Overview

Substances cross the epithelium either transcellularly (through apical and basolateral membranes via channels, carriers and pumps) or paracellularly (through tight junctions), then move into peritubular capillaries by bulk flow driven by Starling forces. The basolateral Na⁺/K⁺-ATPase keeps intracellular Na⁺ low, so Na⁺ enters across the apical membrane down its gradient, coupled to other solutes (secondary active transport). Water follows solute osmotically wherever aquaporins are present.

Fraction of filtered Na⁺ reabsorbed by segment: PCT ≈65–67% (NHE3, Na⁺-coupled cotransport) → thick ascending limb ≈25% (NKCC2) → DCT ≈5–7% (NCC) → collecting duct ≈2–5% (ENaC); <1% is excreted (FENa <1%). Water: PCT ≈65–67%, descending limb ≈15–20%, collecting duct ≈5–20% (ADH-dependent); the ascending limb and DCT are water-impermeable.

Carrier-mediated reabsorption shows a transport maximum (Tm): when the filtered load of glucose exceeds the capacity of SGLT2/SGLT1 (plasma glucose above ≈180–200 mg/dL, the renal threshold), glucose appears in the urine. The fraction reabsorbed in the PCT stays roughly constant when GFR changes (glomerulotubular balance).

Location: Throughout the renal tubule and collecting duct.

Function

Conserve water, Na⁺, Cl⁻, HCO₃⁻, glucose, amino acids and other valuable solutes
Regulate final excretion of electrolytes and water

Physiology: Filtered vs excreted per day: water ≈180 L vs ≈1.5 L (>99% reabsorbed); Na⁺ ≈25 000 mmol vs ≈150 mmol (>99%); glucose ≈180 g vs 0; HCO₃⁻ ≈4300 mmol vs ≈0; urea ≈50% reabsorbed.

Clinical significance

Diuretics — sites of action

PCT: acetazolamide (carbonic anhydrase), SGLT2 inhibitors, mannitol (osmotic; also descending limb). Thick ascending limb: loop diuretics — furosemide, bumetanide (NKCC2). DCT: thiazides (NCC). Collecting duct: K⁺-sparing — spironolactone/eplerenone (mineralocorticoid receptor), amiloride/triamterene (ENaC); tolvaptan (V2 receptor antagonist; aquaretic). Diuretics acting upstream of the collecting duct increase distal Na⁺ delivery and flow → K⁺ and H⁺ loss (hypokalaemic metabolic alkalosis).

Fractional excretion of sodium (FENa)

FENa = (U_Na × P_Cr) / (P_Na × U_Cr) × 100. <1% in prerenal AKI (avid tubular reabsorption); >2% in acute tubular necrosis (damaged tubules). Unreliable on diuretics (use fractional excretion of urea, <35% prerenal).

Mnemonics

Na⁺ reabsorption by segment

65–25–5–3: PCT ≈65%, loop ≈25%, DCT ≈5%, collecting duct ≈3%.

Test yourself

Antidiuretic hormone increases water reabsorption in the collecting duct mainly by:

Inserting aquaporin-2 into the apical membrane of principal cells via V2 receptors and cAMP
Inserting aquaporin-1 into the thin descending limb
Opening ENaC channels in intercalated cells
Constricting the efferent arteriole via V1 receptors

Answer: Inserting aquaporin-2 into the apical membrane of principal cells via V2 receptors and cAMP

ADH binds V2 receptors on the basolateral membrane of principal cells → Gs → cAMP → PKA → fusion of AQP2-containing vesicles with the apical membrane. Water exits basolaterally via AQP3/AQP4. AQP1 in the PCT and descending limb is constitutive.

A patient with recurrent calcium oxalate stones is started on a thiazide diuretic. How does this help?

It enhances Ca²⁺ reabsorption in the distal convoluted tubule, lowering urinary calcium
It inhibits NKCC2, increasing calcium excretion
It alkalinises the urine to dissolve oxalate
It suppresses parathyroid hormone secretion

Answer: It enhances Ca²⁺ reabsorption in the distal convoluted tubule, lowering urinary calcium

Blocking NCC lowers intracellular Na⁺ in DCT cells, which increases basolateral Na⁺/Ca²⁺ exchange and apical Ca²⁺ entry via TRPV5 (plus enhanced proximal reabsorption from mild volume contraction) → hypocalciuria. Loop diuretics have the opposite effect.