In one breath
The curve plots Hb saturation against PO₂. It is S-shaped: steep between about 10 and 60 mmHg, where a small fall in PO₂ unloads a lot of O₂ in the tissues, and flat above about 60–70 mmHg, where a fall in PO₂ barely lowers saturation, which is a safety margin for the lungs. P50 (normally 27 mmHg) sums up affinity: a right shift raises P50 and releases more O₂; a left shift lowers P50 and holds O₂ tighter.
Builds on: Oxygen transport · Leads to: Carbon dioxide transport · Hypoxia · Acclimatization to high altitude
Oxygen–hemoglobin dissociation curve
- Also called the oxy-Hb equilibrium (or association) curve. It shows how the O₂ saturation of Hb varies with PO₂ from 0 to 100 mmHg.
- Saturation rises with PO₂, but not in a straight line. Cooperative binding (the T-to-R change in Oxygen transport) bends it into an S (sigmoid) shape.
- The S shape does two jobs: Hb fills up at the high PO₂ of the lungs, and it gives up a lot of O₂ for a small drop in PO₂ in the tissues.
| Landmark | PO₂ (mmHg) | Hb saturation |
|---|---|---|
| P50 | 27 | 50% |
| Mixed venous blood | 40 | ~75% |
| Start of the plateau | 60 | ~90% |
| Arterial blood | 95–100 | ~97–98% |
Steep phase
- PO₂ 10–60 mmHg. Here saturation climbs rapidly with each small rise in PO₂; it reaches about 90% at 60 mmHg.
- Significance:
- Loading: a small rise in PO₂ gives a large rise in saturation.
- Unloading: read in reverse (60 down to 10 mmHg), a small fall in tissue PO₂ releases a large amount of O₂. This is where the tissue capillaries operate.
- The shifts caused by H⁺ and CO₂ act mainly on this part of the curve, so a right shift here releases even more O₂ in active tissue.
Plateau phase
- The curve begins to flatten near 60 mmHg and is almost flat by 70 mmHg. Raising PO₂ from 60 to 100 mmHg adds only a little more bound O₂.
- Significance:
- Safety margin. At high altitude or in lung disease, if PaO₂ falls from about 95 to 60 mmHg, Hb still stays about 90% saturated, so the O₂ carried falls only by 5–10%. Quite a lot of lung function can be lost before saturation suffers.
- No gain from “extra” oxygen in a normal person. If alveolar PO₂ rises from 100 to 120 mmHg, saturation goes only from about 97% to 98%. So hyperventilating or breathing 100% O₂ at sea level barely raises O₂ content, because Hb is already full.
- The exception: someone whose PaO₂ is low (lung disease, high altitude) has plenty of deoxy-Hb, so for them extra O₂ does raise saturation.
P50
- P50 is the PO₂ at which Hb is 50% saturated. It is the standard index of Hb’s affinity for O₂.
- Normal adult value at sea level: 27 mmHg.
- A change in P50 moves mainly the steep part of the curve.
| P50 | Affinity of Hb for O₂ | Effect | |
|---|---|---|---|
| Right shift | ↑ (above 27) | ↓ | O₂ released more easily to tissues |
| Left shift | ↓ (below 27) | ↑ | O₂ picked up more easily, released less |
Factors affecting Hb-binding affinity with oxygen
The rule of thumb: an exercising muscle is warm, acidic and full of CO₂, and every one of those shifts the curve to the right, which unloads more O₂ exactly where it is needed.
The effect of CO₂ and H⁺ on Hb’s O₂ affinity is called the Bohr effect (more at Carbon dioxide transport).
Temperature
- A rise in temperature shifts the curve right (lower affinity). A fall shifts it left.
- Active tissue is warmer, so it receives more O₂.
pH
- A fall in pH (acidosis) shifts the curve right; a rise (alkalosis) shifts it left. This drop in affinity with acid is the Bohr effect.
- In tissue capillaries, CO₂ enters the red cells and lowers their pH, so O₂ is released.
- Under normal conditions Hb takes up about 0.7 mol of H⁺ for every 1 mol of O₂ it releases.
A slip in your book
Your book credits the 1904 discovery to “Christian Bohr and Niels Bohr”. The 1904 paper was by Christian Bohr, Karl Hasselbalch and August Krogh. Niels Bohr, Christian’s son, was the Nobel physicist. The book’s own “Scientist contributed” box also says 1903, so the two dates disagree. In the exam, “Christian Bohr (1904)” is safe.
Carbon dioxide
- CO₂ released by metabolism forms H⁺ (lowering pH), which shifts the curve right.
- CO₂ also acts directly: it binds the uncharged amino (–NH₂) groups of Hb to form carbamino groups. The added negative charge changes the shape of Hb and lowers its O₂ affinity.
- So the right shift in acidosis is partly from the pH and partly from CO₂ binding to Hb itself.
- Active tissue gets a double benefit: metabolic vasodilation brings more blood, and the local high CO₂ and acidity make that blood give up its O₂ more readily.
2,3-DPG
- Red cells have no mitochondria, so they make energy by anaerobic glycolysis. A side product is 2,3-diphosphoglycerate (2,3-DPG), also called 2,3-bisphosphoglycerate (2,3-BPG). Red cells hold far more of it than other cells, roughly one molecule per Hb molecule.
