Transcribed by Leslie Afable 5/2/14

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Organ Systems Lecture 48 Endocrine System Integration by Dr. Schiff & Dr.
Lopez

**WARNING Dr. Lopez did not post the powerpoint slides when this transcript was
created so the slide numbers may or may not correspond to the actual slides of her
powerpoint if she ever posts it**

Slide 1 Organ Systems 2014 Endocrine System Integration

Dr. Joel Schiff OK, while we are waiting for the audio-visual people, does anyone
here know how to turn that damn thing on? Anyway, one thing that Dr. Hammer
brought up was HEMOGLOBIN A1C and at which point it popped into my head, I
never mentioned that yesterday, so lets do so now. As I said, glucose tends to bind
to glycosylate proteins. One of the proteins it binds to is hemoglobin because, of
course, glucose can get into red blood cells among other things. So what happens is
depending on how much glucose, youre average plasma glucose level is more or
less proportional to the concentration, binds to the hemoglobin in your red blood
cells. Now, red blood cells have a lifetime of a few months and then they break down
and go away. So basically every red blood cell in your body has been exposed to, on
average, a few months of your hemoglobin levels. So if you measure how
glycosylated the hemoglobin is and hemoglobin A1C is a sort of code or a descriptive
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term for the glucose bound hemoglobin molecules. It gives you basically a measure
of the average plasma glucose level over the past couple of months or three months
because any red cell that is older than three months are gone. Their hemoglobin has
been broken down and recycled and digested and replaced. So the usefulness of the
hemoglobin A1C is as a measure of the average plasma glucose level over
about a 3 month period.

Now, as Dr. Hammer said at the end, it doesnt describe whether youve been
swinging up or down or have been absolutely perfectly level, which of course is
impossible, but it gives an average of the glucose levels and therefore is a measure
of how well the diabetes in a person is controlled. Now normal people, you sitting
here assuming you dont have any diabetes or pre-diabetic condition, have a plasma
glucose of about 70-110 or 80-100 mg/dL. That tends to correspond to a
hemoglobin A1C level and what is measured is a percentage of hemoglobin
molecules that have glucose bound to them. Of about 5.3% or 5.2% (something like
that), that would be the ideal normal. The theory is that since the average glucose
concentration in your plasma is what causes a lot of the bad effects of diabetes, the
microvascular effects in the retina and the kidney and the major circulatory effects
in the lower extremities that lead to the amputations. The closer you can keep your
average glucose levels to that of a normal person who doesnt get these problems,
the better off you are. So the ideal is to keep plasma hemoglobin A1C levels at about
5.3%. If now, no one with diabetes is able to do that, if you can get below some
standards, then they figure you are doing very well. The standards have changed
over the years. And also the standards for children who you know are going to sneak
the candy bar occasionally are different from the standards for adults who
presumably have the will power to not eat the candy bar if they know it might cause
them to go into renal failure. So the goal set in quotes is probably not to get 9.3..
5.3% but 20 years ago, 30 years ago they would say under 9% is pretty good. Then it
became under 8%. Then they kept saying under 7%. Now its under 6% and even
less than that is the goal of a lot of intensive glucose monitoring therapies. So I just
wanted to let you know what this hemoglobin A1C is all about. And we have
someone here? No..

Dr. Lopez Were going to talk about things in general before I show pictures and
have to show actual cells.

