1. Hypoxia
Compiled by Associate Professor of Pathophysiology Department
Arsenteva Ekaterina Vladimirovna
Ev.arsenteva@yandex.ru
Lecturer: Professor of Pathophysiology Department
Vlasova Tatyana Ivanovna
v.t.i@bk.ru
11. Respiratory hypoxia
due to:
• alveolar hypoventilation,
• impaired oxygen diffusion through the air-
blood barrier,
• dissociation of the ventilation-perfusion ratio,
• reduced perfusion with blood of the lungs.
11
24. Urgent reaction.
Cardiovascular system
Heart (by activation of sympathetic system):
• Tachycardia.
• Increased shock release of blood from the heart.
• Increase in the minute volume of blood circulation (cardiac blood
flow).
• Increased linear and volumetric blood flow velocity in the vessels.
Vascular system (by activation of sympathetic system and release of
catecholamines; by accumulation in the myocardium and brain tissue
of metabolites with a vasodilator effect):
• centralization of the blood flow (due to expansion of arterioles and
increased blood supply to the brain and heart, narrowing of the lumen
of arterioles and reduction of the blood supply in other organs and
tissues)
24
25. Urgent reaction.
Blood system
• Activation of the release of red blood cells from the bone
marrow and blood depot;
• Increased degree of Hb02 dissociation in tissues;
• An increase in the affinity of Hb for oxygen in the
capillaries of the lungs.
25
26. Urgent reaction.
Biological oxidation cell’s system
•Improving the efficiency of the processes of assimilation of oxygen and
oxidation substrates by the tissues of the body and their delivery to
mitochondria;
•Activation of oxidation and phosphorylation enzymes;
•Increasing the degree of conjugation of the oxidation and
phosphorylation of adenine nucleotides: ADP, AMP, and creatine;
• Activation of the glycolytic oxidation pathway.
26
27. Permanent compensation.
Biological oxidation systems.
Providing optimal energy supply of functioning structures and the level
of plastic processes by:
- Increase in the number of mitochondria and the number of
mitochondrial cristae.
- An increase in the number of enzyme molecules of tissue respiration in
each mitochondria, as well as the activity of enzymes, especially
cytochrome oxidase.
- Improving the efficiency of biological oxidation and its conjugation
with phosphorylation.
- Improving the efficiency of the mechanisms of anaerobic resynthesis
of ATP in cells.
27
28. Permanent compensation.
Biological oxidation systems.
Providing optimal energy supply of functioning structures and the level
of plastic processes by:
- Increase in the number of mitochondria and the number of
mitochondrial cristae.
- An increase in the number of enzyme molecules of tissue respiration in
each mitochondria, as well as the activity of enzymes, especially
cytochrome oxidase.
- Improving the efficiency of biological oxidation and its conjugation
with phosphorylation.
- Improving the efficiency of the mechanisms of anaerobic resynthesis
of ATP in cells.
28
29. Permanent compensation.
Respiration systems.
The system regulates a level of gas exchange by:
- Hypertrophy of the lungs and an increase in the area of the alveoli,
in the capillaries in the interalveolar septa, in the level of blood flow
in these capillaries.
- Increase the diffusion ability of the air-blood barrier of the lungs.
- Improving the efficiency of the ventilation-perfusion ratio.
-Hypertrophy and increase in the power of the respiratory muscles.
- Ascending the vital capacity of the lungs
29
30. Permanent compensation.
Cardiovascular system.
Heart:
- Moderate balanced hypertrophy of all structural elements of the
heart: myocardium, vascular bed, nerve fibers.
- Increase in the number of functioning capillaries in the heart.
- Reducing the distance between the capillary wall and the sarcolemma
of the cardiomyocyte.
- Increasing the number of mitochondria in cardiomyocytes and the
effectiveness of biological oxidation reactions. In this regard, the heart
spends 30-35% less oxygen and metabolic substrates than in a state that
is not adapted to hypoxia.
- Improving the efficiency of transmembrane processes (ion transport,
substrates and metabolic products, oxygen, etc.).
- Increase in the power and speed of interaction of actin and myosin in
cardiomyocyte myofibrils.
- Improving the efficiency of adrenal and cholinergic systems of heart
regulation.
30
31. Permanent compensation.
Cardiovascular system.
Vascular system:
Reduction of myogenic arteriole tone and
reduction of the reactive properties of the walls
of resistive vessels to vasoconstrictors/
-Increasing the number of functioning capillaries
in tissues and organs.
