Anatomy Of The Airways

The airways (constituting the lungs) may be viewed as a series of dividing passageways originating at the trachea and terminating at the alveolar sacs.

In the context of aerosol design and delivery, such a "static" overview represents a satisfactorily simple model. However, many factors beyond the anatomy of the airways are relevant to the therapeutic use of aerosols.

Structure

The airways are often described as the pulmonary tree, in that their overall form resembles a tree. The tree trunk is analogous to the trachea of the airways that bifurcates to form main bronchi. These divide to form smaller bronchi that lead to individual lung lobes, three lobes on the right side and two on the left side. Inside each lobe, the bronchi undergo further divisions to form new generations of smaller caliber airways, the bronchioles. This process continues through the terminal bronchioles (the smallest airway not involved with an alveolus), the respiratory bronchioles (which exhibit alveoli protruding from their walls), and alveolar ducts and terminates in the alveolar sacs. In the classic model of the airways (as described by Weibel [1]), each airway divides to form two smaller "daughter" airways (Fig. 1); as a result, the number of airways at each generation is double that of the previous generation. The model proposes the existence of 24 airway generations in total, with the trachea being generation 0 and the alveolar sacs being generation 23.

In passing from the trachea to the alveolar sacs, two physical changes occur in the airways that are important in influencing airway function. Firstly, the airway caliber decreases with increasing generations, for example, tracheal diameter 1.8 cm versus alveolar diameter 0.04 cm (Fig. 2). This permits adequate penetration of air to the lower airways for a given expansion of the lungs. Secondly, the surface area of the airways increases with each generation, to the extent that the total area at the level of the human alveolus is on the order of 140 m2 [2]. The alveolus is the principal site of gas exchange in the airways, a function compatible with the increased surface area that promotes extensive and efficient diffusional gas exchange between the alveolar space and the blood in alveolar capillaries (vide infra). The relatively small change in cross-sectional area that occurs over the 19 generations of airways between the trachea and the terminal bronchiole (from 2.5 to 180 cm2) [3] fosters the rapid, bulk flow of inspired air down to the terminal bronchiole. By contrast, the cross-sectional area increases greatly in the four generations between the terminal bronchiole and the alveolar sac (from 180 to 10,000 cm2) [3], which results in a significant decrease in the velocity of airflow to the extent that the flow velocity fails to exceed that of diffusing oxygen molecules [4]. Accordingly, diffusion assumes a greater role in determining the movement of gases in these peripheral airways.

The various levels of the airways may be categorized functionally as being either conducting or respiratory airways. Those airways not participating in gas

Figure 1 Model of airway according to Weibel. (Modified from Ref. 1.

exchange constitute the conducting zone of the airways and extend from the trachea to the terminal bronchioles. This region is the principal site of airway obstruction in obstructive lung diseases, such as asthma. The respiratory zone includes airways involved with gas exchange and comprises respiratory bronchioles, alveolar ducts, and alveolar sacs. As such, conducting and respiratory zones of the airways may be distinguished simply by the absence or presence of alveolar pockets (which confer the gas exchange function). Regions within each zone may be classified further on a histological basis. For example, the contribution of cartilage to the airway wall is one means of differentiating the trachea from bronchi and bronchioles because cartilage exists as incomplete rings in the trachea, regresses to irregularly shaped plates in bronchi, and is absent from bronchioles. Also, respiratory bronchioles may be discriminated from terminal bronchioles by the presence of associated alveoli.

Other histological changes are evident downward throughout the pulmonary tree, and the cellular profile of each region has distinctive effect on

Figure 2 Graph of airway diameter and cross-sectional area as a function of airway generation.

functional aspects of the airways under physiological and pathophysiological conditions.

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