1 Regulatory Mechanisms

Breath-holding time in a normal healthy adult is 45 to 55 seconds.

However, by practice, breathing can be held for a long period.

Respiration is subjected to variation, even under normal physiological conditions.

For example, emotion and exercise increase the rate and force of respiration.

But the altered pattern of respiration is brought back to normal within a short time by some regulatory mechanism.

Regulatory mechanisms responsible for quiet regular breathing are:

1. Nervous or neural mechanism.
2. Chemical mechanism.

2 Nervous Mechanism

Nervous mechanism that regulates respiration includes:

1. Respiratory centers.
2. Afferent nerves.
3. Efferent nerves.

3 Respiratory Centers

Respiratory centers are bilaterally situated in reticular formation of brainstem.

Depending upon the situation in brainstem, respiratory centers are classified into two groups:

1. Medullary centers
   1. Dorsal respiratory group of neurons.
   2. Ventral respiratory group of neurons.
2. Pontine centers
   1. Apneustic center.
   2. Pneumotaxic center.

4 Medullary Centers

1. Dorsal Respiratory Group of Neurons

Situation

Dorsal respiratory group of neurons are diffusely situated in nucleus of tractus solitarius which is present in upper medulla oblongata.

Usually, all these neurons are collectively called inspiratory center.

Type of Neurons

All the neurons of dorsal respiratory group are inspiratory neurons and generate inspiratory ramp by virtue of their autorhythmic property.

Function

Dorsal group of neurons are responsible for basic rhythm of respiration.

Experimental Evidence

Electrical stimulation of dorsal group of neurons in animals by using needle electrode causes contraction of inspiratory muscles and prolonged inspiration.

2. Ventral Respiratory Group of Neurons

Situation

Ventral respiratory group of neurons are present in nucleus ambiguus and nucleus retroambiguus.

Both the nuclei are situated in medulla oblongata, anterior and lateral to the nucleus of tractus solitarius.

Earlier, ventral respiratory group neurons were collectively called expiratory center.

Ventral respiratory group has both inspiratory and expiratory neurons. Inspiratory neurons are in central area of the group. Expiratory neurons are in caudal and rostral areas of the group.

Function

Normally, ventral group neurons are inactive during quiet breathing and become active during forced breathing.

During forced breathing, these neurons stimulate both inspiratory muscles and expiratory muscles.

Experimental Evidence

Electrical stimulation of inspiratory neurons in ventral group in animals causes contraction of inspiratory muscles and prolonged inspiration.

Stimulation of expiratory neurons causes contraction of expiratory muscles and prolonged expiration.

5 Pontine Centers

1. Apneustic Center

Situation

Apneustic center is situated in the nuclei of reticular formation of lower pons.

Function

Apneustic center increases depth of inspiration by acting directly on dorsal respiratory group of neurons.

Experimental Evidence

Stimulation of apneustic center causes apneusis.

Apneusis is an abnormal pattern of respiration, characterized by prolonged inspiration followed by inefficient short expiration.

2. Pneumotaxic Center

Situation

Pneumotaxic center is situated in the dorsolateral part of reticular formation in upper pons.

It is formed by neurons in the medial parabrachial and subparabrachial nucleus.

Subparabrachial nucleus is also called parabrachial Kolliker-Fuse nucleus.

Function

Primary function of pneumotaxic center is to control the pulmonary respiratory centers, particularly the dorsal group.

It acts through the apneustic center.

Pneumotaxic center inhibits the apneustic center so that the dorsal group neurons are inhibited.

Because of this, inspiration stops and expiration starts.

Thus, pneumotaxic center influences the switching between inspiration and expiration.

Pneumotaxic center increases respiratory rate by reducing the duration of inspiration.

Experimental Evidence

Stimulation of pneumotaxic center does not produce any typical effect, except slight prolongation of expiration, by inhibiting the dorsal respiratory group through apneustic center.

Destruction or inactivation of pneumotaxic center results in apneusis.

6 Connections of Respiratory Centers

Efferent Pathway

Nerve fibers from respiratory centers leave brainstem and descend in spinal cord and terminate on the motor neurons in the anterior horn cells of cervical and thoracic segments of spinal cord.

