Critical States in Respiratory Tuberculosis in Adults - N.I. Fomichova 2010

Prerequisites for the Development of Critical States in Respiratory Tuberculosis

Critical states should be understood as pathological processes that increase the risk of disease progression, may lead to severe complications, acute Impairment of Vital organ Functions, and Metabolic Disorders, thereby causing justifiable concern for the patient's survival and necessitating intensive care or resuscitation measures.

Pulmonary Tuberculosis is a condition that, due to the mechanisms of pathological processes occurring in the patient's body, is frequently accompanied by critical emergencies.

The primary function of the Lungs is external Respiration, which ensures the uptake of oxygen into the Blood and the elimination of carbon dioxide. Therefore, the main factors in the Pathogenesis of emergency conditions in patients with pulmonary diseases, including tuberculosis, are oxygen deficiency—which may manifest as hypoxemia (decreased oxygen tension in the blood)—along with hypocapnia or hypercapnia (decreased or increased carbon dioxide tension, respectively).

In patients with pulmonary tuberculosis, Hypoxia is caused by a reduction and limitation of the alveolar diffusion surface, or by the narrowing and obstruction of the Airways.

The exchange of oxygen and carbon dioxide between the external environment and the blood takes place in the alveoli, which are enveloped by a network of vessels—the terminal Branches of the pulmonary artery, capillaries, and postcapillary venules. In addition, there is another capillary system whose function is to supply blood specifically to the lung tissue itself. It originates from the systemic Circulation. The vessels of this system contain 1–2% of all pulmonary blood. On average, the capillaries are in contact with 70 m² of the lung surface, across which gas exchange occurs.

Between the alveolar air and the capillary blood, a very thin (0.4–1.5 µm) alveolocapillary membrane is formed, through which oxygen and carbon dioxide pass easily. The gases traverse two layers of Cells—the alveolar epithelium (type I and type II alveolar cells), the capillary endothelium—and the interstitial space between them. Thus, The pathway of oxygen and carbon dioxide comprises 5 cellular layers, 2 basement membranes, and 6 aqueous solutions. The cellular membranes present the greatest resistance to gas diffusion. Under normal conditions, The rate of oxygen and carbon dioxide exchange across the alveolocapillary membrane is so high that an almost complete gas equilibrium is established between the blood flowing through the pulmonary capillaries and the air in the alveoli. The duration of blood-air contact is 0.6–1.0 s. For complete oxygen diffusion into the blood, 0.2–0.25 s is sufficient, while for carbon dioxide, 0.1 s is enough, since carbon dioxide dissolves in Lipids and Water 23 times more actively than oxygen.

Diffusion of gases from the alveolar air occurs due to the partial pressure gradient, on the one hand, and the solubility of gases in lipids (which form The basis of the membranes) and water, on the other. Blood flow velocity also plays an important role. Therefore, normocapnia or hypocapnia may be observed during respiratory hypoxia and The Development of hypoxemia.

To supply oxygen to all processes of tissue respiration, the human lungs contain approximately 300 million alveoli within the respiratory zone proper, along with 8 billion capillaries (compared to 10 billion capillaries in the entire systemic circulation) (E. R. Weibel, D. M. Gomez, 1962). The total alveolar surface area ranges from 50 to 90 m².

At rest, the lungs of a healthy person contain approximately 400–600 ml of blood (or 10–12% of the total circulating blood volume). The cross-sectional area of the Pulmonary Circulation capillaries is nearly 80% larger than that of the systemic circulation. During normal hemocirculation, a portion of the pulmonary capillaries remains unfilled with blood; hence, the reserve capacity of the lesser circulation vessels can accommodate 2–3 times more blood. A further increase in the pulmonary blood volume leads to an elevated pressure in the pulmonary artery. At rest, about 5 liters of blood are oxygenated and cleared of carbon dioxide in the pulmonary capillaries within 1 minute (A. G. Hinechynsky, 1956). One of the Specific features of the pulmonary microvasculature is the presence of arteriovenous shunts, through which a portion of venous blood enters the Veins, bypassing the capillaries. A small amount of blood from the systemic circulation, draining from the lung tissue, also enters the lesser circulation.

