Oxygen-Hemoglobin Dissociation Curve: Shifts & Factors | NEET PG 2026

A 45-year-old man with COPD presents with oxygen saturation of 88% on room air. You administer supplemental oxygen, raising his PaO2 from 55 to 70 mmHg. His saturation jumps to 94%. Later, a septic patient has a PaO2 of 70 mmHg but a saturation of only 88%. Same PaO2, different saturations—why? The answer lies in the oxygen-hemoglobin dissociation curve and the factors that shift it. This single sigmoid curve explains oxygen loading in lungs, unloading in tissues, and why certain patients desaturate precipitously. NEET PG loves this topic.

QUICK ANSWER

The oxygen-hemoglobin dissociation curve is a sigmoid curve relating the partial pressure of oxygen (PaO2) to hemoglobin oxygen saturation (SaO2). Normal P50 (PaO2 at 50% saturation) is 26.7 mmHg. Right shift (increased P50) decreases hemoglobin's oxygen affinity, favoring tissue oxygen release—caused by increased temperature, CO2, 2,3-DPG, and decreased pH. Left shift (decreased P50) increases oxygen affinity, favoring oxygen loading—caused by opposite factors plus carbon monoxide and fetal hemoglobin.

NEET PG RELEVANCE

The oxygen-hemoglobin dissociation curve appears in 4-6 questions across NEET PG papers annually. Focus areas include factors causing right vs left shift, Bohr effect mechanism, clinical scenarios (exercise, altitude, CO poisoning, stored blood), and P50 interpretation. Recent papers emphasize 2,3-DPG physiology, fetal hemoglobin advantages, and methemoglobinemia.

What is the oxygen-hemoglobin dissociation curve?

• The oxygen-hemoglobin dissociation curve is a graph that shows how oxygen and hemoglobin work together. It has oxygen pressure on the bottom and hemoglobin oxygen saturation on the side. The oxygen-hemoglobin dissociation curve is actually shaped like an S. This S shape is because of the special way that hemoglobin binds to oxygen. The oxygen-hemoglobin dissociation curve is very important to understand how oxygen and hemoglobin work together in our bodies.
• Hemoglobin is like a car that can seat four people. The first person who gets in, which is an oxygen molecule, has a time getting a seat.. Once that person is in, it becomes easier for the next person to get in. Each new oxygen molecule that gets in makes it easier for the one to get a seat. When three of the seats are filled with oxygen molecules, the last oxygen molecule can get in easily. This is because the seats are now very easy to get into. Hemoglobin works in a way with oxygen molecules.
• Hemoglobin has a way of working together with oxygen. This happens because of the way the hemoglobin molecule is shaped. Hemoglobin can be in two shapes: the T shape and the R shape. The T shape is not very good at holding onto oxygen. The R shape is really good at holding onto oxygen. When oxygen binds to hemoglobin, it helps to change the shape from the T shape to the R shape. This is why the graph of oxygen binding to hemoglobin has a sigmoid shape. 
• The curve's shape has profound physiological significance. The flat upper portion means saturation remains high (>90%) even as PaO2 drops from 100 to 60 mmHg—providing a safety buffer. The steep middle portion allows efficient oxygen unloading in tissues where PaO2 is 20-40 mmHg—small pressure changes release large amounts of oxygen.

 What is the P50?

• The partial pressure of oxygen at which hemoglobin is fifty percent saturated is called P50. It is a measure of how the hemoglobin in our blood is doing its job. The normal P50 is 26.7 mmHg, which people often round to 27 mmHg, under certain conditions. These standard conditions include a pH of 7.4, a PaCO2 of 40 mmHg, and a temperature of 37°C.
• The P50 is a way to understand how well hemoglobin holds onto oxygen. It is like a point on a curve. If you know the P50 and the shape of the curve, which is, like an S shape, you can figure out the whole curve of the P50. 
• When the P50 increases, it is like the curve shifts to the right. This means that hemoglobin does not hold onto oxygen much. So hemoglobin releases oxygen easily. 
• The P50 is decreased, which is also called a shift. This means that hemoglobin has an affinity for oxygen. The hemoglobin holds onto oxygen tightly. This is good for picking up oxygen in the lungs. It can be bad for getting oxygen to the tissues. The hemoglobin is really good at holding onto oxygen, so it does not let go of it easily. This can be a problem because the tissues need oxygen to work properly. 
• The clinical utility of P50 becomes apparent in blood transfusion and hemoglobinopathies. Stored blood loses 2,3-DPG, causing left shift (P50 ~18 mmHg)—it loads oxygen fine but doesn't release it well. Certain hemoglobin variants have abnormally high or low P50, causing cyanosis or polycythemia, respectively.

