Regulation of renal blood flow

Definitions & Key takeaways

Renal blood flow is regulated by the autonomic nervous system, hormones, and local autoregulation mechanisms. The autonomic nervous system, primarily the sympathetic nervous system, can increase or decrease renal blood flow by constricting or dilating renal arterioles. This is accomplished by the release of certain hormones. For example, adrenaline and angiotensin II increase arteriolar resistance and decrease renal blood flow, whereas atrial and brain natriuretic peptide decrease arteriolar resistance and increase renal blood flow. In autoregulation, the kidneys keep blood flow and the glomerular filtration rate constant, even when the blood pressure range changes.

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Introduction0:00–0:24

The kidneys’ main job is to filter the blood to remove the waste - so it shouldn’t be surprising that they receive about a quarter of the blood that the heart pumps with each beat.
On average, the heart pumps out almost 5 liters of blood every minute, so one-quarter of that - or 1.25 liters - flows into the renal artery every minute.

Glomerulus0:24–1:12

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.
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, blood filtration starts in the glomerulus, where a urine precursor called filtrate is formed.

Glomerular filtration rate1:12–2:01

The amount of blood filtered into the nephrons by all of the glomeruli each minute is called the glomerular filtration rate, and it’s actually just a small fraction of the blood that gets to the kidneys, because the glomerulus doesn’t allow red blood cells and proteins to pass through and be excreted into the urine.
So right from the start, what passes through the glomerulus is mostly plasma - which normally makes up about 55% of blood.
What is more, the glomerulus only filters about 20% of that plasma in one go. So when all is said and done, of those around 1.25 liters that the heart pumps out every minute, glomerular filtration rate is normally around 125 milliliters.
This filtrate then enters the renal tubule. 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.

Renal tubule2:01–2:43

As filtrate makes its way through the renal tubule, waste and molecules such as ions and water are exchanged between the tubule and the peritubular capillaries until blood is filtered of any excess.
Finally, 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.
Now, renal blood flow is proportional to the pressure gradient, which is the difference in pressure between the renal artery and the renal vein, divided by the resistance in the renal arterioles.

Renal blood flow2:43–3:04

So a high systemic blood pressure and a low resistance in the renal arterioles, leads to a high renal blood flow and, in turn, glomerular filtration rate, and vice versa.

Adrenaline3:04–4:02

Regulation of renal blood flow is mainly accomplished by increasing or decreasing arteriolar resistance. There are two key hormones that act to increase arteriolar resistance and, in turn, reduce renal blood flow: adrenaline and angiotensin.
Adrenaline, also known as epinephrine, is a hormone secreted by the adrenal gland right above the kidneys, in response to sympathetic stimulation.
Adrenaline produces a “fight-or-flight” response by binding to adrenergic receptors on cells all over the body. Adrenaline binds to alpha-1 adrenergic receptors along the afferent and efferent arterioles, and causes the smooth muscle cells that wrap around those arterioles to contract, making the afferent and efferent arterioles quickly constrict.
The increased arteriole resistance leads to a low renal blood flow. So when you’re being chased by a kangaroo, and the “fight or flight” mode is on, blood flow is basically diverted away from the kidneys and towards more important tissues like your leg muscles.

Angiotensin II4:02–5:40

Angiotensin II, on the other hand, is synthesized in response to low blood pressure, by endothelial cells that line the blood vessels throughout the body.
Angiotensin II is the final product in a cascade of reactions that start with renin, an enzyme produced in the kidneys by specialized smooth muscle cells, called juxtaglomerular cells, which can be found in the walls of the afferent arterioles.
When there’s low blood pressure, renin is released in the blood, where it cleaves angiotensin I from angiotensinogen. Now, endothelial cells in general, but mostly those lining the vessels in the lungs, make an enzyme called angiotensin converting enzyme - or ACE for short, which converts angiotensin I to angiotensin II.
Angiotensin II then travels through blood, and when it reaches the kidneys, it binds to angiotensin receptors along the afferent and efferent arterioles.
Just like adrenaline, it causes those arterioles to constrict and, as before, 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.

