Nephron Explorer
Turn a nephron in three dimensions and watch the loop build the gradient that lets the collecting duct concentrate urine, or a diuretic destroy it.
Simulator
Drag the scene to turn it, or use the arrow keys. Space plays and pauses.
- Urine osmolality Above plasma, so water is being conserved.
- 1035 mOsm/kg
- Urine volume 0.557 mL/min.
- 0.801 L/day
- Free water clearance Negative means water is being retained. Zero means the loss is isotonic, whatever the volume.
- -1.36 mL/min
- Medulla at the tip Built by the ascending limb. Nothing can concentrate urine past it.
- 1200 mOsm/kg
- Solute excreted ADH does not change this. It moves water, not solute.
- 829 mOsm/day
- Filtered water reabsorbed
- 99.54 %
- Glomerulus filters plasma at roughly 300 mOsm/kg, holding back cells and protein.
- Proximal tubule reabsorbs about two thirds of the filtrate, solute and water together.
- Descending limb leaks water into the concentrated medulla, so the fluid concentrates.
- Ascending limb pumps salt out while holding water in, so the fluid dilutes.
- Distal tubule trims sodium finely, still watertight to water without ADH.
- Collecting duct reabsorbs water only as ADH permits, setting the final concentration.
- Tubular fluid
- Plasma
Citing this tool
Last updated . Add the date you accessed it as well, which a citation of a page that can change asks for. If a specific result matters, cite the permalink from the tool’s share row instead of this page: it reproduces the exact parameters.
The equation
Countercurrent multiplication, Kuhn and Ryffel (1942)
The loop exists to make the medulla salty
Everything else on this page follows from that one sentence. The thick
ascending limb pumps sodium and chloride out into the surrounding tissue
while staying watertight, so salt accumulates in the medulla without water
following it. That salt, together with urea recycled from the collecting duct, is why the
deep tissue reaches 1200 mOsm/kg when blood is at 300. This model
counts every osmole alike, so the salt pumping stands in for both.
Now look at what the descending limb does with that. It is the opposite kind of tube: permeable to water, largely impermeable to salt. Sitting in concentrated tissue, it simply loses water outward, so the fluid inside it concentrates as it descends without anything being pumped at all. Turn the scene and watch the two limbs run side by side. They are one continuous tube doing opposite jobs, and each one makes the other possible.
That mutual dependence is where the word multiplier comes from. Salt pumped out of the ascending limb raises the tissue osmolality, which pulls more water out of the descending limb, which delivers saltier fluid back around the bend for the ascending limb to pump. A modest single pass, run in that loop, compounds into a gradient four times plasma. It is also why the blockade slider bites so hard: halving the pumping costs you far more than half the gradient.
The proximal tubule removes two thirds of the filtrate and changes nothing
This is the fact most people get wrong, so it is worth watching directly. Set the scene running and follow a parcel through the first coil. The tube thins dramatically, because two thirds of the volume has gone. The colour does not shift at all.
Solute and water leave together, in the proportions they arrived in, so the concentration of what remains is exactly what it was. The proximal tubule is a bulk reclaimer, not a concentrator. Reabsorbing most of the filtrate and reabsorbing it selectively are different jobs, and this segment only does the first.
ADH cannot beat the medulla
Antidiuretic hormone opens water channels in the collecting duct, and that is the whole of its action here. It does not pump water. It permits water to move down a gradient that something else built.
So the ceiling on urine concentration is not set by how much ADH is present. It is set by the medulla, which is why the readouts show the medullary tip osmolality next to the urine osmolality: the second can approach the first and never pass it. Push the ADH slider to 1 and the urine meets the tip exactly. There is nowhere further to go.
Now do the experiment that makes the point. Drag the loop blockade to 1 and then move ADH across its whole range. Nothing happens. With the gradient gone there is no downhill for water to run, so the hormone has no lever to pull. Structure first, hormone second.
Why a loop diuretic is more than a blocked pump
A drug that blocks the ascending limb has two effects, and the second one is larger than the first.
The direct effect is the obvious one: salt that would have been reabsorbed stays in the tubule and leaves in the urine. Watch the solute excretion readout climb as you drag the blockade.
The indirect effect is that the gradient the whole kidney depends on was being built by the segment you just blocked. It collapses, so the descending limb has nothing to concentrate against, the diluting segment stops diluting, and the collecting duct loses the ability to move water in either direction. The kidney can no longer make urine concentrated or dilute. It can only make a lot of it, at roughly plasma osmolality.
The number urine volume cannot give you
Two of the settings on this page produce about eight litres a day and mean completely different things. Free water clearance is what tells them apart.
| Setting | Urine | Free water clearance |
|---|---|---|
| ADH 0, loop intact | Large, dilute | Strongly positive |
| ADH 1, loop fully blocked | Large, isotonic | Zero |
| ADH 1, loop intact | Small, concentrated | Negative |
A patient losing eight litres of dilute urine is heading for a rising plasma sodium. A patient losing eight litres of isotonic urine is heading for an empty circulation with a normal sodium. Volume alone cannot distinguish those, and free water clearance does it in one number: it is the volume of pure water the kidney is adding to the body, so a negative value means water is being kept.
Why urine volume is solute divided by concentration
The equation above is not a formula to memorise so much as a way of seeing what the collecting duct actually does. The solute arriving there is fixed by the segments upstream, none of which respond to ADH. The duct then reabsorbs water until the fluid reaches whatever concentration the medulla and ADH permit. The volume left over is simply the solute divided by that concentration.
