypobaropathy and called compressed-air disease (see). The exogenous type G. arises and when the general barometric pressure is normal, but the partial pressure of oxygen in inhaled air is lowered, napr, during the works in mines, wells, at malfunctions in system of a kislorodoobespecheniye of a cabin of the aircraft, in submarines, deep devices, diving and protective suits, etc., and also during operations at failure of the narcotic and respiratory equipment.
At exogenous G. the anoxemia develops, i.e. tension of oxygen in an arterial blood, saturation of hemoglobin oxygen and its general content in blood decreases. The direct pathogenetic factor causing the frustration observed in an organism at exogenous G. are the lowered tension of oxygen and the related shift of a pressure gradient of oxygen, adverse for gas exchange, between capillary blood and the fabric environment. Can also exert negative impact on an organism hypocapny (see), quite often developing at exogenous G. in connection with a compensatory hyperventilation of lungs (see. Lung ventilation ). The expressed hypocapny leads to deterioration in blood supply of a brain and heart, an alkalosis, balance upset of electrolytes in internal environment of an organism and to increase in consumption by fabrics of oxygen. In similar cases addition to inhaled air of small amounts of carbon dioxide gas, eliminating a hypocapny, can significantly facilitate a state.
If along with a lack of oxygen of air there is a considerable concentration of carbon dioxide gas that the hl meets. obr. in various working conditions, G. can be combined with hypercapnia (see). The moderate Hypercapnia does not exert negative impact on exogenous G.'s current and can even render a favorable effect which is connected by hl. obr. with increase in blood supply of a brain and myocardium. The considerable Hypercapnia is followed by acidosis, disturbance of ionic balance, decrease in saturation of an arterial blood oxygen and other adverse effects.
A hypoxia at the pathological processes breaking supply or utilization of oxygen with fabrics.
1. Respiratory (pulmonary) Type. results from insufficiency of gas exchange in lungs in connection with alveolar hypoventilation, disturbances of the ventilating and perfused relations, excess shunting of a venous blood or at difficulty of diffusion of oxygen. Alveolar hypoventilation can be caused by disturbance of passability of respiratory tracts (inflammatory process, foreign bodys, a spasm), reduction of a respiratory surface of lungs (hypostasis of a lung, pneumonia), an obstacle for a raspravleniye of lungs (pheumothorax, exudate in a pleural cavity). It can be caused also by immobilization of the osteoarticular device of a thorax, paralysis or a spastic condition of respiratory muscles (a myasthenia, poisoning of a curare, tetanus), and also disorder of the central regulation of breath in connection with reflex or direct influence on a respiratory center of pathogenic factors.
Hypoventilation can arise at strong irritation of receptors of respiratory tracts, sharp morbidity of respiratory movements, hemorrhages, a tumor, an injury in a medulla, overdose narcotic and hypnagogues. In all these cases the minute volume of ventilation does not correspond to requirement of an organism, the partial pressure of oxygen in an alveolar air and tension of oxygen in the blood proceeding through lungs therefore saturation of hemoglobin and the oxygen content in an arterial blood can decrease considerably decreases. Also removal from an organism of carbonic acid is usually broken, and the Hypercapnia joins G. At sharply developing alveolar hypoventilation (e.g., at obstruction of respiratory tracts a foreign body, paralysis of respiratory muscles, bilateral pheumothorax) arises asphyxia (see).
Disturbances of the ventilating and perfused relations in the form of uneven ventilation and perfusion can be caused by local disturbance of passability of respiratory tracts, distensibility and elasticity of alveoluses, irregularity of a breath and exhalation or local disturbances of a pulmonary blood-groove (at a spasm of bronchioles, emphysema of lungs, a pneumosclerosis, local zapustevat a vascular bed of lungs). In such cases pulmonary perfusion or lung ventilation becomes insufficiently effective from the point of view of gas exchange and the blood flowing from lungs is insufficiently enriched with oxygen even at the normal total minute amount of breath and a pulmonary blood-groove.
At a large number of an arteriovenous anastomosis venous (on gas structure) blood passes into arterial system of a big circle of blood circulation, passing alveoluses, on an intra pulmonary arteriovenous anastomosis (shunts): from bronchial veins in a pulmonary vein, from a pulmonary artery in a pulmonary vein, etc. At endocardiac shunting (see. Heart diseases inborn ) there is a dumping of a venous blood from the right departments of heart in left. Such disturbances on the effects for gas exchange are similar to true insufficiency of external respiration, though belong, strictly speaking, to circulator frustration.
The respiratory type G. connected with difficulty of diffusion of oxygen is observed at the diseases which are followed by so-called alveolocapillary blockade when the membranes dividing a gaseous fluid of alveoluses and blood (a sarcoidosis of a lung, asbestosis, emphysema) are condensed and also at intersticial hypostasis of a lung.
2. Cardiovascular (circulator) Type. arises at the disturbances of blood circulation leading to insufficient blood supply of bodies and fabrics. Reduction of amount of the blood proceeding through fabrics in unit of time can be caused by a hypovolemia, i.e. the general degrowth of blood in an organism (at massive blood loss, dehydration of an organism at burns, cholera, etc.), falling of cardiovascular activity. Often various combinations of these factors meet. Cardiac disturbances can be caused by damage of a cardiac muscle (e.g., a heart attack, a cardiosclerosis), an overload of heart, disturbances of electrolytic balance and noncardiac regulation of cordial activity, and also the mechanical factors complicating cardiac performance (a tamponade, an obliteration of a cavity of a pericardium, etc.) In most cases the major indicator and a pathogenetic basis of circulator G. of a cordial origin is reduction of minute volume of heart.
Circulator G. of a vascular origin develops at excessive increase in capacity of a vascular bed owing to reflex and tsentrogenny disturbances of vasculomotor regulation (e.g., massive irritation of a peritoneum, oppression of the vasculomotor center) or paresis of vessels as a result of toxic influences (e.g., at serious infectious diseases), allergic reactions, disturbances of electrolytic balance, at insufficiency of catecholamines, glucocorticoids and others patol, states at which the tone of vascular walls is broken. Can arise in connection with widespread changes of walls of vessels of system microcirculation (see), the increase in viscosity of blood and other factors interfering normal advance of blood through a capillary network. Circulator G. can have local character at insufficient inflow of an arterial blood to body or the site of fabric (see. Ischemia ) or difficulty of outflow of a venous blood (see. Hyperemia ).
The difficult combinations of various factors changing at development patol, process, napr, acute cardiovascular insufficiency at a collapse of various origin, shock, an addisonovy disease, etc. are the cornerstone of quite often circulator G.
Hemodynamic indicators in different cases of circulator G. can vary over a wide range. The normal tension and the oxygen content in an arterial blood, decrease in these indicators in a venous blood and a high arteriovenous difference on oxygen is characteristic of gas composition of blood in typical cases.
3. Blood (gemichesky) Type. results from reduction of oxygen capacity of blood at anemias, a hydremia and disturbance of ability of hemoglobin to connect, transport and give to fabrics oxygen. The expressed G.'s symptoms at anemias (see) develop only at considerable absolute reduction of a packed red cells or sharply lowered hemoglobin content in erythrocytes. Anemias of this kind arise at exhaustion of a marrowy hemopoiesis on the soil hron, bleedings (at tuberculosis, a peptic ulcer, etc.), hemolysis (at poisoning with hemolitic poisons, heavy burns, malaria, etc.), at oppression of an erythrogenesis toxic factors (e.g., lead, ionizing radiation), at an aplasia of marrow, and also at deficit of the components necessary for a normal erythrogenesis and synthesis of hemoglobin (a lack of iron, vitamins, etc.).
Oxygen capacity of blood goes down at hydremias (see), at gidremichesky to a plethora (see). Disturbances of transport properties of blood concerning oxygen can be caused by qualitative changes of hemoglobin. Most often such form of gemichesky G. is observed at poisoning with carbon monoxide (formation of carboxyhaemoglobin), methemoglobin formers (see. Methemoglobinemia ), and also at some genetically caused anomalies of hemoglobin.
