Control of Breathing: Rhythmogenesis Flashcards
what structure in the body controls breathing?
how is ventilation stopped?
You need a brain to breathe (unlike the heart)
Transection of CNS between medulla and the spinal cord stops ventilation by interrupting nervous outflow to diaphragm
what are the 2 systems that breathing is controlled by?
Our breathing is controlled by:
behavioural system (controls breathing voluntarily)
metabolic system (controls breathing involuntarily).
explain how breathing can be driven by a ‘metabolic system’
what syndrome occurs as a result of only breathing through this mechanism?
This breathing occurs as a result of metabolism:
Some patients only have this mechanism to breathe. This is called ‘Locked in Syndrome’
Cause: Brainstem stroke (basilar artery)
Symptoms:
Patient is unable to move or breathe voluntarily (except eyes)
Patient has a regular breathing pattern (not irregular like a normal person)
explain how breathing can be driven by a ‘behavioural system’
what syndrome occurs as a result of only breathing through this mechanism?
This is our voluntary breathing
Some patients only have this mechanism to breathe. This is called ‘Ondine’s Curse’ (central hypoventilation syndrome)
They are only able to breathe when they think about it
If they stop being aware of their breathing - they stop breathing
Cause: Patients with medullary tumour (or congenital)
Symptoms:
Unable to sleep without mechanical ventilation, otherwise they would die.
Irregular breathing pattern when awake
what is breathing regulated by?
Breathing is regulated by feedback and feedforward control
Feedback regulation:
It is the drive for homeostatic metabolic mechanisms.
It is set by Paco2: as Paco2 goes up we breathe more to get rid of it.
Feedforward regulation:
related to behavioural changes, e.g. speech, cough, exercise, laughing, yawning all change our breathing.
what are the 2 areas of the brain that respiratory control centres resides in?
- Brainstem (particularly within medulla and part of pons) –> autonomic control
Mechanism:
- Chemical information from blood is detected by chemoreceptors
- Levels of O2/CO2 change due changes in in oxygen consumption (V.O2) and/or CO2 production (V.CO2)
- Mechanical information from periphery (mainly form lungs, airways, thoracic cage) is detected by mechanoreceptors
- Simple feedback loop: the information detected by mechano/chemo receptors is carried by afferents from periphery into brainstem. The brainstem can then modulate the autonomic system outflow via efferents to the respiratory muscles.
- This is done to ensure alveolar ventilation matches metabolism.
- This ensures that Paco2 is held around 5 kPa
- This is important as it will maintain pH at 7.4 and PaO2 at 13kpa. - Cortical → voluntary control
- Is able to override autonomic control
explain why this graph has recordings of the phrenic and internal intercostal nerve?
what does this tell us about the type of breathing it is?
Phrenic nerve: An Inspiratory neurone enabling diaphragm to contract
Internal intercostal nerve: Expiratory neurone stimulating internal intercostal muscles to contract in expiration
In the trace there is activity in the internal intercostal => must be ‘non-quiet breathing’ (active breathing)
what are the 3 phases to ‘non-quiet’ breathing?
There are 3 phases to ‘non-quiet’ breathing when considering neural substrates:
- I Phase: True inspiratory phase
Diaphragm contracts gradually in a ‘ramp’ like manner –> Inspiratory ‘ramp’ - PI Phase: post-inspiratory phase
Part of expiration
Diaphragm does not stop contracting immediately, but relaxes gradually.
Therefore there is still a trace from the phrenic nerve, as it is still firing to diaphragm to regulate relaxation. - E-2 Phase: true expiratory phase
Diaphragm is silent so this is called the ‘ true expiratory pause’
Expiratory neurones now fire and inspiratory neurones stop
Any active expiratory accessory respiratory muscles are contracting
The Brainstem generates an automatic respiratory rhythm
Medulla at base and pons above
It contains 4 respiratory neurones
what are the 4 respiratory neurones?
position and inspiratory/expiratory?
- Dorsal respiratory group (DRG) - located on dorsal surface of medulla
Part of an inspiratory nucleus - Ventral respiratory group (VRG) - located on the ventral surface of medulla
Made up of 2 components:
1 expiratory component -> generates expiration
1 inspiratory component -> generate inspiration - Pontine respiratory group (PRG) - located in the pons
Contains both inspiratory and expiratory components - Botzinger Complex - located at rostral (front) end of DRG
Contains mainly expiratory component
how does each side of the brainstem work?
