Updated: 7/7/2021

The Nephron

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Overview

 
Proximal Convoluted Tubule
  • The major function of the proximal convoluted tubule (PCT) is
    • isosmotic reabsorption of solutes and water which is imperative for maintaining the extracellular fluid (ECF)  
      • this is accomplished by a number of co-transporters such as
        • Na+-glucose co-transporter (SGLT)
          • 100% of the filtered glucose is reabsorbed
        • Na+-amino acid co-transporter
          • 100% of the filtered amino acids are reabsorbed
        • Na+-phosphate co-transporter
        • Na+-H+ exchange
  • Note that the PCT can be divided into an early and late PCT
    • Na+ is reabsorbed in both portions of the PCT but via different mechanisms
      • early PCT
        • Na+ is primarily reabsorbed with HCO3-
          • 85% of the filtered HCO3- is reabsorbed
        • Na+ is also reabsorbed with glucose, amino acids, and other organic solutes (e.g., lactate and citrate)
      • late PCT
        • Na+ is primarily reabsorbed with Cl-
  • There are a number of hormones that act on the PCT and they include
    • parathyroid hormone (PTH)
      • inhibits the Na+-phosphate co-transporter 
    • angiotensin II
      • stimultes the Na+-H+ exchange
  • Medications that act on this portion of the nephrone includes
    • carbonic anhydrase inhibitors (e.g., acetazolamide)
    • osmotic diuretics (e.g., mannitol)
Thin Descending Loop of Henle
  • The thin descending loop of Henle is permeable to water but not ions
    • water moves out of the loop into the interstitium resulting in the tubular fluid becoming more concentrated (hyperosmotic)
Thick Ascending Loop of Henle
  • The major function of the thick ascending loop of Henle is to reabsorb NaCl without water
    • this is accomplished by the Na+-K+-2Cl cotransporter
      • loop diuretics (e.g., furosemide) act on these transporters
      • reabsorption of solutes without water makes the tubular fluid dilute (thus why this is the diluting segment)
  • There is also paracellular reabsorption of Ca2+ and Mg2+
    • this is driven by the lumen-positive potential difference generated by K+ backleak
Distal Convoluted Tubule and Collecting Duct
  • The distal convoluted tubule (DCT) can be divided into an early and late DCT
    • early DCT
      • reabsorbs 5% of the filtered sodium via a Na+-Cl cotransporter
        • this is the site of action of thiazide (e.g., hydrochlorothiazide and metolazone) diuretics
          • thiazides are organic acids that bind to the Cl site of the transporter
      • it is impermeable to water and thus dilutes the tubular fluid (thus called the cortical diluting segment)
    • late DCT and collecting duct
      • both of these segments of the nephron are anatomically and functionally similar
      • there are 2 major cell types
        • principal cells
          • Na+ is reabsorbed via epithelial Na+ channels (ENaC)
            • aldosterone increases Na reabsorption via increased protein synthesis of ENaC and Na+-K+-ATPase
              • aldosterone also stimulates K+ secretion via acting on K+ channels
            • K+-sparing diuretics (e.g., spironolactone, amiloride, and triamterene) impair Na+ reabsorption
              • spironolactone is an aldosterone antagonist
              • amiloride and triamterene act at the level of Na+ channels
          • anti-diuretic hormone (ADH) increases water permeability of the principal cells 
            • this is accomplished by binding to V2 receptors and subsequently resulting in increased aquaporin-2 (AQP2) channel expression
          • there is a Ca2+-Na+ exchange in the basolateral membrane of the principle cell
            • PTH increases Ca2+ reabsorption by increase exchange activity
        • α-intercalated cells
          • secretion of H+ is accomplished by 2 active transport mechanisms
            • H+-ATPase
              • this enzyme is stimulated by aldosterone
            • H+-K+ ATPase
              • H+ is secreted in exchange for K+

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