The counter-current mechanisms in the kidney

This chapter seems relevant to the aims of Section H1(iv) from the 2023 CICM Primary Syllabus, which expects the exam candidate to "explain the counter-current mechanisms in the kidney". This is a popular choice for renal questions in the CICM First Part exam, and trainees are encouraged to compose a ready answer because the subject is complex enough to bury the unprepared candidate. For example, the college comments from 2011 record that though some candidates "elected to draw the loop of Henle and vasa recta... and answer the question from it", it was a hilariously doomed approach because "mistakes in these diagrams only confused their answers further". In short, be clear about what you plan to say about the countercurrent mechanism.

Representative questions from the past papers include the following:

The usual wording is "explain" or "describe", which are apparently direct synonyms because the examiners' expectations are the same for each. To facilitate rapid revision, the following short explanation/description is offered:

  • The "single effect":
    • The thick ascending limb of the loop of Henle extracts solutes from the tubule fluid 
    • This transfers the solutes to the renal medulla
    • The renal medulla then becomes hyperosmolar (1200 mOsm/kg)
    • This facilitates the removal of water from the thin descending limb of the loop of Henle
    • Thus, fluid in the thin descending limb also becomes hyperosmolar
  • Countercurrent multiplication of the single effect
    • The movement of hyperosmolar fluid up into the thick ascending limb continuously delivers more solute
    • Thus, more solute is transferred to the medullary interstitium
    • The hyperosmolarity of the interstitium then extracts more water from the descending tubule fluid, maintaining its hyperosmolarity
    • The concentration gradient maintained in this way reduces the energy cost of extracting solutes from the thick ascending limb.
  • Countercurent exchange in the vasa recta
    • The vasa recta are permeable to water and solutes
    • Solutes diffuse into the descending vasa recta, and then back out again as the blood returns via the ascending vasa recta
      • These vessels also have slower flow because of increased crossection, increasing the efficiency of solute exchange
    • This mechanism prevents the washout of concentrated inner medullary solutes
    • More water returns via the ascending vasa recta, removing reclaimed water from the renal medulla
  • Role of intrarenal urea recycling:
    • Proximal cortical collecting duct is permeable to water but not to urea.
    • Water can move out of the cortical collecting duct, but urea cannot, which causes the concentration of urea in the duct
    • Distal collecting duct is permeable to urea
    • Thus, the concentrated urea can move into the renal interstitum
    • From there, it can be absorbed into the ascending limb fluid, and recycled
    • Vasopressin increases the permeability of the collecting duct to urea.
  • The osmolalities at different points in the tubule are:
    • Renal interstitial osmolality values:
      • Cortex osmolality: 300 mOsm/kg
      • Outer medulla: 800 mOsm/kg
      • Inner medulla:  1200 mOsm/kg
    • Loop of Henle osmolality values:
      • Proximal tubule, straight part: 300 mOsm/kg
      • Descending limb: 800 mOsm/kg
      • Hairpin turn: 1200 mOsm/kg
      • Ascending thin limb: 800 mOsm/kg
      • Ascending thick limb: 100 mOsm/kg, at the end

There is vast amounts of literature to describe this mechanism, in the shape of simple words, pictures, video, spoken word performance and parlour game. Sidestepping the most obvious question ("why did you decide you needed to add another resource"), the single best peer-reviewed article on this subject is Pallone et al (2003), being free and written in an accessible way. 

An explanation of the countercurrent mechanism in the kidney

"A countercurrent system is a system in which the inflow runs parallel to, counter to, and in close proximity to the outflow for some distance", helpfully offers Ganong. In fact, this is the definition that appears countless times across different sources, producing the impression of legitimacy through consensus. To explain this highly dynamic mechanism would probably benefit from some sort of moving pictures, but this famously obstinate author refuses to record sound and video, leaving only static media. Using words and images to explain something like this would obviously require an abundance of both.  To make matters worse, the death of Adobe Flash has laid to waste vast ranges of the internet, among which were some extremely helpful animations.  Thus, for lack of a better option. another sequence of U-shaped tubes is produced for the reader, which has no clear advantage over any other similar sequence of tubes.

The "single effect" 

So: first, let us consider what would be happening if there was equilibrium in the tubule and in the interstitium. That's right, nothing. Nothing would be happening.


