Respiratory Regulation

Human cells are reliant on aerobic metabolism. Obtaining O2 from the environment and transporting it to the tissues while excreting the byproduct of cellular respiration (CO2) are processes key to survival and must be closely regulated. Chemoreceptors in the lungs and tissues sense changes in the concentration of respiratory gasses and send messages to the CNS, which, in turn, modifies breathing parameters such as the respiratory rate or tidal volume to compensate for any imbalance. Disruption of this control mechanism can be caused by severe disease and also result in severe disease.

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Respiratory Centers

Respiratory centers are specialized neuron clusters located in the medulla oblongata. They regulate 2 respiratory parameters in response to changing demands:

  • Respiratory frequency (rate): determined by how long the respiratory center is active
  • Depth of breath (tidal volume): determined by how the respiratory center stimulates the respiratory muscles


  • Dorsal respiratory group neurons (DRG)
  • Ventral respiratory group neurons (VRG)
  • Pneumotaxic center
  • Apneustic center 
  • Pre-Bötzinger complex

Respiratory groups

  • DRG: 
    • Sets rhythm and frequency of inhalation, and thus also the respiratory rate (during quiet breathing, exhalation is passive and does not require stimulus)
    • Intrinsic oscillator:
      • Spontaneously sends repetitive signals
      • Induces repetitive contraction of the diaphragm, creating negative pleural pressure and inflation of alveoli
  • VRG:
    • Not used during normal quiet breathing, only engaged in forced exhalation
    • Stimulates abdominal muscles to forcefully exhale during increased respiratory need
  • Pneumotaxic center:
    • Switches off inspiratory signal produced by DRG
    • Limits inspiration duration setting the depth of breathing and determining rate of respiration
  • Other respiratory centers:
    • Cerebral cortex: conscious override of autonomous control of breathing
    • Hypothalamus and limbic system: override the breathing cycle during fear or excitement
Respiratory control centers Respiratory regulation

Respiratory control centers

Image by Lecturio. License: CC BY-NC-SA 4.0

Regulation of the Respiratory Centers

Respiratory centers set the rate and depth of breathing. Changes in O₂, CO₂, and H+ concentrations are sensed by central and peripheral chemoreceptors, which regulate the activity of the respiratory centers to match metabolic and situational needs.

Regulation of respiratory centers by central chemoreceptors

Central chemoreceptors are located in the medulla oblongata and regulate respiratory center activity based on changes in blood gases.

  • PCO₂: 
    • Increase → increase of H+ in the brain (carbonic anhydrase action on CO₂ permeating the blood–brain barrier) → stimulation of central chemoreceptors → stimulation of respiratory centers → increased depth and rate of breathing → decrease PCO₂
    • Decrease → decreased respiratory rate or even apnea 
  • Partial pressure of O₂ (PO₂): no direct effect on respiratory centers 
  • A decrease in arterial pH can increase ventilation even if PO₂ and PCO₂ are normal.

Regulation of respiratory centers by peripheral chemoreceptors

Peripheral chemoreceptors are located in the carotid bodies and aortic bodies and are more responsive to blood gases than central chemoreceptors.

  • PCO₂:
    • Sensed directly and indirectly as H+ by peripheral chemoreceptors
    • Has similar effects on respiratory centers as central chemoreceptors
    • Much less potent stimulus than direct stimulation of central chemoreceptors
  • PO₂:
    • Decrease → depolarization of type I (glomus) cells → activation of calcium channels → docking and fusing of neurotransmitters by intracellular calcium → picked up by afferents and send a signal to the brain → increase in the rate of breathing
    • Has a modest effect on ventilation, primarily when PO₂ is 30–60 mm Hg

Regulation of respiratory centers by other receptors in the lungs

  • Irritant receptors: 
    • Sense: 
      • Dust
      • Cold air
      • Chemical irritants
    • Cause:
      • Cough
      • Bronchoconstriction
  • Muscle and joint receptors:
    • Sense position of the chest wall during respiration
    • Provide feedback about adequacy of rate and depth of breathing
  • Stretch receptors:
    • Sense extent of inflation of the lung parenchyma
    • Terminate inspiration before damage is done to the lungs
  • J receptors:
    • Sense pulmonary edema
    • Cause shallow breathing
Receptors along the respiratory tract

Receptors along the respiratory tract, and in muscles and joints of the thorax

Image by Lecturio. License: CC BY-NC-SA 4.0


  1. Hall, J.E., Hall, M.E. (2021). Guyton and Hall Textbook of Medical Physiology (14th ed.). Elsevier.
  2. Powers, K.A., Dhamoon, A.S. Physiology, pulmonary ventilation, and perfusion (2021). StatPearls. Treasure Island (FL): StatPearls Publishing.
  3. J. Gordon Betts et al. Anatomy and Physiology. Retrieved April 26, 2021, from

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