The combination of normal tension of oxygen in an arterial blood with the lowered its contents, in hard cases — to 4 — 5 is characteristic of gemichesky G. about. %. At formation of carboxyhaemoglobin and a methemoglobin saturation of the remained hemoglobin and dissociation of oxyhemoglobin in fabrics can be complicated owing to what tension of oxygen in fabrics and in a venous blood is much lowered at simultaneous reduction of an arteriovenous difference of the oxygen content.
4. Fabric Type. (not quite precisely — gistotoksichesky G.) arises owing to disturbance of ability of fabrics to absorb oxygen from blood or in connection with reduction of efficiency biol, oxidations because of sharp reduction of interface of oxidation and phosphorylation. Utilization of oxygen fabrics can be at a loss as a result of oppression biol, oxidations by various inhibitors, disturbances of synthesis of enzymes or damage of membrane structures of a cell.
The poisoning with cyanides can serve as a typical example of the fabric G. caused by specific inhibitors of respiratory enzymes. Getting to an organism, ions of CN-very actively connect to trivalent iron, blocking final enzyme of a respiratory chain — cytochrome oxydase — and suppressing oxygen consumption by cells. Specific suppression of respiratory enzymes is caused also by ions of sulfide, antimitsin And, etc. Structural analogs of natural substrates of oxidation can block activity of respiratory enzymes as competitive inhibition (see. Antimetabolites ). Arises at influence of the substances blocking functional groups of protein or a coenzyme, heavy metals, arsenites, monoiodoacetic to - you, etc. Fabric G. because of suppression of various links biol, oxidations arises at overdose of barbiturates, some antibiotics, at surplus of hydrogen ions, influence of toxic agents (e.g., a lewisite), toxicants biol, origins, etc.
Disturbance of synthesis of respiratory enzymes can be fabric G.'s cause at deficit of some vitamins (thiamin, Riboflavinum, pantothenic to - you, etc.). Disturbance of oxidizing processes results from damage of membranes of mitochondrions and other cellular elements that is observed at radiation injuries, overheating, intoxication, heavy infections, uraemia, a cachexia, etc. Quite often fabric G. arises as secondary patol, process at G. of exogenous, respiratory, circulator or gemichesky type.
At the fabric G. connected with disturbance of ability of fabrics to absorb oxygen, tension, saturation and the oxygen content in an arterial blood can remain normal till the known moment, and in a venous blood considerably exceed normal amounts. Reduction of an arteriovenous difference of the oxygen content is a characteristic sign fabric, arising at disturbance of tissue respiration.
A peculiar option G. of fabric type arises at sharply expressed dissociation of processes of oxidation and phosphorylation in a respiratory chain. Consumption by fabrics of oxygen at the same time can increase, however significant increase in a share of the energy disseminated in the form of heat leads to power «depreciation» of tissue respiration. There is a relative insufficiency biol, oxidation, at a cut, despite high intensity of functioning of a respiratory chain, resynthesis of makroergichesky connections does not cover requirement of fabrics, and the last are in essence in a hypoxemic state.
A number of substances ekzo-and an endogenous origin concerns to the agents separating processes of oxidation and phosphorylation: dinitrophenol, Dicumarinum, gramicidin, pentachlorophenol, some microbic toxins, etc., and also hormones of a thyroid gland — thyroxine and triiodothyronine. One of the most active separating agents is 2 — 4-dinidgrofenol (DNF), under the influence of certain concentration to-rogo oxygen consumption by fabrics amplifies and along with it there are metabolic shifts characteristic of hypoxemic states. Hormones of a thyroid gland — thyroxine and triiodothyronine in a healthy organism along with other functions carry out a role fiziol, the regulator of extent of interface of oxidation and phosphorylation, influencing, thus, heat generation. Excess of thyroid hormones leads to inadequate strengthening of heat production, the increased oxygen consumption by fabrics and along with it to deficit of makroerg. Some of the main wedge, symptoms thyrotoxicosis (see) have at the heart of G., resulting from relative insufficiency biol, oxidations.
Mechanisms of action of various separating agents on tissue respiration are not identical and in some cases are still insufficiently studied.
In development of some forms of fabric G. an important role is played by the processes of free radical (non-enzymatic) oxidation going with participation of molecular oxygen and fabric catalysts. These processes are activated at impact of ionizing radiation, supertension of oxygen, deficit of some vitamins (e.g., tocopherol) which are natural antioxidants, i.e. inhibitors of free radical processes in biol, structures and also at poor supply of cells by oxygen. Activation of free radical processes leads to destabilization of membrane structures (in particular, lipidic components), to change of their permeability and specific function. In mitochondrions it is followed by dissociation of oxidation and phosphorylation, i.e. leads to development of the form of a fabric hypoxia described above. Thus, strengthening of free radical oxidation can act as fabric G.'s prime cause or be the secondary factor arising at other types G. and leading to development of its mixed forms.
5. The mixed Type. it is observed most often and represents a combination of two or more main Types. In certain cases the hypoxemic factor in itself influences several links fiziol, systems of transport and utilization of oxygen. E.g., carbon monoxide, actively taking up with bivalent iron of hemoglobin, in the increased concentration has also direct toxic effect on cells, inhibiting cytochromenzymatic system; nitrites along with formation of a methemoglobin can act as the separating agents; barbiturates suppress oxidizing processes in fabrics and at the same time oppress a respiratory center, causing hypoventilation. In similar cases there are hypoxemic conditions of the mixed type. Similar states arise at simultaneous impact on an organism of several the factors, various on the mechanism of action, causing G.
Boley difficult patol, the state arises, e.g., after massive blood loss when along with disturbances of a hemodynamics the Hydremia as a result of the strengthened fluid influx from fabrics and the raised reabsorption of water in renal tubules develops. It leads to reduction of oxygen capacity of blood, and at a certain stage of a posthemorrhagic state gemichesky G. can join circulator G., i.e. reactions of an organism on posthemorrhagic hypovolemia), having adaptive character from the point of view of a hemodynamics, become the reason of transition of circulator G. in mixed.
The mixed form G. is often observed, the mechanism a cut is that initially arisen hypoxemic condition of any type, having reached a certain degree, inevitably causes dysfunctions of various bodies and systems participating in ensuring delivery of oxygen and its utilization in an organism. So, at the heavy G. caused by insufficiency of external respiration function of the vasculomotor centers, the carrying-out system of heart suffers, sokratitelny ability of a myocardium decreases, permeability of vascular walls, synthesis of respiratory enzymes is broken, there is a disorganization of membrane Structures of cells, etc. It leads to disturbance of blood supply and assimilation by fabrics of oxygen therefore join primary respiratory type G. circulator and fabric. Practically any serious hypoxemic condition has the mixed character (e.g., at traumatic and other types of shock, a coma of various origin, etc.).
Adaptive and compensatory reactions. At influence of the factors causing G., the first changes in an organism are connected with inclusion of the reactions directed to preservation homeostasis (see). If adaptive reactions are insufficient, in an organism functional disturbances begin; at the expressed G.'s degree there are structural changes.
Adaptive and compensatory reactions are coordinate carried out at all levels of integration of an organism and only conditionally can be considered separately. Distinguish the reactions directed to adaptation to rather short-term acute G., and the reactions providing steady adaptation to less expressed, but it is long existing or repeating. Reactions to short-term G. are carried out by means of available in an organism fiziol, mechanisms and usually arise immediately or soon after the beginning of action of a hypoxemic factor. For adaptation to long-term G. in an organism there are no pro-created mechanisms, and there are only genetically determined premises providing gradual formation of mechanisms of adaptation to a constant or repeating. The important place among adaptive mechanisms belongs to systems of transport of oxygen: respiratory, cardiovascular and blood, and also to fabric disposal systems of oxygen.
