CO2 carriage in blood

Describe the ways in which CO2 is carried in the blood (99B5)
Describe the role of haemoglobin in the carriage of carbon dioxide in the blood (97A3)

Carbon dioxide is carried in 3 forms

1. dissolved CO2
2. bicarbonate
3. carbamino compounds

1. Dissolved CO2

• Follows Henry's Law
  => amount dissolved is proportional to partial pressure
• is 20-25 times more soluble than O2
• at 37degrees, solubility = 0.0308 mmol/L/mmHg
• (?roughly, 0.0835mL of CO2 is dissolved in 100mL of blood per mmHg of PCO2)

2. Bicarbonate

CO2 + H2O <-CA-> H2CO3 <-> H + HCO3

• The second step occurs rapidly (pKa'=6.1) 
• Carbonic acid (H2CO3) forms a very small percentage (<1%)
• The first step occurs very slowly in plasma,
  BUT occurs rapidly in RBC due to presence of carbonic anhydrase (CA) (zinc containing enzyme)

Chloride shift

In RBC, as H2CO3 is formed (with aid of CA), it breaks down to H + HCO3

=> HCO3 diffuse out easily

=> H+ doesn't really diffuse out because RBC membrane is relatively impermeable to cations

=> As [H+] builds up, chloride diffuse into RBC to maintain electrical neurality (in accordance to Gibbs-Donnan equilibrium)
aka "chloride shift"

[See diagram 6.5 in West p81]

• Exchange of HCO3 and Cl (Hamburger effect) occurs at the transporter "capnophorin", which is a band 3 protein
• H+ are buffered by histidine

Osmolarity increase, and water enters RBC as a result

=> slight increase in RBC volume as CO2 is taken up.

3. Carbamino compound

• Formed by CO2 binding to terminal amino groups in blood protein.
• To much lesser extent amino groups in the side chains of arginine and lysine.
• Globin in haemoglobin is the most significant.
  => as with bicarbonate, RBC is the main stage.
• Hb-NH2 + CO2 <-> Hb-NH-COOH <-> Hb-NH-COO + H
  => at normal pH, almost completely dissociates
• Hb-NH-COOH is called "carbamino haemoglobin"
• Responsible for 30% of the CO2 eliminated in lung
• Not really affected by PCO2

Imidazole group of histidine

• Imidazole group of the amino acid histidine is the only real effective buffer in the normal range of pH (pKa 6.8)
• The buffering power of plasma protein is more or less proportional to their histidine content.
• Haemoglobin has 38 histidine residues, far more than plasma proteins

Buffering

Both carbonic acid and carbamino haemogoblin almost completely dissociate

=> H+ are produced

=> buffered by histidine

As haemoglobin becomes reduced (i.e. deoxyHb)

=> it becomes less acid / better base

=> it becomes a better buffer

Haldane effect

Haldane effect refers to the increased ability of blood to carry CO2 when haemoglobin gives up oxygen.

Haldane effect is due to:

• DeoxyHb is 3.5 times more effective than oxyHb in forming carbamino compounds.
  => accounts for 70% of the Haldane effect
• DeoxyHb is a better buffer than oxyHb, thus improving CO2 carriage as bicarbonates
  => accounts for 30% of the Haldane effect

NB: Bohr effect refers to increased unloading of O2 from Hb when carbon dioxide is loaded
(causing pH drop, and thus right shift in oxygen dissociation curve)

CO2 dissociation curve

[See diagram...]

• more linear than O2 dissociation curve
• more steep than O2 dissociation curve
  => smaller change in PCO2 when content changes
• as PaO2 drops, affinity for CO2 increases
  => CO2 dissociation curve moves to the LEFT (Haldane effect)

Carriage in arterial blood vs venous blood

Arterial blood contains 48 mLs of CO2 per 100mL blood.

Venous blood contains 52 mLs of CO2 per 100mL blood.

Total carriage

• 5% - Dissolved CO2
• 90% - Bicarbonate
• 5% - Carbamino compounds

% Contribution to A-V difference

(i.e. % of CO2 eliminated at lung)

• 10% - Dissolved CO2
• 60% - Bicarbonate
• 30% - Carbamino compounds

Additional notes

Due to storage of CO2 as bicarbonate, changes in PaCO2 due to changes in ventilation takes a little longer to equilibrate than PaO2.

 

Factors affecting PCO2 in steady state

Alveolar CO2 conc. x alveolar ventilation = CO2 output

• Alveolar ventilation
• Concentration effect
  => when inert gases are taken up rapidly, PACO2 is increased due to concentration effect
• CO2 output
• Inspired FICO2

Examiner's comment

• relative importance of each CO2 carriage method in arterial and venous blood
• why the percentage differ in the way it differs
• Haldane effect and its importance
• include chloride shift
• ? effects on haematocrits
• carboxyhaemoglobin refers to carbon MONOxide with haemoglobin
• carbaminohaemoglobin is CO2 with haemoglobin

 

To be added later

????Factors that move the CO2 dissociation curve