WEBVTT
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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
00:10:07.099 --> 00:10:12.034
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
00:11:11.095 --> 00:11:15.096
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
00:11:35.009 --> 00:11:40.027
Ramsburgh may have introduced you to and that's
00:11:40.027 --> 00:11:43.046
as a cell shrinks
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it basically
00:11:45.071 --> 00:11:50.042
is undergoing a process of autophagy, it's eating itself, it's digesting
00:11:50.042 --> 00:11:52.019
various of its
00:11:52.019 --> 00:11:55.003
organelles and so forth
00:11:55.003 --> 00:12:00.038
one of the things that happens
from this digestive process is that there
00:12:00.038 --> 00:12:02.369
may be residual products
00:12:02.369 --> 00:12:04.057
left afterwards and
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they
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tend to be pigmented products which we've
00:12:07.077 --> 00:12:10.087
we refer to as lipofuscin
00:12:10.087 --> 00:12:13.061
00:12:13.061 --> 00:12:18.055
here's a liver where particularly in
this area, the central area, the cells
00:12:18.055 --> 00:12:20.054
are shrunken and you'll
00:12:20.054 --> 00:12:23.085
notice this is not a particularly good photo, but you'll notice they are brown
00:12:23.085 --> 00:12:25.037
and that's
00:12:25.037 --> 00:12:28.006
because of a relative concentration of lipofuscin there
00:12:28.006 --> 00:12:29.829
they've been undergoing
00:12:29.829 --> 00:12:31.031
autophagy
00:12:31.031 --> 00:12:36.035
and the residual products are piling
up and sometimes we refer to this as pigment atrophy
00:12:36.035 --> 00:12:38.009
or brown atrophy
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and i've seen shrunken livers where there's perhaps half the mass of the usual liver
00:12:42.044 --> 00:12:43.001
and they're really
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definite
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brown
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rather than the ordinary
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liver color
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because of this sort of accumulation
00:12:50.869 --> 00:12:53.019
Okay so
00:12:53.019 --> 00:12:57.007
much for smaller than normal, let's go to the flip side
00:12:57.007 --> 00:13:00.959
and look at situations where the tissue
or the organ may be larger
00:13:00.959 --> 00:13:02.029
than normal
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and this
00:13:03.048 --> 00:13:07.004
can come about in two ways
00:13:07.004 --> 00:13:11.088
you can have an increase in the size of
the cells in the tissue
00:13:11.088 --> 00:13:15.008
and we refer to that as hypertrophy
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
00:13:19.015 --> 00:13:21.007
Now let's go back
00:13:21.007 --> 00:13:23.074
up to hypertrophy
00:13:23.074 --> 00:13:28.022
let me point out that size increase isn't simply cell swelling, you know
00:13:28.022 --> 00:13:32.061
about the phenomenon of cell swelling, which involves a net accumulation of water
00:13:32.061 --> 00:13:35.062
that we wouldn't call hypertrophy
00:13:35.062 --> 00:13:39.065
in hypertrophy, the cells enlarge because of an increased
00:13:39.065 --> 00:13:41.006
synthesis
00:13:41.006 --> 00:13:43.048
of cellular components
00:13:43.048 --> 00:13:44.779
i'll show you that in a
00:13:44.779 --> 00:13:46.012
moment
00:13:46.012 --> 00:13:48.002
again hyperplasia
00:13:48.002 --> 00:13:51.074
involves an increase in cell number so you'd look
00:13:51.074 --> 00:13:55.007
for hyperplasia only in tissues that are capable of
00:13:55.007 --> 00:13:57.079
dividing in the adult state
00:13:57.079 --> 00:14:00.049
another was a permanent sort of tissue
00:14:00.049 --> 00:14:03.083
you're not going to get hyperplasia ordinarily in muscle
00:14:03.083 --> 00:14:05.006
you're not going to get
00:14:05.006 --> 00:14:11.026
hyperplasia, well muscle is probably the best example. but in other
00:14:11.026 --> 00:14:12.093
organs, you may
00:14:12.093 --> 00:14:16.052
get hyperplasia along with hypertrophy
00:14:16.052 --> 00:14:17.095
but conceptually hypertrophy
00:14:17.095 --> 00:14:22.399
is increase in cell size, hyperplasia is increase in cell
00:14:22.399 --> 00:14:24.249
number
00:14:24.249 --> 00:14:26.072
the
00:14:26.072 --> 00:14:33.073
best example of hypertrophy is in muscular tissues
00:14:33.073 --> 00:14:35.053
it's a response
00:14:35.053 --> 00:14:38.077
hypertrophy in muscle is a response to an overload
00:14:38.077 --> 00:14:42.057
or unusual workload or what not
00:14:42.057 --> 00:14:46.038
now you need a lot of imagination for this, but imagine i went in for bodybuilding
00:14:46.038 --> 00:14:48.032
which i never will
00:14:48.032 --> 00:14:51.067
and you know you you pump three hundred
pounds like this
00:14:51.067 --> 00:14:53.015
and after a while couldn't
00:14:53.015 --> 00:14:55.078
get into the lab coat. Bulging
00:14:55.078 --> 00:14:59.027
muscles, i told you, imagination.