Reactions of system of breath to G. are expressed in increase in alveolar ventilation due to deepening of breath, increase of respiratory excursions and mobilization of reserve alveoluses. These reactions arise reflex owing to irritation of hl. obr. chemoceptors of an aortal and carotid zone and a brainstem the changed gas composition of blood or the substances causing fabric. Increase in ventilation is followed by strengthening of pulmonary blood circulation. At repeating or hron. In the course of adaptation of an organism correlation between lung ventilation and perfusion can become more perfect. The compensatory hyperventilation can cause hypocapnies), edges is in turn compensated by the exchange of ions between plasma and erythrocytes strengthened by removal of bicarbonates and main phosphates with urine, etc. Long G. in certain cases (e.g., during lifetime in mountains) is followed by increase in a diffusion surface of air cells at the expense of a hypertrophy of pulmonary fabric.
Compensatory reactions of the blood circulatory system are expressed by increase of cordial reductions, increase in mass of the circulating blood due to emptying of blood depots, increase in a venous inflow, stroke and minute output of heart, speed of a blood-groove and the redistribution reactions providing preferential blood supply of a brain, heart and other vitals by means of expansion in them of arterioles and capillaries. These reactions are caused by reflex influences from baroreceptors of a vascular bed and the cumulative neurohumoral changes inherent to.
Regional vascular reactions considerably are defined by also vasodilating effect of ATP decomposition products (ADF, AMF, adenine, adenosine and inorganic phosphorus) which collect in the fabrics testing a hypoxia. At adaptation to longer G. there can be a formation of new capillaries that leads along with stable improvement of blood supply of body to reduction of diffusion distance between a capillary wall and mitochondrions of cells. Due to hyperfunction of heart and changes of neuroendocrinal regulation there can come the hypertrophy of a myocardium having compensatory and adaptive character.
Reactions of system of blood are shown by increase in oxygen capacity of blood due to the strengthened washing away of erythrocytes from marrow and the activation of an erythrogenesis caused by the strengthened formation of erythropoietic factors (see. Erythropoetins ). Properties are of great importance hemoglobin (see), allowing to connect almost normal amount of oxygen even at considerable decrease in partial pressure of oxygen in an alveolar air and in blood of pulmonary vessels. So, at pO 2 , equal 100 mm of mercury., oxyhemoglobin makes 95 — 97%, at pO2 80 mm of mercury. — apprx. 90%, and at pO 2 50 mm of mercury. — nearly 80%. Along with it oxyhemoglobin is capable to give to fabrics a large amount of oxygen even at moderate decrease in pO 2 in an intercellular lymph. The strengthened dissociation of oxyhemoglobin in the fabrics testing a hypoxia is promoted by the acidosis developing in them since during the strengthening of hydrogen ions oxyhemoglobin chips off oxygen more easily. Development of acidosis is connected with change of the exchange processes causing accumulation milk, pyroracemic and others organic to - t (see below). At adaptation to hron. Permanent increase in content in blood of erythrocytes and hemoglobin is observed.
In muscular bodies adaptive value has increase in contents myoglobin (see), having ability to connect oxygen even at its low tension in blood; the formed oxymioglobin serves as a reserve of oxygen which it gives at falloff of pO2, promoting maintenance of oxidizing processes.
Fabric adaptive mechanisms are implemented at the level of disposal systems of oxygen, synthesis of makroerg and their expenditure. Such mechanisms are restriction of functional activity of the bodies and fabrics which are directly not participating in providing transport of oxygen, increase in an associativity of oxidation and phosphorylation, strengthening of anaerobic synthesis of ATP due to activation of glycolysis. Resistance of fabrics to G. increases also as a result of excitement of gipotalamo-pituitary system and the strengthened products of glucocorticoids which stabilize membranes of lysosomes. At the same time glucocorticoids activate some enzymes of a respiratory chain and promote some other metabolic effects of adaptive character.
Increase in quantity of mitochondrions per unit mass cells and respectively increase of power of a disposal system of oxygen is of great importance for permanent adaptation to G. Activation of the genetic device of cells responsible for protein synthesis of mitochondrions is the cornerstone of this process. Consider that as an incentive signal for such activation serves a certain degree of deficit of makroerg and corresponding increase in potential of phosphorylation.
However compensatory and adaptive mechanisms have a certain limit of functional reserves in this connection the condition of adaptation to G. at excessive intensity or big duration of influence of the factors causing G. can be replaced by the stage of exhaustion and a decompensation leading to the expressed functional and structural disturbances up to irreversible. These disturbances in various bodies and fabrics are not identical. E.g., the bone, a cartilage, a sinew are insensitive to G. and can keep normal structure and viability within many hours at complete cessation of supply with oxygen. The nervous system is most sensitive to G.; its various departments differ in unequal sensitivity. So, at complete cessation of supply with oxygen signs of disturbance in bark of big cerebral hemispheres are found in 2,5 — 3 min., in a myelencephalon — in 10 — 15 min., in gangliya of a sympathetic nervous system and neurons of intestinal textures — more than in 1 hour. At the same time the departments of a brain which are in wild spirits suffer more than slowed down.
In development of G. there are changes of electric activity of a brain. After the nek-ry eclipse period in most cases there is a reaction of activation which is expressed in desynchronization of electric activity of bark of big hemispheres and strengthening of fluctuations of high frequency. Reaction of activation is followed by a stage of the mixed electric activity consisting from delta and beta waves at preservation of frequent fluctuations. Further delta waves begin to dominate. Sometimes transition to a delta rhythm happens suddenly. At further deepening of G. of an elektrokortikogramm (EKOG) breaks up to the separate groups of fluctuations of irregular shape including polymorphic delta waves in combination with low fluctuations of more high frequency. Gradually amplitude of all wave modes falls and there comes full electric silence that corresponds to deep structural disturbances. Sometimes it is preceded by the low-amplitude frequent fluctuations appearing on EKOG after disappearance of slow activity. The specified changes of EKOG can develop very quickly. So, after the termination of breath bioelectric activity reduces to zero in 4 — 5 min., and after a stop of blood circulation even quicker.
The sequence and expressiveness of functional disturbances at G. depends from etiol, a factor, rate of development of G., etc. E.g., at the circulator G. caused by acute blood loss redistribution of blood can be observed for a long time, as a result to-rogo a brain it is supplied with blood better than other bodies and fabrics (so-called centralization of blood circulation) and therefore, despite high sensitivity of a brain to G., he can suffer to a lesser extent, than peripheral bodies, napr, kidneys, a liver where the irreversible changes leading to death after an exit of an organism from a hypoxemic state can develop.
Change of a metabolism before everything arises in the field of carbohydrate and energy balance, closely connected with biol. oxidation. In all cases of G. primary shift is the deficit of makroerg which is expressed in reduction of content of ATP in cells at simultaneous increase in concentration of products of its disintegration — ADF, AMF and inorganic phosphate. As a characteristic indicator of G. serves increase in so-called potential of the phosphorylation representing the relation. In some fabrics (especially in a brain) even more precursory symptom of G. is reduction of content of creatine phosphate. So, after complete cessation of blood supply brain fabric in several seconds loses apprx. 70% of creatine phosphate, and in 40 — 45 sec. it completely disappears; slightly more slowly, but in very short terms the content of ATP falls. These shifts are caused by lag of formation of ATP from its expenditure in processes of life activity and arise that easier, than functional activity of fabric is higher. Strengthening of glycolysis in connection with loss of an inhibiting effect of ATP on key enzymes of glycolysis, and also as a result of activation of the last ATP decomposition products is a consequence of the specified shifts (also other ways of activation of glycolysis at G. are possible). Strengthening of glycolysis leads to fall of the contents of a glycogen and to increase in concentration of pyruvate and a lactate. To substantial increase of contents milk to - you promote its also slowed down inclusion in further turning into of a respiratory chain and difficulty of the processes of resynthesis of a glycogen going in normal conditions with consumption of ATP. Surplus milk, pyroracemic and some other organic to - t promotes development of metabolic acidosis (see).
