Transcribed by Sofiya Khazanovich July 28, 2014

General Pathology Lecture 14 Cellular Accumulations and Calcifications by Dr. Phelan

Slide 1 Intracellular Accumulations and Calcifications
Phelan: Dr. McCutcheon said youd like to know something about the format of the exam for next week,
which I think its about time for us to tell you. There will be 50 questions on the exam, there will be 10
very short answer, I will warn you that for Dr. McCutcheons short answers, if she asks you to give her
the cytokines she wants all of them, not one. So in other words you have to give her a complete answer
if shes asking for plural. So watch the questions, and dont just give one. Usually its pretty clear except
sometimes people would like to get away with 1 when theres 2 or 3 that fit the answer, so Im warning
you ahead of time. There should be, again 40 multiple choice. Weve divvied them out a bit among us.
Most of them obviously are from Dr. McCutcheon. I think shes doing 32 multiple choice and between
Dr. Casey and myself, were splitting the other 8. And then when it comes to the short answers, shes
writing five of them and Im writing five of them and they're coming from both Dr. Kinnallys material,
the conference that I did with you, and the material that were doing today. The material were doing
today is much simpler than what youve been working with and its mostly descriptive terms that youre
going to be seeing throughout the pathology course. As we look at the kinds of changes that happen
morphologically, either in terms of the way tissue looks or the way histopathology looks or sometimes
the presence of some of these accumulations or calcifications is a part of how the diagnosis is made. So
its mostly descriptive terms that you need to know, and again I think this is a lot less complex than what
youve been working with in immunology, and so it seemed to make sense to put this at the end with
our last lecture for this whole section of the course before the exam. It goes together with the cellular
changes that we had more in the beginning of the course.

Slide 2 Endogenous and Exogenous
Phelan: When it comes to pigments and collections of materials that end up in tissue and cells, there are
actually two very basic sources. One of them is called endogenous and one is called exogenous. And if its
endogenous it means that whatever that material is, its a product of some kind of abnormal synthesis
or abnormal or normal metabolism that makes that product that is going to get picked up by cells. If its
exogenous it comes from outside of the body and minerals are a good example of this, and the products
of infectious agents are another example of the kind of materials that might come as exogenous agents.
So endogenous comes from within the body and the body is making that material through some kind of
metabolism, normal or abnormal, and it says here abnormal but we have some examples where its kind
of a normal process that gets us where were going. Exogenous is always going to come from outside.

Slide 3 Accumulations
Phelan: There are a couple of possibilities for your accumulations. One of them is that theres an
endogenous substance, and theres a normal endogenous substance that the more than normal amount
is being produced. So the substance is normal, the amount is abnormal. And so, the rate of metabolism
thats needed to remove that material is inadequate to get rid of it. Youll see some of these as we move
along. The other possibility is that the body is producing an abnormal substance. And that it is again
endogenous, but the substance itself is abnormal. The first one, the substance is normal and theres just
too much of it, the second one is the substance itself is abnormal, and then when its abnormal body
doesnt work exactly in the same way to try to get rid of it, and sometimes it gets hung up in tissue and
cells because the body just doesnt have the mechanism for getting rid of that abnormal material. And
sometimes the cell, the material collects because theres an enzyme is missing, and youll see theres
certain diseases where that is the pathogenesis of the disease.

Slide 4 Pathways of Abnormal Intracellular Accumulations
Transcribed by Sofiya Khazanovich July 28, 2014

Phelan: We can have an inadequate removal of a normal substance, that can be because its not possible
to package and transport the material, we can have an endogenous substance that collects because
there are genetic defects, and some of these are linked to the one to the slide that I gave you before,
theres just a variety of different mechanisms for getting these kinds of accumulations within cells and
tissues. There is the possibility that you may have a metabolite that doesnt degrade and these are a
whole group of diseases called storage diseases. And theres a family of storage disease, Ill use them as
an example in this part of the course and as we move later on into the genetic component of this course
well talk about those diseases individually. Another possibility is that the cell doesnt have the
machinery to degrade the substance and cant get it transported to other sites. The difference here after
you know a little bit about cell biology, you can figure probably come up with a list yourself of all of the
possibilities for having some abnormal stuff getting stuck in cells.

