Oxygen-hemoglobin dissociation curve

Definitions & Key takeaways

The oxygen-hemoglobin dissociation curve is a graphical representation of the relationship between the amount of oxygen bound to hemoglobin and the partial pressure of oxygen in the blood. The curve is sigmoidal, with a steep slope at low partial pressures of oxygen and a more gradual slope at higher partial pressures. This allows hemoglobin to bind oxygen efficiently at a wide range of partial pressures, ensuring that the body's tissues receive an adequate supply of oxygen.

However, factors like PCO2, pH, temperature, 2-3-DPG, hemoglobin type, and carbon monoxide can all affect the oxygen-hemoglobin affinity, causing a shift in the oxygen-hemoglobin dissociation curve to the right or left, as they make hemoglobin more or less likely to unload oxygen in the tissues.

Chapters:

Watch video only

Introduction0:00–0:15

The oxygen-hemoglobin dissociation curve shows how the hemoglobin saturation with oxygen (SO2,), is related to the partial pressure of oxygen in the blood (PO2).

Hemoglobin and oxygen saturation0:15–1:54

Hemoglobin is the main protein within red blood cells, and it’s made of four globin subunits, each containing a heme group capable of binding one molecule of O2.
So each hemoglobin protein can bind 4 molecules of oxygen. But each hemoglobin isn’t always 100% saturated or bound by oxygen.
A hemoglobin molecule might have no oxygen bound, and be 0% saturated, called deoxyhemoglobin, and it will take on a tense state shape, or T-state; or it might have one oxygen bound and three open spots, meaning that particular protein would be 25% saturated; or two filled spots and two open spots—50%; or 3 spots filled and one spot open—75%, or all spots filled and 100% saturated.
All of these states - where oxygen is bound to hemoglobin - are called oxyhemoglobin, changing to its relaxed state, or R-state with each O2 molecule that binds.
And since there are millions of hemoglobin molecules in a single cell and millions of red blood cells, the hemoglobin saturation of oxygen is the average saturation among all of these proteins.
Now it turns out that hemoglobin absorbs different wavelengths of light as it gets more and more oxygenated. A technique called pulse oximetry uses this property of hemoglobin to figure out what the average oxygen saturation across millions of hemoglobin proteins.

Partial pressure1:54–3:21

The main factor that influences oxygen saturation is the partial pressure of oxygen in the blood, measured in millimeters of mercury (mm Hg).
So for example, at a partial pressure of 25mmHg, hemoglobin proteins might be 50% saturated, called P50; and at a partial pressure of 100mmHg, they might be 98% saturated, meaning most are fully saturated.
And when these points are plotted, the curve takes on a sigmoidal shape. In practical terms, this sigmoidal shape means that hemoglobin has an increasing affinity for O2 as the number of bound O2 molecules goes up.
So binding that 4th O2 molecule is much easier than binding that first O2 molecule. This is called positive cooperativity.
Around 60mmHg, the vast majority of the hemoglobin subunits have bound oxygen, so the curve starts to level off. That’s why in arterial blood where the partial pressure of oxygen is around 100mmHg, hemoglobin get fully saturated with oxygen.
And why in the venous capillaries of tissues, where the partial pressure of oxygen is about 40mmHg, hemoglobin is only about 75% saturated with oxygen.
In other words, about a quarter of the oxygen that’s bound to the hemoglobin gets dropped off, or unloaded, in the tissues.

