Pneumocystis jirovecii pneumonia pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Pathophysiology
Pneumocystis jirovecii (previously classified as Pneumocystis carinii) was previously classified as a protozoa. Currently, it is considered a fungus based on nucleic acid and biochemical analysis.
The risk of pneumonia due to pneumocystis jirovecii increases when CD4 levels are less than 200 cells/μl. In these immunosuppressed individuals the manifestations of the infection are highly variable.[1] The disease attacks the interstitial, fibrous tissue of the lungs, with marked thickening of the alveolar septa and alveoli and leading to significant hypoxia which can be fatal if not treated aggressively; ergo, LDH levels increase and gas exchange is compromised. Oxygen is less able to diffuse into the blood, leading to hypoxia. Hypoxia, along with high arterial carbon dioxide (CO2) levels, stimulates ventilation, thereby causing dyspnea.
Life Cycle
The complete life-cycles of any of the species of Pneumocystis are not known, but presumably all resemble the others in the genus. The terminology follows zoological terms, rather than mycological terms, reflecting the initial misdetermination as a protozoan parasite. All stages are found in lungs and because they cannot be cultured, direct observation of living Pneumocystis is difficult. The trophozoite stage is the vegetative state. It is single-celled and appears amoeboid (multilobed) and closely associated with host cells. Globular cysts eventually form that have a thicker wall. Within these ascus-like cysts, eight spores form which are released through rupture of the cyst wall. The cysts often collapse forming crescent-shaped bodies visible in stained tissue. It is not known for certain if meiosis takes place within the cysts, or what the genetic status is of the various cell types - see DPDx life-cycle diagram.
This is a generalized life cycle proposed by John J. Ruffolo, Ph.D. (Cushion, MT, 1988) for the various species of Pneumocystis. These fungi are found in the lungs of mammals where they reside without causing overt infection until the host's immune system becomes debilitated. Then, an oftentimes lethal pneumonia can result. 1 Asexual phase: trophic forms replicate by mitosis 2 to 3. Sexual phase: haploid trophic forms conjugate 1 and produce a zygote or sporocyte (early cyst) 2. The zygote undergoes meiosis and subsequent mitosis to produce eight haploid nuclei (late phase cyst) 3. Spores exhibit different shapes (such as, spherical and elongated forms). It is postulated that elongation of the spores precedes release from the spore case. It is believed that the release occurs through a rent in the cell wall. After release, the empty spore case usually collapses, but retains some residual cytoplasm 4. A trophic stage, where the organisms probably multiply by binary fission is also recognized to exist. The organism causes disease in immunosuppressed individuals.
References
- ↑ Hughes WT (1996). Pneumocystis Carinii. In: Barron's Medical Microbiology (Barron S et al, eds.) (4th ed. ed.). Univ of Texas Medical Branch. (via NCBI Bookshelf) ISBN 0-9631172-1-1.