00:14:59.027 --> 00:15:00.042
the
00:15:00.042 --> 00:15:03.409
muscles of the bodybuilder
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
00:15:06.429 --> 00:15:07.075
this
00:15:07.075 --> 00:15:09.689
represents
00:15:09.689 --> 00:15:10.047
hypertrophy
00:15:10.047 --> 00:15:15.004
of muscle, there isn't any real increase in the number of muscle cells
00:15:15.004 --> 00:15:18.078
but any individual muscle cells instead of being this big around is this big around
00:15:18.078 --> 00:15:20.009
and it
00:15:20.009 --> 00:15:23.001
represents actually a synthesis of more
00:15:23.001 --> 00:15:26.007
contractile machinery
00:15:26.007 --> 00:15:27.829
in the muscle, it's a response
00:15:27.829 --> 00:15:30.034
to the work
00:15:30.034 --> 00:15:33.084
now a place where we see this that isn't so trivial
00:15:33.084 --> 00:15:35.003
is
00:15:35.003 --> 00:15:37.018
is, for instance, heart muscle
00:15:37.018 --> 00:15:41.005
that is subjected to an abnormal load
00:15:41.005 --> 00:15:44.094
for instance, a left ventricle
00:15:44.094 --> 00:15:51.094
having to pump blood in a patient with uncontrolled hypertension
00:15:51.094 --> 00:15:55.007
in other words, the systemic blood pressure is elevated, the arteriolar resistance is elevated
00:15:55.007 --> 00:15:58.439
and every time that poor old left ventricle
00:15:58.439 --> 00:16:02.082
tries to eject blood, it's doing it against an increased head of pressure
00:16:02.082 --> 00:16:06.089
those muscles are going to undergo
hypertrophy
00:16:06.089 --> 00:16:07.097
or
00:16:07.097 --> 00:16:11.009
let's say the valve, the so-called
aortic valve, which is a valve between
00:16:11.009 --> 00:16:17.047
the left ventricle and the aorta, as the blood flows out, if that valve gets narrowed
00:16:17.047 --> 00:16:20.011
the poor old ventricle has to squeeze harder to get
00:16:20.011 --> 00:16:23.003
the blood out to maintain life, it will
undergo hypertrophy
00:16:23.003 --> 00:16:24.139
not hyperplasia
00:16:24.139 --> 00:16:25.119
but hypertrophy
00:16:25.119 --> 00:16:26.059
and the
00:16:26.059 --> 00:16:29.037
heart gains weight
00:16:29.037 --> 00:16:31.031
the ventricle becomes thick
00:16:31.031 --> 00:16:35.092
and the cells become enlarged. I'll illustrate this for you.
00:16:35.092 --> 00:16:37.049
here is
00:16:37.049 --> 00:16:41.042
don't pay attention to the color, there have been
some post-mortem changes here but
00:16:41.042 --> 00:16:43.739
this is a bread loaf slice
00:16:43.739 --> 00:16:45.041
of a normal heart
00:16:45.041 --> 00:16:47.919
you're looking at the right ventricle
over here
00:16:47.919 --> 00:16:52.209
left ventricle over here ordinarily, this is normal, the right ventricle is very thin
00:16:52.209 --> 00:16:57.014
because it pumps against a lesser head of pressure in the pulmonary circuit. The left ventricle
00:16:57.014 --> 00:16:59.559
,that's about normal thickness,
00:16:59.559 --> 00:17:01.002
now the next slide
00:17:01.002 --> 00:17:05.036
is not a photo trick and again
don't worry about the colors, but the next
00:17:05.036 --> 00:17:12.021
slide is taken from an individual with high blood pressure
00:17:12.021 --> 00:17:15.015
now that first heart probably weighed
00:17:15.015 --> 00:17:18.819
oh in the neighborhood of three hundred, three hundred and twenty five grams
00:17:18.819 --> 00:17:20.045
this heart weighed closer
00:17:20.045 --> 00:17:24.022
to the six or seven hundred grams, i don't remember precisely, but
00:17:24.022 --> 00:17:28.005
it kind of speaks for itself, there is more muscle
there
00:17:28.005 --> 00:17:31.099
and again this is not hyperplasia, this is
hypertrophy
00:17:31.099 --> 00:17:36.045
and it looks something like this. i know you don't know much of this histology
00:17:36.045 --> 00:17:37.088
but just
00:17:37.088 --> 00:17:41.046
think of these as cross-sections of these cylindrical muscle cells
00:17:41.046 --> 00:17:42.086
and this is
00:17:42.086 --> 00:17:44.091
a normal myocardium
00:17:44.091 --> 00:17:45.063
and
00:17:45.063 --> 00:17:50.052
let's just cast your eyeballs around and look at the approximate
00:17:50.052 --> 00:17:54.083
average diameter
00:17:54.083 --> 00:17:55.057
the next slide
00:17:55.057 --> 00:17:58.059
is taken with the same optics in the microscope
00:17:58.059 --> 00:18:04.006
from a hypertrophic heart, now you got this?
