Primary tuberculosis - Pathogenesis

Primary tuberculosis is accompanied by damage to the lymph nodes, lungs, pleura, and sometimes other organs: kidneys, joints, bones, peritoneum. The area of specific inflammation can be very small and remain hidden during examination. With a large volume of damage, it is usually detected during clinical and radiological examination of the patient.

There are three main forms of primary tuberculosis:

• tuberculosis intoxication;
• tuberculosis of the intrathoracic lymph nodes;
• primary tuberculosis complex.

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Tuberculosis intoxication

Tuberculous intoxication is an early clinical form of primary tuberculosis with minimal specific damage. It develops in people with relatively minor functional disorders in the immune system. As a result of the formation of toxic products, transient bacteremia and toxemia occur, increasing the specific sensitization of tissues to mycobacteria and their metabolic products and increasing the tendency to pronounced toxic-allergic tissue reactions.

Mycobacteria in tuberculosis intoxication are mainly found in the lymphatic system, gradually settling in the lymph nodes and causing hyperplasia of lymphoid tissue. As a result, micropolyadenopathy develops, characteristic of all forms of primary tuberculosis.

Tuberculous intoxication is manifested by various functional disorders, high sensitivity to tuberculin and micropolyadenopathy. The duration of tuberculous intoxication as a form of primary tuberculosis does not exceed 8 months. It usually proceeds favorably. The specific inflammatory reaction gradually subsides, isolated tuberculous granulomas undergo connective tissue transformation. Calcium salts are deposited in the zone of tuberculous necrosis and microcalcifications are formed.

Sometimes tuberculosis intoxication becomes chronic or progresses with the formation of local forms of primary tuberculosis. The reverse development of tuberculosis intoxication is accelerated by treatment with anti-tuberculosis drugs.

Tuberculosis of the intrathoracic lymph nodes

Tuberculosis of the intrathoracic lymph nodes is the most common clinical form of primary tuberculosis, affecting various groups of intrathoracic lymph nodes. Inflammation most often develops in the lymph nodes of the bronchopulmonary and tracheobronchial groups, usually without involvement of lung tissue in the specific process. Tuberculous lesions of the lymph nodes of the bronchopulmonary group are often called bronchoadenitis.

After infection with Mycobacterium tuberculosis, a hyperplastic reaction develops in the lymph nodes with subsequent formation of tuberculous granulomas. The progression of specific inflammation leads to gradual replacement of lymphoid tissue with tuberculous granulations. The area of caseous necrosis can significantly increase over time and spread to almost the entire lymph node. Paraspecific and nonspecific inflammatory changes occur in the adjacent tissue, bronchi, vessels, nerve trunks, and mediastinal pleura. The pathological process progresses and affects other, previously unchanged lymph nodes of the mediastinum. The total volume of local damage can be quite significant.

Depending on the size of the affected intrathoracic lymph nodes and the nature of the inflammatory process, the disease is conventionally divided into infiltrative and tumorous (tumor-like) forms. The infiltrative form is understood to be a predominantly hyperplastic reaction of the lymph node tissue with minor caseous necrosis and perifocal infiltration. The tumorous form is associated with pronounced caseous necrosis in the lymph node and a very weak infiltrative reaction in the surrounding tissues.

The course of uncomplicated tuberculosis of the intrathoracic lymph nodes is often favorable, especially with early diagnosis and timely treatment. Perifocal infiltration resolves, calcifications form at the site of caseous masses, the lymph node capsule hyalinizes, and fibrous changes develop. Clinical recovery with the formation of characteristic residual changes occurs on average 2-3 years after the onset of the disease.

Complicated or progressive course of tuberculosis of the intrathoracic lymph nodes can lead to specific damage to the lung tissue. Lymph-hematogenous and bronchogenic generalization of the process is observed in patients with progressive disorders in the immune system, which deepen against the background of tuberculosis. More often this occurs with late detection of the disease and inadequate treatment.

