Overview

Na⁺ reabsorbed≈5–7% of filtered load

Length≈5 mm

The DCT begins just beyond the macula densa and coils in the cortex before joining a collecting duct through the connecting tubule. Its cells reabsorb Na⁺ and Cl⁻ via the apical Na⁺–Cl⁻ cotransporter (NCC), the target of thiazide diuretics; it is impermeable to water, so it further dilutes the tubular fluid (the cortical diluting segment), to ≈50–100 mOsm/kg.

The DCT is the principal site of regulated Ca²⁺ reabsorption: Ca²⁺ enters through apical TRPV5 channels, is buffered by calbindin-D28k and is extruded basolaterally by the Na⁺/Ca²⁺ exchanger (NCX1) and Ca²⁺-ATPase; PTH and calcitriol stimulate this pathway. Mg²⁺ enters via TRPM6. The late DCT and connecting tubule begin to express ENaC and respond to aldosterone, and the WNK kinase system adjusts NCC activity to balance Na⁺ and K⁺ handling.

Location: Renal cortex, between the macula densa and the connecting tubule/collecting duct.

Anatomy

Histology: Simple cuboidal epithelium, no brush border, cells smaller and paler than PCT so more nuclei per cross-section; wider, clear lumen.

Function

Reabsorb ≈5–7% of filtered NaCl (NCC)
Further dilute tubular fluid (water-impermeable)
Regulated Ca²⁺ reabsorption (PTH, calcitriol) and Mg²⁺ reabsorption

Regulation: PTH (↑Ca²⁺ reabsorption), aldosterone (late DCT), angiotensin II and WNK kinases (NCC).

Clinical significance

Thiazide diuretics

Hydrochlorothiazide, chlortalidone and indapamide block NCC: moderate natriuresis, first-line antihypertensives. Increased distal Ca²⁺ reabsorption causes hypocalciuria (useful in calcium stone prevention, but can cause hypercalcaemia). Adverse effects: hypokalaemia, metabolic alkalosis, hyponatraemia, hyperuricaemia (gout), hyperglycaemia, hyperlipidaemia — "hyperGLUC".

Gitelman syndrome

Autosomal recessive loss of NCC — mimics chronic thiazide use: hypokalaemic metabolic alkalosis, hypomagnesaemia and hypocalciuria, normal blood pressure. Milder and later in onset than Bartter syndrome.

Test yourself

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.