03-11-22 - Ventilation - the Neural Control of Breathing and Ventilation Flashcards
Learning outcomes
- Describe the location of the primary respiratory centre
- Describe the role of the VRG in the medulla in the neural control of respiration
- Describe the role of the pons in the neural control of respiration
- Describe the levels at which the basic pattern of neural activity can be altered
- Describe the inputs to the medulla which affect respiration
How is alveolar ventilation rate adjusted?
What are the 4 major sites for this adjustment?
- Alveolar ventilation rate is normally adjusted so that PO2 and PCO2 in the arterial blood are hardly altered, even during heavy exercise and other respiratory stresses
- 4 major sites for this adjustment:
1) Respiratory control centre (source of central pattern generator)
* In the medulla oblongata and pons of the brainstem
2) Central chemoreceptors in the brain
* Central chemoreceptors, first localized to areas on the ventral surface of the medulla, now are thought to be present in many locations within the brainstem, cerebellum, hypothalamus and midbrain
3) Peripheral chemoreceptors
* In the aortic arch and bifurcation of the common carotid
4) Pulmonary mechanoreceptors
* In the lungs
What are the 2 primary muscles of inspiration?
What are the 4 secondary muscles of inspiration?
What are the 2 secondary muscles of expiration?
What are they each innervated by?
Where is the location of their motor neuron?
Where do cranial nerves originate?
What cranial nerves come from the:
* Cerebrum (2)
* Midbrain (2)
* Pons (4)
* Medulla Oblongata (4)
- Cranial nerves that originate from the:
- Cerebrum
1) Olfactory nerve (CN I)
2) Optic nerve (CN II) - Midbrain
3) Oculomotor nerve (CN III)
4) Trochlear nerve (CN IV) - Pons
5) Trigeminal nerve (CN V)
6) Abducens nerve (CN VI)
7) Facial nerve (CN VII)
8) Vestibulocochlear nerve (CN VIII) - Medulla oblongata
9) Glossopharyngeal nerve (CN IX)
10) Vagus nerve (CN X)
11) Accessory nerve (CN XI)
12) Hypoglossal nerve (CN XII)
What effect do 3 different transections (transverse cuts) of the brainstem/spinal cord have on respiration?
- Effects 3 different transections (transverse cuts) of the brainstem/spinal cord have on respiration:
1) Section below the level of the pons (ponto-medullary transection)
* The basic rhythm of respiration continues
* Integrated phrenic nerve activity remained
* Integrated CNX11 activity remained (accessory nerve)
2) Section the spinal cord below C3-C5
* The intercostal muscles are paralysed
* Internal and external intercostal muscles are innervated by thoracic spinal cord ventral horn
3) Section below the medulla (spino-medullary transection)
* All breathing ceases
* No integrated phrenic nerve activity
* Integrated CNX11 activity remained
* Although ventilation stops, respiratory activity continues in muscles innervated by motor neurons whose cell bodies reside in brain stem (i.e nostrils still flare etc)
* Suggests this area is an important aspect for normal breathing pattern
Why is the term ‘respiratory centres’ probably incorrect?
What is a more accurate term?
Where these ‘centres’ located?
What are the roles of these centres?
What are the 3 groups that make up the respiratory centre?
- The term ‘respiratory centres’ is probably incorrect, as it implies there are discrete anatomical regions that can be identified macro- or microscopically
- Better description would be diffuse networks that are active together to bring about the respiratory effect
- These ‘centres’ are located in medulla oblongata and pons
- These centres collect sensory information about O2 and CO2 levels in blood and determine signals sent to respiratory muscles, which leads to alveolar ventilation
- The respiratory centre is made up of three major respiratory groups of neurons, two in the medulla and one in the pons.
- These groups are the:
1) Pontine respiratory group (PRG)
2) Dorsal (posterior) respiratory group (DRG)
3) Ventral (anterior) respiratory group (VRG)
What are the 3 groups that make up the respiratory centre?