Insufficiency of oxidizing processes involves some other the exchange shifts accruing in process of G. Zamedlyaetsya's deepening intensity of exchange of phosphoproteins and phospholipids, the content in serum of the main amino acids decreases, the content in fabrics of ammonia increases and the maintenance of a glutamine falls, there is a negative nitrogenous balance.
As a result of disorders of lipidic exchange the giperketonemiya develops, with urine are emitted acetone, acetoacetic and beta and hydroxy-butyric to - you.
Exchange of electrolytes, and first of all processes of active movement and distribution of ions on biol, membranes is broken; the amount of extracellular potassium increases, in particular. Processes of synthesis and enzymatic destruction of the main mediators of nervous excitement, their interaction with receptors and some other the important metabolic processes proceeding with consumption of energy of energy-rich bonds are broken.
There are also secondary disbolism connected with the acidosis, electrolytic, hormonal and other shifts inherent to. At further deepening of G. also glycolysis is oppressed, processes of destruction and disintegration amplify.
Macroscopic signs of G. are not numerous and are not specific. At some forms of a hypoxia developments of stagnation in skin and mucous membranes, a venous plethora and hypostasis of internals, especially a brain, lungs, abdominal organs, dot hemorrhages in serous and mucous membranes can be observed.
The most universal sign of a hypoxemic condition of cells and fabrics and an important pathogenetic element G. is increase in passive permeability biol, membranes (basal membranes of vessels, cellular covers, membranes of mitochondrions, etc.). Disorganization of membranes leads to escaping of subcellular structures and cells of enzymes in an intercellular lymph and blood that plays an essential role in mechanisms of secondary hypoxemic alteration of fabrics.
A precursory symptom of G. is disturbance of a microcirculator bed — a staza, plasmatic treatment and necrobiotic changes of vascular walls with disturbance of their permeability, an exit of plasma in perikapillyarny space.
Microscopic changes of parenchymatous bodies at acute G. are expressed in granular, vacuolar or fatty dystrophy of parenchymatous cells, disappearance from cells of a glycogen. At sharply expressed G. there can be sites of a necrosis. In intercellular space hypostasis, Mucoid or fibrinoid swelling up to a fibrinoid necrosis develop.
At a severe form of acute G. early come to light various extent of defeat of neurocytes up to irreversible.
In cells of a brain find vacuolation, a chromatolysis, a hyperchromatosis, crystal inclusions, pycnosis, acute swelling, the ischemic and homogenizing condition of neurons, cells shadows. At a chromatolysis sharp reduction of number of ribosomes and elements of a granular and agranular reticulum is observed, the quantity of vacuoles increases (fig. 1). At sharp increase in an osmiofiliya of a kernel and cytoplasm of mitochondrions sharply there are numerous vacuoles and dark osmiofilny bodies, tanks of a granular reticulum are expanded (fig. 2).
Changes of ultrastructure allow to allocate the following types of damage of neurocytes: 1) cells with light cytoplasm, the reduction of quantity of organellas damaged by a kernel, focal destruction of cytoplasm; 2) cells with increase in an osmiofiliya of a kernel and cytoplasm that is followed by changes of almost all components of neuron; 3) cells with increase in quantity of lysosomes.
In dendrites there are vacuoles of various sizes, melkogranulyarny osmiofilny material is more rare. An early symptom of injury of axons is swelling of mitochondrions and destruction of neurofibrilla. Considerably some synapses change: the presynaptic shoot bulks up, increases in sizes, the quantity of synoptic bubbles decreases, sometimes they stick together and located on nek-rum distance from synaptic membranes. In cytoplasm of presynaptic shoots there are osmiofilny threads which do not reach considerable length and do not get a form of a ring, mitochondrions considerably change, there are vacuoles, dark osmiofilny bodies.
Expressiveness of changes of cells depends on G. V weight heavy G.'s cases there can be a deepening of pathology of a cell after elimination of the reason which caused G.; in the cells which do not have signs of serious damages within several hours later 1 — 3 days and later it is possible to find structural changes of various weight. Further such cells are exposed to disintegration and phagocytosis that leads to formation of the centers of a softening; however also gradual recovery of normal structure of cells is possible.
In glial cells dystrophic changes are also observed. In astrocytes a large number of dark osmiofilny granules of a glycogen appears. Oligodendrogliya tends to proliferation, the quantity of cells satellites increases; in them the mitochondrions which bulked up, deprived of cristas, large lysosomes and accumulations of lipids, excess quantity of elements of a granular reticulum are visible.
In endothelial cells of capillaries thickness of a basal membrane changes, a large number of phagosomas, lysosomes, vacuoles appears; it is combined with perikapillyarny hypostasis. Changes of capillaries and increase in number and volume of shoots of astrocytes testify to wet brain.
At hron. morfol, changes of nervous cells are usually less expressed; glial cells of c. N of page at hron. Become more active and strenuously proliferate. Disturbances in a peripheral nervous system consist in a thickening, crimpiness and disintegration of axial cylinders, swelling and disintegration of myelin covers, spherical swellings of nerve terminations.
For hron. Delay of regenerative processes at damage of fabrics is characteristic: oppression of inflammatory reaction, delay of formation of granulations and epithelization. Oppression of proliferation can be connected not only with insufficient power ensuring anabolic processes, but also with excess receipt in blood of glucocorticoids that leads to lengthening of all phases of a cellular cycle; at the same time transition of cells from a post-mitotic phase in a phase of synthesis of DNA especially clearly is blocked. Hron. Leads to decrease in lipolytic activity in this connection development of atherosclerosis accelerates.
Disturbances of breath in typical cases of the acute accruing G. are characterized by several stages: after the activation which is expressed in deepening of breath and (or) increase of respiratory movements there is a dispnoetichesky stage which is shown various disturbances of a rhythm, irregularity of amplitudes of respiratory movements. Further the terminal pause in the form of a temporary cessation of breathing and the terminal (agonal) breath presented by the rare, short powerful respiratory excursions which are gradually weakening before complete cessation of breath follows. Transition to agonal breath can happen also without terminal pause through a stage of the so-called apneystichesky breath which is characterized by long inspiratory delays or through a stage of alternation of agonal respiratory excursions to usual and gradual reduction of the last (see. Agony ). Some of these stages can sometimes be absent. Dynamics of breath at the accruing G. is defined by the afferentation coming to a respiratory center from various receptor educations excited by the shifts happening at a hypoxia in internal environment of an organism and change of a functional state respiratory center (see).
Disturbances of cordial activity and blood circulation can be expressed in the tachycardia amplifying parallel to weakening of mechanical action of the heart and reduction of a stroke output (so-called threadlike pulse). In other cases sharp tachycardia suddenly is replaced by the bradycardia which is followed by the blanching of the person, a cold snap of extremities cold then and an unconscious state. Quite often there are various disturbances of the carrying-out system of heart and frustration of a rhythm up to fibrillation of auricles and ventricles (see. Arrhythmias of heart ).
The ABP tends in the beginning to increase (if G. is not caused by a circulatory unefficiency), and then in process of development of a hypoxemic state more or less quickly decreases that is caused by oppression of the vasculomotor center, disturbance of properties of vascular walls, reduction of cordial emission and minute volume of heart. Due to the hypoxemic alteration of the smallest vessels, change of a blood-groove through fabrics there is a frustration of system of microcirculation which is followed by difficulty of diffusion of oxygen from capillary blood in cells.
Functions of digestive organs are broken: secretion of digestive glands, motor function of a digestive tract.
Function of kidneys undergoes complex and ambiguous changes which are connected with disturbances of the general and local hemodynamics, hormonal influence on kidneys, shifts of acid-base and electrolytic balance, etc. At considerable hypoxemic alteration of kidneys insufficiency of their function up to complete cessation of formation of urine and uraemia develops.
