Breathlessness and control of breathing (awake)

Question 1

What are the functions of the respiratory muscles

Answer 1

§ Maintenance of arterial PO2, PCO2 and pH (with pH being the MOST IMPORTANT).
o pH is almost always maintained constant but PO2 can always change without serious consequence.
§ Defence of the airways and lungs (sneeze, cough, yawn).
§ Exercise (fight/flight).
§ Speech, singing, blowing, laughing, crying (express emotion).
§ Control of intra-thoracic and infra-abdominal pressures (e.g. defecation, belching and vomiting).

The last 4 are voluntary- midbrain control

Question 2

What is breathing controlled by

Answer 2

Breathing is controlled by the medulla (metabolic controller), the cortex (behavioural controller) and reflexes
Skeletal muscles are striates- therefore we can control them

Question 3

What is minute ventilation and how is it calculated

Answer 3

§ VT = Tidal Volume
§ TTOT = Total time for respiratory cycle.
§ VE = Minute ventilation (tidal volume x frequency) – i.e. the volume of air exchanged in one minute
= Vt x GO/Ttot (s)

Question 4

Why do we have control of breathing

Answer 4

It is an evolutionary advantage to communicate by sound

Question 5

Give another equation for minute ventilation

Answer 5

𝑉𝐸= 𝑉𝑇/𝑇𝐼 𝑥 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.
o This is known as the neural drive.
§ TI/TTOT = Inspiratory duty cycle – i.e. the proportion of time spent actively ventilating.

brain controls breathing by setting rate of discharge to respiratory muscles

Question 6

Describe breathing in normal subjects

Answer 6

§ Normal VE = ~6Lmin-1.
§ Normal Tidal Volume = 0.5L.
§ Normal inspiratory Duty Cycle (TI/TTOT) = ~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.
o The neural drive (VT/TI) also increases to satisfy more ventilation.

Question 7

What does the inspiratory flow rate reflect

Answer 7

how hard the muscles are being driven- how we determine how much we are going to breathe- brain sets discharge to produce a certain flow
many switches- when inspiration/ expiration starts or stops

Question 8

Why does breathing change with a mouthpiece

Answer 8

Patient becomes more aware of their breathing
Breathe more slowly and deeply
But amount similar- metabolic demands have not changed

Question 9

Roughly, how long do we spend inspiring

Answer 9

Less than 40% of each breath

Question 10

Describe breathing in light exercise

Answer 10

Response of controller is to increases discharge rate to respiratory muscles, muscles contract faster- increasing mean inspiratory flow
In heavy exercise, ventilation can increase 15 fold and VT/TI will increase in proportion
TI and TE decrease proportionally- therefore frequency increases proportionally.
Vt will increase as increase in VT/TI is greater than the shortening of the TI
TI/Ttot does not change

Question 11

Why does TI/Ttot not change

Answer 11

No controller for proportion spent in inspiration
Instead we have controllers for TI and TE
But VT/TI controllers are responsive to metabolic change

Question 12

Describe the determinants of tidal breathing in disease

Answer 12

Chronic Bronchitis, Emphysema and COPD:
§ 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.
§ REMEMBER: people with obstructive lung disease have difficulty expiring.

They will have same response to exercise as control is the same

Question 13

Summarise the different controllers in breathing

Answer 13

Automatic bulbopontine controller (Brainstem- pons)

Behavioural Suprapontine control (widely distributed)- most important is the motor cortex

Question 14

Describe the automatic bulbopontine controller

Answer 14

Involuntary or “metabolic” centre, in the medulla (bulbo–pontine brain)
Metabolic centre responds to metabolic demands for and production of CO2 (V´CO2) and determines, in part, the “set point” for CO2, generally monitored as PaCO2.