What is each group responsible for?
What nerves/neurons do some of these groups receive sensory supply from/giveoff?
Where are lung mechanoreceptors found?
What is their function?
1) Pontine respiratory group (PRG)
* Found in the pons of the brainstem
* includes two areas, known as the pneumotaxic centre and the apneustic centre.
* Involved in the phase transition between inspiration and expiration, and the reflex effects of lung mechanoreceptors on ventilation
* Mechanoreceptors are found throughout the entire respiratory tract.
* They supply the brain stem respiratory network with information about the mechanical status of the lungs and chest, contribute to the control of respiratory activity, and initiate protective reflexes such as cough.
2) Dorsal (posterior) respiratory group (DRG)
* Located in the posterior medulla
* Responsible for basic rhythm of quiet inspiration by triggering inspiratory impulses
* Receives input from vagus and glossopharyngeal nerves
* Also has neurons that exit the spinal cord in the phrenic nerve and send impulses to the motor nerves of diaphragm
* Also gives motor supply to external intercostal muscles.
3) Ventral (anterior) respiratory group (VRG)
* Located in the anterior medulla
* Has inspiratory and expiratory input
* Thought to be more important in forced breathing
* Has neurons that send impulses to abdominal and intercostal muscles
Dorsal respiratory group (DRG).
Where are most of the dorsal respiratory group neurons found?
What sensory input does the DRG receive?
What do neurons in the DRG emit?
What do these bursts involve?
What 2 ways can these ramps be altered?
- Most of the dorsal respiratory group (DRG) neurons are located within the nucleus tractus solitarius in the medulla
- The DRG receives sensory input from organs of thorax and abdomen
- Neurons in the DRG emit repetitive bursts of inspiratory neuronal action potentials (cause of repetitive bursts not known)
- These bursts Involve a respiratory ramp for 2 seconds followed by cessation for 3 seconds
- 2 ways can these ramps be altered:
1) Controlling rate of increase of ramp (heavy breathing, ramp increases rapidly so lungs fill rapidly)
2) Controlling limiting point at which ramp suddenly stops (control rate of respiration)
What 2 places are ventral respiratory group neurons (VRG) found?
What 2 things do VRG neurons not participate in?
What 3 things do VRG neurons participate in?
- Ventral respiratory group neurons are found in the:
1) Nucleus ambiguus
2) Nucleus retroambigualis - 2 things VRG neurons don’t participate in:
1) VRG Neurons are almost totally inactive during normal quiet breathing
2) VRG neurons don’t participate in basic rhythmical oscillation
- 3 things VRG neurons do participate in
1) During increased respiratory drive, ventral respiratory area contributes to extra respiratory drive
2) Electrical stimulation of a few neurons in the ventral group causes inspiration, stimulation of others causes expiration
3) Especially important in providing powerful expiratory signals to abdominal muscles during heavy expiration (type of overdrive mechanism)
What is the role of centres in the pontine respiratory group?
Where in the pons is the pneumotaxic centre located?
What is the primary effect of the pneumotaxic centre?
How does it do this? What does this ultimately regulate?
- Centres in the pontine respiratory group (pneumotaxic and apneustic centres) modulate, but are not essential for, normal respiratory output
- The pneumotaxic centre is located dorsally in nucleus parabrachialis medialis of upper pons
- The primary effect of the pneumotaxic centre is to control switch-off point of inspiratory ramp (so controls filling phase of lung cycle)
- This is done through the strength of the pneumotaxic signal
- Strong pneumotaxic signal - inspiration may last for less than 0.5 second while a weak pneumotaxic signal - inspiration may last for 5 or more seconds
- This ultimately regulates the rate at which we breath
What is the ultimate goal of ventilation?
Where are central chemoreceptors located?
What 2 things do they detect?
Where are peripheral chemoreceptors located?
What 3 things do peripheral chemoreceptors detect?