Slide 2 Endocrine Glands Release Their Secretory Product..
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Dr. Lopez We talked about the difference between endocrine and exocrine glands.
So one difference is that endocrine glands dont have ducts, they develop in a
similar way to the exocrine glands but the ducts disappear. So instead of releasing
their secretions through a duct to a bodily surface, either on your skin or your gut
tube for example, they will have their secretions go into the interstitial tissue
around them and they will make their way into the circulation so the endocrine
glands will have a lot of FENESTRATED CAPILLARIES nearby. Thats in order to
facilitate the uptake of the secretions into the bloodstream. You want something
very permeable so thats why you tend to have fenestrated capillaries near
endocrine glands. The other important conceptual thing to know about endocrine
glands is that their secretions are acting at a DISTANCE from the cell so they are
traveling through the bloodstream to go to an organ that can be really far away. So
the pituitary gland will secrete hormones and will act ALL OVER the body and not
necessarily right next to the pituitary gland. And I just mentioned their secretions
are called HORMONES. So hormones are the secretions of endocrine glands. You
can have protein hormones or steroid hormones. The protein hormones are water
soluble versus the steroid hormones that are fat soluble. So thats going to make a
difference in how they are going to effect their target cells. Steroid hormones, since
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they are fat soluble, just diffuse directly through the plasma membrane of the target
cell and dont need an intermediary to get into the cell. But the protein hormones
cant do that, they have to bind to a receptor on the cell surface and thats going to
activate a secondary messenger inside the cell. So the signaling mechanism is a little
bit more complex in that regards.

Slide 3 Pituitary Gland

Dr. Lopez Any physiological thoughts on that? (directed to Dr. Schiff)

Dr. Schiff Not really, well what you have to remember.. ..first of all, as Dr. Lopezs
excellent slides would be showing right now but you have got them all anyway, is
the fact that these hormones once they reach their target cell have to act on
receptors. The location of the receptor depends on the type of hormone because a
peptide hormone for example or a protein hormone cant really get into the cell by
itself. So they bind to extracellular cell surface receptors and will trigger some sort
of second messenger mechanism or something like that. Whereas the steroid
hormones are lipid soluble so they can penetrate through the cell membrane and get
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to the inside of the cell. Somewhere in the cytoplasm you will find cytoplasmic
located receptors which will bind them and will act as sort of ESCORTS to bring
them to the nucleus where they can act as transcription initiators or something like
that.

Dr. Lopez Sounds good to me.

Dr. Schiff By the way if you have any questions at all at any point, just let us know
because its hard to focus on where the hard part is before next weeks quiz. Then we
know where the hard parts are but were not talking about the subject anymore.

Dr. Lopez So now I would show you beautiful pictures of each of the organs but
basically all the pictures I have for this integration lecture are the same ones from
the original histology lecture so you can just picture everything in your mind. So..

Dr. Schiff Or on your laptop if you have it. ::giggles::

Dr. Lopez Yeah, so first off is the pituitary. Remember that that is going to develop
from 2 different embryological origins. One part is going to be the neurohypophysis
thats going to.. ..hello.. ..here come my pictures. The neurohypophysis is going to be
NEURAL in origin so in the adult the neurohypophysis is basically just axons
projecting down from the brain. The adenohypophysis is developing from ORAL
ECTODERM and so its going to EPITHELIUM. When you look at a slide of the whole
pituitary gland, its really easy to distinguish the two parts because the
adenohypophysis is going to be made up of lots of little cells that are in close
proximity to one another because its epithelium and theyre touching. The
neurohypophysis is going to look very pale and youre not going to see many nuclei.
The only nuclei you will see there are going to be from the glial cells, the
PITUOCYTES. Here we go. So thank you.

Dr. Schiff You werent touching anything when it went on ::giggles::.

Dr. Lopez So up here this is what I was talking about (refers to top left figure). The
reddish area here is going to be the adenohypophysis. The pars distalis, pars
intermedia, and pars tuberalis. This is a closeup of that. The brownish part back
here is the neurohypophysis and thats the pars nervosa and the infundibulum. So
this is all epithelium, this red stuff is all epithelium. So first off the
adenohypophysis, and were usually talking about the PARS DISTALIS, the cells
there you can classify them based on how they stain. So if they are acidophilic you
all them ACIDOPHILS. If they are basophilic, you call them BASOPHILS. If they are
neither, if they dont stain very well you call them CHROMOPHOBES, that means
afraid of color because they dont stain very well. With the light microscope staining
like this, you cant tell what hormones they are actually producing. You can just kind
of narrow it down. So acidophils will produce GROWTH HORMONE or
PROLACTIN. Basophils will produce TSH, LH, FSH and ACTH. I am disappointed
that very few people questioned why ACTH is a BASOPHIL. Because if ACTH is a
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polypeptide, it should theoretically be in the acidophil category but what is
happening is that the precursor molecule for ACTH stains basophilic so thats why
the cell that makes it will stain basophilic and it will be classified as a basophil.