To maintain optimal gas composition in arterial blood and Tissues under pathological conditions, immediate and long-term respiratory, hemodynamic, and tissue adaptation mechanisms are activated: the rate and depth of breathing and Heart rate change, the erythrocyte count and Hemoglobin level increase, the affinity of hemoglobin for oxygen rises, and the oxyhemoglobin dissociation curve shifts.

If these mechanisms fail to maintain the arterial blood gas composition at an optimal level, hypoxemia, hyper- or hypocapnia (possibly also normocapnia) develop as manifestations of respiratory failure.

The stages of external respiration are ventilation, gas diffusion, and pulmonary perfusion. In respiratory diseases, one or all three of these stages may be impaired, though one usually predominates.

External respiration depends on: airway patency, elastic and non-elastic resistance of the lung tissues, diaphragmatic excursion, and chest wall mobility. Impairments of external respiration caused by restricted chest wall mobility occur in Pleurisy, pleural adhesions, pneumosclerosis, etc. The mechanics of respiration depend on the elasticity of the lungs and the chest wall. When these are impaired, the vital capacity, total lung capacity, and tidal volume decrease, while the minute ventilation increases. All of this negatively impacts gas exchange. Currently, about 23 generations of Bronchi are distinguished. The length and diameter of each successive bronchus decrease. Starting from the 4th bronchial generation, due to a significant increase in their number, the cross-sectional area increases substantially. While the cross-sectional area of the airways from the nostrils to the 4th generation is about 2–2.5 cm², at the level of the 23rd generation the total cross-sectional area of the bronchioles reaches 11,400 cm². The bronchial tree is generally divided into 3 zones: the conducting zone (generations 1–16), the transitional zone (generations 17–19), and the respiratory zone (generations 19–23).

Bronchial patency depends on their diameter and length, as well as on deformations and surface irregularities. Airflow through the bronchi is normally laminar. However, eddy currents and turbulence may naturally develop at the sites of bronchial branching. During quiet breathing, the volumetric airflow rate is 0.3–0.5 L/s. Air conditioning—warming, humidifying, and purifying—takes place within the respiratory passages of the lungs. Deformations and surface irregularities of the bronchi cause turbulence that is more pronounced than under normal physiological conditions, which impairs bronchial patency. Patency is further compromised by bronchial spasms and hypotonia, decreased elasticity of the lung tissue, stenoses, inflammatory mucosal thickening, sputum accumulation, tumors, and dyskinesia of the tracheobronchial tree. Bronchial patency is particularly hindered by Atrophy of the elastic fibers in the respiratory segments, as well as in the membranous part of the Trachea and Bronchi. When obstruction occurs in isolated small bronchi, external respiration remains unaffected. When patency is obstructed in the Larynx, trachea, and large bronchi, inspiratory dyspnea occurs; when medium and small bronchi are affected, expiratory dyspnea develops.

Bronchial patency and respiratory mechanics ensure pulmonary ventilation, which is characterized by stable air Temperature and gas partial pressures. Normally, the partial pressure of oxygen in the alveoli reaches 100–110 mm Hg (13.3–14.7 kPa), and that of Carbon dioxide is 40 mm Hg (5.3 kPa). Impaired pulmonary ventilation is accompanied by dyspnea, which fails to provide effective gas exchange. In poorly ventilated lung segments, the partial pressure of oxygen drops and the elimination of carbon dioxide worsens. All of this negatively affects both blood gas composition and METABOLISM.

As air flows into the smaller bronchi, the total cross-sectional area increases, leading to a sharp decrease in airflow velocity. This facilitates the mixing of inhaled air with alveolar air, its warming, and the maintenance of a constant gas composition in the alveoli. When the number of functioning bronchioles decreases, this process is severely disrupted. Inadequately warmed air enters the alveoli and fails to mix properly with the alveolar air, resulting in hypoxemia and alveolar overcooling.

