Normal Lung VII

The alveolar epithelium is covered primarily by type I and type II epithelial cells. The characteristics of the alveolar septal wall in normal human lung is shown in Fig. 12. Type I epithelial cells are thin squamous epithelial cells having an average surface area of approximately 7000 µm2 (Table 2). Their highly attenuated cytoplasm has an average thickness of only 0.36 µm. The alveolar epithelium contains approximately equal numbers of type I and type II cells. The type II cell is cuboidal in shape and is commonly found at junctions of alveolar septa and along the alveolar surfaces surrounding intrapulmonary vascular and airway structures. Alveolar type II epithelial cells have conspicuous mitochondria and an extensive Golgi apparatus, indicating a high synthetic role for these cells. They are characterized chiefly by the presence of large numbers of small microvilli on the apical surface (Fig. 13) and of unique secretory granules, known as lamellar bodies. Each type II cell contains 100 to 200 lamellar bodies. These are composed of tightly packed whirls of surfactant, which give these bodies their lamellar appearance on cross-section. The continued secretion of lamellar contents replenishes surfactant at the alveolar air-liquid interface. Alveolar type II cells are connected to adjacent type I cells with a relatively impermeable tight junction. These junctions contain three to five junctional strands on electron microscopy of freeze-fracture replicas. Type II cells have four known primary functions: (1) They secrete surfactant. (2) They act as an ion pump, moving fluid from the alveolar spaces into the subjacent interstitial spaces. Type II cells move sodium from the alveolar lumen to the interstitium via an apical sodium channel regulated by cyclic AMP. Water passively follows the sodium movement. (3) They repair alveolar injury. These cells are the progenitor cells for alveolar epithelium and can regenerate alveolar type I epithelium. (4) They control alveolar inflammation. Type II alveolar epithelial cells secrete antiinflammatory cytokines. They also secrete antioxidants, including the extracellular superoxide dismutase enzyme. Type II cells have been shown to secrete nitric oxide by the activation of nitric oxide synthase. The secretion of both antioxidant enzymes and nitric oxide by type II cells is induced by the proinflammatory cytokines interferon-g and tumor necrosis factor-a, suggesting a role for these cells in the control of inflammatory functions.

FIG. 12. Transmission electron micrograph showing the alveolar septum from a normal human lung. An efficient exchange of O2 and CO2 between inspired air and red blood cells is promoted by the large gas exchange surface with minimal distances (arrow) across the epithelial, interstitial, and endothelial components of the alveolar septa. I, type I alveolar epithelial cell; II, type II alveolar epithelial cell; c, capillary endothelial cell. Bar = 1 µm.

TABLE 2. Characteristics of alveolar septal cells in normal human lung

FIG. 13. Scanning electron micrograph of the alveolar septal surface showing several type II alveolar epithelial cells surrounded by type I epithelium. Type II cells are identified by their distinctive microvilli. In this micrograph, the overlying surfactant layer was removed by fixatives.

The shape of alveoli in vivo approximates a smooth partial circle. Smoothing of the folds on the alveolar surface is accomplished by folding of alveolar septal membranes into the capillaries and by filling of tissue depressions with alveolar lining fluid containing surfactant at its surface. Changes in alveolar size are thought to occur primarily by folding and unfolding of the alveolar pleats, and this process minimizes stress tension on alveolar septal cells.

Stability of alveoli with their small radius of curvature requires a highly surface-active material at the air-liquid interface. La Place's Law describes the relationship of the alveolar pressure (P) required to keep an alveolus open with alveolar surface tension (t) and radius of curvature (r):

According to this principle, as the radius falls during exhalation, the surface tension must also fall, or the required pressure to maintain open alveoli would rise. As alveolar pressure falls during exhalation, this scenario would result in alveolar collapse with each breath. Surfactant prevents alveolar collapse. As the radius of alveoli decreases, the surfactant phospholipids are packed more tightly and surface tension is reduced. Thus, alveolar surface tension and the radius of alveoli in vivo fall synchronously, and alveolar stability is maintained.

Surfactant is a complex mixture of lipids and proteins synthesized by alveolar type II epithelial cells. The primary lipids include saturated phosphatidylcholine and phosphatidylglycerol. Surfactant also contains a number of proteins, three of them identified as surfactant proteins A, B, and C. Each of these facilitates the spreading and recycling of surfactant. A fourth surfactant protein, SP-D, is produced and secreted by type II cells but is not known to be a part of surfactant. It is thought to play a role in antibacterial defense.