0:00:06.056,0:00:10.059
(From M1 Patients and Populations at University of Michigan Medical School. Lecture by Gerald Abrams, MD.)[br]You see the title is Disturbances of Growth in Neoplasia.
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This is one of the
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probably the only time
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in the sequence where pathology really[br]meshes with what else is going on.
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We will spend
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much of the two hours today and[br]then an hour Wednesday
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on the subject of neoplasms, that is[br]tumors
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this will feed into Dr Gruber's 11 o'clock lecture on Wednesday on the genetics
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aspects of neoplasia and[br]then a very interesting MDC in the afternoon,
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dealing with some clinical aspects of[br]those same things.
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But before we settle down
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to the subject of neoplasms, tumors and such,
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i want to spend a bit of time giving you[br]a few notions and definitions in visual images
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images
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dealing with other
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abnormalities of growth short of[br]new place, in other words there are some other
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some other
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disturbances in the size of cells[br]tissues and organs
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the
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mode of cellular proliferation and even
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lead the way that cells mature
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and
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look at a few of these[br]abnormalities first before we get onto the main
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subject
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let me begin
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very simply with
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situations
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in which you might
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encounter a bunch of cells, a tissue, an organ
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smaller than normal
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smaller than you expect
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and it runs
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something like this
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it makes pretty good sense that the one way[br]that you could end up with a tissue
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that's abnormally small
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organized abnormally small is a[br]developmental situation
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where it never grew up
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sort of a dwarfed tissue
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or organ
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and on the other hand
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there are situations
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as i think you're already familiar with
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when an organ or tissue reaches a[br]definitive adult size and then shrinks
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that process i think you know from[br]Ramsburgh's lecture we call
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atrophy
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so those are two kinds
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situations and i want to run[br]through first
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this list of developmental problems
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that we have encounter from time to time
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the most complete sort of defect
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you might encounter is when the[br]embryonic rudiment
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of an organ
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simply doesn't develop, it's a screw up in embryogenesis
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and then there is no organ
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laid down
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and we referred to that
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process as agenesis
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there's a slight variation on the theme[br]and that is where the rudiment of the organ
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may be
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laid down in the embryo, but
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the thing never grows
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non-descript nubbin' of nothing
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and that sometimes is referred to as aplasia
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those two terms are essentially[br]synonymous
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it's an absence
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an absence of the tissue
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and I'll
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give you an example, a very striking example of this
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here's an autopsy specimen, let me orient you to it
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this is the urinary bladder down here
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here is
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a ureter on one side going up and connecting with a very respectable looking kidney
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here's the other ureter, boom!
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there was nothing outside the
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it's not a camera trick, there's nothing outside there, it just ended
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that way
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now that is an example of the unilateral renal
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agenesis
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or aplasia, i don't care which word you use
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this sort of thing is compatible with[br]long happy life and this is strictly an incidental finding
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i don't remember anymore what this individual died of
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but it had nothing
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relating to the
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urinary tract
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so it's just a failure on one side for that
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kidney to develop. Agenesis or aplasia.
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sometimes we see this bilaterally. Both
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kidneys are not there
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and that
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of course is not compatible with life whereas this sort of thing is
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now
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the next step up from
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agenesis or aplasia
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is a situation where the
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the organ rudiment is laid down in the[br]embryo, and indeed
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grows but not
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as much as it should
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so you end up with something
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smaller than normal because of
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well we might call it loosely a growth failure, and that we call
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hypoplasia
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hypo meaning under or less than
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and there's an example, let me take you[br]through this one, it's a little bit confusing
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here's
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the bladder
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this happens to be the aorta, forget[br]about that, here's the bladder
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the ureter
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on one side going up to a very decent looking
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kidney
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here is the ureter on the other side, sort[br]of stunted
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here's
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a little shrunken
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well, i shouldn't say shrunken, but a tiny, miniature
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kidney there
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that represents a unilateral
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renal hypoplasia
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again sort of an embryonic defect
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if you will
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sometimes we see this bilaterally
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and it could be all degrees, it could[br]be something between this and this or something
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even less than this and as long as
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you put it under the microscope and you see
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the structure of kidney, but there's not enough of it, it's too small. that's hypoplasia.
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i've shown you urinary tract here, these sorts of defects, agenesis and hypoplasia
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occur in
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other organs
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and organ systems as well, i just happen[br]to have these pictures on hand
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one of things you'll encounter when you[br]get over in the hospital because we're sort of
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a funnel for odd things
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is fairly often
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kids born with what we call hypoplastic left heart
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and that's the situation
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where the chambers of the left side[br]of the heart and even sometimes a portion
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of the aorta
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simply don't develop properly, and there are little tiny nubbin's on the heart
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and this hypoplastic left heart[br]syndrome is lethal unless some pretty fancy
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surgery is done to intervene for a while
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so you will see that hypoplastic left heart
