Lung, Epithelium - Necrosis

Necrosis (Figure 1, Figure 2, Figure 3, and Figure 4) and degeneration are considered to be parts of the continuum of cell damage, with necrosis representing irreversible cell damage and degeneration representing reversible cell damage. The light microscopic features of necrosis include nuclear pyknosis, karyorrhexis, or karyolysis, cell swelling, loss of cellular detail, cell fragmentation, and cytoplasmic hypereosinophilia (in which the cytoplasm often has a homogeneous appearance). Large areas of necrosis (Figure 2, Figure 3, and Figure 4) may also have disrupted tissue architecture, large areas of necrotic debris, loss of staining intensity, and inflammatory cells. Necrosis of the epithelial cells lining the airways as a result of toxic injury is often characterized by sloughing of necrotic cells or cellular debris into the lumen. The light microscopic hallmarks of reversible cell damage include cellular swelling, cytoplasmic vacuolation, perinuclear clear spaces, formation of cytoplasmic blebs, loss of normal apical blebs from Clara cells, and loss of cilia. In some cases, detachment of viable cells from the epithelial surface and nuclear condensation (pyknosis) and cellular shrinkage of scattered cells within the epithelium, suggestive of imminent death of individual cells, may be interpreted as epithelial degeneration because it may be consistent with reversible damage to an epithelial surface, and evidence of outright necrosis may be lacking. Other lesions often accompany necrosis and degeneration, such as inflammation and hemorrhage.

The anatomic location of necrotic lesions may vary due to the physicochemical properties of the test agent or the susceptibility of a particular cell type to the test agent. The epithelium of the terminal bronchioles and alveolar ducts (i.e., the centriacinar region) and alveoli are particularly susceptible to injury due to the large surface area and fragility of the alveolar type I cells, the metabolic activity of P450 enzymes in Clara cells, and the generally thinner mucous layer.