CO₂ transport: bicarbonate, the chloride shift, Bohr vs Haldane
Blood carries carbon dioxide in three forms, mostly as bicarbonate made inside the red cell. One rule then separates the Bohr effect from the Haldane effect.
Describe the three forms of CO₂ transport and distinguish the Bohr effect from the Haldane effect.
The short version
- CO₂ is carried as bicarbonate, carbamino compounds and dissolved CO₂; bicarbonate is the largest share in every version of the split.
- Carbonic anhydrase in the red cell makes carbonic acid from CO₂ and water, which splits into H⁺ and HCO₃⁻.
- HCO₃⁻ leaves the cell in exchange for Cl⁻ (the chloride shift), so venous plasma has slightly less chloride than arterial plasma.
- Bohr: CO₂ and H⁺ change haemoglobin's grip on oxygen. Haldane: oxygen changes haemoglobin's grip on CO₂ and H⁺.
- Deoxyhaemoglobin carries more CO₂, so blood picks up CO₂ in the tissues and oxygenation releases it in the lungs.
The puzzle: where did the chloride go?
Take blood from an artery and blood from a vein and compare the plasma. The venous plasma has slightly less chloride.[1]
The explanation is part of CO₂ transport, which this lesson follows from tissue to lung. It also separates two effects that students often mix up, the Bohr effect and the Haldane effect.
It builds on one idea from the last lesson: a right shift of the oxygen curve means haemoglobin lets go of oxygen more easily.[2]
Three forms of carbon dioxide transport
Every cell that burns fuel makes carbon dioxide, and blood must carry it to the lungs. It travels in three forms: bicarbonate, carbamino compounds and dissolved CO₂.[1][3]
| Form | Usual teaching figure | Total CO₂ in arterial blood |
|---|---|---|
| Bicarbonate | about 70 | about 90 |
| Carbamino compounds | about 20 | about 5 |
| Dissolved CO₂ | about 10 | about 5 |
Textbook splits vary. The usual teaching figure is about 70 / 20 / 10[5]. If you count all the CO₂ in arterial blood, bicarbonate is about 90 percent, with about 5 percent carbamino and 5 percent dissolved[3][6]. Bicarbonate is the largest in every version.
One molecule into the red cell: carbonic anhydrase
Follow one molecule. It leaves a tissue cell and diffuses into a red blood cell. Inside, the enzyme carbonic anhydrase combines it with water to make carbonic acid. The acid splits into a hydrogen ion and bicarbonate.[1][3]
catalysed by carbonic anhydrase
The chloride shift
The bicarbonate leaves the cell through an exchanger, and chloride enters in its place. That swap is the chloride shift.[1][3][4]
This answers the opening puzzle: chloride in venous plasma is slightly lower than in arterial plasma, because chloride moved into the red cells as bicarbonate moved out.[1]
The carbamino form
The carbamino form is simpler. Carbon dioxide binds directly to amino groups on the globin chains of haemoglobin.[1][3]
Deoxyhaemoglobin binds carbon dioxide about 3.5 times better than oxyhaemoglobin.[1][3]
In the lungs everything runs in reverse. Bicarbonate re-enters the cell, carbon dioxide is regenerated, and it diffuses out to be exhaled.[4][6]
Bohr effect vs Haldane effect
The Bohr effect is carbon dioxide and acid changing haemoglobin's grip on oxygen. In the tissues, CO₂ and H⁺ lower haemoglobin's affinity for oxygen, which shifts the curve right and releases oxygen.[2][4]
The Haldane effect is oxygen changing haemoglobin's grip on carbon dioxide. When haemoglobin gives up its oxygen in the tissues, deoxyhaemoglobin picks up more CO₂ and more H⁺. When it takes up oxygen in the lungs, it lets them go, so CO₂ is released.[3][4]
| Bohr effect | Haldane effect | |
|---|---|---|
| What changes what | CO₂ and H⁺ change oxygen binding | Oxygen changes CO₂ and H⁺ binding |
| In the tissues | Lower O₂ affinity, curve shifts right, O₂ released | Deoxyhaemoglobin picks up more CO₂ and H⁺ |
| In the lungs | CO₂ and H⁺ fall, O₂ affinity rises, O₂ loads | Oxygenation releases CO₂ |
Arterial vs mixed venous CO₂ content
Mixed venous blood carries about 2 mmol/L more total carbon dioxide than arterial blood, and most of that extra is bicarbonate.[1][6]
The Haldane effect helps create this gap, because deoxygenated blood can carry more carbon dioxide at the same pressure.[3][6]
Practice question
Original · USMLE styleA 32-year-old woman is studied in a physiology experiment. Mixed venous blood entering her pulmonary capillaries has a PO₂ of 40 mmHg and a PCO₂ of 47 mmHg. As haemoglobin becomes oxygenated in the capillaries, CO₂ is released from the blood.