Question 15

Describe the pontine neurones

Answer 15

The pontine respiratory group consists of expiratory and inspiratory neurones
their role is to regulate the dorsal respiratory group and possible the ventral respiratory group (neuron groups in the medulla

Question 16

Describe the different groups of neurons in the medulla involved in respiratory control

Answer 16

Dorsal- situated in the nucleus tractus solitarius
ventral- situated in the nucleus ambiguous and the nucleus retroambigualis
The Botzinger complex- situated rostral to the nucleus ambiguus

Question 17

Describe the role of the dorsal group

Answer 17

Contains neurone bodies of upper motor neurons
Inhibit expiratory neurons in the ventral group
Excite lower motor neurons to the respiratory muscles- increasing ventilation

Question 18

Describe the role of the ventral group

Answer 18

Contain inspiratory upper motor neurones which go on to supply their lower motor neurones external intercostals and accessory muscles

Question 19

Describe the role of the Botzinger complex

Answer 19

Contains only expiratory neurons
Inhibits inspiratory neurons in both the ventral and dorsal groups
By exciting expiratory neurones in the ventral group

Ventral and botzinger- expiration
Dorsal- inspiration

Question 20

Describe the motor homunculus in the motor cortex

Answer 20

Diaphragm between shoulder and trunk- will fire when we want to take a deep breath in voluntary breathing
In vocalisation- will also activate larynx and jaw muscles and communication with diaphragm

Question 21

Describe the voluntary control of breathing

Answer 21

Behavioural centre controls acts such as breath holding, singing
Metabolic will always override the behavioural
The limbic system (survival responses [suffocation, hunger, thirst]), and frontal cortex (emotions) and sensory inputs (pain, startle) may influence the metabolic centre.
Other parts of cortex, not under voluntary control, influence the metabolic centre, such as emotional responses.
Sleep via reticular formation influences the metabolic centre

Question 22

Summarise the metabolic control of breathing

Answer 22

Metabolic controller central H+ receptor- dominant- responds to changes in H+ in ECF
Raised H+ conc will increase the impulse frequency to the respiratory spinal motor neurones and then down the phrenic nerve to the diaphragm to increase ventilation
It will also switch TI and TE on and off to ventilate
Impulses also sent to Upper airway muscles: dilated on inspiration and narrowed on expiration to ensure smooth air flow - controlled by metabolic controller
Feedback: lung has stretch and irritant receptors, respiratory muscles have muscle spindle and blood receptors have chemoreceptors that all signal back to the metabolic concentration to lead to alteration of timing to control breathing

Question 23

Describe the voluntary control of breathing

Answer 23

Behavioural controller can let you hold your breath by inhibiting respiratory spinal motor neurones
Coughing can also affect this

Question 24

Describe the emotional control of breathing

Answer 24

Emotions (frontal cortex)— limbic system — reticular formation — can override metabolic central H+ receptor
NREM inhibits reticular formation
Sensory (pain, startle) effects can also stimulate reticular formation

Question 25

Summarise the peripheral chemoreceptors

Answer 25

The well perfused carotid body “tastes” arterial blood
It lies at the junction of the internal and external carotid arteries in the neck
It is a rapid response system for detecting changes in arterial PCO2 and PO2

Question 26

Describe the different types of peripheral receptors

Answer 26

Carotid sinus- carotid bodies
Aortic arch -aortic bodies
Stimulation has both cardiovascular and respiratory effects- carotid bodies have a greater effect on respiration

Question 27

Describe the different cell types in carotid bodies

Answer 27

type 1- sensitive to hypoxia
type 2- structural and metabolic- like the glial cells
It is believed that the type 1 glomus cells release a neurotransmitter when stimulated by hypoxia - affecting the discharge rate of the carotid body afferent fibres

Question 28

What are peripheral chemoreceptors sensitive to

Answer 28

PaO2
PaCO2
pH
Blood flow 
Temp

Question 29

Describe the innervation of the carotid bodies

Answer 29

Supplied by the autonomic NS
SNS- vasoconstriction- increasing sensitivity to hypoxia
PSNS- vasodilation- decreasing sensitivity to hypoxia

Question 30

Describe the sensitivity of the carotid bodies to PaO2

Answer 30

Sensitivity to changes begins at 500mHg

But relatively little response occurs until it is reduced below 100mHg

Question 31

Why is it important that carotid bodies respond to PaO2 and not Pvo2

Answer 31

Carotid sinus has a rich blood flow for their size- and therefore, in spite of their high metabolic rate, the arterial-venous O2 difference is small

