What are the functions of the proximal tubule, cortical collecting duct, medullary collecting duct, and loop of Henle in the nephron?

Nephron Component Functions

The proximal tubule is the major site of reabsorption, the loop of Henle refines salt and water reabsorption and sets up the medullary concentration gradient, the cortical collecting duct is the major site of regulation of sodium and potassium excretion, and the medullary collecting duct is the major site of regulation of water balance/urine volume.

Proximal Tubule: Major Site of Reabsorption

• The proximal tubule reabsorbs approximately 60-70% of filtered water and NaCl, an even greater proportion of NaHCO3, and nearly all filtered nutrients including glucose and amino acids 1
• This segment is responsible for reclaiming almost all filtered bicarbonate, glucose, and amino acids, as well as 40% or more of filtered sodium, fluid, chloride, and phosphate 2
• SGLT2 proteins are expressed in the proximal convoluted tubule where they mediate glucose reabsorption 3
• The proximal tubule functions as a high-capacity delivery-responsive reabsorptive site, with the early proximal tubule having particularly high transport capacity that adapts dynamically to changes in filtration 2
• Potassium is filtered at the glomerulus and reabsorbed in the proximal tubule, with less than 10% of filtered potassium reaching the distal nephron 3, 4

Loop of Henle: Refines Salt and Water Reabsorption, Sets Up Medullary Concentration Gradient

• The loop of Henle, specifically the thick ascending limb, contains the Na⁺K⁺2Cl⁻ cotransporter which is the main site of action for loop diuretics 3
• This segment plays a critical role in establishing and maintaining the medullary concentration gradient through countercurrent multiplication 5
• The loop reabsorbs potassium that was filtered and not reabsorbed in the proximal tubule 3
• Transport in the loop of Henle modulates glomerular filtration via tubuloglomerular feedback (TGF), creating a homeostatic mechanism that responds to distal delivery 5

Cortical Collecting Duct: Major Site of Regulation of Sodium and Potassium Excretion

• The cortical collecting duct is where aldosterone exerts its primary effects on sodium reabsorption through epithelial sodium channels (ENaC) 3
• Potassium excretion in the distal nephron and collecting duct is stimulated by aldosterone, increased urine flow, and increased delivery of sodium to the distal nephron 3
• Aldosterone antagonists (spironolactone) are more effective than loop diuretics in managing sodium balance because they target this critical regulatory site 3
• The cortical collecting tubule raises the fractional solute contribution and absolute concentration of urea in fluid delivered to the outer medullary collecting duct 6

Medullary Collecting Duct: Major Site of Regulation of Water Balance/Urine Volume

• The inner medullary collecting duct has two major functions: it adds net urea to the papillary interstitium and allows generation of maximally concentrated urine through osmotic water equilibration 6
• This segment is where antidiuretic hormone (ADH/vasopressin) exerts its primary effect on water reabsorption, making it the principal site for regulating final urine volume and concentration 6
• The medullary collecting duct can produce urine with osmolality higher than papillary interstitial osmolality due to inequalities in reflection coefficients of urea and sodium chloride 6

Common Pitfall to Avoid

• Do not confuse the distal tubule with the collecting duct system—while both are involved in fine-tuning electrolyte balance, the collecting duct (both cortical and medullary segments) is the primary site where aldosterone acts and where final urine concentration is determined 3, 6