At the so-called fulminant G. coming, e.g., at inhalation of nitrogen, methane, helium without oxygen hydrocianic to - you high concentration, are observed fibrillation and a cardiac standstill, the most part a wedge, changes is absent since very quickly there is a complete cessation of the vital functions of an organism.
Hron, the forms G. arising at a long circulatory unefficiency, breath at the diseases of blood and other states which are followed by permanent disturbances of oxidizing processes in fabrics are clinically characterized by increased fatigue, an asthma and heartbeat at small physical. to loading, the decrease in immune responsiveness, reproductive ability and other frustration connected with gradually developing dystrophic changes in various bodies and fabrics. In bark of big hemispheres both at acute, and at hron. The functional and structural changes which are the main in a wedge, a picture G. and in the predictive relation develop.
The hypoxia of a brain is observed at disturbances of cerebral circulation, depressed cases, acute cardiovascular insufficiency, a cross heart block, poisoning with carbon monoxide and at asphyxia of various origin. Of a brain can arise as a complication at heart operations and the main vessels, and also in the early postoperative period. At the same time develop various nevrol, syndromes and mental shifts, and prevail all-brain symptoms, diffusion disorder of functions of c. N of page.
Active internal inhibition is originally broken; excitement, euphoria develops, critical evaluation of the state decreases, the motive concern appears. After the period of excitement, and it is frequent and without it symptoms of oppression of a cerebral cortex appear: slackness, drowsiness, a sonitus, a headache, dizziness, desires to vomiting, perspiration, the general block, an oglushennost and more expressed disorders of consciousness. I can" appear clonic and tonic spasms, an involuntary urination and defecation.
At the expressed G. the soporous state develops: patients are deafened, slowed down, sometimes perform elementary tasks, but after numerous repetition, and quickly stop vigorous activity. Duration of a soporous state fluctuates of 1,5 — 2 hours to 6 — 7 days, sometimes to 3 — 4 weeks. Periodically consciousness clears up, however patients remain deafened. Come to light inequality of pupils (see. Anisocoria ), irregularity of palpebral fissures, nystagmus (see), asymmetry of nasolabial folds, dystonia of muscles, increase in tendon jerks, belly reflexes are oppressed or are absent; there are patol, pyramidal symptoms of Babinsky, etc.
At longer and deep air hunger there can be mental disorders in a look korsakovsky syndrome (see) which is sometimes combined with euphoria, apatiko-abulichesky and astheno-depressive syndromes (see. Apathetic syndrome , Asthenic syndrome , Depressive syndromes ), disturbances of touch synthesis (the head, extremities or all body seem as if grown dumb, others, the sizes of parts of a body and surrounding objects — changed, etc.). The psychotic state with paranoid and hypochiondrial experiences is often combined with verbal hallucinations on a sad and alarming affective background. In evening and night hours there can be episodes in the form of delirious, delirious and oneiric and delirious and amental states (see. Amental syndrome , Delirious syndrome ).
Convulsive syndrome and hyperkinesias (see) at G. are shown variously. Usually spasms arise series under the influence of an external irritant; the myoclonias beginning with face muscles, hands are most often noted then other groups of muscles of top and bottom extremities, an abdominal wall are involved; quite often after this tonic spasms develop: bending upper and extension of the lower extremities, sometimes prevails a tone of razgibatel, arises opisthotonos (see), sometimes gormetoniya (see). In certain cases the convulsive syndrome begins with an opisthotonos. Usually at the patient one type of spasms is replaced by another. Disorder of consciousness at a convulsive syndrome — from an oglushennost and a sopor to easy degree of a coma. At a convulsive syndrome of myoclonic character or at myoclonias (see) in combination with subcrustal hyperkinesias the long course of soporous coma is noted.
At heavy G. coma develops, patients do not react to irritants.
At an easy coma insignificant Meningeal symptoms quite often are defined. Pupils are narrowed, their reaction to light is reduced, the tone of muscles of extremities is usually lowered. Corneal reflexes are kept, tendon jerks are raised or oppressed. Appear a bilateral Babinski's reflex (see. Babinsky reflex ), sometimes reflexes of oral automatism, protective reflexes (see).
At further increase of G. there is a deepening of coma. The respiratory rhythm is broken, patol, Cheyn's breath — Stokes, Kussmaul, etc. sometimes develops. Hemodynamic indicators unstable. Corneal reflexes are lowered, the dispersing squint, an anisocoria, the floating movements of eyeglobes can come to light. The tone of muscles of extremities is weakened, tendon jerks are more often oppressed, are less often raised, the bilateral Babinski's reflex sometimes comes to light.
It is clinically possible to allocate four degrees of an acute hypoxia of a brain.
I degree of. it is shown by block, an oglushennost, an alarming condition or psychomotor excitement, euphoria, increase in the ABP, tachycardia, dystonia of muscles, a clonus of feet (see. Clonus ). Tendon jerks are raised with expansion of reflexogenic zones, belly reflexes are oppressed; there is patol, a Babinski's reflex, etc. Insignificant anisocoria, irregularity of palpebral fissures, nystagmus, weakness of convergence, asymmetry of nasolabial folds, deviation (deviation) of language. These disturbances remain at the patient from several hours to several days.
II degree it is characterized by a soporous state during of several hours to 4 — 5 days, is more rare than several weeks. At the patient the anisocoria, irregularity of palpebral fissures, paresis of a facial nerve on the central type, reflexes from mucous membranes are observed (corneal, pharyngeal) are lowered. Tendon jerks are raised or lowered; there are reflexes of oral automatism, bilateral pyramidal symptoms. There can periodically be clonic spasms which are usually beginning with a face, then passing to extremities and a trunk; disorientation, easing of memory, disturbance of mnestichesky functions, psychomotor excitement, delirious and amental states.
III degree it is shown by a deep sopor, easy, and sometimes and the expressed coma. Quite often there are clonic spasms; myoclonias of face muscles and extremities, tonic spasms with bending upper and extension of the lower extremities, hyperkinesias of type choreas (see) and the automated gesticulation, oculomotor disturbances. Reflexes of oral automatism, bilateral patol are observed, reflexes, tendon jerks are more often reduced, there are grasp and sucking reflexes, the muscle tone is lowered. At G. of the II—III degree there are a hyperhidrosis, hypersalivation, dacryagogue; resistant can be observed hyper thermal syndrome (see).
At the IV degree The deep coma develops: oppression of functions of bark of big cerebral hemispheres, subcrustal and trunk educations. Skin is cold to the touch, a face of patients amimichno, eyeballs are not mobile, pupils wide, the photoharmose is absent; the mouth is half-open, the slightly opened eyelids rise in a step to breath, a cut falteringly, arrhythmically (see. Biotovsky breath , Cheyna — Stokes breath ). Cordial activity and vascular tone fall, sharp cyanosis.
Then the coma develops terminal, or ultraboundary; functions of bark of big hemispheres, subcrustal and trunk formations of a brain die away.
Vegetative functions are sometimes oppressed, the trophicity is broken, the water salt metabolism changes, acidosis of fabrics develops. Life is supported by the artificial respiration and means toning cardiovascular activity.
At a conclusion of the patient from a coma functions of the subcrustal centers, further — bark of a cerebellum, the highest cortical functions, mental activity are recovered in the beginning; there are passing motive frustration — involuntary random motions of extremities or an ataxy; a promakhivaniye and an intentsionny tremor during the performance of a finger-nose test. Usually for the second day after escaping of a coma and normalization of breath the stupor and the expressed adynamy are observed; within several days at a research reflexes of oral automatism, bilateral pyramidal and protective reflexes are caused, visual and acoustical agnosia, apraxia are sometimes noted.
Mental disturbances (night episodes of an abortal delirium, disorder of perception) remain within 3 — 5 days. Patients within a month are in the expressed asthenic state.
