Lecture 23- Control of Breathing Flashcards
Aim of Control of breathing
To maintain the “interior” milieu:
- normal PaO2
- Normal PaCO2
- Normal pH
To meet the requirements of tissues during exercise or stress (eg; sepsis or other disease state)
Protect arterial PO2 by minimising A-aDO2 - gas exchange crucial
Minimise work of respiratory muscles- respiratory mechanics crucial to efficiency
Ondines Curse
Single point mutation in Phox2b gene of the RTN/pFRG centre.
Phox2b is involved in rising CO2 response, so suffers have a low response rate. This is not an issue during the day, as breathing is stimulated by many other factors.
HOWEVER: during sleep, many of these factors diminish! Normally when we sleep, we reset and increase our threshold of CO2 by 1/2kp, stop breathing until our CO2 rises to that level and we are stimulated to breath.
But for sufferers when they change their CO2, stop breathing, but they don’t respond (inadequate drive)and just continue not breathing! Eventually get hypoxic and breath unless their brains are already shutting down
Pons and Medulla important sites
Where it all happens.
Site of stimulus to breathe: preBottinger complex (preBotC)
active expiration: RTN/pFRG
Input to breathing
Rhythm Generator ??
Need to breath is like a pacemaker, but unlike the heart (simple), it is an ‘inspiratory oscillator’
-This is because it has to vary amplitude of insp/exp in a responsive way.
Two main oscillators:
preBotC: inspiration
RTN/pFRG: inspiratory “off” switch to allow expiration. Also can switch on active expiration.
What feeds into the Rhythm generator? Then that feeds into?…
1-Suprapontine modulators (what we can control)
2-Neuro-modulators (from all areas of the brainstem, NTs, hypoxia, CO2 levels) eg; adrenergic peptides, CKS
3-Sensory Modulators eg lungs, muscles, chest wall
Then the Rhythm generator feeds into a ‘central pattern generator’
Suprapontine modulators
Volitional: phonation, breath holding, hyperventilation
Emotional: laughing, sighing, crying
AIM of having patternogenesis system? whats the point? What does your pattern consist of?
you have the mechanically most EFFICIENT pattern for the task at hand (ie; the least work of breathing)
PATTERN: frequency, depth (tidal V) and insp/exp timing
Hypoxia understaing
- Complex and poorly understood
- HIF-alpha deal with hypoxia
Sensed in the aortic bodies and carotid bodies by ‘peripheral chemoreceptors’
Aortic Bodies
-Transmit via Vagus nerve
in the Aortic arch, sense pO2, pCO2 and pH.
-larger response if both pO2 and pCO2 change (weak chemoreceptors compared to carotid bodies)
-Stretch receptors detecting BP (crucial role) involved in CV and resp responses to exercise, stress and disease
Carotid Bodies
At bifurcation of the carotid arteries
- Account for all of the hypoxic drive but only 20% hypercapnic drive
- Feed via glossopharyngeal nerve to brainstem resp centres at level of RTN/pFRG
Carotid chemoreceptors
Doesn’t detect oxygen content in blood, but the aterial pressure of O2 in the plasma passing it (PaO2 not CaO2)> activates glomer cell > trigger up glossopharyngeal nerve to brainstem > breathe harder
Therefore low [O2], high [CO2] high [H+] lead to increased ventilation.
Happens rapidly, but if you make someone hypoxic slow, it can have a slow response (different transmitters)
Hypoxic drive varies; at birth
Carotid body CO2 sensing, surgical trauma
Powerful PaCO2 sensor IF not suppressed by normal PaO2
Prone to surgical trauma (only need one carotid body for adequate control of ventilation)
Not for breath by breath control
Hypoxia and normaocapnic
Normocapnic: Ventilation normal till ~60mmHg, but normally we blow off more CO2 (hyperventilate so CO2 falls), so not as breathless as you would expect decreasing overall response
Where DO we see a hypoxic response?
Not used much unless sick or have severe lung disease or normal subjects at altitude.