Slide 5 Intracellular Accumulations
Phelan: And so what are the intracellular accumulations that were going to focus on? One of them is
fluid, and weve already talked about that with Dr. Kinnally when we talked about hydropic swelling,
where in certain circumstances when the cells are damaged, the cell picks up more fluid and collects in
the cell and we get a very swollen looking, very pale staining, if we do our histopathology staining, pale
staining cells. Lipids will collect in cells under certain circumstances and Ill show you some. The storage
diseases are usually in the category of lysosomal storage disease, and its the lysosomal enzymes that
are defective, and they're different enzymes that are responsible for different storage diseases. We can
collect proteins and there are some diseases in which the protein collection is one of the destructive
components of the diseases even if it isnt the major mechanism of the disease itself. Glycogen can get
stored in cells, and then theres a whole host of endogenous pigments that can get collected in cells, and
then there are some exogenous pigments and well talk about those as well.

Slide 6 Image
Phelan: So heres one, again these are from your textbook, one of the mechanisms and here what were
looking at here is a normal cell, and the normal cell is not obviously doesnt have fat globules in the cell,
but whats happening here is the abnormal metabolism leads to collection and here its collection of lipid
material in the cell.

Slide 7 Image
Phelan: Another one of the mechanisms, and here theres a defect in protein folding and transport and
so we accumulate some abnormal proteins in the cell.

Slide 8 Image
Phelan: Here is an example of the lack of an enzyme and different enzymes degrade different
substances, and so in the lysosomal storage diseases theres a group of them and each one of them is
different and they're related to a different enzyme.

Slide 9 Image
Phelan: This one is just an example of the ingestion of materials that are indigestible, and so the cell sort
of has indigestion in this circumstance and this can be endogenous material or exogenous material, and
pigments that are coming from outside of the body like tattooing would fit into this metallic tattooing
would fit into this category of cellular accumulations.

Slide 10 Intracellular Accumulation: Lipids Fat
Transcribed by Sofiya Khazanovich July 28, 2014

Phelan: If we go through each one of those different categories that we looked at before Im not going
to do the hydropic collection because youve done that with Dr. Kinnally, so as you look at water
collection in the cell, go back as youre studying Dr. Kinnallys material on hydropic swelling of cells and
thats the water accumulation in cells. When we start looking at fat or lipids, you have a whole
mechanism thats normal. And if we didnt have this, we would be eating all the time, many of us as
were studying are eating all the time anyway but thats not the point. We dont have to be, we can eat
several meals a day and the body has the ability to store nutrients, but it certainly has the ability to store
fat. And fat storage for the most part is reversible, and it doesnt interfere with the function of the
adipose tissue or fat cells. Abnormal is related to, um, storage of fat is related to overeating and the
storage, the excess calories as fat, were going to talk about this more when we get to nutrition and
obesity later in the course because there are some, if you like research, some exciting new mechanisms
looking at the way the body regulates what we eat and what we want to eat, and theres even a
syndrome where the individual with that syndrome just eats constantly and is never satiated and just
continues to eat, forever until that person gets sick from the amount of food intake. And there are
studies looking at how you would try to modify that constant need to eat. But then we have in this
country as you all know an obesity epidemic, and there are a number of different ways of looking at it,
where the excess calories are stored as enormous amounts of fat. Diabetes and alcoholism are both
settings where triglycerides will accumulate in the liver cells and the liver cells actually look yellow, and
you will talk about that a bit in systems pathology, and as you get into the next semester. Fatty liver,
another word for that is steatosis. It relates to the accumulation of fat in the liver.

