Physiology · Renal, fluids and acid–base
Renal handling of H⁺ and bicarbonate !
- Mechanism
- Exam priority: medium
The kidney reclaims all filtered bicarbonate and makes new bicarbonate by excreting the acid that metabolism produces.
Updated 2026-11-01
Also called: Net acid excretion, Ammoniagenesis, Titratable acid
See it in 3D: Kidneys
What it is
Thousands of mmol of bicarbonate are filtered each day, and metabolism produces fixed acids the lungs cannot remove. The kidney does two jobs: reclaim filtered bicarbonate (mainly in the proximal tubule) and generate new bicarbonate by excreting H⁺ bound to urinary buffers: phosphate (titratable acid) and ammonia (as NH₄⁺). Ammonium is the route that can rise several-fold in chronic acidosis.
How it works, step by step
- In the tubular cell, carbonic anhydrase forms H⁺ and HCO₃⁻ from CO₂ and water.
- H⁺ goes into the lumen (NHE3 proximally; H⁺ pumps in the collecting duct) and HCO₃⁻ crosses the basolateral membrane into blood.
- If the secreted H⁺ meets filtered HCO₃⁻, that bicarbonate is merely reclaimed (no net gain).
- If it binds HPO₄²⁻ and leaves as H₂PO₄⁻, the HCO₃⁻ that entered the blood is new: titratable acid.
- The proximal tubule deaminates glutamine, producing NH₄⁺ (to urine) and new HCO₃⁻ (to blood).
- NH₃ is recycled in the medulla and, in the collecting duct, traps H⁺ as NH₄⁺, which cannot cross back.
- In chronic acidosis ammoniagenesis rises over days; it is the main renal defence.
The nephron: segments, transporters and diuretics
Na⁺ reabsorbed ≈ 65–70%Water reabsorbed ≈ 65–70%
Proximal tubule
- What it does: Reabsorbs ≈ 65–70% of filtered Na⁺ and water (isosmotically), nearly all glucose and amino acids, ≈ 80% of HCO₃⁻ and most K⁺ and phosphate. Secretes organic acids and bases (many drugs) and makes NH₄⁺ from glutamine.
- Transporters: NHE3 (Na⁺/H⁺) with carbonic anhydrase; SGLT2 (early segment, ≈ 90% of glucose) and SGLT1; NaPi-2a (phosphate); basolateral Na⁺/K⁺-ATPase.
- Hormones: Ang II stimulates NHE3 (more Na⁺ and HCO₃⁻: contraction alkalosis); PTH inhibits NaPi-2a (phosphaturia) and activates 1α-hydroxylase (active vitamin D).
- Drugs: Carbonic anhydrase inhibitors (1), SGLT2 inhibitors (2) and osmotic diuretics (3, with the thin descending limb).
- Disorders: Fanconi syndrome (loses glucose, amino acids, phosphate and HCO₃⁻); type 2 (proximal) renal tubular acidosis; familial renal glucosuria (SGLT2).
- Glomerulus and arterioles
- Proximal tubule
- Thin descending limb
- Thin ascending limb
- Thick ascending limb
- Distal convoluted tubule
- Collecting tubule and duct
- Juxtaglomerular apparatus (macula densa)
- Cortex
- Medulla
- Interstitial osmolality (≈ 300 → 1200 mOsm/kg)
The nephron: segments, transporters and diuretics
Na⁺ reabsorbed ≈ 2–5%Water reabsorbed variable (ADH)
Collecting tubule and duct
- What it does: Fine tuning: reabsorbs ≈ 2–5% of Na⁺, secretes K⁺ and H⁺ and reabsorbs water as ADH allows (urine from ≈ 50 to ≈ 1200 mOsm/kg). Principal cells handle Na⁺, K⁺ and water; intercalated cells handle acid–base.
- Transporters: Principal: ENaC, ROMK and BK (K⁺ secretion; BK is flow-driven), apical AQP2 (ADH) and basolateral AQP3/4. α-intercalated: H⁺-ATPase and H⁺/K⁺-ATPase (secrete acid). β-intercalated: pendrin (secrete HCO₃⁻). Inner medulla: urea transporters (ADH).
- Hormones: Aldosterone (more ENaC, ROMK, Na⁺/K⁺-ATPase and H⁺-ATPase); ADH via the V2 receptor → cAMP → AQP2 insertion; atrial natriuretic peptide curbs Na⁺ reabsorption.
