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(From M1 Patients and Populations at University of Michigan Medical School. Lecture by Gerald Abrams, MD.)
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
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
then an hour Wednesday
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on the subject of neoplasms, that is
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
then a very interesting MDC in the afternoon,
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dealing with some clinical aspects of
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
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
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
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
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
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
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
definitive adult size and then shrinks
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that process i think you know from
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
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
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
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
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
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
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
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
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
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
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
to have these pictures on hand
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one of things you'll encounter when you
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
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
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
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
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
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
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
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undergo atrophy with shrinkage of individual cells
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sometimes loss of cells or both
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but it's a secondary change after the
the organ has reached its definitive size
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some
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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
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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
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areas where the tissues tend to simply shrink
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starvation
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you don't
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feed a person enough calories, starvation will produce
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atrophy. there's a hierarchy of organs which i don't want to go into
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for instance, the brain doesn't atrophy
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in that situation
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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
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disuse
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just plain old disuse will cause atrophy
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it could be very striking
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i don't know if any of you have been in this situation, but you have an acute injury
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like, oh let's say,
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a bad knee, for some reason, just self splinting
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not using that leg in the same way
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will cause a shrinkage within a few weeks
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you can get a loss in circumference of a thigh
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i don't know how many of you are skiiers
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that have gotten into
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trouble and ended up with let's say a cast on an extremity
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for a number of weeks and when that cast comes off, you've got a shriveled leg
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compared to the other one
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that is disuse atrophy
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an extreme example of that is something we call neurogenic atrophy, if you cut
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the motor
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nerve going to a muscle
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then that muscle can't work at all and is getting
no signals
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it'll really shrink, it's a tremendous sort of atrophy
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then
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well, i'll stop this list with one more
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many tissues in the body are
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the way they are because they have a
certain endocrine support
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they depend on a certain level of a particular
hormone, and if you withdraw that hormone, the tissue
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will undergo atrophy. Morphologically
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it's pretty
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straight forward, i'm not going to show you much of this
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it's simply the tissue
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is smaller
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you look at it under the microscope and the
individual cells are smaller
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the number of cells, that's a tougher thing to deal
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with, but basically it's a small tissue
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sometimes there's partial fibrous replacement as the tissues shrink
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we call that fibrous atrophy
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sometimes
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this seems to be an increase in adipose
tissue, marbling the tissue, we call that fatty atrophy
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but basically the business cells of the tissue
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are smaller
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there's one variation on this theme that
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Ramsburgh may have introduced you to and that's
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as a cell shrinks
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it basically
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is undergoing a process of autophagy, it's eating itself, it's digesting
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various of its
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organelles and so forth
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one of the things that happens
from this digestive process is that there
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may be residual products
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left afterwards and
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they
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tend to be pigmented products which we've
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we refer to as lipofuscin
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here's a liver where particularly in
this area, the central area, the cells
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are shrunken and you'll
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notice this is not a particularly good photo, but you'll notice they are brown
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and that's
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because of a relative concentration of lipofuscin there
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they've been undergoing
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autophagy
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and the residual products are piling
up and sometimes we refer to this as pigment atrophy
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or brown atrophy
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and i've seen shrunken livers where there's perhaps half the mass of the usual liver
270
00:12:42,044 --> 00:12:43,001
and they're really
271
00:12:43,001 --> 00:12:44,639
definite
272
00:12:44,639 --> 00:12:46,038
brown
273
00:12:46,038 --> 00:12:47,699
rather than the ordinary
274
00:12:47,699 --> 00:12:48,649
liver color
275
00:12:48,649 --> 00:12:50,869
because of this sort of accumulation
276
00:12:50,869 --> 00:12:53,019
Okay so
277
00:12:53,019 --> 00:12:57,007
much for smaller than normal, let's go to the flip side
278
00:12:57,007 --> 00:13:00,959
and look at situations where the tissue
or the organ may be larger
279
00:13:00,959 --> 00:13:02,029
than normal
280
00:13:02,029 --> 00:13:03,048
and this
281
00:13:03,048 --> 00:13:07,004
can come about in two ways
282
00:13:07,004 --> 00:13:11,088
you can have an increase in the size of
the cells in the tissue
283
00:13:11,088 --> 00:13:15,008
and we refer to that as hypertrophy
284
00:13:15,008 --> 00:13:19,015
you can have an increase in the number
of cells in the tissue, we call that hyperplasia
285
00:13:19,015 --> 00:13:21,007
Now let's go back
286
00:13:21,007 --> 00:13:23,074
up to hypertrophy
287
00:13:23,074 --> 00:13:28,022
let me point out that size increase isn't simply cell swelling, you know
288
00:13:28,022 --> 00:13:32,061
about the phenomenon of cell swelling, which involves a net accumulation of water
289
00:13:32,061 --> 00:13:35,062
that we wouldn't call hypertrophy
290
00:13:35,062 --> 00:13:39,065
in hypertrophy, the cells enlarge because of an increased
291
00:13:39,065 --> 00:13:41,006
synthesis
292
00:13:41,006 --> 00:13:43,048
of cellular components
293
00:13:43,048 --> 00:13:44,779
i'll show you that in a
294
00:13:44,779 --> 00:13:46,012
moment
295
00:13:46,012 --> 00:13:48,002
again hyperplasia
296
00:13:48,002 --> 00:13:51,074
involves an increase in cell number so you'd look
297
00:13:51,074 --> 00:13:55,007
for hyperplasia only in tissues that are capable of
298
00:13:55,007 --> 00:13:57,079
dividing in the adult state
299
00:13:57,079 --> 00:14:00,049
another was a permanent sort of tissue
300
00:14:00,049 --> 00:14:03,083
you're not going to get hyperplasia ordinarily in muscle
301
00:14:03,083 --> 00:14:05,006
you're not going to get
302
00:14:05,006 --> 00:14:11,026
hyperplasia, well muscle is probably the best example. but in other
303
00:14:11,026 --> 00:14:12,093
organs, you may
304
00:14:12,093 --> 00:14:16,052
get hyperplasia along with hypertrophy
305
00:14:16,052 --> 00:14:17,095
but conceptually hypertrophy
306
00:14:17,095 --> 00:14:22,399
is increase in cell size, hyperplasia is increase in cell
307
00:14:22,399 --> 00:14:24,249
number
308
00:14:24,249 --> 00:14:26,072
the
309
00:14:26,072 --> 00:14:33,073
best example of hypertrophy is in muscular tissues
310
00:14:33,073 --> 00:14:35,053
it's a response
311
00:14:35,053 --> 00:14:38,077
hypertrophy in muscle is a response to an overload
312
00:14:38,077 --> 00:14:42,057
or unusual workload or what not
313
00:14:42,057 --> 00:14:46,038
now you need a lot of imagination for this, but imagine i went in for bodybuilding
314
00:14:46,038 --> 00:14:48,032
which i never will
315
00:14:48,032 --> 00:14:51,067
and you know you you pump three hundred
pounds like this
316
00:14:51,067 --> 00:14:53,015
and after a while couldn't
317
00:14:53,015 --> 00:14:55,078
get into the lab coat. Bulging
318
00:14:55,078 --> 00:14:59,027
muscles, i told you, imagination.