Slide 11 Image
Phelan: And here on your left side is the cells of the normal liver and the color of a normal liver, and
then the fatty liver where theres just collections of fat within the parenchyma of the liver, and the liver
is enlarged and takes on a yellow color.

Slide 12 Intracellular Accumulation: Lipids - Cholesterol
Phelan: Then another lipid that collects is cholesterol, and cholesterol is something that the source is cell
membrane components as they break down. We see cholesterol in atherosclerosis, and if you get a
chance to see the vessels in atherosclerosis you can actually see what are called cholesterol clefts and ill
show them to you a little bit, which are the crystals of cholesterol. Cholesterol, or lipids, are dissolved in
the xylene and in the mechanism that we use for processing tissue, and so cholesterol will not stain, its
clear spaces and fat doesnt stain, but what we see is the morphology or the outline of the adipocyte or
the fat cell, and the morphology of the cholesterol crystal that is not exactly a crystal, but the
cholesterol collection that forms in an unusual kind of shape in the tissue. Macrophages will ingest
cholesterol, and they dont get rid of it very well, and I think Dr. McCutcheon showed you this early on in
one of the sessions that I was here, and we call them foamy macrophages because they look like they
are bubbly because they collect this material. And in necrotic areas, the macrophages are ingesting
whatever they can find and part of that is related to cell membrane material and it gives them
cholesterol to collect. Cholesterolosis is a disease where the body just produces way too much
cholesterol that collects in tissue and so we see this cholesterol in many tissues in the body.

Slide 13 Image
Phelan: If you look at the picture on the left that is what was an artery that has been opened and is now
flat. The normal color of that artery would not be yellow. Whats happened is theres cholesterol thats
just collected throughout that tissue. If we look over here at a blood vessel we have a much thickened
vessel and then you cant see real well but the cholesterol is collecting in this thickened vessel.

Transcribed by Sofiya Khazanovich July 28, 2014

Slide 14 Image
Phelan: Here, we have what are called foamy macrophages or foam cells. Youll sometimes see them
called foamy histiocytes, but since they're really is not a cell that is a true, there is no real histiocyte, the
histiocyte is a macrophage, these are exactly the same cells and this is the foamy appearance. You might
be able to see it better on your laptops than you can see it here. If you look toward the edge of this, we
have more epithelial cells, and then in here we have connective tissue and here are the macrophages
that have collected this material that has come from degenerating cells.

Slide 15 Image
Phelan: This is a picture I took and its from a lesion thats called a periapical inflammatory lesion, when
a tooth usually from caries, the caries is close enough to the pulp of the tooth which you now know a
little bit about teeth I think, and the pulp becomes necrotic, because of the microorganisms that have
invaded the pulp from the carious lesion, and this pulp of the tooth now sends out a number of
inflammatory mediators out of the pulp tissue which was viable fibrous connective tissue with small
blood vessels, tiny capillaries and small nerve fibers, and sends these mediators out into the tissue at
the apex and we get some inflammatory and immunologic changes at the apex of the tooth, and here
what were looking at is lots of inflammatory cells but these clear cells are all macrophages that are
ingesting as much of the debris as they can, and they're ingesting lipid material and so we get this foamy
macrophages at the apex of the tooth.

Slide 16 Image
Phelan: This is another picture that I took of cholesterol clefts, and those are these long kind of skinny
pointed end clear spaces in the tissue. And if you look at this on your own computer, very closely, youll
see that at the edges of these clefts there are some multinucleated cells. Those are actually
multinucleated giant cells, they're macrophages that are trying their hardest to phagocytize these
cholesterol clefts, and they're very unsuccessful at it, so the macrophages just line up around the edges
of these cholesterol clefts in the tissue. But the cholesterol clefts in the tissue tell us that in the area we
have tissue, usually epithelial tissue thats degenerating.