31
33. Permanent compensation.
Blood system.
1. Increase in the affinity of deoxyhemoglobin for
oxygen in the capillaries of the lungs significantly.
2. Activation under the influence of ischemia and
hypoxia
education in the kidney erythropoietin
stimulating erythropoiesis
The increase in blood oxygen capacity
33
35. Permanent compensation.
Metabolic processes
- High efficiency and lability of the reactions of anaerobic
resynthesis of ATP.
-The economical use of oxygen and metabolism substrates in
the reactions of biological oxidation and plastic processes.
-Reducing intensity of metabolic processes
-The dominance of anabolic processes in tissues compared with
catabolic.
-High power and mobility of transmembrane ion transfer
mechanisms.
35
36. Permanent compensation.
Nervous and endocrine systems.
Nervous system:
- Increased resistance of neurons to hypoxia and ATP
deficiency, as well as to some other factors/
- Hypertrophy of neurons and an increase in the number
of nerve endings in tissues and organs.
- Increased sensitivity of receptor structures to
neurotransmitters.
Endocrine system :
- A lesser degree of stimulation of the adrenal medulla,
hypothalamic-pituitary-adrenal and other systems.
- Increased sensitivity of cell receptors to hormones.
36
38. Thank you for your
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Editor's Notes
Hypoxia is a typical pathological process that develops as a result of insufficiency of biological oxidation. It leads to a violation of the energy supply of functions and plastic processes in the body.
Hypoxia is often combined with hypoxemia (a decrease in the oxygen content in the blood)
Due to the severity of hypoxia
Normobaric exogenous hypoxia (restriction of oxygen in the body with air at normal barometric pressure)
The causes:
finding people in small and / or poorly ventilated spaces
Violations of air regeneration and / or oxygen mixture supply for breathing in flying and deep-seated vehicles, etc.
Non-compliance with the method of artificial ventilation.
Causes of hypobaric exogenous hypoxia: a decrease in barometric pressure when climbing to a height (more than 3,000–3,500 m, where the p02 of air is reduced to about 100 mm Hg) or in a pressure chamber.
Under these conditions, development of either mountain or altitude or decompression sickness is possible.
• Mountain sickness is observed when climbing into the mountains, where the body is exposed to not only low oxygen content in the air and low barometric pressure, but also more or less pronounced physical exertion, cooling, increased insolation and other factors of the middle and high mountains.
Altitude sickness develops in people who are raised to a greater height in open aircraft, on lift chairs, and also when pressure in the pressure chamber decreases. In these cases, mainly reduced p02 in the inhaled air and barometric pressure affect the body.
Decompression sickness occurs with a sharp decrease in barometric pressure (for example, as a result of depressurization of aircraft at altitudes above 10,000–11,000 m). At the same time, a life-threatening condition is formed, which differs from an acute mountain or altitude sickness disease by acute or even fulminant course.
Endogenous hypoxia in most cases are the result of pathological processes and diseases leading to inadequate transport of oxygen to organs, metabolism substrates and / or their use by tissues. Hypoxia of varying severity and duration may also develop as a result of a sharp increase in the body's need for energy due to significantly increased loads (for example, with a sharp increase in physical activity). At the same time, even the maximum activation of oxygen-transport and energy-producing systems is not capable of eliminating energy deficiency (overloading hypoxia).
Substrate hypoxia due to decrease content of substanses which need to produce ATP except oxigen (for ex. Decrease in content of glucose)
The main parts of the pathogenesis of exogenous hypoxia include arterial hypoxemia, hypocapnia, gas alkalosis, alternating with acidosis; arterial hypotension, combined with the hypoperfusion of organs and tissues.
• Decrease in oxygen tension in arterial blood plasma (arterial hypoxemia) is the initial and main link of exogenous hypoxia. Hypoxemia leads to a decrease in the oxygen saturation of Hb, the total oxygen content in the blood and, as a result, to impaired gas exchange and metabolism in the tissues.
• Reduced blood pressure in hypocapnia. It occurs as a result of compensatory hyperventilation of the lungs (due to hypoxemia).
• Gas alkalosis is the result of hypocapnia. However, it should be remembered that if there is a high content of carbon dioxide in the inhaled air (for example, when breathing in a confined space or under production conditions), exogenous hypoxemia can be combined with hypercapnia and acidosis.