319
00:14:59,027 --> 00:15:00,042
the
320
00:15:00,042 --> 00:15:03,409
muscles of the bodybuilder
321
00:15:03,409 --> 00:15:06,429
you've all seen pictures of this and maybe some of you are into this sort of sport
322
00:15:06,429 --> 00:15:07,075
this
323
00:15:07,075 --> 00:15:09,689
represents
324
00:15:09,689 --> 00:15:10,047
hypertrophy
325
00:15:10,047 --> 00:15:15,004
of muscle, there isn't any real increase in the number of muscle cells
326
00:15:15,004 --> 00:15:18,078
but any individual muscle cells instead of being this big around is this big around
327
00:15:18,078 --> 00:15:20,009
and it
328
00:15:20,009 --> 00:15:23,001
represents actually a synthesis of more
329
00:15:23,001 --> 00:15:26,007
contractile machinery
330
00:15:26,007 --> 00:15:27,829
in the muscle, it's a response
331
00:15:27,829 --> 00:15:30,034
to the work
332
00:15:30,034 --> 00:15:33,084
now a place where we see this that isn't so trivial
333
00:15:33,084 --> 00:15:35,003
is
334
00:15:35,003 --> 00:15:37,018
is, for instance, heart muscle
335
00:15:37,018 --> 00:15:41,005
that is subjected to an abnormal load
336
00:15:41,005 --> 00:15:44,094
for instance, a left ventricle
337
00:15:44,094 --> 00:15:51,094
having to pump blood in a patient with uncontrolled hypertension
338
00:15:51,094 --> 00:15:55,007
in other words, the systemic blood pressure is elevated, the arteriolar resistance is elevated
339
00:15:55,007 --> 00:15:58,439
and every time that poor old left ventricle
340
00:15:58,439 --> 00:16:02,082
tries to eject blood, it's doing it against an increased head of pressure
341
00:16:02,082 --> 00:16:06,089
those muscles are going to undergo
hypertrophy
342
00:16:06,089 --> 00:16:07,097
or
343
00:16:07,097 --> 00:16:11,009
let's say the valve, the so-called
aortic valve, which is a valve between
344
00:16:11,009 --> 00:16:17,047
the left ventricle and the aorta, as the blood flows out, if that valve gets narrowed
345
00:16:17,047 --> 00:16:20,011
the poor old ventricle has to squeeze harder to get
346
00:16:20,011 --> 00:16:23,003
the blood out to maintain life, it will
undergo hypertrophy
347
00:16:23,003 --> 00:16:24,139
not hyperplasia
348
00:16:24,139 --> 00:16:25,119
but hypertrophy
349
00:16:25,119 --> 00:16:26,059
and the
350
00:16:26,059 --> 00:16:29,037
heart gains weight
351
00:16:29,037 --> 00:16:31,031
the ventricle becomes thick
352
00:16:31,031 --> 00:16:35,092
and the cells become enlarged. I'll illustrate this for you.
353
00:16:35,092 --> 00:16:37,049
here is
354
00:16:37,049 --> 00:16:41,042
don't pay attention to the color, there have been
some post-mortem changes here but
355
00:16:41,042 --> 00:16:43,739
this is a bread loaf slice
356
00:16:43,739 --> 00:16:45,041
of a normal heart
357
00:16:45,041 --> 00:16:47,919
you're looking at the right ventricle
over here
358
00:16:47,919 --> 00:16:52,209
left ventricle over here ordinarily, this is normal, the right ventricle is very thin
359
00:16:52,209 --> 00:16:57,014
because it pumps against a lesser head of pressure in the pulmonary circuit. The left ventricle
360
00:16:57,014 --> 00:16:59,559
,that's about normal thickness,
361
00:16:59,559 --> 00:17:01,002
now the next slide
362
00:17:01,002 --> 00:17:05,036
is not a photo trick and again
don't worry about the colors, but the next
363
00:17:05,036 --> 00:17:12,021
slide is taken from an individual with high blood pressure
364
00:17:12,021 --> 00:17:15,015
now that first heart probably weighed
365
00:17:15,015 --> 00:17:18,819
oh in the neighborhood of three hundred, three hundred and twenty five grams
366
00:17:18,819 --> 00:17:20,045
this heart weighed closer
367
00:17:20,045 --> 00:17:24,022
to the six or seven hundred grams, i don't remember precisely, but
368
00:17:24,022 --> 00:17:28,005
it kind of speaks for itself, there is more muscle
there
369
00:17:28,005 --> 00:17:31,099
and again this is not hyperplasia, this is
hypertrophy
370
00:17:31,099 --> 00:17:36,045
and it looks something like this. i know you don't know much of this histology
371
00:17:36,045 --> 00:17:37,088
but just
372
00:17:37,088 --> 00:17:41,046
think of these as cross-sections of these cylindrical muscle cells
373
00:17:41,046 --> 00:17:42,086
and this is
374
00:17:42,086 --> 00:17:44,091
a normal myocardium
375
00:17:44,091 --> 00:17:45,063
and
376
00:17:45,063 --> 00:17:50,052
let's just cast your eyeballs around and look at the approximate
377
00:17:50,052 --> 00:17:54,083
average diameter
378
00:17:54,083 --> 00:17:55,057
the next slide
379
00:17:55,057 --> 00:17:58,059
is taken with the same optics in the microscope
380
00:17:58,059 --> 00:18:04,006
from a hypertrophic heart, now you got this?
381
00:18:04,006 --> 00:18:04,071
The point
382
00:18:04,071 --> 00:18:08,809
those cells are really increased in diameter, don't worry about this, I don't expect you to
383
00:18:08,809 --> 00:18:11,049
pick this up on the quiz
384
00:18:11,049 --> 00:18:13,007
but just to show you
385
00:18:13,007 --> 00:18:14,003
the increase
386
00:18:14,003 --> 00:18:19,019
and what this represents really is an increase, a very striking increase
387
00:18:19,019 --> 00:18:21,058
in the myofibrillar contractile machinery
388
00:18:21,058 --> 00:18:24,079
of these cells
389
00:18:24,079 --> 00:18:28,679
so this is clearly an adaptive
390
00:18:28,679 --> 00:18:30,052
phenomenon
391
00:18:30,052 --> 00:18:33,056
and it works very well up to a point
392
00:18:33,056 --> 00:18:38,092
the heart can't keep getting more and more and more hypertrophic
393
00:18:38,092 --> 00:18:40,069
i've never seen a heart
394
00:18:40,069 --> 00:18:42,081
weigh much more than a kilogram
395
00:18:42,081 --> 00:18:44,309
and that's rare
396
00:18:44,309 --> 00:18:45,049
but beyond that
397
00:18:45,049 --> 00:18:46,809
it doesn't work
398
00:18:46,809 --> 00:18:51,299
and one of the reasons that it doesn't work
is that the vascularity of the blood supply
399
00:18:51,299 --> 00:18:53,008
of the heart
400
00:18:53,008 --> 00:18:56,017
muscle doesn't keep up
401
00:18:56,017 --> 00:18:59,038
with too much hypertrophy and pretty soon
402
00:18:59,038 --> 00:19:03,067
the muscle to capillary ratio is unfavorable
403
00:19:03,067 --> 00:19:06,095
and it plateaus, it can't go any further
404
00:19:06,095 --> 00:19:12,012
and then what you get is the onset of apoptosis in cells and actually some
405
00:19:12,012 --> 00:19:17,001
fibrous replacement of the myocardium so it doesn't work indefinitely
406
00:19:17,001 --> 00:19:17,061
actually some
407
00:19:17,061 --> 00:19:19,084
of the proteins that are formed
408
00:19:19,084 --> 00:19:22,081
are not necessarily normal either
409
00:19:22,081 --> 00:19:23,089
so hypertrophy
410
00:19:23,089 --> 00:19:30,045
is nice and adaptive up to a point, but beyond that
411
00:19:30,045 --> 00:19:33,091
i might mention that before we leave hypertrophy that this also goes on in other types of