Slide 4 Pituitary Gland

Dr. Lopez If you look at the PARS NERVOSA back here its very pale staining in
comparison because its mostly just axons. You will see HERRING BODIES which
are dilations in the axons. All the nuclei you see will be the pituocytes, the glial cells,
and these axons are going to release VASOPRESSIN which is also known as ADH
and OXYTOCIN. All of that is made up in the hypothalamus and travels down the
axons to be released here in the pars nervosa.

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Slide 5 Blood Supply

Dr. Lopez So the anterior part of the pituitary and the posterior part, the pathways
of these hormones are different. For the posterior its pretty straight forward, the
hormones are made by these neurons in the hypothalamus and they travel down
through the infundibulum to the PARS NERVOSA and they are released into the
blood back here into this capillary bed.

Dr. Schiff So here effectively you have presynaptic neurons without a synapse.

Dr. Lopez Yeah. So instead of the neurotransmitter being like put into a synapse for
another neuron for example, the hormones are going into the bloodstream to travel
throughout the body. For the PARS DISTALIS, the adenohypophysis, whats going to
happen is these neurons up here in the hypothalamus will secrete RELEASING
HORMONES into the bloodstream and they are going to travel through these
PORTAL VEINS to get to the PARS DISTALIS, where they will effect the
ACIDOPHILS and BASOPHILS and stimulate them to secrete their own hormones.
Those are going to go into the CAPILLARY BED here and get into the bloodstream to
go where ever they need to go.

Slide 6 Pituitary Gland Chromophil Hormones
Transcribed by Leslie Afable 5/2/14

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Dr. Lopez This is the summary table that we had before. So I can post this online so
you can look at it. This is all of the hormones released by the adenohypophysis
cells.

Slide 7 Pituitary Gland Summary
Transcribed by Leslie Afable 5/2/14

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Dr. Lopez This is a table kind of summarizing how this all works. So the
hypothalamus will create ADH and OXYTOCIN which will travel down the neurons
of the NEUROHYPOPHYSIS and be released into the BLOOD to effect their target
organs. OR it will secrete RELEASING HORMONES that go into the blood to affect
the ADENOHYPOPHYSIS which will then secrete its hormones and they will go
through the blood to those target organs. So theres a different pathway or pattern
for the anterior pituitary vs the posterior pituitary.

Dr. Schiff One other thing you should be aware of is that in addition to PROLACTIN
RELEASING HORMONE, there are also PROLACTIN INHIBITING HORMONES. The
LACTOTROPES in the pituitary are capable of releasing prolactin, EVEN IN THE
ABSENCE OF HYPOTHALAMIC INPUT. They only stop when they receive a prolactin-
inhibiting hormone, which there seem to be multiple ones of. At least one of which is
simply DOPAMINE.
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Slide 8 Thyroid Gland

Dr. Lopez So any pituitary questions? So next up is your THYROID. Its really easy
to identify if you see a picture. Youll see these circular/oval shaped structures with
COLLOID inside. So these are all FOLLICLES. The only thing you might mistake or
mix this up with is the PARS INTERMEDIA of the pituitary because that will have
CYSTS that might look similar but the thyroid has SO MANY follicles, the entire slide
will probably be filled up with these circular shapes with usually pink colloid inside.
So two kinds of cells. So know the follicles are lined by FOLLICULAR CELLS. Those
are the ones that are making the THYROID HORMONES. They are going to change
shape based on how active they are. So if theyre not very active, theyll be pretty
SQUAMOUS like up top here. The more active they get the TALLER they get so
down here theyre pretty CUBOIDAL but they can get COLUMNAR as well. They
have pretty obvious looking nuclei here, roundish nuclei. Youll see groups of cells
between the follicles. Besides blood vessels and things there, you will have
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PARAFOLLICULAR CELLS. They are PALER than the follicular cells. So these are all
follicular cells here but the larger paler cells that are adjacent to the follicles are the
parafollicular cells. They are also called C-CELLS or CLEAR CELLS. They are
producing CALCITONIN and so thats going to be involved in blood calcium
regulation. So the more calcitonin that these produce, the.. if these produce
calcitonin, the blood calcium levels will drop. Everyone good with that?