ANP & BNP5:40–6:53

Now, other hormones come into play when it comes to decreasing arteriolar resistance and increasing renal blood flow. First off, there’s atrial natriuretic peptide or ANP, secreted by the atria of the heart, and brain natriuretic peptide or BNP secreted by the ventricles of the heart - despite the name suggesting otherwise.
Fun fact: it’s only named after the brain because it was first discovered in pig brain extracts. Both these ANP and BNP get secreted when there’s an increased cardiac workload, and the walls of the atria or ventricles get stretched.
ANP and BNP bind to specific natriuretic peptide receptors expressed by smooth muscle cells, and initiate a cascade of intracellular events that results in the dilation of afferent arterioles and constriction of efferent arterioles, increasing renal blood flow.
Other molecules that lower arteriolar resistance and increase renal blood flow are prostaglandins. The kidneys produce prostaglandin E2 and prostaglandin I2 in response to sympathetic stimulation, and it makes both the afferent and efferent arterioles dilate a bit, to make sure renal blood flow doesn’t get too low even during those fight-or-flight situations.
After all, the last thing you need after a quick getaway from a kangaroo is kidney damage from too little blood flow. Finally, there’s dopamine - which is synthesized by cells in the brain and the kidneys.

Dopamine6:53–7:23

In the brain, dopamine functions as a neurotransmitter. In addition to that, in the brain and the rest of the body, it binds to specific, dopaminergic receptors on smooth muscle cells, constricting the capillaries in our skin and muscles, and dilating the small vessels around vital organs, such as the heart and the kidneys.
With vasodilation of both the afferent and efferent arteriole, low concentrations of dopamine increase renal blood flow.

Autoregulation7:23–8:21

Now let’s switch gears and look at autoregulation, which refers to local mechanisms within the kidney that keep renal blood flow and glomerular filtration rate constant over a range of systemic blood pressures.
In other words, the mechanisms that allow the kidney’s to adjust their own arteriole resistance to keep renal blood flow constant even when blood pressure might range between 80 mmHg and 200 mmHg.
Autoregulation can be seen graphically. When systolic blood pressure falls below 80 mmHg, renal blood flow is also low.
At 80 mmHg, renal blood flow reaches an optimal value, and the smooth muscle cells in the arteriole wall are completely relaxed.
Between 80 and 200 mmHg, the smooth muscle cells gradually become more constricted as blood pressure rises, maintaining a constant renal blood flow.
Above 200 mmHg, renal blood flow increases parallel to renal blood pressure. There are two mechanisms of kidney autoregulation.

Myogenic mechanism8:21–8:45

First, there’s an arteriole smooth muscle reaction - called the myogenic mechanism, which is based on a reflex of smooth muscle cells to contract when they are stretched by blood coming in at high pressures.
The more they get stretched by the blood which is what happens when pressures are high, the more they want to contract which causes vasoconstriction of the afferent and efferent arteriole.
Second, there’s the tubuloglomerular mechanism, which involves the distal convoluted tubule and the glomerulus. It turns out that a part of the distal convoluted tubule loops around and gets quite close to the afferent arteriole.

Tubuloglomerular mechanism8:45–9:55

This region where they are in close contact is called the juxtaglomerular apparatus - with juxta meaning “next to” the glomerulus.
Now, in this region of the distal convoluted tubule, there’s a group of cells collectively called the macula densa. These macula densa cells 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 a 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. In response to the increased fluid and sodium and chloride ions, macula densa cells release adenosine, which diffuses over to the nearby afferent arteriole, acting as a paracrine signal.
This increases arteriolar resistance and reduces the glomerular filtration rate in an autoregulatory fashion. All right, as a quick recap: Adrenaline and angiotensin II, increase arteriolar resistance and decrease renal blood flow, whereas atrial and brain natriuretic peptide, decrease arteriolar resistance and increase renal blood flow.

Review9:55–10:29

In autoregulation, the kidneys keep blood flow constant over a wide range of systolic blood pressure. There’s the myogenic mechanism, which is when smooth muscle cells contract when stretched, and the tubuloglomerular mechanism, when macula densa cells secrete adenosine which has a paracrine effect on the afferent arteriole making it vasoconstrict.