412
00:19:33,091 --> 00:19:35,067
of muscle
413
00:19:35,067 --> 00:19:36,009
as you may
414
00:19:36,009 --> 00:19:40,043
know for instance, the wall of the urinary bladder is muscle but
415
00:19:40,043 --> 00:19:43,061
this kind of muscle is what we call smooth muscle
416
00:19:43,061 --> 00:19:46,051
but if there is a chronic obstruction to
bladder outflow
417
00:19:46,051 --> 00:19:48,066
you get a very thick muscular bladder
418
00:19:48,066 --> 00:19:51,066
the same kind of response
419
00:19:51,066 --> 00:19:55,048
hypertrophy of the muscle cells
420
00:19:55,048 --> 00:19:57,077
we return to hyperplasia
421
00:19:57,077 --> 00:19:59,919
lots of examples i can give you
422
00:19:59,919 --> 00:20:00,044
of increased
423
00:20:00,044 --> 00:20:02,004
in
424
00:20:02,004 --> 00:20:02,098
the number of cells
425
00:20:02,098 --> 00:20:05,001
in the tissue
426
00:20:05,001 --> 00:20:07,096
and a nice example i think you've all
been there
427
00:20:07,096 --> 00:20:09,012
one way or another
428
00:20:09,012 --> 00:20:11,015
there's a callus that forms
429
00:20:11,015 --> 00:20:13,001
in the skin
430
00:20:13,001 --> 00:20:14,059
if you have a
431
00:20:14,059 --> 00:20:17,016
ill-fitting pair of shoes and something is rubbing
432
00:20:17,016 --> 00:20:18,023
on the spot
433
00:20:18,023 --> 00:20:21,077
or God forbid if you have to do manual
labor
434
00:20:21,077 --> 00:20:26,024
some concerted length of time
435
00:20:26,024 --> 00:20:29,659
you develop calluses. You've all had this happen. This is an example of
436
00:20:29,659 --> 00:20:31,062
hyperplasia
437
00:20:31,062 --> 00:20:33,023
It's a response to this overwork stimulus
438
00:20:33,023 --> 00:20:35,075
which increases
439
00:20:35,075 --> 00:20:40,046
or leads to an increase in number of cells in the system
440
00:20:40,046 --> 00:20:42,001
let me illustrate this
441
00:20:42,001 --> 00:20:44,079
give you a little histology
442
00:20:44,079 --> 00:20:47,082
this is basically normal skin
443
00:20:47,082 --> 00:20:49,011
on the palmar surface of the hand
444
00:20:49,011 --> 00:20:50,078
this is the dermis, the connective tissue part
445
00:20:50,078 --> 00:20:51,088
this is the
446
00:20:51,088 --> 00:20:56,038
epidermis, the epithelial portion
447
00:20:56,038 --> 00:20:58,065
now this is a renewing
448
00:20:58,065 --> 00:21:00,659
cell system
449
00:21:00,659 --> 00:21:01,025
normally
450
00:21:01,025 --> 00:21:06,023
a certain number of cells are mitosing down here in the basal layer
451
00:21:06,023 --> 00:21:08,086
and daughter cells are moving out and maturing
452
00:21:08,086 --> 00:21:13,007
as they move on out
453
00:21:13,007 --> 00:21:16,016
and this upper layer where you see no nuclei is the
454
00:21:16,016 --> 00:21:18,038
so-called stratum corneum
455
00:21:18,038 --> 00:21:20,003
it's like a layer of shingles on the roof
456
00:21:20,003 --> 00:21:23,064
these cells undergo progressive changes
457
00:21:23,064 --> 00:21:26,052
in armor plate there
458
00:21:26,052 --> 00:21:30,018
so the normal palmar skin is set with a certain cell population
459
00:21:30,018 --> 00:21:31,419
and a certain
460
00:21:31,419 --> 00:21:36,017
balance where certain cells come and go
461
00:21:36,017 --> 00:21:38,075
i'll show you the callus
462
00:21:38,075 --> 00:21:41,048
keep this picture in mind
463
00:21:41,048 --> 00:21:44,007
and this represents the hyperplasia of the callus
464
00:21:44,007 --> 00:21:47,000
now you've got
465
00:21:47,000 --> 00:21:49,009
a much thicker cell population
466
00:21:49,009 --> 00:21:51,057
it's still a very orderly cell population
467
00:21:51,057 --> 00:21:55,008
the cells are being born down here and are maturing up here
468
00:21:55,008 --> 00:21:56,055
there's actually
469
00:21:56,055 --> 00:21:58,095
so much thickening going on here that I couldn't
470
00:21:58,095 --> 00:22:00,032
get it all on one picture
471
00:22:00,032 --> 00:22:02,061
at the same magnification
472
00:22:02,061 --> 00:22:03,095
here is the beginning of the stratum
473
00:22:03,095 --> 00:22:05,006
corneum
474
00:22:05,006 --> 00:22:07,929
there's the rest of it
475
00:22:07,929 --> 00:22:10,077
and that is a callus
476
00:22:10,077 --> 00:22:12,022
So you see there is a tremendous
477
00:22:12,022 --> 00:22:16,031
hyperplasia here in response to this mechanical stimulus
478
00:22:16,031 --> 00:22:18,069
Now the nice thing
479
00:22:18,069 --> 00:22:25,001
about hyperplasia, and also applies to hypertrophy, if you get rid of
480
00:22:25,001 --> 00:22:28,007
the noxious stimulus,
481
00:22:28,007 --> 00:22:29,419
things pretty much
482
00:22:29,419 --> 00:22:32,074
wind back to normal. You can't always do that, but
483
00:22:32,074 --> 00:22:34,028
if you can, if you quit
484
00:22:34,028 --> 00:22:37,073
raking the ground or whatever you're doing,
485
00:22:37,073 --> 00:22:39,086
pretty soon those hands will be the ones you know and love.
486
00:22:39,086 --> 00:22:41,061
The calloused thins out
487
00:22:41,061 --> 00:22:45,069
and you go back to normal. Now
488
00:22:45,069 --> 00:22:46,081
I could give you
489
00:22:46,081 --> 00:22:52,017
other happier examples, maybe, I'll give you one.
490
00:22:52,017 --> 00:22:53,086
In a hormone sensitive
491
00:22:53,086 --> 00:22:55,071
tissue that responds
492
00:22:55,071 --> 00:22:58,034
that response with hyperplasia
493
00:22:58,034 --> 00:23:00,066
here is a normal
494
00:23:00,066 --> 00:23:03,041
lobule. This is kind of a potential
495
00:23:03,041 --> 00:23:04,095
secretory unit,
496
00:23:04,095 --> 00:23:07,076
a normal lobule of an adult female breast.
497
00:23:07,076 --> 00:23:08,098
I don't want to go into detail, but
498
00:23:08,098 --> 00:23:11,053
just to show you the little terminal
499
00:23:11,053 --> 00:23:15,013
units forming this lobule. During pregnancy
500
00:23:15,013 --> 00:23:16,799
and lactation,
501
00:23:16,799 --> 00:23:17,005
this tremendous
502
00:23:17,005 --> 00:23:19,094
hormonal stimulus to these cells
503
00:23:19,094 --> 00:23:20,096
makes them undergo
504
00:23:20,096 --> 00:23:22,033
hyperplasia
505
00:23:22,033 --> 00:23:23,419
and that lobule
506
00:23:23,419 --> 00:23:24,062
, take a look
507
00:23:24,062 --> 00:23:26,035
at the size there
508
00:23:26,035 --> 00:23:27,051
enlarged
509
00:23:27,051 --> 00:23:30,007
couldn't even get the whole lobule on the screen there
510
00:23:30,007 --> 00:23:33,002
This is a lactating mammary gland
511
00:23:33,002 --> 00:23:34,063
there's a tremendous
512
00:23:34,063 --> 00:23:38,012
increase in the number of cells, actually some hypertrophy
513
00:23:38,012 --> 00:23:40,044
in individual cells, but basically
514
00:23:40,044 --> 00:23:41,087
a whole lot of hyperplasia
515
00:23:41,087 --> 00:23:44,032
there, and it responds to
516
00:23:44,032 --> 00:23:46,071
the hormone.
