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The primary function of the lungs is gas exchange. Specifically, this involves the transport of oxygen (O2) into the blood, and the elimination of carbon dioxide (CO2) from the blood. In addition, the lungs serve as minor organs of metabolism and elimination for a number of xenobiotics, a source of insensible water loss, and a means of temperature regulation. Air is conducted through proximal airways, made up of columnar epithelium and mucin-secreting goblet cells. Oxygen exchange occurs in distal airways, through type I pneumocytes, which make up most of alveolar surface area. Type II pneumocytes, which secrete surfactant, take up less pulmonary surface area.

Cellular oxygen use is dependent on many factors, including respiratory drive; percentage of oxygen in inspired air; airway patency; chest wall and pulmonary compliance; diffusing capacity; ventilation–perfusion mismatch; hemoglobin content; hemoglobin oxygen loading and unloading; cellular oxygen uptake; and cardiac output. Xenobiotics have the unique ability to impair each of these factors necessary for oxygen use and result in respiratory dysfunction (Table 28–1). This chapter illustrates how xenobiotics interact with the mechanisms of gas exchange and oxygen use. Discussion of chronic occupational lung injury is beyond the scope of this text; the reader is referred to a number of reviews for further information.5

TABLE 28–1Respiration as a Target of Common Xenobiotics


Respiratory Drive

Respiratory rate and depth are regulated by the need to maintain a normal partial pressure of carbon dioxide (PCO2) and pH. Most of the control for ventilation occurs at the level of the medulla, although it is modulated both by involuntary input from the pons and voluntary input from the higher cortices. Changes in PCO2 are measured primarily by a central chemoreceptor, which measures cerebralspinal fluid pH, and secondarily by peripheral ...

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