Main mechanisms of external breathing disorder


The disorder of external breath arise for want of operation of the various factors of the external and internal environment, however all of them on the mechanism of development are united in three groups - ventilating, diffusing and perfusing. Most seriosly by manifestation of disorder of external breath the respiratory unsufficiency is, as a result of which the gas structure of blood is changed and arises dispnea. On character of dispnea it is possible to make submission about the reason of a pathology. In particular, the deep and often breath arises for want of intimately cardiac vascular of unsufficiency and anemias, deep and rare - for want of stenosis of respiratory paths, often and surface - for want of inflammation or edema easy.

Rather frequently respiratory unsufficiency arises for want of disorder regulation of influences on the part of respiratory centre. Excitability of respiratory centre is reduced for want of damages of the central nervous system: a sclerosis, spasms of vessels of a brain, insults, squeezing of a brain by a tumour, toxicel operation on respiratory centre of somnolent and narcotic preparations. The periodic breath, which for want of it arises, testifies to an oppression of respiratory centre. The breath of a type Cheyne-Stokes is more often observed for want of functional changes, and breath of a type Biott - for want of organic damages of a brain. From peripheral mechanisms primary significance have the violations of adequate reduction of respiratory muscles.

Respiratory insufficiency the clinic-physiological concept. This such pathological state, when the tension 2 in blood arterial is reduced (arterial hypoxemia) and the tension 2 exceeds 50 mm Hg (hypercapnia). Most just characterizes respiratory insufficiency a degree arterial hypoxemia.

Many specialits consider as respiratory insufficiency also such state, when the respiratory parameters of blood are within the limits of physiological variation, but it is provided with excessive action of external breath device, which exhausts and limits reserve possibilities of an organism.



Forms of respiratory insufficiency


On clinical course is distinguished two forms of respiratory insufficiency acute and chronic. They differ among themselves on speed of functional disturbances increase.


Acute respiratory insufficiency understand such state, when this syndrome develops fast, within minutes, of hours or day and has propersity impetuously to progress. Fast accures arterial hypoxemia, hypercapnia, develops acidosis, there are disorders of the central nervous system. All this can be completed coma and death.

Typical example of acute respiratory insufficiency is asphyxia. This state, theatening for life, when in blood dont enter oxygen, and from blood the carbonic gas is not removed. Asphyxia occurs, as a rule, owing to sharp contraction or complete closing of respiratory ways. More often it happens for want of external compression of respiratory ways, find in them of foreign bodies, narrowing larynx (allergic edema), find in respiratory ways and alveolars of liquid (sink, aspiration of vomit mass), swelling of lung, double-side pneumothorax. Besides asphyxia can arise in case of a strong oppression of respiratory centre, disturbance of transfer of impulses in neuro-muscular synapses (on respiratory muscles), massive traumas of thorax. Duration acute asphyxia the person 3-4 mines.

In course of asphyxia is distinguished three periods. The first period is characterized by excitation of respiratory centre, increase of cardiac rate and increase of arterial pressure. The excitation of respiratory centre is stipulated, mainly, accumulation in an organism of carbonic gas, which acts directly and reflective. Some significance in stimulation of breath has oxygen tension in blood and irritation of aorta and sinoauriculares zones chemoreceptors. In the beginning of the first period breath has character of inspiratory dispnea when the breath prevails above an exhalation. At the end of the first period the breath is delayed, and begin to prevail powerful expiration movement (expirational dispnea). The increase of arterial pressure also is explained by delay of carbonic gas. The second period of asphyxia is characterized by predominance of the parasympathetic nervous system. The breath becomes significant less often. The cardiac rate decreases, arterial pressure is reduced. In the third period the oppression both frequencies is stoped, and depth of breath, then breath temporarity is stoped (preterminal pause), and on background of stop there are some single, more and more low respiratory movements (gasping-breath). The appearance it is explained to that after a paralysis of respiratory centre are excited of neurons caudal part of medulla oblongata. They also give some respiratory movements before the complete stop of breath.


The chronic respiratory insufficiency is characterized by slower increase of hypoxemia and hypercapnia, and they do not reach such degree, as for want of acute insufficiency due to the expense of inclusion of compensator mechanisms (erythrocytosis, increase of hemoglobin in erytrocytes).

It is known, that the external breath is provided with three processes ventilating lung, diffusion of gases (2 and 2) through alveolar wall and pathogenesis of blood through capillaries lung. (film 1), (film 2) The disorder of any of these processes can serve as the reason of respiratory insufficiency. On pathogenesis is distinguished two forms of respiratory insufficiency ventilation and alveolar-respiratory.



Ventilation respiratory insufficiency


The essence of ventilation insufficiency is that in a alveolars for unit time enter less air than in norm. This state is called alveolar-hypoventilation. The reasons of alveolar hypoventilation can be or connected to the apparatus of breath, or are not connected to it (outlungs of the reason). To outlungs to the reasons the following concern.







1.    Disturbance of respiratory centre function, due to by effects of medical drugs, cerebral-brain traumas with epidural or subdural hematoma malignant tumours of brain, absceses of brain, meningitis, disorder brain circulation blood.


2. Disorder of the motoneurons function of spinal cord, which innervation respiratory muscles (tumour of spinal cord, syringomyelia, poliomyelitis).


3. Disorder of the function nervous-muscular device of breath: ) lesion of nerves for want of avitaminosis, inflammation, trauma; b) blockade of impulses transfer in nervous muscular synapses myasthenia, action of myorelaxantes; c) lesion of respiratory muscles-myositis, dystrophies, periodic paralysis, hypocaliemia, hypophosphoremia.


4. Limitation of thorax mobility, which can be caused by inherent or ecquired deformation of ribs and vertebral, ossification of costales cartilages, grown of preular parts, ascites, meteorism, obesity, pain for want of neuralgia of intercostales nerves.


5. Disorder of thorax integrity and pleural cavity (pneumothorax).


The reasons of respiratory insufficiency, which are connected to the apparatus of breath, concern disorders of air ways patency and decrease of an amount of functioning alveoles. Depending on pathogenesis is distinguished three forms of ventilation respiratory insufficiency -obstructive, restrictive and dysregulative (disorder of breath due to disorders central regulation).


Obstructive insufficiency. Obstruction of respiratory ways is narrowing their lumen and increase of resistance to movement of air. The damage can be located as in upper respiratory ways (with diameter of 2 mm and more), and in lower respiratory ways (diameter up to 2 mm).

Upper respiratory paths is understood cavity of mouth, nasal meatuses, pharynx, larynx, trachea, large bronchus.

Obstruction it may be is caused internal and externals mechanical trauma. Internal trauma most frequently it arises as complication of trachea-intubation, less often after operation on larynx. External mechanical trauma fractures of lower jaw, cervical cartilages, larynx cartilages, epiglossus, trachea, damage of language basis, mouth, neck. The mechanism of obstruction is spasm, edema also paralysis of voice slot, damage or off set of larynx cartilages, hematoma, edema of mucous membrane or serrounding tissues. Variety of an internal trauma burns and inhalating of poisoning gases. In these cases develops edema of mucous upper respiratory paths(film 3).