What Causes the Right Shift of the Curve?

When the curve shifts to the right, it means that the hemoglobin-oxygen affinity is decreased. This is a thing because it means that oxygen is released more easily to the tissues that need it. The tissues in our body that are working hard and need a lot of oxygen send out signals. When they do this, it helps the oxygen get to where it's needed.

This is really important for tissues that're very active and need a lot of oxygen to keep working properly. The right shift is, like, a way to make sure that the tissues get the oxygen they need.

Increased Temperature

• The higher temperature affects the way hemoglobin and oxygen work together in our blood. It makes them move around more, which changes how they interact. This change helps our muscles get the oxygen they need where it is needed the most.
• Our muscles need oxygen to keep working, so exercising muscles generate heat, and this heat helps our muscles get the oxygen from the hemoglobin.
• When someone has a fever, it affects their body. For example, if a patient has a fever of 40°C, their body is able to get oxygen to their tissues from the hemoglobin in their blood.
• This is because the fever changes the way the hemoglobin works. On the other hand, if someone's body temperature is too low, which is called hypothermia, it has the opposite effect. 
• Carbon dioxide has an impact on how well hemoglobin can carry oxygen. This happens in two ways:

        Carbon dioxide can change the way hemoglobin works with oxygen.

Carbon dioxide does this by affecting the hemoglobin in our blood.

• The pH reduction happens because of carbon dioxide. When carbon dioxide mixes with water, it makes acid. This process is like an equation: carbon dioxide and water make carbonic acid, which then breaks down into hydrogen ions and other stuff.
• They help keep the hemoglobin stable by sticking to parts of it, like the histidine residues. This is really important for the hemoglobin to work properly.
• The Bohr effect is really interesting. It occurs when the level of carbon dioxide in the blood increases, and the pH level in the blood decreases. This makes the curve move to the right. The Bohr effect works in a cool way. When the Bohr effect happens in the blood vessels in tissues, the high level of carbon dioxide helps the blood release oxygen.
• On the other hand, the Bohr effect helps the blood pick up oxygen in the tiny blood vessels in the lungs when the level of carbon dioxide in the blood goes down. The Bohr effect is very important for the Bohr effect to work; the level of carbon dioxide and the level of pH in the blood have to be just right.

Decreased pH (Independent of CO2)

• The hydrogen ions will move the curve to the right. This is not related to the effects of carbon dioxide. When our body does not get oxygen, it can make lactic acid, and this is called lactic acidosis. We also see this shift in people with diabetic ketoacidosis and renal tubular acidosis.
• All these conditions cause the curve to move to the right, which helps our body deliver oxygen to the tissues that really need it, like the ones that are not getting enough oxygen, the hypoxic tissues. 

Increased 2,3-DPG

• It binds to the cavity of deoxyhemoglobin. This helps to stabilize the T state of the 2,3-DPG and deoxyhemoglobin. It also reduces the oxygen affinity of the 2,3-DPG and deoxyhemoglobin.
• One molecule of 2,3-DPG will bind to one hemoglobin tetramer. The 2,3-DPG binds to the chains of the hemoglobin tetramer.

Conditions increasing 2,3-DPG:

• Chronic hypoxia (high altitude, chronic lung disease, cyanotic heart disease)
• Anemia
• Hyperthyroidism
• Pyruvate kinase deficiency

Conditions decreasing 2,3-DPG:

• The stored blood does not last long, and it gets used up within one to two weeks.
• Septic shock
• Hypophosphatemia
• Hexokinase deficiency

The 2,3-DPG response to chronic hypoxia represents a crucial adaptation. Within hours of ascending to altitude, 2,3-DPG rises, right-shifting the curve and improving tissue oxygen delivery despite lower arterial PaO2. This complements the ventilatory and erythropoietic responses to hypoxia.

Also Read: Physiology Important Questions For NEET PG/FMGE

What makes the curve shift to the left?

• When the curve shifts to the left, it is because of the Left Shift of the Curve. Some things that cause the Left Shift of the Curve to happen are changes in the market or in people's behavior. For example, the Left Shift of the Curve can happen when people are willing to pay money for something, which makes the Left Shift of the Curve occur. The Left Shift of the Curve is a thing to understand because it helps us know what is going on with the curve and why it is shifting to the left.
• When you see a shift, it means that the hemoglobin and oxygen are sticking together really tightly. This is good for picking up oxygen in the lungs because the oxygen binds to the hemoglobin easily. However, it is not so good for the rest of the body because the hemoglobin does not want to let go of the oxygen, so the tissues do not get the oxygen they need from the hemoglobin. 