517
00:23:46,071 --> 00:23:51,056
When the hormonal stimulus is withdrawn at the end of lactation, things pretty much
518
00:23:51,056 --> 00:23:55,002
go back to normal, plus or minus a little stretching of the connective tissue
519
00:23:55,002 --> 00:23:57,002
but the epithelial
520
00:23:57,002 --> 00:24:02,299
population goes back to normal.
521
00:24:02,299 --> 00:24:06,007
That's hyperplasia, tends to be reversible
522
00:24:06,007 --> 00:24:09,068
under very nice elegant control
523
00:24:09,068 --> 00:24:11,091
in some situations
524
00:24:11,091 --> 00:24:13,083
got to throw this in. Not all good news.
525
00:24:13,083 --> 00:24:15,093
In some situations, the hyperplasia
526
00:24:15,093 --> 00:24:17,038
527
00:24:17,038 --> 00:24:18,073
isn't necessarily
528
00:24:18,073 --> 00:24:22,053
adaptive and good. We see
529
00:24:22,053 --> 00:24:25,047
examples of hyperplasia, I'll show two of them.
530
00:24:25,047 --> 00:24:28,012
531
00:24:28,012 --> 00:24:29,062
They're probably responses
532
00:24:29,062 --> 00:24:34,075
to the subtly abnormal endocrine stimulation, somehow
533
00:24:34,075 --> 00:24:36,045
we don't exactly know.
534
00:24:36,045 --> 00:24:40,065
but, i think one for the guys, one for the girls
535
00:24:40,065 --> 00:24:43,062
this is something that is going to afflict about
536
00:24:43,062 --> 00:24:46,071
forty nine percent of us in the room, one way or the other.
537
00:24:46,071 --> 00:24:48,005
and this is
538
00:24:48,005 --> 00:24:50,084
a cross cut of the prostate
539
00:24:50,084 --> 00:24:51,065
and the
540
00:24:51,065 --> 00:24:54,035
prostate normally is about the size
541
00:24:54,035 --> 00:24:56,013
of a golf
542
00:24:56,013 --> 00:24:59,048
ball, a walnut, a good sized walnut
543
00:24:59,048 --> 00:25:00,082
and it's right at the base
544
00:25:00,082 --> 00:25:08,000
the bladder and the urethra. The outflow tract goes through the prostate.
545
00:25:08,000 --> 00:25:08,034
You're looking at a cross-section there
546
00:25:08,034 --> 00:25:10,046
and you see the urethra there.
547
00:25:10,046 --> 00:25:11,096
The normal prostate would be
548
00:25:11,096 --> 00:25:15,019
nice and smooth across the cut surface.
549
00:25:15,019 --> 00:25:15,095
Here you see
550
00:25:15,095 --> 00:25:21,001
a bunch of lumps and this represents
551
00:25:21,001 --> 00:25:23,004
hyperplasia of
552
00:25:23,004 --> 00:25:26,031
glandular and muscular tissue, glandular tissue undergoes tremendous hyperplasia.
553
00:25:26,031 --> 00:25:29,041
we don't know why, and the
554
00:25:29,041 --> 00:25:31,044
problem with
555
00:25:31,044 --> 00:25:33,059
is not simply walk around with a tennis ball
556
00:25:33,059 --> 00:25:39,018
there instead of a walnut, but it rests on the base of the bladder
557
00:25:39,018 --> 00:25:41,072
and urethra and can cause outflow problems.
558
00:25:41,072 --> 00:25:46,027
and also urinary tract problems.
559
00:25:46,027 --> 00:25:49,053
I'll give you a little tidbit that's absolutely useless.
560
00:25:49,053 --> 00:25:53,039
Eunuchs don't get prostatic hyperplasia,
561
00:25:53,039 --> 00:25:58,052
but it's not a very popular preventative measure.
562
00:25:58,052 --> 00:26:02,095
so there's an example, it's not a neoplasm, it's strictly hyperplasia, but it's out of
563
00:26:02,095 --> 00:26:05,039
kilter and not good.
564
00:26:05,039 --> 00:26:07,007
for
565
00:26:07,007 --> 00:26:07,096
the rest of you
566
00:26:07,096 --> 00:26:09,044
we'll talk about
567
00:26:09,044 --> 00:26:11,035
a very common condition
568
00:26:11,035 --> 00:26:13,078
called fibrocystic change in the breast
569
00:26:13,078 --> 00:26:15,029
now this is
570
00:26:15,029 --> 00:26:18,062
a non-descript looking piece of tissue
571
00:26:18,062 --> 00:26:19,047
but if it were perfectly normal
572
00:26:19,047 --> 00:26:20,094
mostly
573
00:26:20,094 --> 00:26:23,061
it would be a yellowish background
574
00:26:23,061 --> 00:26:25,062
because the breast is largely fatty tissue
575
00:26:25,062 --> 00:26:27,022
and not
576
00:26:27,022 --> 00:26:30,073
those big yawning things there. So what's happened in this breast
577
00:26:30,073 --> 00:26:34,028
it's, first of all, increase in fibroblast
578
00:26:34,028 --> 00:26:38,039
fibrous connective tissue, see these white streaks
579
00:26:38,039 --> 00:26:39,096
and this represents part of the duct system.
580
00:26:39,096 --> 00:26:42,000
where the cells increase in number
581
00:26:42,000 --> 00:26:44,559
and fluid is accumulated in
582
00:26:44,559 --> 00:26:45,095
what we call cysts,
583
00:26:45,095 --> 00:26:46,076
a cyst
584
00:26:46,076 --> 00:26:48,058
is a hollow space filled with fluid
585
00:26:48,058 --> 00:26:51,089
lined with epithelium
586
00:26:51,089 --> 00:26:54,076
and so we call this fibrocystic change.
587
00:26:54,076 --> 00:26:56,064
In and of itself, it's very
588
00:26:56,064 --> 00:27:00,016
common, in and of itself it's no big deal.
589
00:27:00,016 --> 00:27:01,052
I'll show you
590
00:27:01,052 --> 00:27:04,094
what happens conceptually, here again here's the
591
00:27:04,094 --> 00:27:09,029
normal breast, this is a lobule like I showed you before and this is
592
00:27:09,029 --> 00:27:15,046
part of the duct system leading to that lobule. That's normal. Now in a fibrocystic
593
00:27:15,046 --> 00:27:17,012
change, what you see
594
00:27:17,012 --> 00:27:17,045
is
595
00:27:17,045 --> 00:27:19,559
this little garbled
596
00:27:19,559 --> 00:27:20,097
Here's a lobule
597
00:27:20,097 --> 00:27:22,061
that has undergone
598
00:27:22,061 --> 00:27:26,097
hyperplasia, pretty evident
599
00:27:26,097 --> 00:27:28,559
and the duct system, the lining is also
600
00:27:28,559 --> 00:27:35,085
undergone hyperplasia, the ducts are dilating and eventually form cysts.