- The ultimate goal of ventilation is to maintain proper levels of PO2, PCO2 & pH (H+)
- Central chemoreceptors are located in the central respiratory centre in the medulla
- 2 things central chemoreceptors detect:
1) Hypercapnia (increased PCO2)
2) Acidosis (decreased pH) - Peripheral chemoreceptors are located in the carotid body at the bifurcation of the common carotid and aortic bodies in the aortic arch
- 3 things peripheral chemoreceptors detect:
1) Hypoxia (decreased PO2)
2) Hypercapnia (PCO2)
3) Acidosis (pH)
How was the location of central chemoreceptors identified?
Where were chemosensitive neurons also found?
What are neurons in this area very sensitive to?
- Hans Loeschke, Marianne Schlafke and Robert Mitchell applied acidic solutions to particular areas
- When acid solution was applied to candidate regions near ventrolateral medulla, ventilation increased, meaning central chemoreceptors are located here
- Chemosensitive neurons have also been identified bilaterally beneath ventral surface of the medulla and in medullary raphe inside
- Neurons in these area very sensitive to H+ ions (which may be only important direct stimulus)
Where are chemosensitive neurons located? What are they sensitive to?
What can H+ ions not move across?
What happens in the CSF when blood PCO2 is increased?
How will central chemoreceptors respond?
Why can a rise in PCO2 cause greater changes in pH in CSF than blood?
- Chemosensitive neurons (which act as chemoreceptors) are located bilaterally beneath ventral surface of the medulla in the blood brain barrier (BBB)
- They are very sensitive to H+ ions (may be only important direct stimulus)
- H+ ions do not cross the blood brain barrier very well, however gases, such as CO2 and O2 can cross easily
- When blood PCO2 increases, PCO2 can diffuse across the BBB, resulting in an increase in the PCO2 in the interstitial fluid of the medulla and CSF
- CO2 can then combine with H20 to form H+ ions by the action of carbonic anhydrase, which decreases pH
- The central chemoreceptors can then increase firing to increase ventilation, eliminate CO2 faster, and decrease pH
- 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
How do PO2 levels excite nerve endings?
What cells do bodies that contain chemoreceptors have?
What do they synapse on to?
What autonomic innervation does the carotid body have?
What is the sensory supply of the carotid body?
- How low PO2 excites nerve endings is still largely unknown
- Bodies that contain chemoreceptors have multiple highly characteristic glandular-like cells (Glomus cells – Type 1 cells)
- Glomus cells synapse directly or indirectly with nerve endings
- They also have type 2 sustentacular cells that act as support cells
- The carotid body has both sympathetic and parasympathetic innervation
- The carotid body also has sensory supply from the 9th cranial nerve (glossopharyngeal nerve aka the carotid sinus nerve)
What 3 things can peripheral chemoreceptors of the carotid body sense change in?
Under what circumstances can it sense these changes?
- 3 things can peripheral chemoreceptors of the carotid body sense change in:
1) Decreased arterial PO2
* At normal values of PCO2 and pH a decrease of PO2 causes progressive in firing rate of the glossopharyngeal nerve (aka the carotid sinus nerve)
2) Increase in arterial PCO2
* Results show graded increases in PCO2 at a fixed blood pH (7.45) and fixed PO2 (80mmHg), produced graded increases in firing rate of glossopharyngeal nerve
3) Decrease in arterial pH (metabolic acidosis)
* Blood pH (7.25) and fixed PO2 (80mmHg), firing rate of carotid sinus nerve is greater over all PCO2 values
What is the final shared common pathways for the pathways of changing PO2, PCO2, and pH in the glomus cell of the carotid body?
How does this common pathway work?
- The final shared common pathways for the pathways of changing PO2, PCO2, and pH in the glomus cell of the carotid body is the K+ channel in the glomus cell
- All pathways lead to the K+ channel being blocked, which results in L-type voltage gated calcium channels opening
- This causes the exocytosis of neurotransmitter towards the post-synaptic membrane of the afferent glossopharyngeal nerve, triggering an action potential
What 2 other sources does the respiratory system receive input from?
