Acid-Base Control of Respiration

Question 1

what are the fluid-filled spaces called in the brain? - what are they? (4)

what is the fluid inside them called?

Answer 1

fluid-filled spaces: **cerebral ventricles:

• lateral ventricles
• third ventricles
• fourth ventricles**

fluid: cerebral spinal fluid

Question 2

where does blood -> CSF?
what does this mean that CSF components are?

what is the normal pH of CSF?

Answer 2

• *choriod plexus**
• water and small ions transported out of capillaires in tissues (choriod plexus)
• fluid that escapes: CSF
• location: lateral ventricles
• function: retains proteins, but allows water and electrolytes to go into CSF: no proteins

-pH of CSF: 7.2

Question 3

describe the difference in pH buffering capacity of blood and CSF - why?

Answer 3

• CSF = lower pH buffering capactiy c.f. blood
  due to lack of proteins

Question 4

describe pathway of Co2 in the blood -> bicarbonate and protons in brain
what detects differences of pH in brain & where located?

Answer 4

• Co2 diffuses through BBB -> CSF
• reacts with H20 = carbonic acid
• carbonic acid converted to protons and bicarbonate by **carbonic anhydrase
• centralchemoreceporsonmedulla**oblongata (ventral surface) sense to pH of CSF

Question 5

explain the negative feedback of decreased ventilation causing increased ventilation

Answer 5

decreased ventilation:

• causes more Co2 in blood
• causes more co2 in CSF
• increases CSF acidity (more protons in the CSF)
• detected by chemoreceptors
• increased synapses to **respiratory neurons in medulla
• causesincreased rate and depth of breathing:** co2 blown off = decreased CO2 & decreased ventilation

Question 6

?? pH regulates breathing rate

Answer 6

CSF pH regulates breathing rate

Question 7

which receptors determine the rate of breathing?
which receptors determine when inspiration stops?

where do u find ^ and what is MoA?

Answer 7

• *-rate** of breathing: central chemoreceptors
• when inspiration stops: lung stretch receptors

lung stretch receptor location: bronchioles and small bronchi
MoA:
- increase firing during lung inflation
- signal, via vagus nerve to resp. centre in pons and medulla when lungs fully inflated
- inhibits inspiration

Question 8

what are irritant receptors and what do they detect? & where located?
function?

what are J-recepotrs? what do they cause? when?

Answer 8

irritant detectors:

• **mechanoreceptors
• t**rachea and large bronhi
• cause cough reflexes**

j-receptors

• chemoreceptors
• stimulate and increase in ventilation
• respond to events like pulm. oedema, pneomonia

Question 9

what does this graph show:

with regards to ventilation response of alveolar partial presure of CO2?
what is effect of hypoxia with regards to hypercapnia?

Answer 9

• ventilation response of alveolar partial presure of CO2 is linear: breathing increaeses when partial pressure of co2 increases
• graphs become steeper when partial pressure of o2 is low: hypoxia enhances the respiratory response to hypercapnia

Question 10

what is the main chemical drive of ventiliation?

explain whether hypoxia is important for driving ventilation

Answer 10

• there is very little increase of ventilation when oxygen decreases / hypoxia: only when we get to very low oxyxgen - below 60 mm Hg, do we see an increase in ventilation rate (bottom two lines)
• when hyercapnia occurs - quickly drives increase in ventilation

main chemical drive of ventilation is the level of carbon dioxide, as sense by acidity of CSF.
but
hypoxia is important: it increases the sensitivity of resp. centres to hypercapnia but its not itself a powerful drive for ventilation until it becomes severely low.

Question 11

where is hypoxia detected? (2)
describe innervation pathway from ^ to the brainstem resp. centre

Answer 11

peripheral chemoreceptors:
-carotid bodies at the bifurcation of the common carotid arteires
AND
- aoritc bodies

• both detect reduced PaO2 & plasma pH

pathways:
aortic bodies –> vagus nerve -> resp. centre
carotid bodies–> short carotid sinus nerve -> glassopharyngeal nerves -> brainstem

Question 12

which cranial nerve is the glassopharnygeal nerve?

Answer 12

CN IX

Question 13

what are the two types of cells that are found in the carotid bodies?

Answer 13

carotid body cells:

• type 1 glomus cells: release NT (including ACh) that stimulate glosspharyneal afferent nerves
• *- type 2 glomus cells:** resemble glia

Question 14

describe MoA of hypoxia being detected and causing AP

Answer 14

• hypoxia causes closure of K channels
• causes depolarisation
• depol. triggers voltage-sensitve Ca2+ channels
• triggers release of ACh
• act on receptors @ afferent nerve fibres adjacent to glomus cell = AP

Question 15

what is the Hering-Breur Inflation Reflex?