Question 32

Describe the central chemoreceptors

Answer 32

Tonically active and vital for maintenance of respiration- 80% of drive for ventilation is by stimulation of these chemoreceptors
When inactivated - respiration ceases
Readily depressed by drugs (opiated and barbiturates)

Question 33

Where are the central chemoreceptors located

Answer 33

Ventrolateral surface of the medulla close to the exit of cranial nerves 9 and 10
Anatomically separate from the medullary respiratory control centre

Question 34

What do the central chemoreceptors respond to

Answer 34

H+ in surrounding brain tissue and CSF
PaCO2
Not sensitive to conc of H+ in blood or PaO2

Question 35

Describe the diffusion of ions across the blood-brain barrier

Answer 35

Poor
Blood levels of H+ and HCO3- have relatively little effect on the conc in CSF- and thus have little effect on the central chemoreceptors
CO2 can pass freely by diffusion and on entering, it increases the H+ conc- stimulating the central chemoreceptors
Cerebral vasodilation that accompanies a high PaCO2 also enhances its diffusion

Question 36

Why is pH of the CSF lower than that of the blood and what happens in disease

Answer 36

CSF- contains much less protein and so has a lower buffering capacity- changes in pH in CSF for a given change in PCO2 is greater than that of the blood
Long raised PaCO2- hypoventilation (COPD and obesity)- compensatory change in HCO3- across the blood-brain barrier (produced by glial cells) to compensate- much quicker than renal compensation for blood pH - therefore CSF pH has more important effects on changes in the level of ventilation and arterial PCO2.

Question 37

Summarise the central coordination of breathing

Answer 37

No single pacemaker, as in the heart
“group pacemaker” activity coming from about 10 groups of neurons in the medulla near nuclei of IX and X cranial nerves
One group, the pre–Botzinger complex, in ventro–cranial medulla, near 4th ventricle, seems essential for generating the respiratory rhythm, and has been called the “gasping centre”.
Coordination of pre–Botzinger complex with the other “controllers” may be needed to convert “gasping” into an orderly and responsive respiratory rhythm.

Question 38

Describe the central control of breathing during different phases of inspiration

Answer 38

Discrete groups of neurons in the medulla discharge at different phases of the respiratory cycle and have different functions
Early inspiratory initiates inspiratory flow via 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 larynx and pharynx.
Expiratory augmenting may activate expiratory muscles when ventilation increases on exercise.
Late expiratory may signal the end of expiration and onset of inspiration, and may dilate the pharynx in preparation for inspiration.

Question 39

Describe the reflex control of breathing in response to irritants

Answer 39

Rapidly adapting receptors- involved in lung defence- role in cough reflex
Transitory responses and may be sensitised by inflammatory mediators
Vth nerve: afferents from nose and face (irritant)
IXth nerve: from pharynx and larynx (irritant)
Xth nerve: from bronchi and bronchioles (irritant and stretch)
irritant receptors leading to cough, sneezing etc are “defensive”

Question 40

Describe the reflex control of breathing in response to stretch

Answer 40

Slow adapting- important in breathing- not cough reflex- produce sustained responses
Stimulated by inflation
Xth nerve: from bronchi and bronchioles (irritant and stretch)
Hering–Breuer reflex from pulmonary stretch receptors senses lengthening and shortening and terminates inspiration and expiration, but weak in humans (ventilatory responses in denervated lungs post–transplantation are normal).

Thoracic spinal cord: from chest wall and respiratory muscles
(spindles ~ “stretch”)

Question 41

Describe the Hering-Breuer reflex

Answer 41

Inflation leads to decreased respiration
Deflation reflex is the opposite- deflation leads to increased respiration

These reflexes are active in the first year of life but are weak in adults- and so don’t determine the rate or depth of breathing
However, they are seen in tidal volumes above 1L and so may play a role in exercise

afferent fibres travel to the respiratory centres via the vagus nerve:
terminating inspiration
regulation of the work of breathing
reinforcement of respiratory rhythm in the first year of life

