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.

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).

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.

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.

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

Sources: Carbon Dioxide (CO2) in Blood: MedlinePlus Medical Test (MedlinePlus, US National Library of Medicine, 2026); CO2 blood test: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Arterial Blood Gas (ABG) Test: MedlinePlus Medical 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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Representative model, for educational purposes only.