Neural control of respiration

I. Voluntary control center

✓ It is located in the cerebral cortex.
✓ They send impulses to respiratory motor neurons via corticospinal tracts.

II. Automatic control center located in the medulla oblongata and pons
✓ The neurons of this system are located in the pons and medulla.
✓ They send impulses to the respiration motor neurons in the spinal cord via the descending tracts.
✓ Inspiratory motor neurons are phrenic motor neurons in C3 to C5 and external intercostals neurons
throughout thoracic cord.
✓ Expiratory motor neurons are internal intercostals motor neurons in the thoracic cord.
✓ Expiratory motor neurons are inhibited when inspiratory motor neurons are active, and vice versa. It is
called reciprocal innervation.
✓ Brain stem respiratory neurons are of 2 types, I and E neurons.
✓ I neurons discharge during inspiration.
✓ E neurons discharge during expiration. During quiet breathing, expiration is passive and E neurons are quiet.
✓ When ventilation is increased , E neurons become active.

A. Medullary systems
1. Pre-Botzinger complex
2. Respiratory centre

B. Pontine centres
1. Pneumotaxic centre
2. Apneusis centre

A. Medullary systems
The main components of the respiratory control pattern generator responsible for automatic respiration are
located in the medulla
1. Pre-Botzinger Complex
Location: between nucleus ambiguus and the lateral reticular nucleus
Composition: a small group of pacemaker cells
Functions: They produce automatic rhythmic discharge. They also contact the hypoglossal nuclei, and the
tongue is involved in the regulation of the airway resistance.

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 2. Respiratory centre
It is made up of 2 groups of neurons.
1. Dorsal group
Location: In and near the NTS (nucleus of tractus solitarius)
Composition: It is made up of I neurons.
It receives information from lung stretch receptors from airway and respiratory chemoreceptors.
2. Ventral group
Location: Extend through the NA (nucleus ambiguous and NRA (nucleus retroambiguus)
Composition: It is made up of I neurons in the centre and E neurons at the rostral and caudal ends.
Function Rostral group inhibit I neurons during expiration.
However, lesions of these neurons do not abolish respiratory activity, and they apparently project to the pre-
Bötzinger pacemaker neurons.
B. Pontine centres
1. Pneumotaxic centre
Location: upper pons (medial parabrachial and Kolliker-Fuse nuclei )
Composition: I and E – neurons, neurons active in both phases of respiration
Function: inhibit respiration, switching inspiration and expiration
2. Apneustic centre
Location: lower pons
Function: Stimulates inspiration, producing a deep and prolonged inspiratory gasp (apneusis).

III. Vagal afferent inhibits the inspiratory motor neurons. After vagotomy, inspiratory activity is prolonged (apneusis).

Transection of the Brain stem

1. Below the medulla
Respiration stops.
2. Above the pons
Respiration intact.
3. Between Pons and Medulla
Respiration present but irregular.
4. Destruction of Pneumotaxic centre
(a) With vagi intact
Respiration becomes slower, tidal volume becomes greater.
(b) With vagi cut Inspiratory time becomes prolonged (apneusis)

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 Cerebral cortex

Pneumotaxic centre

Pons
Apneustic centre

PBC

DRG VRG Medulla

RMN in spinal cord

vagus

Lung stretch receptor Respiratory muscles

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 Chemical regulation of respiration

Changes in blood chemistry (a rise in PCO2 and H+ concentration, and a fall in PO2) stimulates respiratory centre via
respiratory chemoreceptors. Changes in opposite direction has slight inhibitory effect.

There are two types of respiratory chemoreceptors.

Central chemoreceptor
✓ located on ventral surface of medulla oblongata.
✓ monitor the H+ concentration of CSF including the brain ISF.
✓ CO2 enter the CSF and brain ISF, then CO2 is promptly hydrated, the resultant H2CO3 dissociate, the resultant H+
stimulate the central chemoreceptors.

Peripheral chemoreceptor
➢ carotid bodies and aortic bodies.
➢ carotid bodies are located near carotid bifurcation on each side. Aortic bodies are situated near arch of
aorta.
➢ afferent from carotid bodies and aortic bodies ascend to medulla via glossopharyngeal (IX) and vagus (X)
nerves.
➢ stimulated by a rise in arterial PCO2, arterial H+ concentration, decline in arterial PO2, a rise in plasma
potassium and lobelline (respiratory stimulants).
➢ Low PO2 causes closure of K+ channel of type I cell. This reduces K+ efflux, which causes depolarization.
Ca++ channel open. Ca++ influx causes release of dopamine which leads to excitation of afferent nerve
endings.