Respiratory impairment progresses when the pulmonary respiratory surface decreases, and particularly when its diffusion properties are impaired. At rest, satisfying The Human Body's oxygen demands requires only 1/12 of the surface area of the respiratory Regions of the lungs (B. Pavlov, 1966). The exclusion of 2/3 of the pulmonary surface is tolerated satisfactorily, provided the reduction in respiratory volume occurs gradually. This demonstrates the vast compensatory reserve of the lungs. The lungs of a healthy person ventilate 7,000–10,000 liters of air per day. Before penetrating the capillaries, the oxygen in the ventilated air must first dissolve in lipids and cross the blood-air barrier. Therefore, the diffusion of oxygen and carbon dioxide depends not only on the magnitude of the respiratory surface area, but also on the thickness of the cellular and basement membranes, the partial pressure gradient of gases between the alveoli and blood, the diffusion coefficient, and the state of the membrane.

Respiratory insufficiency causes metabolic disorders within cells and the development of dystrophic changes in Organs. Impaired pulmonary ventilation can disturb respiratory regulation, further exacerbating respiratory failure. Hypoxic hypoxia induces vasospasm of pulmonary arterioles, leading to pulmonary Hypertension. Other causes of pulmonary hypertension include the obliteration of the lesser circulation vascular bed, increased blood viscosity, elevated Cardiac Output, and disseminated intravascular coagulation syndrome. Thus, impaired pulmonary ventilation in tuberculosis acts as a triggering mechanism for the development of such life-threatening conditions as pulmonary hypertension and pulmonary edema.

It has been established (U. Euler, G. Liljestrand, 1948) that pulmonary arterial pressure rises both when the oxygen content in the alveolar air decreases and when blood oxygen saturation drops (M. M. Mirrakhimov, 1977; I. Widimsky, 1978). According to literature data, if the hydrostatic pressure in the pulmonary capillaries exceeds 30 mm Hg (normally 6–9 mm Hg) or 3.2–3.7 kPa, conditions are created for fluid transudation from the capillaries into the interstitial space, leading to pulmonary edema. The risk of pulmonary edema increases if pulmonary hypertension is combined with hypoproteinemia, increased permeability of the alveolocapillary membranes, decreased adsorptive capacity of Lymphatic vessels, and Impairment of the pulmonary surfactant system.

Furthermore, hypoxia alters oxidation-reduction processes in the patient's body, decreasing aerobic Glycolysis and increasing anaerobic glycolysis. This leads to an accumulation of under-oxidized metabolic intermediates (lactic, ketoglutaric, and pyruvic acids), which exert a toxic effect on the patient's body. Impaired elimination of carbon dioxide from the blood results in gaseous acidosis, which can cause cerebral edema and sudden death.

Pulmonary hypertension is the main cause of Hemoptysis and Pulmonary Hemorrhage in chronic pulmonary tuberculosis. Dystrophic processes and tissue destruction may be complicated by Spontaneous pneumothorax. In the presence of inflammatory processes in the lungs, oxygen deficiency is compounded by endogenous intoxication resulting from the action of microbial toxins and an excess of intermediate and end-products of metabolism generated within the affected lung tissue.

Hypoxia, intoxication, and Circulatory Disorders in the lesser circulation, combined with deep vein Thrombosis of the lower extremities, can lead to thrombosis and embolism of the pulmonary artery, as well as pulmonary infarction.

In addition to respiratory functions, the non-respiratory Functions of the lungs may also suffer, including protective, filtering, metabolic, excretory, absorptive, thermoregulatory, fluid-balance maintenance, and reservoir functions. The intact mucosa of the trachea and bronchi reliably protects the body against infection thanks to the mucociliary apparatus. In the respiratory regions of the lungs, protection against infection is provided by surfactant and alveolar macrophages. The barrier function of the lungs also encompasses the antibacterial and antiviral properties of mucus, which are attributable to the presence of Lysozyme, lactoferrin, interferon, and IMMUNOGLOBULINS. An important role in the lung barrier function is played by alveolar macrophages and lymphoid elements located not only in the mediastinal Lymph Nodes but also in the bronchi.

Breaching the lung barrier defense due to the damaging action of endogenous and exogenous factors promotes the development of a pathological process that ultimately leads to respiratory impairment, hyperventilation, hypoxia, and hyper- or hypocapnia. Such patients frequently require intensive care, emergency medical intervention, and occasionally resuscitation measures.