Slide 17 Proteins
Phelan: Another category is proteins, and in renal disease there increased reabsorption of protein into
vesicles in the proximal renal tubules and then theres spilling out of protein into the urine. This
mechanism occurs in a number of different kinds of renal diseases. There is a malignancy called multiple
myeloma that is a malignancy of cells that you now know well, plasma cells, that are busy producing
enormous amounts of protein that is abnormal protein, and that protein again is collected in the
kidneys, and unless the disease is treated there is again kidney damage. The renal disease didnt start
the process but the disease itself is damaging the kidneys. Alzheimers disease is filaments in the brain
that are being studied again its protein collections in the brain. Exactly what the meaning of these and
how the disease works is not real clear. And then in alcoholics, there is something called alcoholic
hyaline, and I havent talked about hyaline yet but what it is is keratin, and its collections of keratin and
the term hyaline and Im going to spend a bit of time on it in a moment, is a descriptive term, its not a
thing. It means that it is a red, it stains red with eosin, and it looks very shiny and so alcoholic hyaline is
intermediate filaments of keratin, it isnt some substance called hyaline, hyaline is just the descriptor.

Slide 18 Hyalin (Glassy)
Phelan: Hyalin is an adjective. Its really not a substance. Alcoholic hyaline has gotten that name and so
within pathology we always confuse you by different names of things, but hyaline just is a descriptor of
this glassy material, and in a number of different disease theres hyalinization of the tissue that is part of
Transcribed by Sofiya Khazanovich July 28, 2014

the description of the histopathology of the condition and so we see this hyelinized tissue under the
microscope and we describe it and then that description is part of that disease. So in atherosclerosis we
can see hyelinized arteries. Do you remember a type of necrosis that I gave you that was an example of
a red circular ring around the blood vessel? Does anybody remember that? It is a characteristic finding in
some autoimmune diseases and so if you take a biopsy you see this blood vessel with a kind of a bright
red hyelinized ring, and theres a name, youve forgotten it already? Theres a name for that kind of
necrosis, and I told you Im not exactly sure that it is true necrosis but it has that name. Anybody
remember? Fibrinoid necrosis is an example of hyalinization of the tissue around the blood vessel and I
really cannot tell you exactly what the mechanism is because the tissue changes and makes this dense
kind of ring of tissue that if we stain it with hematoxylin and eosin which is our normal stain for looking
at tissue, that ring around the blood vessel is a hyelinized ring and the name for that finding under the
microscope is fibrinoid necrosis. And so the pathologist would describe it as fibrinoid necrosis but if you
ask me how did those cells die or did they die and what are we looking at I dont think anybody could
tell you. But fibrinoid necrosis is that morphologic histopathologic picture of a blood vessel that is
surrounded by a hyelinized ring, a red glassy ring, and actually when you look at it under the microscope
it kind of looks like its shining at you, its not dull. You have to look at it sometime and youll see it. But
its the eosin, the red stain material, that makes it look so red. Basement membrane, when youre
looking at epithelium and youre looking at that bright red line that is basement membrane, thats
hyelinized, that red line. Amyloid is a material that is produced in some diseases and if you look at it
again in the tissue under a microscope, and the tissue has been stained with hematoxylin and eosin, you
would get this red shiny looking material on the slide under the microscope. You do not see hyaline, but
anything hyelinized unless youve actually processed it for histopathology and actually stained it with
hematoxylin and eosin. Its the eosin stain that gives you the red color. So theres no hyaline floating
around in the body, its what we look at when we have processed the tissue and stained it. Again its an
adjective and a function of our processing of tissue that gives us this red color that we call hyaline.
Russell bodies are kind of cute and I like to show them off when you come into the lab and look at the
microscope. When we look at a periapical inflammatory lesion or many oral pathology lesions that are
inflammatory, there are lots of plasma cells in the oral environment. And what do plasma cells produce?
Immunoglobulins, and then they release them. And what we will see sometimes under the microscope is
a plasma cell thats just swollen up like a balloon and they're kind of scattered in the inflammatory
infiltrate and you see this bright red cell that looks like its popping out of the slide, again because of this
red red stain, and thats the hyelinized appearance of plasma cells when they're full of immunoglobulins.
All plasma cells dont look hyelinized but these things called Russell bodies do.

