Fundamentals of respiratory physiology

The main (though not the only) function of the lungs is to ensure normal gas exchange. External respiration is the process of gas exchange between atmospheric air and blood in the pulmonary capillaries, which results in arterialization of the blood composition: oxygen pressure increases and CO2 pressure decreases. The intensity of gas exchange is primarily determined by three pathophysiological mechanisms (pulmonary ventilation, pulmonary blood flow, diffusion of gases through the alveolar-capillary membrane), which are provided by the external respiration system.

Pulmonary ventilation

Pulmonary ventilation is determined by the following factors (A.P. Zilber):

1. mechanical ventilation apparatus, which primarily depends on the activity of the respiratory muscles, their nervous regulation and the mobility of the chest walls;
2. elasticity and distensibility of the lung tissue and chest;
3. airway patency;
4. intrapulmonary distribution of air and its correspondence to blood flow in different parts of the lung.

When one or more of the above factors are disrupted, clinically significant ventilation disorders may develop, manifested by several types of ventilatory respiratory failure.

Of the respiratory muscles, the most significant role belongs to the diaphragm. Its active contraction leads to a decrease in intrathoracic and intrapleural pressure, which becomes lower than atmospheric pressure, resulting in inhalation.

Inhalation is accomplished through active contraction of the respiratory muscles (diaphragm), and exhalation occurs mainly due to the elastic pull of the lung itself and the chest wall, creating an expiratory pressure gradient, which under physiological conditions is sufficient to expel air through the airways.

When it is necessary to increase the volume of ventilation, the external intercostal, scalene and sternocleidomastoid muscles (additional inspiratory muscles) contract, which also leads to an increase in the volume of the chest and a decrease in intrathoracic pressure, which facilitates inhalation. Additional expiratory muscles are considered to be the muscles of the anterior abdominal wall (external and internal oblique, straight and transverse).

Elasticity of lung tissue and chest wall

Elasticity of the lungs. The movement of air flow during inhalation (into the lungs) and exhalation (out of the lungs) is determined by the pressure gradient between the atmosphere and the alveoli, the so-called transthoracic pressure (P _tr / _t ):

Рtr/t = Рalv _- Рatm _where Рalv _is alveolar pressure and Рatm _is atmospheric pressure.

During inhalation, P _alv and P _tr/t become negative, during exhalation, they become positive. At the end of inhalation and at the end of exhalation, when the air does not move along the airways and the glottis is open, P _alv equals P _atm.

The level of P _alv in turn depends on the value of intrapleural pressure (P _pl ) and the so-called elastic recoil pressure of the lung (P _el ):

Elastic recoil pressure is the pressure created by the elastic parenchyma of the lung and directed into the lung. The higher the elasticity of the lung tissue, the greater the decrease in intrapleural pressure must be for the lung to expand during inspiration, and, consequently, the greater the active work of the inspiratory respiratory muscles must be. High elasticity promotes faster collapse of the lung during expiration.

Another important indicator, the inverse of the elasticity of the lung tissue - apathetic lung compliance - is a measure of the lung's compliance when it is straightened. The compliance (and the magnitude of the elastic recoil pressure) of the lung is influenced by many factors:

1. Lung volume: at low volume (e.g. at the beginning of inspiration) the lung is more flexible. At high volume (e.g. at the height of maximum inspiration) the lung compliance decreases sharply and becomes zero.
2. Content of elastic structures (elastin and collagen) in lung tissue. Emphysema of the lungs, which is known to be characterized by a decrease in the elasticity of lung tissue, is accompanied by an increase in lung extensibility (a decrease in elastic recoil pressure).
3. Thickening of the alveolar walls due to their inflammatory (pneumonia) or hemodynamic (blood stagnation in the lung) edema, as well as fibrosis of the lung tissue significantly reduce the extensibility (compliance) of the lung.
4. Surface tension forces in the alveoli. They arise at the interface between gas and liquid, which lines the alveoli from the inside with a thin film, and tend to reduce the area of this surface, creating positive pressure inside the alveoli. Thus, surface tension forces, together with the elastic structures of the lungs, ensure effective collapse of the alveoli during exhalation and at the same time prevent the straightening (stretching) of the lung during inhalation.

The surfactant lining the inner surface of the alveoli is a substance that reduces surface tension.

The higher the surfactant's activity, the denser it is. Therefore, during inhalation, when the density and, accordingly, the activity of the surfactant decreases, the forces of surface tension (i.e., the forces that tend to reduce the surface of the alveoli) increase, which contributes to the subsequent collapse of the lung tissue during exhalation. At the end of exhalation, the density and activity of the surfactant increase, and the forces of surface tension decrease.