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one more term on that list that i gave[br]you, i just defined it and i want to illustrate it
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and that is atresia
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a-t-r-e-s-i-a, atresia
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which is a situation and again it's a[br]developmental failure where a channel
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a normal opening or channel fails
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to stay open
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fails to form properly so you end up with a closure where you should have
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a channel
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something let's say along the GI tract or along a duct
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where it simply disappears because it never[br]opened up properly. That's atresia.
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Now the second situation
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i mentioned back on that list
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other than developmental is a situation
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where the organ has reached
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a definitive size and undergoes a process of atrophy
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atrophy can come about really in in[br]two ways
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first of all
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every single cell in the tissue could shrink
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by some percentage
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and that would produce a smaller tissue, a smaller organ
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or
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a certain number of cells as they start out with a million cells in the population
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and
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some of them disappear by apoptosis
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and you end up
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with eight hundred thousand cells, that's going to be a shrunken tissue
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so a tissue can
0:07:54.929,0:07:58.719
undergo atrophy with shrinkage of individual cells
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sometimes loss of cells or both
0:08:02.419,0:08:06.879
but it's a secondary change after the[br]the organ has reached its definitive size
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some
0:08:09.099,0:08:12.809
examples of atrophy as some of you may know already
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is perfectly physiologic in the, let's say, fetus
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as various things form and come and go
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there's atrophy
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there's certainly atrophy of fetal structures
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in the neonatal period
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umbilical vessels and that sort of thing undergo
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atrophy
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there are examples
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of physiologic atrophy
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as one matures into adult life, the tonsils shrink
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the thymus shrinks
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and so forth
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there are these things which are expected and physiologic
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when
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it comes to pathologic forms of atrophy, there are many reasons why
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this can happen, one that Dr
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Ramsburgh may have mentioned is ischemia
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if you rob a tissue of its blood supply, let's say, not enough to kill it
0:09:02.047,0:09:04.068
but really to cut it down, there's
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such a thing as ischemic atrophy
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and you'll see that in arteriosclerotic
0:09:10.026,0:09:14.051
areas where the tissues tend to simply shrink
0:09:14.051,0:09:16.028
starvation
0:09:16.028,0:09:17.041
you don't
0:09:17.041,0:09:20.084
feed a person enough calories, starvation will produce
0:09:20.084,0:09:25.038
atrophy. there's a hierarchy of organs which i don't want to go into
0:09:25.038,0:09:27.043
for instance, the brain doesn't atrophy
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in that situation
0:09:28.709,0:09:32.299
but the adipose tissue does, the liver does, and so forth
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that's starvation atrophy
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in the case of muscular tissues
0:09:37.065,0:09:38.069
disuse
0:09:38.069,0:09:41.057
just plain old disuse will cause atrophy
0:09:41.057,0:09:43.013
it could be very striking
0:09:43.013,0:09:47.399
i don't know if any of you have been in this situation, but you have an acute injury
0:09:47.399,0:09:48.083
like, oh let's say,
0:09:48.083,0:09:53.076
a bad knee, for some reason, just self splinting
0:09:53.076,0:09:56.028
not using that leg in the same way
0:09:56.028,0:09:58.529
will cause a shrinkage within a few weeks
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you can get a loss in circumference of a thigh
0:10:04.027,0:10:06.021
i don't know how many of you are skiiers
0:10:06.021,0:10:07.099
that have gotten into
0:10:07.099,0:10:12.034
trouble and ended up with let's say a cast on an extremity
0:10:12.034,0:10:17.017
for a number of weeks and when that cast comes off, you've got a shriveled leg
0:10:17.017,0:10:19.011
compared to the other one
0:10:19.011,0:10:22.053
that is disuse atrophy
0:10:22.053,0:10:26.024
an extreme example of that is something we call neurogenic atrophy, if you cut
0:10:26.024,0:10:26.076
the motor
0:10:26.076,0:10:29.028
nerve going to a muscle
0:10:29.028,0:10:33.022
then that muscle can't work at all and is getting[br]no signals
0:10:33.022,0:10:37.099
it'll really shrink, it's a tremendous sort of atrophy
0:10:37.099,0:10:39.027
then
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well, i'll stop this list with one more
0:10:42.013,0:10:45.039
many tissues in the body are
0:10:45.039,0:10:48.058
the way they are because they have a[br]certain endocrine support
0:10:48.058,0:10:54.028
they depend on a certain level of a particular[br]hormone, and if you withdraw that hormone, the tissue
0:10:54.028,0:10:58.067
will undergo atrophy. Morphologically
0:10:58.067,0:10:59.048
it's pretty
0:10:59.048,0:11:02.319
straight forward, i'm not going to show you much of this
0:11:02.319,0:11:02.091
it's simply the tissue
0:11:02.091,0:11:04.029
is smaller
0:11:04.029,0:11:08.189
you look at it under the microscope and the[br]individual cells are smaller
0:11:08.189,0:11:11.095
the number of cells, that's a tougher thing to deal
0:11:11.095,0:11:15.096
with, but basically it's a small tissue
0:11:15.096,0:11:19.074
sometimes there's partial fibrous replacement as the tissues shrink
0:11:19.074,0:11:23.027
we call that fibrous atrophy
0:11:23.027,0:11:23.074
sometimes
0:11:23.074,0:11:28.011
this seems to be an increase in adipose[br]tissue, marbling the tissue, we call that fatty atrophy
0:11:28.011,0:11:31.001
but basically the business cells of the tissue
0:11:31.001,0:11:32.073
are smaller
0:11:32.073,0:11:35.009
there's one variation on this theme that
0:11:35.009,0:11:40.027
Ramsburgh may have introduced you to and that's
0:11:40.027,0:11:43.046
as a cell shrinks
0:11:43.046,0:11:45.071
it basically
0:11:45.071,0:11:50.042
is undergoing a process of autophagy, it's eating itself, it's digesting
0:11:50.042,0:11:52.019
various of its
0:11:52.019,0:11:55.003
organelles and so forth
0:11:55.003,0:12:00.038
one of the things that happens[br]from this digestive process is that there
0:12:00.038,0:12:02.369
may be residual products
0:12:02.369,0:12:04.057
left afterwards and
0:12:04.057,0:12:05.002
they
0:12:05.002,0:12:07.077
tend to be pigmented products which we've
0:12:07.077,0:12:10.087
we refer to as lipofuscin
0:12:10.087,0:12:13.061
0:12:13.061,0:12:18.055
here's a liver where particularly in[br]this area, the central area, the cells
0:12:18.055,0:12:20.054
are shrunken and you'll
0:12:20.054,0:12:23.085
notice this is not a particularly good photo, but you'll notice they are brown
0:12:23.085,0:12:25.037
and that's
0:12:25.037,0:12:28.006
because of a relative concentration of lipofuscin there
0:12:28.006,0:12:29.829
they've been undergoing
0:12:29.829,0:12:31.031
autophagy
0:12:31.031,0:12:36.035
and the residual products are piling[br]up and sometimes we refer to this as pigment atrophy
0:12:36.035,0:12:38.009
or brown atrophy
0:12:38.009,0:12:42.044
and i've seen shrunken livers where there's perhaps half the mass of the usual liver
0:12:42.044,0:12:43.001
and they're really
0:12:43.001,0:12:44.639
definite
0:12:44.639,0:12:46.038
brown
0:12:46.038,0:12:47.699
rather than the ordinary
0:12:47.699,0:12:48.649
liver color
0:12:48.649,0:12:50.869
because of this sort of accumulation
0:12:50.869,0:12:53.019
Okay so
0:12:53.019,0:12:57.007
much for smaller than normal, let's go to the flip side
0:12:57.007,0:13:00.959
and look at situations where the tissue[br]or the organ may be larger
0:13:00.959,0:13:02.029
than normal
0:13:02.029,0:13:03.048
and this
0:13:03.048,0:13:07.004
can come about in two ways
0:13:07.004,0:13:11.088
you can have an increase in the size of[br]the cells in the tissue
0:13:11.088,0:13:15.008
and we refer to that as hypertrophy
0:13:15.008,0:13:19.015
you can have an increase in the number[br]of cells in the tissue, we call that hyperplasia
0:13:19.015,0:13:21.007
Now let's go back
0:13:21.007,0:13:23.074
up to hypertrophy
0:13:23.074,0:13:28.022
let me point out that size increase isn't simply cell swelling, you know
0:13:28.022,0:13:32.061
about the phenomenon of cell swelling, which involves a net accumulation of water
0:13:32.061,0:13:35.062
that we wouldn't call hypertrophy
0:13:35.062,0:13:39.065
in hypertrophy, the cells enlarge because of an increased
0:13:39.065,0:13:41.006
synthesis
0:13:41.006,0:13:43.048
of cellular components
0:13:43.048,0:13:44.779
i'll show you that in a
0:13:44.779,0:13:46.012
moment
0:13:46.012,0:13:48.002
again hyperplasia
0:13:48.002,0:13:51.074
involves an increase in cell number so you'd look
0:13:51.074,0:13:55.007
for hyperplasia only in tissues that are capable of
0:13:55.007,0:13:57.079
dividing in the adult state
0:13:57.079,0:14:00.049
another was a permanent sort of tissue
0:14:00.049,0:14:03.083
you're not going to get hyperplasia ordinarily in muscle
0:14:03.083,0:14:05.006
you're not going to get
0:14:05.006,0:14:11.026
hyperplasia, well muscle is probably the best example. but in other
0:14:11.026,0:14:12.093
organs, you may
0:14:12.093,0:14:16.052
get hyperplasia along with hypertrophy
0:14:16.052,0:14:17.095
but conceptually hypertrophy
0:14:17.095,0:14:22.399
is increase in cell size, hyperplasia is increase in cell
0:14:22.399,0:14:24.249
number
0:14:24.249,0:14:26.072
the
0:14:26.072,0:14:33.073
best example of hypertrophy is in muscular tissues
0:14:33.073,0:14:35.053
it's a response
0:14:35.053,0:14:38.077
hypertrophy in muscle is a response to an overload
0:14:38.077,0:14:42.057
or unusual workload or what not
0:14:42.057,0:14:46.038
now you need a lot of imagination for this, but imagine i went in for bodybuilding
0:14:46.038,0:14:48.032
which i never will
0:14:48.032,0:14:51.067
and you know you you pump three hundred[br]pounds like this
0:14:51.067,0:14:53.015
and after a while couldn't
0:14:53.015,0:14:55.078
get into the lab coat. Bulging
0:14:55.078,0:14:59.027
muscles, i told you, imagination.
