Tubular Function by Nephron Segment
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Direct answer
Each nephron segment is a transport specialist: the proximal convoluted tubule reabsorbs about 65% of filtered sodium, water, bicarbonate and practically all glucose and amino acids (isosmotically, through sodium-coupled transporters like SGLT2 and the carbonic anhydrase-dependent bicarbonate mechanism); the thick ascending limb reabsorbs another 25% of sodium via the NKCC2 cotransporter while remaining water-impermeable, so it dilutes the urine and builds the medullary gradient; the distal convoluted tubule handles about 5% via the thiazide-sensitive NCC cotransporter; and the collecting duct finishes the job under aldosterone (ENaC) and ADH (aquaporin-2). Glucose illustrates transport maximum physiology — filtered load above about 375 mg/min exceeds reabsorption, and glycosuria appears at plasma levels around 180 mg/dL.
What you must remember
- Proximal tubule (65%): isosmotic sodium and water reabsorption; all glucose (SGLT2 about 90%, SGLT1 the rest), amino acids, phosphate (PTH-inhibited NPT2a) and 80% of bicarbonate (carbonic anhydrase — acetazolamide target); secretes organic anions and cations (PAH, creatinine, penicillins).
- Glucose titration curve: threshold at plasma glucose about 180 mg/dL, transport maximum about 375 mg/min (slightly lower in women); the gap between them is the splay, from nephron heterogeneity — renal glycosuria (SGLT2 mutations) has glycosuria with normal plasma glucose.
- Thick ascending limb (25%): Na-K-2Cl cotransporter (NKCC2, furosemide site), impermeable to water ("diluting segment"); the lumen-positive potential from potassium back-leak drives paracellular calcium and magnesium reabsorption.
- Distal convoluted tubule (5%): NCC thiazide-sensitive cotransporter; parathyroid hormone drives transcellular calcium reabsorption here (TRPV5), which is why thiazides lower urine calcium and prevent calcium stones.
- Collecting duct: principal cells (aldosterone-inducible ENaC and ROMK; ADH-V2 receptor inserts aquaporin-2) and intercalated cells (alpha-type secretes H+ via H-ATPase and reabsorbs potassium and bicarbonate; beta-type secretes bicarbonate).
- Passive players: urea recycles in the inner medulla (ADH-sensitive UT-A urea transporters), and the vasa recta counter-exchange preserves what the loops build.
- Drug-mapping shortcut: acetazolamide (proximal carbonic anhydrase), loop diuretics (NKCC2), thiazides (NCC), amiloride (ENaC), spironolactone (mineralocorticoid receptor), SGLT2 inhibitors (proximal glucose) — the segment map doubles as the diuretic map.
How to work through a tubular disorder
A child with polyuria, glycosuria, aminoaciduria and phosphaturia despite normal plasma glucose has Fanconi syndrome — global proximal tubular failure (from cystinosis, Wilson disease, tenofovir or myeloma), and each piece follows the segment's job description: glucose and amino acids can no longer be reclaimed, phosphate loss produces rickets, and bicarbonate wasting gives a type 2 renal tubular acidosis because the 80% bicarbonate reclaim fails, so urine pH stays high once plasma bicarbonate falls below the reduced threshold.
Contrast a patient with nephrogenic diabetes insipidus on lithium: the collecting duct principal cells lose aquaporin-2 responsiveness, so ADH arrives but no water channels insert — polyuria with inappropriately dilute urine that fails to concentrate even after desmopressin (the water deprivation test pattern that separates it from central diabetes insipidus, where desmopressin works). Bartter syndrome (NKCC2 defect, mimicking a loop diuretic with hypercalciuria) and Gitelman syndrome (NCC defect, mimicking a thiazide with hypocalciuria and hypomagnesaemia) complete the transportopathies — the electrolyte pattern of each is the segment's signature written in chemistry.
Where students slip
Students say "the proximal tubule reabsorbs everything" — it is quantitatively dominant but qualitatively incomplete (only about 65% of sodium; fine-tuning happens downstream under hormonal control). The second slip is the direction of the lumen-positive potential in the thick ascending limb: potassium back-leak through ROMK makes the lumen electrically positive, which is why calcium and magnesium follow paracellularly — lose that, and the explanation for loop-diuretic hypercalciuria versus thiazide hypocalciuria collapses. In viva, the splay question tests understanding beyond memorisation: why glycosuria begins at 180 mg/dL when Tm arithmetic alone would predict later — because nephrons differ in transport capacity and some spill early.
Frequently asked questions
Which segment reabsorbs the bulk of the filtrate and how?
The proximal convoluted tubule: about 65% of sodium and water isosmotically, along with all glucose and amino acids and about 80% of filtered bicarbonate via carbonic anhydrase-dependent hydrogen ion secretion.
Why is the thick ascending limb called the diluting segment?
It reabsorbs sodium chloride through NKCC2 but is impermeable to water, so tubular fluid becomes hypotonic — the foundation of both dilute urine production and the medullary concentration gradient.
What produces the splay in the glucose titration curve?
Nephron heterogeneity: different nephrons have different filtration and reabsorption capacities, so some saturate and spill glucose before the average transport maximum is reached.
How do thiazides reduce urine calcium?
By inhibiting NCC in the distal convoluted tubule they enhance transcellular calcium reabsorption through TRPV5, lowering urinary calcium — the basis for thiazide use in recurrent calcium stone prevention.
Which cells and channels execute aldosterone and ADH action?
Principal cells: aldosterone induces ENaC and Na-K ATPase for sodium retention; ADH acts on V2 receptors to insert aquaporin-2 water channels, their defects producing salt wasting and diabetes insipidus respectively.