Pneumocystosis - Causes and Pathogenesis

Causes of pneumocystosis

The cause of pneumocystosis is P. jiroveci, a microorganism whose taxonomic position has not been determined. Most researchers classify it as a protozoan (subtype Sporozoa, class Haplospora). However, in recent years, evidence has accumulated that pneumocystis are closer to fungi in terms of ribosomal RNA nucleotide sequences. This is an extracellular parasite with a predominant tropism for lung tissue, affecting first- and second-order pneumocytes. Only one species of P. jiroveci has been identified, but antigenic differences have been found between strains isolated from humans and some animals.

There are also disagreements in assessing the stages of pneumocystis development. Some authors distinguish four morphological forms, while others believe that there are only three. The first form, trophozoite, is an oval or amoeboid cell measuring 1-5 μm. Outgrowths extend from its surface, with the help of which trophozoites tightly adhere to the lung epithelium, so they are difficult to detect in sputum. The second form, precyst, is an oval cell measuring 2-5 μm that does not have outgrowths. The precyst wall consists of three layers, and there are several lumps (dividing nuclei) in the cytoplasm. The third form, cyst, is a cell measuring 3.5-6 μm, its walls also consist of three layers. Up to 8 intracystic bodies with a diameter of 1-2 μm and a two-layer membrane are found in the cytoplasm. The intracystic bodies come out when the cysts are destroyed and become extracellular trophozoites, starting a new life cycle of the pathogen. Pneumocystis do not penetrate the host cells during replication, but attach to their surface. There is no data on the production of toxins by Pneumocystis. Pneumocystis are not cultured on nutrient media.

The duration of survival of pneumocystis in the environment has not been studied, but the pathogen's DNA is present in the air of rooms where patients are located. Pneumocystis are sensitive to sulfonamides (sulfamethoxazole) in combination with pyrimidines (trimethoprim), sulfones (dapsone), some antiprotozoal agents (pentamidine, metronidazole), nitrofurans (furazolidone).

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Pathogenesis of pneumocystosis

The pathogenesis of Pneumocystis pneumonia is associated with mechanical damage to the walls of the pulmonary interstitium. The entire life cycle of Pneumocysts occurs in the alveoli, to the wall of which they are very tightly attached. Pneumocysts need a large amount of oxygen to develop. Gradually multiplying, they fill the entire alveolar space, capturing ever larger areas of lung tissue. With close contact of trophozoites with the walls of the alveoli, damage to the lung tissue occurs, the extensibility of the lungs gradually decreases, and the thickness of the alveolar walls increases by 5-20 times. As a result, an alveolar-capillary block develops, which leads to severe hypoxia. The formation of atelectasis areas aggravates the violation of ventilation and gas exchange. In patients with immunodeficiency states, a marked decrease in the number of CD4 + lymphocytes (less than 0.2x10 ⁹ /l) is critical for the development of Pneumocystis pneumonia.

In Pneumocystis pneumonia, three stages of the pathological process in the lungs are distinguished: edematous (lasts 7-10 days), atelectatic (1-4 weeks), emphysematous (duration varies). At autopsy, the lungs are enlarged, dense, heavy, pale purple; the lung tissue is easily torn, on the cut it has a marbled appearance with a grayish-bluish tint, the discharge is viscous.

Histological examination at the edematous stage reveals foamy-cellular masses in the lumen of the alveoli and terminal bronchioles, containing clusters of pneumocysts, around which neutrophils, macrophages and plasma cells accumulate. Such foamy alveolar exudate is not found in other diseases - it is a pathognomonic sign of pneumocystosis. At the atelectatic stage, plethora, cellular infiltration of the interalveolar septa with their subsequent destruction are found, which is most pronounced in the recurrent course of the disease in HIV infection. If recovery occurs at the last stage, a gradual reverse development of the process occurs. In relapses in AIDS patients, fibrocystic changes in the lungs may occur.

In AIDS, dissemination of pneumocysts occurs in 1-5% of cases: almost any organ can be affected. In this case, an isolated focus of extrapulmonary pneumocystosis or a combination of pulmonary and extrapulmonary lesions can develop.