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The respiratory system is responsible for gas exchange, elimination of certain xenobiotics, insensible water loss, temperature regulation, and minor metabolic processes. The principal function of the respiratory system is gas exchange, which occurs in the more than 300 million alveoli that make up approximately 90% of the human lung volume. The average resting adult inhales about 8 L/min of air (a tidal volume of about 500 mL) and averages 16 breaths/min, and this volume can be increased exponentially by increasing the respiratory rate and tidal volume as occurs during exertion. In a 24-hour period, an average adult human at rest will be exposed to 11,500 L of air. There are a number of protective mechanisms within the respiratory system to prevent exposure to xenobiotics, but these mechanisms can be overwhelmed. The principles of respiratory system function are covered extensively in Chap. 28.

The respiratory tract performs several important physiologic functions. Its most important role involves the transfer of oxygen to hemoglobin across the pulmonary endothelium. This transfer facilitates oxygen distribution throughout the body to permit effective cellular respiration. Diverse xenobiotics act at unique points in this distribution pathway to limit or impair tissue oxygenation. For example, whereas opioids and neuromuscular blockers induce hypoventilation, carbon monoxide and methemoglobin inducers prevent loading and unloading of oxygen onto and off hemoglobin. Certain xenobiotics prevent adequate oxygenation of hemoglobin at the level of pulmonary gas exchange. Two mechanistically distinct groups of xenobiotics are capable of interfering with gas exchange: simple asphyxiants and pulmonary irritants. Impairment of transpulmonary oxygen diffusion, regardless of the etiology, reduces the oxygen content of the blood and results in tissue hypoxia.


Unlike most xenobiotic exposures, simple asphyxiant and pulmonary irritant poisonings frequently occur on a mass scale due to the magnitude of these exposures. For example, the large-scale emission of carbon dioxide (CO2) from Lake Nyos, a carbonated volcanic crater lake in Cameroon, West Africa, resulted in nearly 2,000 human deaths and many more livestock deaths (Chap. 2).8In this disaster, simple asphyxiation was likely because medical evaluation of both survivors and fatalities demonstrated neither signs of cutaneous or pulmonary irritation nor toxicologic abnormalities.128 Exposure to compressed liquefied gases, which expand several hundredfold on depressurization or warming, accounts for a substantial number of workplace injuries.114

Irritant gases similarly result in mass casualties. For this reason, chlorine and phosgene were used in battle during World War I, resulting in thousands of Allied deaths (Chap. 126). Atmospheric sulfur dioxide and oxides of nitrogen are the primary components of photochemical smog. During the London Fog incident in 1952, 4,000 deaths occurred, primarily from respiratory causes.102 Similar smog incidents continue to occur around the globe. Relatedly, the diverse irritants found in fire smoke are a major cause of death after smoke inhalation.113

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