Neural Control of Respiration

Question 1

What are the main muscles involved in respiration and what are the nerves innervating them ?

Answer 1

Diaphragm and Intercostals

Phrenic and Intercostal nerves

Question 2

Explain the process of expiration, focusing on the action of the nerves innervating the muscles responsible for respiration.

Answer 2

Neurons cease the discharge of action potentials and the chest recoils back to FRC (basic pattern).

Question 3

Draw a graph demonstrating a) change in number of active inspiratory nerves and b) tidal volume, over the cycle of respiration.

Answer 3

Refer to slide 4 of lecture on “Neural Control of Respiration”.

During inspiration, activity of inspiratory neurons increases steadily, apparently through a positive feedback mechanism. At the end of inspiration, activity shuts off abruptly (but still some inspiratory neurons active) and expiration takes place through recoil of elastic tissue.

Question 4

Describe the experimental evidence which helps us better understand where the rhythmic pattern of respiration originate, and explain the implications of this evidence on the origin of the rhythmic pattern of respiration.

Answer 4

1. If the brainstem is cut above the level of the pons, the basic rhythm continues
2. If all the afferent nerves to the brainstem are cut, the basic rhythm continues
3. If you section the spinal cord below C3-C5, the intercostal muscles are paralysed
4. If you section below the medulla, all respiration ceases

Hence,

a) the respiratory muscles themselves do not have an intrinsic rhythmicity (unlike the heart).
b) the brainstem contains all the components to generate a rhythmic pattern of respiration (i.e. if stimulate various areas of the brainstem, you can alter the pattern of breathing)

Question 5

Where is respiratory rhythm generated ?

Answer 5

Medulla Oblongata and Pons, both in the brainstem (specifically in respiratory centers), controls diaphragm, intercostals, central chemoreceptors, peripheral chemoreceptors, and other receptors.
Cortex and other brain areas can influence the medulla.
However, cortex and other areas can by-pass the medulla and affect the lower motor neurones directly (i.e. affect diaphragm and intercostals, to consciously decide to hold your breath or alter ventilation rates).

Question 6

Identify the main mechanisms of regulation of respiration.

Answer 6

• Nervous or neural

* Chemical

Question 7

Define respiratory centers.

Answer 7

A series of nerve centers (contain both afferent and efferent nerves) -the apneustic, pneumotaxic, and medullary respiratory centers- in the medulla and pons that coordinate respiratory movements.

Question 8

Why is the term “respiratory center” a misnomer ?

Answer 8

Because “respiratory center” describes diffuse networks, possibly at higher density which are active together to bring about the respiratory effect, rather than discrete anatomical regions or bodies that can be identified macro- or microscopically.

Question 9

Identify the main ways to control blood pH. Which one is more useful ? Why ?

Answer 9

Urination

Breathing (more useful, because more frequent)

Question 10

Where are the respiratory centers located ?

Answer 10

In the medulla and pons

Question 11

What is the function of the respiratory centers?

Answer 11

Collect sensory information about the levels of oxygen and carbon dioxide in blood that determines the signal sent to respiratory muscles (stimulation of these muscles provides respiratory movements which produce alveolar ventilation).

Question 12

Does the process of breathing normally take a lot, or a little energy ? Why ?

Answer 12

Pattern of breathing is aimed to minimise the amount of work done (economy of energy, evolutionary beneficial). For instance lungs are kept partially inflated even at the end of expiration, which allows for its inflation with less energy than would be required if it had been full deflated.

Question 13

List the respiratory centers. State and show their location on an image of the brainstem.

Answer 13

Pontine Centres:

1. Pneumotaxic (located in upper Pons)
2. Apneustic (located in lower Pons)

Medullary Centres:
1. Inspiratory (located in upper part of medulla oblongata)
2. Expiratory (located in medulla oblongata, anterior and lateral to the inspiratory
centre)

For location, refer to slide 9 of lecture on “Neural Control of Breathing”.

Question 14

Identify the function of the medullary respiratory centers.

Identify the muscles and nerves involved with each center.

Answer 14

Inspiratory = Driving inspiration. Diaphragm and external intercostals involved. Exclusively inspiratory neurons inside it.

Expiratory = Centre is inactive during quiet breathing and when inspiratory centre is active, but during forced breathing or when inspiratory centre is inhibited it becomes active. Drives internal intercostals.
Mixture of inspiratory and expiratory neurons inside it.

Question 15

Identify the other names of inspiratory and expiratory respiratory centers.

Answer 15

Inspiratory centre (= Dorsal Respiratory Group (DRG))

Expiratory centre (=Ventral Respiratory Group (VRG))

Question 16

Identify the function of the pontine respiratory centers.

Answer 16

Pneumotaxic centre: Controls medullary respiratory centres, especially the inspiratory centre through the apnuestic centre. It influences inspiratory centre so that duration of inspiration is under control.

