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 Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. 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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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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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 Diaphragm The diaphragm is a large, dome-shaped muscle that separates the thoracic cavity from the abdominal cavity. The diaphragm consists of muscle fibers and a large central tendon, which is divided into right and left parts. As the primary muscle of inspiration, the diaphragm contributes 75% of the total inspiratory muscle force. 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 Cerebral cortex The cerebral cortex is the largest and most developed part of the human brain and CNS. Occupying the upper part of the cranial cavity, the cerebral cortex has 4 lobes and is divided into 2 hemispheres that are joined centrally by the corpus callosum. Cerebral Cortex: conscious override of autonomous control of breathing
    • Hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus and limbic system Limbic system The limbic system is a neuronal network that mediates emotion and motivation, while also playing a role in learning and memory. The extended neural network is vital to numerous basic psychological functions and plays an invaluable role in processing and responding to environmental stimuli. 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 Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs

  • Irritant receptors: 
    • Sense: 
      • Dust
      • Cold air
      • Chemical irritants
    • Cause:
      • Cough
      • Bronchoconstriction
  • Muscle and joint receptors:
    • Sense position of the chest wall Chest wall The chest wall consists of skin, fat, muscles, bones, and cartilage. The bony structure of the chest wall is composed of the ribs, sternum, and thoracic vertebrae. The chest wall serves as armor for the vital intrathoracic organs and provides the stability necessary for the movement of the shoulders and arms. 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 Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs
  • J receptors:
    • Sense pulmonary edema Pulmonary edema Pulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure. 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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