CC BY
0PATHOPHYSIOLOGY OF BRONCHIAL ASTHMA. Oltinov Sardor
Tashkent Pediatric Medical Institute. Tashkent https://doi.org/10.5281/zenodo.13933306
ARTICLE INFO
ABSTRACT
Qabul qilindi: 05- Oktyabr 2024 yil
Ma'qullandi: 10- Oktyabr 2024 yil
Nashr qilindi: 15- Oktyabr 2024 yil
KEY WORDS
bronchial obstruction, vagus, inflammatory mediators, shortness of breath.
Bronchial asthma is a non-infectious chronic disease of the respiratory tract. Knowing its pathophysiology helps a lot. It helps to avoid sudden attacks. Bronchospasm (narrowing of the bronchial space) due to specific immunological (sensitization and allergy) or non-specific mechanisms, characterized by recurrent wheezing, shortness of breath, asthma attacks, chest tightness and manifested by cough.
Bronchial obstruction is partially or completely reversible, a chronic inflammatory disease of the respiratory tract in which many cells and cellular elements are involved, spontaneously or under the influence of treatment. Chronic inflammation leads to the development of bronchial hyperreactivity, which causes repeated wheezing, shortness of breath, chest congestion, and coughing, especially at night and early in the morning. These episodes are usually associated with widespread but variable airway obstruction in the lungs, which often resolves spontaneously or with treatment. The main link of bronchial asthma of any genesis is an increase in the reactivity of the bronchial tree. It is caused by a violation of the autonomic regulation of smooth muscle tone and the effect of inflammatory mediators, and leads to periodically reversible obstruction of the bronchi, which leads to increased airway resistance, overstretching of the lungs, focal hypoventilation and incompatibility. manifested by resulting hypoxemia. Mechanism of the autonomic nervous system: pi-, p2-and a-adrenergic receptors are located in smooth muscle cells. Stimulation of p2-adrenergic receptors reduces bronchial reactivity in patients with bronchial asthma, but blockade of p-adrenergic receptors in healthy individuals does not cause significant changes in bronchial reactivity. Normally, the tone of the bronchial smooth muscles is mainly regulated by the parasympathetic fibers of the vagus nerve. The use of drugs that block the transmission of impulses through parasympathetic fibers leads to dilation of the bronchi, and the excitation of these fibers causes bronchospasm. The tone of the smooth muscles of the bronchi also changes under the influence of afferent fibers coming from the receptors of the bronchi and forming the vagus nerve. The sympathetic nervous system usually plays an insignificant role in regulating the activity of bronchial muscles, but its role increases in bronchial asthma. As a result of stimulation of unmyelinated fibers (S-type afferent fibers located in the wall of bronchi and alveoli) by inflammatory mediators, neuropeptides such as substance P are released, which cause bronchoconstriction, swelling of the mucous membrane, and increased
mucus secretion. One of the biochemical factors is calcium. Calcium plays a major role in the contraction of bronchial muscles, because the ATP-dependent calcium pump, which removes calcium from the cell, is involved in maintaining the membrane potential of smooth muscle cells. An increase in the concentration of intracellular calcium leads to the contraction and decrease of smooth muscles. In addition, an increase in intracellular calcium concentration causes the release of histamine, anaphylactic factor of eosinophil chemotaxis, and anaphylactic factor of neutrophil chemotaxis from mast cells. Adrenergic receptors are thought to be involved in regulating calcium levels in mast cells. Cyclic nucleotides (cAMP and cGMP) are involved in the regulation of bronchial smooth muscle cell contraction and cell degranulation. The release of mediators by mast cells under the influence of M-anticholinergics and prostaglandin F2a is associated with an increase in the level of cGMP. Stimulation of a-adrenergic receptors leads to a decrease in the level of cAMP, which also causes degranulation of mast cells. Stimulation of p-adrenergic receptors leads to an increase in cAMP levels and, consequently, inhibition of mast cell degranulation. Adenosine receptor blockade is also believed to inhibit degranulation. Heparin, thromboxanes, serotonin, free oxygen radicals, kinins, neuropeptides, proteases and cytokines are also involved in the pathogenesis of exogenous bronchial asthma.
Effects of inflammatory cells:
• Mastocyte cells. Activation of these cells occurs when allergens interact with IgE on the surface of mast cells in exogenous bronchial asthma. In the case of endogenous asthma, activation of mast cells may occur in response to osmotic stimuli, such as in exercise-induced asthma. When activated, they release mediators that cause bronchospasm (histamine, cysteinyl leukotrienes, prostaglandin D2). Leukotrienes and prostaglandins are formed from arachidonic acid. Eosinophils. The number of eosinophils increases in the airways.
