Late Distal Tubule and Collecting Duct Transport

  • The late distal tubule and collecting ducts represent the final functional segment of the nephron after which any remaining tubular fluid is excreted as urine. By this segment, the vast majority of solutes and water have been resorbed and thus the late distal tubule and collecting ducts are only responsible for a small fraction of total resorption. However, this represents the major locus of regulated tubular resorption and given the enormous quantities of glomerular filtration that occur per minute, even small changes in resorption rates at this segment can have enormous impacts on the composition of the body's extracellular fluid. Modulation of water, sodium, chloride, and potassium resorption all occur in the late distal tubule and collecting duct. In addition, this segment is a major contributor to hydrogen excretion and thus plays an important role in acid-base homeostasis.
  • Although tubule epithelial cells are functionally uniform in other nephronic segments, epithelial cells of the late distal tubule and collecting duct display functional specialization for resorption of distinct molecules. Principal Cells are involved in water and sodium resorption but secrete potassium whereas Intercalated Cells are involved in potassium resorption and hydrogen secretion. Finally, it is important to point out that the epithelium of this segment is highly impermeable and thus displays little in the way of paracellular transport of water or solutes.

Molecular mechanisms of late distal tubule and collecting duct transport
Late Distal Tubule and Collecting Duct Transport is carried out by two different cell types with different properties. Principal cells harbor luminal sodium and potassium channels that allow for sodium resorption and potassium secretion, powered by a basolateral Na-K ATPase. Principal cells also display a regulated transcellular permeability to water in response to ADH via aquaporin membrane water channels. Intercalated cells are characterized by the capacity to secrete hydrogen ions via a luminal H+-ATPase and resorb potassium through an as-yet poorly defined mechanism that may involve active exchange of potassium for hydrogen via a luminal H-K ATPase.

Transport Mechanisms
  • Principal Cells
    • The resorptive capacity of Principal Cells is largely powered by a basolateral NaK ATPase which generates low intracellular Na+ and high intracellular K+ concentrations. This basolateral primary active transport of sodium and potassium is then used to actuate luminal resorption of sodium and secretion of potassium through specific ion channels.
    • Water resorption by principal cells largely occurs transcellularly through water-specific channels known as aquaporins whose presence at the membrane is highly regulated. These water channels are sequestered in an inactive state within intracellular vesicles in the principal cell cytoplasm and are inserted into the luminal membrane in response to the presence of ADH. In this way, the presence of ADH substantially increases the permeability of the late distal tubule and collecting duct to water, thus triggering water resorption (See ADH Physiology).
  • Intercalated Cells
    • Hydrogen is secreted by Intercalated Cells via primary active transport using a luminal H+ ATPase. This process and its regulation are covered in more detail in renal acid excretion. Additionally, potassium can be resorbed by intercalated cells although the mechanism of this process is poorly understood. One mechanism may be an HK ATPase that actively resorbs K+ ions while secreting hydrogen ions.