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# Bicarbonate–CO₂ buffer system

The bicarbonate–CO₂ pair buffers blood acids; the lungs control CO₂ and the kidneys control bicarbonate.

Updated 2026-11-01

## Key facts

- CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻; carbonic anhydrase speeds the first step in red cells and renal tubules.
- Henderson–Hasselbalch: pH = 6.1 + log ([HCO₃⁻] / (0.03 × pCO₂)). The pH depends on the ratio, not on either value alone.
- It works well despite a pKa of 6.1 because it is an open system: the lungs remove CO₂ in minutes and the kidneys adjust HCO₃⁻ over days.
- Other buffers: haemoglobin (histidines), plasma proteins, phosphate (mainly in urine) and bone.
- The 'total CO₂' on a chemistry panel is almost all bicarbonate.

## In detail

- Metabolism produces volatile acid every day (CO₂, removed by the lungs) and fixed acid (sulfuric, phosphoric, lactic, keto acids), which the kidneys must excrete.
- When a fixed acid enters the blood, HCO₃⁻ neutralises it and becomes CO₂, which is breathed out; plasma HCO₃⁻ falls and becomes a marker of the acid load.
- The kidney reclaims almost all filtered HCO₃⁻ in the proximal tubule and makes new HCO₃⁻ by excreting H⁺ as titratable acid (phosphate) and as ammonium (NH₄⁺) made from glutamine.
- The lungs respond in minutes: chemoreceptors sense H⁺ and CO₂ and change ventilation; so respiratory compensation is fast and renal compensation takes 3 to 5 days.
- In the red cell, CO₂ becomes HCO₃⁻, which leaves in exchange for Cl⁻ (chloride shift); the H⁺ is buffered by deoxygenated haemoglobin (Haldane effect).

**Also called**
Henderson–Hasselbalch equation, Bicarbonate buffer

## Clinical notes

- In COPD with chronic CO₂ retention the kidney raises HCO₃⁻; over-ventilating such a patient produces a post-hypercapnic alkalosis.
- Carbonic anhydrase inhibitors (acetazolamide) waste bicarbonate in the urine and cause a normal-anion-gap metabolic acidosis.
- In advanced chronic kidney disease ammonium production fails and metabolic acidosis appears.

## Related conditions

- [Respiratory acidosis](https://durgical.com/en/conditions/respiratory-acidosis/)
- [Metabolic alkalosis](https://durgical.com/en/conditions/metabolic-alkalosis/)
- [Chronic obstructive pulmonary disease (COPD)](https://durgical.com/en/conditions/chronic-obstructive-pulmonary-disease/)
- [Chronic kidney disease](https://durgical.com/en/conditions/chronic-kidney-disease/)

## Related

- [Acid–base interpretation (step by step)](https://durgical.com/en/biochemistry/topics/acid-base-interpretation/)
- [Acid–base compensation rules](https://durgical.com/en/biochemistry/topics/acid-base-compensation-rules/)
- [Hemoglobin and 2,3-BPG](https://durgical.com/en/biochemistry/enzymes/hemoglobin-and-2-3-bpg/)

## Test yourself

Think of the answer, then tap the question to see it.

## Why does bicarbonate buffer well at pH 7.4 when its pKa is 6.1?

Because it is an open system: the lungs remove the CO₂ formed and the kidneys replace HCO₃⁻, so the ratio is held.

## Which enzyme speeds the hydration of CO₂?

Carbonic anhydrase (a zinc enzyme), found in red cells and renal tubules.

## How does the kidney make new bicarbonate?

By excreting H⁺ bound to phosphate (titratable acid) and as ammonium made from glutamine; each H⁺ excreted returns one HCO₃⁻ to the blood.

## Which compensation is faster, respiratory or renal?

Respiratory (minutes to hours); renal compensation takes 3 to 5 days to complete.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Carbon Dioxide (CO2) in Blood: MedlinePlus Medical Test](https://medlineplus.gov/lab-tests/carbon-dioxide-co2-in-blood/) (MedlinePlus, US National Library of Medicine, 2026); [CO2 blood test: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/003469.htm) (MedlinePlus, US National Library of Medicine, 2026); [Arterial Blood Gas (ABG) Test: MedlinePlus Medical Test](https://medlineplus.gov/lab-tests/arterial-blood-gas-abg-test/) (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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