0:14:59.027,0:15:00.042
the
0:15:00.042,0:15:03.409
muscles of the bodybuilder
0:15:03.409,0:15:06.429
you've all seen pictures of this and maybe some of you are into this sort of sport
0:15:06.429,0:15:07.075
this
0:15:07.075,0:15:09.689
represents
0:15:09.689,0:15:10.047
hypertrophy
0:15:10.047,0:15:15.004
of muscle, there isn't any real increase in the number of muscle cells
0:15:15.004,0:15:18.078
but any individual muscle cells instead of being this big around is this big around
0:15:18.078,0:15:20.009
and it
0:15:20.009,0:15:23.001
represents actually a synthesis of more
0:15:23.001,0:15:26.007
contractile machinery
0:15:26.007,0:15:27.829
in the muscle, it's a response
0:15:27.829,0:15:30.034
to the work
0:15:30.034,0:15:33.084
now a place where we see this that isn't so trivial
0:15:33.084,0:15:35.003
is
0:15:35.003,0:15:37.018
is, for instance, heart muscle
0:15:37.018,0:15:41.005
that is subjected to an abnormal load
0:15:41.005,0:15:44.094
for instance, a left ventricle
0:15:44.094,0:15:51.094
having to pump blood in a patient with uncontrolled hypertension
0:15:51.094,0:15:55.007
in other words, the systemic blood pressure is elevated, the arteriolar resistance is elevated
0:15:55.007,0:15:58.439
and every time that poor old left ventricle
0:15:58.439,0:16:02.082
tries to eject blood, it's doing it against an increased head of pressure
0:16:02.082,0:16:06.089
those muscles are going to undergo[br]hypertrophy
0:16:06.089,0:16:07.097
or
0:16:07.097,0:16:11.009
let's say the valve, the so-called[br]aortic valve, which is a valve between
0:16:11.009,0:16:17.047
the left ventricle and the aorta, as the blood flows out, if that valve gets narrowed
0:16:17.047,0:16:20.011
the poor old ventricle has to squeeze harder to get
0:16:20.011,0:16:23.003
the blood out to maintain life, it will[br]undergo hypertrophy
0:16:23.003,0:16:24.139
not hyperplasia
0:16:24.139,0:16:25.119
but hypertrophy
0:16:25.119,0:16:26.059
and the
0:16:26.059,0:16:29.037
heart gains weight
0:16:29.037,0:16:31.031
the ventricle becomes thick
0:16:31.031,0:16:35.092
and the cells become enlarged. I'll illustrate this for you.
0:16:35.092,0:16:37.049
here is
0:16:37.049,0:16:41.042
don't pay attention to the color, there have been[br]some post-mortem changes here but
0:16:41.042,0:16:43.739
this is a bread loaf slice
0:16:43.739,0:16:45.041
of a normal heart
0:16:45.041,0:16:47.919
you're looking at the right ventricle[br]over here
0:16:47.919,0:16:52.209
left ventricle over here ordinarily, this is normal, the right ventricle is very thin
0:16:52.209,0:16:57.014
because it pumps against a lesser head of pressure in the pulmonary circuit. The left ventricle
0:16:57.014,0:16:59.559
,that's about normal thickness,
0:16:59.559,0:17:01.002
now the next slide
0:17:01.002,0:17:05.036
is not a photo trick and again[br]don't worry about the colors, but the next
0:17:05.036,0:17:12.021
slide is taken from an individual with high blood pressure
0:17:12.021,0:17:15.015
now that first heart probably weighed
0:17:15.015,0:17:18.819
oh in the neighborhood of three hundred, three hundred and twenty five grams
0:17:18.819,0:17:20.045
this heart weighed closer
0:17:20.045,0:17:24.022
to the six or seven hundred grams, i don't remember precisely, but
0:17:24.022,0:17:28.005
it kind of speaks for itself, there is more muscle[br]there
0:17:28.005,0:17:31.099
and again this is not hyperplasia, this is[br]hypertrophy
0:17:31.099,0:17:36.045
and it looks something like this. i know you don't know much of this histology
0:17:36.045,0:17:37.088
but just
0:17:37.088,0:17:41.046
think of these as cross-sections of these cylindrical muscle cells
0:17:41.046,0:17:42.086
and this is
0:17:42.086,0:17:44.091
a normal myocardium
0:17:44.091,0:17:45.063
and
0:17:45.063,0:17:50.052
let's just cast your eyeballs around and look at the approximate
0:17:50.052,0:17:54.083
average diameter
0:17:54.083,0:17:55.057
the next slide
0:17:55.057,0:17:58.059
is taken with the same optics in the microscope
0:17:58.059,0:18:04.006
from a hypertrophic heart, now you got this?
0:18:04.006,0:18:04.071
The point
0:18:04.071,0:18:08.809
those cells are really increased in diameter, don't worry about this, I don't expect you to
0:18:08.809,0:18:11.049
pick this up on the quiz
0:18:11.049,0:18:13.007
but just to show you
0:18:13.007,0:18:14.003
the increase
0:18:14.003,0:18:19.019
and what this represents really is an increase, a very striking increase
0:18:19.019,0:18:21.058
in the myofibrillar contractile machinery
0:18:21.058,0:18:24.079
of these cells
0:18:24.079,0:18:28.679
so this is clearly an adaptive
0:18:28.679,0:18:30.052
phenomenon
0:18:30.052,0:18:33.056
and it works very well up to a point
0:18:33.056,0:18:38.092
the heart can't keep getting more and more and more hypertrophic
0:18:38.092,0:18:40.069
i've never seen a heart
0:18:40.069,0:18:42.081
weigh much more than a kilogram
0:18:42.081,0:18:44.309
and that's rare
0:18:44.309,0:18:45.049
but beyond that
0:18:45.049,0:18:46.809
it doesn't work
0:18:46.809,0:18:51.299
and one of the reasons that it doesn't work[br]is that the vascularity of the blood supply
0:18:51.299,0:18:53.008
of the heart
0:18:53.008,0:18:56.017
muscle doesn't keep up
0:18:56.017,0:18:59.038
with too much hypertrophy and pretty soon
0:18:59.038,0:19:03.067
the muscle to capillary ratio is unfavorable
0:19:03.067,0:19:06.095
and it plateaus, it can't go any further
0:19:06.095,0:19:12.012
and then what you get is the onset of apoptosis in cells and actually some
0:19:12.012,0:19:17.001
fibrous replacement of the myocardium so it doesn't work indefinitely
0:19:17.001,0:19:17.061
actually some
0:19:17.061,0:19:19.084
of the proteins that are formed
0:19:19.084,0:19:22.081
are not necessarily normal either
0:19:22.081,0:19:23.089
so hypertrophy
0:19:23.089,0:19:30.045
is nice and adaptive up to a point, but beyond that
0:19:30.045,0:19:33.091
i might mention that before we leave hypertrophy that this also goes on in other types of
0:19:33.091,0:19:35.067
of muscle
0:19:35.067,0:19:36.009
as you may
0:19:36.009,0:19:40.043
know for instance, the wall of the urinary bladder is muscle but
0:19:40.043,0:19:43.061
this kind of muscle is what we call smooth muscle
0:19:43.061,0:19:46.051
but if there is a chronic obstruction to[br]bladder outflow
0:19:46.051,0:19:48.066
you get a very thick muscular bladder
0:19:48.066,0:19:51.066
the same kind of response
0:19:51.066,0:19:55.048
hypertrophy of the muscle cells
0:19:55.048,0:19:57.077