• Decreased systemic blood pressure (hypotension), combined with tissue hypoperfusion, is largely a consequence of hypocapnia. C02 is one of the main factors regulating the vascular tone of the brain. A significant decrease in pC02 is a signal to the narrowing of the lumen of the arterioles of the brain, heart, and reduction of their blood supply. These changes cause significant bodily disorders, including the development of syncope and coronary insufficiency (manifested by angina, and sometimes myocardial infarction).
In parallel with these abnormalities, impaired ionic balance is detected both in cells and in biological fluids: extracellular, blood plasma (hypernatremia, hypokalemia and hypocalcemia), lymph, cerebrospinal fluid.
Respiratory hypoxia The cause of respiratory (respiratory) hypoxia is a lack of gas exchange in the lungs is respiratory failure.
Pathogenesis of respiratory hypoxia The development of respiratory failure may be due to alveolar hypoventilation, reduced perfusion with blood of the lungs, impaired oxygen diffusion through the air-blood barrier, dissociation of the ventilation-perfusion ratio.
Regardless of the origin of respiratory hypoxia, the initial pathogenetic link is arterial hypoxemia, usually combined with hypercapnia and acidosis.
• Alveolar hypoventilation is characterized by the fact that the volume of ventilation of the lungs per unit of time is lower than the body's need for gas exchange during the same time. This condition is the result of a violation of the biomechanical properties of the breathing apparatus and a disorder in the regulation of ventilation of the lungs.
Violations of the alveolar ventilation can be obstructive and restrictive.
- Causes of obstructive disorders: edema of the walls of the bronchi and bronchioles, tumors, foreign bodies in the lumen of the airways.
- Causes of disorders of the restrictive type (due to a decrease in the elastic properties of the lungs and their elasticity): extensive pneumonia, atelectasis, edema and pulmonary fibrosis, pneumo- or hemothorax, rigidity of the bone and cartilage apparatus of the chest, significant volume of exudate in the pleural cavity.
- Disorders of respiratory regulation mechanisms.
Causes of disorders: direct effect of damaging factors on the neurons of the respiratory center (for example, hemorrhage, swelling, edema, inflammation in the medulla oblongata or areas of the bridge) and reflex effects in the form of:
- afferential deficit that excites the neurons of the respiratory center (for example, during drug poisoning);
- an excess of stimulating impulses, leading to frequent shallow breathing (for example, during stress, neurosis, encephalitis);
- an excess of inhibitory afferentation (for example, during irritation of the mucous membrane of the nasal passages and trachea by chemicals or mechanically, in acute tracheitis and bronchitis).
• Violation of oxygen diffusion through the air-blood barrier
Causes: Thickening and / or compaction of the components of the alveolocapillary membrane. This leads to a more or less pronounced alveolocapillary separation of the gas environment of the alveoli and the blood of the capillaries. This phenomenon is observed in interstitial pulmonary edema, diffuse fibrosis of the interstitium of the lungs (for example, in fibrosing alveolitis), pneumoconiosis (conditions characterized by focal and diffuse hyperproduction of connective tissue in the lungs, for example, in silicosis, asbestosis, sarcoidosis).
• Dissociation of the ventilation-perfusion ratio
Causes:
- Violation of the patency of the bronchi and / or bronchioles.
- Reduced tensile properties of the alveoli.
- Local decrease in blood flow in the lungs. Such changes are observed, for example, in bronchospasm and pneumosclerosis of various origins, pulmonary emphysema, embolism or thrombosis of the branches of their vascular bed. This leads to the fact that some regions of the lungs are normally ventilated, but not sufficiently perfused with blood, some, on the contrary, are well supplied with blood, but insufficiently ventilated. In this regard, hypoxemia is detected in the blood flowing from the lungs.
• Reduction of blood perfusion of lung. Causes:
- Reduction of BCC (hypovolemia).
- Lack of contractile function of the heart.
- Increased resistance to blood flow in the vascular bed of the lungs (pre- and / or postcapillary hypertension).
- Increased air pressure in the alveoli and / or airways.
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Opening of arteriovenous anastomoses and discharge of blood through intra- and extrapulmonary shunts from right to left, by passing the capillaries of the alveoli.