Then, let us activate some sodium/chloride/potassium channels in the ascending limb. The result is a movement of ions into the interstitial fluid, which lowers the osmolality of the tubular fluid, and raises the osmolality of the interstitial fluid.

Now, we have an osmotic gradient between the descending tubule and the interstitium. Because the thin descending limb is famously water-permeable, water effortlessly migrates into the interstitium until an equilibrium is achieved between these two compartments. One might expect this to produce some sort of dilutional change in the interstitial fluid, but no - the extra water is carried away by the vasa recta, which means the osmolality of the tubular fluid in the thin descending limb will always trend towards the osmolality of the interstitium.

This whole scenario - where solute extraction from the ascending limb leads to increased interstitial osmolality and water extraction from the descending limb - is generally referred to as the single effect. The term is not used consistently in the literature, but appears in papers often enough for it to seem like it is A Thing in renal physiology. It seems to date back to the very earliest representation of this countercurrent process by Werner Kuhn and Kaspar Ryffel in 1942. In their paper, they referred to an Einzeleffect which seems to require Vervielfältiguüg (duplication or multiplication) in order to produce the observed concentration gradient. The countercurrent multiplication of this one ion-pumping effect is the origin of the medullary concentration gradient, they posed; and it appears later authors have reproduced the terminology in English without any modification

So, let us now add some new fresh glomerular filtrate, to produce a countercurrent flow and multiply this "single efect":

Countercurrent multiplication of the single effect

The countercurrent flow here refers to the fact that flow in the ascending and descending tubules is happening in opposite directions. In contrast, concurrent flow would be flow going in the same direction down both vessels. 


As it comes out of the proximal tubule, the fluid has an osmolality close to that of normal blood, as absorption of water and solutes in the proximal tubule is isoosmolar. As it enters the thin descending limb, it displaces some of the concentrated tubular fluid from the bend of the loop and up into the ascending limb. The ascending tubule transfers some solutes out of the tubule and into the interstitium, making the interstitium more hyperosmolar; except this time, there is something of a concentration gradient in play, which means the ions have to be pumped "uphill".

Again the hyperosmolar interstitium dehydrates the contents of the water-permeable descending limb.  And, as before, the distal ascending limb ends up removing even more electrolytes from the tubular contents, leaving behind some rather dilute tubular fluid. In short, by this point, the cyclicality of this process becomes apparent to most people. In spite of that, usually tube diagrams of the countercurrent mechanism continue for another cycle, as if expecting that those who have not yet grasped the concept will surely grasp it if only somebody were to patiently repeat it to them again without adding any new explanatory material.


Without insulting the reader with any further diagrams, the gist of this is that a small difference in osmotic pressure generated by a single effect (the effect of ion pumps in the thick ascending limb) ends up being multiplied by the countercurrent flow which brings fluid of increasingly higher and higher osmolality to the aforementioned pumps, allowing their One Weird Trick to produce increasingly higher and higher interstitial osmolalities. Moreover, even as the osmolality climbs higher and higher, the gradient between the tubular fluid and the intersititum remains relatively stable, which means the ion pumps never have to pump against a very high gradient, making this whole thing a lot more efficient. On the basis of these italicised underlined elements, this process is generally referred to as the countercurrent multiplier effect.

Magnitude of the countercurrent magnifier effect

How much does this multiplier mechanism multiply the medullary interstitial solute concentration? What are the values in the tubules of the living human kidney? One might be tempted to retort tartly that surely this must depend on the individual kidney, and in any case the understanding of the mechanism is more important than memorising numbers. Unfortunately, this is both true, and a terrible attitude to adopt for the CICM First Part Exam, which is built on the foundation of memorising pointless values. Specifically, in their comments for Question 4 from the first paper of 2020 the examiners insisted ungrammatically that "values for osmolality at the cortex & medulla and within the different parts of the LOH was required". 

What's a reputable resource for these sort of data? The college's need for quotable numbers does not diminish the fact that most of the values are measured in experimental animals, and not even from whole animals but often from tortured chunks of kidney. Moreover, they all give different values, and have different starting conditions. To make matters worse, the osmolality of the renal medulla varies  widely in the course of normal renal function. As an example, in some hamster experiments by Schmidt-Nielsen et al (1983), inner medulla osmolality was measured in states of minimal diuresis, maximal diuresis, and everything in between. The range of values spanned from 670 to 3330 mOsm/kg.

