Control of ventilation

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Control of ventilation refers to the physiological mechanisms involved in the control of physiologic ventilation, which refers to the movement of air into and out of the lungs. Ventilation facilitates respiration. Respiration refers to the utilization of oxygen and production of carbon dioxide by the body as a whole, or by individual cells.[1] Under most conditions, the partial pressure of carbon dioxide () controls the rate of pulmonary ventilation.

The most important function of breathing is blood gas homeostasis (i.e. the regulation of the partial pressures of oxygen, , and carbon dioxide, , in the arterial blood). The effector of this homeostat is centered primarily on the manner in which the lungs are ventilated.

The sensors for the arterial blood gas regulator are situated in the aortic and carotid bodies, which are primarily sensitive to the partial pressure of oxygen () in the arterial blood, and the anterior and lateral surfaces of the medulla oblongata in the brain stem which measures the partial pressure of carbon dioxide () and pH of the cerebrospinal fluid and consequently the arterial blood.

Information from these sensors is conveyed along nerves to the respiratory center in the brain stem. The respiratory center is situated in the reticular formation and other parts of the brainstem, and consists of 4 interconnected and interacting components:

  1. Inspiratory center - reticular formation, medulla oblongata
  2. Expiratory center - reticular formation, medulla oblongata
  3. Pneumotaxic center - various nuclei of the pons
  4. Apneustic center - nucleus of the pons

From the respiratory center the skeletal muscles of ventilation, in particular the diaphragm,[2] are alternately activated to cause air to move in and out of the lungs.

Involuntary control of respiration[edit]

Ventilatory pattern[edit]

The pattern of motor stimuli during breathing can be divided into inspiratory and expiratory phases. Inspiration shows a sudden, ramped increase in motor discharge to the inspiratory muscles (including pharyngeal dilator muscles). Before the end of inspiration, there is a decline in motor discharge. Exhalation is usually silent, except at high minute ventilation rates.

The mechanism of generation of the ventilatory pattern is not completely understood, but involves the integration of neural signals by respiratory control centers in the medulla and pons. The nuclei known to be involved are divided into regions known as the following:

  • medulla (reticular formation)
  • pons
    • pneumotaxic center.
      • Coordinates speed of inhalation and exhalation
      • Sends inhibitory impulses to the inspiratory area
      • Involved in fine tuning of respiration rate.
    • apneustic center
      • Coordinates speed of inhalation and exhalation.
      • Sends stimulatory impulses to the inspiratory area – activates and prolongs inhalate (long deep breaths)
      • Overridden by pneumotaxic control from the apneustic area to end inspiration

There is further integration in the anterior horn cells of the spinal cord.[citation needed]

Control of ventilatory pattern[edit]

Ventilation is normally unconscious and automatic, but with the possibility of partial or complete superimposition of voluntary, conscious alternative patterns of ventilation. Thus the emotions can cause yawning, laughing, sighing (etc.), social communication causes speech, song and whistling, while entirely voluntary overrides are used to blow out candles, and breath holding (to swim, for instance, underwater). Hyperventilation may be entirely voluntary or in response to emotional agitation or anxiety, when it can cause the distressing hyperventilation syndrome.

The ventilatory pattern is also temporarily modified by complex reflexes such as sneezing, straining, burping, coughing and vomiting.

Determinants of ventilatory rate[edit]

Ventilatory rate (minute volume) is tightly controlled and determined primarily by blood levels of carbon dioxide as determined by metabolic rate. Blood levels of oxygen become important in hypoxia. These levels are sensed by blood gas chemoreceptors on the surface of the medulla oblongata for pH, and the carotid and aortic bodies for oxygen and carbon dioxide. Afferent neurons from the carotid bodies and aortic bodies are via the glossopharyngeal nerve (CN IX) and the vagus nerve (CN X), respectively.

