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Distal convoluted tubule: regulated calcium and magnesium reabsorption

Distal tubule · 8-10% Ca2+ TRPV5 PTH

The DCT and connecting tubule are the only sites of active, transcellular, hormonally regulated calcium reabsorption (~8-10% of the filtered load) and the last site of magnesium reabsorption. Because no water is reabsorbed here, calcium moves against its gradient and needs a dedicated apical channel.

Traced from the start

  1. Glomerular filtration barrier
  2. Proximal tubule: Na+/H+ exchange and bicarbonate reclamation
  3. Thick ascending limb of Henle (NKCC2)
  4. Distal convoluted tubule: regulated calcium and magnesium reabsorption

Detail

Reabsorbs
~8-10% of filtered Ca2+ (transcellular, against a gradient) and ~5-10% of Mg2+; the segment that fine-tunes final excretion
Transporter
Apical TRPV5 (Ca2+) and TRPM6 (Mg2+); cytosolic calbindin-D28k ferries Ca2+; basolateral NCX1 (3 Na+ : 1 Ca2+) and PMCA1b pump it out
Hormone
PTH and calcitriol increase TRPV5, calbindin and NCX1 so less Ca2+ is lost; EGF signalling drives TRPM6; FGF23 also enhances TRPV5
Diuretic
Thiazides reduce urinary calcium, mostly through volume contraction increasing passive proximal Ca2+ reabsorption and partly by increasing NCX1 drive in DCT cells; loop diuretics do the opposite
Note
Calcium that escapes here is excreted: there is no downstream rescue

When it goes wrong

Thiazide therapy

Hypocalciuria (used for recurrent calcium oxalate stones and idiopathic hypercalciuria) and mild hypercalcaemia that can unmask primary hyperparathyroidism

Cetuximab (EGF receptor blockade), cisplatin, aminoglycosides, alcohol or Gitelman syndrome

Renal magnesium wasting (high fractional Mg excretion) with hypomagnesaemia, secondary hypocalcaemia (Mg2+ is needed for PTH release) and refractory hypokalaemia; contrast with proton-pump inhibitors, which cause gut loss with low urinary Mg

Familial hypocalciuric hypercalcaemia (inactivating CaSR) versus primary hyperparathyroidism

Both raise serum Ca2+ with non-suppressed PTH, but FHH has a urinary calcium:creatinine clearance ratio under 0.01 while hyperparathyroidism is usually over 0.02; parathyroidectomy does not help FHH

Practise this structure

2 questions in the bank tagged Ionised Calcium.

A 22-year-old woman is brought to the emergency department 30 minutes after an argument at home, breathing rapidly and deeply. She complains of tingling around…

Foundations · middle twist

A 22-year-old woman is brought to the emergency department after 30 minutes of rapid, deep breathing that began during an argument. She reports tingling around…

Foundations · middle twist