One of the most important aspects of the mammalian kidney is its ability to adjust both the volume and osmolarity of urine, depending on the animal′s water and salt balance and the rate of urea production. In situations of high salt intake and low water availability, a mammal can excrete urea and salt with minimal water loss in small volumes of hyperosmotic urine. But if salt is scarce and fluid intake is high, the kidney can get rid of the excess water with little salt loss by producing large volumes of hypoosmotic urine (as dilute as 70 mosm/L, compared to about 300 mosm/L for human blood). This versatility in osmoregulatory function is managed with a combination of nervous and hormonal controls.
One hormone that is important in regulating water balance is antidiuretic hormone (ADH).
ADH is produced in the hypothalamus of the brain and is stored in and released from the posterior pituitary gland, which is positioned just below the hypothalamus. Osmoreceptor cells in the hypothalamus monitor the osmolarity of blood; when it rises above a set point of 300 mosm/L (perhaps due to water loss from sweating or to ingestion of salty food), more ADH is released into the bloodstream and reaches the kidney. The main targets of ADH are the distal tubules and collecting ducts of the kidney, where the hormone increases the permeability of the epithelium to water. This amplifies water reabsorption, which reduces urine volume and helps prevent further increase of blood osmolarity above the set point. By negative feedback, the subsiding osmolarity of the blood reduces the activity of osmoreceptor cells in the hypothalamus, and less ADH is then secreted. But only the gain of additional water in food and drink can bring osmolarity all the way back down to 300 mosm/L.
Conversely, if a large intake of water has reduced blood osmolarity below the set point, very little ADH is released. This decreases the permeability of the distal tubules and collecting ducts, so water reabsorption is reduced, resulting in increased discharge of dilute urine. (Increased urination is called diuresis, and it is because ADH opposes this state that it is called anti diuretic hormone.) Alcohol can disturb water balance by inhibiting the release of ADH, causing excessive urinary water loss and dehydration (which may cause some of the symptoms of a hangover). Normally, blood osmolarity, ADH release, and water reabsorption in the kidney are all linked in a feedback loop that contributes to homeostasis.
A second regulatory mechanism involves a specialised tissue called the juxtaglomerular apparatus (JGA), located near the afferent arteriole that supplies blood to the glomerulus. When blood pressure or blood volume in the afferent arteriole drops (for instance, as a result of reduced salt intake or loss of blood), the enzyme renin initiates chemical reactions that convert a plasma protein called angiotensinogen to a peptide called angiotensin II. Functioning as a hormone, angiotensin II raises blood pressure by constricting arterioles, decreasing blood flow to many capillaries, including those of the kidney. Angiotensin II also stimulates the proximal tubules of the nephrons to reabsorb more NaCl and water. This reduces the amount of salt and water excreted in the urine and consequently raises blood volume and pressure. Another effect of angiotensin II is stimulation of the adrenal glands to release a hormone called aldosterone. This hormone acts on the nephrons′ distal tubules, making them reabsorb more sodium (Na+) and water and increasing blood volume and pressure. In summary, the renin–angiotensin–aldosterone system (RAAS) is part of a complex feedback circuit that functions in homeostasis. A drop in blood pressure and blood volume triggers renin release from the JGA. In turn, the rise in blood pressure and volume resulting from the various actions of angiotensin II and aldosterone reduce the release of renin.
The functions of ADH and the RAAS may seem to be redundant, but this is not the case. Both increase water reabsorption, but they counter different osmoregulatory problems. The release of ADH is a response to an increase in the osmolarity of the blood, as when the body is dehydrated from excessive water loss or inadequate intake of water. However, a situation that causes an excessive loss of both salt and body fluids—an injury, for example, or severe diarrhea—will reduce blood volume without increasing osmolarity. This will not induce a change in ADH release, but the RAAS will respond to the fall in blood volume and pressure by increasing water and Na+ reabsorption. ADH and the RAAS are partners in homeostasis; ADH alone would lower blood Na+ concentration by stimulating water reabsorption in the kidney, but the RAAS helps maintain balance by stimulating Na+ reabsorption.
Still another hormone, a peptide called atrial natriuretic factor (ANF), opposes the RAAS. The walls of the atria of the heart release ANF in response to an increase in blood volume and pressure. ANF inhibits the release of renin from the JGA, inhibits NaCl reabsorption by the collecting ducts, and reduces aldosterone release from the adrenal glands. These actions lower blood volume and pressure. Thus, ADH, the RAAS, and ANF provide an elaborate system of checks and balances that regulate the kidney′s ability to control the osmolarity, salt concentration, volume, and pressure of blood. The precise regulatory role of ANF is an area of active research.
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