If you don’t have a strong enough hypoxic drive, you can’t climb everest
Correcting hypoxia
Put him on Oxygen (but if they have pneumonia they are shunting blood through consolidatedso some blood is still never going to see O2)
Improve blood gases
Why is the man still a bit breathless even after correcting his hypoxia
-Fever
-inflammatory CKs
-stress response (raised catecholamines)
C&j receptor stimulation
Hypoxic AND hypercapnic
As BOTH PAO2 and PACO2 are up he is having to breath way more (more breathless)
High HCO3- indicates
chronic hypercapnia
How do we know our CO2 levels are high?
CO2 equilibriates to H+ ions in the brain. Chemoreceptors respnd to increased H+ in the interstitual fluid (not CSF)
Ventilatory response to increased PaCO2
Different to O2. variable between humans, we breathe harder.
Initial rapid phase: seconds (rapid acidification of CSF + augmented carotid vody stimulation by PaCO2)
Slower phase - minutes (due to a change [H+] in highly buffered medullary interstitium
Gradual diminution of VE response- hours (renal compensation with HCO3- retention, soak up CO2)
Carotid bodies response to CO2
powerful responder to CO@ that is usually supressed by normoxia. Therefore it’s brought to life by hypoxia.
CO2 response drive
We don’t Normally really respond to PaCO2 until over ~40
Sleep: increases by ~o.5kp
Morphine: CO2 responsiveness slugs
Anasthetic: even more so slugged
if less hypoxic but more hyperapnic and acidotic (and obtunded) what do we do?
Decress the O2 (but not completely) and commense non-innvasive ventilation via mask ventilation to imrove VE and lower PaCO2
1) increased O2 releases hypoxic pulmonary VC so now blood is going to shitty bits of the lung that cant ventilated, and CO2 isn’t getting blown off, CO2 accumulates.
2) Due to depressed CO2 response (already had one and medication), and we took away the hypoxia and therefore the hypoxic drive, but he has no other so ventilation decreases, and CO2 levels are increasing, less blown off
Inspiration centre activates muscles
Diaphragm, external intercostals, tongue and larynx
active expiration centre activates muscles
Abdominals, internal intercostals, tongue and larynx
Essential for adequate cough and expiration on heavy exercise
Lung Sensors
Irritant Receptors (RAR)
Stretch Receptors (SAR)
J& C receptors
Irritant receptors (rapidly adapting receptors
Located near the carina and large bronchi between bronchi epithelial cells
- Responsible for irritant reflexes (cough reflex; cough, bronchospasm, mucus production, tachypnea)
- Stimulated by noxious gases, cigarette smoke, inhaled dust, cold air and mechanical stimuli.
Stretch receptors (slowly adapting receptors)
Hering-Breuer refllex
-In the smooth muscle of the bronchi and posterior trachea activated by stretch (vid 9th):
increased output and volume, therefore inhibits further inflation (inspiration offswith), relaxes tracheobronchial muscle and prolongs expiration
-Respond to mechanical stimulus (stretch) clinically in humans tidal V must exceed 0.8-1.0L before any stimulation
J-receptors
C-fibres (unmyelinated afferents)
The majority of afferent fibres and 2 classes
1) Pulmonary C
2) Bronchial C receptors in bronchial interstitium
Excited by BOTH chemical and mechanical stimuli
- histamine, prostoglandins
- vascular distention
Stimulation results in reapid shallow breathing, bronchoconstriction and mucus production
J- receptors and excess exercise
If you push yourself too hard in exercise, switch of O2 to muscles > muscle weakness and termination of exercise.
Stops bleeding into lungs, tell us when we are going to hard
Pattern of breathing during exercise
- Breath fast
- Pause, not increasing breathing (breathless)
- Breathing increases (2nd wind)
CO2 has tiny fluxuations
How is exercise regulation
Feedforward:
-Link from resp centres to corticospinal tract
PAG (key integrating command centre) and RTN
Feed back:
Thinly myelinated afferents from muscles to NTS and chemoreceptor neurons in Ventral lateral medulla