Read the readouts while you move ADH and you can watch this happen: solute excreted does not budge, urine osmolality rises, and volume falls in exact inverse proportion. It also explains osmotic diuresis, which no model based on fractions of water reabsorbed can express. Give the duct far more solute, as uncontrolled glucose does, and the volume rises even though the concentrating machinery is working perfectly.
Common mistakes
- Thinking the proximal tubule concentrates urine. It removes most of the volume and leaves the concentration untouched. The concentrating happens in the descending limb and the collecting duct.
- Thinking ADH pumps water. It opens channels. Without a gradient, open channels move nothing, which is exactly what the fully blocked loop demonstrates.
- Expecting the ascending limb to change the volume. It is watertight. Salt leaves, water cannot, so the volume entering is the volume leaving. That is the only reason it can dilute.
- Reading a large urine volume as water loss. Check the osmolality. Isotonic polyuria is salt and water leaving together, and it drops the circulating volume without touching plasma sodium.
- Assuming ADH controls how much sodium is excreted. It does not. It governs water. Sodium excretion is aldosterone’s territory and the loop’s, which is why the solute readout ignores the ADH slider entirely.
- Trusting the low GFR settings too far. The model scales linearly, so it will happily report a concentrated trickle at a GFR of 20. A real kidney that damaged has usually lost its medullary gradient too, and produces urine stuck near plasma osmolality however dehydrated the patient is.
Model and assumptions
- Method
- Exact expression, no time stepping
- Repeatability
- Deterministic. The same link gives the same numbers on any machine.
What it assumes
- Osmolality along the tubule is evaluated from position, with no time stepping and no transient.
- A steady state: the corticomedullary gradient is taken as established rather than built up.
- One representative nephron, so it does not distinguish cortical from juxtamedullary populations.
Numerical accuracy
No method error to report: the result is a closed-form expression evaluated directly, with no time stepping to accumulate error. What remains is double-precision rounding, of order one part in 10^16 per operation.
Common questions
Why does the loop of Henle need two limbs going opposite ways?
Because each limb makes the other one work. The ascending limb pumps salt out into the medulla while staying watertight, which concentrates the tissue. The descending limb is the opposite kind of tube, permeable to water and not to salt, so sitting in that concentrated tissue it loses water outward and the fluid inside it concentrates without anything being pumped. That saltier fluid then rounds the bend and arrives at the ascending limb, which has more salt to pump than it otherwise would. A modest single pass, run around that loop, compounds into a gradient four times the concentration of blood. One limb alone could not do it, which is why the arrangement is called a countercurrent multiplier rather than simply a pump.
Can ADH concentrate urine without the loop working?
No, and this is the most useful thing on the page to convince yourself of. ADH opens water channels in the collecting duct; it does not pump water. Open channels only move water if there is a gradient for it to run down, and that gradient is built by the ascending limb. Set the loop blockade to 1 and then move ADH across its entire range: the urine osmolality does not change at all. This is why the readouts show the medullary tip osmolality beside the urine osmolality. The second can approach the first and can never exceed it, whatever the hormone is doing.
Why does the proximal tubule not change the concentration?
Because it reabsorbs solute and water together, in the proportions they arrived in. Two thirds of the filtrate volume leaves in that first coil, which is why the tube visibly thins, and the concentration of what remains is exactly what it was when it was filtered. Reabsorbing most of the filtrate and reabsorbing it selectively are two different jobs, and the proximal tubule only does the first. The selective work happens further along, in the limbs of the loop and in the collecting duct.
Why do loop diuretics cause such a large diuresis?
They have two effects and the second is bigger than the first. Directly, salt that would have been reabsorbed by the ascending limb stays in the tubule and leaves in the urine, taking water with it. Indirectly, and more importantly, the segment being blocked is the one that builds the medullary gradient in the first place. That gradient collapses, so the descending limb has nothing to concentrate against, the diluting segment stops diluting, and the collecting duct can no longer move water in either direction. The kidney loses the ability to make urine either concentrated or dilute, and produces a large volume at roughly plasma osmolality.
What does free water clearance tell me that urine volume does not?
Which way water is actually moving. Two settings on this page both produce around eight litres a day and mean opposite things. No ADH with an intact loop gives dilute urine and a strongly positive free water clearance, so mostly water is being lost and the plasma sodium will rise. A fully blocked loop gives the same volume at plasma osmolality with a free water clearance of exactly zero, so salt and water are leaving together in the proportions they exist in the body, and the circulating volume falls while the sodium stays normal. A negative value means the kidney is retaining water. Volume alone cannot distinguish those three situations and this one number does.
Why can a failing kidney not concentrate urine?
Because concentrating depends on the medullary gradient, and the damage that reduces filtration usually damages the machinery that builds it. Urine stuck near plasma osmolality however dehydrated the patient is, called isosthenuria, is a classic finding in advanced kidney disease. Worth knowing as a limitation of this model rather than a feature of it: the numbers here scale linearly with GFR, so the low settings will happily report a small volume of well-concentrated urine. A real kidney at that filtration rate has generally lost the gradient too, and it also has to keep excreting the same daily solute load, which it manages by reabsorbing a smaller fraction rather than by excreting less.