Bleeding in respiratory ways is observed after operating interferences on head and neck, after tonsilectomy, tracheostomy. Sometimes bleeding happens spontaneous, for example from nose. The bleeding especially is dangerous when the patient is in coma or under narcosis, that is when the drainage of respiratory paths is impossible. Aspiration of foreign body is observed in children in the age from 6 months to 4 years more often. In the adult aspiration of foreign body occurs, usually, during reception of food, especially in state of alcoholic intoxication. Ather causes of ebstruction lower respiratory ways necrotic ludvig`s angina (suprogenis necrotic flegmona of oral bottom cavity of an infectious origin), subpharynx abscess, which cause is aerobic and anaerobic microflora, ngioneurotic edema, which develops as response on allergen and is accompanied of nettle-rash, asthma, rhinitis.


To obstruction of lower respiratory ways results aspiration of the liquid environments of vomit mass, of blood, of water, and allergy response mainly on medical preparations antibiotics and protein substitutes. It develops immediately, during 30 mines and appears hardly expressed laryngo- and bronchospasm.


Obstructive respiratory insufficiency arises also for want of chronic unspecific diseases lung chronic bronchitis, emphysema, bronchoectasis, bronchial astma (film 4).



Emphysema is an illness, in which rupture interalveolar septums and lungs capillaries. (film 5) By basis it is considered degraded collagen and elastic fibres of proteolytic enzymes, which thrown out from phagocytes under influences of the external factors microorganisms, dust particles, tobacco smoke. In etiology of emphysema some role is allocated of hereditary predisposition, which essence consists in synthesis of defective collagen and elasthyne, insufficient synthesis of proteolytic enzymes inhibitors.

The mechanism of obstruction for want of emphysema explain so. Walls of bronchioles very thin and pliable. The lumen them is supported transpulmonaris more pressure. The more elasticity lung, the should be transpulmonaris more pressure to overcome elastic recoil. Bronchioles for want of it will be in an extended state. When the elasticity lung is reduced, it is enough for their stretch low transpulmonaris pressure. The force, which acts on walls bronchioles from within, decreases and also their lumen is narrowed. The decrease of lumen conducts to sharp increase of resistance to movement of air. As a result of it the breath is difficulty. But even more exhalation is difficulty. For want of emphysema it becomes active. the pressure in pleurae cavity increases, and bronchioles are compressed from the outside of lungs fabric. With the cource of time bronchioles compress completely, and the exhalation becomes impossible. Air becomes isolated in alveoles, which remain is blowed up.


The mechanism of obstruction for want of bronchial asthma is multicomponent. At the first place is ccumulation of viscous glasslike mucus in bronchus. It is connected with hypertrophy of mucous glands and hyperproductions by them mucus (hypercrinia). The viscous mucus is difficultly discharge and congest (mucostasis). The important role in the mechanism of mucostasis plays hyperplasia of goblet cells, which supersede cells of ciliata epithelium. Besides, arises edema mucous, spasm of circular and longitudinal smooth bronchus muscules. In the patients with bronchial asthma develops increased reactivity of bronchial muscles on specific and unspecific stimulus. The highest degree hyperreactivity is observed at once time or after an attack. Strong stimulus, which provokes bronchoconstriction in the patients of bronchial asthma, is the physical load.


Restrictive insufficiency. This form of respiratory insufficiency arises, when the extensibility lung is reduced, that is when they be not capable easily to be straightened. To carry out a breath, it is necessary to increase transpulmonary pressure, and it can be made at the expense of increase of respiratory muscles action.



restrictive insufficiency arises in case inflammation and edema lung. Owing to arterial both venous hyperemia and swelling of interstitial tissue the alveoles is compressed from the outside and completely are not straightened.



By often cause is fibrose lung, that is grow up rough fibrose connective tissue on place perished elements of parenhima, elastic fibres and capillaries. By fibrose are finished such illnesses, as emphysema, silicosis, anthracosis and other. To decreasing of extensibility lung may lead disturbance of surfactant system. Under surfactant is understood surface-active substances, which reduce a surface tension in an alveole. influencing on a surface tension, surfactant regulates elastic recoil of lung. as the major function it is necessary to consider prevention of alveolares collapse. It acts as the antistick factor, providing stability of alveole.

The deficiency of surfactant can arise in case of insufficient synthesis it or excessive remove from a surface of alveoles. The insufficient synthesis is characterized for illness of hyaline membranes in newborn, for want of which destroy intraalveolares septum and in alveoles is stored hyaline with epithelial cells and form elements of blood. Ecquired decrease of surfactant is observed for want of asphyxia, acidosis, pneumonia, pollution of air. The defect of surfactant predetermines high surface tension of alveoles and high resistance lung for want of expansion by their inhaled air.

Besides, by cause of restrictive insufficency may be thelectasis ( fall of alveoles and stopping of their ventilation), neumothorax, deformation of thorax, paralysis of respiratory muscles.


Disorder of the central regulation of breath. Under influence reflective, humoral and direct influences the respiratory centre changes the function. Those disorders of breath regulation, which limit alveolar ventilation, can serve as the reason of respiratory insufficiency. It is distinguished the following forms of breath disturbances central genesis.


Bradypnea rare breath. It can arise reflectative in case of increase of arterial pressure (reflex from baroreceptors of aorta and carotide bodies), and also for want of hyperoxia (reflex from hemoreceptors of the same zones). The deep and rare breath arises for want of narrowing of upper respiratory ways. It is named stenotic. The reason bradypnea happens a direct lesion of neurons of respiratory centre for want of long hypoxia, under influence of narcotic substances, for want of organic changes in a brain (inflammation, insult) or functional disorders of the central nervous system (neurosis, hysteria).


Polypnea (tachypnea) friquent surface breath. It arises reflectative for want of to fever, hysteria, pain in area of thorax, peritoneum, pleura.


Hyperpnea deep and friquent breath. It has compensator character, however excessive stimulation of respiratory centre in pathological conditions (decrease of partial pressure 2, anemia, acidosis) provokes rather intensive breath, which can lead to washout 2 from organism and paralysis of respiratory centre. For want of diabetic mellitus there is a so-called noisy breath (Kussmauls breath), due to metabolic acidosis.


Apnea temporary stopping of breath. This manifestation of inhibition neurons of respiratory centre under influence hypoxia or intoxication, for want of organic lesion of brain. Apnea occurs affer hyperventilation, when tension of 2 in blood is dropped lower threshold for respiratory centre of level, and also during fast rise of arterial pressure (reflex from baroreceptors of vessels).


Periodic breath. This such disorder of respiratory rhythm, when the periods of respiratory movements alternate with periods of apnea. There are two main types of periodic breath Chein-Stoks and Bioth. In the first case the amplitude of respiratory movements cyclic is increased up to expressed hyperpnoe and decreases to apnea. For want of breath Bioth amplitude of respiratory movements is constant. The appearance of periodic breath is sign of respiratory centre hypoxia (insufficiency of heart, uremia, meningitis, encephalitis).