Ventilatory response to CO2

✓ Normal arterial PCO2 is 40 mmHg.
✓ When rise in arterial PCO2, ventilation is stimulated via both the peripheral and central chemoreceptors.
✓ CO2 enter the CSF and brain ISF, then CO2 is promptly hydrated, the resultant H2CO3 dissociate, the resultant H+
stimulate the central chemoreceptors.
✓ Increased ventilation increases the excretion of CO 2. Therefore, arterial PCO2 falls to normal.
✓ There is a linear relationship between respiratory minute volume and PCO 2.
✓ But, there is upper limit to this linearity.
✓ When PCO2 of inspired gas is closed to alveolar PCO2, elimination of CO2 becomes difficult.
✓ When CO2 content of inspired air is more than 7 %, alveolar and arterial PCO2 begins to rise abruptly in
spite of hyperventilation.
✓ Accumulation of CO2 in the body (hypercapnia) depress the CNS, including the respiratory center.
✓ This produces headache, confusion and coma (CO2 narcosis).
✓ Decrease in PCO2 depress the respiratory center and shallow breathing results.

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Ventilatory response to oxygen lack
➢ A fall in arterial PO2 stimulates periphery chemorecepotrs. This stimulates respiratory centre resulting in
hyperventilation.
➢ Stimulation is slight when PO2 is > 60 mmHg. Appreciable respiratory stimulation is seen when PO2 < 60
mmHg. There are two reasons for this.
➢ When the arterial PO2 falls, Hb becomes less saturated with O2. Hb- binds more H+ than does oxyHb.
There is a slight decrease in the H+ concentration of arterial blood. The fall in H+ concentration tends to
inhibit respiration.
➢ When the arterial PO2 falls, ventilation is stimulated. Alveolar PCO2 falls and this tends to inhibit
respiration.
➢ When PO2 < 60 mmHg, stimulatory effect of respiration override inhibitory effects of a fall in arterial H +
concentration and PCO2.

Ventilatory response to Acid Base balance

➢ In metabolic acidosis (e.g. diabetic ketoacidosis), there is pronounced respiratory stimulation (Kussmaul
Breathing). The hyperventilation decreases alveolar PCO2 and thus produces a compensatory fall in blood
H+ concentration.
➢ In metabolic alkalosis (e.g. loss of H+ in vomiting), ventilation is depressed and arterial PCO2 rises, raising
the H+ concentration towards normal.
➢ Hyperventilation that is not due to a rise in arterial H + concentration causes respiratory alkalosis.
Hypoventilation that is not due to a fall in arterial H+ concentration causes respiratory acidosis.

Effects of Hypoxia on CO2 response

Hypoxia makes the individual more sensitive to increased in PCO2.

Effects of H+ on CO2 response

The stimulatory effects of H+ and CO2 on respiration appears to be additive. The same amount of respiratory
stimulation is produced by lower arterial PCO2 levels.

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↓ Arterial PO2 ↑ Arterial H+ ↑ Arterial PCO2

Peripheral chemoreceptors Central chemoreceptors

Medullary respiratory neurons

RMN in spinal cord

Respiratory muscles

↑ventilation

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Nonchemical influences on respiration

I. Reflexes from airways and lungs

1. Lung inflation → Stretch receptors → Vagal afferent → shortening of inspiration (Hering Breuer reflex)
2. Chemicals → irritant receptors → Vagal afferent → bronchoconstriction & hypernoea
3. Hyperinflation & chemicals → J receptors → Vagal afferent → apnoea followed by rapid breathing (pulmonary
chemoreflex)

II. Coughing and Sneezing (protective reflexes)

- temporarily modified
- coughing → deep inspiration followed by forced expiration, glottis is then suddenly opened
- sneezing → similar, glottis is continuously open

III. Afferents from higher centres

Limbic system → respiratory neurons in medulla
Neocortex → respiratory motor neurons in spinal cord (voluntary control)
Since voluntary and automatic control of respiration are separate, automatic control is sometimes disrupted
without loss of voluntary control. This clinical condition is called Ondine’s curse.

IV. Afferents from proprioceptors

- stimulate respiratory neurons
- increase ventilation during exercise

V. Visceral reflexes
- vomiting, swallowing, drinking, yawning and hiccupping suppress respiration

VI. Baroreceptor stimulation

- inhibit respiration

Breath holding

Respiration can be inhibited voluntarily for some time, but eventually the voluntary control is overridden.
✓ Breaking point: The point at which breathing can no longer be voluntarily inhibited.
✓ Breaking is due to rise in arterial PCO2 and fall in PO2.
✓ After removal of carotid bodies → longer breath holding
✓ Breathing 100 % oxygen before breath holding → Breaking point is delayed.
✓ Hyperventilating the room air before breath holding → Breaking point is delayed.
✓ Gas mixture low in PO2 and high in PCO2 → additional 20 seconds or more.
✓ Psychological factors also play a role.

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