Apnuestic centre: Increases depth of inspiration by acting on inspiratory centre.

Question 17

Describe the path of the afferent and efferent nervous pathways for respiration.

Answer 17

Afferent pathway: deliver impulses via vagus
(movement of thoracic region and lungs) and glossopharyngeal nerves (impulses from chemoreceptors), to respiratory centers.

Efferent pathway: nerves from respiratory centre leave brain in anterior part of lateral column in spinal cord, terminate in motor neurons in cervical and thoracic segments of spinal cord, and supply phrenic (controls diaphragm) and intercostal (controls intercostals), thereby driving inspiration and expiration.

Question 18

Identify the factors which affect the respiratory centers.

Answer 18

1. Impulses from higher centres
2. stretch receptors of lung slowly adapting pulmonary receptors
3. ‘J’ receptors, or pulmonary C-fibres
4. Irritant receptors of lungs
5. Proprioreceptors
6. Thermoreceptors
7. Pain receptors
8. Cough reflex
9. Sneezing reflex
10. Deglution reflex

Question 19

Describe the impulses from higher centers , in affecting the respiratory centers.

Answer 19

Impulses from cerebral cortex, limbic system, hypothalamus, can stimulate or inhibit respiratory centres directly.

Question 20

Describe the role of stretch receptors of lung (slowly adapting pulmonary receptors), in affecting the respiratory centers.

Answer 20

= Hering-Breur Reflex
Smooth muscle of upper airways has slowly adapting stretch receptors. When lung is inflated these neurons send impulses to DRG (i.e. inspiratory center) via the vagus nerve. This input is inhibitory, limiting inspiration, prevents overinflation of lungs. Active more in first year of life and during strenuous exercise when tidal volume over 1 liter.

Question 21

Describe the role of ‘J’ receptors, or pulmonary C-fibres, in affecting the respiratory centers.

Answer 21

• Juxtacapillary receptors present in wall of alveoli, in close contact with pulmonary capillaries.
• Stimulated during conditions like pulmonary oedema, congestion, pneumonia, Also from endogenous chemicals such as histamine (i.e. inflammatory process in lungs).
• Stimulation of J receptors induces apnea – temporary suspension of breathing- followed by rapid shallow breathing + induces mucus secretion + induces bronchoconstriction.

Question 22

Describe the role of irritant receptors of the lungs, in affecting the respiratory centers.

Answer 22

• Situated on walls of bronchi and bronchioles
• Rapidly adapting receptors –powerfully stimulated by inhalation of irritants (e.g. harmful chemicals like ammonia, or cigarette smoke)
• Induces rapid shallow breathing, mainly from shortening of expiration + also, and possibly confusingly, long deep augmented breaths, which are taken by mammals every 5-20 mins on average to reverse slow collapse of lungs that occurs during quiet breathing + induces coughing + induces bronchoconstriction

Question 23

Describe the role of proprioreceptors of the lungs, in affecting the respiratory centers.

Answer 23

• Situated in chest wall (in joints, muscles, tendons)
• Aim is for reflexes from muscles and joints to stabilise ventilation (i.e. normal breathing) in the face of changing mechanical conditions

1) In joints, e.g. measure the velocity of rib movement
2) In tendons –found within muscles of respiration (diaphragm and intercostals), detect strength of muscle contraction
3) In muscle spindles – monitors length of fibers both statically and dynamically – length and velocity.

Question 24

Identify some of the external receptors which affect the respiratory centers.

Answer 24

Thermoreceptors, pain receptors.

Question 25

Describe the role of thermoreceptors and pain receptors, in affecting the respiratory centers.

Answer 25

Thermoreceptors – cutaneous, supply signals to cerebral cortex, stimulates respiratory centre, hyperventilation

Question 26

Describe the role of pain receptors, in affecting the respiratory centers.

Answer 26

Pain receptors – supply signals to cerebral cortex, again stimulates respiratory centres, induces hyperventilation

Question 27

Describe the role of cough reflex, in affecting the respiratory centers.

Answer 27

• Protective reflex caused by irritation of parts of respiratory tract beyond nose (eg larynx, trachea and bronchi)
• Stimulates vagus nerve and cough induced
• Deep inspiration followed by forceful
expiration with closed glottis
• Glottis opens and explosive outflow or air at high velocity

Question 28

Describe the role of sneezing reflex, in affecting the respiratory centers.

Answer 28

• Irritation of nasal mucous membranes

* Deep inspiration followed by forceful expiration with opened glottis.

Question 29

Describe the role of deglutition reflex, in affecting the respiratory centers.

Answer 29

• Respiration arrested during swallowing of food (=swallowing apnea or deglutition apnea)

Question 30

Describe the effect of the cortex on ventilation.