- Drugs: ENaC blockers (6) and mineralocorticoid receptor antagonists (7): K⁺-sparing (risk of hyperkalemia). V2 receptor antagonists (8, vaptans): aquaretics.
- Disorders: Liddle syndrome (overactive ENaC: hypertension, hypokalemia, low renin and aldosterone); nephrogenic diabetes insipidus (V2 or AQP2, lithium); type 1 distal renal tubular acidosis (H⁺ secretion fails: urine pH > 5.5, hypokalemia, stones) and type 4 (hypoaldosteronism: hyperkalemia); SIADH (excess ADH).
- Glomerulus and arterioles
- Proximal tubule
- Thin descending limb
- Thin ascending limb
- Thick ascending limb
- Distal convoluted tubule
- Collecting tubule and duct
- Juxtaglomerular apparatus (macula densa)
- Cortex
- Medulla
- Interstitial osmolality (≈ 300 → 1200 mOsm/kg)
Equations
- UNH4·V
- ammonium excreted
- TA
- titratable acid
- UHCO3·V
- bicarbonate lost in urine
At steady state, NAE matches daily fixed-acid production.
180 L/day × 24 mmol/L ≈ 4300 mmol/day to be reclaimed.
Approximate figures
| Parameter | Value | Note |
|---|---|---|
| Fixed-acid production (Western diet) | ≈50–100 mmol/day | sulfuric and phosphoric acid from protein |
| Filtered HCO₃⁻ | ≈4300 mmol/day | |
| Minimum urine pH | ≈4.5 | |
| Ammonium excreted | ≈30–40 mmol/day; many times more in chronic acidosis |
Approximate values for a healthy adult at rest; each laboratory sets its own ranges.
Renal tubular acidoses: where it fails
| Type | Defect | Urine pH | Plasma K⁺ |
|---|---|---|---|
| Distal (type 1) | H⁺ not secreted in the collecting duct | > 5.5 always | Low |
| Proximal (type 2) | Lower threshold for HCO₃⁻ reclamation | < 5.5 once HCO₃⁻ has fallen | Low |
| Type 4 (hypoaldosteronism) | Little aldosterone or resistance: ↓ ammoniagenesis | < 5.5 | High |
Clinical notes
- Distal RTA goes with nephrocalcinosis and stones: alkaline urine, hypercalciuria and low urinary citrate.
- In chronic kidney disease too few nephrons make ammonium: metabolic acidosis appears, first with a normal and later a high anion gap.
- Hyperkalaemia suppresses ammoniagenesis and hypokalaemia stimulates it: potassium and acid travel together.
Test yourself
Think of the answer, then tap the question to see it.
Why can reabsorbing filtered bicarbonate not by itself correct a metabolic acidosis?
It only prevents loss of what was already in plasma. To correct acidosis the kidney must generate new HCO₃⁻ by excreting H⁺ as titratable acid or as NH₄⁺.
Which acid-excretion route rises most in chronic metabolic acidosis, and where does it come from?
Ammonium: the proximal tubule deaminates more glutamine, sending NH₄⁺ to urine and new HCO₃⁻ to blood. Titratable acid barely rises because it depends on filtered phosphate.
A child with hyperchloraemic acidosis has a urine pH of 6.5 despite the acidosis, plus hypokalaemia and nephrocalcinosis. Which RTA fits?
Distal (type 1): the collecting duct cannot secrete H⁺ and urine never drops below 5.5; alkaline urine and hypercalciuria favour calcium deposition.
Why does volume contraction tend to maintain an alkalosis?
Angiotensin II increases proximal NHE3 and aldosterone stimulates distal H⁺ secretion: the kidney reclaims all the HCO₃⁻ instead of excreting the excess.
See it in 3D
The structures of Durgical's 3D anatomy where it happens.
Related topics
- Buffers and the Henderson–Hasselbalch equation
- Proximal tubule transport
- Distal tubule and collecting duct
- Metabolic acidosis, the anion gap and compensation
- Metabolic alkalosis and its compensation
- Potassium balance
Related conditions
- Normal anion gap (hyperchloraemic) metabolic acidosis
- Metabolic alkalosis
- Hypokalaemia
- Chronic kidney disease
In Biochemistry
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); Distal renal tubular acidosis: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2024); Proximal renal tubular 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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Representative model, for educational purposes only.