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INTRODUCTION

KEY POINTS

  • 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.

RESPIRATORY TRACT STRUCTURE AND FUNCTION

Oronasal Passages

Structure

The respiratory tract is divided into the upper respiratory tract (extrathoracic airway passages above the neck) and lower respiratory tract (airway passages and lung parenchyma below the pharynx) (Fig. 15–1). The upper respiratory tract 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.

FIGURE 15–1

Major regions of the respiratory tract and predicted fractional deposition of inhaled particles in the extrathoracic, bronchial, and alveolar region of the human respiratory tract during (solid line) oral or (dashed) nasal breathing. (Adapted from Oberdörster G, Oberdörster E, Oberdörster J. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect. 2005;113:823–839.)

The airflow through the nasal passage is complex, and the resistance of this region limits the amount of air that can be inhaled through the nose. The nasal passages are lined with stratified squamous epithelium in the anterior vestibule, nonciliated cuboidal/columnar epithelium in the anterior chamber, and ciliated pseudostratified respiratory epithelium in the remainder of the passage including the turbinates. The turbinates also contain airflow pressure- and temperature-sensing neural receptors linked to the trigeminal nerve.

Sensory Functions

Humans can distinguish more than 5000 odors. Although the detection threshold concentrations can be low, a concentration only 10 to 50 times above the detection threshold value often is the maximum intensity that can be detected by humans. For this reason, smell often identifies the presence or absence of odor rather than quantifies concentration. In addition, odor thresholds vary greatly between individuals (>1000 fold) and can be altered by allergies or nasal infections, and individuals can acclimate to odors. The chemosensory functions of the nasal ...

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