The loop of Henle is the U-shaped section of each kidney tubule responsible for concentrating your urine. It does this by creating a gradient of increasing saltiness from the outer edge of the kidney (the cortex) deep into its interior (the medulla), where the concentration of dissolved particles rises from about 300 mOsm/L to roughly 1,200 to 1,400 mOsm/L. Without this gradient, your kidneys could not pull water back from urine before it leaves your body, and you would lose dangerous amounts of fluid every day.
How the Loop Is Built
The loop of Henle has three functionally distinct segments. The thin descending limb dips downward into the medulla. It is studded with water channels called aquaporin-1 (AQP1), making it extremely permeable to water but relatively impermeable to salt and urea. Next comes the thin ascending limb, which reverses course and heads back toward the cortex. This segment lacks AQP1 but expresses a chloride channel (ClC-K1), so it lets chloride pass through while keeping water inside the tubule. Finally, the thick ascending limb completes the return trip. This is the workhorse segment: it actively pumps sodium, potassium, and chloride out of the tubular fluid using a transporter called NKCC2, and it reabsorbs about 25 to 30 percent of all the sodium chloride that originally entered the kidney’s filtration system.
Not all loops are the same length. About 85 percent of your nephrons (the kidney’s filtering units) are cortical nephrons with short loops that barely dip into the medulla. The remaining 15 percent are juxtamedullary nephrons with long loops that plunge deep into the inner medulla. These long-looped nephrons are the ones most responsible for generating the steep osmotic gradient that allows maximum urine concentration. They are served by specialized blood vessels called the vasa recta rather than ordinary capillary networks.
The Countercurrent Multiplier
The loop of Henle concentrates urine through a process called countercurrent multiplication. The name comes from the fact that fluid flows in opposite directions in the two limbs of the loop, and this arrangement amplifies a small difference in salt concentration into a large gradient across the entire medulla.
Here is what happens step by step. As fluid enters the thick ascending limb, NKCC2 transporters pump sodium, potassium, and chloride out of the tubule and into the surrounding tissue. Because the thick ascending limb is waterproof, water stays behind, and the fluid inside the tubule becomes more dilute while the tissue around it becomes saltier. That extra salt in the tissue now draws water out of the neighboring descending limb, which is highly permeable to water. Losing water makes the fluid inside the descending limb more concentrated as it travels deeper into the medulla. When that concentrated fluid eventually rounds the bend and enters the ascending limb, there is even more salt available for the pumps to push out. Each pass through the loop ratchets the medullary saltiness a little higher, building the gradient from 300 mOsm/L at the cortex boundary to over 1,200 mOsm/L at the tip of the medulla.
Experiments in mice missing the AQP1 water channel confirm how critical water movement in the descending limb is. Without AQP1, water permeability in the descending limb drops about 8.5-fold, and the kidneys cannot produce maximally concentrated urine. Solute entry alone is not enough; osmotic water transport out of the descending limb is essential.
What the Loop Actually Reabsorbs
Under normal conditions, the loop of Henle reabsorbs roughly 25 to 26 percent of the filtered water and about 40 percent of the filtered sodium. The water leaves primarily through the descending limb, while the sodium exits through the ascending limb. This split is the key to the whole system: separating water reabsorption from salt reabsorption is what makes the urine progressively more dilute in the ascending limb and the surrounding tissue progressively more concentrated.
The thick ascending limb also drives the reabsorption of calcium and magnesium through a less direct route. When NKCC2 pumps ions out of the tubular fluid, it creates a small positive electrical charge inside the tubule lumen. That charge pushes calcium and magnesium ions out through the spaces between cells (the paracellular pathway). If NKCC2 is blocked, the electrical charge disappears, and the kidney loses calcium and magnesium along with sodium.
Urea’s Role in the Gradient
Salt is not the only molecule building the medullary gradient. Urea contributes a significant share, especially in the deepest part of the medulla. The collecting ducts, which run parallel to the loops of Henle, release urea into the inner medullary tissue. This raises the urea concentration in the surrounding fluid, which in turn draws water out of the descending limbs and collecting ducts, further concentrating their contents.
Urea also recycles within the medulla. Specialized urea transporters (UT-A2) in the descending limbs allow urea to move between tubule segments and blood vessels. Blood vessels ascending out of the medulla pick up urea, then deliver it back down through the descending vessels, keeping urea trapped in the inner medulla rather than letting it escape into the general circulation. During antidiuresis (when the body is conserving water), this recycling intensifies and the gradient steepens. During diuresis (when you are well-hydrated), the gradient relaxes.
How the Vasa Recta Protects the Gradient
A normal capillary bed running through the salty medulla would quickly wash out the gradient by carrying dissolved solutes away. The vasa recta avoids this problem through its hairpin shape, which mirrors the loop of Henle. As blood descends into the medulla, it picks up salt and loses water, equilibrating with the increasingly concentrated tissue. As it ascends back toward the cortex, the reverse happens: it loses salt and regains water. Because blood flow through the vasa recta is slow, these exchanges never fully complete, so blood leaving the medulla is slightly saltier than blood entering it. This removes just enough water to prevent the medulla from swelling, without stripping away the solutes that the loop of Henle worked to deposit.
Why Loop Diuretics Work Here
Loop diuretics, among the most powerful water pills prescribed for conditions like heart failure and severe edema, target the loop of Henle directly. They compete with chloride for a binding site on the NKCC2 transporter in the thick ascending limb, shutting it down. With NKCC2 blocked, sodium and chloride stay inside the tubule instead of being pumped into the medullary tissue. The medullary gradient weakens, less water is pulled out of the collecting ducts, and urine volume increases sharply. The same blockade eliminates the electrical charge that normally drives calcium and magnesium reabsorption, which is why these medications can lower blood levels of both minerals over time.
The potency of loop diuretics reflects just how much work the thick ascending limb normally does. Blocking a single transporter in this one segment is enough to increase water and salt excretion dramatically, because 25 to 30 percent of all filtered sodium passes through NKCC2 on its way back into the body.