oxygen carriage and delivery to tissues

Question 1

describe the structure of Haem.

Answer 1

Haem consists of 4 pyrrole groups arranged in a porphyrin ring with a Fe2+ haem group in the centre.

Question 2

where does O2 bind? what is this called?

Answer 2

O2 binds to the Fe2+ haem group in the centre. This is called oxygenation.

Question 3

What does a Hb saturation of 50% mean?

Answer 3

An Hb saturation of 50% means that 50% of the Hb molecules are fully bound with 4 molecules of O2 while the remaining 50% have no O2 bound to them at all.

Question 4

Describe co-operative binding.

Answer 4

Each O2 that has bound increases the Hb affinity for O2. Co-operative binding means that once one molecules of O2 has bound, Hb molecule is more likely to bind further O2. The affinity for O2 increases with each additional O2 molecule until the Hb is fully loaded.

Question 5

what does co-operative binding produce?

Answer 5

Co-operative binding produces a sigmoid shaped normal O2 Hb dissociation curve.

Question 6

what two things is O2 delivery to tissues facilitated by?

Answer 6

O2 dissociation curve and haemoglobin facilitate the delivery of O2 to tissues.

Question 7

what does the O2 saturation of Hb depend on?

Answer 7

The O2 saturation of Hb depends on the PO2 to which it is exposed.

Question 8

Describe the relationship between PO2 and Hb saturation with O2.

Answer 8

Haemoglobin binds oxygen reversibly. If the PO2 is high as in the lungs, the haemoglobin molecule has an increased affinity for O2 and binds O2, whereas if the PO2 is low as in respiring tissues, the haemoglobin has a reduced affinity for O2 and releases the O2 to these tissues. Therefore, % Hb saturation with O2 increases as PaO2 increases until maximum saturation is reached at a PaO2 of about 10.6kPa.

This means that haemoglobin gives up O2 to mixed venous blood with a PaO2 of 5.3kPa and at a high PaO2 of 13.3kPa as in the lungs, the haemoglobin takes up O2.

However, there is not a linear relationship between PaO2 and Hb saturation as a big drop in PaO2 only drives a small change in saturation.

Question 9

what allows increased respiration without increasing ventilation or blood flow?

Answer 9

There is a large functional reserve in O2 supply which means that tissues don’t extract all of the O2 available to them in the blood; they cant extract a higher proportion when demand rises.

Question 10

How does the functional reserve vary? Talk about the heart and kidney.

Answer 10

under normal conditions, the heart extracts most of the O2 available to it which means that there is very little functional reserve. To increase O2 delivery, blood flow must increase. This renders cardiac muscle sensitive to ischaemic stress.

On the other hand, the kidney receives 25% of cardiac output but extracts very little O2 relative to its cardiac output meaning the mixed venous blood leaving the kidney has a high Hb saturation.

Question 11

At what Pao2 is hypoxic drive activated?

Answer 11

The hypoxic drive is activated at a PaO2 of about 8kPa.

Question 12

what factors affect O2 affinity for Hb?

Answer 12

Temperature, H+ conc. (Bohr shift), 2,3- bisphosphoglyceric acis (2,3-BPG)

Question 13

What does the affinity for Hb alter?

Answer 13

O2 uptake and delivery from the lungs and to the tissues respectively.

Question 14

What does a decrease in O2 affinity for Hb mean?

Answer 14

A decreased affinity means that the dissociation curve shifts to the right, the Hb saturation is lower at any given PaO2 and there is increased delivery of O2 to tissues.

Question 15

what is the effect of increased temperature on affinity of Hb for O2?

Answer 15

Affinity is reduced- the curve shifts to the right, Hb saturation is lower at any given PaO2.

Question 16

Describe the Bohr effect.

Answer 16

respiring cells produce an increased amount of H+ and CO2 which reduces the affinity of Hb for O2, which in turn results in increased O2 delivery to respiring tissues.

The H+ ion binds to the globin chain and produces a conformational change stabilising the deoxyhaemoglobin. This decreases its affinity for O2 and increases tissue delivery.

Question 17

A chronic change in pH from 7.4 to 7.2 can increase O2 delivery by…..

Answer 17

15%

Question 18

What is the benefit of the Bohr effect?

Answer 18

Acute changes in pH occur frequently and alter O2 delivery. In this way, the Bohr effect allows higher O2 delivery to more metabolically active tissues. metabolically active tissues produce more CO2 and require more O2 to respire aerobically. anaerobic respiration will also increase H+. The pH goes up by 0.04 pH units in moderate exercise and by 0.2 pH units in strenuous exercise.

Question 19

what does the Bohr effect do the O2 dissociation curve?

Answer 19

The Bohr effect i.e. increased [H+] shifts the dissociation curve to the right –> increased delivery to tissues

Question 20

The Bohr effect doesn’t effect O2 binding to Hb in the lungs because..

Answer 20

The Bohr effect is a local response

Question 21

What is 2,3- BPG?

Answer 21

2,3- BPG is an intermediate of glycolysis in red blood cells.

Question 22

when is 2,3-BPG produced?

Answer 22

2,3-BPG is produced at high altitude and other states of permanent hypoxia such as lung disease, heart disease and anaemia.

Question 23

What does 2,3-BPG do?

Answer 23

2,3-BPG binds between the lysine and histidine residues of the beta globin chains and stabilises deoxy-haemoglobin, reducing its affinity for O2. This shifts the O2 dissociation curve to the right and increases delivery to tissues.

Question 24

Why does the HbF have a greater affinity for O2?

Answer 24

HbF has a greater affinity for O2 than HbA (at any PaO2) as it does not contain beta globin chains which 2,3-BPG binds to. This is important as it allows the foetus to extract O2 and placenta to act as a gas exchange body.