00:18:04.006 --> 00:18:04.071
The point
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
00:18:08.809 --> 00:18:11.049
pick this up on the quiz
00:18:11.049 --> 00:18:13.007
but just to show you
00:18:13.007 --> 00:18:14.003
the increase
00:18:14.003 --> 00:18:19.019
and what this represents really is an increase, a very striking increase
00:18:19.019 --> 00:18:21.058
in the myofibrillar contractile machinery
00:18:21.058 --> 00:18:24.079
of these cells
00:18:24.079 --> 00:18:28.679
so this is clearly an adaptive
00:18:28.679 --> 00:18:30.052
phenomenon
00:18:30.052 --> 00:18:33.056
and it works very well up to a point
00:18:33.056 --> 00:18:38.092
the heart can't keep getting more and more and more hypertrophic
00:18:38.092 --> 00:18:40.069
i've never seen a heart
00:18:40.069 --> 00:18:42.081
weigh much more than a kilogram
00:18:42.081 --> 00:18:44.309
and that's rare
00:18:44.309 --> 00:18:45.049
but beyond that
00:18:45.049 --> 00:18:46.809
it doesn't work
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
00:18:51.299 --> 00:18:53.008
of the heart
00:18:53.008 --> 00:18:56.017
muscle doesn't keep up
00:18:56.017 --> 00:18:59.038
with too much hypertrophy and pretty soon
00:18:59.038 --> 00:19:03.067
the muscle to capillary ratio is unfavorable
00:19:03.067 --> 00:19:06.095
and it plateaus, it can't go any further
00:19:06.095 --> 00:19:12.012
and then what you get is the onset of apoptosis in cells and actually some
00:19:12.012 --> 00:19:17.001
fibrous replacement of the myocardium so it doesn't work indefinitely
00:19:17.001 --> 00:19:17.061
actually some
00:19:17.061 --> 00:19:19.084
of the proteins that are formed
00:19:19.084 --> 00:19:22.081
are not necessarily normal either
00:19:22.081 --> 00:19:23.089
so hypertrophy
00:19:23.089 --> 00:19:30.045
is nice and adaptive up to a point, but beyond that
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
00:19:33.091 --> 00:19:35.067
of muscle
00:19:35.067 --> 00:19:36.009
as you may
00:19:36.009 --> 00:19:40.043
know for instance, the wall of the urinary bladder is muscle but
00:19:40.043 --> 00:19:43.061
this kind of muscle is what we call smooth muscle
00:19:43.061 --> 00:19:46.051
but if there is a chronic obstruction to
bladder outflow
00:19:46.051 --> 00:19:48.066
you get a very thick muscular bladder
00:19:48.066 --> 00:19:51.066
the same kind of response
00:19:51.066 --> 00:19:55.048
hypertrophy of the muscle cells
00:19:55.048 --> 00:19:57.077
we return to hyperplasia
00:19:57.077 --> 00:19:59.919
lots of examples i can give you
00:19:59.919 --> 00:20:00.044
of increased
00:20:00.044 --> 00:20:02.004
in
00:20:02.004 --> 00:20:02.098
the number of cells
00:20:02.098 --> 00:20:05.001
in the tissue
00:20:05.001 --> 00:20:07.096
and a nice example i think you've all
been there
00:20:07.096 --> 00:20:09.012
one way or another
00:20:09.012 --> 00:20:11.015
there's a callus that forms
00:20:11.015 --> 00:20:13.001
in the skin
00:20:13.001 --> 00:20:14.059
if you have a
00:20:14.059 --> 00:20:17.016
ill-fitting pair of shoes and something is rubbing
00:20:17.016 --> 00:20:18.023
on the spot
00:20:18.023 --> 00:20:21.077
or God forbid if you have to do manual
labor
00:20:21.077 --> 00:20:26.024
some concerted length of time
00:20:26.024 --> 00:20:29.659
you develop calluses. You've all had this happen. This is an example of
00:20:29.659 --> 00:20:31.062
hyperplasia
00:20:31.062 --> 00:20:33.023
It's a response to this overwork stimulus
00:20:33.023 --> 00:20:35.075
which increases
00:20:35.075 --> 00:20:40.046
or leads to an increase in number of cells in the system
00:20:40.046 --> 00:20:42.001
let me illustrate this
00:20:42.001 --> 00:20:44.079
give you a little histology
00:20:44.079 --> 00:20:47.082
this is basically normal skin
00:20:47.082 --> 00:20:49.011
on the palmar surface of the hand
00:20:49.011 --> 00:20:50.078
this is the dermis, the connective tissue part
00:20:50.078 --> 00:20:51.088
this is the
00:20:51.088 --> 00:20:56.038
epidermis, the epithelial portion
00:20:56.038 --> 00:20:58.065
now this is a renewing
00:20:58.065 --> 00:21:00.659
cell system
00:21:00.659 --> 00:21:01.025
normally
00:21:01.025 --> 00:21:06.023
a certain number of cells are mitosing down here in the basal layer
00:21:06.023 --> 00:21:08.086
and daughter cells are moving out and maturing
00:21:08.086 --> 00:21:13.007
as they move on out
00:21:13.007 --> 00:21:16.016
and this upper layer where you see no nuclei is the
00:21:16.016 --> 00:21:18.038
so-called stratum corneum
00:21:18.038 --> 00:21:20.003
it's like a layer of shingles on the roof
00:21:20.003 --> 00:21:23.064
these cells undergo progressive changes
00:21:23.064 --> 00:21:26.052
in armor plate there
00:21:26.052 --> 00:21:30.018
so the normal palmar skin is set with a certain cell population
00:21:30.018 --> 00:21:31.419
and a certain
00:21:31.419 --> 00:21:36.017
balance where certain cells come and go
00:21:36.017 --> 00:21:38.075
i'll show you the callus
00:21:38.075 --> 00:21:41.048
keep this picture in mind
00:21:41.048 --> 00:21:44.007
and this represents the hyperplasia of the callus
00:21:44.007 --> 00:21:47.000
now you've got
00:21:47.000 --> 00:21:49.009
a much thicker cell population
00:21:49.009 --> 00:21:51.057
it's still a very orderly cell population
00:21:51.057 --> 00:21:55.008
the cells are being born down here and are maturing up here
00:21:55.008 --> 00:21:56.055
there's actually
00:21:56.055 --> 00:21:58.095
so much thickening going on here that I couldn't
00:21:58.095 --> 00:22:00.032
get it all on one picture
00:22:00.032 --> 00:22:02.061
at the same magnification
00:22:02.061 --> 00:22:03.095
here is the beginning of the stratum
00:22:03.095 --> 00:22:05.006
corneum
00:22:05.006 --> 00:22:07.929
there's the rest of it
00:22:07.929 --> 00:22:10.077
and that is a callus
00:22:10.077 --> 00:22:12.022
So you see there is a tremendous
00:22:12.022 --> 00:22:16.031
hyperplasia here in response to this mechanical stimulus
00:22:16.031 --> 00:22:18.069
Now the nice thing
00:22:18.069 --> 00:22:25.001
about hyperplasia, and also applies to hypertrophy, if you get rid of
00:22:25.001 --> 00:22:28.007
the noxious stimulus,
00:22:28.007 --> 00:22:29.419
things pretty much
00:22:29.419 --> 00:22:32.074
wind back to normal. You can't always do that, but
00:22:32.074 --> 00:22:34.028
if you can, if you quit
00:22:34.028 --> 00:22:37.073
raking the ground or whatever you're doing,
00:22:37.073 --> 00:22:39.086
pretty soon those hands will be the ones you know and love.
