The kidneys are highly vascular organs responsible for filtering blood, with their blood flow and filtration rate precisely regulated by a complex interplay of hormonal and intrinsic mechanisms to maintain homeostasis.
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the kidneys main job is to filter the
blood to remove 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
blood from the renal artery flows into
smaller and smaller arteries eventually
reaching the tiniest of arterioles
called the afferent arterioles after the
afferent arterial 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 a 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 doesn't 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
now blood filtration starts in the
glomerulus where a 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 percent
of blood
what's more the glomerulus only filters
about 20 percent of that plasma in one
go so when all is said and done of the
around 1.25 liters at the heart pumps
out every minute the glomerular
filtration rate is normally
approximately 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 ace ending and a descending
limb and finally the distal convoluted tubule
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
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
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
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 the 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
constrict
the increased arterial 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
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
arterioles
when there's low blood pressure renin is
released in the blood where it cleaves
angiotensin 1 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
angiotensin ii then travels through the
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 arterial 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 than
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 arterials constrict and this
decreases both renal blood flow and
glomerular filtration rate
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 anp and bnp get secreted when
there's an increased cardiac workload
and the walls of the atria or ventricles
get stretched
amp and bnp bind to specific natriuretic
peptide receptors expressed by smooth
muscle cells and initiate a cascade of
intracellular events that result in the
dilation of afferent arterioles and the
construction of efferent arterials
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
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 arterioles low
concentrations of dopamine increase
renal blood flow
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 to
adjust their own arterial resistance to
keep renal blood flow constant even when
blood pressure might range between 80
millimeters of mercury and 200
millimeters of mercury
autoregulation can be seen graphically
when systolic blood pressure falls below
80 millimeters of mercury renal blood
flow is also low
at 80 millimeters of mercury renal blood
flow reaches an optimal value and the
smooth muscle cells in the arterial wall
are completely relaxed between 80 and
200 millimeters of mercury the smooth
muscle cells gradually become more
constricted as blood pressure rises
maintaining a constant renal blood flow
above 200 millimeters of mercury renal
blood flow increases parallel to renal
there are two mechanisms of kidney autoregulation
autoregulation
first there's an arterial 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
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
second there's the tubular glomerular
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 arterial
this region where they are in close
contact is called the juxtaglomerular
apparatus with juxta meeting next to the glomerulus
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 increases
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
all right as a quick recap
adrenaline and angiotensin ii increase
arteriolar resistance and decrease renal
blood flow whereas atrial and brain
natriuretic peptides decrease arteriolar
resistance and increase renal blood flow
in autoregulation the kidneys keep blood
flow constant over a wide range of
systolic blood pressures
there's the myogenic mechanism which is
when smooth muscle cells contract when
stretched and the tubular glomerular
mechanism when macula densa cells
secrete adenosine which has a paracrine
effect on the afferent arteriole making
helping current and future clinicians
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