Pathological Patterns of Breathing



Grokka breathing




Cheyne-Stokes breathing



Biot breathing





Kussmaul breathing










Dyspnea. This sensation of air shortage and simultaneously necessity to strengthen breath. The person consciously tries to be saved of unpleasant sensations. In a unconscious state dyspnea it does not happen. In conditions of pathology dyspnea can cause the following factors: ) insufficient oxygenation of blood in lung (low partial pressure of oxygen in inhaled air, difficulty of ventilation lung, disorder of lungs hemodynamics); b) disorder of gases transport by blood (insufficiency of blood flow, anemia, inactivation of hemoglobin); c) metabolic acidosis (diabetis mellitus); d) functional and organic lesion of brain (hysteria, encephalitis, insult). In creation of dyspnea the large role belongs to reflexes from respiratory ways, parenhima of lung, aorta and carotide bodies.

The breath for want of dyspnea as a rule is friquent and deep, and exhalation becomes active. Depending on with what components of breath inhalation or the exhalation prevails is distinguished inspiratory and expiratory dyspnea. The first type of dyspnea is observed for want of asphyxia, second for want of bronchial asthma and emphysema.



Alveolar-respiratory insufficiency


This type of respiratory insufficiency arises in that case, when is reduced gas exchange between alveolar air and blood. Two variants of such insufficiency are possible: 1) due to inadequacy of ventilation and perfusion of lung; 2) owing to difficulty diffusion of gases through alveolar wall.


Disturbances of correlationventilation / perfusion. That the gas structure of blood was supported, the important significance has not only absolute value of alveolar ventilation, but also normal ratio between alveolar ventilation and perfusion of lung. The amount of blood, which proceeds through lung for 1 mines, is equalled 4.5-5.0 L that is approximately answers the value of cardiac output. But even in healthy persons this blood is distributed in lung tissue non-uniformly: one alveoles perfusioning more, other less. And therefore it is important, that and inhaled air was distributed adequately, that is according to intensity of blood flow, as under alveolar ventilation is understood ventilation not all, and only of perfusion alveoles. That volume of inhaled air, which is distributed in alveoles, where blood flow is absent or sharply is reduced, does not take part in gas exchange between alveolar air and blood of lung capillaries and does not support gas composition of blood.

The optimum ratio of alveolar ventilation and perfusion of lung makes 4:5. It can be changed to side of increase or to side of decrease. the increase of correlation ventilation / perfusion is characterized for effect of dead space. The predominance perfusion above ventilation is characterized for effect of vein-arterial shunt. In both cases normal gas composition of blood to supply impossible. If the ventilation prevails the tension of oxygen in blood flowing from alveoles will be sufficient, but from blood too much carbonic acid will be remove. As the consequence arises hypocapnia. If the ventilation lags from perfusion arises hypoxemia and hypercapnia.

In clinic frequently there are cases, when decreases perfusion of lung. It is being in case disturbance of the right heart contraction (infarct of myocardium, cardiosclerosis, myocarditis, exudative pericarditis), heart insufficiency and vessels (stenosis of lung artery, stenosis of right atrio-ventricular ostium, shock), thrombembolism of lung artery.


disturbances of diffusion have not the so important significance in pathogenesis of respiratory insufficiency, as disorders of ventilation and perfusion. Nevertheless sometimes diffusion the ability of alveoles becomes the defining factor. Diffusion ability of lung decreases for want of alveolar surface decrease (resection of lung, cavity, abscess, atelectasis, emphysema) or thickening of a alveolar-capillary membrane (fibrosis, sarcoidosis, pneumoconiosis, sclerodermya, pneumonia, emphysema, has swelled lung). Disorder of gases transition through alveolar membrane name as a syndrome of alveolar-capillary blockade. The main clinical symptom it is hypoxemia.













The problem of an oxygen deficiency invokes practical concern in clinic of internal illnesses (preventive maintenance and treatment of a myocardial infarction, diseases of the system of breathing, anemias), in neurologic clinic (preventive maintenance and treatment of ischemic damages of the brain), in surgical clinic (treatment obliteric endarteriitis, operations on life important organs), in obstetric practice (strife with a hypoxia of a fetus and neonatal). Professional selection of high-resistant to hypoxia people, and also acclimatization to an oxygen depletion has become a relevant problem of medicine.

During evolutionary development the alive organisms have acquired an effective method of energy obtaining biological oxidation. It is possible only under condition of continuous tissues maintenance by oxygen. The main stocks in an organism are in significant 0.025-0.030 l/kg of body weight, that is approximately 2l for the person of 70 kg weight. Therefore the disorder of any stage of the oxygen transport from air to tissues is called an oxygen starvation or in other words hypoxia.




Hypoxia is typical pathological process, which arises owing to insufficient oxygen supply of tissues or insufficient use it by tissues. Hypoxia underlies many diseases or accompanies with them. Four main hypoxia types are distinguished hypoxic, hemic, circulational and histotoxic.



Characteristics of hypoxia different kinds








oxygen capacity of blood






arterial blood

quantity 2






saturation 2






p2 mmHg






venous blood

quantity 2






saturation 2






p2 mmHg






arterial - venous difference of 2










Hypoxic hypoxia

The essence of this hypoxia kind is oxygen tension reducion in arterial blood, the hemoglobin saturation by oxygen decreases and as a result the contents of oxygen decreases. Thus hypoxemia develops.

Some reasons to cause tension reduction of oxygen in blood, which is flowing from lung are known. First of all, it is necessary to mention the partial oxygen pressure decrease in inhaled air. (film 6) The person meets this factor ascent on the mountain (climbers, contributors). On a sea level the partial oxygen pressure is equalled to 159 mm Hg, at the height of 5500 m - only 80 mm Hg, that is less twice. Diffusion of oxygen from alveoles into blood occurs with the influence of a partial oxygen pressure difference in alveolar air and blood. The higher this gradient is the faster oxygen diffusion in pulmonary blood capillaries is made. Thus, the gradient of partial oxygen pressure (2) is the major physical factor, which advances oxygen from air in blood.

As a rule, action of low partial oxygen pressure in a human organism is short-term. The chronic influence is tested by the inhabitants of mountain areas. 92 % the population of earth has put up at low districts (up to 500 m). At the height of 500- 2000 m live 250 mln persons, at height up to 3000 m - more than 50 mln, on mountains (3000-5300 m) - more than 30 mln. The greatest amount of mountains inhabitants is in Asia (Hymalai) and Southern America (Andes). The industrial development of useful mineral in Andes are conducted at the height of 2000 m.

The decrease of partial oxygen pressure in the air in low districts is possible when it is replacement by other gases. For example, the oxygen can be replaced with methan in mines, carbonic gas- in shafts, argon -on some productions.

The second hypoxical hypoxia variety is connected to respiratory insufficiency, with main processes disorder, which provide external breath, ventilation, diffusion and perfusion. Respiratory, hypoxia results the gas metabolism disorder of the lung function for normal partial oxygen pressure in atmospheric air. In practice any external breath disorders can cause a respiratory hypoxia.