00:22:39.086 --> 00:22:41.061
The calloused thins out
00:22:41.061 --> 00:22:45.069
and you go back to normal. Now
00:22:45.069 --> 00:22:46.081
I could give you
00:22:46.081 --> 00:22:52.017
other happier examples, maybe, I'll give you one.
00:22:52.017 --> 00:22:53.086
In a hormone sensitive
00:22:53.086 --> 00:22:55.071
tissue that responds
00:22:55.071 --> 00:22:58.034
that response with hyperplasia
00:22:58.034 --> 00:23:00.066
here is a normal
00:23:00.066 --> 00:23:03.041
lobule. This is kind of a potential
00:23:03.041 --> 00:23:04.095
secretory unit,
00:23:04.095 --> 00:23:07.076
a normal lobule of an adult female breast.
00:23:07.076 --> 00:23:08.098
I don't want to go into detail, but
00:23:08.098 --> 00:23:11.053
just to show you the little terminal
00:23:11.053 --> 00:23:15.013
units forming this lobule. During pregnancy
00:23:15.013 --> 00:23:16.799
and lactation,
00:23:16.799 --> 00:23:17.005
this tremendous
00:23:17.005 --> 00:23:19.094
hormonal stimulus to these cells
00:23:19.094 --> 00:23:20.096
makes them undergo
00:23:20.096 --> 00:23:22.033
hyperplasia
00:23:22.033 --> 00:23:23.419
and that lobule
00:23:23.419 --> 00:23:24.062
, take a look
00:23:24.062 --> 00:23:26.035
at the size there
00:23:26.035 --> 00:23:27.051
enlarged
00:23:27.051 --> 00:23:30.007
couldn't even get the whole lobule on the screen there
00:23:30.007 --> 00:23:33.002
This is a lactating mammary gland
00:23:33.002 --> 00:23:34.063
there's a tremendous
00:23:34.063 --> 00:23:38.012
increase in the number of cells, actually some hypertrophy
00:23:38.012 --> 00:23:40.044
in individual cells, but basically
00:23:40.044 --> 00:23:41.087
a whole lot of hyperplasia
00:23:41.087 --> 00:23:44.032
there, and it responds to
00:23:44.032 --> 00:23:46.071
the hormone.
00:23:46.071 --> 00:23:51.056
When the hormonal stimulus is withdrawn at the end of lactation, things pretty much
00:23:51.056 --> 00:23:55.002
go back to normal, plus or minus a little stretching of the connective tissue
00:23:55.002 --> 00:23:57.002
but the epithelial
00:23:57.002 --> 00:24:02.299
population goes back to normal.
00:24:02.299 --> 00:24:06.007
That's hyperplasia, tends to be reversible
00:24:06.007 --> 00:24:09.068
under very nice elegant control
00:24:09.068 --> 00:24:11.091
in some situations
00:24:11.091 --> 00:24:13.083
got to throw this in. Not all good news.
00:24:13.083 --> 00:24:15.093
In some situations, the hyperplasia
00:24:15.093 --> 00:24:17.038
00:24:17.038 --> 00:24:18.073
isn't necessarily
00:24:18.073 --> 00:24:22.053
adaptive and good. We see
00:24:22.053 --> 00:24:25.047
examples of hyperplasia, I'll show two of them.
00:24:25.047 --> 00:24:28.012
00:24:28.012 --> 00:24:29.062
They're probably responses
00:24:29.062 --> 00:24:34.075
to the subtly abnormal endocrine stimulation, somehow
00:24:34.075 --> 00:24:36.045
we don't exactly know.
00:24:36.045 --> 00:24:40.065
but, i think one for the guys, one for the girls
00:24:40.065 --> 00:24:43.062
this is something that is going to afflict about
00:24:43.062 --> 00:24:46.071
forty nine percent of us in the room, one way or the other.
00:24:46.071 --> 00:24:48.005
and this is
00:24:48.005 --> 00:24:50.084
a cross cut of the prostate
00:24:50.084 --> 00:24:51.065
and the
00:24:51.065 --> 00:24:54.035
prostate normally is about the size
00:24:54.035 --> 00:24:56.013
of a golf
00:24:56.013 --> 00:24:59.048
ball, a walnut, a good sized walnut
00:24:59.048 --> 00:25:00.082
and it's right at the base
00:25:00.082 --> 00:25:08.000
the bladder and the urethra. The outflow tract goes through the prostate.
00:25:08.000 --> 00:25:08.034
You're looking at a cross-section there
00:25:08.034 --> 00:25:10.046
and you see the urethra there.
00:25:10.046 --> 00:25:11.096
The normal prostate would be
00:25:11.096 --> 00:25:15.019
nice and smooth across the cut surface.
00:25:15.019 --> 00:25:15.095
Here you see
00:25:15.095 --> 00:25:21.001
a bunch of lumps and this represents
00:25:21.001 --> 00:25:23.004
hyperplasia of
00:25:23.004 --> 00:25:26.031
glandular and muscular tissue, glandular tissue undergoes tremendous hyperplasia.
00:25:26.031 --> 00:25:29.041
we don't know why, and the
00:25:29.041 --> 00:25:31.044
problem with
00:25:31.044 --> 00:25:33.059
is not simply walk around with a tennis ball
00:25:33.059 --> 00:25:39.018
there instead of a walnut, but it rests on the base of the bladder
00:25:39.018 --> 00:25:41.072
and urethra and can cause outflow problems.
