Alveolar regions

Aerosols reach the alveolar space depending on their particle size and physico-chemical characteristics. Small particles that reach the alveiilar region (see Sections 2.3.7 and 3.1.1) may reach the circulation through the lymphatic drainage of the alveolar region. 

Figure 5. Doses averaged over all epithelial cells in the bronchial and alveolar regions of the lung per unit exposure to potential alpha-energy as a function of aerosol size, compared with doses to basal cells for several models of airway size and clearance behaviour.

Upper respiratory tract irritation can occur from inhalation of a medicinal gas, vapor, or aerosol. For assessing the potential of an inhalant to cause URT irritation, the mouse body plethysmographic technique (Alarie, 1966, 1981a, b) has proven to be extremely usefid. This technique operates on the principle that respiratory irritants stimulate the sensory nerve endings located at the surface of the respiratory tract from the nose to the alveolar region. The nerve endings in turn stimulate a variety of reflex responses (Alarie, 1973 Widdicombe, 1974) that result in characteristic changes in inspiratory and expiratory patterns and, most prominently, depression of respiratory rate. Both the potency of irritation and the concentration of... 

Crapo JD, Young SL, Fram EK, Pinkerton KE, Barry BE, Crapo RO (1983) Morphometric characteristics of cells in the alveolar region of mammalian lungs. Am Rev Respir Dis 128(2 Pt 2) S42-S46... 

The situation is, however, different in the alveolar region of the lung where the respiratory gas exchange takes place. Its thin squamous epithelium is covered by the so-called alveolar surface liquid (ASL). Its outermost surface is covered by a mixture of phospholipids and proteins with a low surface tension, also often referred to as lung surfactant. For this surfactant layer only, Scarpelli et al. [74] reported a thickness between 7 and 70 nm in the human lung. For the thickness of an additional water layer in between the apical surface of alveolar epithelial cells and the surfactant film no conclusive data are available. Hence, the total thickness of the complete ASL layer is actually unknown, but is certainly thinner than 1 gm. 

The size of the fibrous particles that appear to induce disease in the animal models is compatible with the measured respiratory range in humans (Lipp-man, 1977). Most particulate deposition takes place not in the upper or conducting portion of the airways but in the alveolar region of the pulmonary tree (the respiratory unit). Some surface deposition may occur at bifurcations in the bronchial tree, but the actual amount at each location is influenced by anatomy, specific to the species—probably to an individual—as well as the variety of fiber. A large proportion of airborne particulates are rejected as part of the normal clearance mechanisms in animals, but in humans clearance mechanisms may be compromised by smoking, for example. We are unaware of any experiments on fiber toxicity using smoking rats ... 

Other substances that can accumulate within the body include poorly soluble particulates that are deposited in the alveolar region of the lungs, substances that bind irreversibly to endogenous proteins, and certain metals and ions that interact with the crystal matrix of bone. The properties of these substances are such that the body cannot readily remove them hence they gradually build up with successive exposures and the body burden can be maintained for long periods of time. 

Particles with an aerodynamic diameter of 1-5 p are deposited in the airways (tracheobronchial regions) hy sedimentation under gravitational forces. As the alveolar regions are approached, the velocity of the airflow decreases significantly, allowing more time for sedimentation. The very small particles, generally less than 1 p, that penetrate to the alveoli are deposited there mainly hy diffusion. 

XB = tracheobronchial (trachea, bronchi, bronchioles to terminal bronchioles) pu = pulmonary (respiratory bronchioles, alveolar region)... 

On the other hand, particles from fossil fuel combustion and gas-to-particle conversion are generally much smaller (< 2.5-/Am diameter) and fall in the respirable size range. These particles can reach the alveolar region where gas exchange occurs. This region is not coated with a protective mucus layer, and here the clearance time for deposited particles is much greater than in the upper respiratory tract hence the potential for health effects is much greater (Phalen, 1984). 

Particles of aerodynamic diameter greater than 5 pm deposit primarily in the upper airways or mouth and throat region, while a significant percentage of those less than 1 pm do not deposit but are exhaled (Darquenne et al. 1997). Therefore, for optimum deposition in the alveolar region and systemic delivery, particles have to be between 1 and 5 pm. 

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