On the alveolar hypoventilation arises in such cases:

) an oppression of respiratory centre overdose of drugs, brain swelling, brain insult;

b) patency of respiratory ways disorder dyphteria, laryngospasm, larynx swelling, getting into tracheal foreign body;

c) thorax damage;

d) respiratory muscles and intercostals of nerves disease.

Oxygen diffusion disorder through alveolar wall happens in case of respiratory lung surface decrease (athelectasis, pneumothorax, hydrothorax), thickening and change of alveolar wall histological structure (fibrosis, swelling, pneumoconiosis, pneumonia).

Some role in development of respiratory type hypoxic hypoxia belongs to lung perfusion disorders, and one more point - disorders of perfusional ventilational ratio. Hypoxia arises in case of limited lung perfusion or development so-called intralungs the shunt.

In case of perfusion decrease, pulmonic blood capillaries gets arterialised almost completely ( 95 %), but total arterial blood volume, which departs from pulmonic and gets into general blood circulation, is less of norm. Therefore general blood arterialisation is lower than 95 %.

Pulmonary shunt develops in case of indurations appearance lung tissue with partial bronchioles obturation, for example due to pneumonia will be derivated. The ventilation of these inflamations is limited, and perfusia is rather intensive due to hyperemia. Blood, which flows through capillaries at weakly ventilationed areas of the inflammatory lung sites, is not arterialised. Mixing up with oxygenated enough blood from good ventilated alveole, it reduces a general oxygenation degree of arterial blood, which flows out of lung.

Arterial and venous blood mixing takes place in fact of some defects cardio-vascular system, for example, with nonclosure Botalls flowing. General oxygenation of arterial blood is also lower.




Hemic hypoxia

Basis of this hypoxia type is decrease of blood oxygen capacity. Two variants: anemic and toxic are possible.

In case of anemic form, the total circulating hemoglobin level owing to blood loss, erythrocytes hemolysis in blood, channel or bone brain bloodmaking function oppression decreases.

Toxic form arises in case of hemic toxines poisoning. The general content of hemoglobin in blood remains normal, but the contents of functionally active hemoglobin decreases. The part of hemoglobin turns into such compounds, which are not capable to execute oxygen transport function.

More often hemoglobin gets linked with charcoal gas (carbon oxide, CO). This compound is named carboxihemoglobin. Its in 300 times more stable than oxyhemoglobin, therefore hypoxia arises even with insignificant CO concentration in the air. Hemoglobin gets switched out off the transport function, oxygen capacity in blood decreases, hypoxia occurs.

Another one form toxic hemical hypoxia is known, which arises ground methhemoglobinemia origin. Methhemoglobinemia are divided in two groups origin hereditary (primary) and acquired (secondary). Hereditary methhemoglobinemia are stipulated atypic hemoglobin synthesis, derivation of endogenic products, which turn hemoglobin to methhemoglobin; enzymes systems deficiency, which restore methemoglobin into hemoglobin. Among exogenic methemoglobin makers the majors are following: nitrogen compounds (oxides, nitrites), aminocompounds (hydroxilamine, aniline, phenylhydrasine, paraaminobensous acid), oxidizers (chlorates, permanganates, hynones, pyridin, naphtaline), oxy-restoring paint (methylene blue, kresilblau), medications (novocaine, pylocarpine, phenacetine, barbyturates, aspirin, resorcin and others).

In normally the contents of methhemoglobin in blood makes 0,3-3 g/l. Hemoglobin oxydisers can lift its level to extremely high digits. If methhemoglobin concentration reaches up to 75 %, the death occurs.

Methhemoglobinemia is the purest form of hemic hypoxia. Its mechanism is incorporated in erythrocyte itself in heme. It is known, that hemoglobin connects oxygen in labile way not changing the valency of iron atom, which is in two-valent peroxyde form. In action of just mentioned oxidizers there is an orbital electron offset, and the heme iron gets transformed from two-valent into three-valent. Hemoglobin, turning into methhemoglobin (ferrohemoglobin), loses its active centre, and oxygen transport function at the same time. Oxygen capacity of blood decreases.

In natural conditions in the person has got a methhemoglobin continuous derivation. This physiological methhemoglobinemia is stipulated by effect of molecular oxygen upon hemoglobin. In a parallel to methhemoglobin derivation there is a constant demethhemoglobinisation, that is opposite methhemoglobin transformation into hemoglobin. This process is carried out by erythrocytes reductase system and unoxydated products lactate, pyruvate and others. Thus the dynamic equilibrium between the both hemoglobin and methhemoglobin contents, is supported, to hypoxia does not arise.

In conditions of intoxication methhemoglobinmakers can oxidized hemoglobin directly or undirectly. The second mechanism is reduced to enzymes systems damage, which catalyses restoring of methhemoglobin back into hemoglobin.

Showing of methhemoglobinemia depends on individual resistance of an organism on general metabolism intensity on antioxydase and reductase systems activity erythrocytes age and hemoglobin type. The oxidation speed, for example, b F is higher than b .



Circulatory hypoxia

This is such hypoxia kind, which is stipulated by of circulation blood speed decrease, that is oxygen delivery to tissues slowing down. It arises owing to general blood flow slowing down in case of cardio-vascular insufficiency, or owing to local blood supply disorders.


Venous hyperemia

Venous hyperemia is the increasing of blood supply of and organ or tissue because of the difficulties of blood outflow through the veins. A blood inflow under this is not altered or a bit diminished. Venous congestion is caused by such causes, as thrombosis, embolism, pressing of veins by tumor or enhanced neighboring organ. The outflow of blood from veins of greater circle slows in insufficiency of right heart and decreasing of attracting force of thorax (exudative pleurisy, hemo- and pneumothorax).

Venous hyperemia


Sharply expressed venous hyperemia of the digestive channel develops at the thrombosis of portal vein. The overcrowded collateral veins of lower third of esophagus and the hemoroidal veins are sharply expanded, their wall is thinned, what can cause the bleeding dangerous for life.

At the thrombosis of hepatic veins the venous hyperemia of liver and the fatty dystrophy of hepathocytes arise. On the cut the organ has an appearance of nutmeg on gray-yellow background, caused by the fatty dystrophy, the red-dark blue spots are visible these are the overcrowded by venous blood broadened central veins of hepatic lobules. Such liver is called muscat.

Venous stagnation on the lower extremities is observed when there is an impediment for the blood outflow by venous highways. They can be compressed by tumour, pregnant uterus, scars. Venous hyperemia of the lower extremities appeares into the specialists, who are forced to abide permanently in stand-up position. By favourable background for this is the hereditary weakness of valvular veins vehicle.

Venous hyperemia characterize the signs:

) redness with the cyanotic hue; cyanosys is explained by the piling up of restored hemoglobin over 30 % from general amount;

b) local decreasing of the temperature as a result of the limited inflow of arterial blood and surplus heat emission;

c) slowing-down of blood stream;

d) rise of blood pressure in veins dystal from the impediment;

e) the increasing of the volume of the hyperemic tissue (edema) because of the transsudation of liquid from vessels.