- It binds deoxy-Hb 1:1 in the central cavity between the two β chains. Its negative charges (about 3.5) pair with positively charged amino acids (eight of them) lining that cavity, which stabilizes the low-affinity form.
- Result: more 2,3-DPG means a right shift and more O₂ released to the tissues.
- It rises in anemia, exercise and chronic hypoxia (high altitude, chronic lung disease), because hypoxia speeds up red-cell glycolysis.
Factors that affect 2,3-DPG in red cells
| Factor | Effect on 2,3-DPG | Why it matters |
|---|---|---|
| Acidosis (low pH) | ↓ | It slows red-cell glycolysis |
| Fetal Hb | binds it poorly | The γ chains of HbF grip 2,3-DPG less than adult β chains do, so HbF has higher affinity (a left shift) and can pull O₂ from the mother’s blood in the placenta |
| Hormones: growth hormone, thyroxine, testosterone | ↑ | They stimulate its synthesis |
| High altitude | ↑ (a lot) | More O₂ is released to the tissues |
| Hypoxia (low PO₂) | ↑ | |
| Stored bank blood | ↓ | A transfusion of stored blood delivers O₂ poorly at first, which matters most in a hypoxic patient. Citrate-phosphate-dextrose (CPD) storage loses less than acid-citrate-dextrose (ACD) storage |
Myoglobin
- The O₂-binding pigment of muscle. It looks like one Hb subunit and binds one O₂ per molecule.
- Its curve lies far to the left and is hyperbolic, not sigmoid, because there are no subunits to cooperate.
- High affinity means it takes O₂ from blood and stores it, releasing it only when PO₂ gets very low, for example during a sustained contraction that squeezes off the muscle’s blood flow.
- It is more abundant in trained muscle, especially after isometric training. It is also thought to help move O₂ from blood to the mitochondria.
Effect of carbon monoxide (CO)
- CO binds Hb about 210 times more strongly than O₂ does, and it competes for the same sites, forming carboxyhemoglobin (HbCO).
- O₂ content falls sharply: at 60% HbCO, blood carries less than 10 mL O₂/dL. A PCO of only about 1 mmHg is enough to saturate Hb with CO.
- PaO₂ stays normal, because the diffusion of O₂ into plasma is unaffected.
- CO also shifts the curve left, so the little O₂ that is bound is released less readily. It is a double hit, and it can kill if not treated.
- Normal HbCO is 1–2%. In heavy smokers, traffic police and people living in heavy traffic it can be about 10%.
Clinical: why CO poisoning is so dangerous
It produces an anemic type of hypoxia, since the Hb is present but unavailable. It is dangerous without warning signs:
- Undetectable: CO has no colour or smell and does not irritate, so the victim does not notice it.
- PaO₂ is normal, so the chemoreceptors are not stimulated and breathing does not increase.
- Cherry-red colour: HbCO is bright red, which hides the pallor or cyanosis that would signal hypoxia.
Treatment: breathe 100% O₂. The high PO₂ competes CO off the Hb. Hyperbaric O₂ speeds this further. Adding 5% CO₂ to the inspired gas stimulates breathing, which washes CO out faster.
Factors that shift the oxy-Hb dissociation curve
| Shift to the RIGHT (P50 ↑, affinity ↓, O₂ released) | Shift to the LEFT (P50 ↓, affinity ↑, O₂ held) |
|---|---|
| Temperature ↑ | Temperature ↓ |
| pH ↓ (H⁺ ↑) | pH ↑ (H⁺ ↓) |
| PCO₂ ↑ | PCO₂ ↓ |
| 2,3-DPG ↑ | 2,3-DPG ↓ |
| Hypoxia (via 2,3-DPG) | Fetal Hb |
| Carbon monoxide | |
| (also myoglobin’s own curve lies to the left) |
Draw it: the curve and its shifts
- Axes: PO₂ 0–100 mmHg on x; Hb saturation 0–100% on y.
- Draw an S curve through 27 → 50% (dashed lines to both axes: P50), 40 → 75% (v, venous), 60 → 90% and 100 → 97–98% (a, arterial).
- Label the steep phase (10–60) and the plateau (above 60–70).
- Draw one curve to the right (“temp ↑, pH ↓, PCO₂ ↑, 2,3-DPG ↑”) and one to the left (“HbF, CO, temp ↓, pH ↑”); add a hyperbolic myoglobin curve far left if the question asks.
Exam-answer skeleton: "O₂–Hb dissociation curve" (short note)
- Definition and the S shape (with the reason: cooperative binding).
- The labelled diagram with its landmarks.
- Steep phase and its significance (unloading in tissues).
- Plateau phase and its two significances.
- P50: its value and meaning.
- The right-shift and left-shift table; the Bohr effect in one line.
- Applied: CO poisoning, fetal Hb, stored blood.
Asked in exams
- The O₂–hemoglobin dissociation curve and what shifts it: Jan 2010, 4 marks · Aug 2017, 2 marks · Jan 2021, 5 marks · Jan/Feb 2022, 15 marks · May 2022, MCQ · Apr 2023, MCQ · Mar 2024, MCQ