From the motor neurons of spinal cord two sets of nerve fibers arise:

1. Phrenic nerve fibers (C3 to C5) which supply the diaphragm.
2. Intercostal fibers (T1 to T11) which supply the external intercostal muscles.

Afferent Pathway

Impulses from peripheral chemoreceptors and baroreceptors are carried to respiratory centers by the branches of glossopharyngeal and vagus nerves.

Nerve fibers also carry impulses from stretch receptors of lungs to the respiratory centers.

Thus, respiratory centers receive afferent impulses from different parts of body and modulate the movements of thoracic cage and lungs accordingly through efferent nerve fibers.

7 Integration of Respiratory Centers

Role of Medullary Centers

Rhythmic Discharge of Inspiratory Impulses

Dorsal respiratory group neurons maintain normal rhythmicity of respiration by discharging impulses rhythmically.

The impulses are transmitted to respiratory muscles by phrenic and intercostal nerves.

Inspiratory Ramp

Inspiratory ramp is a pattern of discharge from dorsal respiratory group neurons characterized by steady increase in amplitude of the action potential.

To start with, the amplitude of action potential is low due to the activation of only few neurons.

Later, more and more neurons are activated leading to gradual increase in amplitude of the action potential in a ramp fashion.

Impulses of this type of firing from dorsal group neurons are called inspiratory ramp signals.

Duration of Inspiratory Ramp

Impulses from dorsal group of neurons are produced only for 2 seconds during which inspiration occurs.

After 2 seconds, the ramp signals stop abruptly and do not appear for another 3 seconds.

Switching off ramp signals causes expiration.

At the end of 3 seconds, the inspiratory ramp signal appears again in the same pattern, and the cycle is repeated.

Role During Inspiration and Expiration

Normally, during inspiration, dorsal respiratory group neurons inhibit expiratory neurons of ventral group.

During expiration, expiratory neurons inhibit the dorsal group neurons.

Thus, the medullary respiratory centers control each other.

Significance of Inspiratory Ramp Signals

Significance of inspiratory ramp signals is that there is a slow and steady inspiration so that the filling of lungs with air is also steady.

Role of Pontine Centers

Pontine respiratory centers regulate the medullary centers.

Apneustic center accelerates the activity of dorsal group of neurons and the stimulation of this center causes prolonged inspiration.

Pneumotaxic center inhibits apneustic center and restricts the duration of inspiration.

Pre-Bötzinger Complex

8 Factors Affecting Respiratory Centers

1. Impulses from Higher Centers

Higher centers alter the respiration by sending impulses directly to dorsal group neurons.

Impulses from various parts of cerebral cortex such as anterior cingulate gyrus, olfactory tubercle and posterior orbital gyrus inhibit respiration.

Impulses from motor areas and Sylvian area of cerebral cortex produce forced breathing.

2. Impulses from Stretch Receptors of Lungs: Hering-Breuer Reflex

It is initiated by the stimulation of stretch receptors of bronchi and bronchioles.

Stretch receptors give response to stretch of the tissues.

During inspiration, there is stretching of lungs due to entrance of air resulting in stimulation of stretch receptors.

Impulses from stretch receptors pass through vagal afferent fibers to respiratory centers and inhibit the dorsal group neurons.

So, inspiration stops and expiration starts.

Thus, overstretching of lung tissues is prevented.

However, Hering-Breuer reflex does not operate during quiet breathing.

It operates only when the tidal volume is increased beyond 1,000 mL.

This reflex is also called Hering-Breuer inflation reflex since it occurs due to inflation of lungs during inspiration.

The reverse of this reflex is called Hering-Breuer deflation reflex and it takes place during expiration.

During expiration the stretching of lungs is abolished, deflation of lungs occurs.

3. Impulses from ‘J’ Receptors of Lungs

‘J’ receptors are juxtacapillary receptors which are present on the wall of alveoli and having close contact with pulmonary capillaries.

Stimulation of the ‘J’ receptors produces a reflex response, which is characterized by apnea followed by hyperventilation, bradycardia, hypotension and weakness of skeletal muscles.

Role of ‘J’ receptors in physiological conditions is not clear.

However, these receptors are responsible for hyperventilation in the patients affected by pulmonary congestion and left heart failure.

4. Impulses from Irritant Receptors of Lungs

Besides stretch receptors, there is another type of receptors in the bronchi and bronchioles, called irritant receptors.