In case venous stagnation there is the hypoxia, a development degree of which determines the process superventions. For conditions of anoxaemia the parenchime organs elements die and than overgrows a connecting tissue which is more resistant to the hypoxia. Further follows a sclerosis and consolidation (nduration ) of organs. These phenomena are known under the names of liver cirrhosis, cyanotic induration of the spleen and kidneys.





The ischemia (local anemia) is called the diminished organ or tissue blood supply because of the insufficient inflow of arterial blood. There are three types of ischemia by the mechanism of their beginning compressive, obturational and angiospastic.

A compressive ischemia is the result of the artery squeezing by tumor, scar, xudate, ligature, bandage, foreign body.

An obturational ischemia arises at the partial or full closing of artery lumen by thrombus, mbole, by sclerotic plaque. This form is typical for the obliterasing endarteriitis, when vessel lumen narrows because of the productive inflammation of its wall.


An angiospastic ischemia caused by the various chemical and biological irritants which narrow the vessels (trauma, cold, rgotoxine). ngiospasm can happen reflexly at the pathology of internal organs. A typical example of such ischemia is a spasm of coronal vessels and stenocardia paroxysms in patients with ulcerous stomach or duodenum disease, pancreatitis, cholecystitis, bile- and urine lith disease. Angiospasm is typical for all cases of the sympathic hyperactivity, and the constriction of arteries for the account of noradrenaline action on the vessel alpha-adrenoreceptors can be supplemented by the surplus formation of angiotensine . ngiospasm can be caused by the negative emotions such as pain, fear, anger.

The ischemia arising because of the blood redistribution from one organs to other is known separately. The cases, when an ischemia of cerebrum and the loss of consciousness were the supervention of the fast suction of ascytic liquid from abdominal cavity are known. A previous ischemia of internal organs suddenly changed on the hyperemia for an account of outflow of blood from cerebrum. An identical phenomenon is observed at the overdosage of the vesseldilatative substances.

An ischemia is attended with the signs, among which the most typical are:

        pallor of the ischemizated site

        the decreasing of its volume

        local decreasing of the temperature


        the appearance of the paresthesias

A speed of blood flowing in the arterial vessels beneath the impediment is slowed, the blood pressure is low, amount of functioning capillaries is diminished.

The consequences of ischemia depend on the depth of anoxaemia. It can get through without trace or complete by the necrosis of the ischemisated site the infarction, gangrene. There is the large possibility of the necrosis appearance, if the ischemia comes suddenly and continues for long time. The consequences, are usually the more terrible the greater arterial trunk is turned out from bloodflow. The ischemia in heart and brain is very dangerous. These organs are distinguished by high function level, and thus by high need in oxygen.

Myocardial infarction



The kidneys, lungs, spleen are more resistant to the hypoxia but in them frequently happen the infarctions. Their microcirculative streem is built that way, that does not provide the proper collateral bloodflow in the conditions of the obturation of the arterial trunk. Other organs (muscles, bones, skin) suffer from ischemia less.

The important sense have the organic damages of arterial vessels. In patients with arteriosclerosis the infarctions arise more frequent, because the sclerosed vessels are unable to dilate adequately to needs of the blood supply. The cardiac and respiratory insufficiency, anemia contribute to infarction development.



Stasis this is a blood motion stop in the vessels of microcirculative stream, chiefly in the capillaries. There are three varieties of a stasis true (capillary), ischemic and venous.

Stasis in brain vessels

true stasis is caused by various factors by cold and heat, acids, concentrated salts solutions, turpentine. Infectious-toxic stasis appeares in extremities of patients with louse-borne typhus. Stasis is typical also for the acute inflammation in lergisated organism (Arthuse phenomenon ).

In the mechanism of capillary stasis main sense have the changes of reologic blood properties. Morphologically the stasis is expressed by the intracapillary erythrocytes aggregation. This phenomenon is called sladge-phenomenon. The erythrocytes stick together, forming so called monetary olumnes. The hemolysis and clotting of blood under this do not take place. The aggregated erythrocytes makes resistence to the motion of blood and stop it. To the full stop precedes the retardation of blood flow it is the prestasic state, or prestasis. Contributes to the development of stasis a blood condesation because of the rise of capillary walls permeability, that happens at the hyperemia, hypoxia, vasculites, the action of high and low temperatures, allergic processes.

schemic and venous stasis have the same causes as the processes, at which they are observed (schemia, venous hyperemia).





By this term the intravital blood or lymph concertion in vessels and in heart chambers cavities is marked. A clot of blood (lymph), that formed, is called thrombus.

The main factors of thrombforming now are well famous. These are:

        the damage of vascular wall,

        local angiospasm, dhesion and aggregation of the thrombocytes,

        slowing-down of bloodflow,

        disturbance of balance between coagulative, anticoagulative and fibrinolytic blood systems into dominance side of the first of them.


The vessels wall can be damaged in result of mechanical trauma, under action of chemical agents and bacterial endotoxines, in the inflammation, atherosclerosis, hypertensive illness. The damage of vessels frequently has the starting role. From here starts the process of thrombformation. From damaged wall throw out the substances, which activate thrombocytes, assist their adhesion and aggregation, and also to blood coagulation.

Local vasoconstriction after the damage of tissues is conditioned by the spasm of smooth muscles of the arteriols under the influence of noradrenalin, that is excreated in the adrenergic synapses. Vasoconstriction contributes to the release into blood of the tissue thromboplastin, and noradrenalin activates Hagemanns factor. Thanks to the vasoconstriction not only elementary bloodloss is limited, but the local accumulation of hemostatic substunces takes place.

The adhesion of thrombocytes is in their ability to come into contact with deendothelised vascular wall, to connect with its receptors with collagene fibres of basal membrane, to spread and close down the defect. The adhesion takes place double-quickly, during 3-10 . In it, besides the thrombocytic factors, a special plasma albumen Vilebrands factor participates.

Adhesion of thrombocytes


An aggregation is a following stage of thrombforming. Parallel to the adhesion to collagene and other subendothelial structures the thrombocytes begin to stick together. On the spreaded thrombocytes quickly settle the other ones. So the aggregates from 3-20 thrombocytes arte generated, the amount of which quickly increases.

Settling of the circulatory thrombocytes is made by biologically active substunces, among which the most important are two thromboxane 2 and denosinephosphate (DP). They are produced by the settled thrombocytes. hromboxane 2 is derivative of the arachidone acid. ADP is thrown out from the dense granules of thrombocytes together with serotonine.

Pathogenesis of thrombosis


About the significance of slowing-down of bloodflow in thrombforming testify the facts of principal thrombi localization in veins, on lower extremities, in places of vertical blood motion (aneurism, pockets of venous valves), in patients with cardiac insufficiency, attached to the relaxation of the attracting action of thorax, attached to the presence of local impediments for outflow of venous blood.