Oxygen-hemoglobin affinity3:21–7:53

Now, there are a few factors that can cause hemoglobin’s affinity for O2 to change. For example, when CO2 is produced during aerobic metabolism in the tissues, it dissolves into the blood plasma, increasing the PCO2, and increasing the amount of CO2 that gets inside the red blood cells.
Inside the red blood cell, the enzyme carbonic anhydrase catalyzes a reaction with CO2 and water which forms carbonic acid (H2CO3).
Carbonic acid (H2CO3) then splits into a bicarbonate ion (HCO3-) and a hydrogen H+ ions (H+). As more and more H+ start to pile up, the pH starts to fall.
Now, both CO2 and H+ can bind to hemoglobin. CO2 binds to the terminal amino acids in the globin subunits, forming carbaminohaemoglobin; while H+ bind to amino acid side chains that make up the globin subunits.
And even though CO2 and H+ don’t compete for the same binding sites as O2 in hemoglobin, they do stabilize the T-state of hemoglobin.
This results in a decrease in hemoglobin’s affinity for oxygen, forcing the unloading of O2. So, for example, when muscles are working hard, like during exercise, they are producing a lot more CO2, and, as a result, more H+ , which causes the pH to drop.
So O2 is unloaded in the issues that need it most. Another factor is 2,3-diphosphoglyceric acid (2,3-DPG), which is a metabolic byproduct of glycolysis in red blood cells.
When there are hypoxic conditions, like a lack of oxygen, which might develop when a person is at high altitude, 2,3-DPG production increases.
In the middle of the hemoglobin there is a positively charged pocket between the four globin chains where the negatively charged 2,3-DPG is able to bind.
Again, even though 2,3-DPG doesn’t bind in the same place as O2, it stabilizes the T-state of hemoglobin and decreases hemoglobin’s affinity for oxygen, forcing the unloading of O2 in tissues that are in need of it.
Temperature also affects the strength of the bond between oxygen and hemoglobin. The heme component of hemoglobin, which is where the oxygen binds, contains iron, which helps anchor oxygen to hemoglobin.
Higher temperatures affects this bond between iron and oxygen, favoring the T-state of hemoglobin. So, using exercise as an example again, increased activity causes muscles to generate increased heat.
And the rise in even a few degrees in temperature allows for more unloading of O2 , and that helps meet the increased metabolic demands of the muscles.
Finally, hemoglobin’s affinity for oxygen can depend on the type of hemoglobin. For example, Hemoglobin A (HbA), which is the main adult hemoglobin has a lower affinity for oxygen than fetal hemoglobin (HbF).
So, for example, this is important during gestation. Since a baby needs to compete for oxygen with mom, it’s helpful to have a higher affinity for O2 than mom to help efficiently transfer oxygen to the baby.
So in an adult with hemoglobin A, when PCO2, temperature, or 2,3-DPG are high; or pH is low, hemoglobin affinity for oxygen decreases and more oxygen is unloaded in the tissues.
The curve shifts to the right because now a higher PO2, or P50, is needed to overcome these factors and saturate hemoglobin.
On the flip side, when PCO2, temperature, or 2,3-DPG are low; or pH is high; or we’re looking at HbF instead of Hemoglobin A, hemoglobin affinity increases and less oxygen is unloaded in the tissues.
The curve shifts to the left because a lower PO2 is needed to saturate hemoglobin. So far, to be clear, these factors affect hemoglobin’s affinity for oxygen, but not hemoglobin’s capacity to bind oxygen.
Meaning, hemoglobin is still only able to bind four molecules of oxygen, but how easily it does so when there’s a certain partial pressure of oxygen depends on the circumstances.

Carbon monoxide7:53–9:16

Now, one additional situation to consider is when there’s something like carbon monoxide (CO) floating around which actually competes with oxygen for binding spots on hemoglobin.
Hemoglobin’s affinity for CO is 250 times greater than that of O2. So hemoglobin will bind CO, forming carboxyhemoglobin, more readily than it will bind to O2.
And once CO binds, it doesn’t unload easily, making those binding spots unavailable to oxygen. This has two effects.
First, the affinity for hemoglobin to bind O2 increases at the sites not filled by CO. This is an attempt for O2 to compete with CO to bind to hemoglobin but results in less unloading of O2 in the tissues because of increased affinity.
Second, the entire shape of the curve changes from sigmoidal to one that flattens out to a zero slope. Where the curve flattens depends on how saturated hemoglobin is with CO.
For example, if 50% of the binding sites on hemoglobin are filled with CO, the curve will flatten out at about 50% hemoglobin saturation with oxygen.
And as the PCO increases, and more CO binds, the curve will flatten out at lower oxygen saturation values. So, to recap: The oxygen-hemoglobin dissociation curve graphs the relationship between hemoglobin saturation with oxygen and the partial pressure of oxygen in the blood.

Review9:16–9:56

The sigmoidal curve to the graph is the result of positive cooperativity which increases hemoglobin’s affinity for oxygen as more oxygen molecules bind.
But factors like PCO2, pH, temperature, 2-3-DPG, hemoglobin type, and carbon monoxide can all affect the affinity, causing a shift in the oxygen-hemoglobin dissociation curve and make hemoglobin more or less likely to unload oxygen in the tissues.