Antidiuretic hormone

Definitions & Key takeaways

Antidiuretic hormone (ADH), also known as vasopressin, is a hormone that regulates water and electrolytes (e.g. sodium) balance. It does so by increasing water reabsorption into the bloodstream by acting on the kidneys nephrons. ADH is synthesized in the hypothalamus, and released into circulation from the posterior pituitary gland. Its secretion is triggered by states of hypovolemia like hemorrhage, dehydration and thirst.

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Introduction0:00–0:34

Antidiuretic hormone, or ADH, is a peptide hormone that is anti- or against -diuresis which is excessive urine production.
Antidiuretic hormone is also called vasopressin because it causes vasoconstriction - constriction of blood vessels. So antidiuretic hormone prevents making too much urine, which leads to water retention, and vasoconstriction, and together these two actions help increase the blood pressure.
Now, the brain has two interconnected structures: the hypothalamus and the pituitary gland. These two structures are connected by the pituitary stalk.

Hypothalamus & Pituitary Gland0:34–1:24

The hypothalamus is a part of the brain that contains several nuclei, or clusters of neurons. And two of these nuclei, the paraventricular and supraoptic nuclei, contain neurons that secrete ADH.
When ADH is produced, it travels down the axons of these neurons, and these axons have small dilations called Herring bodies, which is where ADH is stored.
When the body needs more ADH, the stored hormone is released and continues down the axon through the pituitary stalk. From there it’s released into the posterior pituitary gland which is interstitial tissue near capillary beds, so that the ADH can easily enter the bloodstream.
Let’s say that it's a super sunny day out and you forget to bring water with you. Well first, as you walk around, you’re constantly losing water through sweat as well as water vapor from your mouth and nose as you breathe out - these are insensible water losses.

Antidiuretic Hormone (ADH)1:24–4:22

Without drinking water, you can quickly get dehydrated. This causes your plasma osmolarity to increase, because the fluid levels in your blood drop, but the total number of solute particles remains roughly the same.
Now, two things now begin to happen simultaneously. First, a region in the brain called the anterior hypothalamus has a cluster of neurons called supraoptic nuclei, which have osmoreceptors that sense even tiny changes in osmolarity, as small as 1 mOsm/L.
These neurons are always sampling the blood that passes by and they have a special channel called aquaporin 4 which allows water to freely enter or exit the cell.
When the blood osmolarity is high, water moves out of these cells into the blood by osmosis, causing the neurons to shrink.
Increases in osmolarity past the normal set point of 290 to 300 mOsm/L, causes the neurons to fire action potentials that signals the hypothalamus to trigger the thirst response - so that we reach for our water bottle.
It also triggers the hypothalamus to produce more ADH which is then released into the blood. ADH travel to the kidneys and act on vasopressin receptor 2, or AVPR2, which is present in the principal cells of the distal convoluted tubule and collecting ducts of the nephrons.
When ADH binds to AVPR2 a G protein inside the cell gets activated which goes on to signal membrane bound adenylyl cyclase to convert ATP to cAMP.
Increased cAMP leads to two things; first it signals the cell to produce more water channel proteins called aquaporin 2, which usually sit in vesicles inside the principal cell, and second, it also causes vesicles loaded with aquaporin 2 to fuse with the cell membrane, so that the aquaporin 2 proteins can embed themselves in the apical surface of the cells - the side facing the lumen of the tubule.
These aquaporins ultimately allow water -- and only water -- to travel out of the lumen of the tubule and into the cells lining the nephron, and ultimately back into the blood.
Just like drinking more water, this dilutes the blood, and returns plasma osmolarity to a normal level. Once the plasma osmolarity returns back to normal, water from the blood enters into the osmoreceptors via osmosis, causing them to swell which stops them from signaling the hypothalamus to produce ADH.

Baroreceptors4:22–6:32

Sometimes, when there’s a large decrease in blood volume, as in case of a massive hemorrhage, or a third degree burn injury, where large amounts of blood plasma is lost, the blood pressure falls significantly.
The low blood pressure is detected by baroreceptors, or pressure receptors, located near the carotid artery in the neck and the arch of the aorta, which signal the hypothalamus to increase ADH secretion.
There are also baroreceptors in the afferent artery of the kidneys called juxtaglomerular cells that when triggered, cause the kidneys to secrete the enzyme renin.
Renin is an enzyme that gets into the plasma, and looks for its primary substrate - angiotensinogen that’s produced by the liver and is always hanging out in the blood.
When they meet up, renin cleaves off a huge chunk of the angiotensinogen protein, leaving behind a tiny fragment called angiotensin I.
A bit like a tiny pearl found within a giant oyster. Angiotensin I floats through the blood, until it reaches various capillaries in the body.
Now, endothelial cells in general, but mostly those lining the vessels in the lungs, have an enzyme on their surface called angiotensin converting enzyme - or ACE for short.
Angiotensin converting enzyme grabs angiotensin I and chop off two of its amino-acids, leaving behind an even smaller protein that’s a really powerful hormone, called angiotensin II.
Angiotensin II stimulates the hypothalamus to make more ADH. Now ADH can increase blood pressure in two ways.
First, ADH increases the number of aquaporin 2 in the distal tubule and collecting duct which reabsorbs water from the urine and replenishes the plasma volume.
And second, ADH acts on smooth muscles cells in the arteries causing them to constrict, which increase the peripheral vascular resistance and the blood pressure.
When that happens, the baroreceptors pick up on the increased blood pressure and send inhibitory signal to the hypothalamus and that makes ADH secretion stop.
Alright, as a quick recap… Antidiuretic hormone, also known as vasopressin, plays an important role in maintaining the plasma osmolarity and blood pressure.

Review6:32–7:06

It acts on the AVPR2 receptor in the distal convoluted tubule and collecting ducts of the nephrons, and increases water reabsorption through aquaporins, which decreases the plasma osmolarity.
It also acts on the AVPR1 receptors in the walls of the blood vessels, and causes vasoconstriction and increase in peripheral resistance, resulting in increase in the blood pressure.