Decreased Temperature, CO2, and Increased pH

• When we look at the things that are opposite of right shift factors, we see that they cause the blood to shift to the left. Things like hypothermia, which is when the body gets too cold, hypocapnia, which happens when you breathe too much and get rid of too much carbon dioxide, and alkalosis, which is when the blood gets too alkaline, all make the blood hold onto oxygen more tightly.
• This is what happens when a patient gets really anxious and starts breathing heavily. They can develop something called alkalosis, which means they have too little carbon dioxide and too much of a certain kind of acid in their blood.
• The oxygen in their blood is not being used properly by their body. This is because the hemoglobin in their blood is holding onto the oxygen tightly, even though there is enough oxygen in their blood.
• As a result, their tissues are not getting oxygen, which can cause some pretty weird symptoms. For example, they might feel numbness around their mouth. Have muscle spasms in their hands and feet.

Decreased 2,3-DPG

• When you get a transfusion with stored blood, it can affect how well your tissues get oxygen. This happens even if your hemoglobin and PaO2 levels are normal. The reason is that the red cells you got from the transfusion take a long time to get back to normal. We are talking 24 to 48 hours. During this time, they need to regenerate something called 2,3-DPG.
• If you get blood or blood that has been stored with special additive solutions like AS-1 or AS-3, the levels of 2,3-DPG in the red cells will be better.

Carbon Monoxide

• When carbon monoxide is bound to hemoglobin, it forms something called carboxyhemoglobin. Carboxyhemoglobin is not able to carry oxygen because carbon monoxide binds to the hemoglobin at the same site as oxygen, so oxygen cannot bind and be carried to the body's tissues. The carbon monoxide binding to hemoglobin makes the parts of the hemoglobin shift toward the R-state, which dramatically increases their ability to hold onto oxygen.
• It also stops the blood from releasing oxygen to the body. This is why Carbon Monoxide poisoning can cause the body's tissues to not get oxygen, even when the blood still has some ability to carry oxygen. 

Fetal Hemoglobin (HbF)

• When 2,3-DPG is not around to help stabilize hemoglobin, it stays in a state that allows it to hold onto oxygen really tightly. This state is called the R-state. It means that fetal hemoglobin is really good at picking up oxygen from the mother's blood. 
• Fetal hemoglobin stays in this high-affinity R-state because it does not have 2,3-DPG to help it switch to a lower-affinity state.
• The P50 of Hemoglobin Fetal is 19 mmHg, but the P50 of Hemoglobin Adult is about 27 mmHg. This difference is important because it means that oxygen can flow from the mother to the fetus.

Also Read: Biostatistics Multiple-Choice Questions for Health Sciences

Methemoglobin

Methemoglobinemia causes the chocolate-brown blood that doesn't redden with oxygen exposure. Causes include oxidizing drugs (dapsone, benzocaine, nitrates), congenital methemoglobin reductase deficiency, and hemoglobin M variants. Treatment is IV methylene blue, which provides an alternative pathway for methemoglobin reduction.

Also Read: Body Fluid Compartments and its Measurement

The Bohr Effect 

When we talk about the Bohr Effect, we are talking about how the blood picks up oxygen in the lungs and then drops it off in parts of the body. The Bohr Effect is important because it helps our bodies get the oxygen they need.

Here are some key things to know about the Bohr Effect:

• The Bohr Effect is pretty cool because it shows us how our bodies are able to adjust to situations. For example, when we are exercising, the Bohr Effect helps our bodies get oxygen to our muscles. The Bohr Effect is a part of how our bodies work, and it is something that we should all know a little bit about.
• The Bohr effect is something that explains how carbon dioxide and the acidity of our blood affect how well hemoglobin can carry oxygen. This Bohr effect is really one of the ways our body regulates itself.
• Our body parts that are working hard, like muscles, produce carbon dioxide. This carbon dioxide goes into the blood cells and, with the help of carbonic anhydrase, it changes into acid and releases hydrogen ions. They help the oxygen get out of the blood cells and into the tissues that need it. This is really important because it means the tissues that are working the hardest get the oxygen they need to keep working.
• At the time when oxygen binds to the blood, it lets go of hydrogen ions, which is the opposite of what is called the Bohr effect. These hydrogen ions then combine with bicarbonate to form carbon dioxide, which we breathe out. This movement of the curve to the left helps the blood pick up oxygen so it can carry oxygen to the tissues in the body.
• The pulmonary capillaries and the oxygen and carbon dioxide in the blood all work together to make sure the body gets the oxygen it needs.
• The reciprocal relationship between oxygen and CO2 binding is called the Haldane effect: deoxygenated hemoglobin carries more CO2 than oxygenated hemoglobin. The Bohr and Haldane effects are two sides of the same coin—molecular linkage between oxygen and CO2 binding that optimizes both oxygen delivery and CO2 removal.

