Pathophysiology of the Respiratory System PDF

## PATHOPHYSIOLOGY OF THE RESPIRATORY SYSTEM ### Chapter 20. Pathophysiology of the Respiratory System #### 20.1. Respiratory insufficiency Respiration is a combination of processes that ensure aerobic oxidation in the body and the formation of the energy which is necessary for life. Respiration...

## PATHOPHYSIOLOGY OF THE RESPIRATORY SYSTEM ### Chapter 20. Pathophysiology of the Respiratory System #### 20.1. Respiratory insufficiency Respiration is a combination of processes that ensure aerobic oxidation in the body and the formation of the energy which is necessary for life. Respiration is supported by the functioning of several systems: - external respiration - transport of gases - internal (tissue) respiration The activities of all these systems are closely interconnected by complex regulatory mechanisms. Disturbance of the functions of each of these systems leads to respiratory failure and a change in the gas composition of the body. Respiratory insufficiency is the pathological case in which the respiratory system cannot provide a normal level of oxygen and carbon dioxide in arterial blood. This leads to the development of hypoxia and depletion of the energy reserves of the body. Respiratory failure can develop primarily as a result of disorders in the external respiration or secondarily - in pathologies of the blood, cardiovascular system and other systems. The causes of respiratory insufficiency can be: - obstruction of the airways, decreasing of the respiratory surface of the lungs, thickening of the alveolar-capillary membranes, diseases of the bronchi and lungs, accompanied by impaired lung perfusion. - pathologies not directly associated with the lungs (damage to the respiratory center, impaired innervation of the muscles involved in breathing, thoracodiaphragmatic pathologies, etc.) According to the pathogenesis, hypoxemic and hypercapnic types of respiratory failure are distinguished. The main manifestation of damage to the lung parenchyma, impaired perfusion and alveolar diffusion is *hypoxemia*, whereas the main manifestation of airway obstruction and weakening of ventilation (hypoventilation) is *hypercapnia*. It should be noted that both hypoxemia and hypercapnia in chronic diseases of the respiratory system with a long course develop to a large extent. Hypoxemia and hypercapnia are clinically manifested by such symptoms as dyspnea, cyanosis. In the early stages of respiratory failure the following compensatory reactions develop in the body: breathing accelerates and deepens, ventilation increases (hyperventilation), the heart rate accelerates (tachycardia), blood circulation is also accelerated, and the respiratory muscles begin to work more intensely. However, increasing hypoxemia leads to depletion of the body's energy reserves, limitation of compensatory abilities, disturbance of acid-base balance and the development of hypoxia. In this case, the activity of the central nervous system and the regulation of respiration are disturbed. Breathing becomes superficial and rare, as a result of hypoventilation of the lungs, hypercapnia deepens. Signs of heart failure join the process, dyspnea and cyanosis increase. The accumulation of toxic metabolic products in the body leads to the change in the acid-base balance. In severe cases, paralysis of the respiratory center and death occur. Acute and chronic forms of respiratory failure are distinguished. Acute respiratory failure occurs during an attack of bronchial asthma, pneumothorax, asphyxia, etc., and chronic respiratory failure occurs in pulmonary fibrosis, pneumoconiosis and other pathologies. In acute respiratory failure, the gas composition of the blood changes rapidly (within a few hours or days), the time for the development of compensatory mechanisms is limited. For example, if acute respiratory failure of the hypoxemic type develops, the hyperventilation of the lungs resulting from this leads to respiratory alkalosis. Thus, during hyperventilation, carbon dioxide is rapidly released through the lungs, and the kidneys for a short time cannot compensate disturbances of acid-base balance. And in acute respiratory failure of hypercapnic type, hypoventilation of the lungs for a short time is replaced by the development of respiratory acidosis. In chronic respiratory failure the changes in the gas composition of the blood develop gradually (during months or years). At the same time, there is enough time to mobilize the compensatory capabilities of the body. Hyperventilation of the lungs develops to prevent hypoxemia. Despite the fact that this may lead to hypocapnia, due to the fact that the process develops gradually, the kidneys for a long time can compensate the acid-base balance. The cardiovascular system joins the compensation process: the work of the heart increases, as a result of myocardial hypertrophy, the stroke volume of the heart increases. Hemopoiesis is activated, erythropoiesis and hemoglobin synthesis are accelerated. Gradually, these