Levels of CO2 rise in the blood when the metabolic use of O2, and the production of CO2 is increased, during, for instance, exercise. The CO2 in the blood is transported largely as bicarbonate (HCO3) ions, by conversion first to carbonic acid (H2CO3), by the enzyme carbonic anhydrase, and then by disassociation of this acid to H+ and HCO3. Build-up of CO2 therefore causes an equivalent build-up of the disassociated hydrogen ions, which, by definition, decreases the pH of the blood. The pH sensors on the brain stem immediately sense to this fall in pH, causing the respiratory center to increase the rate and depth of breathing. The consequence is that the (partial pressure of carbon dioxide) does not change from rest going into exercise. During very short-term bouts of intense exercise the release of lactic acid into the blood by the exercising muscles causes a fall in the blood plasma pH, independently of the rise in the , and this will stimulate pulmonary ventilation sufficiently to keep the blood pH constant at the expense of a lowered .

Mechanical stimulation of the lungs can trigger certain reflexes as discovered in animal studies. In humans, these seem to be more important in neonates and ventilated patients, but of little relevance in health. The tone of respiratory muscle is believed to be modulated by muscle spindles via a reflex arc involving the spinal cord.

Drugs can greatly influence the control of respiration. Opioids and anesthetic drugs tend to depress ventilation, by decreasing the homeostat's response to raised carbon dioxide levels in the arterial blood. Stimulants such as amphetamines can cause hyperventilation.

Pregnancy tends to increase ventilation (lowering plasma carbon dioxide tension below normal values). This is due to increased progesterone levels and results in enhanced gas exchange in the placenta.

Feedback control[edit]

Receptors play important roles in the regulation of respiration; central and peripheral blood gas chemoreceptors, and mechanoreceptors.

  • Central chemoreceptors of the central nervous system, located on the ventrolateral medullary surface, are sensitive to the pH of their environment.[3][4]
  • Peripheral chemoreceptors act most importantly to detect variation of the (partial pressure of oxygen) in the arterial blood, in addition to detecting arterial and pH.
  • Mechanoreceptors are located in the airways and parenchyma, and are responsible for a variety of reflex responses. These include:
    • The Hering-Breuer reflex that terminates inspiration to prevent over inflation of the lungs, and the reflex responses of coughing, airway constriction, and hyperventilation.
    • The upper airway receptors are responsible for reflex responses such as, sneezing, coughing, closure of glottis, and hiccups.
    • The spinal cord reflex responses include the activation of additional respiratory muscles as compensation, gasping response, hypoventilation, and an increase in breathing frequency and volume.
    • The nasopulmonary and nasothoracic reflexes regulate the mechanism of breathing through deepening the inhale. Triggered by the flow of the air, the pressure of the air in the nose, and the quality of the air, impulses from the nasal mucosa are transmitted by the trigeminal nerve to the breathing centers in the brainstem, and the generated response is transmitted to the bronchi, the intercostal muscles and the diaphragm.

Voluntary control of respiration[edit]

In addition to involuntary control of respiration by respiratory neuronal networks in the brainstem, respiration can be affected by higher brain conditions such as emotional state, via input from the limbic system, or temperature, via the hypothalamus, or free will. Voluntary or conscious control of respiration is provided via the cerebral cortex, although chemoreceptor reflexes are capable of overriding it.

While breathing can obviously be controlled both consciously and unconsciously, other basic functions provided by the brainstem cannot be controlled voluntarily. Only conscious control of respiratory neuronal networks in the reticular formation can affect other basic functions regulated by the brainstem, because of the inter-meshed character of the reticular formation, e.g. the heart rate in yoga[5] and meditation ("to take a deep breath").


  1. ^ Barrett, Kim E.; et al. (2012). Ganong's review of medical physiology. (24th ed.). New York: McGraw-Hill Medical. ISBN 0071780033. 
  2. ^ Tortora, G. J. and Derrickson, B. H., (2009). Principles of Anatomy and Physiology – Maintenance and continuity of the human body. 12th Edition. Danvers: Wiley
  3. ^ Coates EL, Li A, Nattie EE. Widespread sites of brain stem ventilatory chemoreceptors. J Appl Physiol. 75(1):5-14, 1984.
  4. ^ Cordovez JM, Clausen C, Moore LC, Solomon, IC. A mathematical model of pH(i) regulation in central CO2 chemoreception. Adv Exp Med Biol. 605:306-11, 2008.
  5. ^ Prasad, K.N. Udupa ; edited by R.C. (1985). Stress and its management by yoga (2nd rev. and enl. ed.). Delhi: Motilal Banarsidass. pp. 26 ff. ISBN 978-8120800007. Retrieved 17 July 2014. 

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