Slide 19 Image
Phelan: Here is a hyelinized change or hyaline change in an alcoholic liver disease. And again the only
reason its read is because the tissue has been cut and processed and stained. This stuff is in there but it
would be a clear color, it would not if you were actually looking at the tissue, we wouldnt be able to
make the distinction between the material and the surrounding cells without some help of processing
and staining.

Slide 20 Image
Phelan: Here is amyloid in the kidney, and again this is all visible red because its been stained with
hematoxylin and eosin and its the eosin.. hematoxylin is the blue stain and it stains nuclei, so we can
see all the nuclei in this tissue, and the combination of hematoxylin and eosin is what gives us the
difference and variation of tissue that allows pathologists to look at the tissue and make some decisions
about the morphology and whether or not were looking at is normal or abnormal.

Transcribed by Sofiya Khazanovich July 28, 2014

Slide 21 Intracellular Accumulation: Lysosomal Storage Diseases
Phelan: Then, there are a group of lysosomal storage diseases and I mentioned those before and they
are a very important group of diseases because some of them are life threatening in infants, and in the
normal setting lysosomes are going to break down lipids and lipopolysaccharides and they do it in the
lysosomal enzymes in the cells will do exactly what they're supposed to do. But in the abnormal in these
diseases in which the lysosomal enzymes are abnormal, the individual ends up with an incompletely
degraded certain substances.

Slide 22 Lysosomal Storage Diseases
Phelan: And the best known of these lysosomal storage disease is one called Tay Sachs disease, and the
Tay Sachs disease you have this material that is collected in neurons and you can see here, and these are
diseases that affect babies and are life threatening and really troublesome diseases . Niemann-Pick is
another one where, Im not going to ask you at this point to learn the name of the enzyme or the
material this is involved but I may ask you later, but its not something Ill put on this exam. We talk
about it a little bit later when we get into genetic diseases. The one that I will tell you right now, and Im
not going to put it on this exam, but the one I do expect you to know, the reason for knowing these is
that they possibly come up, I mean the Tay Sachs and Niemann-Pick, they come up on your board exams
and so weve always included them in the course. I had to learn them when I was a dental student; I
forgot them until I started teaching you guys. They pop up again and we need to know these. But this
Gaucher disease is a condition that people live to adulthood and we might find that there are patients
that have been or have had abnormal collections of macrophages in the jaw and have had abnormal
radiolucencies in the jaw that have been related to that disease and so that one is the one that I ask you
to learn above the others, but we do that later on in the course. But here what they are is diseases that
are the pathogeneses is that the lysosomal enzyme that is necessary to degrade that material is
defective, and so in each one of these diseases its a different storage disease but the material in each
one of them has a different name.

Slide 23 Intracellular Accumulation: Glycogen
Phelan: Another substance that can be accumulated is glycogen and glycogen is part of many tissues in
epithelium, theres lots of glycogen in epithelium if we stained it with another stain wed get to see the
glycogen very dramatically. Have you talked about candidiasis with Dr. Shah? Yes? The cell walls of
candida organisms have a lot of glycogen and so PAS stain is a stain that will highlight glycogen and so
its one of the stains that we use to identify candida organisms in tissue because it stands out and they
stand out from the H&E, H&E its really hard to see them, hematoxylin is so.. but when you use PAS
these candida hyphae just sort of kind of swim out of the epithelium because they become very obvious
to see them. Theres clearly lots of normal glycogen, but the abnormal glycogen is going to collect in a
number of abnormal conditions and one possibility is that we might again have some abnormal enzymes
that are part of the disease structure, and then in uncontrolled diabetics, the glycogen collects in the
kidneys and causes kidney disease related to the collection of glycogen.

