neural and chemical control of breathing

Question 1

what are the neural inputs to ventilation

Answer 1

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

Question 2

where are the respiratory centres located within the brain

Answer 2

located in the brain stem - the pons and medulla

Question 3

what are the two resporatory centres

Answer 3

pons respiratory centres - pneumotaxic centre and apneustic centre
medullary respiratory centres - pre-botzinger complex, dorsal respiratory group and ventral respiratory group

Question 4

what is the dorsal respiratory group

Answer 4

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

Question 5

what regions of the medulla is the ventral respiratory group located in

Answer 5

1. rostral - expiration control (pre-botzinger complex)
2. intermediate - inspiration control mediated through pre-botzinger complex (thought to be the site of respiratory pattern generator)
3. caudal - expiration control

Question 6

what is the function of the hypoglossal nerve, laryngeal nerve, and carotid sinus nerve in the neural organisation of the respiratory muscles

Answer 6

peripheral chemoreceptor feedback

Question 7

what is the function of the vagus nerve in the neural organisation of the respiratory muscles

Answer 7

breathing frequency and volume

Question 8

what is the function of intercostal nerves in the neural organisation of the respiratory muscles

Answer 8

respiratory muscles

Question 9

what is the function of the phrenic nerve in the neural organisation of the respiratory muscles

Answer 9

diaphragm inspiration control

Question 10

what are the inspiratory muscles

Answer 10

sternocleidomastoid
scalenes
external intercostals
parasternal intercostals
diaphragm

Question 11

what are the expiratory muscles

Answer 11

internal intercostals
external abdominal oblique
internal abdominal oblique
transverse abdominalis
rectus abdominis

Question 12

what is the diaphragm and how is it innervated

Answer 12

dome-shaped
sits above the liver
innervated by phrenic nerves - C3-5
moves 1cm in quiet breathing, up to 10cm
major inspiratory muscle

Question 13

what innervates the external intercostals

Answer 13

intercostal nerves at ‘rib level’

Question 14

what is the function of the accessory muscles (sternocleidomastoid and scalenes)

Answer 14

chest expansion
intrapleural pressure falls

Question 15

what is the role of expiratory muscles during quiet breathing

Answer 15

mainly passive during quiet breathing
elastic recoil pressure is sufficient

Question 16

what is forced expiration

Answer 16

exercise, voluntary
e.g. cough, sneeze and defacation
the abdominal wall pushes the guts up against the diaphragm
involves internal intercostals

Question 17

what is the role of the pharynx/larynx in breathing

Answer 17

cranial motorneurons are important for opening/closing glottis, affecting upper airway diameter, flaring nostrils etc

Question 18

what is a respiratory rhythm generator (RRG)

Answer 18

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

Question 19

what are the properties of the RRG

Answer 19

always active even in the absence of conscious input (endogenous cyclical oscillation)
transmit in an orderly sequence to respiratory muscles

Question 20

what parts of the brain influence the RRG

Answer 20

the limbic system - emotion
sensory afferents - pulmonary stretch receptors, peripheral chemoreceptors

Question 21

what are the three phases of the breathing cycle

Answer 21

inspiration
post-inspiration
late expiration

Question 22

what are the 6 types of neuronal discharge

Answer 22

pre-inspiration
early-inspiration
inspiration
late-inspiration
early-expiration
expiration

Question 23

what is the pre-inspiration phase of the RRG

Answer 23

pre-I neurons inhibit excitatory neuronal circuit
expiratory muscles relax

Question 24

what is the early-inspiration phase of the RRG

Answer 24

early-I neurons inhibit output from entire RRG
refractory period
no breathing movements

Question 25

what is the inspiration phase of the RRG

Answer 25

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

Question 26

what is the late-inspiration phase of the RRG

Answer 26

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

Question 27

what is the early-expiration phase of the RRG

Answer 27

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

Question 28

what is the expiration phase of the RRG

Answer 28

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

Question 29

how are breathing patterns changed

Answer 29

central chemoreceptors (medulla surface) and peripheral chemoreceptors (carotid & aortic bodies, and, neuroepithelial bodies) - medullary respiratory centre - DRG - VRG - pre-botzinger complex

Question 30

what occurs during a normal breathing pattern

Answer 30

burst firing of phrenic nerve causes diaphragm contraction and relaxation

Question 31

what occurs during a breathing pattern with increased tidal volume

Answer 31

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

Question 32

how is involuntary breathing rhythm regulated

Answer 32

sensors > controller > effectors sensors = central chemoreceptors, peripheral chemoreceptors and stretch receptors effectors = respiratory muscles

Question 33

what is the role of central chemoreceptors in involuntary breathing rhythm

Answer 33

monitor pCO2 in cerebral spinal fluid

Question 34

what is the role of peripheral chemoreceptors in involuntary breathing rhythm

Answer 34

monitor pO2, pCO2 and pH in blood and mixed lung gases carotid body - blood neuroepithelial bodies - airway

Question 35

what is the role of stretch receptors in involuntary breathing rhythm

Answer 35

hering-breuer reflex inhibition of lung over-inflation (>50% resting tidal) increased breathing frequency following rapid lung deflation (exhalation > pant)

Question 36

what is the role of allergens/ irritant receptors in involuntary breathing rhythm

Answer 36

located along airway - feed into vagus nerve couch, sneeze and bronchoconstriction reflex

Question 37

how does disturbed homeostasis effect breathing

Answer 37

DRAW diagram/mindmap/schematic

Question 38

where are the chemoreceptors located

Answer 38

central = medulla surface peripheral = arterial vasculature and airway

Question 39

what is the % of normal breathing attributed to the chemoreceptors

Answer 39

central = 80% peripheral = 20%

Question 40

what do the chemoreceptors primarily detect

Answer 40

central = pH changes caused by an increase in paCO2 in cerebral spinal fluid peripheral = decreased paO2 in blood and airway

Question 41

what is the response time of the chemoreceptors

Answer 41

central = slow (minutes) peripheral = fast (seconds)

Question 42

what are the response modes of the chemoreceptors

Answer 42

central = linear peripheral = non-linear

Question 43

are the chemoreceptors adaptive by training

Answer 43

central = yes peripheral = no

Question 44

what are central chemoreceptors

Answer 44

control system for normal breathing directly responsible to CO2 driven pH changes in cerebral spinal fluid

Question 45

what is the response of central chemoreceptor to changing alveolar pCO2

Answer 45

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

Question 46

what occurs during shallow water blackout

Answer 46

1. hyperventilation drives paCO2 down 2. low central chemoreceptor sensitivity (caused by breath-hold training) fails to trigger breathing response in time to prevent severe hypoaemia 3. loss of consciousness and drowning

Question 47

what are peripheral chemoreceptors

Answer 47

carotid body - carotid sinus aortic body - aortic arch primary response is to hypoxia also respond to hypercapnia (increased paCO2) and acidosis (decreased pH)

Question 48

how do peripheral chemoreceptors respond to hypoxia

Answer 48

1. response is not linear (increases dramatically below pAO2 = 60mmHg) 2. response is driven by low partial pressure of oxygen and not oxygen concentration or HbO2 saturation. does not occur with anaemia 3. hypercapnia or acidosis raises the sensitivity of chemoreceptor to paO2

Question 49

what is the cellular mechanism of chemoreception

Answer 49

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)

Question 50

give a full overview of the cellular mechanism of chemoreception

Answer 50

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.