The inspiratory center, the site of basic respiratory drive, located dorsally in the medulla, extends the full length of the medulla (Figure 25-1). The neurons within the inspiratory center are located near the termination sites of afferent fibers from the glossopharyngeal (IX) and vagus (X) nerves. These neurons have intrinsic automaticity and normally fire for 2 sec, with a ramp effect of increasing efferent activity to the diaphragm until it abruptly ceases with a 3-sec pause before initiating a new cycle.

Apneustic center

The apneustic center is located in the lower pons. Its role is to antagonize the effects of the pneumotaxic center, and it plays no role in normal respiration. In the Hering-Breuer reflex, bronchiolar stretch receptors feed back to the inspiratory center via the vagus nerve to limit lung overexpansion. This reflex plays a minimal role in normal ventilation but becomes active when tidal volume exceeds 1.5 L (Figure 25-2).

The chemosensitive area is located bilaterally in the medulla several microns beneath the ventral surface (Figure 25-3). This area is extremely sensitive to hydrogen ions (H⁺). However, H⁺ cross the blood-brain barrier poorly, and thus, CO₂ indirectly controls this region through formation of carbonic acid with dissociation to H⁺. When stimulated, this chemosensitive area then stimulates the inspiratory center to increase the rate of rise of the ramp effect and, thus, increases the rate of respiration.

< ?xml:namespace prefix = "mml" />CO2+H2O→H2CO3→H++HCO3–

Therefore, PaCO₂ indirectly influences the level of H⁺ in cerebrospinal fluid and controls respiratory drive. Peak effect is reached within 1 min. The effect begins to wane over the next several hours, and, by 48 h, is only one eighth the peak effect. Compensation is secondary to increased active transport of HCO₃⁻ into the cerebrospinal fluid to neutralize the increased H⁺.

Peripheral

Peripheral chemoreceptors are located in the carotid bodies (cranial nerve IX) and aortic bodies (cranial nerve X). These areas of high blood flow are sensitive to changes in O₂, CO₂, and pH. They stimulate the inspiratory center when Pao₂ decreases; the effect is greatest between 30 and 60 mm Hg (Figure 25-4).

If the mean arterial blood pressure drops below 70 mm Hg, respiratory drive increases. The effect of peripheral chemoreceptors in response to hypoxia is eliminated by as little as 0.1 minimum alveolar concentration of a inhaled anesthetic agent, which may be critical in patients with chronic obstructive lung disease who are dependent on hypoxic respiratory drive. Loss of the carotid body, as may occur with carotid endarterectomy, decreases response to hypoxia, a 30% decrease in responsiveness to changes in PaCO₂, and no change in the resting level of respiration.