Respiratory failure - Causes and pathogenesis

Causes and mechanisms of ventilatory and parenchymatous respiratory failure

Respiratory failure occurs when any of the functional components of the respiratory system is disrupted - the pulmonary parenchyma, chest wall, pulmonary circulation, the state of the alveolar-capillary membrane, nervous and humoral regulation of respiration. Depending on the prevalence of certain changes in the gas composition of the blood, two main forms of respiratory failure are distinguished - ventilatory (hypercapnic) and parenchymatous (hypoxemic), each of which can be acute or chronic.

Ventilatory (hypercapnic) respiratory failure

The ventilatory (hypercapnic) form of respiratory failure is characterized mainly by a total decrease in the volume of alveolar ventilation (alveolar hypoventilation) and minute respiratory volume (MRV), a decrease in the removal of CO2 from the body and, accordingly, the development of hypercapnia (PaCO2> 50 mm Hg), and then hypoxemia.

The causes and mechanisms of development of ventilatory respiratory failure are closely related to the disruption of the process of removing carbon dioxide from the body. As is known, the process of gas exchange in the lungs is determined by:

• level of alveolar ventilation;
• diffusion capacity of the alveolar-capillary membrane in relation to O ₂ and CO ₂;
• perfusion magnitude;
• the ratio of ventilation and perfusion (ventilation-perfusion ratio).

From a functional point of view, all airways in the lungs are divided into conducting pathways and a gas exchange (or diffusion) zone. In the area of conducting pathways (in the trachea, bronchi, bronchioles and terminal bronchioles) during inhalation, there is a progressive movement of air and mechanical mixing (convection) of a fresh portion of atmospheric air with gas that was in the physiological dead space before the next inhalation. Therefore, this area has another name - the convection zone. It is clear that the intensity of enrichment of the convection zone with oxygen and a decrease in the concentration of carbon dioxide, above all, is determined by the intensity of pulmonary ventilation and the value of the minute volume of respiration (MVR).

It is characteristic that as we approach smaller generations of the airways (from the 1st to the 16th generation), the forward movement of the air flow gradually slows down, and at the boundary of the convection zone it stops altogether. This is due to a sharp increase in the total combined cross-sectional area of each subsequent generation of bronchi and, accordingly, to a significant increase in the total resistance of the small bronchi and bronchioles.

The subsequent generations of the airways (from the 17th to the 23rd), including the respiratory bronchioles, alveolar passages, alveolar sacs and alveoli, belong to the gas exchange (diffusion) zone, in which the diffusion of gases through the alveolar-capillary membrane occurs. In the diffusion zone, the "macroscopic" day | blue gases both during respiratory movements and during coughing are completely absent (V.Yu. Shanin). Gas exchange here is carried out only due to the molecular process of diffusion of oxygen and carbon dioxide. In this case, the rate of molecular movement of CO2 - from the convection zone, through the entire diffusion zone to the alveoli and capillaries, as well as CO2 - from the alveoli to the convection zone - is determined by three main factors:

• gradient of partial pressure of gases at the boundary of convection and diffusion zones;
• ambient temperature;
• diffusion coefficient for a given gas.

It is important to note that the level of pulmonary ventilation and MOD have almost no effect on the process of movement of CO2 and O2 molecules directly in the diffusion zone.

It is known that the diffusion coefficient of carbon dioxide is approximately 20 times higher than that of oxygen. This means that the diffusion zone does not create a large obstacle for carbon dioxide, and its exchange is almost entirely determined by the state of the convection zone, i.e. the intensity of respiratory movements and the value of the MOD. With a total decrease in ventilation and minute respiratory volume, the "washing out" of carbon dioxide from the convection zone stops, and its partial pressure increases. As a result, the CO2 pressure gradient _at the boundary of the convection and diffusion zones decreases, the intensity of its diffusion from the capillary bed into the alveoli drops sharply, and hypercapnia develops.

In other clinical situations (for example, in parenchymatous respiratory failure), when at a certain stage of the disease development there is a pronounced compensatory hyperventilation of intact alveoli, the rate of "washing out" of carbon dioxide from the convection zone increases significantly, which leads to an increase in the CO2 pressure gradient _at the boundary of the convection and diffusion zones and increased removal of carbon dioxide from the body. As a result, hypocapnia develops.

Unlike carbon dioxide, oxygen exchange in the lungs and the partial pressure of carbon dioxide in arterial blood (PaO ₂ ) depend primarily on the functioning of the diffusion zone, in particular on the diffusion coefficient of O ₂ and the state of capillary blood flow (perfusion), while the level of ventilation and the state of the convection zone affect these indicators only to a small extent. Therefore, with the development of ventilatory respiratory failure against the background of a total decrease in the minute volume of respiration, hypercapnia occurs first and only then (usually at later stages of the development of respiratory failure) - hypoxemia.

