Describe how the osmotic pressure gradient in renal medulla is formed and the role of osmotic pressure gradient in concentration and dilution of urine?

Answer 1

The osmotic pressure of renal medulla is produced most trough a balance between water and Na+/K+/Cl-/urea+ entering it. First, water enters the medulla going out from the descending limb of Henle's loop and out from the medullar collector ducts. Remember that for water to cross the nephron tubules it is strictly necessary that the tubule cells express the protein aquaporin, i.e., a water channel in all features similar to ion-channels1. A similar channel called UT (for urea transporter) enables that urea cross the tubules wall. Well, aquaporin is constitutively expressed in renal medulla along the descending limb and at the collector ducts. The UT is expressed in medulla at the turn of Henle's loop and at the collector ducts. Both the transporters at the collector ducts are presented at the apical surfaces (inside the tubule) only if the hormone ADH2 is present. Ion channels are highly expressed3 mainly at ascending limb of Henle's loop. A similar membrane structure is present at the vasa recta, i.e., the capillaries that follow the Henle's loop going into the renal medulla and back to the renal cortex. These vessels are permeable too much more permeable to ions than to H2O, and are not permeable to urea and proteins. So, they keep the same osmolarity of the medulla trough ion exchange than trough water exchange. The osmotic gradient in the medulla is created because a lot of water enters the medulla at its highest parts, due to osmosis, coming from the descending limb of Henle's loop (~25% of renal flow4). Ions are also released at the highest parts of the ascending limbs, because of Na+/K+/2Cl- ATPases5 mediating active transport from the tubules to the intercellular fluid of medulla. The balance between ions and H2O being released into medulla creates a hyper-osmotic fluid. The urea going out of the collector ducts increases further this osmolarity, because urine has much more urea than the renal medulla (1000 mM in urine vs. 500 mM in medulla).

The release of this hyper-osmotic fluid into the medulla is the strongest regulator of the H2O re-absorption in the kidney. The reason by which this osmolarity does not increase unlimited is because the vasa recta are continuously washing it out. The blood that passes trough the vasa recta increases in volume, because it receives ions and water, keeping its osmolarity.

While the Na+/K+/2Cl- ATPases acts as a motor pumping the medulla to higher osmolarities, the water crossing the descending limb of Henle's loop passively decreases it. Because of the water re-absorption at the collector ducts are low, it does not interfere too much with the medulla's osmotic pressure. So, despite the medulla's osmotic gradient is too much necessary for renal re-absorption of water, it is of little control by mechanisms which regulate urine production.

The 2nd major site of water re-absorption in the kidney is however at the distal convoluted tube, at the cortex. About 5% of renal flow of water is re-absorbed there, and it can be altered a lot due to the presence of aquaporin in membranes, strictly under the control of ADH. Because the tubules fluid there is iso-osmotic to the cortex (290 mOs), the water transport occurs driven by the active transport of Na+ out from the tubular fluid6.

When ADH levels are low in the blood (possibly due to decreased blood osmolarity or drugs like caffeine and alcohol), too little aquaporin is present at the inner of the distal convoluted tubule, and the transport of Na+ is not followed by water transport. A lot of water remains into the tubule, being excreted as a hypo-osmotic urine reaching even 20 mL/min or 8 L/day. Conversely, if ADH levels are high in the blood (possibly due to increased blood osmolarity), a lot of aquaporin is present at the inner of the distal convoluted tube, enabling water to follows the Na+ active transport. Then, urine acquires a hyper-osmotic character as it crosses the medulla in a low-flux faction, decreasing to about 0.4 ml/min or 500 mL/day. ---- 1Each cell is rounded by a lipid membrane, which does not allow polar molecules to pass because they do not dissolve in it. Substances such as H2O, Na+ (sodium), K+ (potassium), Cl- (chloride) and urea are highly polar, so they cannot pass the cell membranes unless transmembrane proteins create a channel. These proteins form pores too specific, however, allowing only one of H2O, Na+, K+ or urea to pass trough it. There are water-channels (aquaporin), sodium-channels, potassium-channels and urea transporters (not exactly a channel). 2 ADH means Anti-Diuretic Hormone, or vasopressin. It is a protein released by the pituitary gland into the blood when specific neurons detect a slight increase in blood osmolarity, which is kept at 290 mOs. 3 A cell expresses a protein when the cell activates the gene codifying it. Although all cells of the body have the sane genetic code, not all genes are activated at the same cell-type and at the same time. In fact, about only 1% of the genes in human genome is expressed in any cell. There are constitutive genes, which remain activated in a tissue despite any regulation. Other genes are expressed only under specific environmental stimulation, usually due to hormones reaching the cell. 4About 1100 mL/min of blood passes trough kidney (650 mL/min of plasma), of which 120 mL/min enters the renal filtration system, pumped by a pressure gradient of 20 mmHg lower into the Bowman's capsule than in the blood vessels. The non-filtered part goes to the vasa recta and recovers most of it constituents, but a part of its urea and water.

5 Na+/K+/2Cl- ATPases are membrane proteins expressed at the end of the ascending limb of Henle's loop. This region of the loop does not express aquaporin and UT, so it is impermeable to water and urea. The protein hydrolyses intracellular ATP in order to force large amounts of Na+/K+/2Cl- ions out of the tubular fluid and into the tubular cells, from which the ions leave passively, trough ion channels. 6 The active transport here is driven by the classical Na+/K+ ATPase. This protein is present at the outer face of the tubular cells and if forces Na+ ions out of the cells. The fluid Na+ ions enter the cells by passive sodium-channels at the inner face. Similarly, K+ ions enter the cells and the tubular fluid coming from out of the tubules. Because more sodium exits than potassium enters, the Na+/K+ ATPase decreases the osmolarity of the tubular fluid. This does not happen, however, because water can freely cross the tubule walls, following the Na+ ions. The presence of ion channels and Na+/K+ ATPase at this portion of the renal tubules are under the control of the hormone aldosterone.