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  • Inhaled xenobiotics can affect lung tissues directly or distant organs after absorption.
  • Water solubility is a decisive factor in determining how deeply a given gas penetrates into the lung.
  • Particle size is usually the critical factor that determines the region of the respiratory tract in which a particle or an aerosol will deposit.
  • The lung contains most of the enzymes involved in xenobiotic biotransformation that have been identified in other tissues.
  • Asthma is characterized by increased reactivity of the bronchial smooth muscle in response to exposure to irritants.
  • In emphysema, destruction of the gas-exchanging surface area results in a distended, hyperinflated lung that no longer effectively exchanges oxygen and carbon dioxide.

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Exposure to chemicals by inhalation can affect (1) lung tissues and (2) distant organs that are reached after chemicals enter the body by means of inhalation. Indeed, the term inhalation toxicology refers to the route of exposure, whereas respiratory tract toxicology refers to target-organ toxicity, that is, the abnormal changes in the respiratory tract produced by toxicants. Lung tissue can be injured directly or secondarily by metabolic products from organic compounds. However, the most important effect of many toxic inhalants is to place an undue oxidative burden on the lungs.

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Nasal Passages

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Air enters the respiratory tract through the nasal and oral regions (Figure 15–1). The nasal passages function as a filter for particles. Highly water-soluble gases are absorbed efficiently in the nasal passages, which reach from the nostril to the pharynx. Also, nasal epithelia can metabolize foreign compounds. Cytochrome P-450 isozymes have been localized in the nose of several species.

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Figure 15–1
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Predicted fractional deposition of inhaled particles in the nasopharyngeal, tracheobronchial, and alveolar region of the human respiratory tract during nose breathing. Based on data from the International Commission on Radiological Protection (1994). (Drawing courtesy of J. Harkema.) (From Figure 8 in Oberdorster G, Oberdorster E, Oberdorster J: Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113(7):823–839, 2005.)

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Conducting Airways

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The trachea and bronchi are covered with mucus that traps pollutants and debris. The action of the respiratory tract cilia continuously drives the mucous layer toward the pharynx, where it is removed from the respiratory system by swallowing or expectoration. The mucous layer is also thought to have antioxidant, acid-neutralizing, and free radical-scavenging functions that protect the epithelial cells.

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Conducting airways have a characteristic branched bifurcating structure with a progressively decreasing internal diameter. Eventually a transition zone is reached where cartilaginous bronchi give way to noncartilaginous bronchioles, which in turn give way to gas-exchange regions, respiratory bronchioles, and alveoli.

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Gas-Exchange Region

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A ventilatory unit is the anatomical region that includes all alveolar ducts and alveoli distal to each bronchiolar–alveolar duct junction, and it represents ...

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