we return to hyperplasia
0:19:57.077,0:19:59.919
lots of examples i can give you
0:19:59.919,0:20:00.044
of increased
0:20:00.044,0:20:02.004
in
0:20:02.004,0:20:02.098
the number of cells
0:20:02.098,0:20:05.001
in the tissue
0:20:05.001,0:20:07.096
and a nice example i think you've all[br]been there
0:20:07.096,0:20:09.012
one way or another
0:20:09.012,0:20:11.015
there's a callus that forms
0:20:11.015,0:20:13.001
in the skin
0:20:13.001,0:20:14.059
if you have a
0:20:14.059,0:20:17.016
ill-fitting pair of shoes and something is rubbing
0:20:17.016,0:20:18.023
on the spot
0:20:18.023,0:20:21.077
or God forbid if you have to do manual[br]labor
0:20:21.077,0:20:26.024
some concerted length of time
0:20:26.024,0:20:29.659
you develop calluses. You've all had this happen. This is an example of
0:20:29.659,0:20:31.062
hyperplasia
0:20:31.062,0:20:33.023
It's a response to this overwork stimulus
0:20:33.023,0:20:35.075
which increases
0:20:35.075,0:20:40.046
or leads to an increase in number of cells in the system
0:20:40.046,0:20:42.001
let me illustrate this
0:20:42.001,0:20:44.079
give you a little histology
0:20:44.079,0:20:47.082
this is basically normal skin
0:20:47.082,0:20:49.011
on the palmar surface of the hand
0:20:49.011,0:20:50.078
this is the dermis, the connective tissue part
0:20:50.078,0:20:51.088
this is the
0:20:51.088,0:20:56.038
epidermis, the epithelial portion
0:20:56.038,0:20:58.065
now this is a renewing
0:20:58.065,0:21:00.659
cell system
0:21:00.659,0:21:01.025
normally
0:21:01.025,0:21:06.023
a certain number of cells are mitosing down here in the basal layer
0:21:06.023,0:21:08.086
and daughter cells are moving out and maturing
0:21:08.086,0:21:13.007
as they move on out
0:21:13.007,0:21:16.016
and this upper layer where you see no nuclei is the
0:21:16.016,0:21:18.038
so-called stratum corneum
0:21:18.038,0:21:20.003
it's like a layer of shingles on the roof
0:21:20.003,0:21:23.064
these cells undergo progressive changes
0:21:23.064,0:21:26.052
in armor plate there
0:21:26.052,0:21:30.018
so the normal palmar skin is set with a certain cell population
0:21:30.018,0:21:31.419
and a certain
0:21:31.419,0:21:36.017
balance where certain cells come and go
0:21:36.017,0:21:38.075
i'll show you the callus
0:21:38.075,0:21:41.048
keep this picture in mind
0:21:41.048,0:21:44.007
and this represents the hyperplasia of the callus
0:21:44.007,0:21:47.000
now you've got
0:21:47.000,0:21:49.009
a much thicker cell population
0:21:49.009,0:21:51.057
it's still a very orderly cell population
0:21:51.057,0:21:55.008
the cells are being born down here and are maturing up here
0:21:55.008,0:21:56.055
there's actually
0:21:56.055,0:21:58.095
so much thickening going on here that I couldn't
0:21:58.095,0:22:00.032
get it all on one picture
0:22:00.032,0:22:02.061
at the same magnification
0:22:02.061,0:22:03.095
here is the beginning of the stratum
0:22:03.095,0:22:05.006
corneum
0:22:05.006,0:22:07.929
there's the rest of it
0:22:07.929,0:22:10.077
and that is a callus
0:22:10.077,0:22:12.022
So you see there is a tremendous
0:22:12.022,0:22:16.031
hyperplasia here in response to this mechanical stimulus
0:22:16.031,0:22:18.069
Now the nice thing
0:22:18.069,0:22:25.001
about hyperplasia, and also applies to hypertrophy, if you get rid of
0:22:25.001,0:22:28.007
the noxious stimulus,
0:22:28.007,0:22:29.419
things pretty much
0:22:29.419,0:22:32.074
wind back to normal. You can't always do that, but
0:22:32.074,0:22:34.028
if you can, if you quit
0:22:34.028,0:22:37.073
raking the ground or whatever you're doing,
0:22:37.073,0:22:39.086
pretty soon those hands will be the ones you know and love.
0:22:39.086,0:22:41.061
The calloused thins out
0:22:41.061,0:22:45.069
and you go back to normal. Now
0:22:45.069,0:22:46.081
I could give you
0:22:46.081,0:22:52.017
other happier examples, maybe, I'll give you one.
0:22:52.017,0:22:53.086
In a hormone sensitive
0:22:53.086,0:22:55.071
tissue that responds
0:22:55.071,0:22:58.034
that response with hyperplasia
0:22:58.034,0:23:00.066
here is a normal
0:23:00.066,0:23:03.041
lobule. This is kind of a potential
0:23:03.041,0:23:04.095
secretory unit,
0:23:04.095,0:23:07.076
a normal lobule of an adult female breast.
0:23:07.076,0:23:08.098
I don't want to go into detail, but
0:23:08.098,0:23:11.053
just to show you the little terminal
0:23:11.053,0:23:15.013
units forming this lobule. During pregnancy
0:23:15.013,0:23:16.799
and lactation,
0:23:16.799,0:23:17.005
this tremendous
0:23:17.005,0:23:19.094
hormonal stimulus to these cells
0:23:19.094,0:23:20.096
makes them undergo
0:23:20.096,0:23:22.033
hyperplasia
0:23:22.033,0:23:23.419
and that lobule
0:23:23.419,0:23:24.062
, take a look
0:23:24.062,0:23:26.035
at the size there
0:23:26.035,0:23:27.051
enlarged
0:23:27.051,0:23:30.007
couldn't even get the whole lobule on the screen there
0:23:30.007,0:23:33.002
This is a lactating mammary gland
0:23:33.002,0:23:34.063
there's a tremendous
0:23:34.063,0:23:38.012
increase in the number of cells, actually some hypertrophy
0:23:38.012,0:23:40.044
in individual cells, but basically
0:23:40.044,0:23:41.087
a whole lot of hyperplasia
0:23:41.087,0:23:44.032
there, and it responds to
0:23:44.032,0:23:46.071
the hormone.
0:23:46.071,0:23:51.056
When the hormonal stimulus is withdrawn at the end of lactation, things pretty much
0:23:51.056,0:23:55.002
go back to normal, plus or minus a little stretching of the connective tissue
0:23:55.002,0:23:57.002
but the epithelial
0:23:57.002,0:24:02.299
population goes back to normal.
0:24:02.299,0:24:06.007
That's hyperplasia, tends to be reversible
0:24:06.007,0:24:09.068
under very nice elegant control
0:24:09.068,0:24:11.091
in some situations
0:24:11.091,0:24:13.083
got to throw this in. Not all good news.
0:24:13.083,0:24:15.093
In some situations, the hyperplasia
0:24:15.093,0:24:17.038
0:24:17.038,0:24:18.073
isn't necessarily
0:24:18.073,0:24:22.053
adaptive and good. We see
0:24:22.053,0:24:25.047
examples of hyperplasia, I'll show two of them.
0:24:25.047,0:24:28.012
0:24:28.012,0:24:29.062
They're probably responses
0:24:29.062,0:24:34.075
to the subtly abnormal endocrine stimulation, somehow
0:24:34.075,0:24:36.045
we don't exactly know.
0:24:36.045,0:24:40.065
but, i think one for the guys, one for the girls
0:24:40.065,0:24:43.062
this is something that is going to afflict about
0:24:43.062,0:24:46.071
forty nine percent of us in the room, one way or the other.
