Physiology · Renal, fluids and acid–base
Urine dilution, free water and osmotic diuresis !
- Measurement
- Exam priority: medium
The kidney can excrete water without salt (dilute urine) or hold on to it; free-water clearance shows which way it is working.
Updated 2026-11-01
Also called: Free-water clearance, Diluting segment, Polyuria
See it in 3D: Kidneys
What it is
To excrete excess water, the kidney separates salt from water in the thick ascending limb and the distal tubule, which reabsorb NaCl but are water-tight: fluid leaves them dilute (≈100 mOsm/kg). Without ADH, the collecting duct lets that dilute urine through (down to ≈50 mOsm/kg). Free-water clearance (CH₂O) tells how much “pure” water is being excreted (+) or retained (−). In osmotic diuresis, an unreabsorbed solute drags water and sodium out with it.
The nephron: segments, transporters and diuretics
Na⁺ reabsorbed ≈ 25%Water reabsorbed 0%
Thick ascending limb of the loop of Henle
- What it does: Reabsorbs ≈ 25% of filtered Na⁺ but is impermeable to water: the diluting segment (fluid leaves at ≈ 100 mOsm/kg) and the engine of the medullary gradient. The lumen-positive potential drives paracellular Ca²⁺ and Mg²⁺ reabsorption.
- Transporters: Apical NKCC2 (Na⁺-K⁺-2Cl⁻); ROMK recycles K⁺ to the lumen; basolateral ClC-Kb with barttin; claudins 16 and 19 (paracellular path); Ca²⁺-sensing receptor.
- Hormones: ADH (V2) increases NaCl reabsorption; PTH increases Ca²⁺ reabsorption.
- Drugs: Loop diuretics (4): block NKCC2; Na⁺, K⁺, Ca²⁺ and Mg²⁺ are lost (hypokalemia, metabolic alkalosis, hypercalciuria).
- Disorders: Bartter syndrome (like a loop diuretic: hypokalemic alkalosis, hypercalciuria, high renin and aldosterone).
- 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
- V
- urine flow
- Cosm
- osmolar clearance
If U_{osm} < P_{osm}, C_{H2O} > 0.
600 mOsm/day ÷ 1200 mOsm/kg ≈ 0.5 L/day obligatory minimum; ÷ 50 ≈ 12 L/day maximum.
Approximate figures
| Parameter | Value | Note |
|---|---|---|
| Minimum urine osmolality | ≈50 mOsm/kg | |
| Maximum urine osmolality | ≈1200 mOsm/kg | lower in infants and older adults |
| Fluid leaving the ascending limb | ≈100 mOsm/kg | always hypotonic |
| Daily solute excretion | ≈600–900 mOsm | depends on diet (salt, protein) |
| Obligatory minimum urine volume | ≈0.5 L/day |
Approximate values for a healthy adult at rest; each laboratory sets its own ranges.
Polyuria: water or solute
| Type | Urine osmolality | CH₂O | Examples |
|---|---|---|---|
| Water diuresis | Low (< 100–150 mOsm/kg) | Positive | Primary polydipsia, diabetes insipidus |
| Osmotic diuresis | ≈300 mOsm/kg or more | ≈0 or negative | Hyperglycaemia, mannitol, urea after relief of obstruction |
| Inappropriate antidiuresis | High for the serum sodium | Negative | SIADH |
Clinical notes
- In SIADH urine stays concentrated despite hyponatraemia: CH₂O is negative; water restriction works, and isotonic saline can worsen it if the urine is more concentrated than the infused fluid.
- In diabetes insipidus free water is lost: dilute polyuria and hypernatraemia if the person cannot drink.
- Older adults eating little but drinking a lot (or drinking a lot of beer) excrete little solute: they retain water even with low ADH.
Test yourself
Think of the answer, then tap the question to see it.
Someone passes 2 mL/min of urine at 600 mOsm/kg with plasma at 300. What is CH₂O and what does it mean?
Cosm = 600 × 2 / 300 = 4 mL/min; CH₂O = 2 − 4 = −2 mL/min. It is negative: the kidney is retaining free water (ADH-concentrated urine).
Why do thiazides cause hyponatraemia more often than loop diuretics?
They block the distal tubule (diluting segment) but spare the loop and the medullary gradient: the kidney cannot dilute well yet can still concentrate under ADH, so it retains water.
Why can a very low-solute diet cause hyponatraemia even with ADH suppressed?
Maximum urine volume is solute ÷ minimum Uosm. With, say, 250 mOsm/day and 50 mOsm/kg, only ≈5 L/day can be excreted; drinking more makes water accumulate.
How does urine osmolality separate polyuria from osmotic diuresis versus diabetes insipidus?
In osmotic diuresis urine is near or above 300 mOsm/kg (it carries a lot of solute); in diabetes insipidus it is very dilute, below ≈150 mOsm/kg.
See it in 3D
The structures of Durgical's 3D anatomy where it happens.
Related topics
- The countercurrent mechanism, urea recycling and urine concentration
- ADH, thirst and water balance
- Transport in the loop of Henle
- Where and how diuretics act
- Glucose transport maximum and renal threshold
- Fluid shifts between compartments
Related conditions
- Hyponatraemia
- Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
- Type 1 diabetes mellitus
- Hypernatraemia
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: 26.2 Water Balance (OpenStax (Rice University), 2022); 25.9 Regulation of Fluid Volume and Composition (OpenStax (Rice University), 2022); Osmolality Tests: MedlinePlus Medical Test (MedlinePlus, US National Library of Medicine, 2024); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 29). 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.