00:25:41.072 --> 00:25:46.027
and also urinary tract problems.
00:25:46.027 --> 00:25:49.053
I'll give you a little tidbit that's absolutely useless.
00:25:49.053 --> 00:25:53.039
Eunuchs don't get prostatic hyperplasia,
00:25:53.039 --> 00:25:58.052
but it's not a very popular preventative measure.
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
00:26:02.095 --> 00:26:05.039
kilter and not good.
00:26:05.039 --> 00:26:07.007
for
00:26:07.007 --> 00:26:07.096
the rest of you
00:26:07.096 --> 00:26:09.044
we'll talk about
00:26:09.044 --> 00:26:11.035
a very common condition
00:26:11.035 --> 00:26:13.078
called fibrocystic change in the breast
00:26:13.078 --> 00:26:15.029
now this is
00:26:15.029 --> 00:26:18.062
a non-descript looking piece of tissue
00:26:18.062 --> 00:26:19.047
but if it were perfectly normal
00:26:19.047 --> 00:26:20.094
mostly
00:26:20.094 --> 00:26:23.061
it would be a yellowish background
00:26:23.061 --> 00:26:25.062
because the breast is largely fatty tissue
00:26:25.062 --> 00:26:27.022
and not
00:26:27.022 --> 00:26:30.073
those big yawning things there. So what's happened in this breast
00:26:30.073 --> 00:26:34.028
it's, first of all, increase in fibroblast
00:26:34.028 --> 00:26:38.039
fibrous connective tissue, see these white streaks
00:26:38.039 --> 00:26:39.096
and this represents part of the duct system.
00:26:39.096 --> 00:26:42.000
where the cells increase in number
00:26:42.000 --> 00:26:44.559
and fluid is accumulated in
00:26:44.559 --> 00:26:45.095
what we call cysts,
00:26:45.095 --> 00:26:46.076
a cyst
00:26:46.076 --> 00:26:48.058
is a hollow space filled with fluid
00:26:48.058 --> 00:26:51.089
lined with epithelium
00:26:51.089 --> 00:26:54.076
and so we call this fibrocystic change.
00:26:54.076 --> 00:26:56.064
In and of itself, it's very
00:26:56.064 --> 00:27:00.016
common, in and of itself it's no big deal.
00:27:00.016 --> 00:27:01.052
I'll show you
00:27:01.052 --> 00:27:04.094
what happens conceptually, here again here's the
00:27:04.094 --> 00:27:09.029
normal breast, this is a lobule like I showed you before and this is
00:27:09.029 --> 00:27:15.046
part of the duct system leading to that lobule. That's normal. Now in a fibrocystic
00:27:15.046 --> 00:27:17.012
change, what you see
00:27:17.012 --> 00:27:17.045
is
00:27:17.045 --> 00:27:19.559
this little garbled
00:27:19.559 --> 00:27:20.097
Here's a lobule
00:27:20.097 --> 00:27:22.061
that has undergone
00:27:22.061 --> 00:27:26.097
hyperplasia, pretty evident
00:27:26.097 --> 00:27:28.559
and the duct system, the lining is also
00:27:28.559 --> 00:27:35.085
undergone hyperplasia, the ducts are dilating and eventually form cysts.
00:27:35.085 --> 00:27:38.047
and again we don't know exactly why
00:27:38.047 --> 00:27:43.025
this happens, but it represents hyperplasia
00:27:43.025 --> 00:27:48.058
gone wrong.
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.
00:27:59.037 --> 00:28:09.037
I want to move on to proliferation and maturation of cells within a population.
00:28:09.037 --> 00:28:12.005
I'm talking about two particular situations here
00:28:12.005 --> 00:28:13.041
we'll talk first about
00:28:13.041 --> 00:28:17.077
metaplasia and then dysplasia.
00:28:17.077 --> 00:28:23.022
all right, what about metaplasia? We define this as
00:28:23.022 --> 00:28:30.091
a change in the cell population, in which one normal mature special
00:28:30.091 --> 00:28:34.071
cell, I'll clarify this in a moment, but one
00:28:34.071 --> 00:28:37.799
cell type is replaced by another
00:28:37.799 --> 00:28:39.019
normal cell type,
00:28:39.019 --> 00:28:41.007
except it doesn't belong
00:28:41.007 --> 00:28:43.096
there, in other words, it's changed
00:28:43.096 --> 00:28:52.063
that particular location. Now this isn't just a substitution, where this cell
00:28:52.063 --> 00:28:54.003
changes into another cell
00:28:54.003 --> 00:28:56.067
what this is, rather,
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
00:29:02.057 --> 00:29:09.081
where ordinarily the cells mature in this direction, and metaplasia represents
00:29:09.081 --> 00:29:30.061
a switch, under some influence, where they mature in that direction.
00:29:30.061 --> 00:29:36.067
They become more resistant than the normal one and that represents metaplasia.
00:29:36.067 --> 00:29:40.809
Let me illustrate this, try to make sense out of it.
00:29:40.809 --> 00:29:43.056
Here is the lining
00:29:43.056 --> 00:29:45.022
of the
00:29:45.022 --> 00:29:46.017
what we call
00:29:46.017 --> 00:29:49.033
the endocervical canal
00:29:49.033 --> 00:29:54.539
this is the canal that goes up into the uterus. Now normally
00:29:54.539 --> 00:29:56.021
what's going on
00:29:56.021 --> 00:30:00.299
here is that there are certain number of, well, call them stem cells
00:30:00.299 --> 00:30:02.049
or reserved cells that are proliferating
00:30:02.049 --> 00:30:02.051
all the
00:30:02.051 --> 00:30:05.001
time, but they mature
00:30:05.001 --> 00:30:06.044
into these tall
00:30:06.044 --> 00:30:07.036
what we call columnar
00:30:07.036 --> 00:30:09.056
cells, they are
00:30:09.056 --> 00:30:11.091
tall and columnar and they've got
00:30:11.091 --> 00:30:15.083
very pale cytoplasm because they're full of mucus.