Question 42

Describe C- fibres

Answer 42

Stimulation results in:
closure of larynx
rapid, shallow breathing
bradycardia
hypotension
also contribute to breathlessness and heart failure
and despite being afferent nerve endings that can release inflammatory mediators (neurokinins and substance P)

Question 43

Describe receptors in the chest wall

Answer 43

joint receptors- measure the velocity of rib movement
Golgi tendon organs- found in muscles of respiration (diaphragm and intercostals)- detect strength of muscle contraction
muscle spindles- monitor the length of the muscle fibre statically and dynamically (detect muscle length and velocity)

stimulation of these mechanoreceptors (with hypercapnia and hypoxaemia) leads to increased respiratory effort in patients with sleep apnoea- which wakes the person up
helps to stabilise ventilation in terms of tidal volume and frequency

Question 44

Summarise the metabolic controller

Answer 44

Metabolic controller has two parts:
A) central part in medulla responding to H+ ion of ECF
B) peripheral part at carotid bifurcation, the H+ receptors
of the carotid body
CO2 is very diffusible, and H+ changes mirror PCO2 changes, very rapidly for the hyperperfused carotid body, but more slowly in the ECF bathing the medulla. Thus, fast and slow responses exist.

Question 45

Describe CO2 responses in response to hypoxia and acidosis

Answer 45

§ The slope (S) is an index of chemo-sensitivity.
§ B is the apnoeic threshold, sensitive to acid-base status (only operates in sleep).
§ This measures the sensitivity of the metabolic respiratory centre to hydrogen ions by use of a carbon dioxide challenge – breathing into a CO2 primed bag.
§ The respiration into a closed bag maintains rising CO2 levels which raises the minute ventilation in response.
o NOTE: A 30Lmin-1 rise in VE for every 1kPa rise in PaCO2.
§ Green = normoxia while orange = hypoxia (which increases sensitivity of acute CO2 response – mediated by the carotid body).

Question 46

Describe ventilatory responses to hypoxia

Answer 46

This is the response of ventilation to a hypoxic challenge.
§ LEFT – A lowering of alveolar PO2 from 13 à 6kPa at 2 fixed levels of PCO2.
§ Not isocapnic means PCO2 is not controlled and allowed to fall during hypoxic hyperventilation à reduces VE response.
§ RIGHT – Shows (on the 40mmHg) a 30Lmin-1 increase in VE for a 7kPa change in PaO2 (or saturation change of 99% to 60%). HOWEVER, a 30Lmin-1 is also brought about by a 1kPa change in PaCO2 so the system is much more sensitive to changes in PaCO2!
Ventilatory responses to hypoxia are amplified by PaCO2.

Question 47

Why is hypoxic drive important in lung disease (COPD) and high altitude

Answer 47

Hyperventilate in response to hypoxia- therefore PCO2 decreases- increasing the response to hypoxia
Central chemoreceptors have become unresponsive to CO2 and ventilatory drive from the effects of reduced pH by the peripheral chemoreceptors is lessened by renal compensation for the acid-base normality
Administration of high-conc oxygen therapy may abolish the hypoxic drive that the patient was relying on- depressing ventilation and worsening their condition

Question 48

Describe what is being controlled

Answer 48

PaO2 is not as tightly controlled as PaCO2 and H+
SaO2 rather than PaO2 appears to be defended.
Usually, a fall in ventilation causes a fall in PaO2 and a rise in PaCO2, and the fall in PaO2 increases sensitivity of carotid body to PaCO2 and H+ , so ventilation and PaO2 increases, and PaCO2 falls by negative feedback

Question 49

What happens when PaO2 and PaCO2 fall together?

Answer 49

This happens when a fall in inspired PO2 rather than minute ventilation is the primary event- hypoxic hyperventilation
At altitude, several days of acclimatisation are required to adjust for the lower PO2 set point.

