Renin-angiotensin-aldosterone system

Definitions & Key takeaways

The renin-angiotensin-aldosterone system (RAAS) is a hormone system that plays a key role in regulating blood pressure and fluid balance in the body. It is composed of several hormones and enzymes that work together to regulate blood pressure by controlling the amount of fluid in the blood vessels.

Whenever there's a decrease in blood pressure as detected by the baroreceptors of the carotid sinus or aortic arch or the juxtaglomerular cells, the sympathetic nerves getting stimulated, or the macula densa cells sensing less sodium and chloride ions flowing through the tubules, kidneys secrete renin that converts angiotensinogen to angiotensin I, and then angiotensin-converting enzyme converts angiotensin I to angiotensin II.

Angiotensin II causes the efferent arteriole to constrict more than the afferent arteriole, which increases the glomerular filtration rate, it also causes the proximal tubule to reabsorb more sodium ions from the filtrate, increases thirst, and helps increase blood pressure, while it, also, stimulates the adrenal cortex to release aldosterone, which gets the kidneys to retain sodium and water, further raising blood pressure.

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Introduction0:00–1:53

The main job of the cardiovascular system is to keep the blood moving, and to help facilitate that - blood pressure is kept under tight control.
A major way the body does that is through a set of hormones that make up the renin- angiotensin- aldosterone system. But, first things first.
Everything starts in the kidney. Now, within each kidney, blood from the renal artery flows into smaller and smaller arteries, eventually reaching the tiniest of arterioles called the afferent arterioles.
After the afferent arteriole, blood moves into a tiny capillary bed called the glomerulus. The glomerulus is part of the functional unit of the kidney, called the nephron.
There’s about 1 million nephrons in each kidney, and each of them consists of a renal corpuscle - made up of the glomerulus and the Bowman’s capsule surrounding it - and a renal tubule.
The renal corpuscle is where blood filtration begins, and it includes the Bowman’s capsule which surrounds the glomerulus.
Interestingly, once the blood leaves the glomerulus, it does not enter into venules. Instead the glomerulus funnels blood into efferent arterioles which divide into capillaries a second time.
These capillaries are called peritubular capillaries - because they are arranged around the renal tubule. Now, the renal tubule is made up of a proximal convoluted tubule, the nephron loop - also known as the loop of Henle - which has an ascending and a descending limb - and finally the distal convoluted tubule.
As filtrate makes its way through the renal tubule, waste and molecules such as ions and water are exchanged between the tubule until, finally, urine is formed.
At the same time, the peritubular capillaries reunite to form larger and larger venous vessels. The veins follow the path of the arteries, but in reverse - so they keep uniting until they finally form the large renal vein, which exits the kidney and drains into the inferior vena cava.
Okay - now if we zoom into the wall of the afferent arterioles, we’ll find a very special kind of smooth muscle cells, called juxtaglomerular cells, because they’re next to or “juxta” the glomerulus.

Juxtaglomerular cells1:53–4:18

The main job of these cells is to always keep an eye open for signals that the blood pressure needs to rise. These signals can come in three ways.
First, juxtaglomerular cells are mechanoreceptors, and they’re designed to mechanically feel if there’s low blood pressure in the incoming blood.
Second, juxtaglomerular cells are supplied by sympathetic nerve fibers. Sympathetic nerves start firing when there’s something stressful going on, like chasing a bicycle thief.
Sympathetic nerves help boost how hard and how fast the heart beats and cause contraction of smooth muscle cells around arterioles causing vasoconstriction throughout the body, as well as in the juxtaglomerular cells - this boosts blood pressure in stressful situations.
The third signal for juxtaglomerular cells comes from the wall of the distal convoluted tubule, which is where specialized cells called macula densa cells are found.
Macula densa cells are chemoreceptors that can sense when glomerular filtration rate increases based on the quantity of sodium and chloride ions flowing through the tubule.
Here’s how it works: when blood pressure rises, renal blood flow and, as consequence, glomerular filtration rate also increase.
This means that there’s more fluid and more dissolved sodium and chloride ions that reach the macula densa. Now if the opposite happens, and there’s decreased fluid and sodium and chloride ions getting to the macula densa cells, then that sends a signal to the the juxtaglomerular cells in the afferent arteriole.
All three types of signals stimulate the juxtaglomerular cells to secrete renin. Renin is an enzyme that gets into the plasma, and looks for its primary substrate - angiotensinogen.