Common questions
What are the three forms of CO₂ transport in blood?
Bicarbonate, carbamino compounds and dissolved CO₂. The usual teaching figure is about 70, 20 and 10 percent. Counting all the CO₂ in arterial blood gives about 90, 5 and 5. Bicarbonate is the largest in every version.
What is the chloride shift?
Bicarbonate made in the red cell leaves through an exchanger and chloride enters in its place. As a result, venous plasma has slightly less chloride than arterial plasma.
What is the difference between the Bohr effect and the Haldane effect?
In the Bohr effect, carbon dioxide and acid change haemoglobin's grip on oxygen. In the Haldane effect, oxygen changes haemoglobin's grip on carbon dioxide. Bohr: CO₂ changes oxygen. Haldane: oxygen changes CO₂.
How does carbon dioxide bind to haemoglobin?
It binds directly to amino groups on the globin chains, forming carbamino compounds. Deoxyhaemoglobin binds carbon dioxide about 3.5 times better than oxyhaemoglobin.
Transcript
Read the full narration, by chapter687 words
0:00Arterial vs venous plasma: where did the chloride go?
Take blood from an artery and blood from a vein, and compare the plasma. The venous plasma has slightly less chloride. Where did it go, and what does it have to do with carbon dioxide? Today: describe the three forms of carbon dioxide transport, and tell the Bohr effect from the Haldane effect.
0:19Last lesson in one line: the right shift
One idea from the last lesson. A right shift of the oxygen curve means haemoglobin lets go of oxygen more easily. Every cell that burns fuel makes carbon dioxide, and blood must carry it to the lungs.
0:33Three forms of CO2 transport
It travels in three forms. Textbook splits vary. One common version: about 70% as bicarbonate, 20 as carbamino compounds, 10 dissolved. Many US exam resources say 90, five and five. Bicarbonate is the largest in every version.
0:53One molecule into the red cell: carbonic anhydrase
Follow one molecule. It leaves a tissue cell and diffuses into a red blood cell. Inside, an enzyme called carbonic anhydrase combines it with water to make carbonic acid. The acid splits into a hydrogen ion and bicarbonate.
1:10Buffering by deoxyhaemoglobin and the chloride shift
The hydrogen ion is buffered by deoxyhaemoglobin. The bicarbonate leaves the cell through an exchanger, and chloride enters in its place. That swap is the chloride shift. So chloride in venous plasma is slightly lower than in arterial plasma.
1:28The carbamino form
The carbamino form is simpler. Carbon dioxide binds directly to amino groups on the globin chains of haemoglobin. Deoxyhaemoglobin binds carbon dioxide about three and a half times better than oxyhaemoglobin.
1:43In the lungs everything reverses
In the lungs everything runs in reverse. Bicarbonate re-enters the cell, carbon dioxide is regenerated, and it diffuses out to be exhaled.
1:54The Bohr effect
Now the two named effects, which students mix up. The Bohr effect is carbon dioxide and acid changing haemoglobin's grip on oxygen. In the tissues, carbon dioxide and hydrogen ions lower haemoglobin's affinity for oxygen, which shifts the curve right and releases oxygen.
2:13The Haldane effect and a trick to keep them apart
The Haldane effect is oxygen changing haemoglobin's grip on carbon dioxide. When haemoglobin gives up its oxygen in the tissues, deoxyhaemoglobin picks up more carbon dioxide and more hydrogen ions. When haemoglobin takes up oxygen in the lungs, it lets them go, so carbon dioxide is released. A trick: Bohr, carbon dioxide changes oxygen. Haldane, oxygen changes carbon dioxide.
2:41Arterial vs mixed venous CO2 content
Mixed venous blood carries about two millimoles per litre more total carbon dioxide than arterial blood, and most of that extra is bicarbonate. The Haldane effect helps create this gap, because deoxygenated blood can carry more carbon dioxide at the same pressure.
