Osmotic Gradient in Renal Medulla

The osmolarity of the interstitial fluid in the medulla of the kidney is much higher, increasing progressively to about 1200 to 1400 mOsm/L in the pelvic tip of the medulla. What are the factors that contribute to the hyperosmolarity of renal medulla?The osmolarity of interstitial fluid in almost all parts of the body is about 300 mOsm/L, which is similar to the plasma osmolarity. The osmolarity of the interstitial fluid in the medulla of the kidney is much higher, increasing progressively to about 1200 to 1400 mOsm/L in the pelvic tip of the medulla. This means that the renal medullary interstitium has accumulated solutes in great excess of water. Once the high solute concentration in the medulla is achieved, it is maintained by a balanced inflow and outflow of solutes and water in the medulla.
What are the factors that contribute to the hyperosmolarity of renal medulla?

The major factors that contribute to the buildup of solute concentration in the renal medulla are:
1. Active transport of sodium ions and co-transport of potassium, chloride, and other ions out of the thick portion of the ascending limb of the loop of Henle into the medullary interstitium
2. Active transport of ions from the collecting ducts into the medullary interstitium
3. Facilitated diffusion of large amounts of urea from the inner medullary collecting ducts into the medullary interstitium
4. Diffusion of only small amounts of water from the medullary tubules into the medullary interstitium,
far less than the reabsorption of solutes into the medullary interstitium.
Special Characteristics of Loop of Henle That Cause Solutes to Be Trapped in the Renal Medulla.
The most important cause of the high medullary osmolarity is active transport of sodium and cotransport of potassium, chloride, and other ions from the thick ascending loop of Henle into the interstitium. Because the thick ascending limb is virtually impermeable to water, the solutes pumped out are not followed by osmotic flow of water into the interstitium.
The descending limb of Henle's loop is very permeable to water. Therefore, water diffuses out of the descending limb of Henle's loop into the interstitium, and the tubular fluid osmolarity gradually rises as it flows toward the tip of the loop of Henle.