Slide 24 Image
Phelan: And as we get further on into systems pathology what youll see is that in the pathogenesis of
diseases youre actually going to look at how glycogen is involved in the kidney disease and exactly
where its collecting. At this point Im happy if you know that glycogen is one of the things that can be
abnormally stored. And we go into the details a little bit later. This part of the storage problem is really
looking at a list and Im not looking at the pathogenesis so completely. So heres normal muscle over
here, on your left side, and heres abnormal muscle and here even though fat can be stored in muscle,
this much fat being stored in muscle is abnormal and the muscle is not going to function normally. Not
Transcribed by Sofiya Khazanovich July 28, 2014

fat Im sorry, glycogen. The tissue is not going to function normally. And you know, besides striated
muscle its certainly possible in certain disease to have glycogen storage in heart muscle and interfere
with the functioning of heart muscle.

Slide 25 Intracellular Accumulation: Pigments
Phelan: From there we go to a bunch of pigments and of course pigments are colorful and they are
giving us some information about whats happening in the tissue and what is and usually they're
occurring in certain specific circumstances so we can kind of once we see the pigment we can kind of
walk back into the story and try to figure out where it came from. Exogenous pigments are the ones that
come from outside the body and Ill give you a couple of examples of those, and endogenous the same
as we were talking about the other accumulations are substances that are produced within the body.

Slide 26 Exogenous Pigments
Phelan: The exogenous ones we do first because its the easiest to think about. Carbon in coal dust, and
it used to be much more severe in city dwellers than it is now because our environment, our air is less
polluted than it used to be. But there used to be a tremendous amount of carbon in the air that we
breathed when we lived in cities. And so you can tell the difference between someone who lived in the
country and someone who lived in the city and you still kind of can by the amount of blackness that is in
their lungs on an autopsy. You dont see black lungs looking at you or me; you would have to see this if
you were looking at an autopsy specimen of lungs. Tattoos are metallic pigment, some of them are
vegetable pigments, but they are one of the oral lesions, have you talked about amalgam tattoos?
Amalgam tattoo is the silver in the amalgam is the pigmenting agent. And there are certain
circumstances where we in pathology are trying to stain certain parts, reticular fibers, around blood
vessels, and theres certain kind of tissue or fibers that we want to identify, and one of the ways of doing
that is to use a special stain called a silver stain, because the silver stain will actually hone toward those
reticulum fibers or to some of the nerve fibers, and when amalgam which has silver particles in it, gets
embedded into the tissue, whats really interesting is that the tissue most of the time doesnt even
mount an immune response. Either innate or an acquired immune response, the amalgam just sits
there, but what the particles of silver do is they disperse along the collagen fibers and they move away
from the main chunk of amalgam that got sucked into the tissue and they make a greyish blue spot on
the mucosa. And if theyre on the alveolar mucosa usually you can make the diagnosis on the clinical
appearance alone but if they're elsewhere in the oral cavity thats when we usually see them under the
microscope. H&E will stain hematoxylin eosin will stain the epithelium and the underlying connective
tissue but we dont need anything to stain the amalgam in an amalgam tattoo, or the silver, you can
actually see the black dots of this material that are kind of sprinkled in the tissue. And tetracycline is a
drug that pigments bone and dentin. And it is, if youve ever looked at the package insert for tetracycline
theres usually a warning not to give tetracycline, or now its harder to get tetracycline we use
doxycycline most of the time, not to give to children with any developing teeth because the tetracycline
is going to stain the dentin. It doesnt stain the enamel but it stains the dentin and it stains bone. In an
adult it actually does stain the bone, but what happens to bone in adults? It turns over. And so the bone
thats stained is not permanent but the staining in teeth is permanent.