mechanisms are depleted, compensatory hyperventilation of the lungs cannot prevent hypoxemia, and hypoxia is exacerbated. Anaerobic metabolism is enhanced and metabolic acidosis develops. There are three degrees of respiratory failure. In the first degree of respiratory failure, the partial pressure of oxygen in arterial blood (PaO2) does not decrease below 70 mm Hg (normal PaO2 - 96-98 mm Hg). If the patient is engaged in physical work of mild or moderate severity, then dyspnea develops, however, unlike healthy people, the respiratory rate is restored slowly. In respiratory failure of the second degree, PaO2 is in the range of 70-50 mm Hg. In this case, the body's need for oxygen at rest is ensured by compensatory mechanisms. When patients perform light physical work, dyspnea occurs. In the third degree of respiratory failure, PaO2 is below 50 mmHg. In a patient, even in a state of complete rest, dyspnea and cyanosis of the skin are observed. Hypoxemia cannot be completely compensated, thus, organs and tissues undergo deep hypoxia. #### 20.2. Disturbance of external respiration External respiration includes: - ventilation of the lungs - air exchange between the external environment and the alveoli of the lungs; - alveolar diffusion - the exchange of gases (CO2 and O2) between the alveolar air and blood. #### 20.2.1. Disorders of pulmonary ventilation Spirography, pneumotachography and other methods are used to assess the level of pulmonary ventilation. Below are the main indicators characterizing the pulmonary ventilation: - tidal volume (TV) is the volume of air that enters the lungs (or is removed from them) during normal respiratory movements at rest (normally 500-600 ml). 2/3 of this air is involved in alveolar diffusion, and 1/3 of this air is not involved in alveolar diffusion, is the volume of anatomically dead space; - inspiratory reserve volume (IRV) is the volume of air that enters the respiratory tract during deep inspiration (normally 1500-2000 ml); - expiratory reserve volume (ERV) is the volume of air that is discharged through the respiratory tract during deep exhalation (normally 1500-2000 ml); - residual volume of lungs (RVL) is the volume of air that remains in the airways after maximum exhalation (normal 1000-1500 ml); - vital capacity of lungs (VCL) is the volume of air that can enter the lungs with the deepest breath possible after the deepest exhalation. It is equal to the sum of the previous three indicators (normal 3000-4500 ml); - total capacity of lungs (TCL) is the sum of the indicators of all lung volumes (TCL=TV+IRV+ERV+RVL); - respiratory capacity of lungs (RCL) - this indicator is equal to the sum of the tidal volume and the reserve volume of the inspiration; - functional residual capacity of lungs (FRCL) is the volume of air that remains in the airways after a quiet exhalation. This indicator is equal to the sum of the expiratory reserve volume and residual volume. In addition, dynamic indicators characterizing the intensity of changes in pulmonary ventilation per unit of time, which are determined by clinical studies, are of great importance. - minute volume of respiration (MVR) – this indicator is equal to the product of the respiratory volume to the number of respiratory movements per minute: MVR=TV-RR (normal 6-8 l/min), where TV is the tidal volume, RR is the respiratory rate; - minute alveolar ventilation (MAV) - this indicator is determined by the formula below: MAV=RR (TV-VDS) - maximal ventilation of lungs (MVL) is the volume of air, that enters into the lungs and is removed out during 1 minute, when the lungs are working with the maximal force (norm is 80-200 l/min); - maximal vital capacity of lungs (MVCL) - shows the volume of air that is exhaled during the maximal deepest and longest (at least 6 seconds) exhalation after the maximal deepest inhalation; - forced expiratory volume in the first second (FEV-1s) is the volume of air that is to the exhaled with maximum force (speed) in the first second of exhalation; - Tiffno index is a percentage of the ratio of the volume of the forced expiratory volume in the first second (FEV-1s) to the maximal vital capacity of the lungs (MVCL): Tiffno index= FEV-1s/MVCL x100% Normally, this index is 70% or higher. In obstructive pulmonary diseases, this indicator decreases to 40% (due to a decrease in FEV-1s). In restrictive pulmonary diseases, the determination of the Tiffno index loses its meaning. Because, an even greater decrease in MVCL, the Tiffno index can even increase up to 100%. Disturbance of ventilation in the lungs manifests itself in the form of hyper-, hypoventilation and uneven ventilation. In *alveolar hyperventilation*, the volume of pulmonary ventilation increases. At the same time, breathing accelerates and indicators such as MVR, VCL, MVL increase. These changes can also occur in a healthy person in conditions of increased oxygen demand and disappear at rest. The causes of hyperventilation include any pathological process that causes hypoxemia (a decrease in the oxygen