Thus, the ventilatory (hypercapnic) form of respiratory failure indicates the failure of the "breathing pump". It can be caused by the following reasons:

1. Disorders of central regulation of respiration:
   • cerebral edema affecting its stem parts and the respiratory center area;
   • stroke;
   • traumatic brain injuries;
   • neuroinfection;
   • toxic effects on the respiratory center;
   • hypoxia of the brain, for example, in severe heart failure;
   • overdose of drugs that depress the respiratory center (narcotic analgesics, sedatives, barbiturates, etc.).
2. Damage to the apparatus that ensures respiratory movements of the chest, i.e. disruptions in the functioning of the so-called “chest bellows” (peripheral nervous system, respiratory muscles, chest):
   • chest deformities (kyphosis, scoliosis, kyphoscoliosis, etc.);
   • fractures of the ribs and spine;
   • thoracotomy;
   • dysfunction of the peripheral nerves (mainly the phrenic nerve - Guillain-Barré syndrome, poliomyelitis, etc.);
   • disorders of neuromuscular transmission (myasthenia);
   • fatigue or atrophy of the respiratory muscles against the background of prolonged intense coughing, airway obstruction, restrictive breathing disorders, prolonged mechanical ventilation, etc.);
   • a decrease in the efficiency of the diaphragm (for example, when it flattens).
3. Restrictive respiratory disorders accompanied by a decrease in MV:
   • pronounced pneumothorax;
   • massive pleural effusion;
   • interstitial lung diseases;
   • total and subtotal pneumonia, etc.

Thus, most causes of ventilatory respiratory failure are associated with disorders of the extrapulmonary respiratory apparatus and its regulation (CNS, chest, respiratory muscles). Among the "pulmonary" mechanisms of ventilatory respiratory failure, restrictive respiratory failures are of primary importance, caused by a decrease in the ability of the lungs, chest or pleura to straighten during inhalation. Restrictive failures develop in many acute and chronic diseases of the respiratory system. In this regard, within the framework of ventilatory respiratory failure, a special restrictive type of respiratory failure is distinguished, most often caused by the following reasons:

• diseases of the pleura that limit the excursion of the lung (exudative pleurisy, hydrothorax, pneumothorax, fibrothorax, etc.);
• reduction in the volume of functioning lung parenchyma (atelectasis, pneumonia, lung resection, etc.);
• inflammatory or hemodynamically conditioned infiltration of lung tissue, leading to an increase in the “rigidity” of the lung parenchyma (pneumonia, interstitial or alveolar pulmonary edema in left ventricular heart failure, etc.);
• pneumosclerosis of various etiologies, etc.

It should also be taken into account that hypercapnia and ventilatory respiratory failure may be caused by any pathological processes accompanied by a total decrease in alveolar ventilation and minute respiratory volume. Such a situation may arise, for example, with severe obstruction of the airways (bronchial asthma, chronic obstructive bronchitis, pulmonary emphysema, dyskinesia of the membranous part of the trachea, etc.), with a significant decrease in the volume of functioning alveoli (atelectasis, interstitial lung diseases, etc.) or with significant fatigue and atrophy of the respiratory muscles. Although in all these cases, other pathophysiological mechanisms (disturbances in gas diffusion, ventilation-perfusion relationships, capillary blood flow in the lungs, etc.) are involved in the development of respiratory failure. In these cases, as a rule, we are talking about the formation of mixed ventilatory and parenchymatous respiratory failure.

It should also be added that in acute ventilatory respiratory failure, an increase in PaCO2 is usually accompanied by a decrease in blood pH and the development of respiratory acidosis, caused by a decrease in the HCO3/H2CO3 ratio, which, as is known, determines the pH value. In chronic respiratory failure of the ventilatory type, such a pronounced decrease in pH does not occur due to a compensatory increase in the concentration of carbonates in the blood serum.

1. Ventilatory (hypercapnic) respiratory failure is characterized by:

1. total alveolar hypoventilation and a decrease in minute respiratory volume,
2. hypercapnia,
3. hypoxemia (at later stages of respiratory failure),
4. signs of compensated or decompensated respiratory acidosis.

2. The main mechanisms of development of the ventilation (hypercapnic) form of respiratory failure:

1. disruption of central regulation of respiration;
2. damage to the apparatus that provides respiratory movements of the chest (peripheral nerves, respiratory muscles, chest wall);
3. pronounced restrictive disorders accompanied by a decrease in the MOD.

Parenchymatous respiratory failure

Parenchymatous (hypoxemic) form of respiratory failure is characterized by a significant disruption of the process of blood oxygenation in the lungs, which leads to a predominant decrease in PaO2 in arterial blood - hypoxemia.

The main mechanisms of hypoxemia development in the parenchymatous form of respiratory failure:

1. violation of ventilation-perfusion relations (//0) with the formation of right-left-heart "shunting" of blood (alveolar shunt) or an increase in alveolar dead space;
2. reduction in the total functioning surface of the alveolar-capillary membranes;
3. violation of gas diffusion.

Violation of ventilation-perfusion relations

The occurrence of hypoxemic respiratory failure in many diseases of the respiratory organs is most often caused by a violation of ventilation-perfusion relations. Normally, the ventilation-perfusion ratio is 0.8-1.0. There are two possible variants of violations of these relations, each of which can lead to the development of respiratory failure.