Slide 27 Image
Phelan: Here were looking at a lung, and were looking at the carbon thats collected in the lung. You
can kind of see it in the, and again its getting collected in macrophages and the macrophages in the lung
tissue are trying to get rid of it, they dont have any mechanism for getting rid of carbon so it just sits
there in the macrophages in the lung.

Transcribed by Sofiya Khazanovich July 28, 2014

Slide 28 Image
Phelan: This is a patient that has amalgam here and its not really clear quite how she got so much of it in
there, but this heres the hunk of amalgam on the panoramic radiograph. Can you see it right there?
What happens also, this isnt oral pathology but Ill say it now and ill probably say it again. If theres
enough of the piece of amalgam in there then it disperses over time and that amalgam tattoo can
enlarge, it doesnt necessarily stay the same way. What I think probably happened here is that there was
an endodontic procedure with whats called a retrofill which in order to do the endodontic procedure
called an apicalectomy, there is a surgical procedure that goes in at the root of the tooth and actually
cuts off the root of the tooth, and fills it from the root end to make sure that none of the products were
from the pulp can actually escape into the tissue around the root of the tooth but youll talk about that
more when you get to endodontics later on in your careers here.

Slide 29 Image
Phelan: Here is a patient with some tetracycline staining. And notice that it isnt the whole tooth. Notice
that it is a line and its a couple millimeters, but if you look at where the line is, now here there has been
some composites that have been done to try to mask some of the staining, but the staining is occurring
at the point that the tooth was being formed when the tetracycline was administered. And so you can
kind of if you when you get to pediatric dentistry youll do some of this in trying to figure out what the
age is of the child, when the tetracycline was administered. And one of the parents can tell you but
usually you can figure it out yourself. Youll find the same kind of thing with children who have high
fevers at the time their teeth are developing, and there will be a line at the point where the tooth was
developing, so its in certain places on the incisors and then on the molars and depending on where the
tooth was in its formation.

Slide 30 Endogenous Pigments
Phelan: So the endogenous pigments are a little bit more numerous but some of them are going to be
familiar to you and some of them arent. Ferriten and hemosiderin both come from hemoglobin, and
when you see them the most, or the most vividly, is when you have a bruise. And it starts out bright red
and what happens over time? It turns colors. Itll turn brown to green, thats the breakdown of the
hemoglobin and as it breaks down it changes its color. Bilirubin also comes from hemoglobin and it is
part of the mechanism of bile pigment and jaundice. Lipofuscin comes from cell membrane turnover and
it doesnt mean much in terms of theres no pathologic entity thats dependent on lipofuscin but what is
interesting about lipofuscin when we get it in the slide, it is brilliant yellow and it isnt something that
weve stained yellow, thats the color of the pigment. And the melanin of course comes from
melanocytes.

Slide 31 Image
Phelan: So here is some hemosiderin in the tissue, and in the tissue when were looking at the tissue its
usually brown.

Slide 32 Image
Phelan: This is bilirubin pigment and this is a patient with jaundice. Am I missing something?

Slide 33 Image
Phelan: This is some lipofuscin and its these yellow spots that are between the muscle fibers.

Slide 34 Image
Phelan: melanin you can have a lot of patients that have melanin pigmentation of the mucosa.
Transcribed by Sofiya Khazanovich July 28, 2014


Slide 35 Image
Phelan: This is a melanatic or labial melanatic macule which is diagnosed on the basis of its appearance
and its response to sunlight and its location.

Slide 36 Image
Phelan: And then this is actually a patient with melanoma. So were going everywhere here from
melanin that is normal in normal pigmentation of the mucosa in a person that has darker skin, benign
collection of melanin, and this is being produced by malignant melanocytes and thats a melanoma.

