We will now begin discussing the development of the intermediate mesoderm
and the structures that come from it.
We’re gonna start by discussing how the kidneys and suprarenal glands form.
Now, interestingly the renal and reproductive systems are both derived from the intermediate mesoderm
and both are linked atomically and developmentally.
Now, without too much difficulty you can come up with a couple of connections
between the reproductive and urinary systems.
In males, we have the reproductive glands and tracts emptying into the urethra along with the urinary bladder.
In females, we have a separate ureter and separate vaginal opening
but they both empty into the vestibule, however, there are multiple developmental connections
as well particularly that we have the intermediate mesoderm creating a succession of kidneys
and some of those structures will seize to function as kidneys
but contribute to the reproductive system so let’s start the process of examining that development right now.
We’re gonna return to my favorite slide the trilaminar embryo where organogenesis really, really, get started.
We’ve got the notochord on the midline, neurulation is beginning,
got tube formation that’s gonna occur very soon and just beside the somites
we have a little area colored kinda slightly yellowish orange
that is the intermediate mesoderm and it is what’s going to create the kidneys and the gonads.
As the body will fold and the gut tube starts to form,
we wind up with what’s referred to as the nephrogenic chords developing in the intermediate mesoderm.
Now, on the surface of those chords we’re gonna have urogenital ridges formed
in contact with the developing body cavity.
The nephrogenic chords are the primordia of the kidneys
and the urogenital ridges are the primordia of the gonads - the testes and the ovaries.
We’re gonna follow kidney development in this talk
and return in a subsequent talk to the urogenital ridges.
So the nephrogenic chord forms not one, not two,
but three sets of kidneys during development and only the third set becomes our actual adult kidney.
During weeks four to five, we have development of a structure
called the pronephros in the embryonic cervical region and it forms
but very quickly rescinds by the end of week five.
A little bit lower we have the mesonephros or middle kidney
and it actually develops a mesonephric duct and it starts filtering urine,
it actually does start filtering the blood stream but then regresses
but the mesonephric duct remains and becomes an important structure
in both the reproductive and urinary system.
And it’s important to the mature urinary system because of the very, very lowest portion
of the mesonephric duct we get what’s called the ureteric bud,
a little bleb of tissue moves off to the mesonephric duct
and it’s going to induce formation of the final adult kidney and that is called the metanephros.
So we’ve gone from pronephors, to mesonephros, to metanephros
and our adult kidneys actually start developing very far down in our pelvis and will ascend.
So here we can see that the metanephric kidney is shown at the bottom of the picture,
it’s covered by the big kind of pinkly illustrated area there called the mesonephros.
So initially the metanephros and the ureteric
bud are very close to the bladder but it will begin ascending as the mesonephros
starts to degenerate and shrink and the gonads, ovaries, and testes come into existence.
Now as the metanephric kidney gets larger and more mature
it actually starts ascending in the body.
Normally, ascent of this nature isn't caused by differential growth
but as the kidneys move to more and more superior positions in the abdomen’s retroperitoneal region,
they pick up a succession of arteries so they get the arteries from the iliac, vessels and then aorta
and as they go further and further up they get more and more arteries
and as they move old ones die off, new ones grow in.
As they move upward they’re going to encounter the suprarenal glands
also known as the adrenal glands
and I like to think of the adrenal glands sitting on top of these early metanephric kidneys
like the hats on top of the guards, Buckingham Palace
and they will form more superiorly whether or not the kidney is there so the adrenal glands
are very close to kidney but you don’t need a kidney
in order to have a suprarenal gland form and become functional.
Now because a succession of arteries are growing to supply the metanephric kidney
it’s very common to have additional renal arteries having more than one renal artery is very common
and in fact, you can have arteries coming into the superior or inferior pole of the kidney
and those are just referred to as polar renal arteries.
Almost all the time, these additional arteries are clinically unimportant
because they don’t cause any problems
unless you are trying to remove the kidney or an inferior polar kidney obstructs drainage of the ureter
which is trying to take the urine from the kidney to the urinary bladder.