0:24:46.071,0:24:48.005
and this is
0:24:48.005,0:24:50.084
a cross cut of the prostate
0:24:50.084,0:24:51.065
and the
0:24:51.065,0:24:54.035
prostate normally is about the size
0:24:54.035,0:24:56.013
of a golf
0:24:56.013,0:24:59.048
ball, a walnut, a good sized walnut
0:24:59.048,0:25:00.082
and it's right at the base
0:25:00.082,0:25:08.000
the bladder and the urethra. The outflow tract goes through the prostate.
0:25:08.000,0:25:08.034
You're looking at a cross-section there
0:25:08.034,0:25:10.046
and you see the urethra there.
0:25:10.046,0:25:11.096
The normal prostate would be
0:25:11.096,0:25:15.019
nice and smooth across the cut surface.
0:25:15.019,0:25:15.095
Here you see
0:25:15.095,0:25:21.001
a bunch of lumps and this represents
0:25:21.001,0:25:23.004
hyperplasia of
0:25:23.004,0:25:26.031
glandular and muscular tissue, glandular tissue undergoes tremendous hyperplasia.
0:25:26.031,0:25:29.041
we don't know why, and the
0:25:29.041,0:25:31.044
problem with
0:25:31.044,0:25:33.059
is not simply walk around with a tennis ball
0:25:33.059,0:25:39.018
there instead of a walnut, but it rests on the base of the bladder
0:25:39.018,0:25:41.072
and urethra and can cause outflow problems.
0:25:41.072,0:25:46.027
and also urinary tract problems.
0:25:46.027,0:25:49.053
I'll give you a little tidbit that's absolutely useless.
0:25:49.053,0:25:53.039
Eunuchs don't get prostatic hyperplasia,
0:25:53.039,0:25:58.052
but it's not a very popular preventative measure.
0:25:58.052,0:26:02.095
so there's an example, it's not a neoplasm, it's strictly hyperplasia, but it's out of
0:26:02.095,0:26:05.039
kilter and not good.
0:26:05.039,0:26:07.007
for
0:26:07.007,0:26:07.096
the rest of you
0:26:07.096,0:26:09.044
we'll talk about
0:26:09.044,0:26:11.035
a very common condition
0:26:11.035,0:26:13.078
called fibrocystic change in the breast
0:26:13.078,0:26:15.029
now this is
0:26:15.029,0:26:18.062
a non-descript looking piece of tissue
0:26:18.062,0:26:19.047
but if it were perfectly normal
0:26:19.047,0:26:20.094
mostly
0:26:20.094,0:26:23.061
it would be a yellowish background
0:26:23.061,0:26:25.062
because the breast is largely fatty tissue
0:26:25.062,0:26:27.022
and not
0:26:27.022,0:26:30.073
those big yawning things there. So what's happened in this breast
0:26:30.073,0:26:34.028
it's, first of all, increase in fibroblast
0:26:34.028,0:26:38.039
fibrous connective tissue, see these white streaks
0:26:38.039,0:26:39.096
and this represents part of the duct system.
0:26:39.096,0:26:42.000
where the cells increase in number
0:26:42.000,0:26:44.559
and fluid is accumulated in
0:26:44.559,0:26:45.095
what we call cysts,
0:26:45.095,0:26:46.076
a cyst
0:26:46.076,0:26:48.058
is a hollow space filled with fluid
0:26:48.058,0:26:51.089
lined with epithelium
0:26:51.089,0:26:54.076
and so we call this fibrocystic change.
0:26:54.076,0:26:56.064
In and of itself, it's very
0:26:56.064,0:27:00.016
common, in and of itself it's no big deal.
0:27:00.016,0:27:01.052
I'll show you
0:27:01.052,0:27:04.094
what happens conceptually, here again here's the
0:27:04.094,0:27:09.029
normal breast, this is a lobule like I showed you before and this is
0:27:09.029,0:27:15.046
part of the duct system leading to that lobule. That's normal. Now in a fibrocystic
0:27:15.046,0:27:17.012
change, what you see
0:27:17.012,0:27:17.045
is
0:27:17.045,0:27:19.559
this little garbled
0:27:19.559,0:27:20.097
Here's a lobule
0:27:20.097,0:27:22.061
that has undergone
0:27:22.061,0:27:26.097
hyperplasia, pretty evident
0:27:26.097,0:27:28.559
and the duct system, the lining is also
0:27:28.559,0:27:35.085
undergone hyperplasia, the ducts are dilating and eventually form cysts.
0:27:35.085,0:27:38.047
and again we don't know exactly why
0:27:38.047,0:27:43.025
this happens, but it represents hyperplasia
0:27:43.025,0:27:48.058
gone wrong.
0:27:48.058,0:27:59.037
All right, moving right along, what I'm doing is just ticking off these concepts. You can follow this in your reading too.
0:27:59.037,0:28:09.037
I want to move on to proliferation and maturation of cells within a population.
0:28:09.037,0:28:12.005
I'm talking about two particular situations here
0:28:12.005,0:28:13.041
we'll talk first about
0:28:13.041,0:28:17.077
metaplasia and then dysplasia.
0:28:17.077,0:28:23.022
all right, what about metaplasia? We define this as
0:28:23.022,0:28:30.091
a change in the cell population, in which one normal mature special
0:28:30.091,0:28:34.071
cell, I'll clarify this in a moment, but one
0:28:34.071,0:28:37.799
cell type is replaced by another
0:28:37.799,0:28:39.019
normal cell type,
0:28:39.019,0:28:41.007
except it doesn't belong
0:28:41.007,0:28:43.096
there, in other words, it's changed
0:28:43.096,0:28:52.063
that particular location. Now this isn't just a substitution, where this cell
0:28:52.063,0:28:54.003
changes into another cell
0:28:54.003,0:28:56.067
what this is, rather,
0:28:56.067,0:29:02.057
is change in the maturation of stem cells in the population. We've got a proliferating cell population
0:29:02.057,0:29:09.081
where ordinarily the cells mature in this direction, and metaplasia represents
0:29:09.081,0:29:30.061
a switch, under some influence, where they mature in that direction.
0:29:30.061,0:29:36.067
They become more resistant than the normal one and that represents metaplasia.
0:29:36.067,0:29:40.809
Let me illustrate this, try to make sense out of it.
0:29:40.809,0:29:43.056
Here is the lining
0:29:43.056,0:29:45.022
of the
0:29:45.022,0:29:46.017
what we call
0:29:46.017,0:29:49.033
the endocervical canal
0:29:49.033,0:29:54.539
this is the canal that goes up into the uterus. Now normally
0:29:54.539,0:29:56.021
what's going on
0:29:56.021,0:30:00.299
here is that there are certain number of, well, call them stem cells
0:30:00.299,0:30:02.049
or reserved cells that are proliferating
0:30:02.049,0:30:02.051
all the
0:30:02.051,0:30:05.001
time, but they mature
0:30:05.001,0:30:06.044
into these tall
0:30:06.044,0:30:07.036
what we call columnar
0:30:07.036,0:30:09.056
cells, they are
0:30:09.056,0:30:11.091
tall and columnar and they've got
0:30:11.091,0:30:15.083
very pale cytoplasm because they're full of mucus.
0:30:15.083,0:30:22.001
So normally this endocervical canal is lined by this mucus secreting epithelium, very
0:30:22.001,0:30:23.029
slight stimulus
0:30:23.029,0:30:24.065
is all it takes
0:30:24.065,0:30:26.019
and there may be a change
0:30:26.019,0:30:29.001
here you see the normal, here you see a plaque
0:30:29.001,0:30:31.149
of cells that looks a little bit different
0:30:31.149,0:30:33.088
and these cells
0:30:33.088,0:30:35.018
are, well, they're
0:30:35.018,0:30:39.049
odd shapes here, they're maturing into these
0:30:39.049,0:30:43.007
flat cells that we saw on top of the epidermis, and we call this
0:30:43.007,0:30:44.047
these are columnar
0:30:44.047,0:30:47.098
cells, these are squamous cells, we call this squamous
0:30:47.098,0:30:48.079
metaplasia
0:30:48.079,0:30:51.026
very very
0:30:51.026,0:30:52.759
common, some of you
0:30:52.759,0:30:54.539
in this room have this, it's a trivial change
0:30:54.539,0:30:56.023
practically
0:30:56.023,0:31:00.017
ubiquitous in the adult females in the
0:31:00.017,0:31:01.068
endocervix
0:31:01.068,0:31:06.039
it can become quite extreme. Look at this.
