Flashcards in Carbon Dioxide and O2 Sensing Deck (27)
What increases CB firing? What happens in mild to moderate exercise?
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.
Describe the oscillations in PCO2 with respiration
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.
What factors affect the oscillations of alveolar PCO2?
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
What "challenges" do these oscillations face before they reach the CBs?
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
What did Band, 1978 show?
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.
What does the size of the response to the CO2 bolus depend upon? (timing)
The response is gated if the bolus arrives during inspiration
What are the effects on a drop in pH? Chemoreflex response?
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
What did Band (1980) show?
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
What does CBR do to the VE responses?
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
What is the contribution of the central chemoreceptors to the VE response to exercise?
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.
Why is there a transient rise in PaCO2 at the onset of exercise in CBR subjects?
Reflects the slowed ventilatory response to exercise.
Why is there a more sustained increase in PaCO2 in heavy exericse?
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.
What is the normal response to hypoxia? How can it be maximised?
Large increase in VE, maximised by using hypercapnic air
What is the CBR subject response to hypoxia
No response in ventilation. Small response if PaCO2 is increased also.
What is the response to K+ injection? Which study?
Increase in Ve and firing of chemoreceptors
Is arterial K+ seen to change during exercise?
Yes, but there is a mismatch K+ vs VE, so unlikely to be stimulation for ventilation during exercise
Where are the central chemoreceptors?
Ventrolateral medulla, near the exit of CN IX and X
Relationship alveolar ventilation and CSF pH
Linear increase ventilation with progressive acidification of CSF
Experimental evidence of central chemoreceptors?
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.
Which regions show chemoreceptor activity?
VLM including retrotrapezoid nucleus
What did Nattie (1996) conclude?
Each site provides a substantial effect but stimulation of many sites needed to produce the total response
Describe the CO2 diffusion technique using microdialysis/glass pipette
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
What is the RTN and medullary raphe contribution to chemoreceptor response?
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
What is Ondine's curse?
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
How is CO2 responsiveness affected when the CB reflexes are prevented or altered?
Depends on method.
CBD - acute or chronic
OR local perfusion with normoxic, normocapnic blood OR with hypercapnic/hypocapnic blood
Daristotle, 1989 did what with CB?
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