Airway Defense Mechanisms

The exchange surface area of the lung is the largest interface between the body and the environment. Therefore, the lungs have an important set of mechanisms to defend the body from foreign matter. The first line of defense is the upper airways, including the mouth and nose. A major function of the upper airways is to warm and humidify air entering the respiratory system, which prevents drying and cooling of the delicate epithelial barrier in the lungs. Complex air passages in the nose, called turbinates, also help trap large inhaled particles. Inhaled air enters the pharynx from the oronasal cavities, then passes to the larynx and through the vocal cords, and finally enters the trachea. Food and drink are kept out of the lungs by the epiglottis, which moves over the entrance to the larynx during swallowing. The lung is protected from very small particles suspended in the air, called aerosols, by three mechanisms. Large aerosols, with diameters of 1 ^m or more, are removed from inhaled gas by impaction in the nose and pharynx as just described . Impaction traps aerosols when they fail to turn a corner with gas flow, and inertia carries the particle onto a wet mucosal surface. Medium-sized aerosols are trapped in the airways by sedimentation, as the particles fall out of the airflow under their own weight. Sedimentation occurs in the terminal and respiratory bronchioles because the total cross-sectional area of the airways greatly increases, and the forward velocity of inhaled air decreases (see Fig. 4). This is the area at which most soot and coal dust is deposited. The smallest aerosols, with diameters of 0.1 ^m or less, can actually reach the alveoli by diffusion.

Particles that deposit in the lungs and airways are removed by two mechanisms. First, mucociliary transport removes foreign particles from the conducting airways (Fig. 15). Particles deposited in mucus are moved toward the mouth by the continuous beating of cilia on the airway epithelial cells. The cilia beat about 20 times/sec in a coordinated manner to move mucus upward out of the large airways at a speed of about 1-3 cm/min. When mucus reaches the pharynx, it can be swallowed, so deposited particles are removed from the respiratory system. Ciliary function can be impaired by smoking and pollutants such as sulfur and nitrogen oxides. Mucus is actually a complex secretion from the airway epithelium consisting of a gel layer and a sol layer. The top layer, or gel layer, is viscous and sticky to trap particles deposited on the airways. It contains macromolecules, such as mucin. The bottom layer is a less viscous secretion that bathes the 5- to 7-^m-long cilia on the airway epithelium. Therefore, the cilia can move easily in the sol layer, and the gel layer floating on top is moved up and out of the airways. Diseases such as cystic fibrosis and chronic bronchitis can affect mucous secretion. Second, alveolar macrophages provide an additional mechanism for removing particles deposited deeper in the lungs, where the blood-gas barrier must be very thin for gas exchange. Macrophages originate in the bone marrow and circulate in the blood as monocytes before settling in the respiratory zone of the lungs, where the epithelium is not ciliated. They roam the airway surfaces by ameboid action and engulf foreign particles by phagocytosis. Most foreign substances are destroyed by lysozymes inside the macrophage. However, carbon and mineral particles may be stored in residual bodies in the macrophage, which then settles in the interstitium. The effects of mineral dusts are especially insidious, leading to a progressive destruction of lung tissue, and even lung cancer in the case of asbestosis. Normal macrophages that do not settle in the interstitium leave the lung by the mucociliary transport or the lymphatics.

Neutrophils can leave the pulmonary circulation and provide a secondary line of phagocytic defense in the alveoli. Phagocytes, as well as immune cells (see later discussion), may release reactive oxygen species that can cause tissue damage. However, such damage is limited by the antioxidant glutathione, which occurs in surfactant at levels 100 times higher than in other tissues. Pulmonary cells have evolved efficient mechanisms to

FIGURE 15 Cross-sectional schematic of conducting airway showing ciliated epithelial cells interspersed with mucous secretory cells. Mucociliary transport (MCT) moves the sticky surface layer of mucus (gel layer = shaded globules) up the airways by the beating motion of cilia in the less viscous, lower layer of mucus (sol layer = stars). (From Gabriel and Boucher, Chap. 20 in Crystal et al, eds., The lung: Scientific foundations. Philadelphia: Lippincott-Raven, 1997.)

Dealing With Bronchitis

Dealing With Bronchitis

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