L19. Carbon dioxide transport and chemical control of breathing

Question 1

What are the ways CO2 is transported in the blood

Answer 1

1. Dissolved in plasma as CO2; very soluble
2. In form of HCO3- (bicarbonate) which can be rapidly formed in RBC or slowly formed in plasma
3. Combines with proteins to form carbamino groups: eg. Hb-NH2 + CO2.; Hb has higher affinity for CO2 and there is more of Hb than other plasma proteins.
4. As Carbonic acid (H2CO3) and carbonate (CO3(2-) ions.

Question 2

What reaction forms HCO3- (bicarbonate), and what is the catalyst for rapidly formed. What drives this equation to the right?

Answer 2

CO2 + H2O –> H2CO3 –> H+ + HCO3-
Carbonic anhydrase in RBC helps to rapidly form H2CO3 which is the rate limiting step for formation of HCO3-.

The H+ formed is buffered by Hb to form HHb which encourages teh equation to the equation to the right.

Question 3

What is Cl- shift

Answer 3

To maintain electroneutrality of the RBC,
At the lungs: It is exit of Cl- ions in comparison to HCO3- ions entering the RBC
At the tissues: It is entry of Cl- ions compared to HCO3- ions leaving the RBC

Question 4

How does CO2 dissociation curve differ from O2 dissociation curve

Answer 4

There are two curves, one for arterial and one for venous blood. The actual curve is steeper than expected because it is the join between two curves which is linear over the physiological range of PCO2- this makes it very sensitive to changes in PCO2.

There is no plateau of max PCO2 as CO2 is very soluble in plasma so no saturation.

Question 5

What is the Haldane effect

Answer 5

HbO2 has less affinity for CO2 than Hb. This causes arterial blood (mainly HbO2) to have a curve displaced to the right (lower HbCO2 content for same PCO2).
At lower PO2 there is greater affinity for CO2 uptake into tissues. This enhances unloading of CO2 from tissues into blood.

Question 6

What is the location and nerve tract of the Peripheral chemoreceptors to the brain -

checking blood content to the body & head

Answer 6

Aortic arch (aortic bodies) uses vagal nerves (CNX), 
Carotid bifurcation (Carotid bodies) uses glossopharyngeal nerve (CNIX) 

Goes to nucleus tractus solitarii in medulla oblongata: Dorsal respiratory group for the heart.

*Can stimulate central chemoreceptors

Question 7

What are the cell types in peripheral chemoreceptors and what regulates their sensitivity. Where are the cell bodies for their nerves?

Answer 7

They have Type 1 cell: glomus cell detect low PaO2 and (Type 2 cell: supporting cell).

Sensitivity is inversely related to blood flow and therefore symp activation can decrease sensitivity to hypoxia.

Carotid sinus nerve has cell body in the petrosal ganglia and aortic has it in nodose ganglia

Question 8

What are the stimulants of peripheral chemoreceptors

Answer 8

1. Hypoxia, or/ w Hypercapnia (summative as less sensitive to CO2)
2. Haemorrhage, hypotension: reduced delivery of O2
3. Acidosis: low pH
4. Increased symp activities: constricting arterioles, reducing blood flow
5. Sodium cyanide

Question 9

What is the output of the reflex response for activated peripheral chemoreceptors

Answer 9

Increases the rate and depth of breathing (minute ventilation) via brainstem respiratory neurones.

• Symp Tachycardia, peripheral vasoconstriction, activate RASS and release of adrenaline to increase BP

Question 10

What is the location of the Central chemoreceptors

Answer 10

Neurones 0.5 mm beneath the surface of 3 chemo-sensitive regions on Ventral surface of Medulla oblongata, on either side of the basilar artery.

Question 11

What is the stimulants of central chemoreceptors and the output

Answer 11

Chemoreceptors sense increase in H+ (reduction in pH). Not hypoxia.

Plasma H+ cannot cross the blood brain barrier.
CO2 can cross the barrier and forms HCO3- and H+ in the Cerebrospinal fluid (with help of small carbonic anhydrase but mostly spontaneous)

The output is to increase minute volume by acting on brainstem respiratory neurones

Question 12

What are the steps of reflex control of chemoreceptors

Answer 12

Reflex control systems:

1. Chemoreceptor- stimulus causes release of neurotransmitter to stimulate afferent nerve
2. Central Nervous system: Brainstem respiratory network
3. Effector/ target organ:
4. Feedback

Question 13

Describe the ventilatory response to hypoxia

Answer 13

Uses Peripheral chemoreceptors

1. Exponential increase in ventilation as drop in O2
2. Peak ventilatory response around 25 PaO2
3. Depression: direct effect of low O2 on the brain which generates the respiratory rhythm action potential
4. Apnoea; breathing stops. Die or autoresussitate by gasping by medulla oblongata neurons insensitive to hypoxia.

Question 14

Compare the ventilatory response to hypercapnia and hypocapnia

Answer 14

Peripheral and central chemoreceptors react 2:8. Usually flat plateau in ventilation. At above normal CO2, strong Minute ventilation increase.

In Hypocapnia CO2 falls after hyperventilation, so removes stimulation for Central chemoreceptors from firing to increase minute ventilation. This suppresses the hyperventilatory response- tries to get to normal

Question 15

What is Ondines curse

Answer 15

Congenital syndrome where central chemoreceptors have absent transcription factor which is important for breathing during sleep. CO2 stimulates central chemoreceptors which drive breathing in sleep.

Question 16

What are the 5 steps for O2 uptake and CO2 release by the RBC at the Alveolus
Why?

Answer 16

At the lungs there is low CO2 so the steps reverse from at the tissues

1. O2 moves from the alveolus into the RBC to combine with Hb, which will release H+.
2. HCO3- will move back into the RBC because conc gradient. Cl- will exit the RBC.
3. Increased HCO3- and H+ make H2CO3, which makes H2O and CO2 by carbonic anhydrase
4. H2O then moves into the plasma
5. CO2 then diffuses out of the RBC to the alveolus.

Question 17

What is are the 6 steps for CO2 uptake and O2 release by the RBC at the tissues

Answer 17

1. CO2 produced in the tissues diffuses into plasma and RBC where some dissolves.
2. Majority in RBC react with water to make carbonic acid with carbonic anhydrase, Then make Bicarbonate + H+.
3. Bicarbonate diffuses out of RBC into plasma and Cl- moves in to maintain electroneutrality.
4. H+ buffered by HbO2 to prevent lowering pH. Makes O2 + HHb
5. O2 diffuses into tissue
6. CO2 can also combine with HHb to form carbamino compounds.

Question 18

What are main differences between peripheral and central chemoreceptors as well as ventilatory response to hypercapnia

Answer 18

Peripheral chemoreceptors are tonically active at resting conditions.
Sense low O2 (some CO2). Response time is: Within a breath

Central only does H+- hypercapnia but slow response time: 40-50 seconds due to limited carbonic anhydrase. Its response can be inactivated by hyperventilating