pk6 Carriage of O2

Question 1

List the ways by which oxygen is carried in the blood.

Answer 1

Oxygen is carried in the blood by:

1 - Physically dissolving into the plasma.

2 - Binding to haemoglobin in RBCs.

Question 2

What is Henry’s Law?

Answer 2

Henry’s Law:

Dissolved O2 = PO2 * solubility coefficient

Question 3

What is the volume of oxygen that can be dissolved in 1L of blood at 13k Pa?

What is therefore the rate of oxygen delivery to the body by dissolved oxygen alone?

What is the required rate of oxygen delivery?

Answer 3

• Using Henry’s law, at 13 kPa, 3ml of oxygen can be dissolved per L of blood.
• Therefore, at a cardiac output of 5L/min, 15 ml/min of oxygen can be delivered to tissues by dissolved oxygen alone.
• The required rate of oxygen delivery to the body is 250 ml/min.

Question 4

What is the normal concentration of haemoglobin in the blood?

What is the volume of oxygen that can be carried per gram of haemoglobin?

Therefore, what is the volume of oxygen that can be bound to haemoglobin in 1L of blood?

What is therefore the rate of oxygen delivery to the body by haemoglobin-bound oxygen alone?

What is the required rate of oxygen delivery?

Answer 4

• The normal concentration of haemoglobin in the blood is ~150 g/L.
• 1g of haemoglobin can carry ~1.3 ml of oxygen.
• Therefore, the volume of oxygen that can be bound to haemoglobin in 1L of blood is ~200 ml.
• Therefore, at a cardiac output of 5L/min, 985 ml/min of oxygen can be delivered to tissues by hemoglobin-bound oxygen alone.
• The required rate of oxygen delivery to the body is 250 ml/min.

Question 5

Describe the structure of haemoglobin.

How many oxygen atoms can one haemoglobin molecule carry?

Answer 5

• Haemoglobin contains 4 polypeptide globin chains.
• In adults, 2 of these globin chains are alpha chains, and the other 2 are beta chains.
• The chains are non-covalently bound to each other.
• Each globin chain contains a haem group, which contains a single Fe2+ atom. This is the atom to which an O2 molecule can bind.
• Therefore, one haemoglobin molecule can carry 4xO2 = 8 oxygen atoms.

Question 6

What is the average mass of haemoglobin per L of blood?

Answer 6

The average mass of haemoglobin per L of blood is 147g.

Question 7

What is cooperative binding?

Answer 7

• Cooperative binding is the phenomenon in which the binding of oxygen to one haem group in a haemoglobin molecule makes the subsequent binding of more oxygen to other haem groups in the same haemoglobin molecule easier.
• This is also true for unbinding; unbinding in one haem group makes unbinding easier for other haem groups.

Question 8

What is the difference between oxygen content, oxygen capacity and haemoglobin saturation?

Answer 8

• Oxygen content is the quantity of oxygen in a given sample of blood, composed of both dissolved oxygen plus oxygen bound to haemoglobin.
• Oxygen capacity is the maximum quantity of oxygen that can combine with haemoglobin in a sample of blood - it does not include dissolved oxygen.
• Haemoglobin saturation is the ratio of the quantity of oxygen combined with haemoglobin in a given sample to the oxygen capacity of that sample.

Question 9

What determines the extent of oxygen binding to haemoglobin in the blood?

Describe the shape of the haemoglobin dissociation curve.

Answer 9

• The extent of oxygen binding to haemoglobin in the blood is determined by the partial pressure exerted by the oxygen dissolved in the plasma.
• I.e. there is a relationship between haemoglobin saturation and PO2. This is represented by the haemoglobin dissociation curve (which also takes into account dissolved oxygen).
• Where the x axis is PO2 and the y axis is oxygen content, the haemoglobin dissociation curve is an ‘s’ shape, with a large plateau from 8 kPa to 13 kPa.

Question 10

Describe the shape of a haemoglobin saturation graph.

Answer 10

• X axis is PO2 and y axis is haemoglobin saturation.
• The graph is the same shape as a haemoglobin dissociation curve (which uses oxygen content rather than saturation) - an ‘s’ shape with a plateau from 8 kPa to 13 kPa, where 100% saturation occurs.
• The curves look similar because oxygen content, in part, reflects haemoglobin saturation.

Question 11

What is the advantage of the plateau in the haemoglobin dissociation curve?

What is this plateau known as?