0:31:06.039,0:31:14.086
this whole area should be lined by these columnar cells that look this, and instead what we've got here is squamous
0:31:14.086,0:31:20.033
epithelium, looks a lot like the epidermis, doesn't it?
0:31:20.033,0:31:24.015
I would emphasize a couple things
0:31:24.015,0:31:27.073
this is perfectly orderly, you look at this
0:31:27.073,0:31:32.024
and I know you haven't become histologic experts yet
0:31:32.024,0:31:33.008
but that is a perfectly orderly
0:31:33.008,0:31:37.149
squamous epithelium, nothing unusual about it except
0:31:37.149,0:31:38.097
it doesn't belong there.
0:31:38.097,0:31:41.031
So that's an example
0:31:41.031,0:31:43.034
of metaplasia
0:31:43.034,0:31:44.159
in and of itself
0:31:44.159,0:31:45.089
trivial
0:31:45.089,0:31:47.042
or even protective.
0:31:47.042,0:31:49.019
Let's say
0:31:49.019,0:31:52.084
chemical workers were exposed to fumes might develop
0:31:52.084,0:31:53.006
this kind of
0:31:53.006,0:31:59.033
metaplasia in the lining of their trachea and bronchi, that makes them more resistant to whatever they're
0:31:59.033,0:32:02.007
inhaling, smokers develop
0:32:02.007,0:32:03.078
this sort of thing. Now, this could go on
0:32:03.078,0:32:05.047
and something
0:32:05.047,0:32:07.072
else might happen, and this might
0:32:07.072,0:32:09.012
lead to bad
0:32:09.012,0:32:10.071
things, but
0:32:10.071,0:32:12.073
in and of itself, metaplasia
0:32:12.073,0:32:14.061
is perfectly innocent.
0:32:14.061,0:32:16.003
Not so
0:32:16.003,0:32:17.061
with dysplasia.
0:32:17.061,0:32:19.054
D-y-s-p-l-a-s-i-a
0:32:19.054,0:32:23.079
Now morphologically,
0:32:23.079,0:32:42.096
dysplasia is a
0:32:42.096,0:32:45.062
variation, abnormal variation
0:32:45.062,0:32:48.055
in
0:32:48.055,0:32:50.006
the size
0:32:50.006,0:32:51.006
of the cells, the shape of the cells
0:32:51.006,0:32:53.093
the arrangement of the
0:32:53.093,0:32:54.058
cells
0:32:54.058,0:32:57.022
and the maturation of the cells
0:32:57.022,0:32:59.041
too much variation
0:32:59.041,0:33:01.009
in other words
0:33:01.009,0:33:04.034
something very well controlled like this
0:33:04.034,0:33:06.057
this epithelium is very well controlled
0:33:06.057,0:33:08.008
with all the cells down here proliferating
0:33:08.008,0:33:10.062
at a certain rate and maturing gradually
0:33:10.062,0:33:12.002
and so forth
0:33:12.002,0:33:19.025
all of this gets screwed up in dysplasia.
0:33:19.025,0:33:21.029
Here again is a normal squamous
0:33:21.029,0:33:23.028
epithelium, this isn't palmar
0:33:23.028,0:33:28.021
or skin now, this is let's say the lining of the vagina or
0:33:28.021,0:33:32.025
covering of the cervix, one of those, this happens to be cervix
0:33:32.025,0:33:35.034
perfectly normal squamous epithelium, notice how orderly
0:33:35.034,0:33:36.085
it is, it's like a
0:33:36.085,0:33:37.084
kind of like
0:33:37.084,0:33:41.059
a parade where you have cells in
0:33:41.059,0:33:44.006
a certain type down here, they all resemble one another
0:33:44.006,0:33:46.034
in this layer, cells here
0:33:46.034,0:33:49.094
resemble one another, and then there's this maturation
0:33:49.094,0:33:53.046
these flattened out cells, that's occurring in a very orderly
0:33:53.046,0:33:57.086
step fashion. In dysplasia
0:33:57.086,0:34:00.098
of the epithelium, everything gets
0:34:00.098,0:34:08.409
screwed up. All right,
0:34:08.409,0:34:10.329
this is dysplasia.
0:34:10.329,0:34:14.379
and we can see where
0:34:14.379,0:34:18.619
there's a shadow of what you looked at in the preceding slide, but now some things have
0:34:18.619,0:34:20.069
happened, there's more
0:34:20.069,0:34:22.829
variation in any
0:34:22.829,0:34:23.079
layer. In other words,
0:34:23.079,0:34:24.049
0:34:24.049,0:34:29.219
if you look down here, these cells are more variable than those cells were in the basal layer
0:34:29.219,0:34:31.359
in the normal. You look here
0:34:31.359,0:34:33.339
where in the
0:34:33.339,0:34:36.949
preceding slide, every cell in the intermediate zone is perfectly
0:34:36.949,0:34:38.979
like every other cell, there's variation
0:34:38.979,0:34:43.419
here, there's big cells and small cells, round cells and elongated cells
0:34:43.419,0:34:45.009
cells with
0:34:45.009,0:34:48.639
very dark nuclei, cells with lighter nuclei
0:34:48.639,0:34:50.949
and so forth
0:34:50.949,0:34:51.078
and gradually, though, despite
0:34:51.078,0:34:53.539
this mess, there is
0:34:53.539,0:34:54.999
slight
0:34:54.999,0:34:56.009
maturation
0:34:56.009,0:35:01.959
you can see here how this jumble of cells gradually becomes organized
0:35:01.959,0:35:04.689
up here, so what have we got
0:35:04.689,0:35:07.079
we've got abnormal
0:35:07.079,0:35:07.939
variations
0:35:07.939,0:35:11.579
in the size of the cells, the shape of the cells, the arrangement
0:35:11.579,0:35:15.709
of the cells, this is out of order. It's not in a nice, neat, locked set.
0:35:15.709,0:35:16.098
And it's not
0:35:16.098,0:35:21.219
maturing quite properly until it gets to the very top.
0:35:21.219,0:35:23.439
Actually,
0:35:23.439,0:35:28.799
this is trivial for you now, but we grade dysplasia as slight, moderate, severe depending on how much
0:35:28.799,0:35:30.369
normal
0:35:30.369,0:35:32.809
there might be there. But when you see
0:35:32.809,0:35:36.269
this degree of variation, that's a very
0:35:36.269,0:35:39.019
bad thing. There's one other thing
0:35:39.019,0:35:42.499
that's abnormal here, it's a little more subtle, ordinarily
0:35:42.499,0:35:44.969
mitosis occurs only down in this
0:35:44.969,0:35:47.064
basal layer. But these cells
0:35:47.064,0:35:51.519
are goofy enough that they forget about that and they do something very impolite.
0:35:51.519,0:35:53.489
They reproduce out
0:35:53.489,0:35:59.039
in public and you find mitotic figures at all levels of such an epithelium.
0:35:59.039,0:36:00.799
So morphologically,
0:36:00.799,0:36:07.379
this represents a lot of variation.
