Distal Convoluted Tubule and Collecting Duct

Early DCT

The early DCT reabsorbs ions, including sodium, chloride, and calcium. It is impermeable to water.

The macula densa (a specialised group of epithelial cells that senses tubular sodium concentration) lies at the transition between the thick ascending limb and the DCT. Through tubuloglomerular feedback, the macula densa regulates glomerular filtration rate (GFR) and renal blood flow within the same nephron.

Sodium and Chloride reabsorption

The major driving force for ion transport is the Na⁺/K⁺ ATPase transporter on the basolateral membrane. Using ATP, this pump transports 3 sodium ions (Na⁺) out of the cell and 2 potassium ions (K⁺) into the cell, producing a low intracellular sodium concentration.

This sodium gradient drives the secondary active transport of sodium from the tubular lumen through apical Na⁺/Cl⁻ cotransporter (NCC). Chloride exits the cell via basolateral chloride channels into the interstitial fluid, preventing intracellular accumulation.

Thiazide diuretics, used to treat hypertension and heart failure, inhibit the NCC cotransporter, reducing sodium and chloride reabsorption. As a result, less solute is removed from the tubular fluid, limiting urine dilution and subsequent water reabsorption in the collecting duct.

Calcium reabsorption

The DCT is also a site of regulated calcium (Ca²⁺) reabsorption. Calcium enters the cell through apical TRPV5 calcium channels before leaving across the basolateral membrane via both the Na⁺/Ca²⁺ exchanger (NCX1) and a plasma membrane calcium ATPase (PMCA).

The sodium gradient created by Na⁺/K⁺ ATPase provides the driving force for calcium extrusion across the basolateral membrane (through NCX1), maintaining a low intracellular calcium concentration that promotes continued calcium entry from the tubular lumen (through TRPV5). Thus, calcium reabsorption is indirectly driven by the Na⁺/K⁺-ATPase through secondary active transport.

Parathyroid hormone (PTH) also acts here – binding of PTH to its receptor increases calcium reabsorption by increasing the activity of TRPV5, NCX1 and PMCA.

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Figure 1
Summary of ion transport at the distal convuluted tubule.

Late DCT and CD

The late DCT and CD perform the final adjustment of urine composition. There are two main epithelial cell types in this region:

• principal cells – mainly involved in sodium reabsorption and potassium secretion
• intercalated cells – assist in acid-base control by controlling the transport of hydrogen (H⁺) and bicarbonate ions (HCO­₃^–)

Type A (α) intercalated cells act during acidosis to increase pH and type B (β) intercalated cells act during alkalosis to reduce pH.

Sodium reabsorption and K secretion

Principal cells make up the majority of the tubular cells. Their basolateral Na⁺/K⁺ ATPase pump maintains a low intracellular sodium concentration, setting up the gradient for sodium to enter the cell through apical ENaC channels (epithelial Na⁺ channel).

Removal of positively charged sodium ions from the tubular lumen, creates a luminal negative electric potential. This coupled with a high intracellular potassium concentration generated by Na⁺/K⁺ ATPase, promotes the secretion of potassium ions into the DCT lumen through apical ROMK channels.

Aldosterone acts primarily on principal cells, increasing the expression and activity of ENaC, Na⁺/K⁺ ATPase and ROMK channels. The overall effect is increased sodium reabsorption and increased potassium secretion.

Response to Acidosis

Type A intercalated cells are more active during acidosis. They secrete hydrogen ions into the tubular lumen via V-type H⁺ ATPase and H⁺/K⁺ ATPase pumps, increasing systemic pH.

Intracellular bicarbonate is also generated by carbonic anhydrase from carbon dioxide and water, similar to processes occurring in the proximal convuluted tubule (PCT). This HCO₃^– is absorbed into the bloodstream via a basolateral chloride-bicarbonate exchanger.

Unlike the PCT,  type A (α) intercalated cells can actively secrete H⁺ into the lumen against a large concentration gradient, allowing for H⁺ secretion in response to acidosis. Once in the tubular lumen, the hydrogen ions react with filtered phosphate (HPO₄^2-) or ammonia (NH₃) to form  NH₄⁺ and H₂PO₄^–, which are excreted carrying the hydrogen ions with them.

Response to Alkalosis

Conversely, type B (β) intercalated cells become more active during alkalosis. Their H⁺ and HCO₃^– channels are on opposite sides of the cell compared to type A cells, reversing the polarity of acid-base transport. The net effect in type B cells is the secretion of HCO₃^– and reabsorption of H⁺.

Water Reabsorption in the CD

The main role of the CD is the reabsorption of water, through the action of anti-diuretic hormone (ADH or vasopressin) and aquaporins.

In the absence of ADH the CD is relatively impermeable to water. Consequently, water remains within the tubular lumen and dilute urine is produced. ADH primarily acts on principal cells of the collecting duct, to increase the number of aquaporin 2 channels (water channels) in the apical membrane.

ADH binds to basolateral vasopressin 2 receptors (V2R) on the principal cells, which activate adenylyl cyclase, increasing intracellular cyclic AMP. This stimulates the insertion of aquaporin-2 (AQP2) channels into the apical membrane. Luminal water enters the cell through AQP2 channels and exits across the basolateral membrane through aquaporin 3 and 4 channels.

Increasing the number of channels increases the permeability of the cell, increasing water reabsorption from the filtrate to create smaller volumes of more concentrated urine.

Urea Recycling

ADH also increases urea reabsorption in the inner medullary collecting duct by:

• increasing water reabsorption in the outer cortical collecting duct

• increasing the activity of the urea transporters UT-A1 and UT-A3 in the inner medullary collecting duct.

The outer cortical collecting duct is largely impermeable to urea. Therefore, when ADH increases water reabsorption, luminal urea concentration rises as filtrate passes through the collecting duct, producing a high luminal-interstitial concentration gradient of urea in the inner medullary collecting duct.

Urea diffuses down its concentration gradient into the medullary interstitium contributing to the hyperosmotic environment and corticomedullary osmotic gradient of the renal medulla.

Thus, the presence of ADH allows increased water reabsorption and urinary concentration by increasing the medullary osmotic gradient independently of the gradient set up by counter-current multiplication in the loop of Henle.

Some of this urea is excreted in urine whilst some diffuses into the descending limb of the loop of Henle and recycles through the nephron before returning to the CD to again be reabsorbed into the interstitium maintaining the osmotic gradient. Thus, the process is known as urea recycling.

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Figure 2
Urea cycling in the nephron