Regulation of Water Balance

Water Reabsorption

water reabsorption in the nephron

The figure at right summarizes water reabsorption along the nephron. Water reabsorption is a passive process: water is reabsorbed by osmosis. In most of the nephron, water reabsorption is unregulated and coupled to solute reabsorption.

In response to dehydration (increased ECF osmolarity) the kidneys can save water and produce concentrated urine.  The ability to excrete urine that is more concentrated than the extracellular fluid (ECF) depends on the creation of a hyperosmotic environment in the medulla. As the collecting duct descends through the medulla, the increasing osmolarity in the interstitial fluid drives water reabsorption.

However, there is a tremendous variability in water excretion. The urine produced can be either concentrated, or very dilute. How do the kidneys vary their urine concentrating ability? They do so by regulating water reabsorption in the collecting duct.

High Osmolarity in the Medulla

The ability to concentrate urine depends upon the generation of a hyperosmolar environment in the medulla. The loops of Henle are set up so as to concentrate osmolarity in the deepest part of the medulla. This occurs because the ascending and descending limbs have different permeabilities to salt and water.

In the thick ascending limb, there is active reabsorption of ions, but this segment is relatively impermeable to water. As a result, these cells can make the interstitial fluid hyperosmotic relative to the fluid inside the tubule (the filtrate).

In the descending limb, the opposite occurs. These cells donít allow ions to leave the filtrate, but water can freely leave, and it does, being drawn out by the high osmolarity created by the nearby thick ascending limb. This causes the filtrate in the descending limb to become concentrated.

Now, add to this system the countercurrent flow that occurs in the loop of Henle. Countercurrent flow causes the osmolarity differences to multiply as the renal tubule descends into the medulla. The filtrate inside the descending limb becomes progressively more concentrated, but then as it ascends back toward the cortex, active reabsorption of ions causes it to become progressively less concentrated. Effectively, the thick ascending limb transfers osmolarity to the descending limb and medullary interstitial fluid. The result is that osmolarity becomes trapped in the medulla.

Blood flow to the medulla is set up so as to maintain the osmotic gradient. The vasa recta are capillaries that flow in parallel to the loops of Henle. The blood flow in the vasa recta is sluggish, allowing time for the plasma in the vasa recta to equilibrate with the surrounding interstitial fluid. The osmolarity of the plasma inside the vasa recta increases as it descends into the medulla, and then decreases again on the ascending side. This allows blood to flow to the medulla, without eliminating the osmotic gradient.

Regulated Permeability in the Collecting Duct

In humans, the osmotic gradient in the medulla allows the kidneys to produce urine that can be roughly 5 times as concentrated as the ECF. Urine concentration can be varied through the regulation of water permeability in the collecting duct.

The permeability of cell membranes to water depends upon the presence of water channels known as aquaporins. There is a family of aquaporin proteins, with different types being expressed in different tissues. AQP3 (blue in figure) is constitutively expressed on the basolateral surface of cells in the collecting duct. AQP2 is found on the apical surface of these cells, but the number of AQP2 channels on the membrane is regulated by the hormone vasopressin (also known as antidiuretic hormone). When vasopressin binds to its receptor on the collecting duct cells, it stimulates the translocation of AQP2 to the membrane by causing vesicles containing the protein to fuse with the plasma membrane.

Regulation of Vasopressin Secretion

Vasopressin is a hormone that is produced by magnocellular cells, neurosecretory cells whose cell bodies are in the hypothalamus and whose terminals are located in the neurohypophysis (posterior pituitary). The main control of vasopressin secretion is by the hypothalamic osmoreceptors, neurons that sense changes in the osmolarity of the extracellular fluid. If the osmolarity of the ECF increases, the osmoreceptors increase their frequency of action potential firing, and more vasopressin is secreted. Increased action potential firing by the osmoreceptors also stimulates thirst.  If the osmolarity of the ECF decreases, the osmoreceptors decrease their action potential frequency and less vasopressin is secreted.

It can be helpful to remember that an increase in osmolarity reflects a decrease in water concentration.  When increased ECF osmolarity stimulates increased vasopressin secretion, the response in the kidneys is increased reabsorption of water to restore water concentration back to the normal level.

Diabetes Insipidus

Diabetes insipidus is the disorder that occurs when there is a defect in the ability to concentrate urine. Diabetes insipidus can be due to a lack of vasopressin (central diabetes insipidus) or due to a defect in the ability of the kidney to respond to vasopressin (nephrogenic diabetes insipidus). Central diabetes insipidus may be caused by a genetic mutation where vasopressin is missing or defective. Head trauma, a tumor, or injury to the posterior pituitary may also cause central diabetes insipidus. Central diabetes insipidus is treated with vasopressin replacement therapy.

Nephrogenic diabetes insipidus may be caused by a defect in the vasopressin receptor. Another type of mutation that causes the disorder involves a defect in the gene for AQP2. This defect prevents the proper localization of AQP2 proteins on the apical membrane of collecting duct cells. The drug lithium can cause acquired nephrogenic diabetes insipidus. Usually the disorder resolves when the drug is discontinued.

Summary: Homeostasis of ECF Osmolarity

The figure illustrates the regulation of water balance as a negative feedback regulatory system. The regulated variable is the ECF osmolarity. The sensors are the hypothalamic osmoreceptors, which modulate their frequency of action potential firing in response to changes in ECF osmolarity. The effector system that restores ECF osmolarity to its set point involves vasopressin and its effects on water reabsorption in the collecting duct. 

Quick Quiz: Water Balance

Fill-in Answer Correct False Correct Answer
1. In what part of the nephron does regulated water reabsorption occur?
2. What part of the nephron creates the hyperosmolar environment in the medulla?
3. Which part of the loop of Henle (descending limb or ascending limb) is relatively impermeable to water?
4. Vasopressin increases the number of these proteins on the apical membrane of cells in the collecting duct.
5. Vasopressin is secreted from the _________.
6. A deficiency of vasopressin causes _________. (be specific)
7. This drug can cause acquired nephrogenic diabetes insipidus.
8. Supposing a person hasn't drunk water for a while, causing a slight change in plasma osmolarity. What is the sensor that triggers vasopressin secretion?
9. Which of the following stimulates thirst: (increased or decreased) action potential firing by hypothalamic osmoreceptors?

(Spelling must be correct)

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