Subchapter content:

1. Introduction into respiratory control

2. Chemical control of respiration

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Introduction into respiratory control

Respiration is the only one vital function, which can be partially controlled on conscious level. But the word “partially” should be stressed – there are specialized receptors and regulatory mechanism that take over the control of respiratory movements if the homeostasis should be disturbed.

Respiratory centres

There are groups of neurons in medulla oblongata which exercise control over intensity and frequency of respiratory movements. Recent studies have shown that there is no discrete group of neurons which can be described as respiratory center in humans’ brain stem. In fact humans have tens of disperse neuronal groups – mutually interconnected – that intervene in regulation. This continuous entity is called respiratory functional system.

Respiratory functional system is very hard to gasp. There are insufficient experiments questioning its physiological mechanisms. And the concept as whole is unappropriate for use in pre-gradual education.

Physiology posses one model more that describes discrete respiratory centers. Although outdated, knowledge of this model is completely sufficient to provide appropriate medical treatment in majority of clinical cases.

This model describes several neuronal groups localized bilaterally in medulla oblongata. There are three major functional groups:

1) Dorsal respiratory group

2) Ventral respiratory group

3) Pneumotaxic centre

Dorsal respiratory group

Most neurons of dorsal respiratory group are part of solitary tract nuclei, but some can be found all over the length of medulla oblongata. As you may know, solitary tract collects signals from vagal and glossopharyngeal nerves, thus it has complete information concerning current status of lungs’ chemoreceptors, baroreceptors and mechanoreceptors at every moment in time.

Main role of dorsal respiratory group is to act as pacemaker of respiratory movements. Rhythm of these movements is modified by signals from peripheral receptors. Note that rhythm is modified not determined by status of peripheral receptors. Even if all sensory inputs entering medulla oblongata are dissected, the pacemaker is still capable of doing its job.

So called inspiratory signal originates in dorsal respiratory centre. It is composed of repeated spontaneously triggered action potentials, whose frequency is directly proportional to intensity of inspiration. And it also last nearly as long as inspiration does. Inspiratory signal is transmitted to alpha motoneurons in spinal cord, especially ones innervating diaphragma.

After some time cessation occurs. And when inspiratory signal is nearly non existent, expiration follows. Note that inspiration is dependent on inspiratory signal from dorsal respiratory group, but expiration is passive process (at least in resting conditions).

Precise mechanism of inspiratory signals’ cycles is unknown. Theory has it, there in a neuronal circuit which work as follows: inspiratory neuron excites itself and signal is led to alpha motoneurons in spinal cord as well as to another neuron which sends its axon back to the same inspiratory neuron which exited it. This “another neuron” inhibits its inspiratory neuron.

Ventral respiratory group

Ventral respiratory group is localised about 5 mm ventro laterally from dorsal respiratory group, but again its neurons can be found in whole length of medulla oblongata. Majority of neurons belong to nucleus ambiguus.

Contrary to dorsal respiratory group, neurons of ventral respiratory group are not active if breathing at ease. Should breathing become strenuous, neurons activate and frequency of action potential correspond to frequency of neurons from dorsal respiratory group. In fact they are directly connected to each other and dorsal respiratory activates them if needed. Ventral respiratory group innervates alpha motoneurons of auxiliary respiratory muscles.

There is an evidence that direct stimulation of certain neurons from ventral respiratory group initiates inspiration. Don’t forget that groups we are describing are just a mere approximation of complicated reality we call respiratory functional system.

Pneumotaxic centre

Pneumotaxic centre is localized in dorsal part of upper third of pons Varolii. Its main role is regulation of neuronal activity from sources inhibiting dorsal respiratory group. By this action, pneumotaxic centre sets duration of inspiration for every respiratory cycle. In other words it limits inspiration and thus greater activity in pneumotaxic centre increase frequency of respiratory movements. Maximal frequency it can enforce is about 40 inspirations a minute.

Vagal nerve can limit respiration as well as pneumotaxic centre. Its action is called Hering-Breuer inflation reflex. Some vagal fibres conduct information from pulmonary stretch receptors found in wall of bronchi and bronchioles. Receptors are activated by stretching walls of lower airways. Inspiration is terminated should walls stretch beyond physiological levels.

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Chemical control of respiration

As you know main objective of respiratory system is to keep partial pressure of oxygen and carbon dioxide at physiological levels. So it is obvious, there are regulatory mechanisms, which control activity in central respiratory, should pCO₂, pO₂ or pH change.

Direct chemical control of respiratory centres

Direct chemical control is exercised by decreased pH and increased partial pressure of carbon dioxide (in fact this two factors are intertwined – see Subchapter 7/7). Partial pressure of oxygen does not directly regulate activity of respiratory centres. It acts indirectly through chemoreceptors in aorta and carotids.

There is a theory stating chemoreceptor centre lies near the ventral surface of medulla oblongata. Its chemoreceptors are excited, when there is an increase in cerebrospinal fluid concentration of H⁺. H⁺ plasma level increases during acidaemia, but it has no or little direct effect on respiratory centres activity. The reason is simple H⁺ do not cross hematoencephalic barrier. On the other hand CO₂ does. Under influence of enzyme called carbonate dehydratase it undergoes chemical reaction, turning CO₂  into water and bicarbonate.

CO₂ + H₂O → H₂CO₃ → H⁺ + HCO₃^–

 In other words neurons of chemoreceptor centre are activated only by H⁺ which comes from CO₂. Increase in activity of chemoreceptor centre leads to increase in respiratory frequency and volume. Thus alveolar ventilation is increased and hyperventilation occurs. Partial pressure of CO₂ in alveolar gas decrease and due to gradient similar decrease of blood partial pressure follows. Direct effect of this changes is perceived as increase in pH. Precise mechanism how chemoreceptor centre exercise its influence over the dorsal and ventral respiratory group is not known.

Indirect chemical control of respiratory centres

Indirect chemical control of respiratory centre is exercised by peripheral chemoreceptor system. This system detect changes in partial pressure of oxygen as well as partial pressure of carbon dioxide. Groups of chemoreceptors can be found in aorta, carotids and even elsewhere. They collect information about immediate levels of oxygen and carbon dioxide in blood.

Because highest density of chemoreceptors is localized in arcus aortae and carotid bifurcation, we call them aortic corpuscule and carotid corpuscles respectively. Signals from carotid corpuscles are collected by glossopharyngeal nerve and transmitted to solitary tract nuclei. Information from aortic corpuscule is collected by vagal nerve that terminates in solitary tract as well.

When peripheral chemoreceptors detect decrease in oxygen partial pressure they transmit the signal to respiratory centres and hyperventilation occurs. Precise mechanism how do oxygen receptors work is unknown.

Increase in carbon dioxide partial pressure is monitored as well, and hyperventilation is initiated if above normal values are detected. There is a difference between action of peripheral and central chemoreceptors. Central chemoreceptors offers much potent response, but are slow to react due to hematoencephalic barrier. Peripheral chemoreceptors are much more quicker and can normalize subtle pH changes without their central copartner even noticing. If the change in carbon dioxide partial pressure is more prominent, they start the process of normalization and central chemoreceptors take over the control lately.

For example during marathon run increase in pCO₂ occurs due to strenuous muscular activity. When pH is decreased under physiological levels hyperventilation is introduced by peripheral chemoreceptors. Should the activity continues, central chemoreceptor takes over and initiates more potent respiratory response.

Subchapter Authors: Patrik Maďa and Josef Fontana