Physiology · Renal, fluids and acid–base
Metabolic acidosis, the anion gap and compensation !
- Mechanism
- Exam priority: high
In metabolic acidosis the blood loses bicarbonate or gains acid. The lungs breathe more to blow off CO₂ and the kidneys make new bicarbonate.
Updated 2026-11-01
Also called: Kussmaul breathing, Winter's formula
See it in 3D: Kidneys · Medulla oblongata
What it is
Metabolic acidosis is a primary fall in plasma HCO₃⁻, either because an acid is added (which consumes HCO₃⁻) or because HCO₃⁻ is lost through the gut or kidney. The body defends itself in three stages: buffers within seconds, hyperventilation within minutes to hours and increased renal acid excretion over days. The anion gap calculation (Biochemistry page) separates the two big groups of causes.
How it works, step by step
- A strong acid enters (e.g. ketoacids): its H⁺ reacts with HCO₃⁻ to form CO₂ and water, and HCO₃⁻ falls.
- The acid's anion (β-hydroxybutyrate, lactate) stays in plasma unmeasured, raising the anion gap.
- Proteins, phosphate and bone buffer part of the H⁺ over seconds to hours.
- H⁺ stimulates peripheral chemoreceptors; ventilation rises, PaCO₂ falls and pH moves toward normal without reaching it.
- In the proximal tubule, glutamine is converted to NH₄⁺ and new HCO₃⁻; NH₄⁺ is excreted and HCO₃⁻ returns to blood.
- In the collecting duct, α-intercalated cells secrete more H⁺, excreted bound to NH₃ and phosphate.
- If the cause is HCO₃⁻ loss (diarrhea), the kidney retains Cl⁻ and the gap stays normal.
Equations
- PaCO₂
- mmHg
- HCO₃⁻
- mEq/L
Shortcut: PaCO₂ usually resembles the last two digits of the pH (pH 7.25 → PaCO₂ ≈ 25).
- AG
- ≈ 8–12 mEq/L (laboratory dependent)
Add ≈ 2.5 for every 1 g/dL that albumin is below 4. Details and the delta ratio are on the Biochemistry page.
Two families of metabolic acidosis
| Type | What happens | Causes | Clue |
|---|---|---|---|
| High anion gap | An acid with an unmeasured anion is added | Ketoacidosis, lactic acidosis, uremia, methanol, ethylene glycol, salicylates | High unmeasured anion; high osmolar gap with methanol or ethylene glycol |
| Normal gap: gut loss | HCO₃⁻ is lost through the bowel | Diarrhea, fistulas | Negative urine anion gap (high NH₄⁺) |
| Normal gap: renal | The kidney loses HCO₃⁻ or fails to excrete H⁺ | Renal tubular acidosis, carbonic anhydrase inhibitors | Positive urine anion gap |
| Normal gap: dilutional | Lots of Cl⁻ without HCO₃⁻ | Large volumes of 0.9% saline | High Cl⁻ after resuscitation |
Clinical notes
- Diabetic ketoacidosis presents with Kussmaul breathing, fruity breath, dehydration and a high anion gap.
- In shock, hypoperfusion produces lactic acidosis; a high lactate marks severity.
- Acute diarrhea in children can cause hyperchloremic acidosis with hypokalemia.
- In chronic kidney disease, lower NH₄⁺ production leaves an acidosis that harms bone and muscle.
Test yourself
Think of the answer, then tap the question to see it.
A patient has HCO₃⁻ 10 mEq/L and PaCO₂ 32 mmHg: is compensation appropriate?
No. Winter's predicts 1.5 × 10 + 8 = 23 ± 2 mmHg. A PaCO₂ of 32 is higher than expected, so there is also respiratory acidosis (ventilation is not keeping up).
Why does diarrhea cause a normal anion gap acidosis and ketoacidosis a high gap?
In diarrhea HCO₃⁻ is lost and the kidney retains Cl⁻, which takes its place. In ketoacidosis an acid is added whose anion (β-hydroxybutyrate) is not measured and opens the gap.
How does the kidney generate new bicarbonate in metabolic acidosis?
The proximal tubule metabolises glutamine to NH₄⁺ and HCO₃⁻; it excretes NH₄⁺ and returns HCO₃⁻ to blood. The collecting duct secretes H⁺, excreted as NH₄⁺ and titratable acid.
Why can metabolic acidosis raise serum potassium?
Excess H⁺ enters cells and K⁺ leaves to keep electrical neutrality; its secretion in the collecting duct also falls.
See it in 3D
The structures of Durgical's 3D anatomy where it happens.
Related topics
- Reading an arterial blood gas step by step
- Renal handling of H⁺ and bicarbonate
- Buffers and the Henderson–Hasselbalch equation
- Mixed acid–base disorders
- Control of breathing, chemoreceptors and lung reflexes
- Potassium balance
Related conditions
- High anion gap metabolic acidosis
- Normal anion gap (hyperchloraemic) metabolic acidosis
- Diabetic ketoacidosis
- Lactic acidosis
- Methanol poisoning
- Ethylene glycol poisoning
- Chronic kidney disease
- Acute (viral) gastroenteritis
In Biochemistry
- Anion gap and delta ratio
- Albumin
- Bicarbonate–CO₂ buffer system
- Ammonia (ammonium)
- Glutamine
- Acid–base compensation rules
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: 26.5 Disorders of Acid-Base Balance (OpenStax (Rice University), 2022); Metabolic acidosis: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Diabetic ketoacidosis: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); 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).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.