00:30:15.083 --> 00:30:22.001
So normally this endocervical canal is lined by this mucus secreting epithelium, very
00:30:22.001 --> 00:30:23.029
slight stimulus
00:30:23.029 --> 00:30:24.065
is all it takes
00:30:24.065 --> 00:30:26.019
and there may be a change
00:30:26.019 --> 00:30:29.001
here you see the normal, here you see a plaque
00:30:29.001 --> 00:30:31.149
of cells that looks a little bit different
00:30:31.149 --> 00:30:33.088
and these cells
00:30:33.088 --> 00:30:35.018
are, well, they're
00:30:35.018 --> 00:30:39.049
odd shapes here, they're maturing into these
00:30:39.049 --> 00:30:43.007
flat cells that we saw on top of the epidermis, and we call this
00:30:43.007 --> 00:30:44.047
these are columnar
00:30:44.047 --> 00:30:47.098
cells, these are squamous cells, we call this squamous
00:30:47.098 --> 00:30:48.079
metaplasia
00:30:48.079 --> 00:30:51.026
very very
00:30:51.026 --> 00:30:52.759
common, some of you
00:30:52.759 --> 00:30:54.539
in this room have this, it's a trivial change
00:30:54.539 --> 00:30:56.023
practically
00:30:56.023 --> 00:31:00.017
ubiquitous in the adult females in the
00:31:00.017 --> 00:31:01.068
endocervix
00:31:01.068 --> 00:31:06.039
it can become quite extreme. Look at this.
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
00:31:14.086 --> 00:31:20.033
epithelium, looks a lot like the epidermis, doesn't it?
00:31:20.033 --> 00:31:24.015
I would emphasize a couple things
00:31:24.015 --> 00:31:27.073
this is perfectly orderly, you look at this
00:31:27.073 --> 00:31:32.024
and I know you haven't become histologic experts yet
00:31:32.024 --> 00:31:33.008
but that is a perfectly orderly
00:31:33.008 --> 00:31:37.149
squamous epithelium, nothing unusual about it except
00:31:37.149 --> 00:31:38.097
it doesn't belong there.
00:31:38.097 --> 00:31:41.031
So that's an example
00:31:41.031 --> 00:31:43.034
of metaplasia
00:31:43.034 --> 00:31:44.159
in and of itself
00:31:44.159 --> 00:31:45.089
trivial
00:31:45.089 --> 00:31:47.042
or even protective.
00:31:47.042 --> 00:31:49.019
Let's say
00:31:49.019 --> 00:31:52.084
chemical workers were exposed to fumes might develop
00:31:52.084 --> 00:31:53.006
this kind of
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
00:31:59.033 --> 00:32:02.007
inhaling, smokers develop
00:32:02.007 --> 00:32:03.078
this sort of thing. Now, this could go on
00:32:03.078 --> 00:32:05.047
and something
00:32:05.047 --> 00:32:07.072
else might happen, and this might
00:32:07.072 --> 00:32:09.012
lead to bad
00:32:09.012 --> 00:32:10.071
things, but
00:32:10.071 --> 00:32:12.073
in and of itself, metaplasia
00:32:12.073 --> 00:32:14.061
is perfectly innocent.
00:32:14.061 --> 00:32:16.003
Not so
00:32:16.003 --> 00:32:17.061
with dysplasia.
00:32:17.061 --> 00:32:19.054
D-y-s-p-l-a-s-i-a
00:32:19.054 --> 00:32:23.079
Now morphologically,
00:32:23.079 --> 00:32:42.096
dysplasia is a
00:32:42.096 --> 00:32:45.062
variation, abnormal variation
00:32:45.062 --> 00:32:48.055
in
00:32:48.055 --> 00:32:50.006
the size
00:32:50.006 --> 00:32:51.006
of the cells, the shape of the cells
00:32:51.006 --> 00:32:53.093
the arrangement of the
00:32:53.093 --> 00:32:54.058
cells
00:32:54.058 --> 00:32:57.022
and the maturation of the cells
00:32:57.022 --> 00:32:59.041
too much variation
00:32:59.041 --> 00:33:01.009
in other words
00:33:01.009 --> 00:33:04.034
something very well controlled like this
00:33:04.034 --> 00:33:06.057
this epithelium is very well controlled
00:33:06.057 --> 00:33:08.008
with all the cells down here proliferating
00:33:08.008 --> 00:33:10.062
at a certain rate and maturing gradually
00:33:10.062 --> 00:33:12.002
and so forth
00:33:12.002 --> 00:33:19.025
all of this gets screwed up in dysplasia.
00:33:19.025 --> 00:33:21.029
Here again is a normal squamous
00:33:21.029 --> 00:33:23.028
epithelium, this isn't palmar
00:33:23.028 --> 00:33:28.021
or skin now, this is let's say the lining of the vagina or
00:33:28.021 --> 00:33:32.025
covering of the cervix, one of those, this happens to be cervix
00:33:32.025 --> 00:33:35.034
perfectly normal squamous epithelium, notice how orderly
00:33:35.034 --> 00:33:36.085
it is, it's like a
00:33:36.085 --> 00:33:37.084
kind of like
00:33:37.084 --> 00:33:41.059
a parade where you have cells in
00:33:41.059 --> 00:33:44.006
a certain type down here, they all resemble one another
00:33:44.006 --> 00:33:46.034
in this layer, cells here
00:33:46.034 --> 00:33:49.094
resemble one another, and then there's this maturation
00:33:49.094 --> 00:33:53.046
these flattened out cells, that's occurring in a very orderly
00:33:53.046 --> 00:33:57.086
step fashion. In dysplasia
00:33:57.086 --> 00:34:00.098
of the epithelium, everything gets
00:34:00.098 --> 00:34:08.409
screwed up. All right,
00:34:08.409 --> 00:34:10.329
this is dysplasia.