content in the air, anemia, cardiovascular pathology, etc.), an increase in the excitability of the respiratory center (mental illness, neurosis, hysterical reactions, brain tumors, cerebral hemorrhages, intracranial injuries, diabetes mellitus, uremia, the effect of certain drugs, acidosis, etc.), fever, hyperthermia, etc. During decreasing of the respiratory surface of the lungs (pneumonia, pulmonary edema, etc.), hyperventilation can occur as a compensation. In *hyperventilation* hypocapnia and gaseous alkalosis occur. In alkalosis, the dissociation of oxyhemoglobin slows down (the dissociation curve of oxyhemoglobin shifts to the left), tissues cannot absorb oxygen. When compensating for gaseous alkalosis due to the protein system (decreased calcium ionization), *hypocalcemia* develops. Clinical signs that develop during hyperventilation are associated with hypocapnia, alkalosis, and *hypocalcemia*. So, hypocapnia weakens the excitability of the respiratory center and causes spasms of the cerebral vessels. As a result, clinical symptoms such as excitement, insomnia, impaired attention and memory, dizziness, syncope, etc., are observed. As a result of hypocalcemia, the activity of the cardiovascular system is disrupted, arrhythmia, hypotension develops. One of the causes of hypotension is the weakening of the activity of vasomotor centers, which is associated with the spasm of cerebral vessels resulting from hypocapnia. At the same time, patients have numbness of the limbs, paraesthesia. An increase in neuromuscular excitability, convulsions, laryngospasm, as a result of tonic convulsions of the muscles of the hands, a symptom of Trousseau ("obstetrician's hand") appears. In severe cases, respiratory muscle paralysis and death can occur. In *alveolar hypoventilation*, ventilation of the pulmonary alveoli decreases, *hypoxemia*, *hypercapnia* and *gaseous acidosis* develop. Under these conditions, the dissociation of oxyhemoglobin is accelerated (dissociation curve of oxyhemoglobin shifts to the right) and signs of severe hypoxia occur. Alveolar hypoventilation can occur for the following reasons: - Reducing the excitability of the respiratory center. Reducing of the partial pressure of carbon dioxide in arterial blood, alkalosis, increasing blood pressure can cause hypoventilation due to a decrease in the excitability of the respiratory center. In premature infants, hypoventilation is observed due to the underdevelopment of peripheral chemoreceptors and the weakness of exciting afferent influences. Sometimes during severe pain (especially with chest injuries), inhibitory afferent influences increase, and this leads to weakening of ventilation. - Weakening of the respiratory center also occurs with damage to brain tissue (cerebral arteriosclerosis, traumatic brain injuries, swelling and brain tumors, infectious toxic processes), as well as when taking high doses of narcotic and sedative drugs. - Damage to the respiratory muscles and their nerves. Inflammation, autoimmune injuries (for example, *myasthenia gravis*), dystrophic changes (collagenosis, etc.), cramps (tetany, epilepsy, etc.) and traumatic injuries of muscles are involved in breathing lead to the restriction of respiratory movements. Inflammation, paresis and paralysis of the nerves innervating the respiratory muscles (with botulism, tetanus), as well as damage to the spinal cord motor neurons (polio, syringomyelia) also lead to restriction of respiratory movements. Among these pathologies, damage to the diaphragm and phrenic nerve occupies a special place. With paralysis of the phrenic nerve paradoxical breathing occurs. During inhalation, the diaphragm rises up and in exhalation, it goes down, which prevents air from entering and leaving. Sometimes paradoxical breathing is accompanied by an asymmetry in the movements of the right and left halves of the chest. This is called dissociation of breathing (Grocco-Frugoni breathing). - Hypoventilation associated with thoraco-diaphragmatic pathology occurs in diseases accompanied by restriction of movement of the chest and diaphragm. These include congenital defects of the skeletal-cartilaginous apparatus of the chest, rickets, acquired curvature of the spine (kyphosis, lordosis, and scoliosis), arthritis and spondylitis of the costal joints, as well as trauma to the chest, fractures of the ribs, etc. In the above mentioned pathological conditions, difficultness of movement of the chest prevents the expansion and contraction of the lungs, and leads to the hypoventilation. This condition can sometimes occur due to a mechanical cause (for example, as a result of compression of the trunk and chest during earthquakes, trauma, etc.). Restriction of diaphragmatic movements is also observed in meteorism, ascites, excessive obesity, pleurisy, intercostal neuralgia. Hypoventilation associated with bronchi and lung diseases can be observed in chronic bronchitis, bronchiectasis, bronchial asthma, pneumonia, tuberculosis, pneumosclerosis, atelectasis, emphysema, pleurisy, pneumothorax, hydro