Airway lumen

Airway cross-sections have the nominal anatomy shown in Fig. 5.16. Airway surface liquid (AST), primarily composed of mucus gel and water, surrounds the airway lumen with a thickness thought to vary from 5 to 10 mm. AST lies on the apical surface of airway epithelial cells (mostly columnar ciliated epithelium). This layer of cells, roughly two to three cells thick in proximal airways and eventually thinning to a single cell thickness in distal airways, rests along a basement membrane on its basal surface. Connective tissue (collagen fibers, basement membranes, elastin, and water) lies between the basement membrane and airway smooth muscle. Edema occurs when the volume of water within the connective tissue increases considerably. Interspersed within the smooth muscle are respiratory supply vessels (capillaries, arteriovenous anastomoses), nerves, and lymphatic vessels. 

FIGURE 5.18 Vasculature structure along a portion of bronchia muscle. Airway epithelia are not shown in this figure but lie between the submucosal venules and the airway lumen. Modified from Deffe-bach et al. ... 

Airstream neutralization of acid aerosols by NH3 present in the airway-lumen reduces the health risk associated with acid particles by reducing the acid concentration prior to particle deposition.- In addition, the liquid lining of the respiratory tract probably acts as a chemical buffer," further reducing the health hazard posed by inspired acid particles. Principal factors controlling airstream neutralization of acid aerosols, which is considered to be a diffusion-limited process, are particle surface area, and particle... 

Airway lumen Opening in conducting airway through which air moves... 

The exudative inflammatory process and sloughing of epithelial cells into the airway lumen impair mucociliary transport. The bronchial glands are increased in size, and the goblet cells are increased in size and number. Expectorated mucus from patients with asthma tends to have high viscosity. 

While all the aforementioned cell types form the epithelial surface of the airways, basal cells reside deep in the tracheo-bronchial epithelium and are not directly in contact with the airway lumen. Basal cells are considered as the stem cell or progenitor cell of the bronchial epithelium and are pyramidal in shape with a low cytoplasmic/nuclear volume ratio [8, 15-17],... 

As noted earlier, air-velocity profiles during inhalation and exhalation are approximately uniform and partially developed or fully developed, depending on the airway generation, tidal volume, and respiration rate. Similarly, the concentration profiles of the pollutant in the airway lumen may be approximated by uniform partially developed or fully developed concentration profiles in rigid cylindrical tubes. In each airway, the simultaneous action of convection, axial diffusion, and radial diffusion determines a differential mass-balance equation. The gas-concentration profiles are obtained from this equation with appropriate boundary conditions. The flux or transfer rate of the gas to the mucus boundary and axially down the airway can be calculated from these concentration gradients. In a simpler approach, fixed velocity and concentration profiles are assumed, and separate mass balances can be written directly for convection, axial diffusion, and radial diffusion. The latter technique was applied by McJilton et al. 

Gases that do not react irreversibly with epithelial tissue, such as anesthetic gases, may diffuse into the bloodstream and will ultimately be eliminated from the body. A different and earlier model developed by DuBois and Rogers estimates the rate of uptake of inhaled gas from the tracheobronchial tree in terms of diffusion through the epithelial tissue, rate of blood flow, and solubility of the gas in blood. The rate of uptake from the airway lumen is determined by the equation ... 

The ciliated cells are most vulnerable to damage. The most frequent degenerative changes in these cells are loss of cilia, necrosis, and sloughing of cells into the airway lumen. Necrosis and desquamation of nonciliated and secretory cells are less frequently observed. 

Cellular pathophysiology of asthma. Top, Cross-section of the normal airway and the asthmatic ain/vay. Mediators released during the inflammatory process associated with asthma cause bronchoconstriction, mucus secretion, and mucosal inflammation and edema. These changes reduce the size of the airway lumen and increase resistance to airflow, which leads to wheezing and shortness of breath. Bottom, The multitude of inflammatory cells (macrophages, eosinophils, mast cells, neutrophils) and neurotransmitters implicated in asthma pathophysiology. 

The causes of airway narrowing in acute asthmatic attacks (or "asthma exacerbations") include contraction of airway smooth muscle inspissation of viscid mucus plugs in the airway lumen and thickening of the bronchial mucosa from edema, cellular infiltration, and hyperplasia of secretory, vascular, and smooth muscle cells. Of these causes of airway obstruction, contraction of smooth muscle is most easily reversed by current therapy reversal of the edema and cellular infiltration requires sustained treatment with antiinflammatory agents. 

