In one breath
CO₂ travels from the tissues to the lungs in three forms: about 70% as bicarbonate, 23% bound to proteins as carbamino compounds, and 7% dissolved. Carbonic anhydrase in the red cells makes the bicarbonate; the chloride shift swaps it out into plasma. Because deoxygenated Hb holds more CO₂ and H⁺, releasing O₂ in the tissues helps blood take up CO₂, and taking up O₂ in the lungs helps blood let CO₂ go. That second half is the Haldane effect.
Builds on: Oxygen transport · Oxygen–hemoglobin dissociation curve · Leads to: Chemical control of breathing · Asphyxia, hypercapnia and hypocapnia
CO₂ is made mainly by aerobic metabolism of glucose (and when carbohydrate is turned into fat). Venous blood carries it to the lungs, where it is breathed out.
| Form | Share | Where |
|---|---|---|
| Bicarbonate (HCO₃⁻) | ~70% | Formed in red cells, mostly carried in plasma |
| Carbamino compounds | ~23% | Mainly carbamino-Hb in red cells; a little with plasma proteins |
| Dissolved | ~7% | Plasma |
Dissolved form in plasma
- Dissolved CO₂ follows Henry’s law (see Oxygen transport): it is proportional to PCO₂.
- CO₂ is about 20 times more soluble than O₂: its solubility is 0.06 mL/dL per mmHg.
- In venous blood: 46 mmHg × 0.06 ≈ 2.8 mL/dL dissolved.
- Plasma has no carbonic anhydrase, so little carbonic acid forms there. A small amount of CO₂ binds plasma proteins as carbamino-protein.
As bicarbonate ions
-
Most CO₂ diffuses straight into the red cells, which are rich in carbonic anhydrase (CA):
CO₂ + H₂O ⇌ (CA) ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻
-
What happens to the H⁺: the red-cell membrane barely lets H⁺ through, so it stays inside and is buffered by Hb:
H⁺ + HbO₂⁻ ⇌ HHb + O₂
- Binding H⁺ lowers Hb’s O₂ affinity (the Bohr effect), so O₂ is released to the tissue, and the H⁺ is mopped up, so more CO₂ can be converted. The two gases help each other.
- In the lungs everything runs backwards: oxygenation of Hb drives CO₂ back out.
-
The chemistry happens in the red cells, but most of the bicarbonate then rides in the plasma, after the chloride shift.
Chloride shift
- HCO₃⁻ builds up in the red cell and moves out into plasma.
- To keep the cell electrically neutral, Cl⁻ moves in in exchange.
- The exchange is carried by the anion exchanger 1 (AE1) in the red-cell membrane, formerly called the band 3 protein.
- This Cl⁻-for-HCO₃⁻ swap is the chloride shift, also called the Hamburger shift after the scientist who described it.
- In the lungs the shift reverses: HCO₃⁻ goes back into the cell, and Cl⁻ comes out.
Applied: why venous hematocrit is higher
Venous red cells contain about 20% more Cl⁻ than arterial ones. Cl⁻ is osmotically active, so the cells take in water and swell. That makes the venous hematocrit about 3% higher than the arterial one.
Draw it: the chloride shift
Draw a red cell beside a tissue capillary. CO₂ enters, then CO₂ + H₂O → (CA) → H₂CO₃ → H⁺ + HCO₃⁻. Draw H⁺ binding to Hb (with O₂ leaving to the tissue), HCO₃⁻ leaving through AE1 (band 3), and Cl⁻ entering through the same exchanger. Add a small “H₂O in, cell swells” arrow.
As carbamino compound
-
CO₂ binds the free amino (–NH₂) groups of Hb directly, forming carbaminohemoglobin:
CO₂ + Hb–NH₂ ⇌ Hb–NH–COOH
-
Deoxy-Hb binds more CO₂ than oxy-Hb, so unloading O₂ in the tissues boosts this route (part of the Haldane effect).
-
About 23% of CO₂ travels this way.
