In contrast to automatic respiration, voluntary respiration bypasses the respiratory control center in the medulla. The neural activity controlling voluntary respiration originates in the motor cortex, and signaling passes directly to motor neurons in the spine through the corticospinal tracts. The motor neurons to the respiratory muscles act as the final site of integration of the voluntary (corticospinal tract) and automatic (ventrolateral tracts) control of ventilation. Voluntary control of these muscles competes with automatic influences at the level of the spinal motor neurons, and this competition can be demonstrated by breath holding. At the start of the breath hold, voluntary control dominates the spinal motor neurons. However, as the breath hold continues, the automatic ventilatory control eventually overpowers the voluntary effort and limits the duration of the breath hold. Motor neurons also innervate muscles 490 SECTION5Berne & Levy Physiology 15 10 5 0 25 35 45 55 65 PaCO2 (mm Hg) Alveolar ventilation (L/min) Metabolic acidosis Awake normal Sleep Morphine, barbiturates COPD Anesthetic agents •Fig. 25.1 Relationship between Partial Pressure of Arterial Carbon Dioxide (PaCO2) and Alveolar Ventilation in Awake Normal States, during Sleep, after Narcotic Ingestion and Deep Anesthesia, and in the Presence of Metabolic Acidosis. Boththeslopesoftheresponse(sensitivity)andthepositionoftheresponsecurves(threshold,thepointatwhichthecurvecrossesthex-axis[notshown])arechanged,whichindicatesdifferencesinventilatoryresponsesandresponsethresholds.COPD,chronicobstructivepulmonarydisease.
of the upper airway. These neurons are located within the medulla near the respiratory control center. They innervate muscles in the upper airways through the cranial nerves. When activated, they dilate the pharynx and large airways at the initiation of inspiration.
Response to Carbon Dioxide
Ventilation is regulated by PaCO2, PaO2, and pH in arterial blood. PaCO2 is the most important of these regulators. Both the rate and depth of breathing are controlled to maintain PaCO2 close to 40 mm Hg. In a normal awake individual, there is a linear rise in ventilation as PaCO2 reaches and exceeds 40 mm
Hg (Fig. 25.1 ). The ventilatory drive or response to changes in PaCO2 can be reduced by hyperventilation and by drugs that depress the respiratory center and decrease the ventilatory response to both CO2 and O2, such as morphine, barbiturates, and anesthetic agents. In these instances, the stimulus is inadequate to stimulate the motor neurons that innervate the muscles of respiration. It is also depressed during sleep. In addition, the ventilatory response to changes in PaCO2 is reduced if the work of breathing is increased, which can occur in individuals with chronic obstructive pulmonary disease (COPD). This effect occurs primarily because the neural output of the respiratory center is less effective in promoting ventilation as a result of the mechanical limitation to ventilation.
Changes in PaCO2 are sensed by central and peripheral chemoreceptors, and they transmit this information to the medullary respiratory centers. The respiratory control center then regulates minute ventilation and thereby maintains PaCO2 within the normal range. In the presence of a normal PaO2, ventilation increases by approximately 3 L/minute for each 1 mm Hg rise in PaCO2. The response to an increase in PaCO2 is further increased when the PaO2 is low (
Fig. 25.2, ). With a low PaO2, ventilation is greater for any given PaCO2, and the increase in ventilation for a given increment in PaCO2 is enhanced. The slope of the minute ventilation response as a function of the inspired CO2 is termed the ventilatory response to CO2 and is a test of CO2 sensitivity. It is important to recognize that this relationship is amplified by low O2 (see