Oxygen dissociation curve
Oxygen and carbon dioxide transport; the dissociation curve
Almost all oxygen travels bound to haemoglobin, whose S-shaped curve loads oxygen in the lungs and unloads it in the tissues. Most carbon dioxide travels as bicarbonate. Shifts of the curve and carbon monoxide are the most tested details.
Oxygen content
Oxygen is carried in two forms:
- Bound to haemoglobin: 1.34 mL O₂ per gram of fully saturated Hb. With Hb 15 g/dL and 98% saturation that is about 20 mL per 100 mL of blood.
- Dissolved: 0.003 mL per 100 mL per mmHg PO₂, only about 0.3 mL per 100 mL at normal PO₂.
O₂ content ≈ 1.34 × Hb × SaO₂ + 0.003 × PaO₂. Content depends mostly on haemoglobin and saturation; PaO₂ matters mainly through saturation. So:
| Condition | PaO₂ | SaO₂ | O₂ content |
|---|---|---|---|
| Anaemia | Normal | Normal | ↓ |
| Carbon monoxide poisoning | Normal | Measured SpO₂ often falsely normal; true HbO₂ ↓ | ↓ |
| Polycythaemia | Normal | Normal | ↑ |
| High altitude | ↓ | ↓ | ↓ (later compensated by more Hb) |
Oxygen delivery = cardiac output × arterial O₂ content.
The oxygen–haemoglobin dissociation curve
The curve is sigmoid because haemoglobin binds oxygen cooperatively: once one haem binds O₂, the molecule shifts from the tense (T) to the relaxed (R) state and the remaining sites bind more easily.
- The flat top (PO₂ above about 8 kPa / 60 mmHg) keeps saturation high even if alveolar PO₂ falls a little.
- The steep middle lets tissues unload a lot of oxygen for a small fall in PO₂.
- P50 is the PO₂ at 50% saturation: about 3.5 kPa (27 mmHg) for adult Hb.
- Mixed venous blood: PO₂ about 5.3 kPa (40 mmHg), saturation about 75%.
Shifts of the curve
| Right shift (lower affinity, more unloading) | Left shift (higher affinity, less unloading) |
|---|---|
| ↑ CO₂ (Bohr effect) | ↓ CO₂ |
| ↑ H⁺ (acidosis) | Alkalosis |
| ↑ Temperature | Hypothermia |
| ↑ 2,3-BPG (altitude, anaemia, chronic hypoxia) | ↓ 2,3-BPG (stored blood) |
| Exercise | Fetal haemoglobin (HbF) |
| Carbon monoxide, methaemoglobin |
Exercising muscle is hot, acidic and full of CO₂: everything shifts the curve right exactly where oxygen is needed. HbF binds 2,3-BPG poorly, so it has a higher affinity than maternal HbA, pulling oxygen across the placenta.
Carbon monoxide
CO binds haemoglobin about 200–250 times more strongly than oxygen. It: 1. occupies binding sites, reducing oxygen content 2. shifts the remaining curve to the left, so the oxygen still bound is not released to tissues 3. inhibits cytochrome oxidase
PaO₂ is normal, and ordinary pulse oximeters cannot tell carboxyhaemoglobin from oxyhaemoglobin, so SpO₂ reads falsely normal. Measure COHb on co-oximetry. Treatment is 100% oxygen (half-life of COHb falls from about 4–5 hours on air to about 1 hour), with hyperbaric oxygen in selected severe cases. Cherry-red skin is a late and unreliable sign.
Methaemoglobin (iron oxidised to Fe³⁺) cannot carry oxygen and also left-shifts the curve: chocolate-coloured blood and cyanosis that does not improve with oxygen, from nitrites, dapsone, local anaesthetics such as prilocaine and benzocaine. Treat with methylene blue.
Carbon dioxide transport
| Form | Share of CO₂ in blood |
|---|---|
| Bicarbonate | About 70% |
| Carbamino compounds (bound to proteins, mostly Hb) | About 20–23% |
| Dissolved | About 7–10% |
In red cells, carbonic anhydrase converts CO₂ and water to carbonic acid, which splits into H⁺ (buffered by Hb) and HCO₃⁻. Bicarbonate leaves the cell in exchange for chloride: the chloride shift (Hamburger phenomenon), so venous red cells contain more chloride.
