The control of breathing


  • Thuy Bui
  • John Lees

The control of breathing

General introduction: Supply and demand

  • Ultimately the control of breathing is about supply and demand, where the respiratory system (the supplier) provides the blood (the road system connecting supplier and consumer) with the O2 required by our cells (the consumers) to perform aerobic metabolism (at the mitochondria).The respiratory system subsequently then removes the CO2 bye-product of this process
  • Normally supply and demand are in equilibrium and the cellular metabolic requirements are met by the level of O2 delivery and CO2 removal from capillaries, which in turn are in equilibrium with the rate of delivery and removal at the lungs
  • During different levels of metabolic activity however, the balance may be shifted. To cope with this variation in demand, many homeostatic mechanisms function in maintaining optimal levels of respiration. The overall result of these various feedback systems is a tight control of respiration at both the local (the lungs, the distribution centre if you will) and central (the brain, the logistics manager in control of the distribution centre) levels. This process is known as the control of breathing

The 2 levels of control

1. Local control

Location: Alveoli, alveolar capillaries and bronchioles in localised areas of the lung

Role: To ensure blood and gas go to the appropriate parts of the lung for efficient gas exchange

When: There are localized changes in Co2 and O2

Mechanism:  Local adjustments to blood flow (lung perfusion) and oxygen delivery (alveolar ventilation) to alveoli

2. Central control

Location: The respiratory centres (pairs of nuclei located in the medulla oblongata and the pons) modified by sensory neurons (peripheral and in the brain’s cerebrospinal fluid) and higher centres (cerebral cortex)

Role: Adjust the depth and rate of ventilation

When: During both normal breathing and also when there is a larger respiratory demand or conscious control is needed (e.g. during talking)

Mechanism: Both involuntary (respiratory reflexes involving sensory feedback) and voluntary (higher centres of the brain) control via the respiratory centres

1. Local control: Getting to the right place at the right time

  • Local control is automatic control independent of the brain’s activity
  • It consists of adjustments to two components: 

    a) Lung perfusion 

    b) Alveolar ventilation

       Using the supply and demand analogy, it is equivalent to improving the efficiency of the distribution centre by ensuring more trucks are going to where there is the most product for delivery (in the case of lung perfusion) and product is being diverted to where it is most needed (alveolar ventilation)

      a) Lung perfusion

      • Local control via lung perfusion ensures that arteriolar blood flow is diverted to where it is needed in the lung
      • This is achieved through vasoconstriction of arterioles supplying lung areas low in O2
      • For instance, insufficient O2 in a region of alveoli, characterised by a decreased PO2 (the partial pressure of oxygen) is recognised by receptors located in the capillaries. As a consequence,vasoconstriction of arterioles supplying this area occurs, reducing blood flow and therefore preventing wasted perfusion into poorly oxygenated alveoli
      • Conversely, if alveolar PO2 is high,vasodilation will occur delivering more deoxygenated blood to these alveoli aiding optimal gas exchange 


      Lung perfusion

      b) Alveolar ventilation

      • Local control via alveolar ventilation ensures optimum conditions for gas exchange
      • This involves adjusting the size of the bronchioles in response to alveolar PCO2 (the partial pressure of carbon dioxide), thus, altering the airflow into the alveoli
      • For instance, a local increase in alveolar PCO2 leads to local bronchodilationdrawing more air into this area of the lungs and allowing O2 to reach functional alveoli (i.e. those receiving CO2 from the blood) and also facilitating CO2 removal
      • In contrast, a decrease in alveolar  PCO2 leads to bronchoconstriction, resulting in less air delivery to these areas


      Alveolar ventilation

      c) Ventilation/perfusion ratio

      • Ventilation (V): The amount of O2 reaching alveoli (litres/min).

      Normal ventilation: 4 litres of air per minute 

      • Perfusion (Q): The amount of blood flow into the lungs (litres/min) 

      Normal perfusion: 5 litres of blood per minute

      • Ventilation/Perfusion ratio: The ratio between the amount of air entering the alveoli and the amount of blood draining into the lung. Allows an assessment of the efficiency of gas exchange.