In short, the deeper you go in search of the One True Osmolality, the closer you approach the point of no return, beyond which you go insane. One should really just pick a source and stick with it; ideally a resource which represents some sort of mean values with which people are unlikely to disagree. One such resource is Kurbel et al (2002), a review article which describes regional differences in medullary osmolality as "horizons". Apart from this poetic advantage, the authors list three textbooks as their references, suggesting that this diagram was compiled from reputable sources.

  • Renal interstitial osmolality values:
    • Cortex osmolality: 300 mOsm/kg
    • Outer medulla: 800 mOsm/kg
    • Inner medulla:  1200 mOsm/kg
  • Loop of Henle osmolality values:
    • Proximal tubule, straight part: 300 mOsm/kg
    • Descending limb: 800 mOsm/kg
    • Hairpin turn: 1200 mOsm/kg
    • Ascending thin limb: 800 mOsm/kg
    • Ascending thick limb: 100 mOsm/kg, at the end

Countercurrent multiplication and countercurrent exchange

The terms "countercurrent multiplication" and "countercurrent exchange" are not interchangeable. Countercurrent multiplication is something the tubule does to create the high interstitial osmolality, and a large osmolality gradient between the renal medulla and the renal cortex. The countercurrent exchange mechanism is something the vasa recta do to maintain this gradient; or rather to prevent it from being completely destroyed by the constant delivery of comparatively hypoosmolar blood. The readers will be grateful for the input of Dr George Lindley-Jones, who in correspondence pointed out just how rude it would be for blood to simply blast all the way through the kidney in a straight line from cortex to pelvis. At a typical renal blood flow of 1000ml/min, the delivery of fluid with an osmolality of 300 mOsm/kg would rapidly wash out all  solutes and restore isoosmolarity to medullary interstitial fluid, totally wrecking your ability to concentrate urine. To prevent this uncivilised outcome, we have a hairpin microcirculation and a countercurrent exchange mechanism which, in the fewest words possible, represents the endless recirculation of solutes in and out of highly permeable vasa recta vessels.

The microcirculation of the medulla is a system designed to keep salt and urea trapped in the innermost renal medulla.  It achieves this goal by having relatively permeable walls. In this fashion, blood which flows into the medulla ends up becoming highly concentrated because medullary interstitial salt and urea diffuse into it, and blood coming back out of the medulla does not carry any of this salt and urea away because they diffuse back out of the blood just as easily. To borrow words from Wirz (1957),

“all the blood irrigating the medulla enters and leaves the medulla at the corticomedullary boundary, i.e., in an essentially isotonic [to systemic blood] region. In between it may adapt itself to the osmotic pressure of the surroundings by a passive uptake (on its way down) and release (on its way up) of osmotically active solutes.”

At this stage in the explanation of the mechanism one may be tempted to threaten the reader with another U-shaped diagram, and here is a suitably inane one.

countercurrent exchange mechanism involving the vasa recta

However, this image may give the reader the incorrect impression that the blood flow through this system ends up returning some identical volume of blood. Obviously this cannot be the case because the whole point of the inner medulla is to reabsorb water, which is deposited in the medulla by diffusion out of the descending tubule. There's no other way for it to leave (there are no lymphatics down there), so the ascending vasa recta must be carrying it away. This is indeed what is observed experimentally. When micropuncture experiments (Zimmerhackl et al, 1985) measured the protein content of blood in the descending and ascending vasa recta, they confirmed that the rate of water gain by the ascending limb was greater than the rate of water loss from the descending limb. This results in an increased total blood flow, i.e. there is a difference in the volume of blood delivered to the medulla by the descending vasa recta and the volume of blood returned by the ascending vasa recta. It appeared to be approximately doubled in the rat experiment by Holliger et al (1983), who measured a descending flow rate of 5.2 μl/min and an ascending flow rate of 11.3 μl/min, but it would surely vary depending on how much (or how little) diuresis one wishes to have. 

But wait, one might say. How does this reabsorption of water not produce a highly diluted blood in the ascending vasa recta? Surely that would make no sense. In order for blood to politely enter and leave the medulla without knocking over all the osmotic furniture, it must be exiting with the same osmolality as it entered with. This is indeed what happens. The rate of water and solute removal by the ascending vasa recta exactly matches the amount of water and solute removed by the tubules, and these are reclaimed from the urine in such proportions as to maintain body fluid osmolality, i.e. there is enough solute and water returned via the vasa recta to make up an isoosmolar milieu. 