Thus, after the end of exhalation, when the activity of the surfactant is maximum and the surface tension forces that prevent the straightening of the alveoli are minimal, the subsequent straightening of the alveoli during inhalation requires less energy expenditure.

The most important physiological functions of surfactant are:

• increased lung compliance due to a decrease in surface tension forces;
• reducing the likelihood of collapse of the alveoli during exhalation, since at low lung volumes (at the end of exhalation) its activity is maximum, and the forces of surface tension are minimal;
• preventing the redistribution of air from smaller to larger alveoli (according to Laplace's law).

In diseases accompanied by surfactant deficiency, lung rigidity increases, the alveoli collapse (atelectasis develops), and respiratory failure occurs.

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Plastic recoil of the chest wall

The elastic properties of the chest wall, which also have a great influence on the nature of pulmonary ventilation, are determined by the state of the skeletal system, intercostal muscles, soft tissues, and parietal pleura.

At minimum chest and lung volumes (during maximum exhalation) and at the beginning of inhalation, the elastic recoil of the chest wall is directed outward, which creates negative pressure and promotes lung expansion. As the lung volume increases during inhalation, the elastic recoil of the chest wall decreases. When the lung volume reaches approximately 60% of the VC value, the elastic recoil of the chest wall decreases to zero, i.e. to the level of atmospheric pressure. With a further increase in lung volume, the elastic recoil of the chest wall is directed inward, which creates positive pressure and promotes lung collapse during subsequent exhalation.

Some diseases are accompanied by increased rigidity of the chest wall, which affects the ability of the chest to stretch (during inhalation) and collapse (during exhalation). Such diseases include obesity, kyphoscoliosis, pulmonary emphysema, massive adhesions, fibrothorax, etc.

Airway patency and mucociliary clearance

The patency of the airways largely depends on the normal drainage of tracheobronchial secretions, which is ensured, first of all, by the functioning of the mucociliary clearance mechanism and a normal cough reflex.

The protective function of the mucociliary apparatus is determined by the adequate and coordinated function of the ciliated and secretory epithelium, as a result of which a thin film of secretion moves along the surface of the bronchial mucosa and foreign particles are removed. The movement of bronchial secretion occurs due to rapid impulses of cilia in the cranial direction with a slower return in the opposite direction. The frequency of cilia oscillations is 1000-1200 per minute, which ensures the movement of bronchial mucus at a speed of 0.3-1.0 cm / min in the bronchi and 2-3 cm / min in the trachea.

It should also be remembered that bronchial mucus consists of 2 layers: the lower liquid layer (sol) and the upper viscous-elastic gel, which is touched by the tips of the cilia. The function of the ciliated epithelium largely depends on the ratio of the thickness of the yule and gel: an increase in the thickness of the gel or a decrease in the thickness of the sol lead to a decrease in the effectiveness of mucociliary clearance.

At the level of the respiratory bronchioles and alveoli of the mucociliary apparatus ist. Here, cleansing is carried out with the help of the cough reflex and phagocytic activity of cells.

In case of inflammatory damage to the bronchi, especially chronic, the epithelium is morphologically and functionally rebuilt, which can lead to mucociliary insufficiency (a decrease in the protective functions of the mucociliary apparatus) and the accumulation of sputum in the lumen of the bronchi.

Under pathological conditions, the patency of the airways depends not only on the functioning of the mucociliary clearance mechanism, but also on the presence of bronchospasm, inflammatory edema of the mucous membrane and the phenomenon of early expiratory closure (collapse) of the small bronchi.

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Regulation of bronchial lumen

The tone of the smooth muscles of the bronchi is determined by several mechanisms associated with the stimulation of numerous specific receptors of the bronchi:

1. Cholinergic (parasympathetic) effects occur as a result of the interaction of the neurotransmitter acetylcholine with specific muscarinic M-cholinergic receptors. As a result of this interaction, bronchospasm develops.
2. Sympathetic innervation of the smooth muscles of the bronchi in humans is expressed to a small degree, in contrast, for example, to the smooth muscles of the vessels and the heart muscle. Sympathetic effects on the bronchi are carried out mainly due to the effect of circulating adrenaline on beta2-adrenoreceptors, which leads to relaxation of the smooth muscles.
3. Smooth muscle tone is also affected by the so-called "non-adrenergic, non-cholinergic" nervous system (NANC), the fibers of which run as part of the vagus nerve and release several specific neurotransmitters that interact with the corresponding receptors of the bronchial smooth muscles. The most important of these are:
   • vasoactive intestinal polypeptide (VIP);
   • substance R.