Also Read: Nerve Muscle Physiology—Important Questions and Answers

The Double Bohr Effect and Double Haldane Effect

• At the placenta, you have two Bohr effects that happen at the same time: the Bohr effects are working together. The placenta is where these two Bohr effects take place. These Bohr effects are really important at the placenta.
• Maternal side: Fetal CO2 crosses to maternal blood, raising maternal CO2 and lowering pH. This right-shifts the maternal curve, promoting oxygen release.

On the side, carbon dioxide leaves the fetal blood, and this causes a change that helps the blood pick up more oxygen from the mother. The fetal blood is special because it already has a type of hemoglobin that's really good at picking up oxygen. This means the fetal blood can get as much oxygen as possible, which is important for the baby to grow and be healthy. 

The double Haldane effect is really important for CO2 transfer. When maternal blood loses oxygen, it can carry carbon dioxide back to the lungs. On the other hand, fetal blood that is gaining oxygen will release carbon dioxide to the maternal circulation.

This process is crucial for the Haldane effect and carbon dioxide transfer. The double Haldane effect helps with this exchange of carbon dioxide between blood and fetal blood.

These coupled effects create a "push-pull" mechanism maximizing oxygen transfer to the fetus against the partial pressure gradient.

Clinical Significance of Curve Shifts

Exercise Physiology

During exercise, working muscles generate heat, CO2, and lactic acid while consuming oxygen. All three factors right-shift the curve locally, extracting more oxygen from each hemoglobin molecule passing through.

At rest, hemoglobin releases about 25% of its oxygen (saturation drops from ~98% arterial to ~75% venous). During intense exercise, the right shift enables the extraction of 75-85% of carried oxygen, a threefold increase in oxygen delivery without increasing blood flow proportionally.

High Altitude Adaptation

Acute altitude exposure causes hypoxemia. The hyperventilatory response raises pH (respiratory alkalosis), left-shifting the curve and partially offsetting reduced PaO2 through improved oxygen loading.

Over days, 2,3-DPG increases, right-shifting the curve and improving tissue oxygen delivery despite lower arterial saturation. This adaptation takes 24-48 hours to develop and several days to maximize.

The altitude-adapted individual has near-normal tissue oxygen delivery despite arterial PaO2 of 50-60 mmHg, lower than would be tolerated acutely at sea level.

Also Read: Neural Regulation of Respiration: Control & Mechanisms

Carbon Monoxide Poisoning

CO poisoning exemplifies the clinical importance of curve position. A patient with 25% carboxyhemoglobin has:

• 25% of hemoglobin is unavailable for oxygen transport
• Remaining 75% severely left-shifted, unable to release oxygen normally

The effective oxygen delivery is far worse than losing 25% of hemoglobin to anemia would cause. This explains why CO poisoning produces tissue hypoxia and lactic acidosis at carboxyhemoglobin levels that appear survivable.

Treatment with 100% oxygen accelerates CO elimination (half-life drops from 4-5 hours on room air to 60-90 minutes on 100% O2). Hyperbaric oxygen further reduces the half-life and may reduce neurological sequelae.

Massive Blood Transfusion

Patients receiving massive transfusion (replacement of entire blood volume within 24 hours) may experience impaired oxygen delivery despite adequate hemoglobin and PaO2. Stored blood's depleted 2,3-DPG left-shifts the curve.

Monitoring lactate levels helps identify tissue hypoxia. Some protocols recommend using fresher blood for massive transfusion, though 2,3-DPG regenerates within 24-48 hours post-transfusion.

