Tubular disorders by nephron segment
- Table to know
- Exam priority: medium
Each nephron segment has its own transporters; when one fails, the urine and blood tests show a matching pattern.
Also called: Tubulopathies, Channelopathies of the nephron
See it in 3D: Kidneys
What it is
Inherited and acquired tubular disorders are easiest to learn by segment. A defect in a transporter reproduces the effect of the diuretic that blocks it, or the opposite if the transporter is overactive. The lab pattern (potassium, acid–base, blood pressure, urine calcium and glucose) points to the segment.
Key facts
- Hypokalemic alkalosis with normal BP: Bartter or Gitelman (or hidden diuretic use or vomiting); urine Ca²⁺ and Mg²⁺ separate them.
- Hypokalemic alkalosis with hypertension: think mineralocorticoid excess; low renin plus low aldosterone points to Liddle or apparent mineralocorticoid excess.
- Hyperkalemic acidosis: type 4 RTA or pseudohypoaldosteronism; aldosterone level separates deficiency from resistance.
- Normal anion gap acidosis: urine anion gap or urine pH helps place the defect (proximal vs distal).
The nephron: segments, transporters and diuretics
GFR ≈ 125 mL/minFiltrate ≈ 180 L/dayUrine ≈ 1–2 L/day
Tap a nephron segment: what it reabsorbs, its transporters, the hormones, the diuretics that act there and the classic disorders.
- 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)
Tubular disorders by segment
| Disorder | Segment and defect | Lab pattern | Mimics |
|---|---|---|---|
| Fanconi syndrome | Proximal tubule: global failure of reabsorption (inherited, or tenofovir, ifosfamide, myeloma light chains) | Glucosuria with normal glucose, aminoaciduria, phosphaturia, HCO₃⁻ wasting, hypokalemia | No single drug (SGLT2 inhibitor + acetazolamide combined) |
| Proximal (type 2) RTA | Proximal tubule: low HCO₃⁻ reabsorption (carbonic anhydrase, NBCe1) | Normal anion gap acidosis, hypokalemia, urine pH < 5.5 at steady state | Acetazolamide |
| Renal glucosuria | Proximal tubule: SGLT2 (SLC5A2) loss | Glucose in urine with normal blood glucose; otherwise benign | SGLT2 inhibitors |
| Cystinuria | Proximal tubule: dibasic amino acid transporter (cystine, ornithine, lysine, arginine) | Cystine stones, hexagonal crystals, positive nitroprusside test | None |
| Bartter syndrome | Thick ascending limb: NKCC2, ROMK, ClC-Kb or barttin | Hypokalemia, metabolic alkalosis, hypercalciuria, high renin and aldosterone, normal BP | Loop diuretics |
| Gitelman syndrome | Distal convoluted tubule: NCC (SLC12A3) | Hypokalemia, alkalosis, hypocalciuria, hypomagnesemia, normal BP | Thiazides |
| Liddle syndrome | Collecting duct: gain-of-function ENaC (not removed from the membrane) | Hypertension, hypokalemia, alkalosis, low renin and aldosterone | Opposite of amiloride; looks like hyperaldosteronism |
| Pseudohypoaldosteronism type 1 | Collecting duct: ENaC loss or mineralocorticoid receptor resistance | Salt wasting, hyperkalemia, acidosis, high renin and aldosterone | Amiloride, spironolactone |
| Nephrogenic diabetes insipidus | Collecting duct: V2 receptor or AQP2 (inherited), lithium, hypercalcemia, hypokalemia | Large volume of dilute urine, high plasma osmolality, high ADH, no response to desmopressin | ADH antagonists (vaptans) |
| Distal (type 1) RTA | Collecting duct α-intercalated cell: H⁺-ATPase or AE1 (Sjögren, amphotericin B) | Normal anion gap acidosis, urine pH > 5.5, hypokalemia, stones, nephrocalcinosis | None (amphotericin B causes it) |
| Type 4 RTA | Collecting duct: low aldosterone or resistance (diabetic nephropathy, ACE inhibitors, trimethoprim) | Hyperkalemia, mild normal anion gap acidosis, urine pH < 5.5 (low NH₄⁺) | Spironolactone, amiloride, trimethoprim |
Clinical notes
- Surreptitious use of loop diuretics or thiazides gives the same pattern as Bartter or Gitelman; a urine diuretic screen separates them.
- Distal RTA forms calcium phosphate stones because alkaline urine and low citrate favour precipitation.
- Lithium enters principal cells through ENaC and disrupts AQP2 signalling: nephrogenic DI is a common acquired form.
Test yourself
Think of the answer, then tap the question to see it.
A young adult has hypokalemia, metabolic alkalosis, normal blood pressure, low urine calcium and low magnesium. Which segment and transporter are affected?
Distal convoluted tubule, the Na⁺–Cl⁻ cotransporter (NCC): Gitelman syndrome, which mimics a thiazide.
How do Liddle syndrome and primary hyperaldosteronism differ in their hormone levels?
Both give hypertension and hypokalemic alkalosis, but in Liddle renin and aldosterone are both low, because ENaC is overactive by itself; in primary hyperaldosteronism aldosterone is high with low renin.
Why can urine pH be below 5.5 in proximal RTA but not in distal RTA?
In proximal RTA the distal acid pumps work, so once plasma HCO₃⁻ falls below the low threshold the urine is acidified; in distal RTA the H⁺ secretion itself fails.
Which tubular disorder causes hyperkalemia with a mild normal anion gap acidosis, and what is the usual cause in adults?
Type 4 RTA, from low aldosterone or aldosterone resistance, most often diabetic kidney disease or drugs (ACE inhibitors, trimethoprim, spironolactone).
A patient on long-term lithium passes large volumes of dilute urine that do not concentrate after desmopressin. Where is the defect?
Collecting duct principal cells: lithium-induced nephrogenic diabetes insipidus (impaired AQP2 response to ADH).
Connections
See it in 3D1
The structures of Durgical's 3D anatomy where it happens.
In Biochemistry1
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: Fanconi syndrome: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2025); Bartter syndrome: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2025); Gitelman syndrome: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2025); Liddle syndrome: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.