Integrated Respiratory Control

  • We have discussed the individual components which control respiration but take this opportunity to provide an integrated view. The respiratory pattern profoundly influences the rate of alveolar ventilation which in turn determines the partial pressures of arterial oxygen and carbon dioxide and in turn the blood pH. It is no surprise then that these values reciprocally influence the pattern of respiration, allowing for a negative feedback control circuit that helps maintain relatively stable values of arterial oxygen, carbon dioxide, and pH. Below we discuss how this negative feedback control circuit responds to derangements in arterial oxygen, carbon dioxide, and pH. It should be pointed out that in the absence of such derangements the inspiratory center of the brainstem respiratory centers independently maintains the relatively stable respiratory pattern of normal, quiet breathing.
Changes in Arterial Oxygen
  • The peripheral chemoreceptors are the only sensory component which can directly sense and respond to changes in the partial pressure of arterial oxygen. When hypoxemia ensues, the peripheral chemoreceptors are strongly activated and increase respiratory drive by activating the inspiratory brainstem respiratory centers. The resultant increase in alveolar ventilation thus aids in restoring arterial oxygen tension. It should be pointed out that while increased oxygen tensions may reduce afferent stimuli from the peripheral chemoreceptors, this does little to suppress respiration.
Changes to Carbon Dioxide
  • Changes to the partial pressure of arterial carbon dioxide are sensed by both the central and peripheral chemoreceptors; however, modulation of the central chemoreceptors is by far more important in coordinating respiratory changes in response to changing in arterial CO2 tension. Increased arterial partial pressures of CO2 strongly stimulate the central chemoreceptors which send afferent signals to the inspiratory brainstem respiratory centers that increase respiratory drive. The resultant increase in alveolar ventilation results in pulmonary elimination of carbon dioxide and thus restoration of lower arterial carbon dioxide levels. Conversely, decreased arterial partial pressures of CO2 strongly suppress respiratory drive and thus reduce alveolar ventilation, allowing for buildup of arterial carbon dioxide levels.
Changes to pH
  • Changes to blood pH can profoundly modify the respiratory drive as described further in Respiratory Acid-Base Control. Briefly, acidosis increases respiratory drive, thus increasing alveolar ventilation which helps increase the blood pH by breathing off of carbon dioxide. Conversely, alkalosis decreases respiratory drive, thus decreasing alveolar ventilation which helps reduce the blood pH by slowing elimination of carbon dioxide. Changes to the pH of blood are likely sensed by both the central chemoreceptors as well as the aortic bodies of the peripheral chemoreceptors. The peripheral chemoreceptors are likely the dominant afferent sensory stimulus for pH changes whereas the contribution of the central chemoreceptors displays slower kinetics given the extensive time required for free hydrogen ions to cross the relatively impermeable blood brain barrier. These sensors modulate the inspiratory brainstem respiratory centers to coordinate appropriate changes in respiratory drive as described above.

Basic Physiological Algorithm of Respiratory Control
Deviations from normal arterial tensions of oxygen, carbon dioxide, as well as arterial pH are sensed by central and peripheral chemoreceptors. The central chemoreceptors are the major sensory organ of arterial carbon dioxide while the peripheral chemoreceptors are most influential in sensing arterial oxygen and pH. Afferent input from these sensory organs is integrated in the brainstem respiratory centers which then coordinate changes in the muscles of breathing that in turn modulate the alveolar ventilation rate. Ultimately, changes to the alveolar ventilation rate return the arterial gas tensions and pH to their normal values.