Antigens of tuberculous mycobacteria possess toxic and allergic properties that determine The Nature of their biological impact on the body. Complex lipopolysaccharide-polypeptide-nucleic acid complexes are formed in the patient's body, provoking intoxication in tuberculosis.

Under The Influence of excessive chronic irritation caused by antigenic complexes such as endotoxins, trophic and innervation impulses become distorted and assume a pathological character. Tissue metabolism is consequently disrupted, leading to dystrophic processes. An important role in the genesis of dystrophy is played by impaired enzymatic processes in tissues, altered Protein metabolism, and Changes in the PHYSICOCHEMICAL PROPERTIES OF protein and lipid colloids in cells, tissues, and biological fluids.

The dystrophic process disrupts both The Structure of Cells and Tissues and the direction of the physiological processes occurring within them. In tuberculosis, significant diffuse pathological changes occur throughout the entire system of visceral innervation of Internal Organs involved in the metabolism of the digestive, respiratory, cardiovascular, glandular, and excretory systems, leading to profound disorders in The regulation of physiological trophic processes.

Under the influence of toxico-infectious factors in tuberculosis, the Pituitary Gland is activated and functions under high stress, leading to an increased intensity of metabolic processes and visceral organ activity, which at the early stage of tuberculosis development is regarded as a defensive reaction. In the chronic course of the process, prolonged irritation of neuroendocrine function, accompanied by excessive depletion of Hormones in both the Central Nervous system tissue and incretory organs, reveals symptoms of atrophic and degenerative processes. Due to this excessive strain, similar dystrophic processes occur in the Adrenal Glands, affecting both the cortex and the medulla. Adrenal insufficiency disrupts the phosphorylation of CARBOHYDRATES and Fatty acids. Altered protein metabolism leads to the accumulation of nitrogenous waste products in the blood. Electrolyte imbalance results in elevated blood potassium levels. The increased blood potassium concentration caused by adrenal insufficiency, along with the disruption of normal electrolyte ratios in Blood Plasma, leads to vascular tone disorders and an impaired cardiac rhythm. Concurrently, tissue-Water Metabolism is disrupted. Due to increased vascular endothelial permeability, a significant amount of blood plasma passes into the tissues, disturbing normal hemodynamic ratios.

Despite frequent breathing and hyperventilation, oxygen demand decreases. Tissues lose their ability to assimilate oxygen from the blood.

Under the influence of tuberculosis intoxication, oxidative processes in the Liver are weakened, resulting in fatty infiltration of the organ. Since a "fatty" liver has low resistance to toxins, the degeneration of parenchymal tissues is intensified, and cirrhotic processes develop.

In tuberculosis, under conditions of oxygen deficiency, parenchymal organs exhibit an increased production of under-oxidized protein and carbohydrate breakdown products, which is accompanied by the development of metabolic acidosis. The accumulation of such oxidation products in tissues is the primary cause of accelerated breathing in tuberculosis patients. Consequently, to fully rid the tissues of excess organic decomposition products, the body's oxygen demand increases significantly. Due to the failure to meet this demand, under-oxidized metabolic products accumulate in the human body.

In the initial phases of its development, tubercular inflammation does not differ from inflammation of any other Etiology. It consists of three interrelated and interdependent stages: alteration, exudation with Cell emigration, and proliferation.

Alteration is tissue damage ranging from barely noticeable structural and metabolic disorders to pronounced dystrophic and even necrobiotic changes caused by an inflammatory agent—in this case, MBT—which mainly affects cell membranes, particularly lysosomal ones, leading to secondary alteration. During secondary alteration, only some cells perish, while others not only survive but begin to produce BIOLOGICALLY ACTIVE SUBSTANCES, thereby recruiting new cells to the inflammation site both within and outside the focus.

