Counter-Current Mechanisms in the Kidney

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  • The concentrating mechanism depends on the maintenance of increasing osmolality along the medullary pyramids
  • A countercurrent system is a system in which inflow runs parallel to, counter to, and in close proximity to outflow for some distance
  • The loops of Henle act as countercurrent multipliers, which depend on:
  • High permeability of the thin descending limb to water (via aquaporin-1)
  • Active transport of Na+/Cl- out of the thick ascending limb
  • The inflow of tubular fluid from the proximal tubule
  • The outflow of tubular fluid from the distal tubule
Countercurrent multiplie8r.jpg
  • Pumps in the thick ascending limb move Na+ and Cl- into the interstitium, increasing its osmolality to 400mOsm/kg.
  • This equilibrates with fluid in the thin descending limb
  • Isotonic fluid continues to flow into the thin descending limb, and hypotonic fluid flows out of the thick ascending limb
  • Continued operation of the pumps makes the fluid leaving the thick ascending limb even more hypotonic, and hypertonicity accumulates at the apex of the loop
  • In juxtamedullary nephrons with longer loops and thin ascending limbs, the osmotic gradient is spread over a greater distance, and the osmolality at the tip is greater, as the thin ascending limb is relatively impermeable to water but permeable to Na+/Cl-. Greater the length of the loop of Henle, the greater the osmolality that can be reached at the medulla tip
  • The vasa recta acts as countercurrent exchangers:
  • The osmotic gradient in the pyramids would not last long if Na+ and urea in the interstitial spaces were removed from circulation
  • These solutes remain in the pyramids because they diffuse out of the vessels conducting blood out of the vasa recta towards the cortex and into the vessels descending into the pyramid
  • Meanwhile water diffuses from the descending vessels of the vasa recta into the ascending vessels
  • Therefore, solutes recirculate in the medulla and water bypasses it
U09b t04.gif
  • Water is also removed from collecting ducts in the pyramids and enters the general circulation
  • Countercurrent exchange is passive, depending on movement of water, and could not maintain the osmotic gradient along the pyramids if the process of counter-current multiplication in the loops of Henle were to cease

Urea

  • Contributes to the establishment of the osmotic gradient in the medullary pyramids, and to the ability to form a concentrated urine in the collecting ducts
  • Urea transport is regulated by vasopressin - when antidiuresis is high, urea transporter action is increased, which increases the concentrating capacity of the kidney
  • Amount of urea filtered also depends on diet, therefore in high protein diets the kidneys have increased ability to concentrate urine

Osmotic Diuresis

  • Solutes that are not reabsorbed in the proximal tubules produce an osmotic effect as tubular fluid volume decreases and concentration rises - they hold water in the tubules
  • This increased water also causes water to not follow Na+ out of the proximal tubule. This creates a diffusion gradient of Na+ into the tubule, which in turn results in sodium loss as part of the diuresis
  • This effect can occur with diabetes mellitus, or with administration of mannitol - which is filtered but not reabsorbed
  • Water diuresis - amount of water reabsorbed in the proximal nephron is normal, maximal urine flow is ~16ml/min
  • Osmotic diuresis - amount of water reabsorbed is greatly decreased, and very large urine flows can be produced with a concentration approaching that of plasma, despite maximal vassopressin secretion

Relation of Urine Concentration to GFR

  • Magnitude of osmotic gradient along the medullary pyramids is increased when the rate of flow of fluid through the loops of Henle is decreased
  • Therefore, reducing GFR leads to a decrease in fluid involved in the countercurrent mechanism, therefore the rate of flow in the loops declines and the urine becomes concentrated in the absence of vasopressin

Free Water Clearance

  • Allows quantification of net gain or loss of water by excretion of concentrated or dilute urine
  • The difference between urine volume and clearance of osmoles
CH2O = V - (UOsmV)/POsm
  • CH2O is negative when the urine is hypertonic and positive when the urine is hypotonic