ICU Primary Snippet – Renal Physiology – Urine concentrating mechanisms

Describe the physiological mechanism by which the kidney concentrates the urine.

Written by Dr Madhuri Anupindi

The kidneys can concentrate urine to a maximum of 1200-1400mOsm/L due to:

• A high osmolarity of the renal medullary interstitial fluid and
• Presence of anti-diuretic hormone

Maintenance of a hyperosmolar renal medullary interstitium depends on the countercurrent mechanism in the juxtamedullary nephrons involving the loop of Henle and vasa recta and on intrarenal urea cycling.

Countercurrent mechanism:

• The descending limb of the loop of Henle is highly permeable to water but not to solutes à the tubular fluid becomes more concentrated as it descends, and the osmolarity equalises to the renal medulla à becomes maximally concentrated at the bottom of the loop
• Solutes are actively transported out of the thick portion of the ascending limb of the loop of Henle and into the medullary interstitium by Na-K-2Cl co-transporter
  • This establishes a concentration gradient between the interstitial fluid and the tubular lumen of about 200mosm
  • The thick ascending limb is impermeable to water which helps maintain this osmotic gradient
  • Some sodium chloride is also reabsorbed from the thin ascending limb and water remains impermeable which also adds to the high solute concentration of the interstitium
  • As the tubular fluid travels up the ascending limb it becomes less concentrated due to solutes being pumped out without water – it leaves the ascending limb less concentrated then when it entered the descending limb
• The transport of ions out of the thick ascending limb results in a hyperosmotic interstitial fluid à water then moves out of the descending limb into the interstitial fluid due to the concentration gradient à new tubular fluid enters the descending limb which moves the higher osmolar fluid further down the descending limb à an osmotic gradient is formed as more solute is added to the medulla in excess of water à eventually the interstitial osmolarity reaches 1200 to 1400moSm/L.
• The vasa recta are specialised peritubular capillaries of the renal medulla that run parallel to the loops of Henle. They help to maintain the high osmolarity of the interstitial fluid as:
  • The blood flow is low (<5% of total renal blood flow) which helps to minimise solute loss from the interstitium
  • They act as a countercurrent exchanger
    • Blood becomes more concentrated as it descends into the medulla as solute enters from the interstitium and water leaves à has a concentration of about 1200mOsm/L at the tip of the vasa recta (same as the medullary interstitium)
    • As blood ascends towards the cortex the solutes diffuse back into the interstitium and water enters à blood becomes more dilute
    • Consequently, there is little change in the concentration of the interstitial fluid as the blood within the vasa recta is similar in concentration to the interstitium at each level of the medulla. This therefore maintains the high osmolarity of the interstitial fluid.

Intrarenal urea cycling

• Urea contributes almost 50% of the renal medullary interstitial osmolarity. It is freely filtered in the glomerulus but becomes more concentrated in the proximal tubule due to water reabsorption in excess of urea reabsorption. The thick ascending loop of Henle, distal and cortical collecting ducts are impermeable to urea.
• In the presence of ADH there is increased water reabsorption from the cortical collecting tubules and the urea concentration increases rapidly as it is impermeable. More water reabsorption occurs in the inner medullary collecting ducts, further increasing the urea concentration within the tubules. As the medullary collecting ducts are permeable to urea, it diffuses out into the renal interstitium. One of the urea transporters UT-A1 is activated by ADH and thus increases the transport of urea into the interstitium
• The increased urea diffuses into the thin descending and ascending limbs of the loop of Henle and eventually back to the collecting tubules, recirculating many times before it is excreted. This helps maintain the high urea concentration within the interstitium.

Anti-diuretic hormone:

• Required for maximal concentration of urine to be achieved. ADH is activated mainly by increased osmolarity and decreased circulating volume.
• ADH results in the luminal expression of aquaporin channels in the late distal tubule and collecting ducts à water is thus passively reabsorbed into the interstitium, driven by the osmotic gradient established by sodium chloride and urea as outlined earlier à urine is concentrated