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 anatomically and developmentally.
Now, without too much difficulty, you can come up with a couple 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 urethral 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 cease 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 gets started.
We’ve got the notochord on the midline.
Neurulation is beginning.
Gut tube formation is gonna occur very soon and just beside the somites,
we have a little area colored kind of slightly yellow-ish orange.
That is the intermediate mesoderm
and it is what’s going to create the kidneys and the gonads.
As the body wall folds and the gut tube starts to form,
we wind up with what’s then referred to as the nephrogenic cords
developing in the intermediate mesoderm.
Now, on the surface of those cords,
we’re gonna have urogenital ridges form in contact with the developing body cavity.
The nephrogenic cords 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 develop in this talk
and return in a subsequent talk to the urogenital ridges.
So the nephrogenic cord forms not one, not two,
but three sets of kidneys during development
and only the third set becomes our actual adult kidney.
During week’s 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 a ureteric bud,
a little bleb of tissue moves off of the mesonephric duct
and is going to induce formation of the final adult kidney.
And that is called the metanephros.
So we’ve gone from pronephros, 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 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 at Buckingham Palace,
and they will form more superiorly whether or not the kidney is there.
So the adrenal glands are very close to the 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’re 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 and 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, 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’re a 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 is what gives 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 reduced 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 enlarge, 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,
PKD-1 or PKD-2 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 going to result in inappropriate programed cell death in the kidneys, apoptosis,
causing a massive number of cysts to form.
There’s also an autosomal recessive version of it that comes from mutation of the PKHD1 gene.
But the same basic problem is encountered
and is usually gonna be encountered during early infancy.
Okay, thank you very much for your attention and I’ll see you on our next talk.