Oxygen–hemoglobin dissociation curve

The oxygen-haemoglobin dissociation curve, also spelled oxygen-hemoglobin dissociation curve, plots the proportion of haemoglobin in its saturated form on the vertical axis against the prevailing oxygen tension on the horizontal axis. The oxyhaemoglobin dissociation curve is an important tool for understanding how our blood carries and releases oxygen. Specifically, the oxyhaemoglobin dissociation curve relates oxygen saturation (SO₂) and partial pressure of oxygen in the blood (PO₂), and is determined by what is called "haemoglobin's affinity for oxygen"; that is, how readily haemoglobin acquires and releases oxygen molecules into the fluid that surrounds it.

Background

Haemoglobin (Hb), a globular protein, is the primary vehicle for transporting oxygen in the blood. Oxygen is also carried dissolved in the blood's plasma, but to a much lesser degree. Haemoglobin is contained in erythrocytes, more commonly referred to as red blood cells. Under certain conditions, oxygen bound to the haemoglobin is released into the blood's plasma and absorbed into the tissues. Each haemoglobin molecule has the capacity to carry four oxygen molecules. How much of that capacity that is filled by oxygen at any time is called the oxygen saturation. Expressed as a percentage, the oxygen saturation is the ratio of the amount of oxygen bound to the haemoglobin, to the oxygen carrying capacity of the haemoglobin. The oxygen carrying capacity is determined by the amount of haemoglobin present in the blood. The amount of oxygen bound to the haemoglobin at any time is related, in large part, to the partial pressure of oxygen to which the haemoglobin is exposed. In the lungs, at the alveolar-capillary interface, the partial pressure of oxygen is typically high, and therefore the oxygen binds readily to haemoglobin that is present. As the blood circulates to other body tissue in which the partial pressure of oxygen is less, the haemoglobin releases the oxygen into the tissue because the haemoglobin cannot maintain its full bound capacity of oxygen in the presence of lower oxygen partial pressures.

Sigmoidal shape

It is usually a sigmoid plot. A haemoglobin molecule can bind up to four oxygen molecules in a reversible way.

The shape of the curve results from the interaction of bound oxygen molecules with incoming molecules. The binding of the first molecule is difficult. However, this facilitates the binding of the second and third molecules, and it is only when the fourth molecule is to be bound that the difficulty increases, partly as a result of crowding of the haemoglobin molecule, partly as a natural tendency of oxygen to dissociate.

In its most simple form, the oxyhaemoglobin dissociation curve describes the relation between the partial pressure of oxygen (x axis) and the oxygen saturation (y axis). Haemoglobin's affinity for oxygen increases as successive molecules of oxygen bind. More molecules bind as the oxygen partial pressure increases until the maximum amount that can be bound is reached. As this limit is approached, very little additional binding occurs and the curve levels out as the haemoglobin becomes saturated with oxygen. Hence the curve has a sigmoidal or S-shape. At pressures above about 60 mmHg, the standard dissociation curve is relatively flat, which means that the oxygen content of the blood does not change significantly even with large increases in the oxygen partial pressure. To get more oxygen to the tissue would require blood transfusions to increase the haemoglobin count (and hence the oxygen carrying capacity), or supplemental oxygen that would increase the oxygen dissolved in plasma. Although binding of oxygen to haemoglobin continues to some extent for pressures about 50 mmHg, as oxygen partial pressures decrease in this steep area of the curve, the oxygen is unloaded to peripheral tissue readily as the haemoglobin's affinity diminishes. The partial pressure of oxygen in the blood at which the haemoglobin is 50% saturated, typically about 26.6 mmHg for a healthy person, is known as the P50. The P50 is a conventional measure of haemoglobin affinity for oxygen. In the presence of disease or other conditions that change the haemoglobin's oxygen affinity and, consequently, shift the curve to the right or left, the P50 changes accordingly. An increased P50 indicates a rightward shift of the standard curve, which means that a larger partial pressure is necessary to maintain a 50% oxygen saturation. This indicates a decreased affinity. Conversely, a lower P50 indicates a leftward shift and a higher affinity.

The 'plateau' portion of the oxyhaemoglobin dissociation curve is the range that exists at the pulmonary capillaries (minimal reduction of oxygen transported until the p(O₂) falls 50 mmHg).

The 'steep' portion of the oxyhaemoglobin dissociation curve is the range that exists at the systemic capillaries (a small drop in systemic capillary p(O₂) can result in the release of large amounts of oxygen for the metabolically active cells).

To see the relative affinities of each successive oxygen as you remove/add oxygens from/to the haemoglobin from the curve compare the relative increase/decrease in p(O₂) needed for the corresponding increase/decrease in s(O₂).