       The common value for ventilation / perfusion is 4/5 or 0.8

      NB: Local control aims at maintaining an optimal V/Q

      Pathology and the V/Q ratio

      Pathology and the V/Q ratio

      2. Central control

      • As opposed to local control, central control directs respiration via the respiratory centres of the brain
      • These affect the rate and depth of breathing in response to various sensory and higher inputs
      • It consists of two components.....


                                                                 a) Involuntary control

                                                                 b) Voluntary control

           Using the analogy of supply and demand, the brain is acting as a logistics manager, receiving information from various sites along the distribution chain and informing the main distribution centre to respond accordingly. There are two forms of central control

          a) Involuntary control

          • Involuntary control directs the depth and rate of breathing via outputs from the respiratory centres
          • These may be modified upon stimulation from sensory receptors in the lungs, respiratory tract and cerebrospinal fluid to ensure appropriate levels of ventilation

          b) Voluntary control

          • Voluntary control is influenced indirectly by the cerebral cortex and affects the output of the respiratory centres in the medulla oblongata
          • Influential factors include emotion, anticipation of exertion and activities requiring alteration to normal breathing such as playing the trumpet!

          Involuntary control: Normal and forced breathing

          • In order to understand how involuntary control responds to perturbations in the system, we must first understand how the normal rhythm of breathing occurs. This is down to the respiratory centres in the brain. 
          • Each respiratory rhythmicity centre (in the medulla oblongata) includes a dorsal respiratory group (DRG) and a ventral respiratory group (VRG), which function in setting the pace of respiration.
          • These centres’ outputs are modified by the apneustic and pneumotaxic centres of the pons, which regulate the respiratory rate and depth of respiration under the control of other centres of the brain

          Normal breathing cycle (lasting around 5 seconds):

          • Inhalation occurs in first 2 seconds followed by 3 seconds of exhalation 
          • Inhalation: Within the first stage, the DRG (stimulated by the apneustic centres), enhance the activities of the inspiratory muscles
          • Exhalation: In the next 3 seconds, the pneumotaxic centres inhibit the apneustic centres resulting in unstimulated DRG. These no longer stimulate inhalation anymore, causing passive exhalation 

          Forced breathing cycle:

          • During forced breathing, the cooperation of respiratory centres is modified 
          • Inhalation: both the DRG and inspiratory centres of the VRG stimulate the contraction of inspiratory muscles and inhibition of the expiratory centres of the VRG. This leads to relaxation of expiratory muscles, resulting in inhalation
          • Exhalation: The DRG and inspiratory centres of the VRG are inhibited. Meanwhile, expiratory centres of VRG bring about the contraction of expiratory muscles, causing forced expiration 

          The respiratory centres and breathing

          The respiratory centres and breathing

          Involuntary control: Respiratory reflexes

          • The normal pattern of breathing is modified via sensory reflexes in order to accommodate physiological changes and maintain homeostasis
          • In the first stage of this process, different receptors detect changes inside the body and send information to the central controllers (at the medulla) via sensory afferent nerves
          • The output of the controllers is then modified changing the efferent signal to the effectors (the respiratory muscles)
          •  Stimulation can be chemical (i.e. changes in PCO2 and pH detected by chemoreceptors), mechanical(detected by mechanoreceptors) or through changes in blood pressure(recognised by baroreceptors in blood vessel walls)

          Below are some examples of the respiratory reflexes....


          involuntary control

          i) Chemoreceptor reflexes

          • Chemoreceptors detect changes in the chemical composition of the blood and cerebrospinal fluid. They are categorised into two groups:


            1.  Central chemoreceptors:


              Location: On the ventrolateral surface of the medulla oblongata

              Stimulation: changes in pH and in the cerebrospinal fluid 


                    2.  Peripheral chemoreceptors:



              Location: a) In the carotid bodies: At the bifurcation of carotid arteries, innervated by the glossopharyngeal (IX) nerve b) In the aortic bodies:  Above and below the aortic arch, innervated by the vagus (X) nerve

              Stimulation: Detect a decrease in PO2  (hypoxia) and pH. NB: PCO2 affects pH so peripheral chemoreceptors will indirectly respond to increased PCO2 (hypercapnea)



              Homeostasis: The chemoreceptor reflexes in action

              Condition: Hypercapnea (increased arterial PCO2)

              Chemoreception: Detected in cerebrospinal fluid (central chemoreceptors) and arteries (peripheral chemoreceptors)

              Effects: DRG stimulated leading to higher respiratory rate and CO2 clearance


              Hypercapnea makes your lungs hyper!