and hemothorax. It should be noted that with a decrease in the elasticity of the pulmonary alveoli (emphysema), impaired bronchial obstruction (bronchial asthma), and the formation of exudate in the alveoli (in pneumonia), uneven ventilation of the lungs is observed. Moreover, in the part of the lungs that is involved in the pathological process ventilation decreases, and in the healthy part it increases relatively. According to the mechanisms of development obstructive and restrictive types of alveolar hypoventilation are distinguished. The *obstructive type* of hypoventilation (from latin "obstructio" an obstacle) develops when there is an obstacle to the movement of air in the airways. Obstruction can be found in both the upper and lower respiratory tract. The lumen of the upper respiratory tract can be obstructed by a foreign body, various fluids (water, sputum, vomit, etc.) or tumor tissue. In obstruction of the upper respiratory tract difficulty in inhaling (inspiration) and inspiratory dyspnea occurs. Obstruction can also occur as a result of tongue retention during a coma and an epileptic seizure, laryngospasm (for example, as a result of hypocalcemia) and the action of certain drugs (for example, ß-adrenoblockers). Many diseases of the respiratory system are accompanied by the secretion of a large amount of mucus (hyperkrinia) and its high viscosity (dyskrinia). This disrupts the passage of the airways and obstructs the movement of air. In pathologies accompanied by obstruction of the lower respiratory tract (for example, bronchial asthma), expiration is difficult and expiratory dyspnea occurs. Due to the fact that in obstructive hypoventilation, the exhalation act is more disturbed, the residual lung volume increases. VCL may not change for a long time, but ERV, MVR, MVL, FEV-1s and the Tiffno index are significantly reduced. Diseases characterized by airway obstruction are chronic bronchitis, bronchial asthma, emphysema and bronchiectasis, etc. *Chronic bronchitis* is a chronic inflammatory process that develops as a result of prolonged, regular irritation of the mucous membrane of the respiratory tract. It develops after acute bronchitis, often occurs as an independent disease. In the development of the disease, along with an infection of the upper respiratory tract, the pollution of inhaled air (dust, smoke, etc.) is of particular importance. Chronic bronchitis is mainly a smoker's disease. Prolonged cough and sputum production associated with the diseases are associated with edema, obstruction and hypersecretion of mucus. In chronic bronchitis, obstruction occurs at the level of the trachea, bronchi and bronchioles, their walls are deformed. In the walls of the bronchi, deformed as a result of a strong and prolonged cough, extensions occur (bronchiectasis). With a strong cough in the lumen of the alveoli, pressure also increases. Damage and atrophy of pathologically altered alveolar walls and interalveolar septa lead to the development of emphysema. *Bronchiectasis* is characterized by an expansion of the lumen of the bronchi or bronchioles. Bronchiectasis is not an independent disease (in rare cases, congenital bronchiectasis occurs), it occurs as a complication of chronic bronchitis, bronchial asthma and other diseases. In the occurrence of enlargement of the bronchi or bronchioles, two main factors play a role: chronic persistent infection of the respiratory tract, and the presence of obstruction in a certain part of the bronchi or bronchioles. Chronic infection constantly irritates, damages the wall of the bronchi, and leads to its hyperemia and hypersecretion of mucus. Obstruction makes it difficult to clear the airways of mucus, sputum. At the same time, a strong cough occurs by reflex way to eliminate sputum. With prolonged coughing due to a sharp increase in air pressure in the respiratory tract, extensions occur. *Bronchial asthma* is a chronic inflammatory disease of the airways that is characterized by attacks with bronchospasm, airway obstruction, and expiratory dyspnea. So, hyperemia, edema and spasm of bronchioles lead to a narrowing of its lumen, an increase in airflow resistance. As the bronchial lumen is narrowed, the resistance exerted by the bronchus wall increases by several times the air flow (for example, a narrowing of the bronchial lumen by 2 times is accompanied by an increase in resistance by 16 times - Poissel's law), and this creates air flow is a big obstacle. Therefore, the narrowing of the lumen of bronchioles in bronchial asthma sharply increases the work of the respiratory muscles during the act of exhalation, exhalation is difficult and becomes active. Bronchial asthma is a disease with a hereditary predisposition. The allergic component plays an important role in its pathogenesis. The disease is associated with the sensitization of the body to various allergens and the hypersensitivity reaction that occurs when this allergen is re-introduced into the body. Allergens that cause asthma include home