Local hypoventilation of the alveoli. In this variant of parenchymatous respiratory failure, hypoxemia occurs if sufficiently intense blood flow continues through poorly ventilated or non-ventilated alveoli. The ventilation-perfusion ratio is reduced here (V/Q <0.8), which leads to the discharge of venous blood insufficiently oxygenated in these areas of the lung into the left chambers of the heart and the systemic circulation (venous shunting). This causes a decrease in the partial pressure of O2 _in the arterial blood - hypoxemia.

If there is no ventilation in such a section with preserved blood flow, the V/Q ratio approaches zero. It is in these cases that a right-to-left heart alveolar shunt is formed, through which unoxygenated venous blood is "thrown" into the left sections of the heart and the aorta, reducing PaO2 _in arterial blood. Hypoxemia develops by this mechanism in obstructive pulmonary diseases, pneumonia, pulmonary edema and other diseases accompanied by an uneven (local) decrease in alveolar ventilation and the formation of venous shunting of blood. In this case, unlike ventilatory respiratory failure, the total minute ventilation volume does not decrease for a long time, and there is even a tendency towards hyperveptilation of the lungs.

It should be emphasized that in the early stages of parenchymatous respiratory failure, hypercapnia does not develop, since pronounced hyperventilation of intact alveoli, accompanied by intensive removal of CO2 _from the body, completely compensates for local disturbances in CO2 exchange _. Moreover, with pronounced hyperventilation of intact alveoli, hypocapnia occurs, which in itself aggravates respiratory disorders.

This is primarily due to the fact that hypocapnia reduces the body's adaptation to hypoxia. As is known, a decrease in PaCO2 in the blood shifts the hemoglobin dissociation curve to the left, which increases the affinity of hemoglobin to oxygen and reduces the release of O2 _in peripheral tissues. Thus, hypocapnia occurring at the initial stages of parenchymatous respiratory failure additionally increases oxygen starvation of peripheral organs and tissues.

In addition, a decrease in PaCO2 _reduces afferent impulses from the receptors of the carotid sinus and medulla oblongata and decreases the activity of the respiratory center.

Finally, hypocapnia alters the ratio of bicarbonate to carbon dioxide in the blood, leading to an increase in HCO3/H2CO3 and pH and the development of respiratory alkalosis (in which blood vessels spasm and blood supply to vital organs deteriorates).

It should be added that in the late stages of development of parenchymatous respiratory failure, not only blood oxygenation is impaired, but also ventilation of the lungs (for example, due to fatigue of the respiratory muscles or increased rigidity of the lungs due to inflammatory edema), and hypercapnia occurs, reflecting the formation of a mixed form of respiratory failure, combining the signs of parenchymatous and ventilatory respiratory failure.

Most often, parenchymatous respiratory failure and critical reduction in ventilation-perfusion ratio develop in lung diseases accompanied by local (uneven) hypoventilation of the alveoli. There are many such diseases:

• chronic obstructive pulmonary diseases (chronic obstructive bronchitis, bronchiolitis, bronchial asthma, cystic fibrosis, etc.);
• central lung cancer;
• pneumonia;
• pulmonary tuberculosis, etc.

In all of the above diseases, there is, to varying degrees, obstruction of the airways caused by uneven inflammatory infiltration and severe edema of the bronchial mucosa (bronchitis, bronchiolitis), an increase in the amount of viscous secretion (sputum) in the bronchi (bronchitis, bronchiolitis, bronchiectasis, pneumonia, etc.), spasm of the smooth muscles of the small bronchi (bronchial asthma), early expiratory closure (collapse) of the small bronchi (most pronounced in patients with pulmonary emphysema), deformation and compression of the bronchi by a tumor, foreign body, etc. Therefore, it is advisable to distinguish a special - obstructive - type of respiratory failure caused by impaired air passage through large and / or small airways, which in most cases is considered within the framework of parenchymatous respiratory failure. At the same time, with severe obstruction of the airways, in a number of cases pulmonary ventilation and MV are significantly reduced, and ventilation (or more precisely, mixed) respiratory failure develops.

Increase in alveolar dead space. Another variant of change in ventilation-perfusion relations is associated with local disturbance of pulmonary blood flow, for example, with thrombosis or embolism of the pulmonary artery branches. In this case, despite the preservation of normal ventilation of the alveoli, perfusion of a limited area of lung tissue decreases sharply (V / Q > 1.0) or is absent altogether. The effect of a sudden increase in the functional dead space occurs, and if its volume is large enough, hypoxemia develops. In this case, a compensatory increase in the concentration of CO2 in the air exhaled from normally perfused alveoli occurs, which usually completely levels out the disturbance of carbon dioxide exchange in non-perfused alveoli. In other words, this variant of parenchymatous respiratory failure is also not accompanied by an increase in the partial pressure of CO2 _in arterial blood.

Parenchymatous respiratory failure by the mechanism of increase in alveolar dead space and V/Q values most often develops in the following diseases:

1. Thromboembolism of the pulmonary artery branches.
2. Adult respiratory distress syndrome.

Reduction of the functioning surface of the alveolar-capillary membrane

In pulmonary emphysema, interstitial pulmonary fibrosis, compression atelectasis and other diseases, blood oxygenation may decrease due to a decrease in the total functioning surface of the alveolar-capillary membrane. In these cases, as in other variants of parenchymatous respiratory failure, changes in the blood gas composition are primarily manifested by arterial hypoxemia. At later stages of the disease, for example, with fatigue and atrophy of the respiratory muscles, hypercapnia may develop.