Haldane effect: deoxygenated haemoglobin carries more CO₂ (it binds H⁺ and forms carbamino compounds better). In the lungs, oxygenation releases CO₂; in the tissues, unloading oxygen helps pick up CO₂. Giving high-flow oxygen to some COPD patients raises PaCO₂ partly through this effect and partly by removing hypoxic pulmonary vasoconstriction.
How FCPS asks it
Recalls test: factors shifting the curve; why HbF has higher affinity; the shape of the curve and cooperativity; P50; CO poisoning findings and treatment; methaemoglobinaemia and methylene blue; the main form of CO₂ transport; the chloride shift; Bohr versus Haldane effects; oxygen content in anaemia.
Exam trap In anaemia PaO₂ and saturation are normal; oxygen content is low.
Exam trap The Bohr effect is about CO₂ and H⁺ changing O₂ affinity; the Haldane effect is about oxygen changing CO₂ carriage.
Exam trap CO and methaemoglobin shift the curve left, even though both reduce oxygen delivery.
Quick recall
- Content = 1.34 × Hb × Sat (+ a little dissolved).
- Right shift: CO₂, acid, heat, 2,3-BPG, exercise.
- Left shift: HbF, CO, MetHb, alkalosis, cold.
- 70% of CO₂ travels as bicarbonate.
- CO: normal PaO₂, falsely normal SpO₂; give 100% oxygen.
Test yourself on this topic
5 of the 30 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
A man rescued from a house fire is confused, with oxygen saturation of 99% on pulse oximetry. Why might this reading be misleading?
Answer: COHb is read as oxyhaemoglobin
Standard two-wavelength pulse oximeters cannot distinguish carboxyhaemoglobin from oxyhaemoglobin because they absorb light similarly, so saturation reads falsely normal. Carbon monoxide binds haemoglobin with about 240 times the affinity of oxygen and shifts the dissociation curve to the left, causing tissue hypoxia. Co-oximetry on a blood gas measures COHb. Treatment is 100% oxygen, which shortens its half-life.
CO and pulse oximetry
- COHb read as oxyhaemoglobin
- SpO2 falsely normal
- Measure COHb by co-oximetry
- Give 100% oxygen
Remember Normal sats, sick patient: think CO.
Exam trap PaO2 is normal in CO poisoning because dissolved oxygen is unaffected.
Why the other options are wrong
- Oximeters cannot detect any oxygen in smoke Not the reason.
- Carbon monoxide raises PaO2 sharply PaO2 is usually normal; content falls.
- Burns always cause falsely low readings Not true.
- Cyanide turns blood dark blue Not the reason for the reading.
A family is found drowsy with headache in a closed room heated by a gas heater. Pulse oximetry reads 99%. Why can oximetry be misleading here?
Answer: COHb reads like oxyhaemoglobin
Carbon monoxide binds haemoglobin with about 200–250 times the affinity of oxygen, forming carboxyhaemoglobin. This reduces oxygen content and shifts the dissociation curve to the LEFT, so the remaining oxygen is released poorly to tissues. Arterial PO₂ (dissolved oxygen) is normal, and standard pulse oximeters read COHb as oxyhaemoglobin, giving falsely normal readings; CO-oximetry measures COHb directly. Features: headache, dizziness, confusion, cherry-red skin (late, often at autopsy). Treatment: 100% oxygen (halves COHb half-life), hyperbaric oxygen in severe cases.
Carbon monoxide
- Affinity 200–250× O₂
- Curve shifts left; PO₂ normal
- Pulse oximetry falsely normal → use CO-oximetry
- Treat: 100% O₂, hyperbaric if severe
Remember CO steals the seats and then holds on to the remaining oxygen.
Exam trap A normal SpO₂ and normal PaO₂ do not exclude CO poisoning.
Why the other options are wrong
- CO raises the arterial PO₂ PO₂ is normal, not raised.
- CO shifts the curve right CO shifts the curve to the left.
- CO lowers haemoglobin level Haemoglobin concentration is unchanged.
- Oximeters fail in cold rooms Not the reason.
A family found drowsy in a closed room with a gas heater has headache and confusion. Pulse oximetry reads 98%. Why is this reading misleading, and what is the treatment?
