Dyspnea is the perception of the inability to breathe comfortably.2 Although dyspnea is subjective, it has a physiologic basis. Chemoreceptors and stretch receptors interact with the brain and lungs to modulate respirations. Of note, respirations are the only vital sign subject to voluntary control.
Chemoreceptors detect changes in blood oxygen and carbon dioxide and subsequently trigger the respiratory drive centers. Decreased ventilation and increased lung deadspace both elevate PCO2. Lung deadspace expands when lung units are ventilated but not perfused, such as in pulmonary embolism. While elevations in CO2 are a crucial stimulant of respiratory drive, this mechanism is often blunted in patients with chronic lung disease. Other chemoreceptors are responsible for detection of acidosis, which will also increase respiratory drive.
Hypoxemia also modulates respirations through chemoreceptors. When the carotid body senses a minute fall in oxygen tension, it stimulates the brainstem to increase ventilation. The most common cause of hypoxemia is pulmonary ventilation-perfusion mismatch. This imbalance between pulmonary blood flow and alveolar ventilation is usually due to diseases of the heart or lung. Shunt is an extreme form of ventilation-perfusion mismatch and occurs when ventilation to a lung unit is interrupted despite persistent blood flow.3,4 Thus, the blood shunts past this "dummy" area of lung without exchanging gases. During shunt, the body compensates with reflex pulmonary vasoconstriction, which attenuates blood flow to non-ventilated lung units. While b2-adrenergic agents can reverse this vascular response, supplemental oxygen cannot correct hypoxemia produced by shunt.
Heightened airway resistance, elevated lung deadspace, and abnormal lung stiffness all increase the work of breathing.3,5,6 Mechanoreceptors in the face, upper airway, chest wall, and lungs are responsible for a feedback loop that modulates this sensation; vagal J receptors in the lung are important mediators.5 Researchers believe that the mismatch between lung volume and tension in the muscles of respiration is another important factor in patients with increased work of breathing.1
Even "psychogenic" dyspnea has a physiologic basis. Changes in brain neurochemistry and unusual responsiveness to PCO2 may be responsible for the breathlessness of panic disorders.7