Alveolar space

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. 

Martin, T.F., Pistorese, B.P., Chi, E.Y., Goodman, R.B. and Mathay, M.A. (1989). Effects of LTB4 in the human lung recruitment of neutrophils into the alveolar spaces without a change in protein permeability. J. Clin. Invest. 84, 1609-1619. 

Moore BB, Kolodsick JE, Thannickal VJ, et al. CCR2-mediated recruitment of fibrocytes to the alveolar space after fibrotic injury. Am J Pathol 2005 166(3) 675-684. 

Macrophage (peritoneal, pleural, alveolar spaces) Histiocytes (tissues) Monocytes (blood) some cell-mediated responses)... 

Hastings RH, Grady M, Sakuma T, Matthay MA (1992) Clearance of differentsized proteins from alveolar spaces in humans and rabbits. J Appl Physiol 73 1310-1317. 

The positively charged amino acids promote the interaction between the peptide and the negatively charged head groups of the phosphatidylgly-cerol (123-125). The purpose of this particular property has been proposed to facilitate the transition of surfactant phospholipid membranes from the lamellar body to the alveolar spaces (123). 

Because of the complexity of the actual structures, the emphasis in modeling has been on obtaining an average representation, and the variability among individuals tends to be neglected. There are two experimental studies of variability of airway dimensions in living humans as revealed by aerosol-deposition studies. Lapp et al. assessed the size of alveolar spaces in terms of half-life of aerosol persistence during breath-... 

Fig. 3.6 Sketch of an alveolar-capillary unit showing alveolar spaces, cells, and a blood vessel. AM — alveolar macrophage, PMN = polymorphic nucleosite. Other cells indicated Type I and II intraalveolus, a fibroblast in the interstitium, and endothelial cells lining the adjacent capillary. ChTV = chemotaxin.

An immediate response to dust inhalation is the migration of polymorphonuclear leukocytes (PMNs) across epithelial—endothelial junctions to the alveolar space (see Fig. 3.6). Macrophages release a chemotactic factor that mobilizes and attracts PMNs from the pulmonary blood. However, the initial PMN accumulation clears rapidly. 

Paulet and Desbrousses (1970) exposed groups of 10 rats/sex (strain not specified) to chlorine dioxide vapors at a concentrations of 0 or 2.5 ppm (6.9 mg/m ), 7 hours/day for 30 days. The weekly exposure frequency was not reported. Chlorine dioxide-exposed rats exhibited respiratory effects that included lymphocytic infiltration of the alveolar spaces, alveolar vascular congestion, hemorrhagic alveoli, epithelial erosions, and inflammatory infiltrations of the bronchi. The study authors also reported slightly decreased body weight gain and decreased erythrocyte and increased leukocyte levels, relative to controls. Recovery from the pulmonary lesions was apparent in rats examined after a 15-day recovery period. 

Death from adult respiratory distress syndrome was reported in one person who sprayed nickel with a metal arc process without wearing personal protective equipment (Rendall et al. 1994). Several days after the exposure, urinary concentrations of nickel were 700 pg/L, in comparison to levels of <0.1-13.3 pg/L in persons not occupationally exposed to nickel (Sunderman 1993). The death occurred 13 days after the 90-minute exposure to an estimated concentration of 382 mg nickel/m of principally metallic nickel with the majority of particle sizes less than 1.4 pm. Histological examination of the lungs revealed alveolar wall damage and edema in alveolar spaces, and in the kidneys marked tubular necrosis was noted. 

In this profile, a chronic-duration inhalation MRL of 2x lO " mg nickel/m has been derived based on a NOAEL of 0.03 mg nickel/m as nickel sulfate that was identified in a 2-year study of nickel sulfate in rats (NTP 1996c). Chronic active inflammation of the lungs was observed at 0.06 mg nickel/m. The inflammation was described as follows multifocal, minimal-to-mild accumulations of macrophages, and neutrophils and cell debris within alveolar spaces. The prevalence of lung fibrosis was also significantly increased at 0.06 mg nickel/m This chronic-duration inhalation MRL should also be protective of intermediate-duration exposure. 

Body weights of female rats were 6-9% lower than controls during the second year. Hematology examinations completed at a 15 month interim sacrifice showed no effects. The only treatment-related changes noted were in the respiratory tract. Minimal to mild chronic active inflammation was observed at all concentrations at the 7 month interim sacrifice, but only at the two higher concentrations at two years. The inflammation was described as multifocal, minimal to mild accumulations of macrophages, neutrophils and cell debris within alveolar spaces. Fibrosis was observed in 2/54, 6/53, 35/53 and 43/53 male rats, and 8/52, 7/53, 45/53, and 49/53 female rats at 0, 0.03, 0.06, and 0.11 mg/m, respectively. Hyperplasia of the bronchial lymph nodes and atrophy of the olfactory epithelium were observed at the high dose. 

FI G U RE 10.2 Schematic representation of alveolar cells and possible mechanism of transport of molecules from the alveolar space into the circulation. Particles will release molecules of interest (gray circles) into the mucus in which the particle is embedded. The molecule can either be lost in the mucus, taken up by alveolar macrophages by phagocytosis or diffusion, taken up by alveolar epithelial cells by passive or active transport, or bypass the alveolar cells via paracellular transport depending upon the properties of the drug. Once a molecule has reached the extracellular space, the same mechanisms are possible for transport from the extracellular space into the blood. Molecules in the extracellular space may also reach to circulation via the lymph. 

No studies were located regarding absorption of barium in humans following inhalation exposure. However, results of studies with experimental animals suggest that the rate and extent of absorption of barium from the respiratory tract depends on the exposure level, how much barium reaches the alveolar spaces, the clearance rate from the upper respiratory tract, and the solubility of the particular form of barium that was administered. 

It is interesting that the adult human lung has an enormous gas tissue interface, approximately 90 m2, 70 m2 alveolar space. This large surface, together with the blood capillary network surface of 140 m2, with its continuous and profuse blood flow, offers an extremely rapid and efficient medium for the absorption of chemicals from the air, into the alveolar portion of the lungs, and into the bloodstream. 

There are many commercially available nebulizers with differing mass output rates and aerosol size distributions which will be a function of operating conditions, such as compressed air flow rate. As described above, for maximum efficacy, the drug-loaded droplets need to be less than 5 pm. In the treatment or prophylaxis of P.carinii pneumonia with nebulized pentamidine where the target is the alveolar space it is preferable to use nebulizers capable of generating droplets of less than 2 pm. 

Return of gas-depleted blood to the lung As the venous circulation returns blood depleted of anesthetic to the lung, more gas moves into the blood from the lung according to the partial pressure difference. Over time, the partial pressure in the alveolar space closely approximates the partial pressure in the inspired mixture that is, there is no further anesthetic uptake from the lung. 

Washout When the administration of an inhalation anesthetic is discontinued, the body now becomes the source that drives the anesthetic into the alveolar space. The same factors that influence attainment of steady-state with an inspired anesthetic determine the time course of clearance of the drug from the body. Thus, nitrous oxide exits the body faster than halothane. 

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