Gas diffusion disorders

The diffusion coefficient of oxygen is relatively low, its diffusion is impaired in many lung diseases accompanied by inflammatory or hemodynamic edema of the interstitial tissue and an increase in the distance between the inner surface of the alveoli and the capillary (pneumonia, interstitial lung diseases, pneumosclerosis, hemodynamic pulmonary edema in left ventricular heart failure, etc.). In most cases, impaired blood oxygenation in the lungs is caused by other pathophysiological mechanisms of respiratory failure (for example, a decrease in ventilation-perfusion relations), and a decrease in the rate of diffusion of O ₂ only aggravates it.

Since the diffusion rate of CO2 _is 20 times higher than O2 _, the transfer of carbon dioxide through the alveolar-capillary membrane can be impaired only if it is significantly thickened or if there is widespread damage to the lung tissue. Therefore, in most cases, the impairment of the diffusion capacity of the lungs only increases hypoxemia.

• Parenchymatous (hypoxemic) respiratory failure is in most cases characterized by:
  • uneven local alveolar hypoventilation without a decrease in the overall MV rate,
  • severe hypoxemia,
  • at the initial stage of the development of respiratory failure - hyperventilation of intact alveoli, accompanied by hypocapnia and respiratory alkalosis,
  • at later stages of the development of respiratory failure - the addition of ventilation disorders, accompanied by hypercapnia and respiratory or metabolic acidosis (stage of mixed respiratory failure).
• The main mechanisms of development of the parenchymatous (hypoxemic) form of respiratory failure:
  • violation of ventilation-perfusion relationships in obstructive type of respiratory failure or damage to the capillary bed of the lungs,
  • reduction of the total functioning surface of the alveolar-capillary membrane,
  • violation of gas diffusion.

Distinguishing between the two forms of respiratory failure (ventilatory and parenchymatous) is of great practical importance. In the treatment of the ventilatory form of respiratory failure, respiratory support is most effective, allowing the restoration of the reduced minute respiratory volume. On the contrary, in the parenchymatous form of respiratory failure, hypoxemia is caused by a violation of the ventilation-perfusion relationship (for example, the formation of venous "shunting" of the blood), therefore, oxygen inhalation therapy, even in high concentrations (high FiO2), is ineffective. Artificial increase in the MV (for example, with the help of artificial ventilation) is also of little help. Stable improvement in parenchymatous respiratory failure can be achieved only by adequate correction of the ventilation-perfusion relationship and the elimination of some other mechanisms of development of this form of respiratory failure.

Clinical and instrumental verification of obstructive and restrictive types of respiratory failure is also of practical importance, since it allows choosing the optimal tactics for managing patients with respiratory failure.

In clinical practice, a mixed variant of respiratory failure is often encountered, accompanied by both impaired blood oxygenation (hypoxemia) and total alveolar hypoventilation (hypercapnia and hypoxemia). For example, in severe pneumonia, ventilation-perfusion relationships are disrupted and an alveolar shunt is formed, so PaO2 decreases and hypoxemia develops. Massive inflammatory infiltration of lung tissue is often accompanied by a significant increase in lung rigidity, as a result of which alveolar ventilation and the rate of "washing out" of carbon dioxide decrease, and hypercapnia develops.

Progressive ventilation impairment and the development of hypercapnia are also facilitated by severe fatigue of the respiratory muscles and limitation of the volume of respiratory movements when pleural pain appears.

On the other hand, in some restrictive diseases accompanied by ventilatory respiratory failure and hypercapnia, sooner or later bronchial patency disorders develop, ventilation-perfusion ratios decrease, and a parenchymatous component of respiratory failure, accompanied by hypoxemia, joins in. Nevertheless, in any case, it is important to assess the predominant mechanisms of respiratory failure.

Acid-base imbalances

Various forms of respiratory failure may be accompanied by acid-base imbalance, which is more typical for patients with acute respiratory failure, including that developed against the background of chronic respiratory failure that has been going on for a long time. It is in these cases that decompensated respiratory or metabolic acidosis or respiratory alkalosis most often develop, significantly worsening respiratory failure and contributing to the development of severe complications.

Mechanisms for maintaining acid-base balance

The acid-base balance is the ratio of the concentrations of hydrogen (H ⁺ ) and hydroxyl (OH ^- ) ions in the internal environment of the body. The acidic or alkaline reaction of a solution depends on the content of hydrogen ions in it, an indicator of this content is the pH value, which is the negative decimal logarithm of the molar concentration of H ⁺ ions:

PH = - [H ⁺ ].

This means, for example, that at pH = 7.4 (neutral reaction of the environment) the concentration of H ⁺ ions, i.e. [H ⁺ ], is equal to 10 ^-7.4 mmol/l. With an increase in the acidity of the biological environment, its pH decreases, and with a decrease in acidity, it increases.

