Several hormones have specific, important roles in regulating kidney function. They act to stimulate or inhibit blood flow. Some of these are endocrine, acting from a distance, whereas others are paracrine, acting locally.
- Water levels in the body are controlled by antidiuretic hormone (ADH), which is produced in the hypothalamus and triggers the reabsorption of water by the kidneys. Underproduction of ADH can cause diabetes insipidus.
- Aldosterone, a hormone produced by the adrenal cortex of the kidneys, enhances Na reabsorption from the extracellular fluids and subsequent water reabsorption by diffusion.
- The renin-angiotensin-aldosterone system is one way that aldosterone release is controlled.
Antidiuretic hormone (ADH)
ADH, a 9-amino acid peptide released by the posterior pituitary – in brain, works to do the exact opposite. It promotes the recovery of water, decreases urine volume, and maintains plasma osmolarity and blood pressure. It does so by stimulating the movement of aquaporin proteins into the apical cell membrane of principal cells of the collecting ducts to form water channels.
A proper water balance in the body is important to avoid dehydration or over-hydration. The water concentration of the body is monitored by osmoreceptors in the hypothalamus, which detect the concentration of electrolytes in the extracellular fluid. The concentration of electrolytes in the blood rises when there is water loss caused by excessive perspiration, inadequate water intake, or low blood volume due to blood loss. An increase in blood electrolyte levels results in a neuronal signal being sent from the osmoreceptors in hypothalamus.
The hypothalamus produces a polypeptide hormone known as antidiuretic hormone (ADH), which is transported to and released from the posterior pituitary gland. The principal action of ADH is to regulate the amount of water excreted by the kidneys. As ADH (which is also known as vasopressin) causes direct water reabsorption from the kidney tubules, salts and wastes are concentrated in what will eventually be excreted as urine. The hypothalamus controls the mechanisms of ADH secretion, either by regulating blood volume or the concentration of water in the blood. Dehydration or physiological stress can cause an increase of osmolarity above 300 mOsm/L, which in turn, raises ADH secretion and water will be retained, causing an increase in blood pressure. ADH travels in the bloodstream to the kidneys. Once at the kidneys, ADH changes the kidneys to become more permeable to water by temporarily inserting water channels, aquaporins, into the kidney tubules and collecting ducts. . Water moves out of the kidney tubules through the aquaporins, reducing urine volume. The water is reabsorbed into the capillaries lowering blood osmolarity back toward normal. As blood osmolarity decreases, a negative feedback mechanism reduces osmoreceptor activity in the hypothalamus, and ADH secretion is reduced. ADH release can be reduced by certain substances, including alcohol, which can cause increased urine production and dehydration.
Diabetes insipidus (DI)
Diabetes insipidus (DI) is a rare disease that causes frequent urination. Chronic underproduction of ADH or a mutation in the ADH receptor results in diabetes insipidus. If the posterior pituitary does not release enough ADH, water cannot be retained by the kidneys and is lost as urine. To make up for lost water, a person with diabetes insipidus may feel the need to drink large amounts and is likely to urinate frequently, even at night, which can disrupt sleep and, on occasion, cause bedwetting. Because of the excretion of abnormally large volumes of dilute urine, people with diabetes insipidus may quickly become dehydrated if they do not drink enough water. If the condition is not severe, dehydration may not occur, but severe cases can lead to electrolyte imbalances due to dehydration.
Diabetes insipidus should not be confused with diabetes mellitus (DM), which results from insulin deficiency or resistance leading to high blood glucose, also called blood sugar. Diabetes mellitus has two main forms, type 1diabetes and type 2 diabetes. Diabetes insipidus is a different form of illness altogether.
Diuretics and Fluid Volume
A diuretic is a compound that increases urine volume. Three familiar drinks contain diuretic compounds: coffee, tea, and alcohol. The caffeine in coffee and tea works by promoting vasodilation in the nephron, which increases GFR. Alcohol increases GFR by inhibiting ADH release from the posterior pituitary, resulting in less water recovery by the collecting duct. In cases of high blood pressure, diuretics may be prescribed to reduce blood volume and, thereby, reduce blood pressure. The most frequently prescribed anti-hypertensive diuretic is hydrochlorothiazide. It inhibits the Na / Cl– symporter in the DCT and collecting duct. The result is a loss of Na with water following passively by osmosis.
Osmotic diuretics promote water loss by osmosis. An example is the indigestible sugar mannitol, which is most often administered to reduce brain swelling after head injury. However, it is not the only sugar that can produce a diuretic effect. In cases of poorly controlled diabetes mellitus, glucose levels exceed the capacity of the tubular glucose symporters, resulting in glucose in the urine. The unrecovered glucose becomes a powerful osmotic diuretic. Classically, in the days before glucose could be detected in the blood and urine, clinicians identified diabetes mellitus by the three Ps: polyuria (diuresis), polydipsia (increased thirst), and polyphagia (increased hunger).
Aldosterone:
Another hormone responsible for maintaining electrolyte concentrations in extracellular fluids is aldosterone, a steroid hormone that is produced by the adrenal cortex. In contrast to ADH, which promotes the reabsorption of water to maintain proper water balance, aldosterone maintains proper water balance by enhancing Na reabsorption and K secretion from extracellular fluid of the cells in kidney tubules. Because it is produced in the cortex of the adrenal gland and affects the concentrations of minerals Na and K , aldosterone is referred to as a mineralocorticoid, a corticosteroid that affects ion and water balance. Aldosterone release is stimulated by a decrease in blood sodium levels, blood volume, or blood pressure, or an increase in blood potassium levels. It also prevents the loss of Na from sweat, saliva, and gastric juice. The reabsorption of Na also results in the osmotic reabsorption of water, which alters blood volume and blood pressure.
The renin-angiotensin-aldosterone system (RAAS)
Aldosterone production can be stimulated by low blood pressure, which triggers a sequence of chemical release, as illustrated in Figure 1. When blood pressure drops, the renin-angiotensin-aldosterone system (RAAS) is activated. Cells in the juxtaglomerular apparatus, which regulates the functions of the nephrons of the kidney, detect this and release renin. Renin, an enzyme, circulates in the blood and reacts with a plasma protein produced by the liver called angiotensinogen. When angiotensinogen is cleaved by renin, it produces angiotensin I, which is then converted into angiotensin II in the lungs. Angiotensin II functions as a hormone and then causes the release of the hormone aldosterone by the adrenal cortex, resulting in increased Na reabsorption, water retention, and an increase in blood pressure. Angiotensin II in addition to being a potent vasoconstrictor also causes an increase in ADH and increased thirst, both of which help to raise blood pressure.
Figure 1. ADH and aldosterone increase blood pressure and volume. Angiotensin II stimulates release of these hormones. Angiotensin II, in turn, is formed when renin cleaves angiotensin. (credit: modification of work by Mikael Häggström)
| Hormones That Affect Osmoregulation and kidney function | ||
|---|---|---|
| Hormone | Where produced | Function |
| Epinephrine and Norepinephrine | Adrenal medulla | Can decrease kidney function temporarily by vasoconstriction |
| Renin | Kidney nephrons | Increases blood pressure by acting on angiotensinogen |
| Angiotensin | Liver | Angiotensin II affects multiple processes and increases blood pressure |
| Aldosterone | Adrenal cortex | Prevents loss of sodium and water |
| Anti-diuretic hormone – ADH (vasopressin) | Hypothalamus (stored in the posterior pituitary) | Prevents water loss |