Respiratory tract alveolar

Local host defenses of both the upper and lower respiratory tract, along with the anatomy of the airways, are important in preventing infection. Upper respiratory defenses include the mucodliary apparatus of the nasopharynx, nasal hair, normal bacterial flora, IgA antibodies, and complement. Local host defenses of the lower respiratory tract include cough, mucodliary apparatus of the trachea and bronchi, antibodies (IgA, IgM, and IgG), complement, and alveolar macrophages. Mucus lines the cells of the respiratory tract, forming a protective barrier for the cells. This minimizes the ability of organisms to attach to the cells and initiate the infectious process. The squamous epithelial cells of the upper respiratory tract are not ciliated, but those of the columnar epithelium of the lower tract are. The cilia beat in a uniform fashion upward, moving particles up and out of the lower respiratory tract. 

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... 

From a drug delivery perspective, the components of the host defence system comprise barriers that must be overcome to ensure efficient drug deposition as well as retention in and absorption from the respiratory tract. Important non-absorptive clearance mechanisms include mucociliary clearance, alveolar macrophages and metabolism (Figure 6.2). 

The sites of action and effects of ozone and other photochemical oxidants are described in Chapters 8 and 9. Recent work with primates has suggested that ozone is absorbed along the entire respiratory tract, penetrates more into the peripheral nonciliated airways, and causes more lesions in the respiratory bronchioles and alveolar ducts as the inhaled ozone concentration increases from 0.2 to 0.8 ppm. The most common and most severe tissue damage was observed in the respiratory bronchioles. The ciliated cells in the terminal bronchioles and the Type 1 cells in the epithelial layer of the proximal alveoli of rats were the... 

Particle deposition in the respiratory tract can initiate inflammatory responses. With repeated deposition, inflammation becomes chronic, and the site or sites of deposition beeome laden, not only with the particulates, but with several types of cells—fibroblasts, macrophages, leukocytes, and lymphocytes. These cells are normal constituents of the lung, an organ composed predominantly of connective tissue. Lung connective tissue forms the thin membrane that defines the functional alveolar-capillary unit. Inside this air sac and on the membrane are specialized eells required for gas exchange, maintenance, and repair (Fig. 3.6). 

The lower respiratory tract (pulmonary region or alveolar ducts and sacs) is the area where gas exchange occurs. Alveolar sacs, clusters of two or more alveoli, branch from alveolar ducts. It is generally considered that there is a total of approximately 300 million alveoli in the lungs of adult humans. The total alveolar surface area in the lungs of adult humans is... 

Rhabdomyosarcomas developed in rats injected intramuscularly with the powder of either pure cobalt metal or cobalt oxide. In other studies implantation of cobalt caused local fibrosarcomas in rabbits, but inhalation studies in hamsters did not reveal any increase in tumors from cobalt oxide. Lifetime exposure to cobalt sulfate by inhalation resulted in increased incidence of alveolar/bronchiolar neoplasms and a spectrum of inflammatory, flbrotic, and proliferative lesions in the respiratory tract of male and female rats and mice. ... 

Male and female mice exposed at concentrations up to 4mg/m 6 hours/day for 104 weeks had clear evidence of carcinogenicity based on increased incidences of alveolar/bron-chiolar neoplasms. In rats similarly exposed at concentrations up to 2 mg/m there was some evidence of carcinogenicity in male rats and equivocal evidence in females based on the occurrence of alveolar/bronchiolar neoplasms. Exposure to vanadium pentoxide also caused a spectrum of nonneoplastic lesions in the respiratory tract including alveolar and bronchiolar epithelial hyperplasia, inflammation, fibrosis, and alveolar histocytosis of the lung. Elyper-plasia of the bronchial lymph node occurred in female mice, and an unusual squamous metaplasia of the lung occurred in rats. ... 

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. 

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