The pH value is one of the most "rigid" blood parameters. Its fluctuations are normally extremely insignificant: from 7.35 to 7.45. Even small deviations of pH from the normal level towards a decrease (acidosis) or an increase (alkalosis) lead to a significant change in oxidation-reduction processes, enzyme activity, permeability of cell membranes, and other disorders fraught with dangerous consequences for the vital activity of the organism.

The concentration of hydrogen ions is determined almost entirely by the ratio of bicarbonate to carbon dioxide:

HCO3 ^- / H ₂ CO ₃

The content of these substances in the blood is closely related to the process of transfer of carbon dioxide (CO2 ₎ from tissues to the lungs. Physically dissolved CO2 _{diffuses from tissues into the erythrocyte, where, under the influence of the enzyme carbonic anhydrase, the molecule (CO2)} is hydrated to form carbonic acid H2CO3 _, which immediately dissociates to form hydrogen bicarbonate (HCO3-) ions ⁽ H ⁺ ):

CO ₂ + H ₂ O ↔ H ₂ CO ₃ ↔ NCO ^3- + H ⁺

^{Part of the HCO 3-} ions accumulating in erythrocytes, according to the concentration gradient, goes into the plasma. In this case, in exchange for the HCO ^{3- ion, chlorine (Cl-} ) enters the erythrocyte, due to which the equilibrium distribution of electrical charges is disrupted.

The H ⁺ ions formed by the dissociation of carbon dioxide are attached to the myoglobin molecule. Finally, some of the CO2 _can be bound by direct attachment to the amino groups of the protein component of hemoglobin to form a carbamic acid residue (NHCOOH). Thus, in the blood flowing away from the tissues, 27% of the CO2 is carried as bicarbonate (HCO3- ⁾ in the erythrocytes, 11% of the CO2 _forms a carbamic compound with hemoglobin (carbohemoglobin), about 12% of the CO2 _remains in dissolved form or in the form of undissociated carbonic acid (H2CO3), and the remaining amount of CO2 ₍ about 50%) is dissolved as HCO3- ⁱⁿ the plasma.

Normally, the concentration of bicarbonate (HCO ^3- ) in blood plasma is 20 times higher than carbon dioxide (H2CO3). It is at this ratio of HCO ^3- and H2CO3 that the normal pH of 7.4 is maintained. If the concentration of bicarbonate or carbon dioxide changes, their ratio changes, and the pH shifts to the acidic (acidosis) or alkaline (alkalosis) side. Under these conditions, normalization of pH requires the activation of a number of compensatory regulatory mechanisms that restore the previous ratio of acids and bases in the blood plasma, as well as in various organs and tissues. The most important of these regulatory mechanisms are:

1. Buffer systems of blood and tissues.
2. Changes in lung ventilation.
3. Mechanisms of renal regulation of acid-base balance.

Buffer systems of blood and tissues consist of an acid and a conjugate base.

When interacting with acids, the latter are neutralized by the alkaline component of the buffer; when in contact with bases, their excess binds with the acidic component.

The bicarbonate buffer has an alkaline reaction and consists of weak carbonic acid (H2CO3) and its sodium salt - sodium bicarbonate (NaHCO3) as a conjugate base. When interacting with acid, the alkaline component of the bicarbonate buffer (TaHCO3) neutralizes it to form H2CO3, which dissociates into CO2 _and H2O _. The excess is removed with exhaled air. When interacting with bases, the acidic component of the buffer (H2CO3) binds with excess bases to form bicarbonate (HCO3- ⁾, which is then excreted by the kidneys.

The phosphate buffer consists of monobasic sodium phosphate (NaH2PO4), which acts as an acid, and dibasic sodium phosphite (NaH2PO4), which acts as a conjugate base. The principle of action of this buffer is the same as that of the bicarbonate buffer, but its buffering capacity is small because the phosphate content in the blood is low.

Protein buffer. The buffer properties of plasma proteins (albumin, etc.) and erythrocyte hemoglobin are related to the fact that the amino acids they contain contain both acidic (COOH) and basic (NH ₂ ) groups and can dissociate to form both hydrogen and hydroxyl ions depending on the reaction of the medium. Hemoglobin accounts for most of the buffer capacity of the protein system. In the physiological pH range, oxyhemoglobin is a stronger acid than deoxyhemoglobin (reduced hemoglobin). Therefore, by releasing oxygen in the tissues, reduced hemoglobin acquires a higher ability to bind H ⁺ ions. When absorbing oxygen in the lungs, hemoglobin acquires acidic properties.

The buffering properties of blood are essentially determined by the combined effect of all anionic groups of weak acids, the most important of which are bicarbonates and anionic groups of proteins ("proteinates"). These anions, which have buffering effects, are called buffer bases (BB).

The total concentration of buffer bases in the blood is about <18 mmol/l and does not depend on changes in CO2 pressure _in the blood. Indeed, with an increase in CO2 pressure _in the blood, equal amounts of H ⁺ and HCO ^3- are formed. Proteins bind H ⁺ ions, which leads to a decrease in the concentration of "free" proteins with buffer properties. At the same time, the bicarbonate content increases by the same amount, and the total concentration of buffer bases remains the same. Conversely, with a decrease in CO2 pressure in the blood, the proteinate content increases and the bicarbonate concentration decreases.

