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Control of ventilation (control of respiration) 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.

The control unit of ventilation consists of a processor (the breathing centre in the brain) which integrates inputs (emotional, chemical and physical stimuli) and controls an effector (the lungs) via motor nerves arising from the spinal cord. In humans, quiet breathing occurs by the cyclical contraction of the inspiratory muscles, particularly the diaphragm. Inhalation is normally an active process, and exhalation is passive. However, when ventilation is increased (over 40 litres per minute), such as during heavy exercise, muscle activity becomes involved in exhalation. Under these circumstances, the work of breathing over time can exceed the metabolic rate of the rest of the body.

Ventilation is normally autonomic, with only limited voluntary override, but an exception to this is Ondine's curse, where autonomic control is lost.

The pattern neuronal firing when breathing can be divided into inspiratory and expiratory phases. Inspiration shows a sudden ramp 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 centres 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 ambiguus, nucleus parambigualis and the pre-Botzinger complex). The ventral respiratory group controls voluntary forced exhalation and acts to increase the force of inspiration.
  • dorsal respiratory group (nucleus tractus solitarius). The dorsal respiratory group controls mostly inspiratory movements and their timing.
• pons
  • pneumotaxic centre. The pneumotaxic centre is involved in fine tuning of respiration rate.
  • apneustic centre

There is further integration in the anterior horn cells of the spinal cord.

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. 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. Lactic acid produced during anaerobic metabolism lowers pH and thus increases breathing. In aerobic metabolism, one molecule of acid (CO₂) is produced in order to produce 6 molecules of the energy carrier ATP, wheeras in anaerobic metabolism, 6 molecules of lactic acid are produced to produce the same amount of energy.

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, coughing and vomiting.

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, bradycardia, 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.

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.

• Paul, Anthony D., et al., Neuronal Connections of a Ventral Brainstem Respiratory Chemosensitive Area: “Ventral Brainstem Mechanisms and Control of Respiration and Blood Pressure” [1]
• Rabbany, Sina Y., “Breathing Coordination”, Hofstra University [2]
• Webber, Charles L., Jr., Ph.D, Pulmonary Curriculum Function:“Neural Control of Breathing”, Stritch School of Medicine, Loyola University-Chicago [3]