By the adhesion and aggregation of the thrombocytes and by accomplishes a cell phase of thrombforming. Following phase is plasmatic, an it essence comes to the acceleration of blood clotting (hypercoagulation).

There are two mechanisms of activation of this complicated multistaged process internal and external. An internal mechanism begins from Hagemans factor of activation, and external is in outflowing of the tissue thromboplastine in the place of damage. Both they have one destination that is to activate a factor (Stuarts-Prauer), where upon the active thrombin is generated, and further from the fibrinogene the stable fibrin.

Dependency on the contents there are: white, red and mixed thrombs.

In white prevail the leucocytes, it is generated slowly attached to fast blood motion, in arteries.

Red thrombus contains more erythrocytes, it is generated quickly, principal in veins. The most frequently the mixed thrombs are met, in which the leucocytes are in layers with erythrocytes. They are generated in heart cavities, aneurism, varicose broadened veins.


Red thrombs Mixed thrombs


The thrombosis concequences may be favourable and unfavourable. The best variant is asepsis utholysis, when a thrombus swings open for the activation of the fibrinolytic blood system and leucocytes proteolytic enzymes. However big thrombs dissolve seldom, more frequent they extend by connecting tissue (organization of thromb). Growing in of the connecting tissue begins from the place of fastening of the thromb to wall of vessel, from the head.

Thrombus condenses, gets dry, the cracks are generated in it, through of which the blood motion can revive in the vessel. This phenomenon is named recanalisation. A surface of such channels are covered by endothelium, the channels become the vessels. Organized into a thrombus extend the small vessels, which feel it the vascularisation of the thrombe. The organized thrombs are able to calcinate, in them the veins are named phlebitis.

The unfavourable thrombosis completion is septic autholysis of the thromb, its pyogenesis. The reason of purulent melting of thrombus appear the particles, which are carried by blood to different organs. This conduces to the generalisation of purulent inflammation and sepsis development. The thrombosis consequences can be the coronary thromboses, thrombembolias, thrombophlebites.




The embolism is obstructing up of lymphatic or blood vessels by the particles (mbols), which in norm in blood and lymph do not meet.

Embolism is subdivided on exogenous and endogenous.

The exogenous embolism may be:





        made by foreign bodies

Endogenous embolism subdivides on:




        embolism by amniotic fluid


Air embolism is observed, as a rule, at the damage of large veins, in which there is the negative pressure. This happens in cases of fighting or domestic wound of jugular or subclavian veins, at the pneumothorax, operations on heart, after childbearing, when the uteric veins do not close, at the accidental air introduction into vein together with medicines. Air amass in chambers cavities of right heart, drags them apart and is brought into the vessels of the small blood circle.

Gaseous embolism happens at the caisson works. Steeping on the depth, man breathes in gaseous mixture under increasing pressure. Accordingly increases the gases solubility in blood. If theres the necessity of fast diver lifting on the surface, the dissolved gases are not able to expire through the lungs and get across into gaseous state. Blood begins to boil. The gas bubbles, which almost completely consist of the nitrogen, obstruct the vessels. Identical can happen at the dehermetisation of the flying paratus. Embolism of the type complicates the passing of gaseous gangrene.

The bacterial and parasirte embolism is obstructing up of vessels by microorganisms, candidas, protozoon, parasites (trichinels). Frequently microbe embols are generated at the purulent thrombi melting. In obstructed places the metastatic ulcers develop.

Embolism by foreign-bodies comes when into the vessels lumen the bullets, mine splinters and other solids are brought. The heavy bodies move not far, sometimes against the blood flow.

Endogenous embolism is most often caused by the thrombus, that tore off from vascular wall.

Thromembols from veins of greater blood circle and from cavities of right heart are brought for blood motion into pulmonary artery, and that ones, that formed in the cavities of the left heart, bring on the brain infarction, the infarctions of the the kidneys, spleen, gangrene of the mesoperitoneum and lower extremities. Lightly obrupt the thrombus, that formed on the mitral and aortic valves at the rheumatism, protracted septic endocarditis, heart defects.

Fatty embolism arises at the traumatic damage of hypodermic adipose tissue, fractures of long bone, in which the marrow is deputized by fatty tissue, and also at the mistaken injection of medicines, dissolved on oil, into the vessels.

Fatty embolism of lungs


Fat for the blood motion comes into pulmonary artery. Death arises in case obstructing of two thirds of branches of pulmonary artery.

Fatty embolism


Tissue (cellular) embolism develops at the destruction of the tissues by trauma or pathologic process. Under this the tissue pieces or cell groups come into blood streem. The embols become the heart valves pieces at the ulcerous endocarditis, aorta wall pieces at the ulcering of the aterosclerose plaques, pieces of cerebrum at the cranial-cerebral traumas (especially into babies at the childbed trauma), cancer cells. The last ones can extend to the veins wall and lymphatic walls, abrupt from the tumor and metastase into other organs. Here is taken the embolism by the petrificates and the amniotic waters in the pregnant women.

The embols, usually, moves down the blood stream (rthograde embolism). Sometimes the foreign solid bodies under the influence of their own weight lowering into lower posed parts of body against the blood motion (retrograde embolism). The retardation of the bloodflowing and relaxation of the succing force of thorax contributes to this. Into persons with the defects intraatrial or intraventricular septs the embols can go from the right half of the hearts into the left one and further into aorta, passing by the lesser circulation (paradoxical embolism).

Paradoxical embolism


The symptoms of embolism depends, foremost, on its localization. That's why there are the embolisms of the lesser circulation, greater circulation and portal vein.

The threatful complication is the embolism of pulmonary artery. It arises in the patients with thrombosis of lower extremities and the cavity of right heart. Embolism of greater circulation reverberates on the structure and function of the organs, into which the embols are brought.

Embolism of pulmonary artery


The possibility of the necrosis depends on the development of the degree of collaterals and reflex spasm of the obturated and remoted vessels. The major pathogenic link of the embolism of the portal vein is syndrome of the portal hypertension. The internal organs are overflowed by blood, a liquid percolates into the abdominal cavity (scytis). The spleen is enlarged (splenomegaly). The superficial veins of the front stomach wall are widened. From the superficial veins of the esophagus and stomach the bleedings are possible

Pure circulatory hypoxia does not happen really exist. It is observed only as a local phenomenon in fact of separate organs ischemia. If blood circulation disorders seize the large or small circle, other circulatory hypoxia forms are connected for sure.

In case of pure circulational hypoxia the main respiratory parameters in blood are not changed. Oxygen capacity in blood is normal the tension of oxygen in arterial blood is normal, hemoglobin oxygenation is normal too. Hypoxia arises because of volume decreases of oxygen, which is transported to tissues per one a time unit. In case of blood slow passing through tissues the last utilise more oxygen than normally, therefore most indicative change on the part of respiratory blood parameters is arterial-venous difference increase by oxygen. This parameter testifies the blood flow speed decrease and reflects the essence of mentioner hypoxia type.