3:00Your turn: a practice question on the Haldane effect
Your turn. A 32-year-old woman is studied during a physiology experiment. Mixed venous blood entering her pulmonary capillaries has a PaO2 of 40 and a PaCO2 of 47 mm Hg. As haemoglobin becomes oxygenated in the capillaries, carbon dioxide is released from the blood. Which of the following best explains why oxygenation of haemoglobin promotes carbon dioxide release? A, oxygen increases the activity of carbonic anhydrase. B, carbon dioxide lowers haemoglobin's affinity for oxygen. C, oxygen makes carbon dioxide less soluble in plasma. D, oxygenation reverses the chloride shift without any change in carbon dioxide binding to haemoglobin. E, oxyhaemoglobin binds carbon dioxide and hydrogen ions less avidly than deoxyhaemoglobin. Pause here and decide.
4:03The options explained, answer E
A is out: carbonic anhydrase speeds the reaction in both directions regardless, and the oxygen effect works through haemoglobin. B is out: that is true, but it is the Bohr effect, carbon dioxide acting on oxygen binding, the reverse direction. C is out: the Haldane effect works through haemoglobin binding, not through plasma solubility. D is out: bicarbonate does move back into the cell, but the change in haemoglobin binding is part of the effect, so it cannot be left out. So the answer is E. Oxyhaemoglobin binds carbon dioxide and hydrogen ions less avidly than deoxyhaemoglobin, so loading oxygen unloads carbon dioxide. That is the Haldane effect.
4:51Recap and next lesson
Three things to keep. One: carbon dioxide is carried mostly as bicarbonate, made in the red cell, with the chloride shift. Two: Bohr, carbon dioxide changes oxygen binding. Haldane, oxygen changes carbon dioxide binding. Three: deoxyhaemoglobin carries more carbon dioxide, so blood picks up carbon dioxide in the tissues, and oxygenation releases it in the lungs. Next, control of breathing: central and peripheral chemoreceptors.
Sources
Numbers in the text, e.g. [1], point here- Deranged Physiology. Transport of carbon dioxide in the blood. derangedphysiology.com/main/cicm-primary-exam/respiratory-system/Chapter-114/transport-carbon-dioxide-blood
- Deranged Physiology. Factors which influence the affinity of haemoglobin for oxygen. derangedphysiology.com/main/cicm-primary-exam/respiratory-system/Chapter-113/factors-which-influence-affinity-haemoglobin-oxygen
- LITFL. Carbon dioxide transport. partone.litfl.com/carbon_dioxide_transport.html
- TeachMePhysiology. Transport of carbon dioxide in the blood. teachmephysiology.com/respiratory-system/gas-exchange/transport-carbon-dioxide-blood/
- OpenStax. Anatomy and Physiology 2e, 22.5 Transport of gases. openstax.org/books/anatomy-and-physiology-2e/pages/22-5-transport-of-gases
- Europe PMC, PMC12463780 (carbon dioxide carriage and the Haldane effect). pmc.ncbi.nlm.nih.gov/articles/PMC12463780/
The practice question is original and its patient is synthetic. Every fact is checked against the sources above in independent accuracy reviews. Always follow your local guidelines and your own laboratory’s ranges.
Image credits. Illustrations: Servier Medical Art (smart.servier.com), CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/), adapted (recoloured, outlined, labelled): "Blood test - Tube", "Gas exchanges" and "Erythrocyte - Isotonic". Original diagrams: the oxygen curves (schematic), the bicarbonate / carbamino / dissolved bars, the red-cell reaction ladder, the haemoglobin sketches, the arterial vs venous bars (schematic, not to scale) and the question card. No AI-generated teaching images.
Corrections. None so far. Spotted an error? Email info@medservatory.com with the lesson code MS-S1-RESP-007.
For exam study only, not medical advice. Read the medical disclaimer.
In this series
Playlist on YouTube- EP 01Lung volumes and capacities, explained5:26
- EP 02Obstructive vs restrictive lung disease: FEV1/FVC and loops5:23
- EP 03Lung compliance, Laplace and surfactant: why alveoli stay open5:23
- EP 04V/Q mismatch: shunt, dead space and the oxygen test5:18
- EP 05A-a gradient: the alveolar gas equation and the causes of hypoxaemia5:39
- EP 06Oxygen-hemoglobin dissociation curve: P50, shifts and content5:19
- EP 07CO₂ transport: bicarbonate, the chloride shift, Bohr vs Haldane5:29
- EP 08Central vs peripheral chemoreceptors and oxygen-induced hypercapnia5:27
- EP 09Hypoxic pulmonary vasoconstriction and cor pulmonale5:41
- EP 10CO, cyanide and methaemoglobin: why SpO₂ and PaO₂ fool you5:34