Answer 11

• The plateau of the haemoglobin dissociation curve ensures that haemoglobin saturation stays high as PO2 fluctuates.
• In the lungs, this is advantageous as it ensures almost complete loading. E.g. saturation is still 90% at 8 kPa.
• This plateau is known as the association part of the haemoglobin dissociation curve.

Question 12

What is the advantage of the steep part of the haemoglobin dissociation curve?

What is this part known as?

Answer 12

• The steep part of the haemoglobin dissociation curve ensures that haemoglobin saturation decreases quickly as PO2 falls below 8 kPa.
• In tissues, this ensures adequate delivery of oxygen whilst still maintaining high arterial PO2. E.g. saturation decreases by 60% from 8 kPa to 3 KPa.
• Maintaining high arterial PO2 is important because this is the driving force for diffusion.
• This steep part is known as the dissociation part of the haemoglobin dissociation curve.

Question 13

What is the Bohr effect?

List the factors controlling the Bohr effect.

Answer 13

• The Bohr effect is a shift in the haemoglobin dissociation curve (rightwards or leftwards).
• A rightwards shift can be achieved by:

1 - Increasing PCO2.

2 - Decreasing pH.

3 - Increasing temperature.

4 - Increasing 2-3 DPG, which is a byproduct of glycolysis.

• Vice versa will achieve a leftwards shift.
• Note how all of these rightwards shift-inducing factors are what you would expect in a highly metabolically active environment.

Question 14

Why is the Bohr effect useful?

Answer 14

• The Bohr effect is useful for oxygen loading and unloading at different physiological environments:
• A rightwards shift will facilitate oxygen unloading, which is advantageous in tissues that induce a rightwards shift, e.g. highly metabolically active tissues such as muscle.
• However, a rightwards shift has very little effect upon the ability of blood to load oxygen in the lungs, because the association part of the curve (the plateau) is large enough to accommodate the PO2 ranges in the lung even after the rightwards shift.

Question 15

How might the haemoglobin dissociation curve differ for a sample of blood that is stored for a long period of time?

Answer 15

• When blood is stored, 2,3-DPG decreases.

- This causes a leftwards shift in the haemoglobin dissociation curve.

Question 16

What is meant by p50 of haemoglobin?

What is the value for p50 under normal circumstances?

Why is p50 useful?

Answer 16

• p50 is the PO2 required to achieve 50% haemoglobin saturation.
• In normal circumstances, this is 3.5 kPa.
• p50 is useful as it gives an indication as to whether the curve has shifted to the left or right.

Question 17

List 3 factors that negatively affect the O2 capacity of the blood.

Answer 17

Factors that negatively affect the O2 capacity of the blood include:

1 - Low dietary intake of iron.

2 - Anaemia.

3 - CO poisoning.

Question 18

Describe the effect of anaemia on the haemoglobin dissociation curve.

How does anaemia affect oxygen saturation and oxygen content at a given PO2?

What is the consequence of this for oxygen delivery?

Answer 18

• In anemia, the haemoglobin dissociation curve has the shape shape, but is squeezed downwards.
• I.e. at any PO2, the oxygen saturation % will be the same as in a normal patient, but the oxygen content at any PO2 will be considerably lower.
• This means that oxygen delivery is not intolerably impaired.
• Not true for sickle cell anaemia, as explained later in the lecture.

Question 19

List 7 properties of carbon monoxide that make it particularly dangerous.

Answer 19

Carbon monoxide is particularly dangerous because:

1 - It is colourless.

2 - It is tasteless.

3 - It is odourless.

4 - It is non-irritating.

5 - It doesn’t affect breathing rate or volume.

6 - It doesn’t cause breathlessness.

7 - It doesn’t cause cyanosis (the CO-Hb complex is actually slightly pinker than O2-Hb complex).

Question 20

How does carbon monoxide interact with haemoglobin?

Answer 20

Carbon monoxide binds to haemoglobin at the same site as O2, but with 210x the affinity.

Question 21

Why is carbon monoxide poisoning fatal when anaemia affecting the same amount of haemoglobin is not?

Answer 21

• Carbon monoxide poisoning is fatal because it changes the shape of the haemoglobin dissociation curve, whereas anaemia does not.
• This means that carbon monoxide poisoning affects oxygen delivery, whereas anaemia does not (to the same degree).

Question 22

Describe the shape of the haemoglobin dissociation curve with carbon monoxide poisoning.

What is the implication of these changes?

Answer 22

1 - The maximum oxygen content is significantly reduced.