601
00:27:35,085 --> 00:27:38,047
and again we don't know exactly why
602
00:27:38,047 --> 00:27:43,025
this happens, but it represents hyperplasia
603
00:27:43,025 --> 00:27:48,058
gone wrong.
604
00:27:48,058 --> 00:27:59,037
All right, moving right along, what I'm doing is just ticking off these concepts. You can follow this in your reading too.
605
00:27:59,037 --> 00:28:09,037
I want to move on to proliferation and maturation of cells within a population.
606
00:28:09,037 --> 00:28:12,005
I'm talking about two particular situations here
607
00:28:12,005 --> 00:28:13,041
we'll talk first about
608
00:28:13,041 --> 00:28:17,077
metaplasia and then dysplasia.
609
00:28:17,077 --> 00:28:23,022
all right, what about metaplasia? We define this as
610
00:28:23,022 --> 00:28:30,091
a change in the cell population, in which one normal mature special
611
00:28:30,091 --> 00:28:34,071
cell, I'll clarify this in a moment, but one
612
00:28:34,071 --> 00:28:37,799
cell type is replaced by another
613
00:28:37,799 --> 00:28:39,019
normal cell type,
614
00:28:39,019 --> 00:28:41,007
except it doesn't belong
615
00:28:41,007 --> 00:28:43,096
there, in other words, it's changed
616
00:28:43,096 --> 00:28:52,063
that particular location. Now this isn't just a substitution, where this cell
617
00:28:52,063 --> 00:28:54,003
changes into another cell
618
00:28:54,003 --> 00:28:56,067
what this is, rather,
619
00:28:56,067 --> 00:29:02,057
is change in the maturation of stem cells in the population. We've got a proliferating cell population
620
00:29:02,057 --> 00:29:09,081
where ordinarily the cells mature in this direction, and metaplasia represents
621
00:29:09,081 --> 00:29:30,061
a switch, under some influence, where they mature in that direction.
622
00:29:30,061 --> 00:29:36,067
They become more resistant than the normal one and that represents metaplasia.
623
00:29:36,067 --> 00:29:40,809
Let me illustrate this, try to make sense out of it.
624
00:29:40,809 --> 00:29:43,056
Here is the lining
625
00:29:43,056 --> 00:29:45,022
of the
626
00:29:45,022 --> 00:29:46,017
what we call
627
00:29:46,017 --> 00:29:49,033
the endocervical canal
628
00:29:49,033 --> 00:29:54,539
this is the canal that goes up into the uterus. Now normally
629
00:29:54,539 --> 00:29:56,021
what's going on
630
00:29:56,021 --> 00:30:00,299
here is that there are certain number of, well, call them stem cells
631
00:30:00,299 --> 00:30:02,049
or reserved cells that are proliferating
632
00:30:02,049 --> 00:30:02,051
all the
633
00:30:02,051 --> 00:30:05,001
time, but they mature
634
00:30:05,001 --> 00:30:06,044
into these tall
635
00:30:06,044 --> 00:30:07,036
what we call columnar
636
00:30:07,036 --> 00:30:09,056
cells, they are
637
00:30:09,056 --> 00:30:11,091
tall and columnar and they've got
638
00:30:11,091 --> 00:30:15,083
very pale cytoplasm because they're full of mucus.
639
00:30:15,083 --> 00:30:22,001
So normally this endocervical canal is lined by this mucus secreting epithelium, very
640
00:30:22,001 --> 00:30:23,029
slight stimulus
641
00:30:23,029 --> 00:30:24,065
is all it takes
642
00:30:24,065 --> 00:30:26,019
and there may be a change
643
00:30:26,019 --> 00:30:29,001
here you see the normal, here you see a plaque
644
00:30:29,001 --> 00:30:31,149
of cells that looks a little bit different
645
00:30:31,149 --> 00:30:33,088
and these cells
646
00:30:33,088 --> 00:30:35,018
are, well, they're
647
00:30:35,018 --> 00:30:39,049
odd shapes here, they're maturing into these
648
00:30:39,049 --> 00:30:43,007
flat cells that we saw on top of the epidermis, and we call this
649
00:30:43,007 --> 00:30:44,047
these are columnar
650
00:30:44,047 --> 00:30:47,098
cells, these are squamous cells, we call this squamous
651
00:30:47,098 --> 00:30:48,079
metaplasia
652
00:30:48,079 --> 00:30:51,026
very very
653
00:30:51,026 --> 00:30:52,759
common, some of you
654
00:30:52,759 --> 00:30:54,539
in this room have this, it's a trivial change
655
00:30:54,539 --> 00:30:56,023
practically
656
00:30:56,023 --> 00:31:00,017
ubiquitous in the adult females in the
657
00:31:00,017 --> 00:31:01,068
endocervix
658
00:31:01,068 --> 00:31:06,039
it can become quite extreme. Look at this.
659
00:31:06,039 --> 00:31:14,086
this whole area should be lined by these columnar cells that look this, and instead what we've got here is squamous
660
00:31:14,086 --> 00:31:20,033
epithelium, looks a lot like the epidermis, doesn't it?
661
00:31:20,033 --> 00:31:24,015
I would emphasize a couple things
662
00:31:24,015 --> 00:31:27,073
this is perfectly orderly, you look at this
663
00:31:27,073 --> 00:31:32,024
and I know you haven't become histologic experts yet
664
00:31:32,024 --> 00:31:33,008
but that is a perfectly orderly
665
00:31:33,008 --> 00:31:37,149
squamous epithelium, nothing unusual about it except
666
00:31:37,149 --> 00:31:38,097
it doesn't belong there.
667
00:31:38,097 --> 00:31:41,031
So that's an example
668
00:31:41,031 --> 00:31:43,034
of metaplasia
669
00:31:43,034 --> 00:31:44,159
in and of itself
670
00:31:44,159 --> 00:31:45,089
trivial
671
00:31:45,089 --> 00:31:47,042
or even protective.
672
00:31:47,042 --> 00:31:49,019
Let's say
673
00:31:49,019 --> 00:31:52,084
chemical workers were exposed to fumes might develop
674
00:31:52,084 --> 00:31:53,006
this kind of
675
00:31:53,006 --> 00:31:59,033
metaplasia in the lining of their trachea and bronchi, that makes them more resistant to whatever they're
676
00:31:59,033 --> 00:32:02,007
inhaling, smokers develop
677
00:32:02,007 --> 00:32:03,078
this sort of thing. Now, this could go on
678
00:32:03,078 --> 00:32:05,047
and something
679
00:32:05,047 --> 00:32:07,072
else might happen, and this might
680
00:32:07,072 --> 00:32:09,012
lead to bad
681
00:32:09,012 --> 00:32:10,071
things, but
682
00:32:10,071 --> 00:32:12,073
in and of itself, metaplasia
683
00:32:12,073 --> 00:32:14,061
is perfectly innocent.
684
00:32:14,061 --> 00:32:16,003
Not so
685
00:32:16,003 --> 00:32:17,061
with dysplasia.
686
00:32:17,061 --> 00:32:19,054
D-y-s-p-l-a-s-i-a
687
00:32:19,054 --> 00:32:23,079
Now morphologically,
688
00:32:23,079 --> 00:32:42,096
dysplasia is a
689
00:32:42,096 --> 00:32:45,062
variation, abnormal variation
690
00:32:45,062 --> 00:32:48,055
in
691
00:32:48,055 --> 00:32:50,006
the size
692
00:32:50,006 --> 00:32:51,006
of the cells, the shape of the cells
693
00:32:51,006 --> 00:32:53,093
the arrangement of the
694
00:32:53,093 --> 00:32:54,058
cells
695
00:32:54,058 --> 00:32:57,022
and the maturation of the cells
696
00:32:57,022 --> 00:32:59,041
too much variation
697
00:32:59,041 --> 00:33:01,009
in other words
698
00:33:01,009 --> 00:33:04,034
something very well controlled like this
699
00:33:04,034 --> 00:33:06,057
this epithelium is very well controlled
700
00:33:06,057 --> 00:33:08,008
with all the cells down here proliferating
701
00:33:08,008 --> 00:33:10,062
at a certain rate and maturing gradually
702
00:33:10,062 --> 00:33:12,002
and so forth
703
00:33:12,002 --> 00:33:19,025
all of this gets screwed up in dysplasia.
