3. Oxyhaemoglobin dissociation curve Flashcards
OHDC
What is it
What shape is it + why
This defines the relationship between the partial pressure of oxygen
and the percentage saturation of oxygen.
In solutions of blood substitutes, such as perfluorocarbons, this curve is linear,
with saturation being directly proportional to partial pressure.
In solutions containing haemoglobin, however,
the curve is sigmoid-shaped.
This is because as haemoglobin binds each of its four molecules of oxygen,
its affinity for the next increases.
Haemoglobin exists in two forms, an ‘R’ or ‘relaxed’ state in which the affinity for oxygen is high, and a ‘T’ or ‘tense’ state in which affinity for oxygen is low.
As haemoglobin takes up oxygen this effects an allosteric change in the structure of
the molecule, which increases affinity and enhances uptake with each of the
combination steps
Shifts in the OHDC:
left
The curve can be displaced in either direction along the x axis;
movement that is usually quantified in terms of the P50,
which is the partial pressure of oxygen at which
haemoglobin is 50% saturated.
This is normally 3.5 kPa.
The P50 is decreased (leftward shift) by
alkalosis, by reduced PaCO2, by hypothermia, and by reduced concentrations of 2,3-diphosphoglycerate (2,3-DPG).
The curve for fetal haemoglobin (HbF) lies to the left of that for
adult haemoglobin (HbA).
Right shift
A shift to the right is associated with acidosis,
by increased PaCO2, by pyrexia, by anaemia and
by increases in 2,3-DPG.
In most instances, a shift to the right is accompanied by
increased tissue oxygenation.
A better reflection of this is the venous PO2, which can
be determined from the curve, assuming an arteriovenous saturation difference of
25%.
At low PaO2 levels, however (on the steep part of the curve), hypoxia may
outweigh the benefits of decreased affinity and increased tissue off-loading.
Under these circumstances,
a rightward shift is actually deleterious for tissue oxygenation.
At high altitude, with the critical reduction in arterial PO2, the curve shifts to the left.
Haldane effect
The deoxygenation of blood increases its ability to transport CO2.
In the pulmonary capillaries,
oxygenation increases CO2 release,
and in peripheral blood deoxygenation increases uptake.
The double Haldane effect
This applies in the uteroplacental circulation,
in which maternal CO2 uptake increases
while fetal CO2 affinity decreases,
thereby enhancing the transfer of CO2 from fetal to maternal blood.
Bohr effect
This describes the change in the affinity of oxygen for
haemoglobin which is associated with changes in pH.
In perfused tissues,
CO2 enters the red cells to form carbonic acid and hydrogen ions
(CO2 + H2O <-> H2CO3 <-> H+ + HCO3).
The increase in H+ shifts the curve to the right,
decreases the affinity of oxygen and
increases oxygen delivery to the tissues.
In the pulmonary capillaries the process is
reversed, with the leftward shift of the curve enhancing oxygen uptake.
The double Bohr effect:
This is a mechanism which increases fetal oxygenation.
Maternal uptake of fetal CO2 shifts the maternal curve to the right and the fetal curve
to the left.
The simultaneous and reverse changes in pH move the curves in opposite
directions and enhance fetal oxygenation.
Carboxyhaemoglobin
Other ligands can combine with the iron in haemoglobin,
the most important of which is carbon monoxide.
Its affinity for haemoglobin is 300 times that of oxygen,
and not only does it reduce the percentage saturation of oxygen proportionately,
it also shifts the curve to the left.
methaemoglobin:
In methaemoglobinaemia,
The iron is oxidized from the ferrous (Fe2+) to the ferric (Fe3+) form,
in which state it is unable to combine with oxygen.
This happens when haemoglobin acts as a natural scavenger of nitric oxide (NO), when a subject inhales NO or when they receive certain drugs,
including prilocaine and nitrates.
2,3-DPG:
This is an organic phosphate which exerts a
conformational change on the beta chain
of the haemoglobin molecule and
decreases oxygen affinity.
Deoxyhaemoglobin bonds specifically with 2,3-DPG to maintain the ‘T’ (low affinity) state.
Changes in 2,3-DPG levels do alter the P50,
but the clinical significance of this seems to be small.
It is true that concentrations of 2,3-DPG in stored blood are depleted
(and are reduced to zero after 2 weeks) and that it can take up to 48 hours before
pre-transfusion levels are restored.
There is, however, little evidence that massive transfusion is
associated with severe tissue hypoxia, and this is borne out by clinical
experience with such patients.
Abnormal haemoglobins:
Fetal haemoglobin is abnormal only if it persists into adult life, as in thalassaemia.
(It consists of two α-and two γ- or δ-chains,
forming HbA2 or HbF, respectively,
rather than the two α- and two β-chains in the normal adult.)
Haemoglobin S, which is found in sickle cell disease, is formed by the simple
substitution of valine for glutamic acid in position six on the β-chains.
The P50 is lower than normal and the ‘standard’ OHDC for HbS is shifted leftwards.
The anaemia that is associated with the condition then shifts the curve to the right.
There are other haemoglobinopathies, including HbC and HbD (mild haemolytic anaemia
without sickling), HbE, Hb Chesapeake and Hb Kansas.
You will not be expected to
know about these in any detail; they are rare conditions which most anaesthetists
would need to look up in a textbook of uncommon diseases should they encounter a
case in clinical practice.