and household dust, pollen, allergens from domestic animals of epidermal origin - wool, hair, etc., food allergens - citrus fruits, egg white, etc. According to the pathogenetic mechanism of development, atopic and non-atopic forms of bronchial asthma are distinguished. The basis of the pathogenesis of atopic asthma is the type I hypersensitivity reaction. The disease begins in childhood and the phenomena of allergic diseases such as atopic dermatitis, urticaria and others are found in the inheritance. In the pathogenesis of non-atopic asthma, the allergic (immune) mechanism is not involved. In these patients, there is no hereditary predisposition to allergies. In patients with non-atopic asthma, IgE is synthesized within normal limits. However, activation of eosinophils and an increase in the release of mediators from them are also characteristic of this type of asthma. Mediators released from eosinophils damage the bronchial epithelium, increase mucus secretion, which leads to obstruction of the lumen of the bronchi and the muscle layer of the bronchial wall hypertrophies. The reason for the development of this form of asthma is a hyperergic inflammatory reaction of the body to respiratory tract infections (mainly viral infections), cold, and harmful substances contained in the air. As a result of such a hyper-reaction of the respiratory tract, bronchospasm, bronchial obstruction occurs. Chronic irritation and inflammation of the bronchial mucosa lead to a decrease of the threshold of irritation of subepithelial parasympathetic receptors. Moreover, any, even the weakest irritation becomes the cause of the excitation of these receptors and the reflex occurrence of bronchospasm. Infectious and non-infectious types of bronchial asthma are distinguished depending on the type of etiological factor (for example, drug asthma, occupational asthma, etc.). The pathogenesis of both infectious and non-infectious asthma can be associated with allergic, pseudo-allergic and non-allergic mechanisms. For example, aspirin-related asthma related to drug-induced asthma develops according to the pseudo-allergic mechanism. Asthma associated with the profession (for example, rubber, plastic materials, inhaled gases) can develop with allergic and non-allergic mechanisms. *Emphysema* is characterized by obstruction of terminal bronchioles and destructive changes in the walls of the distal part (acini), expansion of the alveolar cavities. In emphysema, as a result of destructive changes in the walls of the alveoli, their elasticity decreases, the interalveolar septum undergo atrophy, they turn into large air "bags" and *expiratory dyspnea* occurs. It is known that bronchioles have a soft and thin wall, due to *transpulmonary pressure* (difference of pressures between the alveolar air and the pleural cavity), their lumen remains open. The greater the elasticity of the wall of the alveoli, the greater the transpulmonary pressure is required for the passage of air in them. This pressure, breaking the elasticity of the alveolar wall, expands the alveoli (opens them). Transpulmonary pressure ensures that the lumen of the bronchi remains open and the alveoli expand during inhalation. In emphysema, the elasticity of the alveolar wall is low, and the resistance exerted by the walls of the bronchioles against the air flow is high. Therefore, when inhaling, transpulmonary pressure easily opens the alveoli, which has lost its elasticity, but cannot keep the bronchioles open. As the lumen of the bronchioles narrows, the resistance of their walls increases, and makes it difficult to remove air returning from the alveoli, i.e., difficulty exhaling (expiratory dyspnea). With a further increase in resistance, the lumen of the bronchi closes and the air in the alveoli falls into the "trap". An important role in the mechanism of emphysema plays the imbalances of the *protease-antiprotease* and *oxidant-antioxidant* systems. So, chronic irritation of the alveolar wall attracts neutrophils and macrophages. From the granules of activated leukocytes, proteases (elastase, collagenase, etc.), the synthesis of activated forms of oxygen increases. Moreover, if there is a lack of antiproteases (for example, *a1-antitrypsin*), proteases are not neutralized; they expose the destruction of the alveolar wall. Therefore, individuals with a hereditary defect in the synthesis of a1-antitrypsin are prone to emphysema. In the development of the disease, smoking is of great importance. Normally, the lungs have a large antioxidant reserve (superoxide dismutase, glutathione). However, due to the chronic exposure to cigarette smoke, this reserve is depleted and antioxidant deficiency occurs. *Restrictive type alveolar hypoventilation* (latin "restrictio" - restriction) occurs when the ability of the lungs to straighten is difficult. This type of hypoventilation can develop due to pulmonary and extrapulmonary causes. Pulmonary pathologies accompanied by a restrictive type of hypoventilation include pneumonia, tuberculosis, a