Irritant receptors are stimulated by chemical agents such as ammonia and sulfur dioxide.

Stimulation of irritant receptors produces reflex hyperventilation along with bronchospasm.

Hyperventilation along with bronchospasm prevents further entry of harmful agents to the alveoli.

5. Impulses from Baroreceptors

Baroreceptors are the receptors which give response to change in blood pressure.

Whenever arterial blood pressure increases, baroreceptors are activated and send inhibitory impulses to vasomotor center in medulla oblongata.

This leads to decrease in blood pressure and inhibition of respiration.

However, in physiological conditions, the role of baroreceptors in regulation of respiration is insignificant.

6. Impulses from Chemoreceptors

Chemoreceptors play an important role in the chemical regulation of respiration.

Details of the chemoreceptors and chemical regulation of respiration are given below.

7. Impulses from Proprioceptors

Proprioceptors are the receptors, which give response to the change in the position of body.

These receptors are situated in joints, tendons and muscles.

Proprioceptors are stimulated during muscular exercise and send impulses to brain particularly, the cerebral cortex through somatic afferent nerves.

Cerebral cortex in turn stimulates the respiratory centers and causes hyperventilation by sending impulses to the medullary respiratory centers.

8. Impulses from Thermoreceptors

Thermoreceptors are cutaneous receptors, which give response to change in environmental temperature.

There are two types of temperature receptors, namely receptors for cold and receptors for warmth.

When body is exposed to cold or when cold water is applied over the body, cold receptors are stimulated and send impulses to cerebral cortex via somatic afferent nerves.

Cerebral cortex in turn stimulates the respiratory centers and causes hyperventilation.

9. Impulses from Pain Receptors

Pain receptors are the receptors which give response to pain stimulus.

Whenever pain receptors are stimulated, impulses are sent to cerebral cortex via somatic afferent nerves.

Cerebral cortex in turn stimulates the respiratory centers and causes hyperventilation.

9 Chemical Mechanism

Chemoreceptors are the sensory nerve endings, which give response to three changes in the concentrations of blood.

Changes in Chemical Constituents of Blood Stimulating Chemoreceptors

1. Hypoxia (decreased partial pressure of oxygen).
2. Hypercapnia (increased partial pressure of carbon dioxide).
3. Increased hydrogen ion concentration.

Types of Chemoreceptors

Chemoreceptors are classified into two groups:

1. Central chemoreceptors.
2. Peripheral chemoreceptors.

10 Central and Peripheral Chemoreceptors

Central Chemoreceptors

Chemoreceptors present in brain are called the central chemoreceptors.

Central chemoreceptors are situated at medulla oblongata, close to dorsal respiratory group of neurons.

This area with chemoreceptors is known as chemosensitive area.

Mechanism of Action

Main stimulant for central chemoreceptors is the increased hydrogen ion concentration.

However, hydrogen ions from blood cannot cross the blood-brain barrier and blood-cerebrospinal fluid barrier.

On the other hand, carbon dioxide can easily cross these barriers and enter the interstitial fluid of brain or cerebrospinal fluid.

There, the carbon dioxide combines with water to form carbonic acid.

Since carbonic acid is unstable, it immediately dissociates into hydrogen ion and bicarbonate ion.

Hydrogen ions stimulate central chemoreceptors.

Chemoreceptors in turn send stimulatory impulses to dorsal respiratory group of neurons causing increased ventilation (increased rate and force of breathing).

Because of this, the excess carbon dioxide is washed out and the respiration is brought back to normal.

Peripheral Chemoreceptors

Chemoreceptors present in carotid and aortic region are called peripheral chemoreceptors.

Mechanism of Action

Whenever partial pressure of oxygen decreases, chemoreceptors are stimulated and send impulses through aortic and Hering’s nerves.

The impulses reach respiratory centers, particularly dorsal group of neurons and stimulate them.

Dorsal group of neurons send stimulatory impulses to respiratory muscles resulting in increased ventilation.

This provides enough oxygen and rectifies the lack of oxygen.

Peripheral chemoreceptors are mildly sensitive to increased partial pressure of carbon dioxide and increased hydrogen ion concentration.

Chemical Regulation of Respiration