Physiology · Renal, fluids and acid–base

Buffers and the Henderson–Hasselbalch equation !

Concept
Exam priority: medium

Buffers soak up surplus acid or base within seconds and stop blood pH from swinging sharply.

Updated 2026-11-01

Also called: Buffer systems, Bicarbonate–CO₂ system

What it is

The body defends a pH of ≈7.40 with three lines: chemical buffers (seconds), the lungs (minutes to hours, adjusting CO₂) and the kidneys (hours to days, adjusting bicarbonate). A buffer is a weak acid and its conjugate base that give up or take up H⁺. The bicarbonate–CO₂ system is the most important extracellular buffer, not because of its pKa but because its two ends are regulated separately: CO₂ by the lungs and HCO₃⁻ by the kidneys.

Equations

Henderson–Hasselbalch (bicarbonate system)pH = 6.1 + log ( [HCO₃⁻] / (0.03 × PCO₂) )

6.1: pKa of the CO₂/HCO₃⁻ pair
0.03: CO₂ solubility (mmol/L per mmHg)
[HCO₃⁻]: mmol/L
PCO₂: mmHg

With HCO₃⁻ 24 and PCO₂ 40: 24/1.2 = 20; log 20 ≈ 1.3; pH ≈ 7.4.

CO₂ hydrationCO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻

Carbonic anhydrase speeds up the first step (red cells, renal tubule).

Arterial blood gas at sea level (approx.)

Parameter	Value	Note
pH	7.35–7.45
PaCO₂	35–45 mmHg
HCO₃⁻	22–26 mmol/L
In Bogotá (~2600 m)	Normal PaCO₂ and HCO₃⁻ somewhat lower	chronic altitude hyperventilation; use local reference values

Approximate values for a healthy adult at rest; each laboratory sets its own ranges.

The body’s buffers

Buffer	Where it works	pKa	Note
Bicarbonate/CO₂	Plasma and interstitium	6.1	Open system: lungs and kidneys set its two ends
Phosphate (HPO₄²⁻/H₂PO₄⁻)	Intracellular and urine	6.8	Forms titratable acid in urine
Proteins and haemoglobin	Cells, red cells	variable (histidine ≈6–7)	Deoxyhaemoglobin binds more H⁺
Bone (carbonate, phosphate)	Skeleton	—	Buffers chronic acidosis at the cost of bone mineral
Ammonia/ammonium	Urine	≈9.2	Traps H⁺ as NH₄⁺; the kidney adjusts how much it makes

Clinical notes

In chronic kidney disease, retained acid is partly buffered by bone, which contributes to bone loss.
If ventilation is fixed (deep sedation, severe COPD), the bicarbonate system loses its advantage: CO₂ generated by buffering is not cleared and pH falls further.

Test yourself

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

If bicarbonate’s pKa (6.1) is far from 7.4, why is it the most important extracellular buffer?

It is an open system: the CO₂ produced when it buffers H⁺ is removed by ventilation, and the kidney replaces HCO₃⁻. Its high concentration and separate regulation of both ends outweigh the distant pKa.

A patient has HCO₃⁻ 12 mmol/L and PaCO₂ 20 mmHg. Roughly what is the pH, and why?

12 / (0.03 × 20) = 12 / 0.6 = 20; log 20 ≈ 1.3; pH ≈ 7.4. The ratio is preserved although both values are badly deranged: look at the context (compensated or mixed disorder).

Why does deoxygenated haemoglobin improve CO₂ carriage in venous blood?

It is a better H⁺ acceptor than oxyhaemoglobin: by taking up the H⁺ released when CO₂ is hydrated, it lets more HCO₃⁻ form in the red cell (Haldane effect).

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Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.

Sources: 26.4 Acid-Base Balance (OpenStax (Rice University), 2022); 26.5 Disorders of Acid-Base Balance (OpenStax (Rice University), 2022); Metabolic acidosis: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2024); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 31). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).

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