704
00:33:19,025 --> 00:33:21,029
Here again is a normal squamous
705
00:33:21,029 --> 00:33:23,028
epithelium, this isn't palmar
706
00:33:23,028 --> 00:33:28,021
or skin now, this is let's say the lining of the vagina or
707
00:33:28,021 --> 00:33:32,025
covering of the cervix, one of those, this happens to be cervix
708
00:33:32,025 --> 00:33:35,034
perfectly normal squamous epithelium, notice how orderly
709
00:33:35,034 --> 00:33:36,085
it is, it's like a
710
00:33:36,085 --> 00:33:37,084
kind of like
711
00:33:37,084 --> 00:33:41,059
a parade where you have cells in
712
00:33:41,059 --> 00:33:44,006
a certain type down here, they all resemble one another
713
00:33:44,006 --> 00:33:46,034
in this layer, cells here
714
00:33:46,034 --> 00:33:49,094
resemble one another, and then there's this maturation
715
00:33:49,094 --> 00:33:53,046
these flattened out cells, that's occurring in a very orderly
716
00:33:53,046 --> 00:33:57,086
step fashion. In dysplasia
717
00:33:57,086 --> 00:34:00,098
of the epithelium, everything gets
718
00:34:00,098 --> 00:34:08,409
screwed up. All right,
719
00:34:08,409 --> 00:34:10,329
this is dysplasia.
720
00:34:10,329 --> 00:34:14,379
and we can see where
721
00:34:14,379 --> 00:34:18,619
there's a shadow of what you looked at in the preceding slide, but now some things have
722
00:34:18,619 --> 00:34:20,069
happened, there's more
723
00:34:20,069 --> 00:34:22,829
variation in any
724
00:34:22,829 --> 00:34:23,079
layer. In other words,
725
00:34:23,079 --> 00:34:24,049
726
00:34:24,049 --> 00:34:29,219
if you look down here, these cells are more variable than those cells were in the basal layer
727
00:34:29,219 --> 00:34:31,359
in the normal. You look here
728
00:34:31,359 --> 00:34:33,339
where in the
729
00:34:33,339 --> 00:34:36,949
preceding slide, every cell in the intermediate zone is perfectly
730
00:34:36,949 --> 00:34:38,979
like every other cell, there's variation
731
00:34:38,979 --> 00:34:43,419
here, there's big cells and small cells, round cells and elongated cells
732
00:34:43,419 --> 00:34:45,009
cells with
733
00:34:45,009 --> 00:34:48,639
very dark nuclei, cells with lighter nuclei
734
00:34:48,639 --> 00:34:50,949
and so forth
735
00:34:50,949 --> 00:34:51,078
and gradually, though, despite
736
00:34:51,078 --> 00:34:53,539
this mess, there is
737
00:34:53,539 --> 00:34:54,999
slight
738
00:34:54,999 --> 00:34:56,009
maturation
739
00:34:56,009 --> 00:35:01,959
you can see here how this jumble of cells gradually becomes organized
740
00:35:01,959 --> 00:35:04,689
up here, so what have we got
741
00:35:04,689 --> 00:35:07,079
we've got abnormal
742
00:35:07,079 --> 00:35:07,939
variations
743
00:35:07,939 --> 00:35:11,579
in the size of the cells, the shape of the cells, the arrangement
744
00:35:11,579 --> 00:35:15,709
of the cells, this is out of order. It's not in a nice, neat, locked set.
745
00:35:15,709 --> 00:35:16,098
And it's not
746
00:35:16,098 --> 00:35:21,219
maturing quite properly until it gets to the very top.
747
00:35:21,219 --> 00:35:23,439
Actually,
748
00:35:23,439 --> 00:35:28,799
this is trivial for you now, but we grade dysplasia as slight, moderate, severe depending on how much
749
00:35:28,799 --> 00:35:30,369
normal
750
00:35:30,369 --> 00:35:32,809
there might be there. But when you see
751
00:35:32,809 --> 00:35:36,269
this degree of variation, that's a very
752
00:35:36,269 --> 00:35:39,019
bad thing. There's one other thing
753
00:35:39,019 --> 00:35:42,499
that's abnormal here, it's a little more subtle, ordinarily
754
00:35:42,499 --> 00:35:44,969
mitosis occurs only down in this
755
00:35:44,969 --> 00:35:47,064
basal layer. But these cells
756
00:35:47,064 --> 00:35:51,519
are goofy enough that they forget about that and they do something very impolite.
757
00:35:51,519 --> 00:35:53,489
They reproduce out
758
00:35:53,489 --> 00:35:59,039
in public and you find mitotic figures at all levels of such an epithelium.
759
00:35:59,039 --> 00:36:00,799
So morphologically,
760
00:36:00,799 --> 00:36:07,379
this represents a lot of variation.
761
00:36:07,379 --> 00:36:13,959
This is a serious change because these cells
762
00:36:13,959 --> 00:36:26,749
are in a sense losing control. They're losing control of proliferation and maturation.
763
00:36:26,749 --> 00:36:28,067
Any number of mutations
764
00:36:28,067 --> 00:36:38,809
that occur in the cell population, this reflects genetic change in the cell, somatic cell
765
00:36:38,809 --> 00:36:56,069
any number of these mutations and this happens. This I want you to remember for the rest of your lives, dysplasia
766
00:36:56,069 --> 00:36:58,419
in other words, I can't tell you
767
00:36:58,419 --> 00:37:12,729
that epithelium absolutely for sure will become cancer, it depends I suppose on the last garbled
768
00:37:12,729 --> 00:37:38,109
mild degree of dysplasia sometimes don't necessarily progress, while very severe degrees of dysplasia can.
769
00:37:38,109 --> 00:37:39,041
Here is a squamous epithelium
770
00:37:39,041 --> 00:37:40,889
with what we call severe
771
00:37:40,889 --> 00:37:42,859
dysplasia, and you can see close
772
00:37:42,859 --> 00:37:45,139
up what's going on here
773
00:37:45,139 --> 00:37:48,579
This basal layer is increased in thickness, a lot of variation
774
00:37:48,579 --> 00:37:49,489
in these cells,
775
00:37:49,489 --> 00:37:51,299
here is
776
00:37:51,299 --> 00:37:56,049
a cell dividing, as they say, out in public and there is an absolute total
777
00:37:56,049 --> 00:37:57,859
jumble
778
00:37:57,859 --> 00:38:01,379
in terms of how these cells are arranged with respect to one another.
779
00:38:01,379 --> 00:38:03,094
We call that a loss of polarity.
780
00:38:03,094 --> 00:38:05,309
And in this instance
781
00:38:05,309 --> 00:38:16,249
it occurred all the way, full thickness of this epithelium.