If the content of non-volatile acids in the blood changes (lactic acid in hypoxia, acetoacetic and beta-hydroxybutyric acid in diabetes mellitus, etc.), the total concentration of buffer bases will differ from normal.

Deviation of the buffer base content from the normal level (48 mmol/l) is called base excess (BE); normally it is zero. With a pathological increase in the number of buffer bases, BE becomes positive, and with a decrease, it becomes negative. In the latter case, it is more correct to use the term "base deficit".

The BE indicator thus allows us to judge shifts in the “reserves” of buffer bases when the content of non-volatile acids in the blood changes, and to diagnose even hidden (compensated) shifts in the acid-base balance.

Changes in pulmonary ventilation are the second regulatory mechanism that ensures the constancy of blood plasma pH. When blood passes through the lungs, reactions occur in erythrocytes and blood plasma that are the opposite of those described above:

H ⁺ + HCO ^3- H2CO3 ↔ CO2+ H2O.

This means that when CO2 is removed from the blood, _an approximately equivalent number of H ⁺ ions disappears from it. Consequently, respiration plays an extremely important role in maintaining the acid-base balance. Thus, if, as a result of metabolic disorders in tissues, blood acidity increases and a state of moderate metabolic (non-respiratory) acidosis develops, the intensity of pulmonary ventilation (hyperventilation) increases reflexively (the respiratory center). As a result, a large amount of CO2 and, accordingly, hydrogen ions (H ⁺ ) are removed, due to which the pH returns to the original level. Conversely, an increase in the base content (metabolic non-respiratory alkalosis) is accompanied by a decrease in the intensity of ventilation (hypoventilation), the CO2 pressure _and the concentration of H ⁺ ions increase, and the shift in pH towards the alkaline side is compensated.

The role of the kidneys. The third regulator of the acid-base balance are the kidneys, which remove H ⁺ ions from the body and reabsorb sodium bicarbonate (NaHCO3). These important processes are carried out mainly in the renal tubules. Three main mechanisms are used:

Exchange of hydrogen ions for sodium ions. This process is based on the reaction activated by carbonic anhydrase: CO ₂ + H ₂ O = H ₂ CO ₃; the resulting carbon dioxide (H2CO3) dissociates into H ⁺ and HCO ^{3- ions. The ions are released into the lumen of the tubules, and an equivalent amount of sodium ions (Na+} ) enters from the tubular fluid in their place. As a result, the body is freed from hydrogen ions and at the same time replenishes its reserves of sodium bicarbonate (NaHCO3), which is reabsorbed into the interstitial tissue of the kidney and enters the blood.

^{Acidogenesis. The exchange of H +} ions for Na ⁺ ions occurs in a similar manner with the participation of dibasic phosphate. Hydrogen ions released into the lumen of the tubule are bound by the HPO4 ^2- anion to form monobasic sodium phosphate (NaH2PO4). At the same time, an equivalent amount of Na ⁺ ions enters the epithelial cell of the tubule and binds with the HCO3- ion ^to form Na ⁺ bicarbonate (NaHCO3). The latter is reabsorbed and enters the general bloodstream.

Ammoniagenesis occurs in the distal renal tubules, where ammonia is formed from glutamine and other amino acids. The latter neutralizes urinary HCl and binds hydrogen ions to form Na ⁺ and Cl ^-. Reabsorbed sodium in combination with the HCO ^3- ion also forms sodium bicarbonate (NaHCO3).

Thus, in the tubular fluid, most of the H ⁺ ions coming from the tubular epithelium are bound to HCO ^3-, HPO4 ^2- ions and excreted in the urine. At the same time, an equivalent amount of sodium ions enters the tubular cells to form sodium bicarbonate (NaHCO3), which is reabsorbed in the tubules and replenishes the alkaline component of the bicarbonate buffer.

Main indicators of acid-base balance

In clinical practice, the following arterial blood parameters are used to assess the acid-base balance:

1. Blood pH is the negative decimal logarithm of the molar concentration of H ⁺ ions. Arterial blood (plasma) pH at 37 C fluctuates within narrow limits (7.35-7.45). Normal pH values do not yet mean the absence of acid-base imbalances and can be encountered in so-called compensated variants of acidosis and alkalosis.
2. PaCO2 is the partial pressure of CO2 _in arterial blood. Normal values of PaCO2 _are35-45 mm Hg in men and 32-43 mm Hg in women.
3. Buffer bases (BB) are the sum of all blood anions with buffering properties (mainly bicarbonates and protein ions). The normal BB value is on average 48.6 mol/l (from 43.7 to 53.5 mmol/l).
4. Standard bicarbonate (SB) is the content of bicarbonate ion in plasma. Normal values for men are 22.5-26.9 mmol/l, for women - 21.8-26.2 mmol/l. This indicator does not reflect the buffering effect of proteins.
5. Base excess (BE) is the difference between the actual value of the buffer base content and their normal value (the normal value is from - 2.5 to + 2.5 mmol/l). In capillary blood, the values of this indicator are from -2.7 to +2.5 in men and from -3.4 to +1.4 in women.