At hron. Increased fatigue, irritability, fieriness, an exhaustion, decrease intellectual mnesticheskikh functions, frustration of the emotional and strong-willed sphere are noted: narrowing of a focus of interest, emotional instability. In far come cases intellectual insufficiency, easing of memory and decrease in active attention are defined; the mood suppressed tearfulness, apathy, indifference, is more rare complacency, euphoria. Patients complain of a headache, dizziness, nausea, frustration of a dream. They are often sleepy in the afternoon and suffer from sleeplessness at night, fall asleep hardly, a dream superficial, discontinuous, is frequent with dreadful dreams. After a dream patients feel tired.
Vegetative disturbances are noted: a pulsation, noise and a ring in the head, blackout, feeling of heat and inflows to the head, tachycardia, heartaches, short wind. Sometimes there are attacks with a loss of consciousness and spasms (epileptiform attacks). In hard cases hron. There can be symptoms of diffusion disorder of functions of c. the N of page corresponding to that at acute.
At an elektroentsefalografichesky research of a brain (see. Elektroentsefalografiya ) at G. the I degrees on EEG (fig. 3, II) decrease in amplitude of biopotentials, emergence of the mixed rhythm with dominance a theta waves with a frequency of 5 fluctuations in 1 sec., with an amplitude of 50 — 60 mkv is noted; increase in reactivity of a brain on external irritants. At G. of the II degree on EEG (fig. 3, III) diffusion slow waves, flashes a theta - and delta waves in all assignments are registered. The alpha rhythm is reduced to amplitude, insufficiently regular. Sometimes the condition of so-called convulsive readiness of a brain in the form of acute waves, multiple spaykovy potentials of paroxysmal categories of high-amplitude waves comes to light. Reactivity of a brain on external irritations is increased. On EEG of patients from G. of the III degree (fig. 3, IV) the mixed rhythm with dominance of slow waves, sometimes paroxysmal flashes of slow waves is registered, at some patients the low amplitude level of a curve, the monotonous curve consisting from high-amplitude (to 300 mkv) regular slow waves a theta - and a delta rhythm is noted. Reactivity of a brain is reduced or is absent; in process of G.'s strengthening on EEG slow waves begin to prevail, curve EEG is gradually flattened.
At patients with the IV degree of G. on EEG (fig. 3, V) is registered very slow, irregular, irregular shape a rhythm (0,5 — 1,5 fluctuations in 1 sec.). Reactivity of a brain is absent. At patients in a condition of an ultraboundary coma reactivity of a brain is absent and gradually there comes so-called bioelectric silence of a brain (fig. 3, VI).
At reduction of the coma phenomena and at removal of the patient from coma sometimes on EEG the monomorphic elektroentsefalografichesky curve consisting from high-amplitude a theta - and delta waves is noted that reveals rough patol, changes — diffusion defeat of structures of neurons of a brain.
The Reoentsefalografichesky research (see. Rheoencephalography ) at G. of I and II degrees increase in amplitude of REG-waves, sometimes increase in a tone of brain vessels comes to light. At G. of III and IV degrees reduction and the progressing decrease in amplitude of REG-waves is registered. Reduction of amplitude of REG-waves at patients with G. III and IV degrees and a progreduated current is reflected by deterioration in blood supply of a brain owing to disturbance of the general hemodynamics and edematization of a brain.
Diagnosis is based on the symptoms characterizing activation of compensatory mechanisms (short wind, tachycardia), signs of damage of a brain and dynamics of the neurologic frustration given researches of a hemodynamics (the ABP, an ECG, cordial emission, etc.), gas exchange, acid-base equilibrium, hematologic (hemoglobin, erythrocytes, a hematocrit) and biochemical (milk and Pyroracemic to - you in blood, sugar, urea of blood, etc.) analyses. Special value has the accounting of dynamics a wedge, symptoms and their comparison to dynamics of elektroentsefalografichesky data, and also indicators of gas composition of blood and acid-base balance.
Diagnosis of such diseases and states as a vascular embolism of a brain, a hematencephalon is of great importance for clarification of origins and G.'s development (see. Stroke ), intoxication of an organism at acute renal failure (see) and a liver failure (see. Hepatargy ), and also hyperglycemia (see) and hypoglycemia (see).
Treatment and prevention
Because in clinical practice usually meet the mixed forms G., happens it is necessary to lay down use of a complex. - the prof. of measures which character depends on G.'s reason in each case.
Transition to breath by normal air or oxygen brings in all cases of G. caused by a lack of oxygen of inhaled air to bystry and if G. did not come far, to complete elimination of all functional disturbances; in some cases addition 3 — 7% of carbon dioxide gas for stimulation of a respiratory center, vasodilatation of a brain and heart, prevention of a hypocapny is reasonable. At inhalation of pure oxygen after rather long exogenous G. not menacing short-term dizzinesses, opacification of consciousness can take place.
At respiratory G. along with oxygen therapy and stimulation of a respiratory center take measures to removal of obstacles in respiratory tracts (change of position of the patient, keeping of language, if necessary — an intubation and tracheotomy), carry out surgical treatment of pheumothorax.
Or in cases of lack of spontaneous breath carry out by the patient with the expressed respiratory insufficiency auxiliary (artificial deepening of independent breath) or artificial respiration, artificial ventilation of the lungs (see). The oxygenotherapy shall be long, continuous at the content in the inhaled mix 40 — 50% of oxygen, sometimes are necessary short-term use of 100% of oxygen. At circulator G. appoint cordial and hypertensive means, hemotransfusion, countershock (see) and other measures normalizing blood circulation; in some cases it is shown oxygen therapy (see). At a cardiac standstill the indirect cardiac massage, electric difibrillation, according to indications — endocardial electric cardiac activation, enter adrenaline, atropine and carry out other measures resuscitation (see).
At gemichesky type G. carry out hemotransfusion or a packed red cells, stimulate a hemogenesis. In cases of poisoning with methemoglobin formers — massive bloodletting and an exchange hemotransfusion; at poisoning with carbon monoxide along with inhalation of oxygen or Carbogenum appoint an exchange hemotransfusion (see. Hemotransfusion ).
In certain cases apply to treatment hyperbaric oxygenation (see) — the method which is in use of oxygen under supertension that leads to increase in its diffusion to hypoxemic sites of fabrics.
To therapy and G.'s prevention apply also the pharmaceuticals possessing the anti-hypoxemic action which is not connected with influence on systems of delivery of oxygen in fabric; some of them increase resistance to G. due to decrease in the general level of life activity, generally functional activity of a nervous system, and reduction of power consumption. To pharmakol, to means of this kind also the neuroleptics, means lowering the body temperature, etc. belong narcotic; some of them apply at surgical interventions together with the general or local (kranio-cerebral) hypothermia to temporary increase in stability of an organism by. In some cases glucocorticoids have favorable effect.
For an intensification of carbohydrate metabolism in certain cases intravenously enter 5% solution of glucose (or glucose with insulin). Improvement of the energy balance and reduction of oxygen requirement at ischemic strokes, according to some authors (B. S. Vilensky, etc., 1976), can be reached by administration of the medicines promoting increase in resistance of tissue of brain to G.: hydroxybutyrate of sodium influences cortical structures, Droperidolum and diazepam (Seduxenum) — is preferential on subcrustal and trunk departments. Activation of energy balance is carried out by administration of ATP and cocarboxylase, an amino-acid link — intravenous administration of Gammalonum and Cerebrolysinum; use the drugs improving digestion of oxygen cells of a brain (desklidium, etc.).
Among chemotherapeutic means, perspective in respect of use for reduction of manifestations of acute G., there are quinones — connections with expressed okislitelno - recovery properties. Protective properties gutimin drugs and its derivatives have.
To the prevention and treatment of wet brain apply corresponding to lay down. measures (see. Swelled also swelling of a brain ).
