Breathlessness and control of breathing (awake)

Question 1

What are the main functions of the respiratory muscles?

Answer 1

• Maintaining arterial PO2, PCO2 and pH -
• Defence of airways and lungs when coughing etc
• Exercise
• Speech
• Sing, blow
• Expressing emotions
• Control of intrathoracic and infra-abdominal pressures e.g. defecation, belching, vomiting

Question 2

How does arterial PO2 differ in neonates/elderly and during the years in between?

Answer 2

It is lower in neonates/elderly

Question 3

What are the two main voluntary and involuntary controls of breathing and which is more important?

Answer 3

Involuntary or metabolic centre = medulla (bulbo-pontine region)

Voluntary or behavioural centre = motor area of cerebral cortex

Metabolic will always override behavioural

Question 4

What can influence the metabolic centre?

Answer 4

There are other parts of the cortex that are not under voluntary control and have an influence on the metabolic centre such as emotional responses. The limbic system and sensory inputs may influence the metabolic centre.

Sleep via the reticular formation (set of interconnected nuclei in the brain stem) also influences the metabolic centre.

Question 5

What is the main driver of breathing and what happens to breathing when we dream?

Answer 5

The main driver of breathing is the diaphragm

Breathing becomes quite disorganised when we’re dreaming

Question 6

What happens to the behavioural controller site when taking deep breaths (voluntarily)?

Answer 6

PET scans show that its becomes more active when you voluntarily take deep breaths.

Question 7

The control of breathing - how is H+ conc detected and how is breathing organised?

Answer 7

• There are on and off switches for the phrenic nerves in the cervical region of the upper spinal cord - this activates the muscles that will move the chest wall and, hence, the lungs.
• Information from the respiratory muscles and the lungs is fed back to the metabolic controller.
• Chemoreceptors in the carotid bodies in the neck sense the hydrogen ion levels in the blood.
• The metabolic controller also has hydrogen ion receptors.
• The metabolic controller activates the upper airway muscles in the neck to dilate the pharynx and the larynx on inspiration and narrow them on expiration.

Question 8

The peripheral chemoreceptor

Answer 8

• The carotid body chemoreceptor is a well vascularised bundle of cells at the junction of the internal and external carotid arteries.
• It tastes arterial blood
• It is a rapid response system for detecting changes in arterial pCO2 and pO2

Question 9

Pacemakers in breathing

Answer 9

• Breathing has many pacemakers that are close together in the brain stem and are inaccessible
• The group pacemaker activity of breathing comes from around 10 groups of neurons in the medulla near the nuclei of cranial nerves IX and X

Question 10

Give an example of a group pacemaker
Location?
How is it coordinated?

Answer 10

• The pre-Botzinger complex (found in the ventro-cranial medulla near the 4th ventricle) seems essential for generating the respiratory rhythm and is called the ‘gasping centre’
• Coordination of the pre-Botzinger complex with the other controllers may be needed to convert gasping into an orderly and responsive respiratory rhythm.

Question 11

How many groups of neurons in the medulla and brain stem are important in tidal breath generation/

Answer 11

Six groups of neurons in the medulla and brain stem have distinct functions in the generation of a tidal breath - they discharge at different phases of the respiratory cycle

Question 12

What are the 6 groups of neurones controlling the phases of the respiratory cycle?

Answer 12

• Early inspiratory initiates inspiratory flow via the respiratory muscles
• Inspiratory augmenting may also dilate pharynx, larynx and airways
• Late inspiratory may signal the end of inspiration, and ‘brake’ the start of expiration
• Expiratory decrementing may ‘brake’ passive expiration by adducting the larynx and pharynx
• Expiratory augmenting may activate expiratory muscles when ventilation increases on exercise
• Late expiratory may sign the end of expiration and onset of inspiration, and may dilate the pharynx in preparation for inspiration

Question 13

What is the importance of the laryngeal and pharyngeal muscles?

