Control of respiration

Control of ventilation refers to the physiological mechanisms involved in the control of physiologic ventilation. Gas exchange primarily 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 brain to regulate the respiration: The first two centers are present on the medulla oblongata whereas the last two centers on the pons region of brain.
 * 1) Inspiratory center
 * 2) Expiratory center
 * 3) Pneumotaxic center
 * 4) Apneustic center

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
 * The pneumotaxic center is 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.

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.

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.


 * 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.

In addition to involuntary control of respiration by the respiratory center, respiration can be affected by conditions such as emotional state, via input from the limbic system, or temperature, via the hypothalamus. Voluntary control of respiration is provided via the cerebral cortex, although chemoreceptor reflex is capable of overriding conscious control.