What are the functions of the distal convoluted tubule?

Functions of the Distal Convoluted Tubule

The distal convoluted tubule (DCT) plays a critical role in electrolyte homeostasis, primarily through sodium, chloride, calcium, and magnesium reabsorption, while also participating in acid-base regulation through its unique transport mechanisms.

Primary Functions of the DCT

Sodium and Chloride Reabsorption

• The DCT reabsorbs approximately 5-10% of filtered sodium and chloride via the thiazide-sensitive sodium chloride cotransporter (NCC) 1
• This electroneutral transport mechanism is the primary target of thiazide diuretics
• The DCT contains the highest density of Na+/K+-ATPase along the nephron, located on its highly amplified basolateral membranes 1

Calcium Handling

• The DCT is critically involved in fine-tuning calcium reabsorption, controlling approximately 15% of filtered calcium 2
• Calcium reabsorption occurs primarily through the transient receptor potential vanilloid 5 (TRPV5) channel, which serves as the gatekeeper of active calcium reabsorption 2
• Impaired calcium transport in the DCT can lead to hypercalciuria 2

Magnesium Regulation

• The DCT is the primary site for active magnesium reabsorption in the kidney
• This occurs predominantly via the transient receptor potential channel TRPM6 1
• Genetic disorders affecting magnesium handling in the DCT lead to hereditary hypomagnesemias 1

Potassium Secretion

• The DCT contributes to potassium secretion, particularly in its later segments
• This process is regulated by several hormones, including aldosterone 3
• Principal cells in the late DCT are primarily responsible for potassium secretion 3

Regulatory Mechanisms

Hormonal Control

• The DCT is a major target for:
  • Aldosterone - increases sodium reabsorption and potassium secretion 3
  • Angiotensin II - enhances sodium reabsorption 1
  • Klotho - modulates calcium and phosphate handling through TRPV5 and sodium phosphate cotransporters 4

Acid-Base Regulation

• The DCT participates in acid-base balance through:
  • Na+/H+ exchange in the early DCT segments 5
  • H+ secretion via H+-ATPase in intercalated cells of the late DCT 5
  • Bicarbonate handling that contributes to overall acid-base homeostasis 5

Clinical Significance

Diuretic Action

• Thiazide diuretics specifically target the NCC in the DCT, inhibiting sodium and chloride reabsorption 6
• The expression of the thiazide-sensitive Na+-Cl- cotransporter in the DCT is 2-fold higher in females than males, explaining sex differences in diuretic response 6

Genetic Disorders

• Several genetic disorders highlight the importance of the DCT:
  • Gitelman syndrome - caused by NCC dysfunction, resulting in hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria 7
  • Familial Hyperkalemic Hypertension - results from overactivity of NCC 1
  • EAST syndrome - affects potassium channels in the DCT 1

Compensatory Mechanisms

• In conditions like Bartter syndrome (which affects the thick ascending limb), the DCT undergoes hypertrophy and hyperplasia to increase sodium reabsorption as a compensatory mechanism 6
• This "diuretic braking phenomenon" involves increased NaCl reabsorption through the sodium chloride cotransporter 6

Structural Characteristics

• The DCT is a short nephron segment positioned between the macula densa and collecting duct 1
• It is largely water impermeable, allowing for electrolyte handling independent of water movement 1
• DCT cells are rich in mitochondria, reflecting their high energy requirements for active transport 1

Understanding the functions of the DCT is essential for comprehending electrolyte disorders, the mechanism of action of thiazide diuretics, and the pathophysiology of various tubulopathies affecting this critical nephron segment.