neural and chemical control of breathing Flashcards
what are the neural inputs to ventilation
breathing movements are not spontaneous
skeletal muscles which control breathing require neural input
neural input can be involuntary (tidal breathing) and voluntary (IRv, ERV, breathing frequency)
chemo-receptive inputs monitor plasma and cerebral spinal fluid composition to maintain ventilatory homeostasis
where are the respiratory centres located within the brain
located in the brain stem - the pons and medulla
what are the two resporatory centres
pons respiratory centres - pneumotaxic centre and apneustic centre
medullary respiratory centres - pre-botzinger complex, dorsal respiratory group and ventral respiratory group
what is the dorsal respiratory group
inspiratory control
located within the Nucleus Tractus Solitarius and is dorsal to the VRG
site of sensory information input
site of central chemoreceptor input
some premotor neurons
what regions of the medulla is the ventral respiratory group located in
- rostral - expiration control (pre-botzinger complex)
- intermediate - inspiration control mediated through pre-botzinger complex (thought to be the site of respiratory pattern generator)
- caudal - expiration control
what is the function of the hypoglossal nerve, laryngeal nerve, and carotid sinus nerve in the neural organisation of the respiratory muscles
peripheral chemoreceptor feedback
what is the function of the vagus nerve in the neural organisation of the respiratory muscles
breathing frequency and volume
what is the function of intercostal nerves in the neural organisation of the respiratory muscles
respiratory muscles
what is the function of the phrenic nerve in the neural organisation of the respiratory muscles
diaphragm inspiration control
what are the inspiratory muscles
sternocleidomastoid
scalenes
external intercostals
parasternal intercostals
diaphragm
what are the expiratory muscles
internal intercostals
external abdominal oblique
internal abdominal oblique
transverse abdominalis
rectus abdominis
what is the diaphragm and how is it innervated
dome-shaped
sits above the liver
innervated by phrenic nerves - C3-5
moves 1cm in quiet breathing, up to 10cm
major inspiratory muscle
what innervates the external intercostals
intercostal nerves at ‘rib level’
what is the function of the accessory muscles (sternocleidomastoid and scalenes)
chest expansion
intrapleural pressure falls
what is the role of expiratory muscles during quiet breathing
mainly passive during quiet breathing
elastic recoil pressure is sufficient
what is forced expiration
exercise, voluntary
e.g. cough, sneeze and defacation
the abdominal wall pushes the guts up against the diaphragm
involves internal intercostals
what is the role of the pharynx/larynx in breathing
cranial motorneurons are important for opening/closing glottis, affecting upper airway diameter, flaring nostrils etc
what is a respiratory rhythm generator (RRG)
a network of interneurons that produce a predictable and repetitive motor pattern
in the case of breathing, inspiratory neurons must be activated before expiratory neurons
what are the properties of the RRG
always active even in the absence of conscious input (endogenous cyclical oscillation)
transmit in an orderly sequence to respiratory muscles
what parts of the brain influence the RRG
the limbic system - emotion
sensory afferents - pulmonary stretch receptors, peripheral chemoreceptors
what are the three phases of the breathing cycle
inspiration
post-inspiration
late expiration
what are the 6 types of neuronal discharge
pre-inspiration
early-inspiration
inspiration
late-inspiration
early-expiration
expiration
what is the pre-inspiration phase of the RRG
pre-I neurons inhibit excitatory neuronal circuit
expiratory muscles relax
what is the early-inspiration phase of the RRG
early-I neurons inhibit output from entire RRG
refractory period
no breathing movements
what is the inspiration phase of the RRG
I neurons ramp fire, as frequency increases so more inspiratory neurons contribute
activate motorneuron circuit to inspiratory muscles and inhibit excitatory and pre-I neural circuits
inspiratory muscles contract as intensity of inspiratory neuron firing increases
expiratory muscles relaxed
what is the late-inspiration phase of the RRG
late-I neurons feedback to suppress inspiratory neuronal firing when at peak intensity.
may involve stretch receptor input
inspiratory muscles relax and lung begins to deflate due to elastic recoil
what is the early-expiration phase of the RRG
early-E neurons repress all inspiratory and expiratory neuronal firing
creates refractory period at peak inhalation
inspiratory muscles relax and lung begins to deflate due to elastic recoil
what is the expiration phase of the RRG
E neurons ramp fire.
