Osmoregulation and the Role of ADH

Osmoregulation is the control of the water content and solute concentration of body fluids, and in humans it is regulated by antidiuretic hormone (ADH), which changes the amount of water the kidneys reabsorb. In brief: when blood becomes too concentrated (for example after sweating), the hypothalamus detects the change, the pituitary gland releases more ADH, the collecting ducts of the kidneys become more permeable to water and the urine becomes small in volume and concentrated. When blood is too dilute, less ADH is released and the urine is large in volume and dilute.

Water balance is essential, because cells swell if the blood is too dilute and shrink if it is too concentrated. This guide explains how water is gained and lost, how the hypothalamus detects changes, how ADH works on the kidney, the negative feedback loop, works through a hot day example with numbers and corrects common mistakes.

How does the body balance water?

Water makes up about 60 percent of adult body mass. The body gains water from drinks, food and from metabolism, as respiration produces water. It loses water as urine, sweat, water vapor in exhaled air and a small amount in feces. In a normal day with moderate temperature, an adult takes in and loses about 2.5 liters.

The kidneys can adjust the volume and concentration of urine to match the balance of water. They can produce a small volume of concentrated urine, down to about 0.5 liters per day, or a large volume of dilute urine, up to many liters per day. The control of water by the kidneys is a type of homeostasis.

How are changes in blood concentration detected?

The concentration of the blood is described by its water potential or osmolality. When a person has not drunk enough, or has lost water by sweating, the blood plasma becomes more concentrated, and its water potential falls. Osmoreceptors, specialized cells in the hypothalamus of the brain, detect the change. If the water potential falls, the osmoreceptors lose water by osmosis and shrink, which triggers nerve impulses. The hypothalamus also stimulates thirst, so the person wants to drink.

How does ADH work?

Antidiuretic hormone (ADH, also called vasopressin) is a peptide hormone made by neurosecretory cells in the hypothalamus and stored and released from the posterior pituitary gland. “Anti-diuretic” means “against urine production”.

1. ADH travels in the blood to the kidneys.
2. It binds to receptors on the cells of the distal convoluted tubule and the collecting duct.
3. This causes vesicles containing water channels (aquaporins) to move to the cell membrane and fuse with it. The membrane becomes much more permeable to water.
4. Water moves from the tubule fluid into the salty medulla by osmosis, and returns to the blood.
5. Less water is lost, and the urine is more concentrated and smaller in volume.

Without ADH, the collecting duct is almost impermeable to water, and the dilute fluid passes straight through as a large volume of dilute urine. ADH is broken down quickly, in minutes, so the level can adjust rapidly.

How is water balance controlled by negative feedback?

If the blood is too concentrated (low water potential):

• Osmoreceptors in the hypothalamus detect the change.
• The posterior pituitary releases more ADH.
• The collecting ducts reabsorb more water.
• Less, more concentrated, urine is produced. The person feels thirsty and drinks.
• The blood water potential rises toward normal, the stimulus is reduced and ADH release decreases.

If the blood is too dilute (high water potential):

• Osmoreceptors detect the change.
• Less ADH is released.
• The collecting ducts reabsorb less water.
• More, dilute, urine is produced.
• The blood water potential falls toward normal.

Alcohol inhibits the release of ADH, which is why drinking alcohol increases urine production and can lead to dehydration. Some diuretic drugs and caffeine also increase urine output.

Dehydration and overhydration compared

Worked example: a day in the heat

A hiker walks for four hours on a hot day. Follow the effects on water balance, assuming that the hiker sweats 2 liters and drinks only 0.5 liter during the hike.

1. Water balance: the loss through sweat is 2.0 L, and the intake is 0.5 L, so the net change is −1.5 L. For a 70 kg person with about 42 L of body water (60 percent), this is a loss of 1.5 ÷ 42 ≈ 3.6 percent of body water.
2. Blood concentration: sweat is dilute compared with the blood (it has less salt than plasma), so blood water potential falls. The blood is more concentrated.
3. Detection: osmoreceptors in the hypothalamus detect the change, and the person feels thirsty.
4. Hormone: the posterior pituitary releases more ADH.
5. Kidney response: the permeability of the collecting ducts increases, more water is reabsorbed and the urine volume falls from 1.4 L per day to as little as 0.5 L per day. The urine becomes dark yellow and concentrated.
6. Correction: drinking restores the water, and the blood water potential returns to normal. ADH levels fall.

If the hiker drinks 2 liters of pure water in a few minutes at the end of the hike, the blood becomes dilute, ADH release drops, and the kidneys produce a large volume of pale urine within an hour or two. Sports drinks containing salt help to restore both water and salts. A loss of more than about 2 percent of body mass as water begins to impair performance, and a loss of more than 10 percent is dangerous.

What can go wrong?

In diabetes insipidus, there is a lack of ADH or the kidneys do not respond to it, so large volumes of dilute urine, up to 20 liters per day, are produced and the person is constantly thirsty. This should not be confused with diabetes mellitus, which involves insulin. In kidney failure, the kidneys cannot control water and salt balance or remove wastes, and treatment includes dialysis or a kidney transplant. Drinking too much water, particularly during endurance events, can cause hyponatremia (a dangerously low sodium concentration in the blood).

How was ADH discovered?

George Oliver and Edward Schäfer showed in 1895 that extracts from the pituitary gland raise blood pressure, and later work showed that they also reduce urine output. Vincent du Vigneaud isolated and synthesized vasopressin and oxytocin in 1953, the first peptide hormones to be synthesized, and received the Nobel Prize in Chemistry in 1955. Peter Agre discovered aquaporins in 1992 and shared the 2003 Nobel Prize in Chemistry.

Which mistakes are common?

Mistake 1: Saying that ADH is made in the pituitary gland

It is made in the hypothalamus and released from the posterior pituitary.

Mistake 2: Reversing the effect of ADH

More ADH means more water reabsorbed and less urine. Less ADH means more urine.

Mistake 3: Saying that ADH acts on the glomerulus or the proximal tubule

It acts on the distal convoluted tubule and the collecting duct.

Mistake 4: Confusing osmoreceptors with the kidneys

Osmoreceptors in the hypothalamus detect the changes. The kidneys are the effector.