tumor, resection of lung tissue, pulmonary edema, pneumosclerosis, atelectasis, etc. Extrapulmonary causes include pleural pathology (pleurisy, pneumo-, hydro-, hemothorax, etc.), processes that disrupt diaphragm mobility (ascites, peritonitis, meteorism, damage to the phrenic nerve, etc.), respiratory muscle disorders (myositis, polyneuritis, tetanus, botulism, etc.), chest excursion difficulties (traumatic injuries of the ribs, intercostal neuralgia, kyphosis, lordosis, scoliosis, etc.). In restrictive hypoventilation, the inspiration process is most damaged, inspiratory dyspnea develops. As a result, the tidal volume, IRV, MCL, VCL decrease, however, due to the fact that the expiratory volume decreases slightly, the Tiffno index remains at a normal level or increases. In both types of hypoventilation, the respiratory muscles work hard, additional muscles are connected to the process. The body spends a lot of energy on the respiratory process and quickly gets tired. The signs of respiratory failure are deepening - hypoxemia, hypercapnia, gas acidosis, tissue hypoxia. With acidosis, the cerebral vessels expand, vascular permeability increases, cerebral circulation is disturbed, intracranial pressure rises and interstitial edema of the brain gradually develops. Under such conditions gas diffusion is difficult and brain tissue cannot absorb oxygen. The development of decompensated secondary acidosis as a result of hypoxia dilates the cerebral vessels even more. Thus, the vicious cycle accelerates the development of cerebral edema and creates a dangerous condition for life. Hypoventilation causes changes in the cardiovascular system. With a decrease in the partial pressure of oxygen in the alveolar air, the tonicity of the vessels of the pulmonary circulation increases reflexively (Euler-Lillestrand reflex). Moreover, hypertension that occurs in the pulmonary circulation may lead to pulmonary edema. Hypertension in the pulmonary circulation also leads to right ventricular failure and the development of a "cor-pulmonary". Erythrocytosis, which occurs compensatory in conditions of hypoxia, increases blood viscosity, further complicates the work of the heart, as a result, blood circulation is weakened and microcirculatory failure occurs. Microcirculatory disorders exacerbate tissue hypoxia and a decompensated stage of respiratory failure develops. The reasons for the restrictive type of alveolar ventilation include atelectasis, pneumothorax, pneumonia, etc. *Atelectasis* is a pathological process characterized by wrinkling of the alveoli and the closure of their lumen. Atelectasis is not an independent disease (nosological unit), but is a pathology that can develop as a result of various diseases of the respiratory system. According to the development mechanism, resorption, compression and contraction types of atelectasis are distinguished. - *Resorption atelectasis* develops as a result of blockage of the lumen of the bronchi by a foreign body, tumor tissue, thick sputum, spasm, which makes it impossible for air to enter the corresponding alveoli. In this case, the air remaining in the alveoli is resorbed, the lumen of the alveoli closes. - *Compression atelectasis* occurs when the lungs are compressed from the outside. The reason for this may be the accumulation of fluid or air in the pleural cavity. In patients with ascites, who have been in bed for a long time, lifting the diaphragm can lead to compression atelectasis. - *Contraction atelectasis* develops, which is an irreversible process, in the lung parenchyma with pneumosclerosis, contraction atelectasis develops. Despite maintaining perfusion of the selected alveoli, due to the fact that they are not ventilated, gas diffusion does not occur in them. The gas composition of the blood changes and hypoxemia develops. If the development of atelectasis is not prevented in a timely manner, it can lead to severe respiratory failure. In *pneumothorax*, air or gases accumulate in the pleural cavity. At this time, pressure increases in the pleural cavity, the lungs are compressed. Air can enter the pleural cavity from the outside (as a result of a wound to the chest) and from the inside (tuberculosis, lung abscess, destruction of the lung tissue in tumors), or as a complication of treatment (in the treatment of cavernous pulmonary tuberculosis). There are closed, open and valvular types of pneumothorax. In the *closed type* of pneumothorax, the air that enters the pleural cavity loses contact with the external environment. In this case, respiratory failure depends on the volume of air entering the pleural cavity. In the *open type* of pneumothorax, air during inspiration and expiration can freely enter the pleural cavity and be removed from there. In this type of pneumothorax, disturbance of pulmonary ventilation depends on the size of the hole (defect) that causes pneumothorax. With a large opening, more air enters the pleural cavity, the lungs cannot expand. During inhalation on the side of the pneumothorax, the volume of the