Circulatory (cardiovascular, hemodynamic) hypoxia develops with local, regional and systemic hemodynamic disturbances. Depending on the mechanisms of development of circulatory hypoxia, ischemic and stagnant forms can be distinguished. The basis of circulatory hypoxia may lie absolute circulatory failure or relative with a sharp increase in tissue oxygen demand (in stress situations).
Generalized circulatory hypoxia occurs in heart failure, shock, collapse, dehydration, DIC syndrom, etc., moreover, if hemodynamic disorders occur in the pulmonary circulation, the oxygenation of the blood in the lungs can be normal and its delivery is disturbed to tissues in connection with the development of venous hyperemia and stagnation in the pulmonary circulation. When violations of hemodynamics in the vessels of the pulmonary circulation, arterial blood oxygenation suffers.
Local circulatory hypoxia occurs in the zone of thrombosis, embolism, ischemia, and venous hyperemia in various organs and tissues.
The hemic (blood) type of hypoxia arises as a result of a decrease in the effective oxygen capacity of the blood and its oxygen transporting function. The transport of oxygen from the lungs to the tissues is almost completely accomplished with the participation of Hb.
The main links to reduce the oxygen capacity of the blood are:
1) the reduction of Hb in a unit of blood volume and in full, for example, with pronounced anemia caused by impaired bone marrow hematopoiesis of various origins, with post-hemorrhagic and hemolytic anemia.
2) a violation of the transport properties of Hb, which may be due either to a decrease in the ability of Hb of erythrocytes to bind oxygen in the capillaries of the lungs, or to transport and deliver the optimal amount of it in the tissues, which is observed in hereditary and acquired hemoglobinopathies.
Quite often, hemic hypoxia occurs when carbon monoxide poisoning ("carbon monoxide"), since carbon monoxide has an extremely high affinity for hemoglobin, almost 300 times greater than the affinity for oxygen to it. When carbon monoxide interacts with blood hemoglobin, carboxyhemoglobin is formed, which lacks the ability to transport and release oxygen.
Carbon monoxide is found in high concentrations in the exhaust gases of internal combustion engines, in domestic gas, etc.
Pronounced impairment of the body's activity develops with an increase in the blood HbCO up to 50% (of the total concentration of hemoglobin). Increasing its level to 70-75% leads to severe hypoxemia and death.
Carboxyhemoglobin has a bright red color, so when it is excessively formed in the body, the skin and mucous membranes become red. Elimination of CO from inhaled air leads to HbCO dissociation, but this process proceeds slowly and takes several hours.
Impact on the body of a number of chemical compounds (nitrates, nitrites, nitric oxide, benzene, some toxins of infectious origin, drugs: phenazepam, amidopirin, sulfonamides, LPO products, etc.) leads to the formation of methemoglobin, which is not capable of carrying oxygen, as it contains the iron oxide form (Fe3 +).
The oxide form of Fe3 + is usually in association with hydroxyl (OH-). MetHb has a dark brown color and it is this shade that the blood and tissues of the body acquire. The formation of metHb is reversible, however, its recovery to normal hemoglobin occurs relatively slowly (within a few hours), when iron Hb again goes into the acidic form. The formation of methemoglobin not only reduces the oxygen capacity of the blood, but also reduces the ability of the active oxyhemoglobin to dissociate with the release of oxygen to the tissues.
Tissue (histotoxic) hypoxia develops due to a violation of the ability of cells to absorb oxygen (during normal delivery to the cell) or due to a decrease in the efficiency of biological oxidation as a result of separation of oxidation and phosphorylation.
The development of tissue hypoxia is associated with the following pathogenetic factors:
1. Violation of the activity of enzymes of biological oxidation in the process:
a) specific binding of the active sites of the enzyme, for example, cyanides and some antibiotics;
b) the binding of the SH groups of the protein part of the enzyme by heavy metal ions (Ag2 +, Hg2 +, Cu2 +), resulting in the formation of inactive forms of the enzyme;
c) competitive blocking of the active center of the enzyme by substances having a structural analogy with the natural substrate of the reaction (oxalates, malonates).
2. Violation of the synthesis of enzymes, which can occur with a deficiency of vitamins B1 (thiamine), VZ (PP), nicotinic acid, etc., as well as cachexia of various origin.
3. Deviations from the optimum physicochemical parameters of the internal environment of the body: pH, temperature, electrolyte concentrations, etc. These changes occur in a variety of diseases and pathological conditions (hypothermia and hyperthermia, kidney, heart and liver failure, anemia) and reduce the effectiveness of biological oxidation .
