Explain the oxyhaemoglobin dissociation curve and the factors that may alter it.
Marks were awarded for an appropriate curve with values, an explanation of the nature of
positive cooperatively and notes on those factors causing changes in the p50 or "shifts” in the
Most candidates were able to provide the required sigmoid shaped curve with appropriate key
value points (p50, venous and arterial points). Better candidates were able to identify p50 as a
measure of avidity or affinity for oxygen and commented on T- Tense and R- Relaxed states,
the role and production of 2,3 DPG , binding to the beta chains (nature of the lack effect on
foetal haemoglobin). Describing the mechanisms associated with factors shifting the curve and
commenting on changes in oxygen content over the steep and flatter parts of the curves gained
additional marks. Candidates are reminded to answer the question asked - no marks were
awarded for a description of dissolved oxygen delivery. Some answers confused the Bohr and
The oxyhaemoglobin dissociation curve is a sigmoidal relationship between the partial pressure of oxygen and the oxygen saturation of haemoglobin:
- This curve describes the changing affinity of haemoglobin for oxygen which occurs with increasing PaO2.
- The flat upper plateau decreases variability in blood oxygen content even with large changes of PaO2
- The steep lower part allows the increased release of oxygen from haemoglobin with only a small change in PaO2
- Positive cooperativity is the main reason behind the non-linearity of this relationship:
- Haemoglobin is a heterotetramer
- It is composed of four subunits
- Each subunit binds oxygen independently.
- Then, once an oxygen molecule is bound to it, the oxygenated subunit increases the oxygen affinity of the three remaining subunits
- This is because of a conformational change produced by each subunit binding oxygen, which mediates the transition from the T state to the R state
- T and R state:
- This refers to two distinct states of the haemoglobin tetramer molecule
- The T ("Tense") state is the deoxygenated form (with 0 O2 molecules)
- The R ("Relaxed") state is the oxygenated state (with 4 O2 molecules)
- One pair of αβ subunits in the fully oxygenated R-state appears rotated by 15° with respect to the other pair of subunits
- The binding of each oxygen molecule changes the state of the tetramer, changing the equilibrium constant for the next O2 molecule to bind the next subunit more easily
The following physiological factors influence the affinity of hemoglobin for oxygen:
- The partial pressure of CO2
- Increasing CO2 shifts the curve to the right
- Hyperventilation and hypocapnia shifts the curve to the left
- pH, independent of CO2
- Decreasing pH (acidosis) shifts the curve to the right
- Alkalosis shifts the curve to the left
- The concentration of 2,3-DPG inside the erythrocytes
- Increased 2,3-DPG (eg. in response to hypoxia or erythropoietin) shifts the curve to the right
- Decreased 2,3-DPG (eg. as a red cell storage lesion ) shifts the curve to the left
- The presence of unusual haemoglobin species
- Methaemoglobin, carboxyhaemoglobin and foetal haemoglobin shift the curve to the left
- Sulfhaemoglobin shifts the curve to the right
- Hyperthermia shifts the curve right
- Hypothermia shifts it left
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- this is an English translation of the original article, which was beautifully titled "Über einen in biologischer Beziehung wichtigen Einfluss, den die Kohlensäurespannung des Blutes auf dessen Sauerstoffbindung übt".
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