Not only absolute but relative blood circulation insufficiency can also cause circulational hypoxia. Relative insufficiency is such a state, when the oxygen consumption exceeds its greatest possible delivery to tissues. As an example one can give an myocardium. In sympathetic hyperactivity, conditions adrenaline stimulates myocardium operation adrenoreceptors cardiomyocytic and increases its oxygen consumption. At the same time adrenaline dilatates the coronary vessels acting β-adrenoreceptors. Although, even the maximal most possible coronary blood flow increase, is still lag behind the increased necessity in oxygen. Hypoxia arises, which is also circulatory.



Histotoxic hypoxia

In this hypoxia kind basis is the tissues inability of oxygen utilisating, therefore its main parameter is the low arterioal-venous difference. Neither, the contents of oxygen in blood, nor its delivery to tissues are not broken, but tissue use it less for one time unit, than it is necessary for maintenance their energy needs. The reason of this phenomenon is the decrease of respiratory enzymes activity.

Three enzymes systems participate in electron transport from substrat to molecular oxygen pyridindependent dehydrogenases, flavindependent dehydrogenases, cytochromes. Any of these systems blockade will result in disorder of electron transport throughout on a respiratory chain and will cause histotoxic hypoxia. Respiratory chain enzymes are oppressed with cyanides, monoiodacetatis, drugs, spirit, formaldehyde, aceton, ethylurethane, sulfurhydrogen, cocain, carbon oxyde and other substances. Typical example of hystotoxical hypoxia cyanic poisoning, which oppresses cytochromoxydase. The cytochromes oxidazing restoring processes get blocked with local anestetics (novocaine). Flavine enzymes lose their activity in case of riboflavine (vit. B2) deficiency. Pyridine enzymes activity is slowing down with nicotine acid deficiency.

These four hypoxia kinds can be isolated seldom. The combination of two or more hypoxia kinds is more often observed in practice. Such combinations are mixed hypoxias.




Metabolism in state of hypoxia

In a basis of hypoxia damaging effect upon the organism stays the P decrease in cells lays. The contents other macroergic compound creatinephosphate decreases in a brain and heart very fast. The P stocks in cells are practically absent. The P synthesis in biological oxidation process during hypoxia lays behind P disintegration by the time of a cell live. The decrease of macroergic compounds in cells results in disorder of all metabolism forms, ultra structural and functional cell damage. Major changes of carbohydrate metabolism are the following: anaerobic glycolysis increase, glycogen stocks exhausting, accumulation of pyruvic and lactic acids, metabolic acidosis.

The protein metabolism disorders manifest in such changes: the synthesis oppression and simultaneously acceleration of fibers disintegration, increase of residual blood nitrogen contents, ammonia accumulation.

The fatty metabolism in case of hypoxia is characterized by such features: intensive fat disintegration in depot, accumulation of fatty acids in tissues, ketoacids accumulation in blood.






Cerebral and heart activity disorder in state of hypoxia

Nervous system is the most sensitive to oxygen starvation. Such digits testify to it. The average intensity of oxygen consumption by an organism at all makes 0,38 ml/mines per 100 g of a body weight. At the same time, the oxygen intensity consumption by human brain makes 3,9 ml/min per 100 g of body weight and the grey substance of brain consumes even more oxygen - up to 10 ml/mines per 100 g of body weight.

Brain cortex neurons can work perfectly in conditions of complete blood flow termination only for 5-6 minutes. Oblongatal brain neurons maintain the complete blood supply termination for 20-30 minutes, spinal cord neurons - up to 60 minutes. Heavy and long hypoxia causes a defect of blood supply and breath centres, reflex activity disorder. Cramps, the unconsciousness appears. The speed of oxygen consumption by a brain begins to decelerate, while the oxygen partial pressure in air falls below 100 mm Hg.

The myocard is very sensitive to oxygen starvation.It takes on the second place after the nervous system. Increasing heavy hypoxia oppresses contract and rhythmic heart activity. In a basis of these disorders the suppression of biological oxidation and energy deficiency lays.






Compensatory responses in state of hypoxia

The compensatory responses of an organism, which are directed to hypoxia removal are divided into four groups respiratory, hemodynamic, bloodly and tissuel.

The respiratory responses appear as dyspnea, with acceleration and deepening of breathing. It is named altitude, or hypoxic, or compensatory. Dispnea arises in reply to an hemoreceptors aortae arc and sinocarotide zones irritation with hypoxic blood. Due to dyspnea pulmonary ventilation is increased. The compensatory significance of lung hyperventilation is not absolute, because after excessive and long hyperventilation occurs hypocapnia. It has an negatively effect upon breath regulation, as carbonic acid intensively washout from blood physiological irritation of respiratory centre. Sudden unconsciousness during the height rise can be explained just by respiratory centre paralysis.


The hemodynamic compensator responses include:

) tachycardia result of sympathetic tonus increase;

b) stock blood volume increase at the expense of adrenaline action upon myocardium adrenoreceptors;

c) cardiac output increase as a result of tachycardia and stock volume increase;

d) the blood flow acceleration - it is connected in main to cardiac output increase;

e) blood circulation centralization that is peripheral vessels narrowing and vessels of the vital organy extension owing to there is redistribution of blood to brain, heart, lung in fact of simultaneous blood supply limitation of skin, muscles, intestines, spleen.

The group of bloodly compensatory responses includes such a responses as:

) erythrocytosis first of all in responce of an blood output from depot, and later by blood form stimulation;

b) the increase of hemoglobin charge in erythrocytes;

c) hemoglobin to oxygen similarity increase in lung (shift of oxyhemoglobin dissociation curve to the left) and decrease it this similarity in tissues (shift of oxyhemoglobin dissociation curve to the right).

Tissuel compensatory responses are the decrease of metabolism, activation of glycolysis, activation of respiratory chain enzymes.