4. Disintegration of biological membranes, caused by the influence of pathogenic factors of infectious and non-infectious nature, accompanied by a decrease in the degree of conjugation of oxidation and phosphorylation, suppression of the formation of high-energy compounds in the respiratory chain. The ability to dissociate oxidative phosphorylation and respiration in mitochondria has: an excess of H + and Ca2 + ions, free fatty acids, adrenaline, thyroxine and triiodothyronine, some drugs (dicoumarin, gramicidin, etc.). Under these conditions, oxygen consumption by the tissues increases. In cases of mitochondrial swelling, separation of oxidative phosphorylation and respiration, most of the energy is transformed into heat and is not used for the resynthesis of macroergs. The effectiveness of biological oxidation is reduced.
With repeated short-term or gradually developing and long-existing moderate hypoxia, the process of adaptation develops.
Adaptation to hypoxia is a gradual increase in the body's resistance to hypoxia, as a result of which it acquires the ability to exist with a lack of oxygen, which was previously incompatible with normal life activity.
There are 4 stages of the adaptation process:
ROS - reactive oxigen species (mediators) – free radicals
The first is the emergency stage (urgent adaptation) —the early stage of hypoxia. There is a cider mobilization of transport systems (hyperventilation of the lungs, an increase in cardiac output, an increase in blood pressure), aimed at maintaining sufficient efficiency of biological oxidation in the tissues.
In response to hypoxia, the sympathetic-adrenal system and the ACTH system are activated — glucocorticoids, mobile energy and plastic resources “in favor” of organs and systems providing urgent adaptation.
At this stage, the activity of the organism proceeds with the full mobilization of functional reserves at the limit of physiological possibilities, but the adaptation effect is not complete. This is combined with the phenomena of functional insufficiency - anemia, a violation of the higher nervous activity, and a drop in weight.
If the actions of the agent that caused the reactions of urgent adaptation to hypoxia continue or periodically repeated for a long time, there is a gradual transition from urgent to long-term adaptation (the second is a transitional stage) during which the body begins to acquire increased resistance to hypoxia.
In case of continuation or repetition of the training action of hypoxia, the third stage is formed - the stage of economical and fairly effective sustainable long-term adaptation.
At this stage, adaptive shifts occurring at the cellular level are realized. With prolonged adaptation to hypoxia:
1. Activation of the hypothalamic-pituitary system and the adrenal cortex;
.
2. Increasing the power of oxygen capture and transport systems (these changes are based on DNA activation and a change in the protein synthesis system):
a) hypertrophy and hyperplasia of the neurons of the respiratory center, which improves the regulation of oxygen supply systems;
b) hypertrophy of the lungs, an increase in their respiratory surface, an increase in the power of the respiratory muscles, hyperfunction of the lungs;
c) cardiac hypertrophy, increase in myocardial contractility, increase in the power of the heart energy supply systems, hyperfunction of the heart;
d) polycythemia, an increase in the oxygen capacity of the blood, the formation of new capillaries in the brain and heart;
e) aerobic cell transformation - fixed by cell inheritance, increased ability to absorb oxygen, based on increasing the number of mitochondria per cell, increasing the active surface of each mitochondria, increasing the chemical affinity of mitochondria to oxygen, increasing oxygen transport from the blood into the cells (epigenome variability of somatic cells );
e) an increase in antioxidant activity to the deoxidation systems;
These mechanisms provide a sufficient supply of oxygen to the body, despite its deficiency in the environment, and the supply of oxygen to tissues.
Adaptation is considered complete if the alkaline reserve is reduced to such a value that the pH of the blood is established within the normal range.
If the training hypoxic exposure ceases, adaptation to it is lost, and maladaptation develops. When this occurs, the "reverse development" of those structural changes that ensured increased stability of the organism occurs.
In the case of a long-lasting and growing action of the hypoxic factor, the adaptive capacity of the organism gradually depletes, long-term adaptation (disadaptation) may occur and decompensation occurs, which is accompanied by an increase in destructive changes in organs and a number of functional disorders (fourth stage, which may manifest itself as chronic mountain syndrome).
Urgent reaction
Heart when adapting to hypoxia
In acute hypoxia, cardiac function is significantly intensified. Reason: activation of the sympathetic-adrenal system.
Mechanisms of adaptation to hypoxia
• Tachycardia.