Slide 9 Parathyroid Glands

Dr. Lopez So behind the thyroid gland you have several PARATHYROID glands. So
here you can tell this is a thyroid because of all the follicles filled with colloid. Then
behind it you have a parathyroid gland right here. All of the cells are in contact with
one another so you dont see these big giant follicles. They are kind of a little darker
in color here.

Slide 10 Parathyroid Glands
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Dr. Lopez This is a magnified version. So here you see parathyroid tissue with
maybe some adipose tissue between them. You have 2 kinds of cells here as well.
CHIEF CELLS, these are like the real parathyroid cells are the ones producing
PARATHYROID HORMONE. Theyre relatively SMALL. They are the majority of the
gland, so all of these are all chief cells here. So small cells with a round nucleus
compared to the OXYPHIL CELLS that are LARGER and PALER. So you can tell the
difference between say this chief cell and this oxyphil cells and they dont really
have a clear function. They might be reserved cells that are stem cells that might
become chief cells. Chief cells secreting parathyroid hormone act in concert with the
C-CELLs of the thyroid gland to regulate blood calcium. So parathyroid hormone will
eventually RAISE your blood calcium levels and calcitonin will eventually LOWER
your blood calcium levels.

Dr. Schiff And remember that parathyroid hormone at least has MULTIPLE
TARGETS and ACTIONS. Calcitonin is relatively simple. It lowers your calcium by
blocking the osteoclasts so that you have less calcium breakdown and the
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equilibrium between osteoblastic and osteoclastic activity is shifted in favor of
osteoblastic activity and calcium is removed from the plasma. Parathyroid hormone
indirectly stimulates, by way of the osteoblasts, indirectly stimulates the clasts so
that you get more bone breakdown but it also has 2 other actions which you should
keep in mind. Parathyroid hormone is the one that tells your kidney cells to convert
25-HYDROXY VITAMIN D into the 125-DIHYDROXY form rather than the 24,25-
DIHYDROXY form and the 125 is the ACTIVE hormone. The other thing that
parathyroid hormone does is that it acts in the distal part of the nephron to promote
calcium reabsorption so that you dont end up losing calcium in your urine because
after all, if your calcium levels are low, which is what would trigger a secretion of
parathyroid hormone in the first place, youd get.. ..you dont want to lose more
calcium in the urine because its LOW to begin with. So here you have a calcium
reabsorption mechanism that is triggered by parathyroid hormone. There is also
further calcium reabsorption that depends on vitamin D which the parathyroid
hormone promoted the synthesis of so you have a double barrel effect promoting
reabsorption of virtually all of the calcium. So when this sort of situation is going on
where you are HYPO-CALCEMIC, you end up losing virtually ZERO calcium in your
urine which makes sense. Ok?

Slide 11 Adrenal Gland: Cortex vs Medulla
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Dr. Lopez Gland has a totally different function than the medulla, different
embryological origin, secretes different kinds of hormones, stimulated by different
things. So in this picture down here, this is a cross section through the adrenal and
the outer area underneath the capsule would be the cortex. So that goes all the way
around. And then the INNER part is the medulla. Remember the CORTEX comes
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from MESODERM while the medulla comes from NEURAL CREST. They secrete
different kinds of hormones. The cortex is stimulated by ACTH. Where did that
come from? The ANTERIOR PITUITARY. The medulla is part of your fight or flight
system so when youre under stress its going to secrete CATECHOLAMINES. Then
the cortex is going to have 3 layers.