High-Yield Points for NEET PG

• The Normal P50 is 26.7 mmHg. This is the PaO2 at which Hemoglobin is 50 percent saturated.
• When the P50 is increased, it means there is a shift, and if decreased, it means there is a left shift of the P50.
• When we think about the things that make our bodies want to release oxygen, we should consider a few key factors. These factors include a decrease in affinity and an increase in oxygen release. To remember these factors, we can use a phrase: "CADET face right!"
• Factors that make our body release oxygen are an increase in carbon dioxide, an increase in acid, an increase in 2,3-DPG, exercise, and an increase in temperature.
• Left shift factors (↑ affinity, ↓ O2 release): opposite of above, PLUS carbon monoxide, fetal hemoglobin, methemoglobin
• Bohr effect: ↑CO2 and ↓pH right-shift curve; operates in tissue capillaries to enhance O2 unloading
• The Haldane effect is about how deoxygenated Hb and oxygenated Hb work with carbon dioxide in our bodies. So, to sum it up, the Haldane effect is about deoxygenated Hb carrying carbon dioxide in our venous blood.
• The fetal hemoglobin, which is also called HbF, has a measure called P50 that is about 19 mmHg. 
• When carbon monoxide binds to hemoglobin, it causes the remaining oxyhemoglobin to shift to the left.
•  Pulse oximetry is not able to find out if someone has carbon monoxide poisoning. This is because it mistakes carbon monoxide hemoglobin for oxyhemoglobin. We need to use co-oximetry to get the result for carbon monoxide poisoning.
• Mnemonic for right shift: "CADET, face Right!" — CO2, Acid, 2,3-DPG, Exercise, Temperature (all increased)
• Mnemonic for left shift factors: "Left is Lucky for the Fetus"—left shift from fetal Hb and factors favoring Loading (cold, alkalosis, low 2,3-DPG)

Also Read: Important Topics in Physiology for NEET-PG 2026

Frequently Asked Questions

What is the Bohr effect?

The Bohr effect describes how increased CO2 and decreased pH reduce hemoglobin's oxygen affinity (right shift). In metabolically active tissues producing CO2 and acid, this promotes oxygen release. In lungs where CO2 is eliminated, the reverse occurs—left shift promotes oxygen loading. This feedback mechanism matches oxygen delivery to metabolic demand automatically.

Why is the oxygen-hemoglobin dissociation curve sigmoid-shaped?

The sigmoid shape results from cooperative oxygen binding. Hemoglobin has four oxygen-binding sites, and binding of each oxygen molecule increases affinity for subsequent molecules (T to R state transition). The first oxygen binds with difficulty (flat lower curve), subsequent binding accelerates (steep middle), and near-complete saturation slows binding (flat upper portion). This shape optimizes both oxygen loading in lungs and unloading in tissues.

What is P50, and why is it clinically important?

P50 is the partial pressure of oxygen at which hemoglobin is 50% saturated—normally 26.7 mmHg. It quantifies hemoglobin's oxygen affinity in a single number. Increased P50 (right shift) improves tissue oxygen delivery but may impair oxygen loading. Decreased P50 (left shift) improves loading but impairs delivery. Abnormal P50 values help diagnose hemoglobinopathies and explain unexpected tissue hypoxia.

How does carbon monoxide poisoning affect the curve?

Carbon monoxide binds hemoglobin with 200-250 times greater affinity than oxygen, forming carboxyhemoglobin that cannot transport oxygen. Additionally, CO binding left-shifts the curve for remaining functional hemoglobin, impairing oxygen release. This dual mechanism (reduced capacity plus impaired release) causes severe tissue hypoxia at carboxyhemoglobin levels that might otherwise seem survivable.

Why does fetal hemoglobin have higher oxygen affinity?

Fetal hemoglobin (HbF, α2γ2) has gamma chains instead of beta chains. Gamma chains have serine at position 143 (versus histidine in beta chains), which cannot bind 2,3-DPG effectively. Without 2,3-DPG stabilizing the T-state, HbF remains in high-affinity R-state with P50 approximately 19 mmHg. This left shift enables the fetus to extract oxygen from maternal blood across the placenta.

What happens to the curve during exercise?

Exercising muscles generate heat, CO2, and lactic acid—all right-shifting the curve locally. This enhanced oxygen release increases extraction from approximately 25% at rest to 75-85% during intense exercise. The right shift allows a threefold increase in oxygen delivery without proportionally increasing blood flow. This automatic matching of oxygen supply to metabolic demand represents physiological optimization

CLINICAL PEARL

"The oxygen-hemoglobin dissociation curve is hemoglobin's resume—it tells you what hemoglobin can do under various conditions." When a patient has adequate hemoglobin and PaO2 but tissue hypoxia (rising lactate), think curve shift. Massive transfusion, CO poisoning, severe alkalosis, and hypothermia all left-shift the curve, trapping oxygen on hemoglobin. Conversely, fever, acidosis, and chronic hypoxia right-shift, liberating oxygen to hungry tissues. In NEET PG and at the bedside, PaO2 tells you lung function; the curve position tells you whether that oxygen reaches mitochondria.

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