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KEY POINTS

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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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INTRODUCTION

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Toxic substances can disrupt the respiratory system and distant organs after chemicals enter the body by means of inhalation. Pathological changes in the respiratory tract also can be a target of blood-borne agents. Inhalation toxicology refers to the route of exposure, whereas respiratory toxicology refers to target organ toxicity. 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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RESPIRATORY TRACT STRUCTURE AND FUNCTION

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Oronasal Passages

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Structure
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The respiratory tract is divided into the upper respiratory tract (extrathoracic airway passages above the neck) and lower respiratory track (airway passages and lung parenchyma below the pharynx) (Figure 15–1). The upper respiratory track reaches from the nostril or mouth to the pharynx and functions to conduct, heat, humidify, filter, and chemosense incoming air. Leaving the nasal passage, air is warmed to about 33°C and humidified to about 98% water saturation. Air is filtered in the nasal passages with highly water-soluble gases being absorbed efficiently. The nasal passages also filter particles, which may be deposited by impaction or diffusion on the nasal mucosa.

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FIGURE 15–1

Predicted fractional deposition of inhaled particles in the nasopharyngeal, tracheobronchial, and alveolar region of the human respiratory tract during nose breathing. (Used with permission of J. Harkema.) (Reproduced with permission from Oberdorster G, Oberdorster E, Oberdorster J: Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles, Environ Health Perspect, 2005 Jul;113(7):823–839.)

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Sensory Functions
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In addition to conducting, conditioning, and filtering air to the lower respiratory tract, a major function of the oronasal passage is chemosensory. Nasal epithelia can metabolize many foreign compounds by cytochrome P450 and other enzymes. Humans can distinguish between more than 5 000 odors. The detection of odor can be protective and can induce avoidance behaviors. Odorant can be added to the otherwise colorless and almost odorless gas used by consumers (e.g., mercaptans to methane), to assist in detecting leaks and thereby ...

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