Control of ventilation

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 uptake of oxygen and the removal of carbon dioxide.^[1] Under most conditions, the partial pressure of carbon dioxide controls the rate of respiration.

The most important function of breathing is gas exchange (of oxygen and carbon dioxide). Thus the control of respiration is centered primarily on how well this is achieved by the lungs.

There are four main centers in the reticular formation and other parts of the brainstem that regulate the respiration rate.

Inspiratory centre - reticular formation, medulla oblongata
Expiratory center - reticular formation, medulla oblongata
Pneumotaxic center - various nuclei of the pons
Apneustic center - nucleus of the pons

The first two centers are present on the medulla oblongata whereas the last two centers on the pons region of brain.

Involuntary control of respiration

Ventilatory pattern

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)
- ventral respiratory group (nucleus retroambigualis, nucleus ambigus, nucleus parambigualis and the pre-Bötzinger complex). The ventral respiratory group controls voluntary forced exhalation and acts to increase the force of inspiration. Regulates rhythm of inhalation and exhalation.
- dorsal respiratory group (nucleus tractus solitarii). The dorsal respiratory group controls mostly inspiratory movements and their timing.
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

Ventilation is normally controlled by the autonomic nervous system, with only limited voluntary override. An exception to this is Ondine's curse, where autonomic control is lost. However, the information transported from the brainstem to the intercostal muscles and the diaphragm involves the somatic nervous system as those are composed of skeletal muscle.^[2]

Determinants of ventilatory rate

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 chemoreceptors in 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 is increased beyond the capacity of the lungs to expel CO₂. CO₂ is stored largely in the blood 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 ion, which, by definition, decreases the pH of the blood.

During moderate exercise, ventilation increases in proportion to metabolic production of carbon dioxide. During strenuous exercise, ventilation increases more than needed to compensate for carbon dioxide production. Increased glycolysis facilitates release of protons from ATP and metabolites lower pH and thus increase breathing.

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 anaesthetic drugs tend to depress ventilation, especially with regards to carbon dioxide response. 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.

Ventilation is temporarily modified by voluntary acts and complex reflexes such as sneezing, straining, burping, coughing and vomiting.

Feedback control

Receptors play important roles in the regulation of respiration; central and peripheral 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 oxygen in the arterial blood, in addition to detecting arterial carbon dioxide 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 centres in the brainstem, and the generated response is transmitted to the bronchi, the intercostal muscles and the diaphragm.

Voluntary control of respiration

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 reflex is 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").

References

^ al.], Kim E. Barrett, ... [et (2012). Ganong's review of medical physiology (24th ed.). New York: McGraw-Hill Medical. ISBN 0071780033.{{cite book}}: CS1 maint: multiple names: authors list (link)
^ Tortora, G. J. and Derrickson, B. H., (2009). Principles of Anatomy and Physiology – Maintenance and continuity of the human body. 12th Edition. Danvers: Wiley
^ Coates EL, Li A, Nattie EE. Widespread sites of brain stem ventilatory chemoreceptors. J Appl Physiol. 75(1):5-14, 1984.
^ 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.
^ 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. {{cite book}}: |first1= has generic name (help)CS1 maint: multiple names: authors list (link)

External links

Paul, Anthony D.; et al. (1995). "Neuronal Connections of a Ventral Brainstem Respiratory Chemosensitive Area". In C. Ovid Trouth (ed.). Ventral brainstem mechanisms and control of respiration and blood pressure. New York: M. Dekker. pp. 517–523. ISBN 0-8247-9514-8. OCLC 32169247. {{cite book}}: External link in |chapterurl= (help); Unknown parameter |chapterurl= ignored (|chapter-url= suggested) (help)
Rabbany, Sina Y., "Breathing Coordination", Hofstra University [1]
Webber, Charles L., Jr., Ph.D, Pulmonary Curriculum Function:"Neural Control of Breathing", Stritch School of Medicine, Loyola University-Chicago [2]

[Ganong-1] .], Kim E. Barrett, ... [et (2012). Ganong's review of medical physiology (24th ed.). New York: McGraw-Hill Medical. ISBN 0071780033.{{cite book}}: CS1 maint: multiple names: authors list (link)

[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

[Coates-3] Coates EL, Li A, Nattie EE. Widespread sites of brain stem ventilatory chemoreceptors. J Appl Physiol. 75(1):5-14, 1984.

[Cordovez-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.

[yoga-reticularis-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. {{cite book}}: |first1= has generic name (help)CS1 maint: multiple names: authors list (link)

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v t e Respiratory physiology
Respiration	breath inhalation exhalation obligate nasal breathing respiratory rate respirometer pulmonary surfactant compliance elastic recoil hysteresivity airway resistance bronchial hyperresponsiveness constriction dilatation mechanical ventilation
Control	pons pneumotaxic center apneustic center medulla dorsal respiratory group ventral respiratory group chemoreceptors central peripheral pulmonary stretch receptor Hering–Breuer reflex
Lung volumes	VC FRC Vt dead space CC PEF calculations respiratory minute volume FEV1/FVC ratio Lung function tests spirometry body plethysmography peak flow meter nitrogen washout
Circulation	pulmonary circulation hypoxic pulmonary vasoconstriction pulmonary shunt
Interactions	ventilation (V) Perfusion (Q) Ventilation/perfusion ratio V/Q scan zones of the lung gas exchange pulmonary gas pressures alveolar gas equation alveolar–arterial gradient hemoglobin oxygen–hemoglobin dissociation curve (Oxygen saturation 2,3-BPG Bohr effect Haldane effect) carbonic anhydrase (chloride shift) oxyhemoglobin respiratory quotient arterial blood gas diffusion capacity (DLCO)
Insufficiency	high altitude death zone oxygen toxicity hypoxia