At psychomotor excitement enter solutions of neuroleptics, tranquilizers, hydroxybutyrate of sodium in the dosages corresponding to a state and age of the patient. In some cases, if excitement is not stopped, then carry out a barbituric anesthesia. At spasms appoint Seduxenum intravenously or a barbituric anesthesia. In the absence of effect and the repeating attacks do artificial ventilation of the lungs with introduction of muscular relaxants and anticonvulsants, an inhalation protoxidic and oxygen anesthesia, etc.
Apply to treatment of effects of G. in the corresponding combinations Dibazolum, Galantaminum, glutaminic to - that, hydroxybutyrate of sodium, drugs gamma aminobutyric to - you, Cerebrolysinum, ATP, cocarboxylase, a pyridoxine, methandrostenolone (Nerobolum), tranquilizers, fortifying means, and also massage and to lay down. physical culture.
In experimental and partly in a wedge. conditions a number of substances — so-called antigipoksant whose antihypoxemic action is connected with their direct influence on processes of biological oxidation is investigated. These substances can be divided into four groups.
The substances which are artificial carriers of electrons capable to unload from surplus of electrons a respiratory chain and OVER - dependent dehydrogenases of cytoplasm concern to the first group. Possible inclusion of these substances as electron sinks in a chain of respiratory enzymes at G. is defined by their redox potential and features of chemical structure. Among substances of this group drug cytochrome C, hydrochinone and its derivatives, methylphenazine, phenazinemetasulphate and some other are investigated.
Action of the second group of antigipoksant is based on property to inhibit energetically invaluable free (not phosphorylating) oxidation in microsomes and an external respiratory chain of mitochondrions that saves oxygen for the oxidation interfaced to phosphorylation. A number of thioamidines of group of a gutimin has similar property.
The third group of anti-hypoxemic means (e.g., fruktozo-1, 6 diphosphate) represents the fosforilirovanny carbohydrates allowing formation of ATP in the anaerobic way and allowing to be carried out a nek-eye to intermediate reactions in a respiratory chain without participation of ATP. The possibility of direct use of the drugs ATP administered from the outside in blood as an energy source for cells is doubtful: in really admissible doses these drugs can cover only very insignificant part of need of an organism for energy. Besides, exogenous ATP can break up already in blood or be exposed to splitting of a nukleozidfosfatazama of an endothelium of circulatory capillaries and others biol, membranes, without informing of high-energy bonds cells of vitals, however it is impossible to exclude completely a possibility of positive influence exogenous ATP on a hypoxemic state.
Carry the substances (e.g., pangamovy to - that) which are taking away products of anaerobic exchange and by that the facilitating kislorodnezavisimy ways of formation of energetically rich connections to the fourth group.
Improvement of power supply can be carried out also by means of a combination of vitamins (With, B 1 , B 2 , B 6 , B 12 , PP, folic, pantothenic acids, etc.), glucose, substances increasing interface of oxidation and phosphorylation.
In prevention of a hypoxia the special trainings raising possibilities of adaptation to a hypoxia (see below) are of great importance.
the Forecast depends first of all on degree and G.'s duration, and also on weight of defeat of a nervous system. Moderate structural changes of cells of a brain are usually more or less reversible, at the expressed changes the centers of an encephalomalacia can be formed.
At the patients who transferred acute G. of the I degree, the asthenic phenomena remain usually no more than 1 — 2 week. After removal from G. of the II degree at some patients the general spasms can arise within several days; during the same period passing hyperkinesias, agnosia, a cortical blindness, hallucinations, attacks of excitement and aggression, dementia can be observed. The expressed adynamy and some frustration of mentality can sometimes remain within a year.
The patients who transferred G. have III degrees, intellectual mnesticheskiye disturbances, disorders of cortical functions, convulsive attacks, disturbances of movements and sensitivity, symptoms of defeat of a brainstem and spinal disturbances can be found also in the remote periods; it is long the psikhopatization of the personality remains.
The forecast worsens at the accruing phenomena of hypostasis and defeat of a brainstem (a paralytic mydriasis, the floating movements of eyeglobes, oppression of a pupillary test on light, corneal reflexes), long and deep coma, not stopped epileptic syndrome, at long oppression of bioelectric activity of a brain.
A hypoxia in the conditions of aviation and space flight
Modern hermetic cabins of airplanes and the oxygen and respiratory equipment reduced G.'s danger to pilots and passengers, however in flight it is impossible to exclude completely a possibility of an emergency (depressurization of cabins, malfunctions in the oxygen and respiratory equipment and installations regenerating air in cabins of spaceships).
In hermetic cabins of various types of high-rise airplanes for technical reasons a little more low pressure of air, than atmospheric therefore the crew and passengers in flight can have a small degree of G. as, e.g., at rise on height of 2000 m is supported. Though individual sets of the high-rise equipment create at big heights the excessive pressure of oxygen in lungs, nevertheless and at their operation emergence moderated is possible.
For aircrew borders of decrease in partial pressure of oxygen in inhaled air and, therefore, borders admissible in flight of are defined. These borders were based on overseeing by stay of healthy people within several hours at the heights up to 4000 m, in the conditions of a pressure chamber or in flight; at the same time lung ventilation and minute volume of blood increases, blood supply of a brain, lungs and heart increases. These adaptive reactions allow to keep efficiency of pilots at the level close to normal.
It is established that pilots can make flights without use of breathing oxygen at the heights up to 4000 m in the afternoon. At night at the heights of 1500 — 2000 m disturbances of twilight sight, and at the heights of 2500 — 3000 m — disorders of color and deep sight are shown that can adversely affect control of airplane, especially during the landing. In this regard in flight it is recommended to pilots not to exceed height of 2000 m at night or to begin breath with oxygen with height of 2000 m. From height of 4000 m breath by oxygen or the gas mixture enriched with oxygen is obligatory since at the height of 4000 — 4500 m symptoms appear hypobaropathy (see). At assessment of the arisen symptoms it is necessary to consider what in certain cases them can be the cause hypocapny (see), at a cut acid-base equilibrium is broken and the gas alkalosis develops.
Big danger of acute G. in flight is connected with the fact that development of the disturbances of activity of a nervous system leading to loss of working capacity proceeds in the beginning subjectively imperceptibly; in certain cases there is euphoria and acts of the pilot and astronaut become inadequate. It caused the necessity of development of the special electrical accessories intended for the prevention of aircrew and persons, examinees in a pressure chamber about development of in them. Work of these automatic signaling devices of a hypoxemic state is based or on determination of partial pressure of oxygen in inhaled air, or on the analysis fiziol, indicators at the persons submitted influence. On the nature of changes of bioelectric activity of a brain, decrease in saturation of an arterial blood oxygen, to the nature of change of heart rate and other parameters by the device defined and signals existence and degree of.
In the conditions of space flights G.'s development is possible in case of refusal revitalization systems of the atmosphere in a cabin of the ship, system of a kislorodoobespecheniye of a space suit at spacewalk, and also in case of sudden depressurization of a cabin of the spaceship during flight. The superacute current of G. caused by process of deoxygenation will bring in such cases to acute development heavy patol, states, a cut is complicated by rough process of gas generation — the exit dissolved in fabrics and blood of nitrogen (decompressive frustration in the narrow sense of the word).
The question of admissible border of decrease in partial pressure of oxygen in air of a cabin of the spaceship and admissible degree of G. at astronauts is solved carefully. There is an opinion that in long space flights, considering adverse influence of zero gravity, it is not necessary to allow G. exceeding that edges arises at rise on height of 2000 m. Therefore, in the presence in a cabin of the normal terrestrial atmosphere (pressure of-760 mm of mercury. and 21% of oxygen in the inhaled gas mixture as it is created in cabins of the Soviet spaceships) temporary decrease in the oxygen content are allowed to 16%. For the purpose of trainings for creation of adaptation to G. an opportunity and expediency of use in cabins of spaceships of the so-called dynamic atmosphere with the periodic decrease in partial pressure of oxygen in physiologically acceptance limits which is combined at the separate moments with small increase (to 1,5 — 2%) the partial pressure of carbon dioxide gas are studied.