2 - The maximum oxygen content is reached at a very low kPa.

3 - The ‘S’ shape of the curve is lost; oxygen content increases very quickly following an increase from 0 kPa.

• The implication of these changes is that tissues must drop to a significantly lower kPa than normal in order to achieve the same delivery of oxygen.

Question 23

List the differences between adult haemoglobin (HbA) and foetal haemoglobin (HbF).

Answer 23

1 - HbF contains 2 alpha chains and 2 gamma chains, whereas HbA contains 2 alpha chains and 2 beta chains.

2 - HbF has slightly less affinity for O2 than HbA.

3 - HbF has considerably less affinity for 2,3-DPG so is leftwards shifted compared to HbA. This is beneficial for the foetus where arterial PO2 is low.

• Therefore, due to point 3, HbF actually has a higher overall affinity for oxygen than HbA.

Question 24

Why is it important for foetal haemoglobin to have a higher affinity for oxygen than adult haemoglobin?

Answer 24

• It is important that foetal haemoglobin has a higher affinity from adult haemoglobin because foetal haemoglobin must pick up oxygen from maternal blood, which contains adult haemoglobin.
• Therefore, in order for oxygen to move into the from the maternal haemoglobin to the foetal haemoglobin, the foetal haemoglobin must have a higher affinity for oxygen than adult haemoglobin.

Question 25

What is HbA2?

How does the haemoglobin dissociation curve differ between HbA and HbA2?

Answer 25

• HbA2 is a variant of haemoglobin which accounts for 2% of adult haemoglobin.
• It consists of 2 alpha chains and 2 delta chains.
• Functionally, there is no difference between HbA and HbA2.

Question 26

What is HbS?

How does the haemoglobin dissociation curve differ between HbA and HbS?

Answer 26

• HbS is a variant of haemoglobin that is present in sickle cell anaemia.
• It consists of 2 alpha chains and 2 mutated beta chains
• HbS crystallises out in low PO2 and low pH, forming rod shapes which distort the shape of RBCs. This occurs when hydrophobic groups on adjacent HbS molecules form bonds, allowing tetramer chains of HbS to form, which can polymerise.
• This results in a rightward shift of the haemoglobin dissociation curve in HbS.
• This means that sickle cell anaemia affects the oxygen delivery to tissues, but not oxygen capacity.

Question 27

What is methemoglobinaemia?

Answer 27

• When exposed to oxidising agents, e.g. pollutants, the Fe2+ in haemoglobin is oxidised to Fe3+.
• This ‘ferric’ form of haemoglobin can’t bind or transport oxygen, causing methemoglobinaemia.

Question 28

What is myoglobin?

How does the haemoglobin dissociation curve differ between HbA and myoglobin?

Answer 28

• Myoglobin is a variant of haemoglobin that is present in muscles.
• It consists of only 1 chain and 1 haem group.
• It functions as a store of O2 in muscle, which is used during exercise when tissues become hypoxic and normal HbA has been depleted of oxygen.
• To accomodate this function, myoglobin’s haemoglobin dissociation curve is left shifted, and appears hyperbolic rather than sigmoidal.
• Myoglobin also shows no Bohr effect.

Question 29

What is the advantage of sickle cell anaemia?

Answer 29

Sickle cell RBCS are resistant to malaria.

Question 30

Define hypoxia.

What is the rate of normal oxygen delivery?

Answer 30

• Hypoxia is an inadequate delivery for the metabolic needs of an organism to maintain normal function.
• Normal oxygen delivery is 925 ml O2 / min.

Question 31

Describe the 4 types of hypoxia.

Answer 31

1 - Hypoxic hypoxia.

• This is low PaO2 (arterial PO2), and a correspondingly low SaO2 (arterial oxygen saturation).
• It is caused by hypoventilation, diffusion limitation, V/Q mismatch and shunting.

2 - Anaemic hypoxia.

• This is normal PaO2 and SaO2, but low O2 content.
• It is caused by anaemia, blood loss, and carbon monoxide poisoning.

3 - Stagnant hypoxia.

• This is low Q in a particular tissue or the whole body.
• It can be caused by shock (i.e. hypovolaemia, cardiac failure etc. affecting the whole body) or stroke (affecting a particular tissue).

4 - Histotoxic hypoxia.

• This is high PvO2 (venous PO2) and SvO2 (venous O2 saturation) because the tissues are unable to utilise oxygen.
• It is caused by cyanide poisoning.