• Increased shock release of blood from the heart.
• Increase in the minute volume of blood circulation (cardiac blood flow).
• Increased linear and volumetric blood flow velocity in the vessels.
Vascular system when adapting to hypoxia
Under hypoxic conditions, the phenomenon of redistribution, or centralization, of the blood flow develops.
The causes and mechanisms of the phenomenon of centralization of blood flow during adaptation to hypoxia:
• Activation in conditions of hypoxia of the sympathetic-adrenal system and release of catecholamines. The latter cause a narrowing of arterioles and a decrease in blood flow through them to most tissues and organs (muscles, abdominal organs, kidneys, hypoderm, etc.).
• Rapid and significant accumulation in the myocardium and brain tissue of metabolites with a vasodilator effect: adenosine, prostacyclin, PgE, kinins, etc. They provide for the expansion of arterioles and an increase in the blood supply to the heart and brain in hypoxia.
Consequences when adapting to hypoxia
• Expansion of arterioles and increased blood supply to the brain and heart.
• Simultaneous narrowing of the lumen of arterioles and reduction of the blood supply in other organs and tissues: muscles, subcutaneous tissue, vessels of the abdominal cavity, kidneys.
Blood system when adapting to hypoxia
Acute hypoxia of any genesis is accompanied by adaptive changes in the blood system:
• Activation of the release of red blood cells from the bone marrow and blood depot (in the latter case, simultaneously with other blood cells).
Reason: high concentration in the blood of catecholamines, thyroid and corticosteroid hormones.
As a result, polycythemia develops in acute hypoxia.
Consequence: an increase in the oxygen capacity of the blood.
• Increased degree of Hb02 dissociation in tissues.
The reasons
- Hypoxemia, especially in capillary and venous blood. In this regard, it is in the capillaries and postcapillary venules that the degree of oxygen Hb02 recovers.
- Acidosis, regularly developing with any type of hypoxia. - Increased under hypoxic conditions, the concentration in erythrocytes of 2,3-diphosphoglycerate, as well as other organic phosphates: ADP, pyridoxal phosphate. These substances stimulate the removal of oxygen from Hb02.
• An increase in the affinity of Hb for oxygen in the capillaries of the lungs. This effect is realized with the participation of organic phosphates, mainly 2,3-diphos-phoglycerate. At the same time, the property of Hb to bind a significant amount of oxygen is important even under conditions of significantly reduced p02 in the capillaries of the lungs.
Biological oxidation systems when adapting to hypoxia
Activation of metabolism is an important link in the emergency adaptation of the organism to acute hypoxia.
It provides:
• Improving the efficiency of the processes of assimilation of oxygen and oxidation substrates by the tissues of the body and their delivery to mitochondria.
• Activation of oxidation and phosphorylation enzymes, which is observed with moderate damage to cells and their mitochondria.
• Increasing the degree of conjugation of the oxidation and phosphorylation of adenine nucleotides: ADP, AMP, and creatine.
• Activation of the glycolytic oxidation pathway. This phenomenon is recorded in all types of hypoxia, especially in its early stages.
The reason for the inclusion of mechanisms for long-term adaptation to hypoxia: repeated or ongoing failure of biological oxidation of moderate severity.
They cause repeated activation of urgent adaptation mechanisms. This ensures the formation of a structural-functional basis for the processes of long-term adaptation to hypoxia. In this case, it is essential that the interval between episodes of moderate hypoxia is not too large or small.
External respiration system when adapting to hypoxia
The system of external respiration provides a level of gas exchange, sufficient for the optimal flow of metabolism and plastic processes in the tissues.
This is achieved by:
- Hypertrophy of the lungs and an increase in this connection: - the area of the alveoli, - the capillaries in the interalveolar septa, - the level of blood flow in these capillaries.
- Increase the diffusion ability of the air-blood barrier of the lungs.
- Improving the efficiency of the ratio of ventilation of the alveoli and their perfusion with blood (ventilation-perfusion ratio).
- Hypertrophy and increase in the power of the respiratory muscles.
- Ascending the vital capacity of the lungs (YES).
Heart when adapting to hypoxia
With long-term adaptation to hypoxia, the strength and speed of the processes of contraction and relaxation of the myocardium increase. As a result, there is an increase in the volume and speed of blood ejected into the vascular bed - shock and heart (minute) emissions.
