Countercurrent Mechanism

  • The Countercurrent Mechanism partially contributes to generation of the corticopapillary osmotic gradient and is the product of juxtamedullary nephrons which possess long loops of Henle that extend far into the renal medulla.
  • Overview
    • Understanding how the countercurrent mechanism operates is aided by a thought experiment in which the entire renal interstitial fluid is assumed to possess a uniform osmolarity equivalant to that of the extracellular fluid, that is 300 mOsm/L. The countercurrent mechanism itself can be thought of as a multi-step cycle whose iterative repetition ultimately results in development of a corticopapillary osmotic gradient.
  • Step 1: Thick Ascending Loop of Henle Transport
    • The Na2ClK Symporter of the thick ascending loop of Henle is a powerful mechanism by which solutes are resorbed from the tubule. These solutes are ultimately deposited in the renal interstitial fluid, thus increasing above 300mOsm/L the local osmolarity of interstitial fluid surrounding the thick ascending loop of Henle.
  • Step 2: Equilibration of Descending Thin Loop of Henle
    • The descending thin loop of Henle is highly water-permeable and receives tubular fluid from the proximal tubule which is roughly isoosmotic with extracellular fluid (~300 mOsm/L). However, the upper portion of the thin descending loop of Henle passes through the areas of locally increased interstitial osmolarity generated by the thick ascending loop of Henle in "Step 1". Given the permeability of the thin descending Henle, water osmotically exits the upper thin descending Henle, thus increasing the osmolarity of its tubular fluid.
  • Step 3: Fluid Flow
    • Given the continuous flow of fluid through the nephron, the osmotically equilibrated fluid in the upper thin descending loop of Henle immediately moves further down the descending limb only to be replaced with fresh 300 mOsm/L tubular fluid from the proximal tubule. Because the fluid flowing down the descending Henle has a higher osmolarity than that of the 300 mOsm/L interstitial fluid, some of its solutes will diffuse into the surrounding interstitium, thus locally increasing the osmolarity of the medullary interstitial fluid. In this way a very minute corticopapillary osmotic gradient has been established with a slightly higher medullary interstitial osmolarity compared to the cortical interstitial osmolarity.
  • Iterative Cycling
    • With each iterative cycle of steps 1-3 the medullary interstitial osmolarity increases thus increasing the size of the corticopapillary osmotic gradient.
  • The corticopapillary osmotic gradient is modulated by ADH whose presence increases the size of the gradient. ADH appears to achieve this by directly stimulating the basolateral NaK ATPase of the thick ascending loop of Henle which in turn enhances the activity of the luminal Na2ClK Symporter. Increased solute resorption by the Na2ClK Symporter enhances Step 1 of the countercurent mechanism and over time results in the production of a wider corticopapillary osmotic gradient.