CO₂ dissociation curve
- A plot of blood CO₂ content against PCO₂, made like the O₂ curve.
| Feature | CO₂ dissociation curve | O₂–Hb dissociation curve |
|---|---|---|
| Shape | Almost a straight line over the working range | Sigmoid |
| Over the working range | Steep and linear between PCO₂ 40 and 46 mmHg | Mostly flat between PO₂ 40 and 100 mmHg |
| Saturation | No saturation point in the physiological range | Saturates near 100 mmHg |
| Volume carried | Blood holds much more CO₂ than O₂ | ~20 mL O₂/dL |
- Because the curve is steep, a small change in PCO₂ loads or unloads a lot of CO₂.
- Worth knowing, though not in your pages: your chapter makes the comparison without giving figures. The standard values are a total CO₂ content of about 48 mL/dL in arterial blood and about 52 mL/dL in venous blood.
- Effect of PO₂: at higher PO₂ the whole curve moves down and to the right. At any given PCO₂, blood holds more CO₂ when its PO₂ is low. This inverse relationship is the Haldane effect.
Haldane effect
- Definition: oxygenation of Hb lowers its affinity for CO₂ (and H⁺), so taking up O₂ in the lungs drives CO₂ out of the blood. The reverse happens in the tissues: releasing O₂ lets blood take up more CO₂.
- Why it happens:
- Oxy-Hb is a stronger acid and binds fewer H⁺, so H⁺ is released, combines with HCO₃⁻ and is breathed out as CO₂.
- Oxy-Hb forms fewer carbamino compounds.
- Named after John Scott Haldane (1860–1936).
- Worth knowing, though not in your pages: the Haldane effect accounts for close to half of the CO₂ unloaded in the lungs.
Bohr effect
- Definition: a rise in PCO₂ or H⁺ (and temperature) lowers Hb’s affinity for O₂, which shifts the O₂–Hb curve right and raises P50.
- In the tissues, CO₂ enters the blood, the pH falls, and Hb gives up more O₂. Tissue oxygenation improves exactly where metabolism is high.
- Mechanism: mainly the drop in pH, since deoxy-Hb binds H⁺ more avidly than oxy-Hb; a rise in temperature adds to it.
- Named after Christian Bohr (1855–1911), a Danish physiologist.
| Bohr effect | Haldane effect | |
|---|---|---|
| What changes | CO₂ / H⁺ | O₂ |
| What it affects | Hb’s affinity for O₂ | Blood’s affinity for CO₂ |
| Curve it shifts | O₂–Hb curve → right | CO₂ curve → down and right |
| Where it matters most | Tissues: helps unload O₂ | Lungs: helps unload CO₂ |
Don't copy your book's one-line summary
The book’s Key Concepts pair the effects confusingly (“Haldane helps loading of O₂… Bohr helps loading CO₂”). Remember it this way instead:
- Bohr is CO₂ pushing O₂ off Hb in the tissues.
- Haldane is O₂ pushing CO₂ off blood in the lungs.
- Each gas helps the other leave.
Exam-answer skeleton: "Describe the transport of CO₂ in blood" (long essay)
- Where CO₂ comes from, and the three forms with their percentages.
- The dissolved form: Henry’s law, solubility 20× O₂, 46 × 0.06; no CA in plasma.
- Bicarbonate: the CA reaction, H⁺ buffered by Hb, then the chloride shift (with a diagram) and why venous Hct is higher.
- Carbamino-Hb: the reaction; deoxy-Hb binds more.
- The CO₂ dissociation curve: its shape compared with the O₂ curve (with a diagram).
- The Haldane effect and the Bohr effect, with the comparison table.
- The reverse events in the lungs.
Asked in exams
- How blood carries CO₂: Dec 2023, MCQ
- Chloride shift: Jul 2012, 2 marks · Jul 2018, 4 marks
- Haldane effect: Jul/Aug 2014, 4 marks · Aug 2017, 4 marks · Sep/Oct 2019, 4 marks