Carbon Dioxide and O2 Sensing

Question 1

What increases CB firing? What happens in mild to moderate exercise?

Answer 1

High mean arterial PCO2

Low mean arterial PO2

Low mean arterial pH [H+]

In mild to moderate exercise there is no change in the mean of these variables. However, the levels do vary with the respiratory cycle.

Question 2

Describe the oscillations in PCO2 with respiration

Answer 2

Expiration - CO2 added to alveolar gas. CO2 concentration and PCO2 rises.

Inspiration - CO2 added to alveolar gas but fresh (CO2 free gas) also added. CO2 concentration and PCO2 falls.

Note - concentration vs quantity. Quantity falls during expiration, rises during inspiration, but concentration is vice versa.

Question 3

What factors affect the oscillations of alveolar PCO2?

Answer 3

Slow deeper breathing will have no effect on slope, but will increase amplitude

Increased CO2 production at same breathing rate will increase both the amplitude and the slope

Question 4

What “challenges” do these oscillations face before they reach the CBs?

Answer 4

Pass through pulmonary veins and then passage through the heart.

Arterial PCO2 oscillations have been recorded as pH oscillations - easier to make rapid response pH electrode

Question 5

What did Band, 1978 show?

Answer 5

CSN discharge show a respiratory oscillation which was accompanied by oscillation in pH, presumably reflecting respiratory oscillations in PCO2.

Also, a larger infusion of saline equilibrated with 100% CO2 caused a larger drop in pH, an increase in CSN firing and an increase in TV. Small infusion showed only a (smaller) increase in TV, no apparent change in firing.

Question 6

What does the size of the response to the CO2 bolus depend upon? (timing)

Answer 6

The response is gated if the bolus arrives during inspiration

Question 7

What are the effects on a drop in pH? Chemoreflex response?

Answer 7

Increase ventilation via phrenic nerve.
Sympathetic stim -> vasoconstriction
Parasympathetic stim -> bradycardia

UNLESS, lung pressure great enough to stimulate SARs which cause a vasodilation and a tachycardia due to dis-inhibition of CVMNs

Question 8

What did Band (1980) show?

Answer 8

Arterial pH and CO2 oscillations do occur in humans.

They increase in amplitude and slope during exericse.

The increase in slope occurs within a few seconds (rapid rise CO delivers more CO2 to the lungs)

TV changes occur BEFORE slope change, so not sole mechanism of VE change with exercise

Question 9

What does CBR do to the VE responses?

Answer 9

Decreases rate of VE increase
Sub-maximal VEmax compared to controls

No extra ventilatory increase associated with the lactic acidosis of heavy exercise

pH more acidic, PaCO2 greater, PACO2 greater in CBR compared to controls

Question 10

What is the contribution of the central chemoreceptors to the VE response to exercise?

Answer 10

The change in pH of the CSF is too slow.

AA and central chemo-R are useless in responding to hypoxia or arterial metabolic acidosis.

Question 11

Why is there a transient rise in PaCO2 at the onset of exercise in CBR subjects?

Answer 11

Reflects the slowed ventilatory response to exercise.

Question 12

Why is there a more sustained increase in PaCO2 in heavy exericse?

Answer 12

Although ventilation rises in proportion to VO2 (work), there is a production of CO2 due to production H+ ions by metabolism shifting equation to the left.

Question 13

What is the normal response to hypoxia? How can it be maximised?

Answer 13

Large increase in VE, maximised by using hypercapnic air

Question 14

What is the CBR subject response to hypoxia

Answer 14

No response in ventilation. Small response if PaCO2 is increased also.

Question 15

What is the response to K+ injection? Which study?

Answer 15

Band, 1985.

Increase in Ve and firing of chemoreceptors

Question 16

Is arterial K+ seen to change during exercise?

Answer 16

Yes, but there is a mismatch K+ vs VE, so unlikely to be stimulation for ventilation during exercise

Question 17

Where are the central chemoreceptors?

Answer 17

Ventrolateral medulla, near the exit of CN IX and X

Question 18

Relationship alveolar ventilation and CSF pH

Answer 18

Linear increase ventilation with progressive acidification of CSF

Question 19

Experimental evidence of central chemoreceptors?

Answer 19

Injection acetzolamide onto specific regions, eg VRG, whilst maintaining respiration and therefore PACO2 via ventilation. Changes in ventilation would alter PaCO2 which may stimulate other chemoreceptors.

Question 20

Which regions show chemoreceptor activity?

Answer 20

NTS
VLM including retrotrapezoid nucleus
VRG
Medullary raphe

Question 21

What did Nattie (1996) conclude?

Answer 21

Each site provides a substantial effect but stimulation of many sites needed to produce the total response

Question 22

Describe the CO2 diffusion technique using microdialysis/glass pipette

Answer 22

No injection or drugs, CO2 diffuses to nearby tissues. Peak pH change at tip and respiratory response within minutes.

Enables multiple tests to be performed on same animal, with fewer non-CO2 effects

Results can be collected from unanaesthetised animal

Question 23

What is the RTN and medullary raphe contribution to chemoreceptor response?

Answer 23

Medullary raphe is only when asleep.

RTN is only when awake. Destruction of RTN caused large depression in response to CO2, suggests it may be key. Very sensitive to PCO2

Question 24

What is Ondine’s curse?

Answer 24

Congenital central hypoventilation syndrome

= respiratory arrest when asleep and a blunted or absent response to hypercapnia

Do not experience dyspnea

Do not increase breathing normally during exercise

Question 25

How is CO2 responsiveness affected when the CB reflexes are prevented or altered?

Answer 25

Depends on method.

CBD - acute or chronic

OR local perfusion with normoxic, normocapnic blood OR with hypercapnic/hypocapnic blood

Question 26

Daristotle, 1989 did what with CB?

Answer 26

Perfused CB with either normoxic, normocapnia blood or hypercapnic, hypoxic blood.

CB + central chemoreceptors are additive, no change in response slope

Hypocapnic blood led to apnoea or respiratory depression

Question 27

What did Pan, 1998 show?

Answer 27

CB important determinant of rest and exercise breathing and CO2 sensitivity.

Following CBDm there is a time-dependent fall in the response to CO2 (PaCO2 seen to increase with denervation). Plasticity eventually compensates and sensitivity of response is seen to increase to nearer pre-CBD levels.