In clinical practice, 3 indicators of acid-base balance are usually used: pH, PaCO2 _and BE.

Changes in acid-base balance in respiratory failure

In many pathological conditions, including respiratory failure, such a large amount of acids or bases can accumulate in the blood that the regulatory mechanisms described above (buffer systems of the blood, respiratory and excretory systems) can no longer maintain pH at a constant level, and acidosis or alkalosis develops.

1. Acidosis is a disturbance of the acid-base balance in which an absolute or relative excess of acids appears in the blood and the concentration of hydrogen ions increases (pH < 7.35).
2. Alkalosis is characterized by an absolute or relative increase in the number of bases and a decrease in the concentration of hydrogen ions (pH > 7.45).

According to the mechanisms of occurrence, there are 4 types of acid-base balance disorders, each of which can be compensated and decompensated:

1. respiratory acidosis;
2. respiratory alkalosis;
3. non-respiratory (metabolic) acidosis;
4. non-respiratory (metabolic) alkalosis.

Aspiratory acidosis

Respiratory acidosis develops with severe total disturbances of pulmonary ventilation (alveolar hypoventilation). The basis of these changes in the acid-base balance is an increase in the partial pressure of CO ₂ in arterial blood PaCO ₂ ).

In compensated respiratory acidosis, the blood pH does not change due to the action of the compensatory mechanisms described above. The most important of these are the 6-carbonate and protein (hemoglobin) buffer, as well as the renal mechanism for the release of H ⁺ ions and the retention of sodium bicarbonate (NaHCO3).

In the case of hypercapnic (ventilation) respiratory failure, the mechanism of increased pulmonary ventilation (hyperventilation) and removal of H ⁺ and CO2 ions in respiratory acidosis has no practical significance, since such patients by definition have primary pulmonary hypoventilation caused by severe pulmonary or extrapulmonary pathology. It is accompanied by a significant increase in the partial pressure of CO2 in the blood - hypercapia. Due to the effective action of buffer systems and, especially, as a result of the inclusion of the renal compensatory mechanism of sodium bicarbonate retention, patients have an increased content of standard bicarbonate (SB) and excess bases (BE).

Thus, compensated respiratory acidosis is characterized by:

1. Normal blood pH values.
2. Increase in partial pressure of CO2 _in the blood (PaCO2 ₎.
3. Increase in standard bicarbonate (SB).
4. Increase in base excess (BE).

Depletion and insufficiency of compensation mechanisms leads to the development of decompensated respiratory acidosis, in which the plasma pH decreases below 7.35. In some cases, the levels of standard bicarbonate (SB) and base excess (BE) also decrease to normal values, indicating depletion of the base reserve.

Respiratory alkalosis

It was shown above that parenchymatous respiratory failure in some cases is accompanied by hypocapnia caused by pronounced compensatory hyperventilation of intact alveoli. In these cases, respiratory alkalosis develops as a result of increased removal of carbon dioxide due to hyperventilation-type external respiration disorder. As a result, the HCO3 ^- / H2CO3 ratio increases and, accordingly, blood pH increases.

Compensation for respiratory alkalosis is possible only against the background of chronic respiratory failure. Its main mechanism is a decrease in the secretion of hydrogen ions and inhibition of bicarbonate reabsorption in the renal tubules. This leads to a compensatory decrease in standard bicarbonate (SB) and to a base deficit (negative BE value).

Thus, compensated respiratory alkalosis is characterized by:

1. Normal blood pH value.
2. Significant decrease in pCO2 in the blood.
3. Compensatory decrease in standard bicarbonate (SB).
4. Compensatory base deficiency (negative BE value).

With decompensation of respiratory alkalosis, blood pH increases, and previously decreased SB and BE values can reach normal values.

Non-respiratory (metabolic) acidosis

Non-respiratory (metabolic) acidosis is the most severe form of acid-base imbalance, which can develop in patients with very severe respiratory failure, severe blood hypoxemia and organ and tissue hypoxia. The mechanism of non-respiratory (metabolic) acidosis development in this case is associated with the accumulation of so-called non-volatile acids (lactic acid, beta-hydroxybutyric, acetoacetic, etc.) in the blood. Let us recall that in addition to severe respiratory failure, non-respiratory (metabolic) acidosis can be caused by:

1. Severe disturbances of tissue metabolism in decompensated diabetes mellitus, prolonged starvation, thyrotoxicosis, fever, organ hypoxia against the background of severe heart failure, etc.
2. Kidney diseases accompanied by predominant damage to the renal tubules, leading to impaired excretion of hydrogen ions and reabsorption of sodium bicarbonate (renal tubular acidosis, renal failure, etc.)
3. Loss of large amounts of bases in the form of bicarbonates with digestive juices (diarrhea, vomiting, pyloric stenosis, surgical interventions). Taking certain medications (ammonium chloride, calcium chloride, salicylates, carbonic anhydrase inhibitors, etc.).

In compensated non-respiratory (metabolic) acidosis, the bicarbonate buffer of the blood is included in the compensation process, which binds acids accumulating in the body. A decrease in the sodium bicarbonate content leads to a relative increase in the concentration of carbonic acid (H2CO3), which dissociates into H2O and CO2. H ^{+ ions bind to proteins, primarily hemoglobin, due to which Na+}, Ca ²⁺ and K ⁺ leave the erythrocytes in exchange for the hydrogen cations entering them.

