Water and Ion Balance: ADH, Aldosterone and Blood Pressure

Clear or dark?

After a long hockey practice on a warm day, your urine is a small amount of dark yellow. After drinking three glasses of water at lunch, it is a large amount of pale yellow. Your kidneys are not just filtering blindly. They are choosing how much water and salt to keep, minute by minute, based on signals from your brain and your heart.

This lesson explains those signals: ADH for water, aldosterone and the renin–angiotensin system for sodium and blood pressure, and ANP for when there is too much. Together they keep the volume and concentration of your blood remarkably steady.

Why concentration matters

The concentration of all dissolved particles in the blood is called its osmolarity. In a healthy person, it stays close to about 290 milliosmoles per litre. If the blood becomes too concentrated, water leaves cells by osmosis and they shrink; if it becomes too dilute, water enters cells and they swell. Brain cells are especially sensitive to this. So the body controls water very carefully.

Water is lost through urine, sweat, breathing and feces, and gained by drinking, eating and as a product of cellular respiration. The kidneys are where the fine adjustments are made.

ADH: the water-saving hormone

Specialized neurons in the hypothalamus act as osmoreceptors. When the blood becomes too concentrated (after sweating, not drinking, or eating salty chips), they shrink slightly and fire more. Two things happen:

1. You feel thirsty.
2. Antidiuretic hormone (ADH) is released. ADH is made by neurons in the hypothalamus, travels down their axons, and is stored in the posterior pituitary, which releases it into the blood.

ADH reaches the distal tubules and collecting ducts. There it binds to receptors on the tubule cells, which triggers the insertion of aquaporins (water channel proteins) into their membranes. Now water can leave the collecting duct by osmosis. Where does it go? Into the very salty medulla around the collecting duct, then into the blood.

Result: more water is returned to the blood, the blood becomes more dilute, and you make a small volume of concentrated urine. When the blood becomes too dilute, ADH release drops, aquaporins are removed, and you make lots of dilute urine. That is negative feedback.

Why is the medulla so salty? The loop of Henle works as a countercurrent multiplier. The ascending limb pumps salt out into the medulla but keeps water in; the descending limb lets water out. Because the two limbs run side by side in opposite directions, the effect builds up, and the deep medulla reaches about 1200 mOsm/L, roughly four times the concentration of blood. That gradient is what lets ADH pull water out of the collecting duct.

Aldosterone and the RAAS: saving salt to save water

ADH controls water directly. But the body also controls sodium, and since water follows sodium by osmosis, controlling sodium is a way to control blood volume and therefore blood pressure.

When blood pressure or blood volume falls (for example after heavy sweating, bleeding or vomiting), special cells near the glomerulus (the juxtaglomerular apparatus) release the enzyme renin. Then a chain of reactions follows:

1. Renin converts angiotensinogen (a protein made by the liver) into angiotensin I.
2. Angiotensin-converting enzyme (ACE), mostly in the lungs, converts angiotensin I into angiotensin II.
3. Angiotensin II constricts arterioles (raising pressure right away), increases thirst, and stimulates the adrenal cortex to release aldosterone.
4. Aldosterone acts on the distal tubule and collecting duct: more Na⁺ is reabsorbed (and more K⁺ is secreted). Water follows the Na⁺, so blood volume and pressure rise.

When blood volume is too high, the walls of the heart's atria are stretched. They release atrial natriuretic peptide (ANP), which does the opposite: it reduces Na⁺ reabsorption and inhibits renin and aldosterone, so more salt and water are lost in the urine.

Medical treatments that act on these systems

High blood pressure (hypertension) is very common in Canadian adults and raises the risk of heart attack, stroke and kidney disease. Several common medicines work by adjusting the systems in this lesson:

• ACE inhibitors block angiotensin-converting enzyme, so less angiotensin II is made. Arterioles relax and less aldosterone is released, so blood pressure falls.
• Diuretics ("water pills") reduce Na⁺ reabsorption in the tubules. More salt, and therefore more water, is lost in urine, lowering blood volume.
• Desmopressin replaces ADH in diabetes insipidus, and is also sometimes used for bedwetting.

Each treatment affects homeostasis in more than one way. For example, some diuretics also increase K⁺ loss, so doctors monitor blood potassium. This is a good example of how changing one part of a feedback system affects others.

Water balance in other animals

• Freshwater fish (like the yellow perch in Lake Simcoe) live in water less salty than their blood, so water constantly enters by osmosis. They drink almost nothing, make large amounts of dilute urine, and actively take in salt through their gills.
• Saltwater fish have the opposite problem: they lose water to the sea. They drink seawater and actively pump excess salt out through their gills.
• Salmon that migrate between the ocean and British Columbia's rivers switch their gill cells' ion pumping when they move between salt and fresh water.
• Desert mammals such as kangaroo rats have long loops of Henle and make extremely concentrated urine.