Answer 30

♠ Both cortical and other areas can by-pass the medulla and affect the lower motor neurones directly.
♠ When consciously decide to hold your breath or alter ventilation rates (voluntary control) there are signals coming from cerebral cortex to medulla, influencing basic pattern generation by the DRG (inspiratory center)
♠ Also, direct pathway from cortex to the lower motor neurones to influence diaphragm and intercostals.
♠ HOWEVER, involuntary control will eventually take over – you can’t hold your breath forever

Question 31

As part of the afferent pathway of respiration, impulses from chemoreceptors are delivered to respiratory centers via glossopharyngeal nerves. Explain the role of these chemoreceptors.

Answer 31

• Respond to changes in chemical constituents of blood or CSF.
• Can respond to:
• Hypoxia
• Hypercapnea – elevated C02 in blood
• Increased H+ concentration (decreased pH)

• Classified into two groups:

1. Central chemoreceptors
2. Peripheral chemoreceptors

Question 32

Describe the location, and actions of central chemoreceptors as part of respiration.

Answer 32

• Situated in medulla oblongata close to DRG (chemosensitive area)

• Action:
- Sensitive to increase in H+ concentration, but H+ cannot cross the BBB or CSF barrier. However, CO2 can cross into CSF, and forms carbonic acid, which is unstable and rapidly dissociates to H+ and bicarbonate. H+ then stimulates central chemoreceptors. Because there is less protein in CSF than plasma, a rise in PaCO2 can cause a larger effect on pH in CSF than in blood (i.e. acidification of CSF by increasing H+ concentration).
Overall, central chemoreceptors are sensitive to arterial PaCO2, not arterial H+, or to Pa02.

Question 33

Describe the location, and actions of peripheral chemoreceptors as part of respiration.

Answer 33

• Close in location to (but distinct from) baroreceptors – recall these are blood pressure monitoring by stretch of vessels (i.e. situated around carotid sinus and aortic arch)
• Specialised receptor cells (glomus type I) that are stimulated primarily by a decrease in PO2 and an increase in H+ (the latter occurring as a result of increased CO2. Synapse with afferent nerves which run to brainstem, sensory portion of cranial nerve CN X from aortic bodies and CN IX from carotid bodies. Chemoreceptors of the carotid bodies more important than those of aortic bodies in respiration, but both stimulated primarily by a decrease in PO2, but also by CO2 (about 10 times less sensitive than central receptors), pH, blood flow, temperature.

Question 34

Explain the process through which peripheral chemoreceptors respond to alterations in PO2.

Answer 34

When oxygen is at okay levels, calcium channels close (and glomus cell quiescent). When oxygen tension falling, potassium channels close which activates calcium channels. Calcium release triggers neurotransmitter release, which transmits an afferent signal to the CNS, leading to ventilation.

Question 35

Describe the influence of PCO2 on ventilation.

Answer 35

• PCO2 most important of pH, PCO2 and PO2 in control of respiration
• CO2 crosses BBB, so as it rises (hypercapnea) in blood, the pH of CSF decreases. This has excitory input to DRG in medulla and resulting increased ventilation “blows off” CO2, reducing arterial PCO2. PCO2 returns to normal, pH returns to normal and stimulus for respiration is reduced.
• If CO2 is decreased, (eg during hyperventilation), ventilation is depressed. At normal PCO2 there is a resting discharge action potential from chemoreceptors. If PCO2 falls the firing rate also falls so there is a corresponding decrease in excitatory input to DRG, with the result of respiration being inhibited.

Question 36

What is a normal value for PCO2 ?

Answer 36

Normal PCO2 = 40 mmHg or 5.3 kPa

Question 37

Describe the influence of PO2 on ventilation.

Answer 37

♦ Peripheral chemoreceptors are sensitive to PO2, central chemoreceptors are not (carotid more important than aortic)
♦ Normally influence is minimal, PO2 must drop to below 60 mmHg or 8 kPa from around 100 mmHg (13.3kPa) before PO2 become a major stimulus for ventilation

Question 38

Describe the effects of COPD on ventilation.

Answer 38

• Overinflated lungs and barrel chest. Cannot deflate lungs as much so often retain some air.
• PCO2 is chronically elevated due to poor ventilation.
• The central and peripheral chemoreceptors become insensitive to PCO2, or they have adjusted to lower than normal O2 and higher than normal CO2.
• Patient relies on decline in PO2 to stimulate breathing - hypoxic drive.
• Risk is that if you place this patient on 100% O2 with a mask, they will cease breathing, because firing rate of peripheral chemoreceptors will fall and depress ventilatory drive (this hypothesis has been challenged)

Question 39

Identify neuromuscular disorders which affect respiration.

Answer 39

Poliomyelis
Botulism
DMD