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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 principle function of the respiratory system is gas exchange, which occurs in the greater than 300 million alveoli that make up approximately 90% of the human lung volume. The average resting adult is exposed to about 8 L/min of air (a tidal volume of about 500 mL) and averages 16 breaths per minute, 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 have been exposed to 11,500 L of air. There are a number of protective systems within the respiratory system to prevent exposure to xenobiotics, but these systems can be overwhelmed. The principles of respiratory system function are covered extensively in Chapter 21.

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 may act at unique points in this distribution pathway to limit or impair tissue oxygenation. For example, whereas opioids and neuromuscular blockers may induce hypoventilation, carbon monoxide and methemoglobin inducers prevent binding of oxygen to 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 may result in tissue hypoxia.

Unlike most xenobiotic exposures, simple asphyxiant and pulmonary irritant poisonings frequently occur on a mass scale because of the nature of the inhalational route. For example, the large-scale emission of carbon dioxide from Lake Nyos, a carbonated volcanic crater lake in Cameroon, West Africa, resulted in nearly 2000 human and many more livestock deaths (see Chap. 2).15 In 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.201 The widespread use of compressed liquefied gases, which expands several hundredfold on depressurization or warming, account for a substantial number of workplace injuries.123,183

Irritant gases similarly may result in mass casualties. For this reason, chlorine and phosgene were used in battle during World War I, resulting in thousands of Allied deaths83 (see Chap. 131). Atmospheric sulfur dioxide and oxides of nitrogen are the primary components of photochemical smog. During the London Fog incident in 1952, 4000 deaths occurred primarily from respiratory causes.171 Similar smog incidents have occurred across the globe. Relatedly, the diverse irritants found in fire smoke are largely responsible for the development of acute lung injury (ALI) after smoke inhalation.180

Unexpected release of other irritant ...

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