Answer 15

name for reflex undergone by Pulmonary stretch receptors

Question 16

what other innervaton ocurs at the carotid bodies? (2)

Answer 16

1) carotid bodies also have efferent nerve fibres from sym & para NS:
- constrict or dilate capillaries as they pass through the carotid body and regulate the pa02

2) plasma pH detected (as well as hypoxia) at carotid bodies and has afferent nerve fibres

Question 17

explain what nerve fibre firing is like for the carotid bodies: at normal arterial PaO2 (~100 mmHg) c.f. when 60 mm Hg (hypoxia).

Answer 17

• At normal arterial PO2 (approx. 100mmHg) the carotid body nerves are nearly silent
• when hypoxia (PO2 of approx) 60mmHg, carotid body response increases: shows that we are not sensitive to hypoxia (if C02 levels are normal)

Question 18

in normal healthy individuals - most of urge to breathe comes from where?

Answer 18

Thus in normal healthy individuals, most of the urge to breathe comes from central chemoreceptors (bc when a normal subject is given a CO2 mixture to breathe, less than 20% of the ventilatory response can be attributed to the peripheral chemoreceptors)

Thus in normal healthy individuals, most of the urge to breathe comes from hypercapnia working on the central chemoreceptors. However, this response is modulated and amplified by arterial hypoxemia, detected in the the peripheral chemoreceptor. (do become active and their action is to potentiate the drive from hypercapnia)

Question 19

where are the groups of neurons that control respiration?
what are the three main groups ? ^

Answer 19

• pons and medulla: where the neurons are that control respiration: aka respiratory centres
• 3 main groups:
  a) medulla
  b) reticulospinal tract
  c) phrenic nerve

Question 20

where do the respiration innervation outputs each of the following arise?

a) medulla
b) reticulospinal tract
c) phrenic nerve

Answer 20

a) medulla: projects down the reticulospinal tract to activate the diaphragm for inspiration
b) reticulospinal tract: arises in the pons and medulla
c) phrenic nerve: arises in the neck from C3, 4, 5 root

Question 21

phrenic nerve supplies
motor innervation for what?
sensory fibres for what?

Answer 21

motor innervation: diaphragm
sensory fibres: diaphragmatic pleura and peritneum

Question 22

what is the role of the nucleus of the solitary tract? (NTS) (2) how does it do this?
which nerves does the NTS recieve inputs from (2), which come from which receptor? (4)

Answer 22

• *nucleus of the solitary tract:**
• function:
  a) The NTS is the integrating centre: it projects to the dorsal respiratory group which contains cells activate the diaphragm, resulting in inspiration
  b) Expiration is passive, therefore only inspiratory group of neurons are present

inputs**:

• pH detectors
• pulmonary stretch,
• cough
• J receptors**

innervation:
- Afferents come up the glossopharyngeal and vagus nerves and synapse in the NTS

Question 23

for forced expiration - which neurons become active? what do they send axons down?

Answer 23

During forced expiration, neurons in the ventral respiratory group in the ventral medulla become active & their axons project down the reticulospinal tract and activate the internal intercostals

Question 24

respiratory centres are modulated by which two other regions in the potine reticular formation?

Answer 24

• *apneustic centre**
• apneustic (‘no breathing’) centre is the second modulating system for the medullary, dorsal and ventral roots
• Stimulation prolongs inspiration: maintains contraction in the diaphragm despite negative feedback from stretch receptors in the lung
• *pneumotaxic centres**
• The pneumotaxic centre modules (mainly by inhibition) the apneustic centre: decreasing tidal volume and respiratory rate

Question 25

what regulates breathing for vocalisation?

can you override the medullary centre for breathing?

Answer 25

The cerebral cortex acts via the pneumotaxic and apneustic centres to regulate breathing for vocalisation

This regulation enables us to talk, sing, hold our breath voluntarily

However, these centres cannot completely override the medullary centres.

Thus, you cannot voluntary stop breathing to the point of death

Question 26

what is cheyne-stokes breathing?

what is this characterise by?

what does it indicate?

Answer 26

• *Cheyne-Stokes breathing**
• If sensory input to the medulla is damaged (NTS/ nerves from glossopharyngeal nerve damaged), then respiration continues but in a form known as Cheyne-Stokes breathing:
• Respiratory centres work spontaneously, without feedback
• characterised by: gradual increase in depth and rate of breathing followed by a gradual decrease, that results in a temporary stop in breathing called an apnoea
• indicates: damage to the brainstem or inputs from respiratory receptors to the brainstem

Question 27

when do u see Cheyne-Stokes breathing occur?

Answer 27

patients with heart failure, strokes that affect the blood supply to the medulla, hyponatremia, traumatic brain injuries and brain tumours of the brainstem.

It can occur in all forms of toxic metabolic encephalopathy

It is a symptom of carbon monoxide poisoning, along with syncope or coma

Often seen after morphine administration

Question 28

dorsal group drives what?
ventral group drives what?

what does apneustic centre drive?
what does pneomotaxic centre do?

Answer 28

dorsal group drives inspiration
ventral group drives expiration if necessary

apneustic: enables voluntary breath holding
pneomotaxic: modulates other centres and allows vocolisation etc