Renin-Angiotensinogen4:18–5:13

Angiotensinogen is a large protein made up of over 400 amino acids 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 that’s just 10 amino acids long.
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, which converts angiotensin I to angiotensin II.
Angiotensin converting enzyme grabs angiotensin I and chop off two of its amino-acids, leaving behind an 8- amino-acid chain that’s a really powerful hormone, called angiotensin II.
“Angio-“ means blood vessel and “-tensin” means making everything more “tense”, so angiotensin II goes to the smooth muscles lining arterioles all over the body, and causes them to tense up or contract which leads to vasoconstriction of those blood vessels, and increases resistance to blood flow.

Angiotensin II5:13–7:20

So, angiotensin II travels through blood and when it reaches the kidneys, it binds to angiotensin receptors along the afferent and efferent arterioles.
There, it causes those arterioles to constrict and the increased arteriole resistance leads to a low renal blood flow. However, there’s a mechanism to ensure that even though less blood gets to the kidneys, glomerular filtration rate remains constant.
The way this is possible, is that the efferent arterioles are much more responsive to angiotensin II then the afferent arterioles.
So, when there are low levels of angiotensin II, only the efferent arterioles constrict, and this makes less blood leave the glomerulus - or said differently, it makes more blood remain in the glomerulus, thereby preserving the glomerular filtration rate.
However, when there are high levels of angiotensin II, both the afferent and efferent arterioles constrict, and this decreases both renal blood flow and glomerular filtration rate.
Angiotensin II also acts on the cells that line the proximal convoluted tubule, making them reabsorb more sodium ions from the filtrate.
And by the process of osmosis, water begins to follow the sodium ions. Angiotensin II also acts on the hypothalamus, which is at the base of the brain, where it stimulates thirst and increases the production of antidiuretic hormone, or ADH.
ADH has it’s main effect on the cells lining the distal convoluted tubule and collecting duct, where it stimulates more aquaporins to get into the luminal surface of the cells.
Aquaporins make these cells more permeable to water, increasing water reabsorption. Ultimately, the increased thirst and water reabsorption increases the total circulating blood volume or blood flow, symbolized as Q.
In addition, the increased peripheral arterial resistance increases the total body resistance, symbolized as R. Since, the change in blood pressure P, equals blood flow Q times resistance R, the blood pressure rises.
But angiotensin II’s work isn’t over yet. It also helps stimulate the adrenal glands which are a pair of glands that sit on top of each kidney.

Aldosterone7:20–8:59

If we slice an adrenal gland open and zoom in, we’ll see that it’s made up of two parts: an inner medulla and an outer cortex.
The cortex is further subdivided into three more layers- the zona glomerulosa, the zona fasciculata, and the zona reticularis.
Angiotensin II stimulates cells in the outermost layer, the zona glomerulosa, to secrete aldosterone. Aldosterone belongs to a class of steroids, or lipid- soluble hormones, called mineralocorticoids, which help regulate the sodium concentration in the body.
Aldosterone does that by acting on the cells that line the distal tubules and collecting ducts. Aldosterone gets into those cells and binds its receptor, forming an aldosterone-receptor complex.
This complex is able to control the expression of genes - increasing levels of some proteins over others. One protein that gets expressed a lot is the sodium/potassium ion pump, which sits on the basal surface of the cells.
These pumps push sodium into the blood and pull potassium into the cells. Ultimately this helps to drive a concentration gradient that pulls sodium and water out of the lumen of the tubule and into the blood.
As before, this helps to boost blood pressure. Keep in mind, though, that this process can take several hours or even days, so it’s considered a late response of the renin- angiotensin- aldosterone system.
All right, as a quick recap, whenever there’s a decrease in blood pressure as detected by the juxtaglomerular cells sensing low blood pressure, the sympathetic nerves getting stimulated, or the macula densa cells sensing less sodium and chloride ions flowing through the tubules, kidneys secrete renin that converts angiotensinogen to angiotensin I, and then angiotensin converting enzyme converts angiotensin I to angiotensin II.

Review8:59–9:47

Angiotensin II causes the efferent arteriole to constrict more than the afferent arteriole, which increases the glomerular filtration rate, it causes the proximal tubule to reabsorb more sodium ions from the filtrate, the efferent arteriole to vasoconstrict, increases thirst, and helps increase blood pressure, while it, also, stimulates the adrenal cortex to release aldosterone, which gets the kidneys to retain sodium and water.