A 66-year-old woman is evaluated in the clinic for worsening shortness of breath over the last year. She has no previous medical problems and is a lifelong nonsmoker. Blood pressure is 126/78 mm Hg, pulse is 82/min, and respirations are 18/min. BMI is 23 kg/m². Physical examination shows a normal oropharynx, flat neck veins, and a midline trachea. Diaphragmatic excursion is decreased bilaterally. Lung auscultation reveals bilateral fine inspiratory crackles. Arterial blood gas analysis is performed while the patient is at rest and after a vigorous walk for several minutes. Arterial partial pressure of oxygen is normal at rest but falls significantly with exercise. Which of the following exercise-related changes is most likely contributing to the latter observation in this patient?

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11ec160b_3b4d_ab9b_9249_b5f3b24c94be_MD0001_00 Oxygen transfer across the alveolar membrane depends on the (1) gas diffusion rate and (2) capillary blood perfusion rate. In healthy lungs, diffusion of oxygen occurs very rapidly: red blood cells become fully saturated with oxygen at only one-third of the total alveolar capillary length. For this reason, oxygen saturation does not fall even with large increases in cardiac output during exercise. In other words, normal oxygen transfer is perfusion limited (ie, diffusion is so fast that oxygen transfer depends on the perfusion rate [cardiac output] only). Diffusion limitation is a mechanism of hypoxia that occurs in diseases that disrupt the alveolar-capillary membrane (eg, emphysema, pulmonary fibrosis). This patient's progressive dyspnea and fine inspiratory crackles are consistent with interstitial lung disease. Fibrotic thickening of the interstitial space (between the air and blood) increases the distance that oxygen must cross, limiting the degree of oxygen diffusion. During exercise, the increase in pulmonary blood flow accelerates transit through the pulmonary capillaries, reducing the time for oxygen extraction. In patients with diffusion limitation, the increased blood flow during exercise can result in exertional hypoxemia, even if oxygenation is normal at rest. (Choices A, B, and D) In healthy individuals, exercise results in increased minute ventilation (ie, product of increased respiratory rate × larger tidal volumes). At the same time, recruitment of apical pulmonary capillaries (increased perfusion) promotes continued ventilation/perfusion (V/Q) matching as ventilation increases. This remarkably stable V/Q matching during exercise enhances oxygen exchange, preventing hypoxemia. Educational objective: Diffusion of oxygen across the alveolar-capillary membrane is normally very rapid. Decreased diffusion rate (eg, interstitial lung disease) can lead to diffusion-limited oxygen transfer, especially when the perfusion rate increases (eg, exertion). __________ References: Physiology, pulmonary, ventilation and perfusion. (http://www.ncbi.nlm.nih.gov/pubmed/30969729)

A 66-Year-Old Woman Is Evaluated in the Clinic for Worsening