Water is removed by the ascending vas arecta because there is a lag in osmolality equilibration between the ascending blood and the surrounding interstitium. At any given moment the concentration of the solutes in the ascending blood is slightly higher than the concentration of the corresponding patch of intersititum. This favours the movement of water into the ascending vasa recta. The blood is constantly moving, which means the gradient is constantly maintained, but it is not a very large gradient because the endothelium of the ascending vasa recta is highly fenestrated and its reflection coefficients for important solutes are extremely low, which means that the solutes equilibrate effortlessly. This assures that the osmolality of the fluid remains very close to that of the surrounding interstitium. 

The other mechanism is  deliberately increased transit time of blood in the ascending vasa recta. This is the "cauda equina" effect in the renal microcirculation, where one descending vasa recta vessel begets several ascending ones. The result is that the brisk flow from the descending vasa recta (about 17 mmHg hydrostatic pressure, in case you're wondering) ends up being split among a whole delta of slow meandering waterways. The slowing of the flow which results from this favours the exchange of ions and water, again favouring the equilibration of solute concentrations, which produces blood that is very nearly iso-osmolar with the medullary interstitium at every level of the medulla.

Therefore, at the corticomedullary junction, the blood returning from the medulla is basically iso-osmolar with the general circulation. However, it is slightly more anaemic and protein-poor,  as the porosity of the membrane is not sufficient for large molecules to be lost or gained during its travels in the inner medulla.  When Sanjana et al  (1975) measured the oncotic pressure in the vasa recta, they reported a value of 26 mmHg in the descending limb and only 18 mmHg in the ascending limb. The expected drop in haematocrit was also detected by numerous authors, though the effect is smaller overall because both descending and ascending vasa recta blood is curiously anaemic (haematocrit values of 0.26 and 0.25 are quoted). The debate around the possible (weird rheological) reasons for this is probably beyond the scope of this chapter.

The role of intrarenal urea recycling

"Urea recycling" is a term used to describe the different effects of vasopressin on water and urea handing in the collecting duct, which produces a situation where highly concentrated urea-rich tubular fluid passes through the inner medulla and contributes even more solute to the hyperosmolar medullary interstitium. Yang et al (2004) and Knepper (1994) is probably the best free explanation of how this happens and how it is regulated.

In short:

  • Fluid delivered into the proximal collecting duct is already enriched with urea.
  • Here, the epithelium is high water-permeable, but not urea-permeable
  • This leads to the net reabsorption of water, but not urea.
  • This concentrates the urea even further.
  • Then, in the distal collecting duct, which is higly urea-permeable, the urea diffuses out of the duct lumen and into the renal papilla.
  • Some of this urea ends up being carried away by the fluid in the ascending thin limb, but because this fluid ends up coming back via the collecting duct, this urea is not lost, but recycled.

The permeability of the proximal cortical collecting duct to urea is quite low; according to Sands & Knepper (1987) it is something like 2×10-5 cm/sec. This makes sense, as the purpose of the entire system is to produce concentrated urine, eliminating urea while reclaiming water. As the cortical duct fluid travels through the duct, much of the water from it would be reclaimed, massively increasing the concentration of urea in the duct( Ullrich et al in 1967 measured values of around 300-500 mmol/L, which was much higher than that of the renal interstitium). Then, in the lower third of the collecting duct (in the inner medulla) the duct lining suddenly becomes extremely urea-permeable (something like 40-50×10-5 cm/sec), and the urea is able to cross into the medulla. From there, it can diffuse into the ascending limb, where it ends up being carried back to the collecting duct, continuing the cycle.

Urea recycling in the renal medulla

To be clear, there's a few other pathways for urea recycling:

  • It is also recycled between the ascending vasa recta (which are carrying urea-rich blood out of the inner medulla) and the descending limb of the loop of Henle (which has a much lower urea concentration). In this way, urea is not carried away by the ascending blood flow.
  • It is also recycled between thick ascending limbs and proximal straight tubules in the cortical medullary rays
  • It is also "recycled" by being exchanged between the ascending and descending vasa recta

To represent these extra pathways on a similar diagram is possible, but messy: 

Urea recycling in the renal medulla


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