• T-lymphocytes. Their number also increases in the respiratory tract. They release specific cytokines (IL-4, IL-5, IL-9 and IL-13, etc.) that affect the process of eosinophilic inflammation and the production of IgE by B-lymphocytes. Regulatory T cells reduce Th2 lymphocytes, so Th2 cell activity may increase when the number of regulatory T cells decreases.
• Dendritic cells capture allergens from the surface of the bronchial mucosa and transport them to regional lymph nodes, where they interact with regulatory T cells.
• Macrophages. Macrophages such as eosinophils and T-lymphocytes increase in the airways. They can be activated when allergens interact with low-affinity IgE, resulting in the release of inflammatory mediators and cytokines.
• Neutrophils. Their number in respiratory tract and sputum increases in patients with severe asthma and smoking.
Inflammatory mediators, histamine and leukotrienes are mediators of the initial phase of the immediate allergic reaction. Histamine causes immediate and short-term bronchospasm, while leukotrienes cause delayed and prolonged bronchospasm. Late-phase mediators of the acute allergic reaction include chemotaxis factors and platelet-activating factor. The latter causes chemotaxis, activates inflammatory cells in the bronchial mucosa and stimulates the synthesis of leukotrienes in these cells. Bronchospasm caused by them appears 2-8 hours after the beginning of an allergic reaction and can last for several days .
Involvement of structural cells of the airways. The structural cells of the airways also contribute to the development of inflammation. Thus, bronchial epithelial cells recognize their mechanical environment, express various proteins and secrete cytokines, chemokines, and lipid mediators. Similar inflammatory proteins are produced by smooth muscle cells. Endothelial cells are involved in the migration of inflammatory cells into the airways. Fibroblasts and myofibroblasts participate in airway remodeling by producing collagen, proteoglycans, and other components of connective tissue. Pathological changes leading to bronchial obstruction affect the mucous membrane, submucosa and muscle layer of the bronchial tree. The pathological process spreads from the trachea and large bronchi to the terminal bronchioles. The following causes narrowing of the bronchi:
• The formation of mucous membranes. In asthma, a thick, viscous mucus is formed, which contains desquamated bronchial epithelium, eosinophils, Charcot-Leyden crystals.
• Changes in the bronchial wall. In asthma, the number of ciliated epithelial cells decreases, while the number of mucus-secreting goblet cells increases and undergoes hyperplasia. Eosinophilic infiltration, swelling and thickening of the basement membrane also occur, infiltration of eosinophils, neutrophils, lymphocytes and macrophages in the submucosa, hypertrophy and swelling of the glands. The muscular membrane of the bronchi is hypertrophied.
• Spasm of bronchial smooth muscles is the most common cause of acute short-term attacks. The duration of seizures and resistance to treatment is associated with swelling of the mucous membrane of the bronchial mucosa and bronchial obstruction.
Obstruction increases with exhalation, because in this case there is a dynamic narrowing of the airways. Due to the obstruction of the bronchi, part of the air is stored in the alveoli, which leads to excessive stretching of the lungs and prolongation of exhalation. Excessive airway resistance leads to an increase in the work of breathing, which leads to the introduction of auxiliary muscles, causing shortness of breath. The process can involve large and medium bronchi, but often the obstruction of small bronchi comes first. Noisy, wheezing is a sign of obstruction of the large bronchi, while shortness of breath and coughing attacks often occur with obstruction of the small bronchi. Obstruction leads to an increase in residual volume, a decrease in VC, and an increase in total lung volume. Due to the obstruction of the airways, their ventilation is reduced. Usually, the perfusion of poorly ventilated areas decreases, but in asthma this does not always happen, the balance between ventilation and perfusion is disturbed, which leads to a decrease in paO2. With mild and moderate attacks of bronchial asthma, hyperventilation occurs, which leads to a decrease in paCO2 and respiratory alkalosis. With severe and prolonged attacks, hypoventilation develops, CO2 increases, and respiratory acidosis occurs. Overdistension of the lungs and reduction of paO2 in the alveoli leads to capillary spasm of the alveoli and an increase in pressure in the pulmonary artery. The main symptoms of bronchial asthma are episodes of shortness of breath, wheezing, coughing and chest congestion. The onset of symptoms after allergen exposure, seasonal variability of symptoms, and the presence of relatives with bronchial asthma or other atopic diseases are important. When combined with rhinitis, asthma symptoms may appear only at certain times of the year or be always present with seasonal worsening.
Used literature:
1. Isaev Yu., Moysyuk L. Bronchial asthma: Conventional and non-conventional methods of treatment. 2008.
2. Global strategy for treatment and prevention of bronchial asthma / pod ed. A. G. Chuchalina . — M.: Atmosfera, 2007
3. Solopov V. N. Asthma. Istinnaya prichina disease. 2006
4. Fadeev P. A. Bronchial asthma. 2010
5. Chuchalin A. G. Bronchial asthma. 1985.
