Can you draw the oxygen dissociation curve of normal adult haemoglobin?How many points on the curve can you indicate with values?The oxygen dissociation curve of adult haemoglobin is a sigmoid curve. The three mainpoints to indicate on the curve are:•Arterial point:pO2 100 mmHg with SaO2 = 97.5%•Mixed venous:pO2 40 mmHg with SaO2 = 75%•P50:pO2 26.6 mmHg with SaO2 = 50%
pO2 0 mmHg, SO2 0% - the originpO2 10 mmHg, S02 10% - just easy to remember & helps get the sigmoid shape.pO2 60 mmHg, SO2 91% - the ‘ICU’ pointpO2 150 mmHg, SO2 98.8% - shows flat upper part of ODCThe ‘ICU point’ can be considered as the point on the curve that separates the steep lowerpart from the flat upper part. This is a bit artificial but a pO2 of 60 mmHg in this sense isconsidered as the lowest acceptable pO2 in an ICU patient because marked desaturationoccurs at pO2values below this point.]What is the mixed venous point?This is the point which represents mixed venous blood. The pO2 here is 40 mmHg and thehaemoglobin saturation is 75%. The oxygen content cannot be specified without furtherinformation (eg [Hb] )Note that the mixed venous point does NOT really lie on the normal ODC as above (& in allthe texts). The increased pCO2 and decreased pH in mixed venous blood mean that themixed venous point must lie on a slightly right shifted ODC rather than the standard ODC.This is the Bohr effect.Fig 4.8 Oxygen Dissociation Curve for Adult Haemoglobin (HbA)…Standard ConditionsTe m p = 3 7 CpH = 7.40BE = 00204060801000255075100Oxyg enSaturation(%)Par tial pressure of Oxygen(mmHg)Arterial pointMixed venous pointP50<<The curve has a sigmoid shapebecause of positive cooperativity.^Sample section from “The Physiology Viva” by Kerry BrandisVisit http://www.AnaesthesiaMCQ.com for detailsfrom:
What is meant by the term ‘P50’?This term is used in reference to the oxygen dissociation curve. It is defined as the partialpressure of oxygen at which the oxygen carrying protein is 50% saturated. It is usually usedin relation to haemoglobin but can also be used for other oxygen bindingproteins such as myoglobin. Though often drawn as a point on the dissociation curve, this isincorrect as the P50 is, by definition, a point on the x-axis as it is a particular pO2value (¬ a pO2-SO2 value pair like the mixed venous point for example.)What is the normal value for the P50 of adult haemoglobin?The P50 of normal adult haemoglobin is 26.6 mmHg.What is the P50 used for?Why was this point on the curve chosen for this purpose?The P50 is used to specify the position of the oxygen dissociation curve (or alternatively, theP50 is an index of oxygen affinity of the oxygen carrying protein. This is whatspecifying the position of the curve is really about).It is the most useful point for specifying the curve’s position because it is on the steepest partof the curve. It is therefore the most sensitive point for detecting a shift of the curve.Specifying the P50 of a curve allows comparison with the position of other curves underdifferent conditions.What does a right shift indicate?What are the causes of a right shift?A right shift indicates decreased oxygen affinity. The P50 is higher for a right shifted curve.A right shift can be caused by an increase in 4 factors:•temperature•[H+]•pCO2•red cell 2,3 DPG level.Can you superimpose on the graph the oxygen dissociation curve for foetal haemoglobin?..The HbF curve is left-shifted (higheroxygen affinity) as compared to theHbA curve because of lower binding of2,3 DPG by HbF.OxygenSaturation(%)Fig 4.9 Oxygen Dissociation Curve for Foetal Haemoglobin (HbF)0255075100020406080100Partial Pressure of Oxygen (mmHg)HbFHbAStandard ConditionsTe m p = 3 7 CpH = 7.40BE = 0Sample section from “The Physiology Viva” by Kerry BrandisVisit http://www.AnaesthesiaMCQ.com for detailsfrom: http://www.AnaesthesiaMCQ.com
How is this curve different?What is the P50 of foetal haemoglobin?The curve has a sigmoid shape very similar to the normal ODC for adult haemoglobin butslightly left shifted. The P50 is lower at about 18 mmHg. (Values between 18 and 20mmHg arequoted in various sources.)Why is the foetal haemoglobin curve shifted to the left?The lower P50 value indicates that the curve is left shifted as compared to the adult curve (iefoetal Hb has a higher oxygen affinity). The reason for this is the reduced binding of 2,3diphosphoglycerate (2,3 DPG) to foetal haemoglobin. 2,3 DPG binds best to the beta chainsof adult haemoglobin and this shifts the curve to the right indicating a decrease in oxygenaffinity. In fact, 2,3 DPG binds most avidly to the beta chains of deoxyhaemoglobin.Foetal haemoglobin consists of 2 alpha chains and 2 gamma chains (ie there are no betachains). Consequently the P50 is lower than that of adult haemoglobin because HbF is lesssensitive to the effects of 2,3 DPG.Could you draw the oxygen dissociation curves for a foetus at term and for the mother atterm using oxygen content on the y-axis (rather then saturation)?The curves are different because ofthe left shift of foetal haemoglobin, the increased [Hb] offoetal blood andthe decreased [Hb] of maternal blood (physiological anaemia).
What is myoglobin?Myoglobin is a haem-containing oxygen binding protein that is present in skeletal muscle. Ithas a role as an oxygen store
The myoglobin curve is a rectangular hyperbola with a very low P50 (2.75 mmHg). It lieswell to the left of the sigmoid-shaped haemoglobin curve. It has a much higher oxygenaffinity.The physiological reason (the advantage): Myoglobin needs to have a P50 less thanhaemoglobin so it can take up oxygen from it. Also, myoglobin needs to be able to load andunload oxygen in the range of pO2 values that occur within the cell. If its P50 was say 20mmHg and intracellular pO2 was 1 to 5 mmHg, then the myoglobin could never loadoxygen. Intracellular pO2 does vary between different cells and within the same cell, but istypically low. Oxidative phosphorylation ceases below a pO2 of about 1 mmHg. It can beseen that myoglobin with a P50 of 2.75 mmHg is well matched to intracellular needs inmuscle cells. It can load oxygen from haemoglobin and can unload its oxygen as cytoplasmicpO2 falls to low levels.The chemical reason (the cause): The reason why the curves are different is because of thediffferent structures of myoglobin and haemoglobin. Myoglobin contains only a single globinchain: its dissociation curve is a rectangular hyperbola. Haemoglobin contains four globinchains and the oxygenation of each chain causes structural changes which increase the affin-ity of the haem of the remaining chains for oxygen. This consequence of sub-unit interactionis known as positive cooperativity and this increasing oxygen affinity as oxygen loads is thecause of the sigmoid shape of the dissociation curve.What is the physiological significance of the shape of the oxygen dissociation curve foradult haemoglobin?The curve can be considered to consist of two parts:•the flat upper part•the steep lower partThe flat upper part acts as a buffer in the sense that the pO2can drop to about 80 mmHg andyet the haemoglobin will still remain highly saturated (96%) with oxygen. This keeps thearterial oxygen concentration high despite impairment in saturation in the lung.