782
00:38:16,249 --> 00:38:20,149
and we now know, from a lot of experience, severe dysplasia
783
00:38:20,149 --> 00:38:22,089
really is
784
00:38:22,089 --> 00:38:23,989
tantamount to cancer
785
00:38:23,989 --> 00:38:27,029
that perhaps hasn't
786
00:38:27,029 --> 00:38:28,007
yet invaded. Now that'll
787
00:38:28,007 --> 00:38:34,459
make sense when we talk about what cancer really is. Without
788
00:38:34,459 --> 00:38:40,179
any evidence of invasion or anything else that cancers usually do
789
00:38:40,179 --> 00:38:43,849
when dysplasia is this severe, we can say this is like carcinoma-in-situ
790
00:38:43,849 --> 00:38:46,599
which means an 'in-place' cancer
791
00:38:46,599 --> 00:38:48,239
pre-invasive
792
00:38:48,239 --> 00:38:51,069
cancer because we know
793
00:38:51,069 --> 00:38:51,809
if this sort of
794
00:38:51,809 --> 00:38:54,649
dysplasia is left alone, probably close
795
00:38:54,649 --> 00:38:56,229
to 100% will
796
00:38:56,229 --> 00:39:02,048
evolve into a cancer if the patient lives long enough.
797
00:39:02,048 --> 00:39:07,609
While I've got this on the screen, I'll point out some cytologic changes that are very important in making
798
00:39:07,609 --> 00:39:09,019
this decision. First of all
799
00:39:09,019 --> 00:39:09,098
you'll notice
800
00:39:09,098 --> 00:39:13,009
there's a lot of variation in size of nuclei. We call that
801
00:39:13,009 --> 00:39:15,209
nuclear pleomorphism.
802
00:39:15,209 --> 00:39:16,469
p-l-e-o
803
00:39:16,469 --> 00:39:18,769
that's a bad sign
804
00:39:18,769 --> 00:39:19,539
and none of these
805
00:39:19,539 --> 00:39:23,339
is absolute, but it's a bad sign.
806
00:39:23,339 --> 00:39:28,669
Some of the nuclei are very dark as you cast your eye around here.
807
00:39:28,669 --> 00:39:32,889
We would call that nuclear hyperchromatism. Too much
808
00:39:32,889 --> 00:39:36,749
colored material in the nucleus.
809
00:39:36,749 --> 00:39:37,119
The nuclei
810
00:39:37,119 --> 00:39:43,759
are very unusually shaped and sometimes
811
00:39:43,759 --> 00:39:44,989
you can't see it, but
812
00:39:44,989 --> 00:39:47,959
sometimes the mitotic figures are themselves
813
00:39:47,959 --> 00:39:51,319
are even abnormal, may see a tripolar mitotic figure
814
00:39:51,319 --> 00:39:53,269
or something like that.
815
00:39:53,269 --> 00:40:01,579
These are all signs of badness in a cell population.
816
00:40:01,579 --> 00:40:13,319
If something like this is left alone, it will proceed to an invasive cancer. Instead of carcinoma-in-situ, we call it invasive.
817
00:40:13,319 --> 00:40:18,039
Put a line underneath all of this and now we turn to the main topic -- Neoplasia.
818
00:40:18,039 --> 00:40:47,559
Spend the rest of this morning and Wednesday morning on this topic. It's ultimately
819
00:40:47,559 --> 00:40:49,339
more cells than there ought to be, it's an increase in cells
820
00:40:49,339 --> 00:40:52,189
it's a lump basically
821
00:40:52,189 --> 00:40:56,219
and these are proliferating cells, they're not just sitting there, they're
822
00:40:56,219 --> 00:41:01,799
they're dividing and making new cells. And, they're cells that have somehow
823
00:41:01,799 --> 00:41:23,219
become autonomous
824
00:41:23,219 --> 00:41:25,279
they don't obey the same start and stop signals
825
00:41:25,279 --> 00:41:28,159
that normal cells do. Their growth
826
00:41:28,159 --> 00:41:34,329
tends to be excessive and uncoordinated with the needs of the host.
827
00:41:34,329 --> 00:41:37,229
In other words, this thing is taking off on its own!
828
00:41:37,229 --> 00:41:45,899
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.
829
00:41:45,899 --> 00:41:59,729
You want to think teleologically, serves no useful purpose, it's not adaptive.
830
00:41:59,729 --> 00:42:04,459
Once the neoplasm is formed, it's off and running,
831
00:42:04,459 --> 00:42:22,849
which is different from hypertrophy and hyperplasia, where once you remove the stimulus, it goes back to normal.
832
00:42:22,849 --> 00:42:31,289
In some countries, it's the word tumor, which now is practically synonymous with neoplasm.
833
00:42:31,289 --> 00:42:38,039
It's also one of the cardinal signs of inflammation, the old meaning of tumor simply means swelling. But
834
00:42:38,039 --> 00:42:48,849
when you say a patient has a tumor, you don't mean swelling, you mean neoplasm. So tumor, neoplasm, same thing.
835
00:42:48,849 --> 00:43:04,092
'oma' usually denotes a neoplasm of some sort, there are exceptions, hematoma is a lump of blood.
836
00:43:04,092 --> 00:43:07,769
Different types of neoplasms are distinguished by their behavior,
837
00:43:07,769 --> 00:43:21,359
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
838
00:43:21,359 --> 00:43:30,709
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.
839
00:43:30,709 --> 00:43:51,016
Looking at all of these characteristics, they are very different from hyperplasia and hypertrophy, which are generally adaptive.
840
00:43:51,016 --> 00:44:20,279
A neoplasm is a living, proliferating cell and
841
00:44:20,279 --> 00:44:27,129
we call this neoplastic transformation, basically, and when speaking of transformed cells, we speak of cells that have acquired
842
00:44:27,129 --> 00:44:30,479
a set of these new characteristics
843
00:44:30,479 --> 00:44:45,017
that define them as neoplastic and, as you will hear, usually
844
00:44:45,017 --> 00:44:48,079
the wrong mutations. We talk about the clonal origin
845
00:44:48,079 --> 00:45:00,299
of neoplasms, in other words, a neoplasm is a clonal proliferation of a transformed cell.
846
00:45:00,299 --> 00:45:03,889
This transformed cell has a lot of characteristics
847
00:45:03,889 --> 00:45:11,499
and behaviors that are quite abnormal and we can see this in vitro when we culture it.
848
00:45:11,499 --> 00:45:13,699
Malignant cells, for instance,
849
00:45:13,699 --> 00:45:31,939
they've often lost control of movement that they display on the surface of a plate. There's
850
00:45:31,939 --> 00:45:55,429
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
851
00:45:55,429 --> 00:46:11,449
in vitro and in vivo, in the host, it manifests a non-equilibrium growth, at some point, and keeps on growing.
852
00:46:11,449 --> 00:46:28,679
You will learn that
853
00:46:28,679 --> 00:46:42,149
there's a difference between benign and malignant. I think this cartoon sums it up well.