Answer: COHb reads as oxyHb; 100% O₂
Carbon monoxide (incomplete combustion from heaters, generators, vehicles) binds haemoglobin with about 240 times the affinity of oxygen, reducing oxygen-carrying capacity, and shifts the remaining oxyhaemoglobin dissociation curve to the left so oxygen is released poorly to tissues; it also inhibits cytochrome oxidase. PaO2 is normal, and conventional two-wavelength pulse oximeters cannot distinguish COHb from O2Hb, so SpO2 appears normal; co-oximetry measures COHb. Features: headache, nausea, confusion, seizures, coma; 'cherry-red' skin is a late, unreliable sign. Treatment is 100% oxygen via a non-rebreather mask (half-life falls from about 5 hours to about 1 hour); hyperbaric oxygen for severe cases or pregnancy.
Carbon monoxide poisoning
- CO binds Hb ~240× more than O2
- Curve shifted left; cytochrome oxidase inhibited
- SpO2 falsely normal; PaO2 normal → use co-oximetry
- Treat: 100% O2 (COHb half-life 5 h → ~1 h); hyperbaric if severe
Remember Normal sats, headache, heater: think CO.
Why the other options are wrong
- Accurate; no treatment SpO2 is falsely reassuring.
- Cyanide; methylene blue Methylene blue treats methaemoglobinaemia.
- MetHb; vitamin C Not the issue here.
- Hypoventilation; naloxone Not the problem.
Which change occurs in red cells stored for several weeks at 4 °C?
Answer: K⁺ leaks, 2,3-DPG falls
Red cells are stored at 2–6 °C in additive solution (SAGM or CPDA-1) for about 35–42 days. Cold slows the Na⁺/K⁺-ATPase, so potassium leaks into the plasma (risk of hyperkalaemia with rapid or massive transfusion, especially in neonates); glycolysis falls, so ATP and 2,3-DPG decline, shifting the dissociation curve to the left and reducing oxygen release until levels recover after transfusion. Citrate anticoagulant can cause hypocalcaemia in massive transfusion. Platelets do not survive cold storage.
Stored red cells
- Stored 2–6 °C, ~35–42 days
- ↑ Plasma K⁺
- ↓ 2,3-DPG → curve shifts left
- Massive transfusion: citrate → low Ca²⁺
Remember Old blood holds its oxygen tight.
Why the other options are wrong
- 2,3-DPG rises, right shift 2,3-DPG falls.
- Potassium enters the cells Potassium leaks out.
- Cells swell and gain ATP ATP falls.
- Platelets increase in the bag Platelets are non-functional in stored red cells.
A 30-year-old woman with pneumonia and iron deficiency has haemoglobin 10 g/dL, SaO₂ 90% and PaO₂ 60 mmHg (8 kPa) on air. What is her approximate arterial oxygen content?
Answer: About 12.2 mL O₂/dL
Oxygen content is the oxygen bound to haemoglobin plus the oxygen dissolved in plasma. Bound oxygen is 1.34 × Hb × SaO₂, here 1.34 × 10 × 0.9, about 12.1 mL/dL. Dissolved oxygen is 0.003 × PaO₂ in mmHg, here 0.003 × 60, about 0.18 mL/dL, giving a total of about 12.2 mL/dL. Normal content is about 20 mL/dL, so her anaemia reduces delivery more than her mild desaturation does.
Oxygen content
- Bound: 1.34 × Hb × SaO₂
- Dissolved: 0.003 × PaO₂ (mmHg)
- Normal about 20 mL/dL
- Haemoglobin matters most
Remember Content depends far more on Hb than on PaO₂.
Exam trap PaO₂ and SaO₂ can be normal while oxygen content is very low in anaemia.
Why the other options are wrong
- About 13.4 mL O₂/dL Leaves out the 90% saturation.
- About 18.1 mL O₂/dL Would need a haemoglobin of about 15 g/dL.
- About 10.8 mL O₂/dL Uses a wrong factor for bound oxygen.
- About 20.1 mL O₂/dL The normal value with Hb 15 and full saturation.
Where this sits in the CPSP syllabus
- Paper 1: Respiratory system, Oxygen and carbon dioxide transport; dissociation curve
- Surgery & Allied, Paper 2: Respiratory system, Oxygen and carbon dioxide transport; dissociation curve
- Medicine & Allied, Paper 2: Respiratory system, Oxygen and carbon dioxide transport; dissociation curve