Development of Alkalosis

The pH of blood depends on the ratio of HCO3 to CO2 concentration: pH = pK + log HCO3 CO2 pK contains the dissociation constant of H2CO3 and the reaction constant of CO2 to H2CO3. Alkalosis (pH > 7.44) thus occurs either when the CO2 concentration in blood is too low (hypocapnia, respiratory alkalosis), or that of HCO3 is too high (metabolic alkalosis). Respiratory alkalosis occurs in hyperventilation (!A3 and p. 82). Causes include emotional excitement, salicylate poisoning, or damage to the respiratory neurons (e.g., by inflammation, injury, or liver failure). Occasionally a lack of O2 supply in the inspiratory air (e.g., at high altitude) causes increased ventilation resulting in an increased amount of CO2 being expired. Numerous disorders can lead to metabolic (i.e., non-respiratory) alkalosis: ! In hypokalemia the chemical gradient for K+ across all cell membranes is increased. In some cells this leads to hyperpolarization, which drives more negatively charged HCO3 from the cell. Hyperpolarization, for example, raises HCO3 efflux from the proximal (renal) tubule cell via Na+(HCO3 )3 cotransport (!A4). The resulting intracellular acidosis stimulates the luminal Na+/H+ exchange and thus promotes H+ secretion as well as HCO3 production in the proximal tubule cell. Ultimately both processes lead to (extracellular) alkalosis. ! In vomiting of stomach contents the body loses H+ (!A6). What is left behind is the HCO3 produced when HCl is secreted in the parietal cells. Normally the HCO3 formed in the stomach is reused in the duodenum to neutralize the acidic stomach contents and only transiently leads to (weak) alkalosis. ! Vomiting also reduces the blood volume. Edemas as well as extrarenal and renal loss of fluid can similarly result in volume depletion (!A4; see also p.122). Reduced blood volume stimulates Na+/H+ exchange in the proximal tubules and forces increased HCO3 reabsorption by the kidneys even in alkalosis. In addition, aldosterone is released in hypovolemia, stimulating H+ secretion in the distal nephron (!A5). Thus, the kidneys ability to eliminate HCO3 is compromised and the result is volume depletion alkalosis. Hyperaldosteronism can lead to alkalosis without volume depletion. ! Parathyroid hormone (PTH) normally inhibits HCO3 absorption in the proximal tubules. Hypoparathyroidism can thus lead to alkalosis. ! The liver forms either glutamine or urea from the NH4 + generated by amino acid catabolism. The formation of urea requires, in addition to two NH4 +, the input of two HCO3 that are lost when urea is excreted. (However, NH4 + is split off from glutamine in the kidney and then excreted as such). In liver failure hepatic production of urea is decreased (!A7), the liver uses up less HCO3 , and alkalosis develops. However, in liver failure respiratory alkalosis often predominates as a result of damage to the respiratory neurons (see above). ! An increased supply of alkaline salts or mobilization of alkaline salts from bone (!A2), for example, during immobilization, can cause alkalosis. ! Metabolic activity may cause the accumulation of organic acids, such as lactic acid and fatty acids. These acids are practically completely dissociated at blood pH, i.e., one H+ is produced per acid. If these acids are metabolized, H+ disappears again (!A1). Consumption of the acids can thus cause alkalosis. ! The breakdown of cysteine and methionine usually produces SO4 2 + 2 H+, the breakdown of arginine and lysine produces H+. Reduced protein breakdown (e.g., as a result of a protein- deficient diet; !A8), reduces the metabolic formation of H+ and thus favors the development of an alkalosis. The extent to which the bloods pH is changed depends, among other factors, on the buffering capacity of blood, which is reduced when the plasma protein concentration is lowered.



The pH of blood is a function of the concentrations of HCO3 and CO2 (!p. 86). An acidosis (pH < 7.36) is caused by too high a concentration of CO2 (hypercapnia, respiratory acidosis) or too low a concentration of HCO3 (metabolic acidosis) in blood. Many primary or secondary diseases of the respiratory system (!p. 6680) as well as abnormal regulation of breathing (!p. 82) can lead to respiratory acidosis (!A3). This can also be caused by inhibition of erythrocytic carbonic anhydrase, because it slows the formation of CO2 from HCO3 in the lung and thus impairs the expiratory elimination of CO2 from the lungs. There are several causes of metabolic acidosis: ! In hyperkalemia (!A4) the chemical gradient across the cell membrane is reduced. The resulting depolarization diminishes the electrical driving force for the electrogenic HCO3 transport out of the cell. It slows down the efflux of HCO3 in the proximal tubules via Na+(HCO3 )3 cotransport. The resulting intracellular alkalosis inhibits the luminal Na+/H+ exchange and thus impairs H+ secretion as well as HCO3 production in the proximal tubule cells. Ultimately these processes lead to (extracellular) acidosis. ! Other causes of reduced renal excretion of H+ and HCO3 production are renal failure (!p.110ff.), transport defects in the renal tubules (!p. 96ff.), and hypoaldosteronism (!A5). (Normally aldosterone stimulates H+ secretion in the distal tubules; !p. 270). ! PTH inhibits HCO3 absorption in the proximal tubules; thus in hyperparathyroidism renal excretion of HCO3 is raised. As PTH simultaneously promotes the mobilization of alkaline minerals from bone (!p.132), an acidosis only rarely results. Massive renal loss of HCO3 occurs if carbonic anhydrase is inhibited, because its activity is a precondition for HCO3 absorption in the proximal tubules. ! Loss of bicarbonate from the gut (!A6) occurs in vomiting of intestinal contents, diarrhea, or fistulas (open connections from the gut or from excretory ducts of glands). Large amounts of alkaline pancreatic juice, for example, can be lost from a pancreatic duct fistula. ! As the liver needs two HCO3 ions when incorporating two molecules of NH4 +; in the formation of urea (!p. 86), increased urea production can lead to acidosis. In this way the supply of NH4Cl can cause acidosis (!A7). In certain circumstances the infusion of large amounts of NaCl solution can lead to an acidosis, because extracellular HCO3 is diluted in this way. In addition, expansion of the extracellular space inhibits Na+/H+ exchange in the proximal tubules as a result of which not only Na+ absorption in the proximal tubules but also H+ secretion and HCO3 absorption is impaired. ! Infusion of CaCl2 results in the deposition of Ca2+ in bone in the form of alkaline salts (calcium phosphate, calcium carbonate). H+ ions, formed when bicarbonate and phosphate dissociate, can cause acidosis. ! Mineralization of bone, even without CaCl2, favors the development of acidosis (!A2). ! Acidosis can also develop when there is increased formation or decreased breakdown of organic acids (!A1). These acids are practically fully dissociated at the blood pH, i.e., one H+ is formed permolecule of acid. Lactic acid is produced whenever the energy supply is provided from anaerobic glycolysis, for example, in O2 deficiency (!p. 84), circulatory failure (!p. 224), severe physical exercise, fever (!p. 20ff.), or tumors (!p.14ff.). The elimination of lactic acid by gluconeogenesis or degradation is impaired in liver failure and some enzyme defects. Fatty acids, "-hydroxybutyric acid and acetoacetic acid accumulate in certain enzyme defects but especially in increased fat mobilization, for example, in starvation, diabetes mellitus (!p. 286ff), and hyperthyroidism. ! A protein-rich diet promotes the development of metabolic acidosis, because when amino acids containing sulfur are broken down (methionine, cystine, cysteine), SO4 2 + 2 H+ are generated; when lysine and arginine are broken down H+ is produced (!A8). The extent of acidosis depends, among other factors, on the bloods buffering capacity.


Adaptation to hypoxia

Hypoxia is not only a damaging, but is also a training factor. During hypoxia training period emergency adaptation is formed first. In case of long hypoxia perfomanse a certain mode the emergency adaptation turns into long-term adaptation. Adapted organisms have got energetic and plastic resources are spent very economically.

In case of the hypoxia training termination the state of desadaptation occurs. The positive properties, of adapted organism bought during trainings, are getting gradually lost.It is important not to infringe a mode of trainings at all stages of adaptive process. The mode disorder is dangerous. Dangerous life disorders arise in such cases, which increase sensitivity to hypoxia. Adaptation, desadaptation, failure adaptation problem is very important. It has practical significance in people selection and preparation for certain professional mastering by the (divers, spaceman) and for examination the territories with extremal life conditions (space, ocean, mountain).