So multiple renal veins are also frequently encountered
and just have to be accounted for anytime a kidney is being removed and those vessels ligated.
Now, kidneys can fail to form - this is known as kidney agenesis
and essentially a kidney will not form unless that ureteric bud comes off of the mesonephric duct
so no ureteric bud, no kidney.
So kidney or renal agenesis can be problematic because you have half the number of kidneys
but a single kidney can do the work that’s needed to keep the body healthy
but it doesn’t have as much flexibility as you would if you had two kidneys as per normal.
As I mentioned before the suprarenal glands form completely separately,
so your adrenal or suprarenal glands will be present on both sides even if there’s only one kidney.
Now, if we have failure of the ureteric bud to create a kidney,
we can envision a few other problems that can occur such as if I have a ureteric bud that splits,
I can wind up with what’s called a bifid ureter, a split ureter.
In this case a single ureteric bud went out from the mesonephric duct,
split and induced the formation of a single kidney but it has two separate ureters
and these can be relatively short or they could be relatively long.
This sometimes can happen if a ureteric bud grows out and splits widely
and induces the formation of two kidneys it is possible to have three -
one on one side, two on the other because of the splitting of the ureteric bud.
The illustration is also showing that occasionally the kidney may rotate
to take the ureter and renal pelvis laterally although that’s fairly uncommon.
When you have a bifid split in the ureteric bud, you can induce the formation of two kidneys
and occasionally you can induce two separate kidneys from two separate ureteric buds
at which point you’re probably going to have two separate ureters
draining all the way back to the urinary bladder so any variation on this theme is theoretically possible.
Other problems that can occur so the kidneys might form normally but fail to ascend.
These pelvic kidneys are not problematic in fact they usually work just fine
and people may be unaware that they have it until an imaging study is done or a surgery is done in the area
and the kidney is encountered, so these pelvic kidneys work just fine
and in fact if surgeons have to transplant a kidney,
it’s a great deal of trouble to try to stick a kidney
into its normal place in the body and transplanted kidneys
tend to be put into the pelvis in this pelvic kidney position
because it’s easy to wire it into the bladder and easy to wire it
into the blood supply nearby at the iliac arteries and veins.
A truly interesting thing happens if the two kidneys are in the pelvis
and before ascending they fuse, these are called horseshoe kidneys
and they are fused kidney made from two and they actually attempt to ascend
but the problem is we've got the inferior mesenteric artery going to the hindgut
and as that kidney ascends retroperitoneally,
it’s going to wind up straddling that inferior mesenteric artery
and it will be unable to go any higher and that straddling of the arteries would give it its horseshoe shape.
As with the pelvic kidney they don’t cause any problems they are functional
and may only be encountered when imaging or exploratory surgery is being done.
Other problems involving kidney development are polycystic kidney disease.
Little cysts and occasional smaller cysts on kidneys are not actually that problematic.
Kidneys are very good at dealing with slightly reduce mass
and you don’t get clinical signs of renal insufficiency until quite a bit of damage has been done
but polycystic kidney disease causes a huge number of cysts to form on the kidney
and generally, you're going to have to remove these because they keep enlarging bigger and bigger
and you will have to have a kidney transplant done on the affected person sooner or later
because these kidneys not only large but become non-functional.
There are two versions of it. Roughly, the autosomal dominant version happens
when you have mutation of one of two genes, PKD1 or PKD2,
which thankfully stand for polycystic kidney disease
and they’re gonna lead to problems in calcium transport in the cilia of the kidney,
that’s gonna result in inappropriate program cell death in the kidneys, apoptosis,
causing a massive number of cyst to form.
There’s also another autosomal recessive version of it that comes from mutation of the PKHD1 gene
but the same basic problem is encountered and it’s usually gonna be encountered during early infancy.
Okay. Thank you very much for your attention, I'll see you on our next talk.