Slide 12 Adrenal Cortex

Dr. Lopez So here are pictures of that. From outer to inner the Zona
GLOMERULOSA is first. So here is your capsule up here from here to here. Then the
zona glomerulosa is this layer. Zona FASCICULATA is this layer and Zona
RETICULARIS is here. Deep to that is the medulla. So you can really see the
difference in staining patterns in this area. So the zona glomerulosa has very
SMALL cells that are arranged in these ROUND clusters. The zona fasciculata has
LARGER cells that are LIGHTLY colored and they look spongy so you can call them
SPONGEOCYTES. Theyre arranged more in columns. The zona reticularis is VERY
DARKLY stained pink acidophilic cells that are in CORDS. Each of these areas is
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stimulated to secrete their hormones by ACTH, but the zona glomerulosa is also
stimulated by ANGIOTENSIN II. So you should know the MAIN DIFFERENCES
between those 3 layers and what they secrete and what those hormones do and how
to distinguish the different cells.

Student Question (cant be heard)
Dr. Lopez Yeah so ACTH stimulates ALL 3 LAYERS of the cortex.

Dr. Schiff But it doesnt drive secretion of aldosterone. Thats mainly regulated by
ANGIOTENSIN II. But you need the TROPHIC effect of the ACTH to maintain the zona
glomerulosa as well as the rest of the adrenal cortex. You dont want it to atrophy.

Dr. Lopez So yeah, the zona glomerulosa is involved in this angiotensin system so
only this outer layer is stimulated by angiotensin II.

Slide 13 Adrenal Medulla

Dr. Lopez OK so going deeper, here is the adrenal medulla. The chromaffin cells in
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the medulla are modified sympathetic neurons. You remember they came from
NEURAL CREST CELLS just like all the other sympathetic ganglia in your body. They
dont have axons and they look different from other neurons. So you have ganglion
cells in the medulla, these look like typical neurons. The majority of the medulla is
made up of these chromaffin cells that dont look that much like neurons to me.
These are the ones that are going to be producing the catecholamines. So here most
all of these are chromaffin cells. This magnified image of ganglion cells down here
and these paler cells are the chromaffin cells. These are going to secrete
epinephrine and norepinephrine into the bloodstream. Everyone happy with the
adrenal gland?

Slide 14 Pineal Gland


Dr. Lopez The last organ we have is the PINEAL GLAND. This is photosensitive
even though its inside your skull and cant get light. In other organisms it is your
THIRD EYE. In some animals, the analogous structure can receive light. Its involved
in regulating your circadian rhythms. Most of the glands, like 95% of it is made up of
PINEALOCYTES and they produce MELATONIN. So thats involved in regulating
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your circadian rhythm. You have some interstitial cells which are glial cells. They are
actually ASTROCYTES and the interesting thing about this gland is that you have
these calcifications called BRAIN SAND, which I just think is a funny term. You can
use that to locate the midline in a radiographic image.

Dr. Schiff The pineal is a single gland, it is not paired like a lot of other things which
is what led the philosopher, De Carte, to assume that that was the location of the
soul. Its not what current physiologists take it to be.

Student Question Does the amount of brain sand increase with age?

Dr. Lopez Yeah, so there arent any clinical problems because of it, but yeah it will
increase as you age. And thats all I have.

Dr. Schiff OK, any questions about anything at all?

Student Question I missed a part, what was the brain sand?

Dr. Lopez Calcium and magnesium will accumulate kind of as a waste product and
so you will get these calcifications that look like little grains of sand, microscopic
grains of sand. They arent going to do anything bad to you but they will just
accumulate there and because they are radio opaque you can see them on X-rays.

Dr. Schiff ok, anything else? Nope. OK, so have a good coffee break or whatever
you do now.