lungs decreases and during exhalation, part of the air discharged from the healthy lung enters into the compressed lung, its volume relatively increases and expels air from the pleural cavity out. In the *valvular type* of pneumothorax, with each act of inhalation, air enters the pleural cavity and when exhaling it cannot escape from there. This is due to the fact that in the area of damage, soft tissues create a valve around the wound opening. When inhaling, the hole opens and when exhaling, it closes. The flow of air continues until the pressure in the pleural cavity is equal to atmospheric pressure. In pneumothorax, the pressure in the pleural cavity rises, the mediastinal organs change their location, the vessels going to the heart are compressed, sucking the ability of the chest decreases, venous congestion occurs, in the compressed lungs blood flow resistance increases, the work of the right half of the heart becomes difficult. Thus, acute respiratory and heart failure occurs. If the development of pneumothorax is not prevented in a timely, this can lead to the death of the patient. *Pneumonia* is an inflammatory process of various origins that develops in the lung tissue. For example, a chronic inflammatory process that develops in the lung tissue due to exposure to mycobacterium tuberculosis is called pulmonary tuberculosis. Chronic inflammatory processes that develop as a result of exposure to industrial dust such as silicon, minerals of asbestos, coal, etc., are called pneumoconiosis. Pneumonitis (or allergic alveolitis) is characterized by damage to the alveoli as a result of an allergic-inflammatory process. The term "pneumonia", used in the clinic, covers lung diseases of infectious and inflammatory origin. From this point of view, distinguish between bacterial (or typical) and non-bacterial (or atypical) pneumonia. Etiological factors of bacterial (typical) pneumonia can be pneumococci, streptococci, staphylococci, klebsiella, etc. These are extracellular microorganisms that multiply in the cavity of the alveoli and lead to the development of an inflammatory process. In this case, a strong exudation and alveolar infiltration occur. Etiological factors of non-bacterial factors (atypical) pneumonia can be mycoplasma, chlamydia, some viruses - adenoviruses, influenza viruses (for example, bird flu virus AH5N1, swine flu virus AH1N1). These infectious factors, passing from the alveolar cavity to the interstitial region, multiply here. In non-bacterial pneumonia, alveolar infiltration is not observed, as with bacterial pneumonia, the course of the disease is atypical. In the development of pneumonia, along with an infectious factor, a weakening of the body's resistance plays an important role. Immunodeficiency conditions, cold, poor nutrition, bad habits (smoking, chronic alcoholism), stress, prolonged bed rest, old age and other factors create favorable conditions for the development of pneumonia. In pneumonia, the lung tissue is damaged, as a result of exudation, alveolar or interstitial edema develops. The respiratory surface of the lungs decreases, the processes of alveolar ventilation and diffusion are disrupted. At the same time, vagus nerve receptors in the wall of the alveoli are excited faster and the Hering-Breuer reflex is enhanced. Thus, inspiratory dyspnea occurs. Acute and chronic pneumonia are distinguished according to the course, community-acquired and nosocomial forms of pneumonia are according to the source of infection. *Pneumonitis* (allergic alveolitis) refers to restrictive pulmonary disease. The basis of the pathogenesis of pneumonitis is the hypersensitivity reaction of the alveoli, interstitial tissue to various types of exogenous antigen. The role of antigen is mainly played by agricultural and household particles (dust). Due to the fact that the disease is more common among agricultural workers (animal husbandry, poultry farming), it is also called "farmer disease". Though allergens that are inhaled in this disease, causing an allergic reaction, are pollen, pneumonitis differs from pollenosis and bronchial asthma. Pollenosis and bronchial asthma develop according to type I hypersensitivity reactions and are characterized by spasm of bronchioles and their damage. But pneumonitis refers to types III and IV of allergic reactions and is manifested by damage and gradual fibrosis of the alveolar wall and interstitial tissue. *Pleurisy* is an inflammatory disease of the pleura. Their development may be associated with lung pathology (pneumonia, primary and metastatic lung tumors, etc.), heart failure (in Dressler syndrome that develops after myocardial infarction, etc.), allergic reactions (e.g., Quincke edema), etc. Dry and exudative pleurisy are distinguished. In exudative pleurisy, fluid accumulates in the pleural cavity. The accumulation of fluid in the pleural cavity is called hydrothorax, the accumulation of blood hemothorax, the accumulation of lymph - chylothorax. The accumulation of fluid in the pleural cavity during pleurisy leads