Question 50

Describe the control of H+

Answer 50

Primarily, the acid–base status of blood and tissues and H+ concentration
Compensatory mechanisms for too much acid or alkali are the lung (fast responder) and kidney (slow responder).
If the lung is the problem, the response will be slow (hours, days)
The causes of acidosis (acidaemia is what is measured) and alkalosis are twofold a) metabolic, b) respiratory

Question 51

What determines H+ conc

Answer 51

[H+] = constant x PaCO2/HCO3–

Strong ion difference: [Na+ + H+] – Cl-

Question 52

Describe metabolic acidosis

Answer 52

Acidosis: excess production of H+
causes: diabetic ketoacidosis, salicylate overdose, renal tubular defects
compensatory mechanisms:
Ventilatory stimulation lowers PaCO2 and H+
Renal excretion of weak (lactate and keto) acids
Renal retention of chloride to reduce strong ion difference

Question 53

Describe metabolic alkalosis

Answer 53

Alkalosis: loss of H+ leads to excess HCO3–
causes: vomiting, diuretics, dehydration
compensatory mechanisms
Hypoventilation raises PaCO2 and H+
Renal retention of weak (lactate and keto) acids
Renal excretion of chloride to increase strong ion
difference

Question 54

Describe respiratory acidosis

Answer 54

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:
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 55

Describe central hypoventilation conditions

Answer 55

Acute:
o Metabolic centre poisoning (drugs).
§ Chronic:
o Vascular/neoplastic disease of MC.
o Congenital central hypoventilation syndrome. ( reduced VE/PaCO2)
o Obesity hypoventilation syndrome (OHS).
o Chronic mountain sickness.

Question 56

Describe peripheral hypoventilation conditions

Answer 56

Acute: muscle relaxant drugs, myasthenia gravis
Chronic: neuromuscular with respiratory muscle
weakness

Question 57

Describe respiratory alkalosis

Answer 57

Mechanism: ventilation in excess of metabolic needs
Causes:
	Chronic hypoxaemia
	Excess H+ (metabolic causes)
	Pulmonary vascular disease
	Chronic anxiety (psychogenic)

Question 58

Describe COPD

Answer 58

Mixture of central (won’t breathe) and peripheral (cannot breathe). Due to lung inefficiency and difficulty of the controller in raising VE sufficiently OR due to metabolic controller becoming insensitive and allowing higher PCO2.
Difficult for muscles to hyperventilate more as they are already hyperventilating to compensate for loss of accessible lung volume

Question 59

What is breathlessness

Answer 59

“Breathless with excitement” “breathless with anticipation”
suspended breathing with an emotional cause (~ without breath)

“out of breath” (~ too much breathing)
normal experience when exercise exceeds a threshold of comfort

Question 60

Describe dyspnoea

Answer 60

DYSPNEA: the medical term for breathlessness but with the connotation of discomfort or difficulty
“do you get breathless at rest/ on exercise”?
At rest, that usually implies difficulty with inspiration or expiration.
On exercise, it means excessive breathing for the task ± difficulty

Question 61

Describe tightness

Answer 61

Tightness: difficulty in inspiring due to airway narrowing; a feeling that the chest is not expanding normally.
Increased work and effort: breathing at a high minute ventilation, or at a normal minute ventilation but at a high lung volume, or against an inspiratory or expiratory resistance

Question 62

Describe air hunger

Answer 62

Air hunger: sensation of a powerful urge to breath, e.g a breath hold during exercise
Experimentally, air hunger is produced by driving breathing with added CO2, while restricting tidal volume by breathing from a bag of fixed volume: very unpleasant.
“Breathing a lot doesn’t worry me; not breathing enough does”
“Yes to increased but satisfied demand, no to increased but unsatisfied demand”

Question 63

Essentially, what is air hunger

Answer 63

Mismatch between VE demanded and VE achieved
Cerebral cortex compares two different afferent inputs:
demand; a copy (corollary) of signal sent by metabolic controller to spinal motor neurones
afferents from lung, chest wall and chemoreceptors (carotid body)- - output

Question 64

Describe breath holding time

Answer 64

tests 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
“break point” is an expression of “air hunger”
BHT ~ stretch receptor drive x metabolic drive

Question 65

How can we measure the intensity of dyspnoea

Answer 65

Intensity of breathlessness/dyspnea can be measured with a Visual Analogue Scale (score 0–10) during an exercise test or during ventilatory stimulation with CO2

Also the subjective BORG scale