activate motorneuron circuit to expiratory muscles
major point of conscious input of breathing
expiratory muscles contract as E firing intensity increases
inspiratory muscles relaxed
how are breathing patterns changed
central chemoreceptors (medulla surface) and peripheral chemoreceptors (carotid & aortic bodies, and, neuroepithelial bodies)
- medullary respiratory centre
- DRG
- VRG
- pre-botzinger complex
what occurs during a normal breathing pattern
burst firing of phrenic nerve causes diaphragm contraction and relaxation
what occurs during a breathing pattern with increased tidal volume
increased action potentials per burst gives stronger diaphragm contraction and deeper breathing
⬆️ total ventilation volume (Ve) = ⬆️Vt + ⬆️frequency
increased burst per minute = increased breathing frequency, when combined with increased action potentials per burst then total ventilation volume increases
how is involuntary breathing rhythm regulated
sensors > controller > effectors
sensors = central chemoreceptors, peripheral chemoreceptors and stretch receptors
effectors = respiratory muscles
what is the role of central chemoreceptors in involuntary breathing rhythm
monitor pCO2 in cerebral spinal fluid
what is the role of peripheral chemoreceptors in involuntary breathing rhythm
monitor pO2, pCO2 and pH in blood and mixed lung gases
carotid body - blood
neuroepithelial bodies - airway
what is the role of stretch receptors in involuntary breathing rhythm
hering-breuer reflex
inhibition of lung over-inflation (>50% resting tidal)
increased breathing frequency following rapid lung deflation (exhalation > pant)
what is the role of allergens/ irritant receptors in involuntary breathing rhythm
located along airway - feed into vagus nerve
couch, sneeze and bronchoconstriction reflex
how does disturbed homeostasis effect breathing
DRAW diagram/mindmap/schematic
where are the chemoreceptors located
central = medulla surface
peripheral = arterial vasculature and airway
what is the % of normal breathing attributed to the chemoreceptors
central = 80%
peripheral = 20%
what do the chemoreceptors primarily detect
central = pH changes caused by an increase in paCO2 in cerebral spinal fluid
peripheral = decreased paO2 in blood and airway
what is the response time of the chemoreceptors
central = slow (minutes)
peripheral = fast (seconds)
what are the response modes of the chemoreceptors
central = linear
peripheral = non-linear
are the chemoreceptors adaptive by training
central = yes
peripheral = no
what are central chemoreceptors
control system for normal breathing
directly responsible to CO2 driven pH changes in cerebral spinal fluid
what is the response of central chemoreceptor to changing alveolar pCO2
very sensitive to small changes in paCO2
e.g. 40-45mmHg paCO2 = double total ventilation
hypoxia makes the response steeper as it may bring central chemoreceptor cells closer to firing threshold
adapt to sustained changes in paCO2 over several days
- relevant to disease, high altitude, free diving and drug action
what occurs during shallow water blackout
- hyperventilation drives paCO2 down
- low central chemoreceptor sensitivity (caused by breath-hold training) fails to trigger breathing response in time to prevent severe hypoaemia
- loss of consciousness and drowning
what are peripheral chemoreceptors
carotid body - carotid sinus
aortic body - aortic arch
primary response is to hypoxia
also respond to hypercapnia (increased paCO2) and acidosis (decreased pH)
how do peripheral chemoreceptors respond to hypoxia
- response is not linear (increases dramatically below pAO2 = 60mmHg)
- response is driven by low partial pressure of oxygen and not oxygen concentration or HbO2 saturation. does not occur with anaemia
- hypercapnia or acidosis raises the sensitivity of chemoreceptor to paO2
what is the cellular mechanism of chemoreception
decreased oxygen, decreased pH or increased carbon dioxide
triggers oxygen of pH sensors which depolarise
opening of voltage-gated Ca2+ channels
neurotransmitter release
glossopharyngeal nerve
brain stem; DRG, VRG
hypoxic ventilatory response (⬆️f and Vt) or hypoxic pulmonary vasoconstrictor response (⬆️pulmonary artery pressure)
give a full overview of the cellular mechanism of chemoreception
1.a. hypoxia - the cell might sense low pO2 by three mechanisms (i) oxygen dissociates from haem-containing protein near K+ channel (ii) low pO2 somehow elevates intracellular cAMP concentration (iii) low pO2 inhibits NADPH-oxidase in mitochondria, raising ratio of reduced to oxidised glutathione
1.b. hypercapnia - elevated pCO2 leads to influx of CO2 into cell and the production of H+
1.c. acidosis - low extracellular pH inhibits acid-ectruding transporters (e.g. Na-H exchangers) and also promotes intracellular acid loading, leading to build-up of H+ inside cell
2. these mechanisms reduce the open-probability of K+ channels
3. inhibition of K+ channels depolarises the cell
4. depolarisation opens voltage-gated Ca2+ channels causing increased Ca2+ entry and increased intracellular Ca2+ concentration
5. elevated intracellular Ca2+ concentration triggers release of neurotransmitters
6. neurotransmitters (dopamine) bind to postsynaptic membrane of afferent nerve fibre, generating action potential that is conducted along the axon of the glossopharyngeal nerve (CN IX) which leads to the medulla.
