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Updated: Jul 7 2021

The Nephron

  • 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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