Factors shifting curve

Many factors influence the affinity of this binding and alter the shape of the curve:

	right shift	left shift
temperature	high	low
2.3-DPG	high	low
p(CO2)	high	low
p(CO)	low	high
pH (Bohr effect)	low (acidosis)	high (alkalosis)
type of haemoglobin	adult haemoglobin	foetal haemoglobin

Left shift of the curve is a sign of haemoglobin's increased affinity for oxygen (eg. at the lungs). Similarly, right shift shows decreased affinity, as would appear with an increase in body temperature, hydrogen ion, 2,3-diphosphoglycerate (also known as bisphosphoglycerate) or carbon dioxide concentration (the Bohr effect)

Carbon monoxide has a much higher affinity for haemoglobin than oxygen does. In carbon monoxide poisoning, oxygen cannot be transported and released to body tissues thus resulting in hypoxia.

With foetal haemoglobin, the shift facilitates diffusion of oxygen across the placenta. The oxygen dissociation curve for myoglobin exists even further to the left.

The causes of shift to right can be remembered using the mnemonic, "CADET, face Right!" for CO2, Acid, 2,3-DPG, Exercise and Temperature.

Factors that Affect the Standard Dissociation Curve

The strength with which oxygen binds to hemoglobin is affected by several factors. In effect these factors shift or reshape the oxyhemoglobin curve ("the standard curve"). The standard curve is shifted to the right by an increase in temperature, 2,3-DPG, or pCO₂, or a decrease in pH.

A rightward shift indicates that the hemoglobin under study has a decreased affinity for oxygen. This makes it more difficult for hemoglobin to bind to oxygen (requiring a higher partial pressure of oxygen to achieve the same oxygen saturation), but it makes it easier for the hemoglobin to release oxygen bound to it. The effect of this rightward shift of the curve increases the partial pressure of oxygen in the tissues when it is most needed, such as during exercise, or hemorrhagic shock.

In contrast, the curve is shifted to the left by the opposite of these conditions. This leftward shift indicates that the hemoglobin under study has an increased affinity for oxygen so that hemoglobin binds oxygen more easily, but unloads it more reluctantly.

Variation of the hydrogen ion concentration

This changes the blood's pH. A decrease in pH shifts the standard curve to the right, while an increase shifts it to the left. This is known as the Bohr effect.

Effects of carbon dioxide

Carbon dioxide affects the curve in two ways: first, it influences intracellular pH (the Bohr effect), and second, CO₂ accumulation causes carbamino compounds to be generated through chemical interactions, which bind to hemoglobin forming Carbaminohaemoglobin. Low levels of carbamino compounds have the effect of shifting the curve to the right, while higher levels cause a leftward shift. However, this isn't the overriding effect of CO₂ accumulation. Only about 5-10% of the total CO₂ content of blood is transported as carbamino compounds.

Most of the CO₂ content (80-90%) is transported as bicarbonate ions. The formation of a bicarbonate ion will release a proton into the plasma. Hence, the elevated CO2 content creates a respiratory acidosis and shifts the oxygen-haemoglobin dissociation curve to the right.

Effects of 2,3-DPG

2,3-Disphosphoglycerate (also 2,3 Bisphosphoglycerate or BPG), or 2,3-DPG, is an organophosphate, which is created in erythrocytes during glycolysis. The production of 2,3-DPG is likely an important adaptive mechanism, because the production increases for several conditions in the presence of diminished peripheral tissue O₂ availability, such as hypoxemia, chronic lung disease, anaemia, and congestive heart failure, among others. High levels of 2,3-DPG shift the curve to the right, while low levels of 2,3-DPG cause a leftward shift, seen in states such as septic shock and hypophosphatemia.

Temperature

Temperature does not have such a dramatic effect compared to the previous factors, but hyperthermia causes a rightward shift, while hypothermia causes a leftward shift.

Carbon Monoxide

Haemoglobin binds with carbon monoxide 240 times more readily than with oxygen. The presence of carbon monoxide on one of the 4 haem sites causes the oxygen on the other haem sites to bind with greater affinity. This makes it difficult for the haemoglobin to release the oxygen to the tissues and has the effect of shifting the curve to the left. With an increased level of carbon monoxide, a person can suffer from severe hypoxemia while maintaining a normal pO₂.

Effects of Methemoglobinemia

Methemoglobinemia is a form of abnormal haemoglobin where ferrous (Fe²⁺), which is normally found in haemoglobin, is converted to the ferric (Fe³⁺) state. This causes a leftward shift in the curve and prevents oxygen from being released.

Foetal Haemoglobin

Foetal haemoglobin (HbF) is structurally different from normal haemoglobin (Hb). The foetal dissociation curve is shifted to the left relative to the curve for the normal adult. Typically, fetal arterial oxygen pressures are low, and hence the leftward shift enhances the placental uptake of oxygen. At the placenta there is a higher concentration of 2,3-DPG formed. This binds more readily to adult haemoglobin but not to foetal haemoglobin. This causes the adult Hb to release more oxygen at the placenta to be taken up by the foetus. Foetal Hb is made up of gamma chains not beta ones, and 2,3-DPG does not bind readily to gamma chains, hence it does not give up its oxygen.

External links

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