0:36:07.379,0:36:13.959
This is a serious change because these cells
0:36:13.959,0:36:26.749
are in a sense losing control. They're losing control of proliferation and maturation.
0:36:26.749,0:36:28.067
Any number of mutations
0:36:28.067,0:36:38.809
that occur in the cell population, this reflects genetic change in the cell, somatic cell
0:36:38.809,0:36:56.069
any number of these mutations and this happens. This I want you to remember for the rest of your lives, dysplasia
0:36:56.069,0:36:58.419
in other words, I can't tell you
0:36:58.419,0:37:12.729
that epithelium absolutely for sure will become cancer, it depends I suppose on the last garbled
0:37:12.729,0:37:38.109
mild degree of dysplasia sometimes don't necessarily progress, while very severe degrees of dysplasia can.
0:37:38.109,0:37:39.041
Here is a squamous epithelium
0:37:39.041,0:37:40.889
with what we call severe
0:37:40.889,0:37:42.859
dysplasia, and you can see close
0:37:42.859,0:37:45.139
up what's going on here
0:37:45.139,0:37:48.579
This basal layer is increased in thickness, a lot of variation
0:37:48.579,0:37:49.489
in these cells,
0:37:49.489,0:37:51.299
here is
0:37:51.299,0:37:56.049
a cell dividing, as they say, out in public and there is an absolute total
0:37:56.049,0:37:57.859
jumble
0:37:57.859,0:38:01.379
in terms of how these cells are arranged with respect to one another.
0:38:01.379,0:38:03.094
We call that a loss of polarity.
0:38:03.094,0:38:05.309
And in this instance
0:38:05.309,0:38:16.249
it occurred all the way, full thickness of this epithelium.
0:38:16.249,0:38:20.149
and we now know, from a lot of experience, severe dysplasia
0:38:20.149,0:38:22.089
really is
0:38:22.089,0:38:23.989
tantamount to cancer
0:38:23.989,0:38:27.029
that perhaps hasn't
0:38:27.029,0:38:28.007
yet invaded. Now that'll
0:38:28.007,0:38:34.459
make sense when we talk about what cancer really is. Without
0:38:34.459,0:38:40.179
any evidence of invasion or anything else that cancers usually do
0:38:40.179,0:38:43.849
when dysplasia is this severe, we can say this is like carcinoma-in-situ
0:38:43.849,0:38:46.599
which means an 'in-place' cancer
0:38:46.599,0:38:48.239
pre-invasive
0:38:48.239,0:38:51.069
cancer because we know
0:38:51.069,0:38:51.809
if this sort of
0:38:51.809,0:38:54.649
dysplasia is left alone, probably close
0:38:54.649,0:38:56.229
to 100% will
0:38:56.229,0:39:02.048
evolve into a cancer if the patient lives long enough.
0:39:02.048,0:39:07.609
While I've got this on the screen, I'll point out some cytologic changes that are very important in making
0:39:07.609,0:39:09.019
this decision. First of all
0:39:09.019,0:39:09.098
you'll notice
0:39:09.098,0:39:13.009
there's a lot of variation in size of nuclei. We call that
0:39:13.009,0:39:15.209
nuclear pleomorphism.
0:39:15.209,0:39:16.469
p-l-e-o
0:39:16.469,0:39:18.769
that's a bad sign
0:39:18.769,0:39:19.539
and none of these
0:39:19.539,0:39:23.339
is absolute, but it's a bad sign.
0:39:23.339,0:39:28.669
Some of the nuclei are very dark as you cast your eye around here.
0:39:28.669,0:39:32.889
We would call that nuclear hyperchromatism. Too much
0:39:32.889,0:39:36.749
colored material in the nucleus.
0:39:36.749,0:39:37.119
The nuclei
0:39:37.119,0:39:43.759
are very unusually shaped and sometimes
0:39:43.759,0:39:44.989
you can't see it, but
0:39:44.989,0:39:47.959
sometimes the mitotic figures are themselves
0:39:47.959,0:39:51.319
are even abnormal, may see a tripolar mitotic figure
0:39:51.319,0:39:53.269
or something like that.
0:39:53.269,0:40:01.579
These are all signs of badness in a cell population.
0:40:01.579,0:40:13.319
If something like this is left alone, it will proceed to an invasive cancer. Instead of carcinoma-in-situ, we call it invasive.
0:40:13.319,0:40:18.039
Put a line underneath all of this and now we turn to the main topic -- Neoplasia.
0:40:18.039,0:40:47.559
Spend the rest of this morning and Wednesday morning on this topic. It's ultimately
0:40:47.559,0:40:49.339
more cells than there ought to be, it's an increase in cells
0:40:49.339,0:40:52.189
it's a lump basically
0:40:52.189,0:40:56.219
and these are proliferating cells, they're not just sitting there, they're
0:40:56.219,0:41:01.799
they're dividing and making new cells. And, they're cells that have somehow
0:41:01.799,0:41:23.219
become autonomous
0:41:23.219,0:41:25.279
they don't obey the same start and stop signals
0:41:25.279,0:41:28.159
that normal cells do. Their growth
0:41:28.159,0:41:34.329
tends to be excessive and uncoordinated with the needs of the host.
0:41:34.329,0:41:37.229
In other words, this thing is taking off on its own!
0:41:37.229,0:41:45.899
It's kind of rebellious, I'm going to grow, I don't give a damn about what's going on over here, I'm not going to listen to your signals.
0:41:45.899,0:41:59.729
You want to think teleologically, serves no useful purpose, it's not adaptive.
0:41:59.729,0:42:04.459
Once the neoplasm is formed, it's off and running,
0:42:04.459,0:42:22.849
which is different from hypertrophy and hyperplasia, where once you remove the stimulus, it goes back to normal.
0:42:22.849,0:42:31.289
In some countries, it's the word tumor, which now is practically synonymous with neoplasm.
0:42:31.289,0:42:38.039
It's also one of the cardinal signs of inflammation, the old meaning of tumor simply means swelling. But
0:42:38.039,0:42:48.849
when you say a patient has a tumor, you don't mean swelling, you mean neoplasm. So tumor, neoplasm, same thing.
0:42:48.849,0:43:04.092
'oma' usually denotes a neoplasm of some sort, there are exceptions, hematoma is a lump of blood.
0:43:04.092,0:43:07.769
Different types of neoplasms are distinguished by their behavior,
0:43:07.769,0:43:21.359
which, I think you all know, is benign and malignant. Cancer is a general term which refers only to malignant neoplasms. I don't want to insult you, but
0:43:21.359,0:43:30.709
just so we're on the same page, there are many neoplasms that are not cancer. Only the malignant ones we refer to as cancer.
0:43:30.709,0:43:51.016
Looking at all of these characteristics, they are very different from hyperplasia and hypertrophy, which are generally adaptive.
0:43:51.016,0:44:20.279
A neoplasm is a living, proliferating cell and
0:44:20.279,0:44:27.129
we call this neoplastic transformation, basically, and when speaking of transformed cells, we speak of cells that have acquired
0:44:27.129,0:44:30.479
a set of these new characteristics
0:44:30.479,0:44:45.017
that define them as neoplastic and, as you will hear, usually
0:44:45.017,0:44:48.079
the wrong mutations. We talk about the clonal origin
0:44:48.079,0:45:00.299
of neoplasms, in other words, a neoplasm is a clonal proliferation of a transformed cell.
0:45:00.299,0:45:03.889
This transformed cell has a lot of characteristics
0:45:03.889,0:45:11.499
and behaviors that are quite abnormal and we can see this in vitro when we culture it.