to atelectasis, respiratory and heart failure. #### 20.2.2. Disorders of alveolar diffusion Alveolar diffusion provides the transition of oxygen from the alveolar cavity to the pulmonary capillaries and carbon dioxide in the opposite direction. In the initial part of the pulmonary capillaries, the partial pressure of oxygen in the blood is less than in the alveolar air, red blood cells are enriched with oxygen as they move in the capillaries. In the blood flowing to the lungs, PO2 is 40 mm Hg, and in blood returning from the lungs to the heart, 100 mm Hg And pCO2 of blood in the initial part of the pulmonary capillaries is 46 mm Hg, and in the final is part 40 mm Hg. The volume and rate of alveolar diffusion depend on various factors: - the difference in gas gradients (O2 and CO2) in the alveolar air and pulmonary capillaries. For example, with a low partial pressure of oxygen in atmospheric air, alveolar diffusion weakens; - the area of the diffuse surface of the lungs, which is normally 180-200 m². In pneumonia, allergic alveolitis, pulmonary edema, emphysema, atelectasis, sclerotic changes in the lung parenchyma, etc., the area of the diffuse surface and the volume of alveolar diffusion are reduced; - the thickness of the alveolar-capillary membranes (ACM). Normally, the thickness of this membrane is 0.2-2 microns. In lung diseases (for example, in respiratory distress syndrome of newborns), the thickness of the ACM increases, and gas diffusion through this membrane decreases; - the molecular weight of diffused gases and their solubility. According to these properties, the diffuse ability of carbon dioxide is 20 times higher than that of oxygen. So, normally within 1 minute, 15 ml of oxygen and 300 ml of carbon dioxide diffuse through the alveolar-capillary membrane. Therefore, in most respiratory diseases, oxygen diffusion is mainly disturbed and hypoxemia develops against the background of normocapnia. Disturbance of the diffusion of carbon dioxide occurs with deeper damage to the ACM (for example, adult respiratory distress syndrome) and this is accompanied by hypercapnia and hypoxemia. Alveolar diffusion also depends on the condition of the pulmonary circulation (perfusion of the lungs). For example, during increasing of the blood flow velocity in the pulmonary capillaries, the red blood cells do not have time to connect with oxygen, because the red blood cells pass through the capillaries for a short time (normally 0.2-0.3 seconds). #### 20.2.3. Disturbance of the lung perfusion Lung perfusion (blood supply to the lungs) may be impaired for the following reasons: decreased pressure in the right ventricle (decreased venous blood flow to the right half of the heart - with shock, collapse, etc.); increased pressure in the left atrium (left ventricular failure, mitral stenosis, etc.); increased resistance in the pulmonary vessels (reflex spasm, thromboemboli of pulmonary arterioles, etc.). Disturbance of lung perfusion can lead to the development of *pulmonary hypertension*, which is characterized by the increase of pressure in the vessels of the pulmonary circulation and occurs for various reasons: - reflex increasing of the tonicity of the pulmonary arterioles during decreasing of the oxygen content in the alveolar air (for example, in hypoventilation) - the Euler-Lillestrand reflex; - reflex spasm of pulmonary arterioles during increasing of pressure in the left atrium, arising from stenosis of the mitral and aortic orifices (Kitayev reflex) or in arterial hypertension, etc.; - during increasing of intra-alveolar pressure. In obstructive diseases accompanied by expiratory dyspnea, as a result of prolonged expiration, pressure in the alveoli rises. In this case, the resistance in the pulmonary vessels increases; - during decreasing of the total area of the capillary network of the lungs (for example, in *pneumosclerosis*); - during increasing of the blood levels of certain biologically active substances (norepinephrine); - in the thickening of the blood, etc. Precapillary, postcapillary and mixed forms of pulmonary hypertension are distinguished. - *Precapillary pulmonary hypertension* develops as a result of increasing of pressure in the pre-capillaries and capillaries during the spasm of pulmonary arterioles, thromboemboli of pulmonary vessels, compression of arterioles by tumor or by enlarged lymph nodes, and increasing of intra-alveolar pressure due to protracted cough. - *Postcapillary pulmonary hypertension* develops as a result of disturbance of blood flow from pulmonary venules and veins to the left side of the heart, which leads to congestion of lungs. It occurs during compression of pulmonary veins by tumor or scar tissue, left-side heart insufficiency, arterial hypertension, etc. *Mixed form of pulmonary hypertension* may develop initially as a precapillary form progressing into the postcapillary form or vice versa. In pulmonary hypertension, hypertrophy of the right part of the heart develops, which is called a "cor-pulmonary". Long-term pulmonary