Each side of the brainstem is independent of the other:
After a mid-sagittal transection, each side of the brain can generate an independent respiratory rhythm.
explain how a respiratory rhythm is generated?
what innervations aid this?
A respiratory rhythm is generated through interactions between various nuclei in the brainstem, the cerebral cortex and higher centres (limbic system and hypothalamus)
- Cerebral cortex: voluntary drive comes from here
- Brainstem: Automatic drive comes from here
Higher centres: these centres drive behavioural respiratory responses
Spinal cord: motor nerves from the spinal cord drive inspiration and expiration
Phrenic nerve –> innervates diaphragm
Inspiratory (I) motor neurones –> innervate inspiratory accessory muscles
Expiratory (E) motor neurones –> innervate expiratory accessory muscles
which brainstem neurone controls quiet breathing?
DRG (within NTS) drives inspiration during quiet breathing
These neurones fire excitatory impulses and the phrenic nerve is activated
Diaphragm contracts during I phase and relaxes at the end of PI phase.
VRG (both inspiratory + expiratory neurones) neurones are not activated
Not needed, as inspiration is activated by DRG and expiration during quiet breathing is passive (uses recoil)
If we vary ventilation, how does control of breathing occur?
You need to be able to vary the drive to the diaphragm and accessory muscles as needed.
This allows you to vary ventilation.
This depends on the inputs of sensory information detected by mechanoreceptors and chemoreceptors
This sensory information is integrated at NTS and can augment (increase) respiration by increasing both inspiratory drive and expiratory drive
with varied ventilation, what is the inspiratory and expiratory drive?
Inspiratory drive:
NTS sends an excitatory drive to the inspiratory neurones of DRG. These neurones then stimulate the diaphragm –> Inspiration.
NTS also sends an excitatory drive to the inspiratory neurones of VRG. These neurones then stimulate the inspiratory accessory muscles –> Inspiration.
Expiratory Drive:
The NTS excites Botzinger Complex
The Botzinger expiratory neurones sends excitatory drive to the expiratory neurones of VRG. These neurones then stimulate the expiratory accessory muscles –> Expiration.
To separate inspiration from expiration - when expiration is excited, inspiration is inhibited (reciprocal inhibition)
Inhibitory drive is sent from VRG expiratory neurones to the DRG inspiratory neurones, thus inhibiting inspiration.
Inhibitory drive from Botzinger expiratory neurones to DRG inspiratory neurones and VRG inspiratory neurones, again inhibiting inspiration.
what does the Pontine respiratory group (PRG) do?
it controls the timing of breaths
Excitation of PRG by NTS is able to influence the timings of breaths by acting on both inspiration and expiration.
It causes augmentation of DRG inspiratory neurones during the inspiratory phase
It also causes inhibition of DRG during expiratory phase
what is the role of the higher centres in controlling breathing?
Higher centres: limbic, hypothalamus etc.
The higher centres receive information about temperature, pain, emotional state, limb proprioceptors (movement)
This information is Integrated in these centres
These centres can then either excite or inhibit the inspiratory neurones of DRG:
Example:
Emotional activity causes us to gasp
Pain makes us hold our breath
High temperature can cause increase in breathing (in animals)
what is the role of the cerebral cortex in controlling breathing?
Provides voluntary control of breathing
The cerebral cortex outputs bypass the brainstem nuclei entirely. (In contrast to output from higher centres)
They go straight to the motor neurones of the spinal cord (connected to diaphragm, Inspiratory & Expiratory accessory muscles).
Both inspiratory and expiratory outputs are produced
Can hold breath if you wish and can voluntarily increase ventilation if you wish.
We can voluntarily control our breathing up to certain point at which then the brainstem nuclei take over and cause rhythm generation to be driven by metabolic demands.
You can take recording from the pre-botzinger complex and hypoglossal nerve CN XII.
Trace A:
Rhythmic activity in CN XII occurs during inspiration
Pre-Botzinger Complex fires at the same time as CN XII, therefore rhythms are linked
Trace B:
In order to differentiate whether the Pre-Botzinger Complex is a pacemaker or network oscillator scientists prevented synaptic activity (by removing extracellular Ca2+) - will be no network oscillating between neurones as synapses will not be working.
If we continue recording, after Ca2+ is removed, you still see output from Pre-Botzinger Complex
Therefore, PBC can fire spontaneously fire without need for synaptic input
This provides some evidence that it an important nucleus for origin of respiratory rhythm.
