Neural Control Of Breathing

Question 1

Why does your breathing change?

Answer 1

To meet demands

Question 2

Why do we need muscles in respiration to function?

Answer 2

To create the forces needed for inspiration and expiration in ventilation to meet demands

Question 3

Why is ventilation regulated?

Answer 3

To meet oxygen demands and carbon dioxide production

Question 4

How is breathing initiated?

Answer 4

Breathing is initiated by neural activation of respiratory muscles which allows movement of these muscles for ventilation. Respiratory muscles are skeletal muscles so they require nervous stimulation to contract.

Question 5

How are contractile signals initiated?

Answer 5

They are initiated within the brainstem and descend via spinal tracts which synapse with the lower motor neurones which innervate the respiratory muscles.
These motor nerves release acetylcholine at the muscles causing them to contract.
So to cause skeletal muscle to contact, it needs neural input.

Question 6

What is the effect of spinal cord injury on neural control of breathing?

Answer 6

In spinal cord injury, the injury affects everything from the injury down. So the higher the level of injury, the greater the impact on breathing.
Phrenic nerves originate at C3-C5 and intercostal muscle nerves originate from T1-T11.

So if there’s injury around C2, the phrenic nerves and intercostal muscle nerves both will be damaged as they’re below C2 so can’t send out neural inputs to the respiratory muscles.
If there’s injury below C5, at least the diaphragm can still work.

Question 7

What are the effects of motor neurone disease and muscular dystrophy?

Answer 7

Motor neurone disease = can’t send neural inputs to skeletal muscle so the muscles can’t contract, hence forced aren’t created for inspiration and expiration in ventilation

Muscular dystrophy = this is weakening and breaking down of skeletal muscle so even if there’s neural input, it’s difficult for the muscles to contract and create the forces needed for ventilation.

Question 8

Which muscles are used in inspiration?

Answer 8

Quiet inspiration = diaphragm

Forced inspiration = diaphragm, external intercostal muscles, pectorals, sternomastoid, scalene

Question 9

Which muscles are used in expiration?

Answer 9

Quiet breathing: elastic recoil

Forced expiration: elastic recoil, internal intercostal muscles, abdominals

Question 10

What determines the basic pattern of ventilation (how deep and often you breathe)?

Answer 10

Central pattern generator (CPG) which is a complex system of neurones in the brainstem (medulla and pons).

Question 11

What is the central pattern generator made up of?

Answer 11

1. Pontine respiratory group (PRG)
2. Dorsal respiratory group (DRG)
3. Ventral respiratory group (VRG)
   They send different signals to different muscles to cause different intensities of contraction and different durations.

Question 12

How is the central pattern generator modulated?

Answer 12

It is modulated by afferent inputs from various receptors and sensors in the body which inform the CPG what level of ventilation is needed to maintain healthy carbon dioxide, oxygen and pH levels.
Inputs from higher somatic and emotional centres also feed into the CPG so breathing can be voluntarily controlled and can be affected by extreme emotional states.

Question 13

How is it impossible to voluntarily asphyxiate one’s self by holding your breath until you die?

Answer 13

Since you have some voluntary control over your breathing, you can hold your breath. For a certain amount of time, this can override the CPG so you can hold your breath. But after a while, you get the urge to breathe due to excess carbon dioxide which will be overpowering or acute hypoxaemia will occur causing loss of consciousness - at this point, the involuntary breathing will begin, so CPG takes over.

Question 14

Give examples of signals from various inputs that are sent to CPG

Answer 14

1. What is the pH in the cerebrospinal fluid?
2. How much carbon dioxide, hydrogen ions and oxygen are in arterial blood?
3. What is the current lung volume? How stretched are the lungs?
4. Is there stimulation from higher emotion centres?

The CPG will take inputs from different sources from different parts of the body and will decide how deeply and often we will have to breathe to meet demands. It sets a rhythm. Ensures the right muscles are stimulated at the right time.

Question 15

Explain how central respiratory chemoreceptors respond (indirectly) to changes in arterial PCO2

Answer 15

The central respiratory chemoreceptors (CRC) are present in the medulla.
CRC respond to hydrogen ions in the cerebrospinal fluid (not in artery as hydrogen ions are impermeable at the blood brain barrier). The amount of hydrogen ions is basically proportional to the amount of carbon dioxide because the hydrogen ions detected are produced from the carbon dioxide diffusing in from arterial blood into cerebrospinal fluid so the greater the hydrogen ion concentration, it means the greater the arterial carbon dioxide concentration.

The information is then sent to the respiratory control centres (at CPG) which determines ventilation.
There is a negative feedback system as e.g if the carbon dioxide levels are high, ventilation will increase to then decrease the carbon dioxide levels.

CRC enable the body to respond when carbon dioxide levels are increased in arterial blood. When carbon dioxide levels are high, that means carbon dioxide is being made but not removed so we need ventilation to increase.

Question 16

Do peripheral respiratory chemoreceptors have a greater impact on ventilation or central respiratory chemoreceptors?

Answer 16

Central respiratory chemoreceptors.

Question 17

How does CRC indirectly respond to blood pH?

Answer 17

Because arterial carbon dioxide can pass through the blood brain barrier into cerebrospinal fluid to produce carbonic acid and then hydrogen ions.

This CRC response to carbon dioxide levels provides the predominant signal involved in regulating ventilation and initiating the urge to breathe (rather than oxygen levels). So when the carbon dioxide levels are too high, that’s what will make you want to breathe more e.g when holding your breath.

Question 18

What other things does CPG take into account?

Answer 18

It integrates information from other inputs such as stretch receptors within lungs that prevent damage due to over inflation, and irritant receptors within the airway that imitate cough.

Question 19

Why is the level of ventilation generally proportional to the arterial carbon dioxide partial pressure?