What are 3 examples of stretch and chemical/irritant receptors?
- 2 other sources the respiratory system receives input from:
1) Stretch and chemical/irritant receptors
2) Higher CNS centres that control non-respiratory activity - 3 examples of stretch and chemical/irritant receptors
1) Slowly adapting pulmonary stretch receptors
2) Rapidly adapting pulmonary stretch (Irritant) receptors
3) C-fibre receptors (J Receptors)
What reflex are slowly adapting pulmonary stretch receptors involved in?
What does this reflex help in doing?
In humans, when is this reflex activated?
Where are slowly adapting pulmonary stretch receptors located?
What are the 2 steps in the Hering-Breuer reflex?
- Slowly adapting pulmonary stretch receptors are involved in the Hering-Breuer reflex (1868)
- This reflex helps to prevent over-inflation of the lungs
- In humans, this reflex is not activated until tidal volume increases to about 3 times normal (i.e. 1.5L / breath)
- Slowly adapting pulmonary stretch receptors are located in muscular portions of walls of bronchi and bronchioles
- 2 steps in the Hering Breuer reflex:
1) Send signals through vagal nerves (CNX) to DRG neurons when lungs overstretched –
2) Feedback response initiated that ‘switches off ‘inspiratory ramp
Where are rapidly adapting pulmonary stretch (Irritant) receptors located?
What are they responsible for?
- Rapidly adapting pulmonary stretch (Irritant) receptors are located in nerve endings in the epithelium of trachea, bronchi, and bronchioles
- These receptors are responsible for coughing and sneezing
Where are C-fibre receptors (J Receptors) located?
What do they respond to?
What are 4 examples of times these receptors may be stimulated?
What 3 things does this stimulation induce?
- C-fibre receptors (J Receptors) are located in alveoli and conducting airways close to capillaries
- C-fibre receptors (J Receptors) respond to chemical and mechanical stimuli
- 4 examples of times these receptors may be stimulated
1) Pulmonary oedema
2) Congestion
3) Pneumonia
4) From endogenous chemicals such as histamine - 3 things this stimulation induces:
1) Shallow breathing
2) Bronchoconstriction
3) Mucus secretion
How are cough reflexes activated?
What does this result in?
What are the 3 phases of the response?
What is the aim of this response?
- The cough reflex is activated when nerve endings of vagus and/or visceral afferent fibres are activated by irritation of the trachea or bronchi
- This results in action potentials travelling to medulla and spinal cord respectively
- 3 phases of the response:
1) Preparatory inspiration
2) Compressive phase
* Glottis closed by vagal efferent activity
* Forced expiration against a closed glottis
* Pressure increases
3) Expulsive phase
* Glottis suddenly opens and trapped air is expelled at high speed by contraction of internal intercostals and abdominal muscles
- The aim of this response is to dislodge mucous covering airways and carry irritant away to mouth, where is can be coughed out or swallowed
Summary of control of respiration
Normal and abnormal respiratory patterns. Describe the following respiratory patterns:
* Eupnoea
* Sigh
* Inspiratory apneusis
* Vagal breathing
* Cheyne-Stokes respiration
* Ataxic breathing
What disease can some of them indicate?
- Respiratory patterns:
1) Eupnoea
* normal breathing
2) Sigh
* larger than normal breath that occurs at regular intervals in normal subjects
3) Inspiratory Apneusis
* prolonged inspirations separated by brief expirations
4) Vagal breathing
* slow, deep inspirations due to vagal interruption
5) Cheyne-Stokes respiration
* Benign respiratory pattern.
* Cycles of gradual decrease in TV, followed by gradual increase in TV, then apnoea
* Suggests bilateral cortical disease, healthy people at high altitude
6) Ataxic breathing
* irregular inspirations, separated by long periods of apnoea
* Suggests medullary lesion
