CO2 Carriage in Blood and Acid-Base Equilibrium Flashcards
What are buffer systems?
Buffer systems: minimise changes in the free
H+ concentration and are usually comprised of a weak acid and weak base in equilibrium.
What are the 3 main buffer systems in the blood?
- Bicarbonate
- Haemaglobin
- Plasma Proteins
Where is CO2 produced, approximately how much is produced per 1L of blood and how is it excreted?
CO2 is produced in mitochondria during the Kreb’s (Citric acid cycle).
Approximately 510ml/L of blood is produced.
CO2 diffuses down a gradient into the blood to get to the alveoli where is then is excreted via respiration.
How is CO2 transported in the blood?
- As a solution dissolved directly in the blood.
PCO2 × solubility coefficient = CO2 concentration in solution - As Bicarbonate Ions
- Carbamino carriage
Describe how Bicarbonate is formed?
Bicarbonate formation is a 2 stage process:
Stage 1: H2O + CO2 combines to form carbonic acid. This reaction is catalysed by carbonic anhydrase*. CO2 + H2O ↔ H2CO3
Stage 2: Carbonic acid reversibly dissociates to form a H+ ion and bicarbonate. H2CO3 ↔ H+ + HCO3−
*Without Carbonic Anhydrase this reaction would take several minutes.
How does carbonic anhydrase work?
Carbonic anhydrase is a zinc containing low molecular weight enzyme. The zinc is the basis of the catalysis:
- Zinc +H2O –> Zn-OH- species + H+
- Histidine molecule removes H+ from the Zn and transfers it to the buffer molecules
- Zn-OH- + CO2 –> ZnHCO3- –> dissociation from zinc.
The reaction is very fast and limited only by the presence of surrounding buffers to provide/remove H+ ions to/from the enzyme.
There are 16 isoenzymes of CA, 11 of which are present in humans.
What is acetazolamide, when is it used and what have studies of acetzolamide shown?
Acetazolamide is a carbonic anhydrase inhibitor, which is used in altitude sickness. (Less HCO3- is produced, resulting in a metabolic acidosis, encouraging the body to hyperventilate, i.e. speeds up acclimitisation.
Studies using acetazolamide has shown that >98% CA activity must be blocked before there is any discernible change in carbon dioxide transport.
What is the henderson hasselbach equation?
The Henderson–Hasselbalch equation can be used to estimate the pH of a buffer solution.
pH= pKa + log [Base]/[Acid] where pKa is the acid dissociation constant
What is the Henderson Hasselbach equation for CO2?
pH = 6.1 + log [HCO3-]/[∝PCO2]
pKa for CO2 = 6.1 but this varies with temperature and pH.
H2CO3 cannot be measured so the term is replaced by “proportional to PCO2”
How does Carbamino Carriage occur?
CO2 combines with amino groups (R-NH2) which forms Carbamic acid (RNCOOH)
Carbamic acid is a weak acid which reversibly dissociates to Carbamate (RNCOO) + H+. This therefore also acts as a buffering system.
An amino group is vital for this reaction therefore it is limited to the ends of protein chains and the side chain amino groups found in lysine and arginine.
Why is pH important in carbamino carriage?
The CO2 competes with H+ to react with the amino group therefore it is less likely to occur in acidic conditions.
Which molecule is most responsible for caramamino carriage in the blood?
Haemaglobin.
Deoxyhaemoglobin is about 3.5 times as effective as oxyhaemoglobin at carbamino carriage.
This is a major contributor to the Haldane effect.
The other contributor to the Haldane effect is changes in the dissociation state of histidine residues in the Hb molecule
What is the Haldane Effect?
The Haldane effect is the principle that CO2 has a higher affinity for deoxyhaemaglobin than oxyhaemaglobin.
Therefore the proportion of carbamino carriage of CO2 in venous blood is higher than arterial blood.
The affinity for haemoglobin to CO2 progressively improves along the systemic capillary system as O2 is delivered to tissues.
What is the Hamburger shift?
The Hamburger shift is another buffering technique within RBC.
Excess HCO3- ions produced in the RBC are actively exported in exchange for Cl- ions facilitated by the ‘Band 3’ membrane protein. This is a ping pong effect rather than simultaneous exchange.
Band 3 membrane proteins are loosely bound to (intracellular) carbonic anhydrase increasing efficiency of removal of HCO3-.
What is hereditary spherocytosis?
Hereditary spherocytosis (HS) is a congenital haemolytic disorder. There are autosomal dominant and autosomal recessive variants.
It results in a gene defect which effects Band 3 membrane proteins. Band 3 is attached to the RBC cytoskeleton, in HS this results in the RBC being a speroidal shape which makes them more prone to haemolysis.
