Regulation of Water Balance

Water Reabsorption

Water reabsorption is a passive process: water is reabsorbed by osmosis. In most of the nephron there is unregulated isosmotic reabsorption of water and solute, in other words, water reabsorption is coupled to solute reabsorption. However, it is possible to reabsorb water independently of solute to produce a concentrated urine; that is urine that has a higher osmolarity than the extracellular fluid.  Regulated water reabsorption occurs from the medullary collecting duct.

The figure at left is a schematic showing the last part of a nephron.  A similar figure can be found in your textbook (Figure 20.4, p. 623).  The ability to excrete urine that is more concentrated than the extracellular fluid (ECF) depends upon the loops of Henle, which function to concentrate osmolarity in the deepest part of the medulla. As the collecting duct descends through the medulla, the increasing osmolarity in the surrounding interstitial fluid drives water reabsorption.

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

Regulated Permeability in the Collecting Duct

In humans, the vertical 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.  The result is more AQP2 proteins on the apical membrane and higher permeability to water.

Regulation of Vasopressin Secretion

Vasopressin is a hormone that is produced by neurosecretory cells, a type of endocrine cell found in the hypothalamus.  As shown in the figure, neurosecretory cells have dendrites, axons, and terminals just like typical neurons. The difference is that the terminals of neurosecretory cells are adjacent to capillaries. Neurosecretory cells secrete regulatory molecules (green dots) that enter the circulation and act as hormones.

Vasopressin is secreted by neurosecretory cells whose cell bodies are in the hypothalamus and whose terminals are located in the posterior pituitary (also called the neurohypophysis). The main control of vasopressin secretion is by the osmoreceptors, neurons that sense changes in the osmolarity of the extracellular fluid. The osmoreceptors are also located in the hypothalamus.  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.

Diabetes Insipidus

Diabetes insipidus is the disorder that occurs when there is a defect in the ability to concentrate urine. The inability to concentrate urine results in polyuria (a high urine volume).  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, which is used in the treatment of bipolar disorder, can cause acquired nephrogenic diabetes insipidus.

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.