Answer 13

In opening up the airways or acting as a ‘brake’ in breathing
A lack of tone in the pharyngeal muscles may play a part in the breathing that occurs at night - obstructive sleep apnoea syndrome

Question 14

Reflex control of breathing and nerves involved

Answer 14

• 5th nerve: afferents from nose and face (irritant)
• 9th nerve: from pharynx and larynx (irritant)
• 10th nerve: from bronchi and bronchioles (irritant and stretch)

Question 15

What do irritant receptors do?

Answer 15

They make you cough and sneeze

Question 16

Hering Breuer Reflex (most well known reflex in lung)

Answer 16

Hering-Breuer reflex from pulmonary stretch receptors senses lengthening and shortening and terminates inspiration and expiration, but weak in humans

Question 17

What are the two parts of the metabolic controller?

Answer 17

Central part in the medulla responding to the hydrogen ion concentration in the extracellular fluid

Peripheral part at the carotid bifurcation (carotid sinus) - there are hydrogen ion receptors here as well

Question 18

What are slow and fast responses?

Answer 18

The change in H+ reflecting changes in PCO2 occur very rapidly in the hyperperfused carotid bodies but more slowly in the ECF bathing medulla - so fast and slow responses exist.

Question 19

Metabolic acidosis

what is it, causes and compensatory mechanisms?

Answer 19

Excess production of H+

Causes: diabetic ketoacidosis, salicylate overdose, renal tubular defects

Compensatory mechanisms:
Ventilatory stimulation to lower PaCO2 and H+,
renal excretion of weak acids (lactate and keto), renal retention of chloride to reduce strong ion difference

Question 20

Metabolic alkalosis

what is it, causes and compensatory mechanisms?

Answer 20

Loss of H+ leads to excess HCO3–

Causes: vomiting, diuretics, dehydration

Compensatory mechanisms:
Hypoventilation raises PaCO2 and H+, renal retention of weak acids and renal excretion of chloride to increase strong ion difference

Question 21

Respiratory acidosis: acute and chronic

Answer 21

The lung fails to excrete the CO2 produced by metabolic processes

Acute: hypoventilation causes PaO2 ↓, PaCO2 and H+ ↑ which stimulates metabolic centre (and carotid body) to increase minute ventilation and restore blood gas and H+ levels.

If the lung cannot cope then:
Chronic: ventilatory compensation may be inadequate for PaCO2 homeostasis but
a) renal excretion of weak acids (lactate and keto)
b) renal retention of chloride to reduce strong ion difference
returns H+ to normal, even though PaCO2 remains high and PaO2 low.

Question 22

Hypoventilation Conditions

Central - acute and chronic

Answer 22

Acute:
- Metabolic centre poisoning (anaesthetics, drugs)

Chronic:

• Vascular/ neoplastic disease of metabolic centre
• Congenital central hypoventilation syndrome
• Obesity hypoventilation syndrome (OHS)
• Chronic mountain sickness

Question 23

Hypoventilation Conditions

Peripheral - acute and chronic

Answer 23

Acute:

• Muscle relaxant drugs
• Myasthenia gravis

Chronic:
- Neuromuscular with respiratory muscle weakness

Question 24

Chronic obstructive pulmonary disease

Answer 24

Mixture of central (won’t breathe) and peripheral (cannot breathe)

Could be due to lung inefficiency and difficulty of the controller in raising ventilation sufficiently

Or could be due to the metabolic controller becoming insensitive and allowing higher PCO2

Question 25

Respiratory alkalosis - mechanism and causes

also same as hyperventilation conditions

Answer 25

Mechanism: ventilation in excess of metabolic needs

Causes:

• Chronic hypoxaemia
• Excess H+ (metabolic causes)
• Pulmonary vascular disease
• Chronic anxiety

Question 26

What is breathelessness?

