Distal convoluted tubule & collecting duct

The distal convoluted tubule (DCT) receives tubular fluid from the thick ascending limb of the loop of Henle. This fluid is hypotonic with an osmolality of ~ 90 mosmol/kg H₂O when it enters the DCT.

The primary role of the DCT is regulation of potassium, sodium, calcium, and pH. The macula densa are also situated in the first segment of the DCT and play an important role in autoregulation.


Sodium reabsorption
The proximal convoluted tubule (PCT) and loop of Henle will have reabsorbed around 90% of filtered Na⁺ ions by the time the tubular fluid reaches the DCT. The remaining 10% is typically reabsorbed in the DCT and collecting duct under the influence of a number of hormones.

There are two main routes for Na⁺ reabsorption from the lumen:

• Na⁺ epithelial sodium channels (ENaC)
• NCC (sodium-chloride cotransporter)

Na⁺ ions are actively pumped out of the tubular cell cytosol into the interstitial fluid by the Na⁺-K⁺-ATPase on the basolateral membrane. This lowers the Na⁺ concentration within the cell and helps create the gradient for Na⁺ ions to move in via the above methods. Of note only NCC transporters are present in the early part of the DCT whereas both NCC and ENaC are present in the distal part of the DCT.


The movement of Na⁺ ions from the lumen into the cells is electrically offset by the excretion of K⁺ ions from cells into the lumen via renal potassium secretory channel ROMK (Renal outer medullary K+ channel) channels.

Potassium secretion

Reabsorption of potassium is typically complete by the time the tubular fluid reaches the DCT. Potassium secretion is primarily regulated by the cells of the late distal tubule. As can be seen from the notes above K⁺ secretion is linked to Na⁺ reabsorption.

K⁺ is actively transported from the interstitial space into principal cells by basolateral Na⁺-K⁺-ATPase pumps then passively secreted via ROMK channels and K⁺/Cl^- cotransporter. The relative negative luminal charge caused by Na⁺ reabsorption helps drive passive movement of K⁺ via ROMK channels. Secretion is driven by the concentration gradient between the cell cytosol and tubular fluid.

Secreted K⁺ is 'washed away' by tubular flow which helps maintain the concentration gradient between the lumen and cell cytosol for secretion. Increased tubular flow therefore increases potassium secretion.

Water reabsorption

The cells of the DCT and collecting duct are impermeable to water except in the presence of antidiuretic hormone (ADH).

ADH stimulates the insertion of aquaporin channels into the apical (lumen side) membrane. When ADH is present water diffuses from the lumen into principal cells through aquaporin channels and then diffuses across the basolateral membrane into the interstitial space. The loss of water concentrates the tubular fluid (which ultimately becomes urine) which reaches a maximum osmolality of 290 mOsmol/kg H₂O by the end of the the cortical portion of the collecting duct.

The tubular fluid at this stage is radically different to plasma and the initial glomerular filtrate collected in Bowmans capsule as large quantities of Na⁺, K⁺, Cl^- and HCO₃^- have been reabsorbed. The DCT and cortical portion of the collecting duct are impermeable to urea which concentrates as water is reabsorbed.

In the medullary portion of the collecting duct water is reabsorbed, in the presence of ADH, due to the high osmolality of the medullary interstitium. Note that the collecting ducts of all nephrons, both cortical and medullary, pass through the medulla and take part in concentrating urine.

Urea

Whilst the DCT and cortical portion of the collecting duct are impermeable to urea, the medullary portion of the collecting duct is relatively permeable to urea.

In the medullary collecting duct urea diffuses along its concentration gradient into the medulla and back into the ascending loop of Henle. Urea is effectively trapped and cycles through the ascending loop, DCT and collecting duct again and again. Urea is a major contributor to the high osmolality of the medulla.


ADH increases medullary collecting duct permeability via activation of epithelial uniporters. This promotes the facilitated diffusion of urea out of the collecting duct and further concentrates urine by increasing medullary osmolality.

Calcium reabsorption

Calcium reabsorption in the DCT is regulated by parathyroid hormone (PTH) and 1,25 dihydroxycholecalciferol (activated vitamin D).

PTH activates Ca²⁺ channels in the apical (luminal) membrane that facilitate the movement of Ca²⁺ from the lumen into the cellular cytosol.

Ca²⁺ is transported from the cytosol into the interstitial fluid by two pumps in the basolateral membrane:

• Ca²⁺-ATPase pump
• Na⁺-Ca²⁺ antiporter

The Ca²⁺-ATPase pump on the basolateral membrane is stimulated by both PTH and activated vitamin D. In the cell binding proteins prevent free calcium ions from building up to dangerous levels.