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[Physiology](https://durgical.com/en/physiology/) · [Renal, fluids and acid–base](https://durgical.com/en/physiology/#s-renal)

# 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

## Key points

- Henderson–Hasselbalch: pH depends on the ratio HCO₃⁻ / (0.03 × PCO₂), not on either value alone; normally ≈20:1.
- Bicarbonate is the main extracellular buffer because it is an open system: the CO₂ produced is breathed off.
- Phosphate (pKa ≈6.8): important inside cells and in urine (titratable acid).
- Proteins, especially haemoglobin: the largest intracellular buffering capacity; they buffer CO₂ inside red cells.
- Isohydric principle: all buffers in a compartment are in equilibrium with the same H⁺.
- Buffers only buy time: acid is truly removed by the lungs (CO₂) or the kidneys (fixed acids).

## 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)

**[HCO 3 −]**
mmol/L

**PCO 2**
mmHg

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

**CO₂ hydration**CO2 + 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)](https://durgical.com/en/conditions/chronic-kidney-disease/) | 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.

## Memory aid

“It’s the ratio that counts”: 20 parts bicarbonate to 1 part carbonic acid gives 7.4; the kidney minds the numerator, the lung the denominator.

## 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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## Related topics

- [Renal handling of H⁺ and bicarbonate](https://durgical.com/en/physiology/renal-handling-of-h-and-bicarbonate/)
- [Reading an arterial blood gas step by step](https://durgical.com/en/physiology/reading-an-arterial-blood-gas-step-by-step/)
- [Respiratory acidosis and alkalosis](https://durgical.com/en/physiology/respiratory-acidosis-and-alkalosis/)
- [Metabolic acidosis, the anion gap and compensation](https://durgical.com/en/physiology/metabolic-acidosis-the-anion-gap-and-compensation/)
- [CO₂ transport and the Haldane effect](https://durgical.com/en/physiology/co-transport-and-the-haldane-effect/)
- [High altitude and acclimatization](https://durgical.com/en/physiology/high-altitude-and-acclimatization/)

## Related conditions

- [Respiratory acidosis](https://durgical.com/en/conditions/respiratory-acidosis/)
- [Chronic kidney disease](https://durgical.com/en/conditions/chronic-kidney-disease/)

## In Biochemistry

- [Bicarbonate–CO₂ buffer system](https://durgical.com/en/biochemistry/topics/bicarbonate-co-buffer-system/)
- [Acid–base interpretation (step by step)](https://durgical.com/en/biochemistry/topics/acid-base-interpretation/)
- [Hemoglobin and 2,3-BPG](https://durgical.com/en/biochemistry/enzymes/hemoglobin-and-2-3-bpg/)

[← All of physiology](https://durgical.com/en/physiology/)

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](https://openstax.org/books/anatomy-and-physiology-2e/pages/26-4-acid-base-balance) (OpenStax (Rice University), 2022); [26.5 Disorders of Acid-Base Balance](https://openstax.org/books/anatomy-and-physiology-2e/pages/26-5-disorders-of-acid-base-balance) (OpenStax (Rice University), 2022); [Metabolic acidosis: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000335.htm) (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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