Thus, compensated metabolic acidosis is characterized by:

1. Normal blood pH level.
2. Decreased standard bicarbonates (SB).
3. Deficiency of buffer bases (negative BE value).

Depletion and insufficiency of the described compensatory mechanisms lead to the development of decompensated non-respiratory (metabolic) acidosis, in which the blood pH decreases to a level of less than 7.35.

Non-respiratory (metabolic) alkalosis

Non-respiratory (metabolic) alkalosis is not typical in respiratory failure.

Other complications of respiratory failure

Changes in the gas composition of the blood, acid-base balance, as well as disturbances in pulmonary hemodynamics in severe cases of respiratory failure lead to severe complications in other organs and systems, including the brain, heart, kidneys, gastrointestinal tract, vascular system, etc.

Acute respiratory failure is more characterized by relatively rapidly developing severe systemic complications, mainly caused by severe hypoxia of organs and tissues, leading to disturbances in their metabolic processes and functions. The occurrence of multiple organ failure against the background of acute respiratory failure significantly increases the risk of an unfavorable outcome of the disease. Below is a far from complete list of systemic complications of respiratory failure:

1. Cardiac and vascular complications:
   • myocardial ischemia;
   • cardiac arrhythmia;
   • decreased stroke volume and cardiac output;
   • arterial hypotension;
   • deep vein thrombosis;
   • TELA.
2. Neuromuscular complications:
   • stupor, sopor, coma;
   • psychosis;
   • delirium;
   • critical illness polyneuropathy;
   • contractures;
   • muscle weakness.
3. Infectious complications:
   • sepsis;
   • abscess;
   • nosocomial pneumonia;
   • bedsores;
   • other infections.
4. Gastrointestinal complications:
   • acute gastric ulcer;
   • gastrointestinal bleeding;
   • liver damage;
   • malnutrition;
   • complications of enteral and parenteral nutrition;
   • acalculous cholecystitis.
5. Kidney complications:
   • acute renal failure;
   • electrolyte disturbances, etc.

It is also necessary to take into account the possibility of developing complications associated with the presence of an intubation tube in the lumen of the trachea, as well as with the implementation of artificial ventilation.

In chronic respiratory failure, the severity of systemic complications is significantly less than in acute failure, and the development of 1) pulmonary arterial hypertension and 2) chronic pulmonary heart disease comes to the fore.

Pulmonary arterial hypertension in patients with chronic respiratory failure is formed under the action of several pathogenetic mechanisms, the main one of which is chronic alveolar hypoxia, leading to the development of hypoxic pulmonary vasoconstriction. This mechanism is known as the Euler-Liljestraid reflex. As a result of this reflex, local pulmonary blood flow adapts to the level of intensity of pulmonary ventilation, so the ventilation-perfusion relationship is not disrupted or becomes less pronounced. However, if alveolar hypoventilation is expressed to a large extent and spreads to large areas of lung tissue, a generalized increase in the tone of the pulmonary arterioles develops, leading to an increase in total pulmonary vascular resistance and the development of pulmonary arterial hypertension.

The formation of hypoxic pulmonary vasoconstriction is also facilitated by hypercapnia, impaired bronchial patency and endothelial dysfunction. Anatomical changes in the pulmonary vascular bed play a special role in the development of pulmonary arterial hypertension: compression and desolation of arterioles and capillaries due to gradually progressing fibrosis of the lung tissue and pulmonary emphysema, thickening of the vascular wall due to hypertrophy of the muscle cells of the media, the development of microthrombosis in conditions of chronic blood flow disorders and increased platelet aggregation, recurrent thromboembolism of small branches of the pulmonary artery, etc.

Chronic pulmonary heart disease develops naturally in all cases of long-term lung diseases, chronic respiratory failure, and progressive pulmonary arterial hypertension. However, according to modern concepts, the long-term process of chronic pulmonary heart disease formation includes the occurrence of a number of structural and functional changes in the right heart chambers, the most significant of which are myocardial hypertrophy of the right ventricle and atrium, expansion of their cavities, cardiac fibrosis, diastolic and systolic dysfunction of the right ventricle, formation of relative tricuspid valve insufficiency, increased central venous pressure, and congestion in the venous bed of the systemic circulation. These changes are due to the formation of pulmonary pulmonary hypertension in chronic respiratory failure, persistent or transient increase in afterload on the right ventricle, increased intramyocardial pressure, as well as activation of tissue neurohormonal systems, release of cytokines, and development of endothelial dysfunction.

Depending on the absence or presence of signs of right ventricular heart failure, compensated and decompensated chronic pulmonary heart disease are distinguished.

Acute respiratory failure is most characterized by the occurrence of systemic complications (cardiac, vascular, renal, neurological, gastrointestinal, etc.), which significantly increase the risk of an unfavorable outcome of the disease. Chronic respiratory failure is more characterized by the gradual development of pulmonary hypertension and chronic pulmonary heart disease.

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