00:34:10.329 --> 00:34:14.379
and we can see where
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
00:34:18.619 --> 00:34:20.069
happened, there's more
00:34:20.069 --> 00:34:22.829
variation in any
00:34:22.829 --> 00:34:23.079
layer. In other words,
00:34:23.079 --> 00:34:24.049
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
00:34:29.219 --> 00:34:31.359
in the normal. You look here
00:34:31.359 --> 00:34:33.339
where in the
00:34:33.339 --> 00:34:36.949
preceding slide, every cell in the intermediate zone is perfectly
00:34:36.949 --> 00:34:38.979
like every other cell, there's variation
00:34:38.979 --> 00:34:43.419
here, there's big cells and small cells, round cells and elongated cells
00:34:43.419 --> 00:34:45.009
cells with
00:34:45.009 --> 00:34:48.639
very dark nuclei, cells with lighter nuclei
00:34:48.639 --> 00:34:50.949
and so forth
00:34:50.949 --> 00:34:51.078
and gradually, though, despite
00:34:51.078 --> 00:34:53.539
this mess, there is
00:34:53.539 --> 00:34:54.999
slight
00:34:54.999 --> 00:34:56.009
maturation
00:34:56.009 --> 00:35:01.959
you can see here how this jumble of cells gradually becomes organized
00:35:01.959 --> 00:35:04.689
up here, so what have we got
00:35:04.689 --> 00:35:07.079
we've got abnormal
00:35:07.079 --> 00:35:07.939
variations
00:35:07.939 --> 00:35:11.579
in the size of the cells, the shape of the cells, the arrangement
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.
00:35:15.709 --> 00:35:16.098
And it's not
00:35:16.098 --> 00:35:21.219
maturing quite properly until it gets to the very top.
00:35:21.219 --> 00:35:23.439
Actually,
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
00:35:28.799 --> 00:35:30.369
normal
00:35:30.369 --> 00:35:32.809
there might be there. But when you see
00:35:32.809 --> 00:35:36.269
this degree of variation, that's a very
00:35:36.269 --> 00:35:39.019
bad thing. There's one other thing
00:35:39.019 --> 00:35:42.499
that's abnormal here, it's a little more subtle, ordinarily
00:35:42.499 --> 00:35:44.969
mitosis occurs only down in this
00:35:44.969 --> 00:35:47.064
basal layer. But these cells
00:35:47.064 --> 00:35:51.519
are goofy enough that they forget about that and they do something very impolite.
00:35:51.519 --> 00:35:53.489
They reproduce out
00:35:53.489 --> 00:35:59.039
in public and you find mitotic figures at all levels of such an epithelium.
00:35:59.039 --> 00:36:00.799
So morphologically,
00:36:00.799 --> 00:36:07.379
this represents a lot of variation.
00:36:07.379 --> 00:36:13.959
This is a serious change because these cells
00:36:13.959 --> 00:36:26.749
are in a sense losing control. They're losing control of proliferation and maturation.
00:36:26.749 --> 00:36:28.067
Any number of mutations
00:36:28.067 --> 00:36:38.809
that occur in the cell population, this reflects genetic change in the cell, somatic cell
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
00:36:56.069 --> 00:36:58.419
in other words, I can't tell you
00:36:58.419 --> 00:37:12.729
that epithelium absolutely for sure will become cancer, it depends I suppose on the last garbled
00:37:12.729 --> 00:37:38.109
mild degree of dysplasia sometimes don't necessarily progress, while very severe degrees of dysplasia can.
00:37:38.109 --> 00:37:39.041
Here is a squamous epithelium
00:37:39.041 --> 00:37:40.889
with what we call severe
00:37:40.889 --> 00:37:42.859
dysplasia, and you can see close
00:37:42.859 --> 00:37:45.139
up what's going on here
00:37:45.139 --> 00:37:48.579
This basal layer is increased in thickness, a lot of variation
00:37:48.579 --> 00:37:49.489
in these cells,
00:37:49.489 --> 00:37:51.299
here is
00:37:51.299 --> 00:37:56.049
a cell dividing, as they say, out in public and there is an absolute total
00:37:56.049 --> 00:37:57.859
jumble
00:37:57.859 --> 00:38:01.379
in terms of how these cells are arranged with respect to one another.
00:38:01.379 --> 00:38:03.094
We call that a loss of polarity.
00:38:03.094 --> 00:38:05.309
And in this instance
00:38:05.309 --> 00:38:16.249
it occurred all the way, full thickness of this epithelium.
00:38:16.249 --> 00:38:20.149
and we now know, from a lot of experience, severe dysplasia
00:38:20.149 --> 00:38:22.089
really is
00:38:22.089 --> 00:38:23.989
tantamount to cancer
00:38:23.989 --> 00:38:27.029
that perhaps hasn't
00:38:27.029 --> 00:38:28.007
yet invaded. Now that'll
00:38:28.007 --> 00:38:34.459
make sense when we talk about what cancer really is. Without
00:38:34.459 --> 00:38:40.179
any evidence of invasion or anything else that cancers usually do
00:38:40.179 --> 00:38:43.849
when dysplasia is this severe, we can say this is like carcinoma-in-situ
00:38:43.849 --> 00:38:46.599
which means an 'in-place' cancer
00:38:46.599 --> 00:38:48.239
pre-invasive
00:38:48.239 --> 00:38:51.069
cancer because we know
00:38:51.069 --> 00:38:51.809
if this sort of
00:38:51.809 --> 00:38:54.649
dysplasia is left alone, probably close
00:38:54.649 --> 00:38:56.229
to 100% will
00:38:56.229 --> 00:39:02.048
evolve into a cancer if the patient lives long enough.