The Second Stage of inflammation is characterized by disorders in local BLOOD AND LYMPH circulation, primarily microcirculation. Immediately after the stimulus acts, an arteriole spasm occurs and quickly passes, followed by arterial hyperaemia as a consequence of The formation of a significant amount of vasoactive substances—inflammatory mediators—in the inflammation focus. Arterial hyperaemia is replaced by venous hyperaemia, which is characterized by changes in: the blood (margination of leukocytes, Swelling of erythrocytes, blood hemoconcentration, microthrombus formation, decreased heparin content); the vascular wall (endothelial swelling, loss of elasticity in venules); and surrounding tissues (edematous tissues compressing veins and lymphatic vessels, which contributes to the development of venous hyperaemia). In the second stage of inflammation, during microcirculation disorders, exudation occurs (the escape of the liquid part of the blood, electrolytes, and Proteins) along with the emigration of neutrophils, monocytes, and lymphocytes. Concurrently, proliferation phenomena arise—a productive inflammation most characteristic of tuberculosis, featuring an increase in cellular elements, their migration into the inflammation zone, and the formation of granulomas.

As a result of cellular transformations within a limited area not exceeding 1 mm², a focus of predominantly productive inflammation is formed, known as a tuberculous granuloma.

Over time, the center of the tubercle may undergo the death of its constituent cells, transforming the granuloma into a focus of caseous necrosis. The development of caseous necrosis leads to destructive changes, as well as deforming and fistulous processes (cavities).

Tuberculosis is an infectious disease in which all body systems are involved in the pathological process to varying degrees. Throughout the course of the disease, the body's reactivity changes, specific and paraspecific alterations occur in various organs and tissues, and dystrophic changes develop in the nervous and endocrine systems.

Thus, the entire diverse course of tuberculosis represents a complex yet unified process of continuous interaction between the Mycobacterium tuberculosis and the patient's body, in which all systems participate.

For the Treatment of tuberculosis patients, anti-tuberculosis drugs are prescribed for a prolonged period; these can strain enzyme systems, disrupt metabolic processes and the functional state of certain organs, and thus cause the development of various adverse reactions. In the issue of the Adverse effects of medications on the patient's body, drug allergy has acquired particular relevance in recent years.

When medicinal substances enter the bloodstream, Protein Complexes (artificial antigens) are formed, which trigger auto-immunization of the patient's body and The production of Antibodies. Allergic changes in the lungs manifest as vasculitis, increased vascular permeability, and lymphoid-histiocytic infiltration of the perivascular tissue.

Allergic manifestations of the adverse effects of anti-tuberculosis drugs may, in rare cases, follow an immediate type of reaction, developing into anaphylactic Shock, which can lead to the patient's death and therefore requires emergency care.

No less of a threat is posed by toxic reactions to anti-tuberculosis drugs, caused by a cytotoxic effect, as well as postoperative complications related to pulmonary tuberculosis. Among the latter, particular hazards include hemorrhages of various origins, thrombosis and thromboembolism in the pulmonary artery system, and respiratory failure resulting from "shock lung" syndrome.

Hemodynamic disturbances in the lesser (pulmonary) circulation play a significant role in the development of pulmonary thrombosis and embolism.

In the lesser circulation, the biochemical properties of blood change, which, combined with sluggish blood flow, promote the occurrence of thromboembolisms in the pulmonary vascular bed.

The causes triggering critical conditions in tuberculosis are diverse: acute hemorrhage, poisoning by anti-tuberculosis drugs, Pulmonary Embolism, impaired respiratory function and gas exchange during pneumothorax, water-electrolyte disorders, allergic or bacterial shock, and others.

Despite the variety of causes triggering critical conditions in patients with respiratory tuberculosis, the primary pathophysiological mechanism of their development is progressive hypoxia, most frequently of a mixed character.

At the onset of the pathological process, compensatory reactions aimed at the oxygenation of the Brain and heart and the maintenance of Blood Circulation are sharply activated. This occurs primarily due to the activation of the sympathoadrenal, pituitary-adrenal, and renin-angiotensin systems, along with The stimulation of the Autonomic nervous system and the reticular Formation of the Brainstem. Compensatory-adaptive reactions subsequently assume a pathological character because, as a result of the centralization of blood circulation, hypoxia in vital organs and systems increases, microcirculation processes are disrupted, anaerobic glycolysis prevails, hypoxia progresses, and, in the absence of timely treatment, patient death typically ensues.