              Condition: Hypocapnea (increased arterial PCO2)

              Chemoreception: Decreased CO2 Detection in cerebrospinal fluid (central chemoreceptors) and inhibition of peripheral chemoreceptors

              Effects: Reduced DRG stimulation leading to lower respiratory rate and CO2 retention




              ii) Hering-Breuer reflexes:

              • The Hering-Breuer reflexes function in controlling the inflation and deflation of the lungs during forced breathing
              • With the cooperation of two reflexes, the volume and stretch of the lungs is controlled to avoid over expansion or over deflation
              • Both of the Hering-Breuer reflexes require activity of pulmonary stretch receptors, known as slowly adapting receptors (SARs)


                 The inflation reflex prevents the lungs from overinflating, which regulates tidal volume of the lungs. When forced inflation occurs, the stretch receptors in the wall of the lung send information to the rhythmicity centres through the vagus nerve. This inhibits the DRG and stimulates the expiratory centre of the VRG leading to active exhalation

                 The deflation reflex on the other hand inhibits the expiratory centres and stimulates the inspiratory centres during a forced exhalation. Receptors located in the alveoli increase the inhibition of expiration in response to a decreased lung volume

                iii) Rapidly adapting receptors and protective reflexes

                • Rapidly adapting receptors respond (usually vagal) to stress and chemical irritant stimuli as well as inflammatory and immunological mediators within the airway
                •  Their function is to protect against the offending irritant, usually through expulsion


                • Coughing is a protective reflex against irritants. This process involves an instant respiratory response from numerous receptors in the larynx, the trachea and the primary bronchi. Rapid shallow breathing and mucous secretion may also occur


                • Sneezing, another protective reflex is produced by stimulation from irritants inside the nasal cavity wall (nasal receptors in the upper respiratory tract)


                • Both coughing and sneezing involve a period of apnea (cessation of respiration) followed by a forceful expulsion of air to remove the irritants from the passageway, thus protecting the respiratory organs
                •  In addition, other recognised rapid reflexes are bronchoconstriction, tachypnoea (rapid breathing) and aspiration (a sniff/swallow reflex)

                iv) J receptors: Inflammation and oedema

                • J receptors located in the alveoli and capillaries are stimulated by pulmonary oedema and products of inflammation in the interstitium of the lungs
                • The receptors send information through bronchopulmonary, unmyelinated C-fibres
                • Once stimulated, C-fibre terminals release sensory neuropeptides, which in turn positively influence rapidly adapting receptors
                •  This stimulation contributes to particular responses such as rapid shallow breathing, decreased tidal volume, increased respiratory rate, mucus secretion and cough

                v) Head's paradoxical reflex

                • In the presence of cold block on vagus nerves, the paradoxical reflex occurs
                • It contradicts the Hering-Breuer inflation reflex in that inflation is no longer inhibited in the lungs
                • Therefore, Head’s paradoxical reflex leads to irregular deep breaths superimposed on normal breathing
                • It is recognized to be important in the first breath of babies and also in augmented breaths of adults (sighs) 

                vi) Muscle spindle reflexes

                • Muscle spindles are sensory receptors that are widely located in the intercostal muscles within the ribcage and are involved in a reflex arc not involving the medulla (sensory neurons synapse directly with motor neurons) 
                • An increase in respiratory load (i.e. muscle stretching) stimulates the contraction of a large number of intercostal muscles around the affected muscle spindles

                vii) Baroreceptor reflexes

                • Baroreceptors, located in the carotid sinus and the aortic arch are mainly responsible for the regulation of blood pressure
                • They do, however also affect respiratory frequency and tidal volume. A decrease in intrasinus pressure brings about a baroreceptor reflex, characterised by increasing respiratory frequency and lowering tidal volume
                • Similarly increased pressure results in decreased respiratory rate



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