Figure 27.20. Comparison of normal and asthmatic airways. The asthmatic airway is characterized by thickened airway smooth muscle that constricts to cause airway narrowing and obstruction. Mucus secreted by epithelial (goblet) cells also contributes to the obstruction of the airway lumen. (Adapted from Life ART illustration series, Lippincott Williams Wilkins, Hagerstown, MD, 1994. This figure was completely redrawn by the author from materials cited.)...

Figure 1.1 Intraepithelial dendritic cells in rat airway wall. Top panel adult rat trachea sectioned through the airway epithelium parallel to the basement membrane stained by immunoperoxidase for la note darkly stained dendritic cells. Middle and bottom panels longitudinal frozen sections of adult (middle) and 8-day-old (bottom) rat trachea stained as in top. Note la dendritic cells in and below airway epithelium of adult, compared to preweanling. L, airway lumen E, airway epithelium S, submucosa. Reproduced with permission from...

Mucosal oedema contributes to the airway narrowing present in asthma. Contraction of endothelial cells in post-capillary venules leads to the formation of gaps which allow the outflow of plasma. This occurs in response to mediators released from inflammatory cells such as H, PGs, LTs, and platelet aaivating factor (PAF) which probably act directly on endothelial cells and bradykinin which may act via neural reflexes. In addition to obstructing the airway lumen, exuded plasma may... 

The lung has a rich autonomic innervation that enables it to modulate the airway lumen available for airflow, the vascular resistance to blood flow, or the matching of these two flows in response to stimuli that impinge on... 

In the first definitive monograph on asthma, published in 1864, Sir Henry Hyde Salter concluded that the airway obstruction in asthma results from bronchoconstriction, mucus plu ng of the airway lumen, and edema of the airway wall (Salter, 1864). Salter s interpretations were probably based on clinical observations rather than on pathological examinations, because post-mortem findings were not described at that time. In fact, the initial histopathological studies of the airways of asthmatics did not recognize the presence of mucosal edema For example, in the first description of a post-mortem examination of a patient who died in status asthmaticus, Leyden concluded that the airflow obstruction resulted from mucus in the airways and that the walls [of bronchi]. ..are not essentially changed (Leyden, 1886). 

There are several consequences of an increase in the permeability of the blood vessels of the airway mucosa. Plasma leakage could result in mucosal edema and the movement of fluid into the airway lumen, both of which could contribute to airflow obstruction. In addition, plasma-derived inflammatory mediators could form in the mucosa and airway lumen, and extravasated plasma proteins could increase the viscosity of sputum. 

Whether an increase in vascular permeability results in mucosal edema depends on the balance between the amount of leakage into the mucosa and the rate of clearance from the mucosa, either through the lymphatics or across the epithelium into the airway lumen. The increase of vascular permeability produced by inflammatory stimuli can result in the bulk flow of plasma into the airway mucosa (Renkin, 1992). The amount of plasma leakage depends upon the number of gaps that form in the endothelium of the leaky vessels, the duration of the gaps and the intravascular pressure that drives the extravasation (Clough, 1991 Taylor and Ballard, 1992). The movement of plasma proteins and other osmotically active solutes into the mucosa can increase the interstitial oncotic pressure, which favors the net movement of fluid out of vessels and further increases the amount of leakage (Taylor and Ballard, 1992). 

Fluid can leave the mucosa through lymphatics or by entering the airway lumen. In this respect the airway epithelium serves as a gate across an escape route for fluid in the interstitium. This escape route has been demonstrated in the airways of the rat by Persson and colleagues (Persson, 1990, 1991 Greiff et al. 1993) ... 

Erjefalt, I. and Persson, C.G.A. (1986). Anti-asthma drugs attenuate inflammatory leakage of plasma into airway lumen. Acta Physiol. Scand. 128, 653-654. 

Olivenstein, R., Xu, L.J. and Martin, J.G. (1994). Microvascular leak into the airway lumen during the early and late response to antigen in rats. Am. J. Respir. Crit. Care Med. 149, A528. 

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