Answer 26

• It is hard to define and is a perception so is subjective
• Breathlessness at rest - implies difficulty with inspiration of expiration (e.g. due to acute bronchospasm of an asthma attack)
• Excessive breathlessness for the task (can be associated with many cardiac or respiratory diseases)

Question 27

What is dyspnoea?

Answer 27

The medical term for breathlessness but with the connotation of discomfort or difficulty

Question 28

What are the three types of breathlessness?

Answer 28

• tightness
• increased work and effort
• air hunger

Question 29

Tightness (breathlessness)

Answer 29

Difficulty in inspiring due to airway narrowing; a feeling that the chest is not expanding normally

Question 30

Increased work and effort (breathlessness)

Answer 30

Breathing at a high or normal minute ventilation but at a high lung volume, or against an inspiratory or expiratory resistance
In other words, breathing against an abnormal mechanical load or breathing a lot

Question 31

Air hunger (breathlessness)

Answer 31

Sensation of a powerful urge to breathe

• May well occur in acute asthmatic attacks where you just can’t get enough air because you haven’t been able to exhale the previous breath.
• Air hunger is similar to suffocation
• It is a mismatch between V.E demand and V.E achieved
• Cerebral cortex compares two different inputs

Demand - a copy of signal sent by metabolic controller to spinal motor neurones
Afferents from lung, chest wall and chemoreceptors (carotid body) - output

Question 32

Scales for measuring breathlessness during an exercise test

Answer 32

• Breathlessness can be scored on the 10-point Borg scale
• 10 is very severe and 1 is nothing
• Subjects score themselves during a task

Question 33

Breath Holding Time (BHT) : what does it test and what is the breakpoint affected by?

Answer 33

• Tests the strength of behavioural versus metabolic controller
• Break point prolonged by increasing lung volume, lowering PaCO2 or by taking an isoxic/isocapnic breath near the break point
• Acute thoracic muscle paralysis with curare does not prolong BHT

Question 34

What is tightly controlled by the body?

Answer 34

PaCO2 and H+

Question 35

What does a fall in VE lead to?

Answer 35

fall in PaO2 and rise in PaCO2 -> fall in PaO2 raises sensitivity of carotid body to PaCO2 and H+ -> VE increases so PaO2 increases

Ventilatory responses to hypoxia are amplified by CO2 (the body system is much more sensitive to CO2)

Question 36

What is the equation for VE?

Answer 36

VE = VT * 60/TTOT

VE = minute ventilation, volume exchanged in a minute
TTOT = total time for respiratory cycle
60/TTOT = resp frequency per min

Question 37

Equation for VE including TI

Answer 37

VE = VT/TI * TI/TTOT

This equation represents the gradient of inspiration multiplied by the proportion of time spent on inspiration.
VT/TI = Mean inspiratory flow – i.e. how powerfully the muscles contract
This is known as the neural drive.

Question 38

What does TI/TTOT tell us?

Answer 38

Inspiratory duty cycle – the proportion of time spent actively ventilating.

Question 39

What is normal VE and tidal volume and TI/TTOT

Answer 39

Normal VE = ~6Lmin-1
Normal Tidal Volume = 0.5L
Inspiratory duty cycle = 40%

Question 40

What happens to minute ventilation parameters during experiments?

Answer 40

• Use of a nose clip reduces breathing rate while VE remains roughly the same but VT increases as breathing is deeper.
• Breathing through a tube increases dead space which increases VE, VT and frequency to clear dead space.
• The neural drive (VT/TI) also increases to satisfy more ventilation.

Question 41

What happens to tidal breathing in diseases like Chronic Bronchitis, Emphysema and COPD?

Answer 41

• Intrathoracic airways are narrowed so difficulty ventilating lungs more on expiration.
• Lower TV as less air can fill the lungs but compensated by a faster breathing rate (equal TI/TTOT).
• People with COPD breathe much shallower and faster but not harder.