Stimulation of VIP receptors leads to pronounced relaxation, and beta receptors to contraction of bronchial smooth muscles. It is believed that neurons of the NANH system have the greatest influence on the regulation of the lumen of the airways (K.K. Murray).

In addition, the bronchi contain a large number of receptors that interact with various biologically active substances, including inflammatory mediators - histamine, bradykinin, leukotrienes, prostaglandins, platelet activating factor (PAF), serotonin, adenosine, etc.

The tone of the smooth muscles of the bronchi is regulated by several neurohumoral mechanisms:

1. Bronchial dilation develops with stimulation:
   • beta2-adrenergic receptors adrenaline;
   • VIP receptors (NANH system) by vasoactive intestinal polypeptide.
2. Narrowing of the bronchial lumen occurs when stimulated by:
   • M-cholinergic receptors acetylcholine;
   • receptors for substance P (NANH system);
   • Alpha-adrenergic receptors (for example, with blockade or decreased sensitivity of beta2-adrenergic receptors).

Intrapulmonary air distribution and its correspondence to blood flow

The unevenness of ventilation of the lungs, which exists in the norm, is determined, first of all, by the heterogeneity of the mechanical properties of the lung tissue. The basal parts of the lungs are ventilated most actively, and to a lesser extent, the upper parts of the lungs. A change in the elastic properties of the alveoli (in particular, in pulmonary emphysema) or a violation of bronchial patency significantly aggravate the unevenness of ventilation, increase the physiological dead space and reduce the effectiveness of ventilation.

Diffusion of gases

The process of gas diffusion through the alveolar-capillary membrane depends

1. from the gradient of partial pressure of gases on both sides of the membrane (in the alveolar air and in the pulmonary capillaries);
2. from the thickness of the alveolar-capillary membrane;
3. from the total surface of the diffusion zone in the lung.

In a healthy person, the partial pressure of oxygen (PO2) in the alveolar air is normally 100 mm Hg, and in venous blood - 40 mm Hg. The partial pressure of CO2 (PCO2) in venous blood is 46 mm Hg, in the alveolar air - 40 mm Hg. Thus, the pressure gradient for oxygen is 60 mm Hg, and for carbon dioxide - only 6 mm Hg. However, the rate of diffusion of CO2 through the alveolar-capillary membrane is approximately 20 times greater than O2. Therefore, the exchange of CO2 in the lungs occurs quite completely, despite the relatively low pressure gradient between the alveoli and capillaries.

The alveolar-capillary membrane consists of a surfactant layer lining the inner surface of the alveolus, alveolar membrane, interstitial space, pulmonary capillary membrane, blood plasma and erythrocyte membrane. Damage to each of these components of the alveolar-capillary membrane can lead to significant difficulty in gas diffusion. As a result, in diseases, the above values of partial pressures of O2 and CO2 in the alveolar air and capillaries can change significantly.

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Pulmonary blood flow

There are two circulatory systems in the lungs: the bronchial blood flow, which is part of the systemic circulation, and the pulmonary blood flow itself, or the so-called pulmonary circulation. There are anastomoses between them under both physiological and pathological conditions.

The pulmonary blood flow is functionally located between the right and left halves of the heart. The driving force of the pulmonary blood flow is the pressure gradient between the right ventricle and the left atrium (normally about 8 mm Hg). Oxygen-poor and carbon dioxide-saturated venous blood enters the pulmonary capillaries through the arteries. As a result of gas diffusion in the alveoli, the blood is saturated with oxygen and cleared of carbon dioxide, resulting in arterial blood flowing from the lungs to the left atrium through the veins. In practice, these values can fluctuate significantly. This is especially true for the level of PaO2 in arterial blood, which is usually about 95 mm Hg.

The level of gas exchange in the lungs with normal functioning of the respiratory muscles, good patency of the airways and little change in the elasticity of the lung tissue is determined by the rate of blood perfusion through the lungs and the state of the alveolar-capillary membrane, through which diffusion of gases occurs under the influence of the gradient of partial pressure of oxygen and carbon dioxide.

Ventilation-perfusion relationship

The level of gas exchange in the lungs, in addition to the intensity of pulmonary ventilation and gas diffusion, is also determined by the ventilation-perfusion ratio (V/Q). Normally, with an oxygen concentration in the inhaled air of 21% and normal atmospheric pressure, the V/Q ratio is 0.8.

All other things being equal, a decrease in arterial blood oxygenation can be caused by two reasons:

• a decrease in pulmonary ventilation while maintaining the same level of blood flow, when V/Q < 0.8-1.0;
• decreased blood flow with preserved alveolar ventilation (V/Q > 1.0).