Session 4 - Carbon dioxide in blood + chemical control of breathing

Question 1

How much Carbon dioxide is in arterial blood compared to oxygen? Why?

Answer 1

21 mmol/L
Almost 2.5x as much Co2. (oxygen = 8.9mmol/L)
Co2 is more soluble than oxygen.

Question 2

Why is control of Co2 important in arterial blood?

Answer 2

Control of Co2 is important as concentration of Co2 determines pH.

Question 3

How does some CO2 react with water in plasma?

Answer 3

CO2 + H20 > H2CO3 > H+ + HCO3-

Forms carbonic acid (H2CO3) which quickly dissociated, forming protons and bicarbonate ions.
Reversible!

Question 4

Which factors affect the pH of plasma?

Answer 4

1) How much CO2 reacts to form H+
2) How much CO2 is dissolved in it
3) The concentration of hydrogen carbonate

Question 5

What affects how much CO2 forms H+?

Answer 5

• More dissolved CO2, pushed reaction to the right, more protons.
• Less dissolved CO2, pushes reaction the left, less protons.

Question 6

How does dissolved CO2 change the pH? What is the main control of this?

Answer 6

• pCO2 Rises - plasma pH FALLS.
• pCO2 falls - plasma pH RISES.
• pCO2 of alveoli is the determining factor, as the amount of CO2 dissolved is directly dependent of partial pressure of CO2.

Question 7

Roughly how much hydrogen carbonate is present in the blood? Which cation is associated with it?

Answer 7

Around 25mmol/L of HCO3-
Main cation is Na+, not H+
Therefore this high bicarbonate conc. is not from CO2 in plasma.

Question 8

Why does most of the dissolved CO2 not react in the plasma?

Answer 8

Due to the high concentration of bicarbonate ions.

Means the equilibrium is pushed to the left, where most CO2 does not react.

Question 9

Why is the pH of blood slightly alkaline?

Answer 9

Due to the dissolved bicarbonate ions.

Question 10

Which equation can be used to calculate the pH of blood from CO2 and bicarbonate concentration?

Answer 10

Henderson Hasselbalch.
pH = pK + Log ([HCO3-]/(pCO2 x 0.23))

pK is a constant = 6.1 at 37C
(0.23 is CO2 solubility constant)

Question 11

Which main factors then are responsible for the pH of arterial blood? What controls these factors?

Answer 11

Ratio of [HCO3-] and pCO2.
Breathing rate changes pCO2.
Kidneys vary excretion of HCO3-

Question 12

What determines the pCO2 of arterial blood?

Answer 12

The rate of ventilation in the lungs.

Question 13

How is hydrogen carbonate produced in the red blood cells?

Answer 13

Carbonic Anhydrase
Reaction is forward, as H+ binds to Haemoglobin, and bicarbonate is removed by the chloride bicarbonate exchanger.
(1 bicarbonate out, 1 chloride in)

This allows bicarbonate to be made more readily in the RBC.
Creates plasma level of 25mmol/L of bicarbonate.

Question 14

What determines the amount of bicarbonate that erythrocytes produce?

Answer 14

The amount of H+ that binds to negative sites in haemoglobin.

Question 15

What is the relationship between plasma [HCO3-] and pCO2?

Answer 15

[HCO3-] doesnt change much with pCO2.

Question 16

How is the amount of HCO3 in the blood controlled?

Answer 16

Kidneys vary the amount by varying secretion.

Question 17

How does hydrogen carbonate buffer extra acid with only minimal changes in pH?

Answer 17

Acids (e.g. lactic, keto, sulphuric) react with bicarbonate forming CO2.
Therefore [HCO3-] goes down.
The extra CO2 is removed by breathing.

Question 18

Why is pCO2 slightly higher in venous blood?

Answer 18

From metabolically active tissues, which produce CO2.

Question 19

How does oxygen binding to Hb affect proton buffering?

Answer 19

• If more O2 binds Hb = R-state, less H+ ions bind. (at lungs)
• If less O2 binds Hb = T-state, more H+ ions bind (at tissues)

Question 20

Why are the proton binding properties of Hb important for CO2 transport in venous system?

Answer 20

At low O2 binding in tissues, T state of Hb allows MORE H+ to bind.
This allows MORE HCO3- to be produced.
This means there is MORE CO2 present in plasma in venous blood.
(in both dissolved and reacted form)

Question 21

Why is there little change in pH in venous blood when more cO2 is dissolved?

Answer 21

More HCO3- produced (as more H+ bind to Hb in R state).
[dissolved CO2] increases a little.
Both increase together, so little change in pH, as pH uses pk + log(HCO3- / pCO2 x 0.23)

Question 22

How is extra CO2, stored as HCO3 in venous blood, removed at the lungs?

