Blood Gas Transport

Question 1

What determines how much gas dissolves in a liquid?

Answer 1

• The concentration of a gas dissolved within a liquid is determined by the partial pressure and solubility of a gas.
• Concentration ∝ partial pressure x solubility.
• If a liquid is placed in contact with a gas, some of the gas will dissolve into it (an amount proportional to the partial pressure of the gas).

Question 2

Why is haemoglobin critical to O₂ transport?

Answer 2

• Oxygen has low solubility in plasma (0.225ml/L/kPa).
• In order to dissolve the amount of O₂ needed to supply tissues, an impossible high alveolar PO₂ would be required.
• The presence of haemoglobin overcomes this problem - it enables O₂ to be concentrated within the blood (increasing the carrying capacity) at gas exchange surfaces and then released at respiring tissues.
• The vast majority of O₂ transported by the blood is bound to haemoglobin (> 98%).

Question 3

How is the oxygen content of blood measured/defined (3 ways)?

Answer 3

1. O2 partial pressure (PaO₂) expressed as kPa ≈ “the partial pressure of O2 within a gas phase (at a gas-liquid interface) that would yield this much O2 in the plasma at equilibrium”
2. Total O₂ content (CaO₂) expressed as ml of O₂ per L of blood (ml/L) ≈ “what volume of O2 is being carried in each litre of blood, including O2 dissolved in the plasma and O2 bound to Hb?”
3. O2 saturation (SaO2 = measured directly in arterial blood, SpO2 = estimated by pulse oximetry), expressed as %, ≈ “What % of total available haemoglobin binding sites are occupied by oxygen?”

Question 4

What does the oxygen-haemoglobin dissociation curve represent? What shape does it have?

Answer 4

• The oxygen-haemoglobin dissociation curve represents the affinity of haemoglobin for oxygen.
• It shows the relationship between O2 concentration, partial pressure and saturation.
• It has a sigmoidal shape.
• The sigmoidal shape of the curve is produced by: -
  
  • Cooperative binding (that the oxygen-haemoglobin affinity increases as more oxygen molecules bind, due to changes in the shape of the protein).
  • Saturation of oxygen sites.

Question 5

Why is haemoglobin so effective at transporting O2 within the body?

Answer 5

1. The structure of haemoglobin produces a high O₂ affinity, therefore, a high level of Hb-O₂ binding (and saturation) requires relatively low PO₂.
2. The concentration of haem groups and haemoglobin contained in the RBCs enables a high carrying ability.
3. The oxygen-haemoglobin binding curve shifts to offload oxygen to demanding tissues.
4. Haemoglobin O₂ affinity changes depending on the local environment, enabling O₂ delivery to be coupled on demand.

Question 6

_____ acts as an O₂ reservoir within muscle tissue and only releases O₂ at low PO₂.

Answer 6

Myoglobin

Question 7

_____ haemoglobin has a higher O2 affinity and effectively steal O2 from maternal Hb.

Answer 7

Foetal

Question 8

What is cyanosis? What are the two types?

Answer 8

• Cyanosis is the purple discoloration of the skin and tissue that occurs when the [deoxyhaemoglobin] becomes excessive.
• The two types are:-
  
  • Central cyanosis -
    
    • Bluish discoloration of core, mucous membranes and extremities.
    • Inadequate oxygenation of blood.
    • E.g. hypoventilation, V/Q mismatch.
  • Peripheral cyanosis -
    
    • Bluish coloration confined to extremities (e.g. fingers).
    • Inadequate O2 supply to extremities.
    • E.g. small vessel circulation issues.

Question 9

What is anaemia? What are its causes and what can it lead to?

Answer 9

• Anaemia is a decrease in the total amount of red blood cells (RBCs) or hemoglobin in the blood, or a lowered ability of the blood to carry oxygen.
• Causes of anaemia (insufficient RBCs or haemoglobin):
  
  • Iron deficiency (↓ production).
  • Haemorrhage (↑ in loss of blood).
• Anaemia can lead to hypoxia.
• Hypoxia can occur despite adequate ventilation and perfusion, if the blood is not able to carry sufficient oxygen to meet tissue demands.

Question 10

What is the difference between hypoxia and cyanosis?

Answer 10

• Hypoxia is the low O2 concentration in the blood and so deficiency in the amount of oxygen reaching the tissues.
• Cyanosis is the visible blueness due to increased levels of deoxygenated haemoglobin.
• This means that cyanosis is absent in conditions such as anaemia (as anaemia is the lack of haemoglobin).

Question 11

How, and why, does the transport of CO2 differ to the transport of O2?