Answer 19

Because of the dominant role of the central respiratory chemoreceptors. For example, if carbon dioxide levels increase, ventilation increases to maintain homeostasis and to keep arterial partial pressure of carbon dioxide within narrow limits.
Hypercapnic drive = increase in ventilation in response to increased carbon dioxide levels. So even at small increase in carbon dioxide levels, ventilation rate will increase.

So when you hold your breath for a long time, you feel that you need to breathe because the carbon dioxide levels are now too high. Even though oxygen levels are low, it’s not because of that you want to breathe/ventilate more (unless the oxygen levels are extremely low).

The level of carbon dioxide is so important because it produced acidity and we need to protect ourselves from that.

pH also affects ventilation but it’s closely related to carbon dioxide levels.

Question 20

What is hypoxic drive?

Answer 20

Hypoxic drive is the increased ventilation in response to decreased partial pressure of oxygen. It only occurs at very low partial pressures of oxygen. This means that only when levels of oxygen is very low, ventilation will increase in response to it.

Question 21

What do peripheral chemoreceptors do?

Answer 21

They respond to carbon dioxide, oxygen and pH levels.
They are activated by a drop in oxygen levels and a rise in carbon dioxide levels. They signal to the medulla respiratory centres (VRG and DRG) via sensory nerves to increase ventilation. Have negative feedback to remove original stimulus.

Peripheral chemoreceptors consist of type 1 glomus cells which are present in carotid and aortic bodies.

Question 22

Give a situation where hypoxic drive takes a greater role than hypercapnic drive

Answer 22

In individuals with COPD. They can’t ventilate properly which results in chronic hypercapnia and hypoxia. CRC responses are reduced in the presence of chronic hypercapnia due to homeostatic mechanisms that compensate for chronic acidification of the cerebrospinal fluid and increase the cerebrospinal fluid pH back to normal, even at high arterial carbon dioxide levels.
In people like this, ventilation is further reduced as the CRC aren’t stimulated as it thinks carbon dioxide levels are fine. This causes a very low oxygen partial pressure so now it’s hypoxic drive (increased ventilation due to low oxygen levels).

Question 23

What is sleep apnoea?

Answer 23

Sleep apnoeas are when you stop breathing for more than 10 seconds during sleep and can produce significant health defects in people.

Negative effects on health: tiredness (due to repeated apnoea-induced waking), cardiovascular complications (e.g MI due to increased cardiovascular stress and sympathetic nervous tone) and metabolic dysfunction (e.g diabetes due to chronic inflammation)

Question 25

What is central sleep apnoea?

Answer 25

This is temporary stopped breathing during sleep caused by dysfunction in the CNS processes that initiate breathing.

Causes:

1. Injury to brainstem caused by stroke or trauma
2. Inhibition of brainstem caused by drugs such as opioids and barbiturates
3. Congenital defects in brainstem signalling processes (called hypoventilation syndrome/Ondine’s Curse whereby individuals lack the capacity to breathe whilst asleep)
4. Insufficient development of relevant structures and pathways in neonates (infantile central sleep apnoea)
5. Altitude e.g Cheyne-Stoke’s respiration

Question 26

What is obstructive sleep apnoea?

Answer 26

It is caused by temporary blockage of the airways/upper respiratory tract. This narrowing can be caused by:

1. Increased pressure on neck due to increased, obesity related, fat deposition
2. Individual variation in facial structures displacing the genioglossus into the airway

Risk factors for obstructive sleep apnoea include obesity, alcohol, sedatives and smoking.

Question 27

How do you differentiate between obstructive and central sleep apnoeas?

Answer 27

You can see whether there are diaphgramatic contractions during the sleep apnoea.

In obstructive sleep apnoeas, there’s increased diaphragmatic effort to try and overcome the upper respiratory blockade.

In central sleep apnoea, the diaphragm fails to respond due to the stopping of the CNS respiratory muscle pathway that initiates breathing.

Question 28

What is Cheyne-Stokes respiration?

Answer 28

It is a particular abnormal breathing pattern and central sleep apnoea involving an oscillating pattern of apnoea and hyperpnoea. Can happen even when not in sleep but it’s more common during sleep. Can also occur to normal individuals when they go to high altitudes.

Periods of apnoea causes hypercapnia and hypoxaemia which stimulates compensatory hyperventilation.
However, due to underlying pathological problem (e.g heart failure or brain injury), the hyperventilatory system overcompensates leading to hypocapnia, respiratory alkalosis and loss of respiratory drive causing a subsequent period of apnoea. Then the cycle begins again until it resolves or the individual is awoken.

Question 29

Clinical example

Answer 29

He lost consciousness underwater because his oxygen levels have gone down so much that there’s little oxygen to brain causing him to faint.

His urge to breathe was weaker (so he fainted instead) because he hyperventilated at the start so carbon dioxide from blood is removed causing less hypercapnia, preventing hypercapnia when he was diving. This means no hypercapnic drive (as carbon dioxide levels are normal/low due to the hyperventilation) so be doesn’t feel the urge to breathe. There is only hypoxic drive which only occurs at very low oxygen levels and by the time that hypoxic drive is reached, he has already fainted.

In a normal dive (without hyperventilation), the carbon dioxide gets high which causes hypercapnic drive (making you feel the need to breathe) which happens before the hypoxic drive.
But when you hyperventilate before a dive, you’ve got rid of loads of the carbon dioxide so the hypercapnic drive is only reached much later so hypoxic drive is reached first which causes you to faint and then your ventilation rate goes up (by CPG).

It’s bad to hyperventilate before freediving because if you faint underwater, when you faint, your CPG kicks in, causing you to breathe in but since you’re underwater, you’ll basically breathe in the water causing you to drown.