These effects are made possible by:
- Moderate balanced hypertrophy of all structural elements of the heart: myocardium, vascular bed, nerve fibers.
- Increase in the number of functioning capillaries in the heart.
- Reducing the distance between the capillary wall and the sarcolemma of the cardiomyocyte.
- Increasing the number of mitochondria in cardiomyocytes and the effectiveness of biological oxidation reactions. In this regard, the heart spends 30-35% less oxygen and metabolic substrates than in a state that is not adapted to hypoxia.
- Improving the efficiency of transmembrane processes (ion transport, substrates and metabolic products, oxygen, etc.).
- Increase in the power and speed of interaction of actin and myosin in cardiomyocyte myofibrils.
- Improving the efficiency of adrenal and cholinergic systems of heart regulation.
Vascular system when adapting to hypoxia
In an adapted organism, the vascular system is able to provide such a level of tissue perfusion with blood that is necessary for their function even in hypoxia.
The basis of this are the following mechanisms:
- Reduction of myogenic arteriole tone and reduction of the reactive properties of the walls of resistive vessels to vasoconstrictors: catecholamines, ADH, leukotrienes, individual PG, etc.
Increasing the number of functioning capillaries in tissues and organs.
This creates the conditions for the development of stable arterial hyperemia in functioning organs and tissues.
Blood system when adapting to hypoxia
With a stable adaptation of the organism to hypoxia, the oxygen capacity of the blood, the rate of Hb02 dissociation, and the affinity of deoxyhemoglobin for oxygen in the capillaries of the lungs increase significantly.
The increase in blood oxygen capacity is the result of stimulation of erythropoiesis and the development of erythrocytosis.
The mechanism of erythrocytosis: activation under the influence of ischemia and hypoxia education in the kidney erythropoietin, stimulating erythropoiesis.
Metabolism when adapting to hypoxia
Metabolic processes in tissues upon reaching a state of sustainable adaptability to hypoxia are characterized by:
- High efficiency and lability of the reactions of anaerobic resynthesis of ATP.
- Reducing their intensity.
- The economical use of oxygen and metabolism substrates in the reactions of biological oxidation and plastic processes.
- The dominance of anabolic processes in tissues compared with catabolic.
- High power and mobility of transmembrane ion transfer mechanisms. This is largely the result of an increase in the efficiency of membrane ATPases, which ensures the regulation of the transmembrane distribution of ions, myogenic arteriole tone, water-salt metabolism, and other important processes.
Regulation systems for adaptation to hypoxia
The systems of regulation of an organism adapted to hypoxia ensure sufficient efficiency, cost effectiveness and reliability of managing its life activity. This is achieved through the inclusion of the mechanisms of the nervous and humoral regulation of functions.
Nervous regulation during adaptation to hypoxia
Significant changes in the higher parts of the brain and in the autonomic nervous system of an organism adapted to hypoxia are characterized by:
- Increased resistance of neurons to hypoxia and ATP deficiency, as well as to some other factors (for example, toxins, lack of metabolism substrates).
- Hypertrophy of neurons and an increase in the number of nerve endings in tissues and organs.
- Increased sensitivity of receptor structures to neurotransmitters. The latter, as a rule, is combined with a decrease in the synthesis and release of neurotransmitters.
Humoral regulation during adaptation to hypoxia
The restructuring of the endocrine system during hypoxia causes:
- A lesser degree of stimulation of the adrenal medulla, hypothalamic-pituitary-adrenal and other systems. This limits the activation of stress response mechanisms and its possible pathogenic effects.
- Increased sensitivity of cell receptors to hormones, which helps to reduce the amount of their synthesis in the endocrine glands.
Changes in gas composition and blood pH (respiratory hypoxia):
• Decrease in p02a and p02v (arterial and venous hypoxemia).
• As a rule, an increase in pC02 (hypercapnia),
• Acidosis (at the early stage of acute respiratory failure - gas, and then non-gas).
• Decrease in Sa02 and Sv02 (saturation of Hb, respectively, of arterial and venous blood).
For circulatory hypoxia, the following are characteristic: a decrease in PaO2, an increase in the utilization of O2 by the tissues due to slower blood flow and activation of the cytochrome system, an increase in the level of hydrogen ions and carbon dioxide in the tissues. Violation of the gas composition of the blood leads to a reflex activation of the respiratory center, the development of hyperpnea, an increase in the rate of dissociation of oxyhemoglobin in the tissues.