Slide 37 Dystrophic Calcification
Phelan: The next category, so weve done this group of accumulations, weve done pigments, and then
the last category of things that get collected in our pathologic exam of tissue are calcifications. And
theres really two different categories of calcifications. One of the categories is called dystrophic
calcifications, and this is the calcification that forms in tissue. Its localized. And it occurs in tissue thats
become necrotic, and the calcification is occurring in that area. In plaques, in atherosclerosis, theres
calcification in the walls of the blood vessels and again thats dystrophic calcification in that abnormal
tissue. And then another form of dystrophic calcification is the formation of stones or liths.

Slide 38 Image
Phelan: And this is a patient with a condition that is actually forming stones in the pulp. Those are pulp
stones. Thats a dystrophic calcification. Here are calcifications forming in the aortic valve, those are
dystrophic calcifications. Even though this is multiple teeth, theyre still localized, and this is a
phenomenon thats occurring in the wall of the aortic valve because the aortic valve is damaged.

Slide 39 Pathologic Stone Formation (Liths)
Phelan: We are, we do have sialoliths, have you done sialoliths? I think I did them with you. Salivary
gland stones. And so we have a number of different salivary gland stones. Phleboliths, are thrombi
which you havent studied yet, but thrombi youre going to study them with Dr. Vernillo a little bit later
after the summer break, thrombi are collections or clots of Im making this way oversimplified,
occurring within the blood vessels and then the blood vessel is trying to organize that clot, and
sometimes that whole process will allow the collection of mineralization and you get stones forming
within the lumen of a blood vessel. Kidney stones are another form of liths.

Slide 40 Image
Phelan: So here Ive shown you these, Im not sure this is the same one, I think I showed you this in the
other class, this is one thats in a minor salivary gland in the upper lip, this is one thats in the
submandibular gland duct and its in the floor of the mouth.

Slide 41 Metastatic Calcifications
Phelan: So we have dystrophic calcifications and the last category for today is one called metastatic
calcifications. When we talk about neoplasia later on in the course, were going to talk about the ability
of malignant tumors to metastasize. It is a major differentiation between a benign tumor and a
malignant tumor. A malignant tumor has the potential to break or have components of that tumor break
off and move through either the lymphoid circulation or the blood circulation, go to someplace else, and
form tumors someplace else. Thats metastasis in tumors. This is not the same. Metastatic calcifications
really dont, its a different use of the word metastatic. You do have some malignancies that might have
metastatic calcifications but what it means is that the amount of calcium thats circulating in blood is
Transcribed by Sofiya Khazanovich July 28, 2014

much greater than normal. And the calcium is then deposited in tissue in many parts of the body. And
thats metastatic calcification, it results from hypercalcemia. Emia means its circulating in blood, hyper
means its too much, so hypercalcemia, youve got too much calcium circulating in blood, and it lands in
tissue. And there are a number of diseases, kidney disease, parathyroid disease, in which theres a
problem with the control of calcium. And if you go back to last year and you think about what controls
calcium, anything that messes up the control of calcium and can lead to an increase in the amount of
calcium circulating in blood has the potential for resulting in metastatic calcifications.

Slide 42 Image
Phelan: And this is a patient, this is the result of hypercalcemia in one patient, and what were looking at
here is in the lung, the calcifications are scattered throughout the lung because they're carried there
through circulation. This patient will also have calcifications in other parts of the body as well not just
the lung. So metastatic calcifications are related to hypercalcemia. Dystrophic calcifications are related
to some kind of local tissue damage in which the mineralization or the calcification occurs in the local
tissue where that problem occurred. And thats it for our accumulations, our pigments, and our
calcifications. At this point Im hoping that you all do extremely well on the exam and I think most of the
material is of course on immunology and if you are studying those study guides youre going to be in
good shape. But dont ignore the other material, its the easy stuff. There will be questions, and whats
happened in the past, is when weve included immunology and other things, students spend so much
time studying the immunology that they completely ignore this simple stuff and they cellular responses
that we did in the beginning and why lose points on that? Its easy. Its really very straightforward,
necrosis, apoptosis, and all of the reversible cellular responses. So please dont ignore that while youre
studying everything to do well in immunology.