Answer 11

1. CO₂ has a higher H₂O solubility than O₂ does - therefore, a greater percentage of CO₂ is transported simply dissolved in plasma (CO₂ ~ 7%, O₂ ~ 1%).
   
   • Concentration = partial pressure X solubility
2. CO₂ binds to haemoglobin at different sites than O₂ does (R–NH2 residues at the end of peptide chains, forming carbamino-Hb, R-NHCOOH), and with a decreased affinity. Thus, a lower percentage of CO₂ is transported in this manner (~ 23%).
3. C​O₂ reacts with water to form carbonic acid, which accounts for the majority (~ 70%) of the CO₂ transported.
   
   • CO₂ + H₂O = H₂CO₃ = H⁺ + HCO3^-

Question 12

What is the Haldane effect?

Answer 12

• The Haldane effect describes hemoglobin’s ability to carry increased amounts of CO2 in the deoxygenated state as opposed to the oxygenated state.
• Oxygenation of blood in the lungs displaces carbon dioxide from haemoglobin, which increases the removal of carbon dioxide.
• The venous blood carries more CO2 than arterial blood.

Question 13

Why might rapid O2 therapy in hypercapnic individuals with COPD be dangerous?

Answer 13

• Starting supplemental oxygen therapy too quickly in patients with severe COPD can be dangerous, as oxygenation of their blood enables it to carry less carbon dioxide due to the Haldane effect.
• As COPD patients chronically hypoventilate their lungs, CO2 builds up within the body – the blood is also able to carry more CO2 due to the low levels of oxygen (they are hypercapnic and hypoxaemic).
• When oxygen levels suddenly increase (e.g. with O2 therapy), carbon dioxide is displaced from the blood, and the blood is able to transport less CO2 bound to Hb and as bicarbonate.
• This leads to sudden very high levels of CO2 within the body which can potentially leads to dangerous acidaemia.
• A healthy individual would simply increase their level of ventilation to get rid of the excess CO2, however the lungs in this patient are not functioning properly due to the COPD.

Question 14

Describe, in detail, how carbon dioxide is brought into the RBC from the tissues (and kept there).

Answer 14

1. CO2 is produced by respiring cells and dissolves in the plasma, then enters the RBCs.
2. Conversion of CO2 + H2O to H₂CO₃ takes place within the RBCs, catalysed by carbonic anhydrase.
3. The effective removal of CO2 by step (2) enables further CO2 to diffuse into the RBC, so that more can enter into the plasma.
4. H₂CO₃ ionises into HCO₃^- and H⁺. The RBC membrane is impermeable to H+, therefore H⁺ cannot leave.
5. There is an accumulation of H⁺ within the cell, and therefore a cessation of step (2). This can be prevented by haemoglobin acting as a buffer and binding H+ (haemoglobinic acid). Also, the movement of O2 from the RBCs to the tissues increases the concentration of deoxyhaemoglobin, thus enabling more CO2 to be transported.
6. The increased HCO₃^- concentration creates a diffusion gradient for HCO₃^- to leave the cell. It is exchanged for Cl^- to maintain electrical neutrality.

Question 15

Describe, in detail, how carbon dioxide is transferred to the lung alveoli from the RBCs.

Answer 15

1. A low P_ACO₂ creates a diffusion gradient for CO2 to diffuse out of the blood into the airspace.
2. An increased P_AO₂ leads to oxygen-haemoglobin binding. Oxyhaemoglobin binds less H+ than deoxyhaemoglobin, increasing the concentration of free H+.
3. Increasing the concentration of free H+ leads to increased H₂CO₃ and, ultimately, CO2, which contributes to CO2 plasma saturation.
4. The changing equilibrium of the carbonic acid reaction also leads to decreased HCO₃^- concentration, as it binds the free H⁺. This creates a diffusion gradient that allows HCO₃^- ions to enter the RBC in exchange for Cl^-.

• The net result of these effects is transport of O2 and CO2 interact:
  
  • Deoxygenated blood carries more CO2.
  • Oxygenation of blood causes CO2 to leave (both points = “the Haldane effect”).

Question 16

What are some clinical aspects of haemoglobin and oxygen transport?

Answer 16

• Insufficient haemoglobin (anaemia).
• Carbon monoxide poisoning - Haemoglobin has >200x the affinity for CO than it does for O2, and they compete for the same binding site.

CO poisoning and anaemia both decrease the oxygen-carrying capacity of the blood by decreasing the available haemoglobin-oxygen sites. The oxygen content decreases whilst saturation of the oxygen binding sites is normal.