Primary tuberculosis complex

Primary tuberculosis complex is the most severe form of primary tuberculosis, affecting both the primary tuberculosis complex and the pathogen, which is associated with high virulence and significant impairment of cellular immunity.

Primary tuberculosis complex is a local clinical form of primary tuberculosis, in which three components of specific damage are distinguished: primary affect with a perifocal reaction, tuberculosis of the regional lymph node and the zone of tuberculous lymphangitis connecting them.

Primary tuberculosis complex with lung and intrathoracic lymph node lesions may develop in two ways. In case of massive airborne infection with virulent mycobacteria tuberculosis, primary pulmonary affect in the form of acinous or lobular caseous pneumonia with a zone of perifocal inflammation occurs at the site of their introduction into the lung tissue. The affect is localized in well-ventilated areas of the lung, usually subpleurally. The inflammatory reaction spreads to the walls of the lymphatic vessels. Mycobacteria tuberculosis penetrate into regional lymph nodes with the lymph flow. The introduction of mycobacteria leads to hyperplasia of lymphoid tissue and the development of inflammation, which after a short-term nonspecific exudative phase acquires a specific character.

This is how a complex is formed, consisting of an affected area of the lung, specific lymphangitis and a zone of tuberculous inflammation in the regional lymph nodes.

In addition, with airborne infection, tuberculosis mycobacteria can penetrate through the intact mucous membrane of the bronchus into the peribronchial lymphatic plexuses and further into the lymph nodes of the lung root and mediastinum, where specific inflammation develops. A nonspecific inflammatory reaction occurs in the adjacent tissues. The resulting disorders lead to lymphostasis and dilation of the lymphatic vessels.

A lymphogenous retrograde pathway of development is possible. When inflammation spreads from a lymph node to the wall of an adjacent bronchus, mycobacteria can penetrate into the lung tissue by the bronchogenic pathway. The introduction of mycobacteria into the lung tissue causes the development of an inflammatory reaction, which usually affects the terminal bronchiole, several acini and lobules. The inflammation quickly acquires a specific character: a zone of caseous necrosis surrounded by granulations is formed. Thus, following the defeat of the intrathoracic lymph nodes, the pulmonary component of the primary tuberculosis complex is formed.

In the primary tuberculosis complex, widespread specific, pronounced paraspecific and nonspecific changes are observed. However, the tendency toward a benign course of the disease remains. Reversal occurs slowly. Early diagnosis of the primary tuberculosis complex and timely initiation of adequate treatment contribute to a positive result.

With the reverse development of the primary tuberculosis complex, perifocal infiltration gradually resolves, granulations transform into fibrous tissue, caseous masses become denser and impregnated with calcium salts. A hyaline capsule develops around the forming lesion. Gradually, a Ghon lesion forms in place of the pulmonary component. Over time, the Ghon lesion may undergo ossification. In the lymph nodes, similar reparative processes occur somewhat more slowly and also end with the formation of calcifications. Healing of lymphangitis is accompanied by fibrous compaction of the peribronchial and perivascular tissues.

The formation of a Ghon focus in the lung tissue and the formation of calcifications in the lymph nodes is a morphological confirmation of clinical cure of the primary tuberculosis complex, which occurs on average 3.5-5 years after the onset of the disease.

In patients with severe immunodeficiency, primary tuberculosis sometimes takes on a chronic, undulating, steadily progressive course. In the lymph nodes, along with slowly forming calcifications, fresh caseous-necrotic changes are found. New groups of lymph nodes are gradually involved in the pathological process, and repeated waves of lymphohematogenous dissemination with damage to previously unchanged parts of the lungs are noted. Foci of hematogenous dissemination are also formed in other organs: kidneys, bones, spleen.

In all forms of primary tuberculosis, the reverse development of the tuberculosis process and clinical cure are accompanied by the death of most mycobacteria and their elimination from the body. However, some mycobacteria are transformed into L-forms and persist in residual post-tuberculosis foci. The altered and incapable of reproduction mycobacteria maintain non-sterile anti-tuberculosis immunity, which ensures relative human resistance to exogenous tuberculosis infection.