Physiological Pharmaceutics

226 Physiological PharmaceuticsFigure 10.4 Cross-section of the alveoliThere are several types of pulmonary alveolar cells. Type I (or small type A), are nonphagocytic,membranous pneumocytes. These surface-lining epithelial cells areapproximately 5 µm in thickness and possess thin squamous cytoplasmic extensions thatoriginate from a central nucleated portion. These portions do not have any organelles andhence they are metabolically dependent on the central portion of the cell. This reduces theirability to repair themselves if damaged.Attached to the basement membrane are the larger alveolar cells (Type II, type B orseptal cells). These rounded, granular, epithelial pneumocytes are approximately 10 to 15µm thick. There are 6 to 7 cells per alveolus and these cells possess great metabolic activity.They are believed to produce the surfactant material that lines the lung and to be essentialfor alveolar repair after damage from viruses or chemical agents.Alveolar-capillary membraneThe blood and alveolar gases are separated by the alveolar capillary membrane (Figure 10.4)which is composed of a continuous epithelium of 0.1 to 0.5 µm thickness, a collagen fibrenetwork, a ground substance, a basement membrane and the capillary endothelium. Theinterstitium is composed of the basement membrane of the endothelium, a groundsubstance, and epithelium. It forms a three dimensional skeleton to which the alveoli andcapillaries are attached. Maximum absorption probably occurs in the areas where theinterstitium is the thinnest (80 nm) since the surfactant is also thin in these areas (15 nm).Drainage of the interstitial fluid occurs by passage into the lymphatics, which often happenslong after passage along the alveolar wall.The thickness of the air-blood barrier varies from 0.2 µm to 10 µm. The barrier isminimal when the thickness is less than 0.5 µm since the epithelium and endothelium arepresent only as thin cytoplasmic extensions and the interstitium exists as a narrow gapbetween mostly fused membranes. When the diameter exceeds 0.5 µm additional structuralelements are present. The minimal barrier thickness is nearly identical in structure anddimensions in all mammalian species that have been investigated. This is in contrast to thealveolar surface areas which increase proportionally with body weight.