Alveolar duct bifurcations

Figure 27.19. Illustration of early asbestos-induced fibroproliferative lesions in a rat inhalation model. (1) Inhaled fibers deposit at alveolar duct bifurcations. (2) Within 24 hr, macrophages accumulate at sites of fiber deposition and become activated by fibers to secrete growth factors. (3) Within 72hr fibroblasts proliferate.

There is an important aspect of the deposition patterns that often escapes the unwary reader, who may be getting the impression that the three compartments can be treated as homogeneous. In fact, it is expected and observed experimentally that the deposition in the upper respiratory tract and central airways, which is primarily by impaction, tends to take place at the bifurcations. It would be expected, however, that in the lower part of the respiratory tract, where sedimentation and diffusion dominate and the gas flow should be essentially laminar, the deposited material would be evenly spread on the surface. Evidence from studies of experimental animals indicates that this is not so [53,54]. Even material that passes all the way through the small airways tends to deposit at the alveolar duct bifurcations, instead of covering evenly the alveolar spaces. 

Figure 2 (A) SEM of an ADB 48 hours after exposure to chrysotile asbestos fibers. Many of the deposited fibers have been covered by the alveolar epithebum (arrows) and others have been phagocytized by AM. (B) Transmission electron micrograph of chrysotile asbestos fibers (arrow heads) that have been transported fiom the alveolar space ( ), through the AE, and are about to he deposited in the underlying alveolar interstitium. An interstitial MC and adjacent extracellular collagen (Q are observed. Abbreviations SEM, scanning electron micrograph ADB, alveolar duct bifurcations AM, alveolar macrophages AE, alveolar epithelium MC, mesenchymal cell.

All inhaled particles evoke an inflammatory response in the lung. In most reported studies the initial inflammatory cells are polymorphonuclear leukocytes (PMNL), and these are followed by an influx of alveolar macrophages (1,41,49,64-68,78,89). In a few studies (55,70) only a macrophage response has been seen, at least when considering cells accumulating at the first alveolar duct bifurcations, the major site of particle impaction in these specific experiments. As a rule, and provided the point of overload (see following) is not reached, there is a reasonably good correlation between the number of particles deposited and... 

The transition zone consists of the respiratory bronchioles (generations 17 to 19), which contain alveoli. At the terminal end, the respiratory zone is composed of parenchyma that contains the alveolar ducts and about 300 million alveoli (alveolar sacs) to provide the gas-exchange surface. Since the surface area expands to such a large extent within the very last generations of bifurcations, the inhalation airflow rapidly slows down to zero velocity so that the movement of gas molecules and the exchange occurs entirely by diffusion (Stocks and Hisloop 2002). 

A host of authors since the early 1990s (e.g., Refs. 24,42-47,52, see Ref. 3 for more of these many references) have performed PLS in various idealized replicas of single-, double-, and triple-bifurcation segments of the lung as well as parts of simplified alveolar ducts. Deposition in the particular respiratory tract segment being simulated can be predicted more accurately with this approach than with the simplified, one-dimensional LDMs or EDMs. 

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