0:45:11.499,0:45:13.699
Malignant cells, for instance,
0:45:13.699,0:45:31.939
they've often lost control of movement that they display on the surface of a plate. There's
0:45:31.939,0:45:55.429
loss of, ordinarily there's control in a cell population where proliferation reaches a certain size, not so with cancer cells. I could go on, there are many different things that occur
0:45:55.429,0:46:11.449
in vitro and in vivo, in the host, it manifests a non-equilibrium growth, at some point, and keeps on growing.
0:46:11.449,0:46:28.679
You will learn that
0:46:28.679,0:46:42.149
there's a difference between benign and malignant. I think this cartoon sums it up well.
0:46:42.149,0:46:52.579
As the neoplasm grows, the number of cells gradually increases, they tend to be cohesive
0:46:52.579,0:46:58.004
there's not any reason for this, just they tend to be cohesive, so as the neoplasm
0:46:58.004,0:47:00.639
grows, and it may grow to a very large
0:47:00.639,0:47:02.489
size, it tends to grow
0:47:02.489,0:47:07.549
by a centrifugal expansion. Now it's not a perfect circle, but
0:47:07.549,0:47:13.039
it tends to grow by expansion. As it expands,
0:47:13.039,0:47:14.909
it frequently will pick up
0:47:14.909,0:47:15.499
a
0:47:15.499,0:47:18.078
condensed capsule of connective tissue as it pushes out
0:47:18.078,0:47:20.169
causes atrophy of surrounding tissues
0:47:20.169,0:47:25.579
and will accumulate a kind of capsule almost and anyway
0:47:25.579,0:47:26.219
at any rate
0:47:26.219,0:47:32.719
it stays local, its size, and it doesn't invade
0:47:32.719,0:47:38.038
adjacent tissues, just pushes them out of the way, or it may press up, but it's like blowing up a
0:47:38.038,0:48:04.479
balloon in the thing. On the average,
0:48:04.479,0:48:07.029
this is not as cohesive as this suggests
0:48:07.029,0:48:11.619
it grows, the cells have a great tendency of invading
0:48:11.619,0:48:12.829
what we call the primary,
0:48:12.829,0:48:16.659
they tend to drift
0:48:16.659,0:48:20.939
away and don't obey the stop and start signals.
0:48:20.939,0:48:22.046
They have a very different relationship
0:48:22.046,0:48:25.091
with the cellular matrix and basically
0:48:25.091,0:48:27.039
they have
0:48:27.039,0:48:32.909
the ability, this is the primary difference, to cut their way
0:48:32.909,0:48:35.519
through
0:48:35.519,0:48:36.066
the adjacent stroma
0:48:36.066,0:48:39.519
and actually invade as clumps of cells,
0:48:39.519,0:48:43.069
lines of cells, individual cells,
0:48:43.069,0:48:44.349
Invasion is one
0:48:44.349,0:48:47.042
of the defining
0:48:47.042,0:48:55.289
characteristics of malignancy. When I said the malignant ones tend to grow faster than benign ones, that's not a defining difference.
0:48:55.289,0:49:03.709
They have to be invasive to be malignant.
0:49:03.709,0:49:05.075
One other, well this sums it up,
0:49:05.075,0:49:08.519
cohesive, expansile, circumscribed, localized
0:49:08.519,0:49:13.119
that's benign. Malignant is poorly circumscribed, invasive, metastasizing.
0:49:13.119,0:49:13.659
That means
0:49:13.659,0:49:21.099
it can spread to distant foci, we'll talk about that in just a moment. But it's invasion
0:49:21.099,0:49:32.399
and metastasis that define malignancy. Benign neoplasms do not metastasize.
0:49:32.399,0:49:37.579
Here's a uterus
0:49:37.579,0:49:41.429
cut sort of in
0:49:41.429,0:49:43.769
sagittal sections, this is the cervix
0:49:43.769,0:49:47.013
down here, this is a normal one half
0:49:47.013,0:49:48.919
this is the cavity here, here is a
0:49:48.919,0:49:52.729
neoplasm.
0:49:52.729,0:49:57.379
Benign or malignant? See, it works.
0:49:57.379,0:49:58.031
This is what you
0:49:58.031,0:49:59.619
probably grew up hearing, a fibroid.
0:49:59.619,0:50:01.088
Uterine fibroid.
0:50:01.088,0:50:04.809
That's a misnomer, because it isn't
0:50:04.809,0:50:08.779
a fibrous tumor, it's a muscular tumor
0:50:08.779,0:50:10.459
one we call a leiomyoma.
0:50:10.459,0:50:13.629
But you can see it's got, just like the cartoon, pushing at the edges.
0:50:13.629,0:50:15.719
You look at that microscopically,
0:50:15.719,0:50:16.619
same sort of thing
0:50:16.619,0:50:18.159
here's a
0:50:18.159,0:50:20.059
tumor, here's the
0:50:20.059,0:50:24.179
edge along here, no invasion.
0:50:24.179,0:50:28.089
Can see it just pushing, pressing along that adjacent line.
0:50:28.089,0:50:31.329
Here's a breast
0:50:31.329,0:50:32.989
that's been
0:50:32.989,0:50:33.819
taken off
0:50:33.819,0:50:37.549
a mastectomy specimen and it's been cut in this plane,
0:50:37.549,0:50:39.539
a section where you can see
0:50:39.539,0:50:41.669
the skin out here, and this is the neoplasm
0:50:41.669,0:50:43.039
very very hard
0:50:43.039,0:50:45.008
to define and circumscribe.
0:50:45.008,0:50:47.209
It's going out in little
0:50:47.209,0:50:48.669
sites in the adjacent
0:50:48.669,0:50:49.589
tissue, even
0:50:49.589,0:50:51.051
way beyond this microscopically
0:50:51.051,0:50:54.013
there are lines of cells that you couldn't see here.
0:50:54.013,0:50:57.229
That's invasion. A benign neoplasm
0:50:57.229,0:50:59.559
wouldn't look like that.
0:50:59.559,0:51:01.419
Here's one that's a little deceptive at first.
0:51:01.419,0:51:02.004
This is a colon cancer,
0:51:02.004,0:51:06.009
we've opened the colon and washed it off. You might
0:51:06.009,0:51:08.519
say, at first, gee that's circumscribed,
0:51:08.519,0:51:10.989
isn't it? Well, not exactly.
0:51:10.989,0:51:13.179
What I did here is
0:51:13.179,0:51:14.093
fix this in formaldehyde
0:51:14.093,0:51:17.539
and then made a cut
0:51:17.539,0:51:21.069
across it, and it looks like
0:51:21.069,0:51:23.269
this. Now this doesn't look so
0:51:23.269,0:51:25.599
awful, but it really is.
0:51:25.599,0:51:30.067
Here's the normal mucous membrane up here, this layer we call sub-mucosa,
0:51:30.067,0:51:33.569
this is the muscular wall of the colon here.
0:51:33.569,0:51:36.509
Here is that mushroom
0:51:36.509,0:51:39.679
and you can see this whitish tissue, this is neoplasm, invade
0:51:39.679,0:51:41.349
all the way through that muscular layer.
0:51:41.349,0:51:44.729
This is invasion.
0:51:44.729,0:51:49.919
This is what it looks
0:51:49.919,0:51:52.639
like microscopically, don't worry about this.
0:51:52.639,0:51:55.269
duct cells, hyperchromatic, pleomorphic nuclei,
0:51:55.269,0:51:58.529
and so forth.
0:51:58.529,0:52:03.459
These cancer cells are cutting right through the colonic wall, it's not that simple,
0:52:03.459,0:52:05.579
but they're cutting right through that colonic wall
0:52:05.579,0:52:08.729
and invading. That constitutes
0:52:08.729,0:52:13.015
the evidence
0:52:13.015,0:52:18.369
that this is a malignant neoplasm.
0:52:18.369,9:59:59.000
Let's take a break.