Adaptation to a hypoxia
Adaptation to a hypoxia — gradually developing process of increase in resistance of an organism to G., as a result to-rogo an organism gains ability to carry out active behavioural reactions at such lack of oxygen which was incompatible with normal life activity earlier. Researches allow to allocate in adaptation to G. four coordinate among themselves adaptive the mechanism.
1. Mechanisms which mobilization can provide sufficient intake of oxygen in an organism, despite its deficit in the environment: a hyperventilation of lungs, the hyperfunction of heart providing the movement of the increased amount of blood from lungs to fabrics, a polycythemia, increase in oxygen capacity of blood. 2. The mechanisms providing despite anoxemias), sufficient intake of oxygen to a brain, heart and other vitals, namely: an arteriectasia and capillaries (a brain, heart, etc.), reduction of distance for diffusion of oxygen between a capillary wall and mitochondrions of cells due to formation of new capillaries, changes of properties of cellular membranes and increase in ability of cells to utilize oxygen due to increase in concentration of a myoglobin. 3. Increase in ability of cells and fabrics to utilize oxygen from blood and to form ATP, despite an anoxemia. This opportunity can be realized due to increase in affinity of cytochrome oxydase (final enzyme of a respiratory chain) to oxygen, i.e. by change of quality of mitochondrions, or increase in quantity of mitochondrions per unit mass of a cell, or due to increase in extent of interface of oxidation with phosphorylation. 4. Increase in anaerobic resynthesis of ATP due to activation glycolysis (see) that is estimated by many researchers as the essential mechanism of adaptation.
A ratio of these components of adaptation in the whole organism such is that at an early stage G. (in an emergency stage of adaptation process) there is a hyperventilation (see. Lung ventilation ). The minute volume of heart increases, the ABP raises a little, i.e. there is a syndrome of mobilization of transport systems which is combined with more or less expressed phenomena of functional insufficiency — an adynamia, disturbances of conditioned-reflex activity, decrease in all types of behavioural activity, falling of weight. Further, with implementation of other adaptation shifts, and in particular that which proceed at the cellular level energetically wasteful hyperfunction of transport systems becomes as if excessive and the stage of rather steady adaptation with a small hyperventilation and hyperfunction of heart, but with high behavioural or labor activity of an organism is established. The stage of economical and rather effective adaptation can be replaced by a stage of exhaustion of adaptation opportunities, edges is shown by a syndrome hron, a hypobaropathy.
It is established that at the heart of increase in power of transport systems and disposal systems of oxygen at adaptation to G. activation of synthesis nucleinic to - t and proteins lies. This activation provides increase in quantity of capillaries and mitochondrions in a brain and heart, increase in mass of lungs and their respiratory surface, development of a polycythemia and other adaptation phenomena. Introduction by an animal of the factors inhibiting synthesis of RNA eliminates this activation and makes impossible development of adaptation process, and introduction of Cofactors of synthesis and predecessors nucleinic to - t accelerates development of adaptation. Activation of synthesis nucleinic to - t and proteins provides formation of all structural changes making a basis of this process.
The increase in power of systems of transport of oxygen and resynthesis of ATP developing at adaptation to G. increases ability of people and animals to adapt to other environmental factors. Adaptation to G. increases force and speed of cordial reductions, the maximum work, to-ruyu can carry out heart; increases the power of sympaticoadrenal system and prevents the exhaustion of reserves of catecholamines in a cardiac muscle observed usually at excessive physical. loadings.
Preliminary adaptation to G. exponentiates development of the subsequent adaptation to physical. to loadings. At the animals adapted to G. increase in extent of preservation of temporary bonds and acceleration of transformation of the short-term, easily erased by extraordinary irritants memory into long-term, stable memory is established. This change of functions of a brain is result of activation of synthesis nucleinic to - t and proteins in neurons and glial cells of a cerebral cortex of the adapted animals. At preliminary adaptation to G. resistance of an organism to various injuries of the blood circulatory system, system of blood and a brain increases. Adaptation to G. was successfully used for prevention of insufficiency of heart at experimental defects, ischemic and sympathomimetic necroses of a myocardium, DOC-salt hypertensia, effects of blood loss, and also for prevention of a behavior disorder of animals in a conflict situation, epileptiform spasms, effect of hallucinogens.
The possibility of use of adaptation to G. for increase in resistance of the person to this factor and increases in the general resistance of an organism in special conditions of activity, in particular in space flights, and also for prevention and therapy of diseases of the person is a subject a wedge. - fiziol, researches.
Bibliography: Anichkov S. V. and Belenky M. L. Pharmacology of himioretseptor of a carotid ball, L., 1962, bibliogr.; Blyumenfeld L. And * Gemoglobin and reversible oxygenation, M., 1957, bibliogr.; Bogolepov N. K. Comas, M., 1962, bibliogr.; Bogolepovn.N, etc. the Elektronnomikroskopichesky research of ultrastructure of a brain of the person at a stroke, Zhurn, a neuropath, and psikhiat., t. 74, No. 9, page 1349, 1974, bibliogr.; Van Lear E. and Stikney the K-hypoxia, the lane with English, M., 1967; In and - the Lensk B. S. Anticoagulants in treatment and prevention of cerebral ishemiya, L., 1976; Vladimirov Yu. And, and Archakov A. I. Peroxide oxidation of lipids in biological membranes, M., 1972; In about y t to e in and the p B, I. Chronic hypoxia, L., 1973, bibliogr.; Gayevskaya M. S. Biochemistry of a brain during the dying and revival of an organism, M., 1963, bibliogr.; Gurvich A. M. Electric activity of the dying and coming to life brain, L., 1966, bibliogr.; To and N sh and N and N. F., To pathological anatomy of the acute and prolonged hypoxia, Arkh. patol., t. 35, Ns 7, page 82, 1973, bibliogr.; To about-tovskiye. T. and Sh and m to e in and the p L. L. Functional morphology at extreme influences, M., 1971, bibliogr.; Meerson F. 3. General mechanism of adaptation and prevention, M., 1973, bibliogr.; it, Mechanisms of adaptation to a high-rise hypoxia, in book: Probl., hypoxias and hyperoxias, under the editorship of G. A. Ste-pansky, page 7, M., 1974, bibliogr.; The multivolume guide to pathological physiology, under the editorship of H. N. Sirotinina, t. 2, page 203, M., 1966, bibliogr.; Negov-s to and y V. A. Patofiziologiya and therapy of an agony and clinical death, M., 1954, bibliogr.; Fundamentals of bioastronautics and medicine, under the editorship of O. G. Gazenko and M. Calvin, t. 1 — 3, M., 1975, bibliogr.; Pashutin V. V. Lectures of the general pathology, p. 2, Kazan, 1881; P e of t r about in I. R «Air hunger head мозга# L., 1949, bibliogr.; about N e, the Role of the central nervous system, an adenohypophysis and bark of adrenal glands at oxygen insufficiency, L., 1967, bibliogr.; Sechenov I. M. Chosen works, M., 1935; Sirotininn. H. Original positions of prevention and therapy of hypoxemic states, in book: Fiziol, and patol * breath, a hypoxia and an oxygenotherapy, under the editorship of A. F. Makarchenko, etc., page 82, Kiev, 1958; H and r N y y A. M. Patofiziologiya of anoxic states, M., 1947, bibliogr.; Barcroft J. The respiratory function of the blood, v, 1, Cambridge# 1925; B e r t P. La pression baromStrique, P., 1878,
H. I. Losev; C. H. Bogolepov, G. S. Burd (not BP.), V. B. Malkin (tousle.), T. 3. Meerson (adaptation).