The counter-current multlier revealedAction in the descending armAction in the collecting duct

You might want to quickly brush up on the basics with the nephron overview.


The loop of Henle is confusing. You can’t describe how it functions by starting at point A and ending at point B, because it’s a dynamic system full of chicken-and-eggs paradoxes. A good way to cope with this is to focus on a particular chicken and worry about finding the egg later. Let’s start with some basics:

  • Water and solutes flow from areas of high concentration to low concentration. Remember that a high concentration of water will produce a dilute fluid, so water flows from dilute to concentrated areas. Solutes such as Na+, on the other hand flow from where they are concentrated to where they are less concentrated.
  • There is a gradient of increasing osmolality from 300 to 1200 mOsmol/kg in the renal medulla. This is generated by the Loop of Henle.
  • This gradient is the driving force for concentrating urine, which involves removing water from the collecting ducts.
  • Different regions of the nephron have different permeability to water and/or solutes. Furthermore, in some region of the nephron, solutes are actively pumped, rather than simply following diffusion gradients.
  • When body pumps Na+, Cl- tends to find a way to follow (e.g. through Cl- channels). Water will follow NaCl, if it can. Differential permeability to water is the secret to the function of the nephron.

The counter current multiplier is in the ascending loop of Henle

The ascending limb of the loop of Henle is probably the easiest - if not the most obvious - place to begin understanding how the loop of Henle creates the osmotic gradient down the medulla that is so crucial to producing concentrated urine. The filtrate in the ascending loop of Henle and blood in the vasa recta (the capillaries that follow in parallel to the loop) flow in opposite directions (counter-current), with the vasa recta running into the medulla. The vasa recta and the interstitial fluid equilibrate freely at all times (which is why the vasa recta is often omitted for “clarity” in textbooks), but the fluid in the vasa recta is moving, and this is crucially important to understanding the loop of Henle: you need to see the currents.

The osmolality of the filtrate at the turn (bottom) of the Loop of Henle is about 1200 mOsmol/kg (we’ll see why later). As filtrate rises towards the cortex, Na+ is pumped out of the ascending loop by an ATPase. Because this region of the nephron is impermeable to water, by the time the filtrate reaches the top of the ascending limb, most of the Na+ has been removed and the filtrate is much more dilute than even blood (around 100 mOsmol/kg). At the same time the interstitium becomes decreasingly hyperosmotic from the depths of the medulla up to the cortex as the filtrate is depleted of sodium to pump out.

The blood in the vasa recta at the top of the ascending loop has a similar osmolality to blood at about 290 mOsmol/kg. As it passes counter-current to the ascending limb, it picks up more and more of the Na+ that has been pumped out, becoming increasingly hyperosmotic until it reaches 1200 mOsmol/kg at the bottom of the loop of Henle. This is why the gradient in the medulla exists: the vasa recta draws Na+ down into the medulla. Without the filtrate flowing in the other direction - pumping Na+ along its length - the gradient wouldn’t exist. This is the counter-current exchange process. Figure 1 illustrates how the process occurs.

loop of henle ascending

Figure 1: The counter-current multiplier of the mammalian kidney. Remember that Na+ is being pumped and that the ascending tubule is not permeable to water. Filtrate in the ascending limb initially has a high solute content (1200 mOsmol/kg), but enters the distal convoluted tubule with an osmolality of about 100 mOsmol/kg). By contrast the vasa recta has an osmolality typical of blood of about 290 mOsmol/kg) as it enters the medulla, which increases to 1200 mOsmol/kg by the time blood reaches the deepest depths. Because the vasa recta and interstitial fluid equilibrate freely, they have the same osmolality, and the gradient that exists is due (in part – see more on urea later) to the vasa recta picking up Na+ from the ascending limb and taking it into the medulla. As blood passes down it moves into a region that is slightly more hypertonic, resulting in more and more Na+ being taken up.

Our next question concerns how the filtrate ends up so concentrated at the turn of the loop of Henle, and the answer is that most of the water has been wrung out of it and put back into the blood as it passes back up the descending limb.

The descending arm of the Loop of Henle produces concentrated filtrate

Why is the filtrate at the turn of the Loop of Henle so concentrated in the first place? The descending loop of Henle has very different properties to the ascending limb and is travelling in the opposite direction. The descending limb is permeable to water, but not to ions. As a consequence of fluid travelling into the increasing hypertonic medullary interstitium (created by the ascending limb; see above), water is withdrawn by osmosis, while the ions are trapped within the tubule. The result is highly concentrated filtrate. The water that is lost from the filtrate is taken up by the ascending vasa recta to dilute blood back to a normal osmolality. Despite all the shenanigans in the Loop of Henle, blood entering and leaving have much the same osmolality. Figure 2 illustrates what goes on in this region of the kidney.

loop of henle descending

Figure 2: Unlike the ascending limb, the descending limb of the Loop of Henle is permeable to water, but not to ions. Fluids flux in the descending limb of the Loop of Henle draws water from the filtrate, restoring plasma osmolality and increasing filtrate concentration at the same time. This is why the filtrate is so concentrated at the bottom of the Loop of Henle, which then drives the counter-current process on the other side of the loop, making the interstitium equally hypertonic.

The collecting duct is where urine is concentrated

Recall that when the filtrate leaves the ascending limb of the loop of Henle it has an osmolality of about 100 mOsmol/kg. This is hardly concentrated – it’s about one third the osmolality of blood. At maximal concentrating power, the human kidney can concentrate urine to about four-fold higher than blood (some animals can do much better than this), so we still haven’t got to the bottom of the process.

Like the descending Loop of Henle, the collecting duct is permeable to water (but this is variable and controlled by antidiuretic hormone (ADH)), which is drawn towards the hypertonic medulla. If the permeability of the collecting duct to water is high (i.e. high ADH), water follows this pathway producing a concentrated urine. From the interstitium, water moves freely into the vasa recta and is carried back to the body. When ADH levels are low, the collecting duct is less permeable to water so that although the osmotic gradient to draw water is still present, water remains in the collecting duct. This produces a higher volume of more dilute urine.

By now, there isn’t much in the way of inorganic salts in the filtrate, which contains much more urea at this stage. The collecting duct is permeable to urea, so some of this diffuses out into the medullary interstium. Here it makes up the other half of the hypertonicity in this region (NaCl being the other half – see above).

renal collecting duct

Figure 3: The production of concentrated urine involves the drawing of water out of the collecting duct and into the vasa recta accompanying the descending loop of Henle. The hypertonic medullary interstitium – the product of the counter current multiplier – is crucial to this process. So long as the collecting duct is permeable to water (i.e. ADH is present), water is drawn out to equilibrate urine with the surrounding tissues. In the absence of ADH, the gradient to draw water remains, but no flux is possible. Under these conditions, urine remains dilute rather than becoming hypertonic.

Animals with incredible powers of urine concentration (typically, desert-dwellers) have longer Loops of Henle, producing a wider gradient of hyperosmolality in the medullary interstitium. If that makes sense to you, then you understand kidneys.

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