854
00:46:42,149 --> 00:46:52,579
As the neoplasm grows, the number of cells gradually increases, they tend to be cohesive
855
00:46:52,579 --> 00:46:58,004
there's not any reason for this, just they tend to be cohesive, so as the neoplasm
856
00:46:58,004 --> 00:47:00,639
grows, and it may grow to a very large
857
00:47:00,639 --> 00:47:02,489
size, it tends to grow
858
00:47:02,489 --> 00:47:07,549
by a centrifugal expansion. Now it's not a perfect circle, but
859
00:47:07,549 --> 00:47:13,039
it tends to grow by expansion. As it expands,
860
00:47:13,039 --> 00:47:14,909
it frequently will pick up
861
00:47:14,909 --> 00:47:15,499
a
862
00:47:15,499 --> 00:47:18,078
condensed capsule of connective tissue as it pushes out
863
00:47:18,078 --> 00:47:20,169
causes atrophy of surrounding tissues
864
00:47:20,169 --> 00:47:25,579
and will accumulate a kind of capsule almost and anyway
865
00:47:25,579 --> 00:47:26,219
at any rate
866
00:47:26,219 --> 00:47:32,719
it stays local, its size, and it doesn't invade
867
00:47:32,719 --> 00:47:38,038
adjacent tissues, just pushes them out of the way, or it may press up, but it's like blowing up a
868
00:47:38,038 --> 00:48:04,479
balloon in the thing. On the average,
869
00:48:04,479 --> 00:48:07,029
this is not as cohesive as this suggests
870
00:48:07,029 --> 00:48:11,619
it grows, the cells have a great tendency of invading
871
00:48:11,619 --> 00:48:12,829
what we call the primary,
872
00:48:12,829 --> 00:48:16,659
they tend to drift
873
00:48:16,659 --> 00:48:20,939
away and don't obey the stop and start signals.
874
00:48:20,939 --> 00:48:22,046
They have a very different relationship
875
00:48:22,046 --> 00:48:25,091
with the cellular matrix and basically
876
00:48:25,091 --> 00:48:27,039
they have
877
00:48:27,039 --> 00:48:32,909
the ability, this is the primary difference, to cut their way
878
00:48:32,909 --> 00:48:35,519
through
879
00:48:35,519 --> 00:48:36,066
the adjacent stroma
880
00:48:36,066 --> 00:48:39,519
and actually invade as clumps of cells,
881
00:48:39,519 --> 00:48:43,069
lines of cells, individual cells,
882
00:48:43,069 --> 00:48:44,349
Invasion is one
883
00:48:44,349 --> 00:48:47,042
of the defining
884
00:48:47,042 --> 00:48:55,289
characteristics of malignancy. When I said the malignant ones tend to grow faster than benign ones, that's not a defining difference.
885
00:48:55,289 --> 00:49:03,709
They have to be invasive to be malignant.
886
00:49:03,709 --> 00:49:05,075
One other, well this sums it up,
887
00:49:05,075 --> 00:49:08,519
cohesive, expansile, circumscribed, localized
888
00:49:08,519 --> 00:49:13,119
that's benign. Malignant is poorly circumscribed, invasive, metastasizing.
889
00:49:13,119 --> 00:49:13,659
That means
890
00:49:13,659 --> 00:49:21,099
it can spread to distant foci, we'll talk about that in just a moment. But it's invasion
891
00:49:21,099 --> 00:49:32,399
and metastasis that define malignancy. Benign neoplasms do not metastasize.
892
00:49:32,399 --> 00:49:37,579
Here's a uterus
893
00:49:37,579 --> 00:49:41,429
cut sort of in
894
00:49:41,429 --> 00:49:43,769
sagittal sections, this is the cervix
895
00:49:43,769 --> 00:49:47,013
down here, this is a normal one half
896
00:49:47,013 --> 00:49:48,919
this is the cavity here, here is a
897
00:49:48,919 --> 00:49:52,729
neoplasm.
898
00:49:52,729 --> 00:49:57,379
Benign or malignant? See, it works.
899
00:49:57,379 --> 00:49:58,031
This is what you
900
00:49:58,031 --> 00:49:59,619
probably grew up hearing, a fibroid.
901
00:49:59,619 --> 00:50:01,088
Uterine fibroid.
902
00:50:01,088 --> 00:50:04,809
That's a misnomer, because it isn't
903
00:50:04,809 --> 00:50:08,779
a fibrous tumor, it's a muscular tumor
904
00:50:08,779 --> 00:50:10,459
one we call a leiomyoma.
905
00:50:10,459 --> 00:50:13,629
But you can see it's got, just like the cartoon, pushing at the edges.
906
00:50:13,629 --> 00:50:15,719
You look at that microscopically,
907
00:50:15,719 --> 00:50:16,619
same sort of thing
908
00:50:16,619 --> 00:50:18,159
here's a
909
00:50:18,159 --> 00:50:20,059
tumor, here's the
910
00:50:20,059 --> 00:50:24,179
edge along here, no invasion.
911
00:50:24,179 --> 00:50:28,089
Can see it just pushing, pressing along that adjacent line.
912
00:50:28,089 --> 00:50:31,329
Here's a breast
913
00:50:31,329 --> 00:50:32,989
that's been
914
00:50:32,989 --> 00:50:33,819
taken off
915
00:50:33,819 --> 00:50:37,549
a mastectomy specimen and it's been cut in this plane,
916
00:50:37,549 --> 00:50:39,539
a section where you can see
917
00:50:39,539 --> 00:50:41,669
the skin out here, and this is the neoplasm
918
00:50:41,669 --> 00:50:43,039
very very hard
919
00:50:43,039 --> 00:50:45,008
to define and circumscribe.
920
00:50:45,008 --> 00:50:47,209
It's going out in little
921
00:50:47,209 --> 00:50:48,669
sites in the adjacent
922
00:50:48,669 --> 00:50:49,589
tissue, even
923
00:50:49,589 --> 00:50:51,051
way beyond this microscopically
924
00:50:51,051 --> 00:50:54,013
there are lines of cells that you couldn't see here.
925
00:50:54,013 --> 00:50:57,229
That's invasion. A benign neoplasm
926
00:50:57,229 --> 00:50:59,559
wouldn't look like that.
927
00:50:59,559 --> 00:51:01,419
Here's one that's a little deceptive at first.
928
00:51:01,419 --> 00:51:02,004
This is a colon cancer,
929
00:51:02,004 --> 00:51:06,009
we've opened the colon and washed it off. You might
930
00:51:06,009 --> 00:51:08,519
say, at first, gee that's circumscribed,
931
00:51:08,519 --> 00:51:10,989
isn't it? Well, not exactly.
932
00:51:10,989 --> 00:51:13,179
What I did here is
933
00:51:13,179 --> 00:51:14,093
fix this in formaldehyde
934
00:51:14,093 --> 00:51:17,539
and then made a cut
935
00:51:17,539 --> 00:51:21,069
across it, and it looks like
936
00:51:21,069 --> 00:51:23,269
this. Now this doesn't look so
937
00:51:23,269 --> 00:51:25,599
awful, but it really is.
938
00:51:25,599 --> 00:51:30,067
Here's the normal mucous membrane up here, this layer we call sub-mucosa,
939
00:51:30,067 --> 00:51:33,569
this is the muscular wall of the colon here.
940
00:51:33,569 --> 00:51:36,509
Here is that mushroom
941
00:51:36,509 --> 00:51:39,679
and you can see this whitish tissue, this is neoplasm, invade
942
00:51:39,679 --> 00:51:41,349
all the way through that muscular layer.
943
00:51:41,349 --> 00:51:44,729
This is invasion.
944
00:51:44,729 --> 00:51:49,919
This is what it looks
945
00:51:49,919 --> 00:51:52,639
like microscopically, don't worry about this.
946
00:51:52,639 --> 00:51:55,269
duct cells, hyperchromatic, pleomorphic nuclei,
947
00:51:55,269 --> 00:51:58,529
and so forth.
948
00:51:58,529 --> 00:52:03,459
These cancer cells are cutting right through the colonic wall, it's not that simple,
949
00:52:03,459 --> 00:52:05,579
but they're cutting right through that colonic wall
950
00:52:05,579 --> 00:52:08,729
and invading. That constitutes
951
00:52:08,729 --> 00:52:13,015
the evidence
952
00:52:13,015 --> 00:52:18,369
that this is a malignant neoplasm.
953
00:52:18,369 --> 99:59:59,999
Let's take a break.