Regulation of renal blood flow

Regulation of renal blood flow

PBL MS2 S1 Exam 3

PBL MS2 S1 Exam 3

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Transcript

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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.

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 an urine precursor called filtrate is formed.

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 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.

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.

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.

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 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.

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.

Sources

  1. "Medical Physiology" Elsevier (2016)
  2. "Physiology" Elsevier (2017)
  3. "Human Anatomy & Physiology" Pearson (2018)
  4. "Principles of Anatomy and Physiology" Wiley (2014)
  5. "Purinergic signaling in inflammatory renal disease" Frontiers in Physiology (2013)
  6. "Intrarenal Purinergic Signaling in the Control of Renal Tubular Transport" Annual Review of Physiology (2010)
  7. "Interactions between adenosine, angiotensin II and nitric oxide on the afferent arteriole influence sensitivity of the tubuloglomerular feedback" Frontiers in Physiology (2013)
  8. "Adenosine A2 receptors modulate tubuloglomerular feedback" American Journal of Physiology-Renal Physiology (2010)