Answer 22

• Hb picks up O2 at lungs, goes into R-State.
• Causes extra H+ it took up to be given up.
• H+ reacts with HCO3- producing CO2.
• CO2 is breathed out.

Question 23

What are carbamino compounds?

Answer 23

Co2 bound directly to amine groups on Hb.
More binds at tissues due to >pCO2.
Given up at lungs.

Question 24

So, which three forms is CO2 transported in?

Answer 24

1) Dissolved CO2
2) As hydrogen carbonate
3) As carbamino compounds

Question 25

How much CO2 is in arterial, and venous blood. What does this show?

Answer 25

Arterial = 21.5 mmol/L
Venous = 23.3 mmol/L
So only 1.8mmol/L is transported.
The rest is part of the pH buffering system.

Question 26

What is hyper/hypo-capnia?

Answer 26

Rise / Fall in pCO2.

Question 27

What is hypoxia?

Answer 27

Fall in pO2.

Question 28

In exercise what happens to pCO2 and pO2?

Answer 28

pO2 drop.
pCO2 increase.
Increased ventilation rate rectifies this.

Question 29

What physiological changes happen in hyperventilation? How is it corrected?

Answer 29

• Increase in ventilation without metabolic change.
  p02 increase
  pCO2 decrease.
  Must decrease ventilation (paper bag?)

Question 30

What happens in hypoventilation? How is it fixed?

Answer 30

Decreased ventilation with no metabolic change.
pCO2 Rises.
pO2 falls.
Ventilation must be increased. (prevent acidosis)

Question 31

What may correction of pO2 changes, without pCO2 change, cause?

Answer 31

E.g Hypoxia.
Less oxygen available, but CO2 remains level.
Breathing increases/ more oxygen available, so more CO2 lost.
Can cause hypocapnia.

Question 32

What problems can increases and decreases in pH outside the normal range cause?

Answer 32

pH < 7.0 enzymes are denatured

pH > 7.6 free calcium concentration drops leading to tetany.

Question 33

How is respiratory alkalosis and acidosis compensated for?

Answer 33

Kidneys will change the secretion of bicarbonate, over 2-3 days, to adjust pH.

Question 34

What is metabolic acidosis, how is it corrected?

Answer 34

When acid produced by tissues reacts with bicarbonate, leading to lower [HCO3-] and fall in pH.

Increase in ventilation lowers pCO2, restores pH to normal balance (restore ratio of pCO2 to bicarb)

Question 35

What is metabolic alkalosis? How is it corrected?

Answer 35

• If plasma [HCO3-] rises (e.g. after vomiting)
• Plasma pH rises.
• metabolic alkalosis.
• Can be compensated for to a degree by decreasing ventilation.

Question 36

How is blood pO2 measured and fedback to the control centres? What happens?

Answer 36

Carotid and aortic bodies have peripheral chemoreceptors.
- Large fall in O2 stimulates:
>Increase breathing
>Changes in heart rate
>Changes in blood flow distribution (e.g. more to brain, kidneys)

Question 37

How are changes in pCO2 detected and rectified in the body?

Answer 37

• Central chemoreceptors in the medulla of the brain are much more sensitive to pCO2.
• Detect changes in arterial pCO2
• Small rise pCO2 > ventilation
• small fall pCO2 < ventilation
  Basis of negative feedback of breathing.

Question 38

Why does HCO3- and H+ not affect the central chemoreceptors in the brain which detect CO2?

Answer 38

Blood brain barrier impermeable to these ions, prevent them affecting the ECF or CSF.

Question 39

Which ion is responsible for stimulating the chemoreceptors in the brain, how is it made?

Answer 39

Protons.
CO2 diffuses across Blood brain barrier.
Carbonic anhydrase catalyses it to H+ and HCO3-.
H+ stimulates the receptors (showing decreased pH)

Question 40

What determines the bicarbonate concentration in the cerebrospinal fluid?

Answer 40

The Choroid plexus cells.
Are responsible for setting ‘baseline’ concentration.
Over time if persistent change in pH, bicarbonate concenrtration of CSF can be corrected by these cells.

Question 41

What may happen the pH control system with persisting hypoxia?

Answer 41

Hypoxia detected by peripheral chemoreceptors.
Ventilation increased.
But pCO2 will FALL further.

SO:

• CSF composition compensates.
• Choroid plexus cells selectively add H+ or HCO3- into CSF, and chemoreceptors ‘accept’ new pCO2 as normal.

Question 42

How would persistent hypercapnia affect the CSF and choroid plexus?

Answer 42

Constant low pH, too acidic for neurones.
choroid plexus cells add HCO3- into CSF.
Receptors accept the new high pCO2 level.