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
00:39:07.609 --> 00:39:09.019
this decision. First of all
00:39:09.019 --> 00:39:09.098
you'll notice
00:39:09.098 --> 00:39:13.009
there's a lot of variation in size of nuclei. We call that
00:39:13.009 --> 00:39:15.209
nuclear pleomorphism.
00:39:15.209 --> 00:39:16.469
p-l-e-o
00:39:16.469 --> 00:39:18.769
that's a bad sign
00:39:18.769 --> 00:39:19.539
and none of these
00:39:19.539 --> 00:39:23.339
is absolute, but it's a bad sign.
00:39:23.339 --> 00:39:28.669
Some of the nuclei are very dark as you cast your eye around here.
00:39:28.669 --> 00:39:32.889
We would call that nuclear hyperchromatism. Too much
00:39:32.889 --> 00:39:36.749
colored material in the nucleus.
00:39:36.749 --> 00:39:37.119
The nuclei
00:39:37.119 --> 00:39:43.759
are very unusually shaped and sometimes
00:39:43.759 --> 00:39:44.989
you can't see it, but
00:39:44.989 --> 00:39:47.959
sometimes the mitotic figures are themselves
00:39:47.959 --> 00:39:51.319
are even abnormal, may see a tripolar mitotic figure
00:39:51.319 --> 00:39:53.269
or something like that.
00:39:53.269 --> 00:40:01.579
These are all signs of badness in a cell population.
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.
00:40:13.319 --> 00:40:18.039
Put a line underneath all of this and now we turn to the main topic -- Neoplasia.
00:40:18.039 --> 00:40:47.559
Spend the rest of this morning and Wednesday morning on this topic. It's ultimately
00:40:47.559 --> 00:40:49.339
more cells than there ought to be, it's an increase in cells
00:40:49.339 --> 00:40:52.189
it's a lump basically
00:40:52.189 --> 00:40:56.219
and these are proliferating cells, they're not just sitting there, they're
00:40:56.219 --> 00:41:01.799
they're dividing and making new cells. And, they're cells that have somehow
00:41:01.799 --> 00:41:23.219
become autonomous
00:41:23.219 --> 00:41:25.279
they don't obey the same start and stop signals
00:41:25.279 --> 00:41:28.159
that normal cells do. Their growth
00:41:28.159 --> 00:41:34.329
tends to be excessive and uncoordinated with the needs of the host.
00:41:34.329 --> 00:41:37.229
In other words, this thing is taking off on its own!
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.
00:41:45.899 --> 00:41:59.729
You want to think teleologically, serves no useful purpose, it's not adaptive.
00:41:59.729 --> 00:42:04.459
Once the neoplasm is formed, it's off and running,
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.
00:42:22.849 --> 00:42:31.289
In some countries, it's the word tumor, which now is practically synonymous with neoplasm.
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
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.
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.
00:43:04.092 --> 00:43:07.769
Different types of neoplasms are distinguished by their behavior,
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
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.
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.
00:43:51.016 --> 00:44:20.279
A neoplasm is a living, proliferating cell and
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
00:44:27.129 --> 00:44:30.479
a set of these new characteristics
00:44:30.479 --> 00:44:45.017
that define them as neoplastic and, as you will hear, usually
00:44:45.017 --> 00:44:48.079
the wrong mutations. We talk about the clonal origin
00:44:48.079 --> 00:45:00.299
of neoplasms, in other words, a neoplasm is a clonal proliferation of a transformed cell.
00:45:00.299 --> 00:45:03.889
This transformed cell has a lot of characteristics
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.
00:45:11.499 --> 00:45:13.699
Malignant cells, for instance,
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
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
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.
00:46:11.449 --> 00:46:28.679
You will learn that
00:46:28.679 --> 00:46:42.149
there's a difference between benign and malignant. I think this cartoon sums it up well.
00:46:42.149 --> 00:46:52.579
As the neoplasm grows, the number of cells gradually increases, they tend to be cohesive
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
00:46:58.004 --> 00:47:00.639
grows, and it may grow to a very large
00:47:00.639 --> 00:47:02.489
size, it tends to grow
00:47:02.489 --> 00:47:07.549
by a centrifugal expansion. Now it's not a perfect circle, but
00:47:07.549 --> 00:47:13.039
it tends to grow by expansion. As it expands,
00:47:13.039 --> 00:47:14.909
it frequently will pick up
00:47:14.909 --> 00:47:15.499
a
00:47:15.499 --> 00:47:18.078
condensed capsule of connective tissue as it pushes out
00:47:18.078 --> 00:47:20.169
causes atrophy of surrounding tissues
00:47:20.169 --> 00:47:25.579
and will accumulate a kind of capsule almost and anyway
00:47:25.579 --> 00:47:26.219
at any rate
00:47:26.219 --> 00:47:32.719
it stays local, its size, and it doesn't invade
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
00:47:38.038 --> 00:48:04.479
balloon in the thing. On the average,
00:48:04.479 --> 00:48:07.029
this is not as cohesive as this suggests
00:48:07.029 --> 00:48:11.619
it grows, the cells have a great tendency of invading
00:48:11.619 --> 00:48:12.829
what we call the primary,
00:48:12.829 --> 00:48:16.659
they tend to drift
00:48:16.659 --> 00:48:20.939
away and don't obey the stop and start signals.
00:48:20.939 --> 00:48:22.046
They have a very different relationship
00:48:22.046 --> 00:48:25.091
with the cellular matrix and basically
00:48:25.091 --> 00:48:27.039
they have
00:48:27.039 --> 00:48:32.909
the ability, this is the primary difference, to cut their way
00:48:32.909 --> 00:48:35.519
through
00:48:35.519 --> 00:48:36.066
the adjacent stroma
00:48:36.066 --> 00:48:39.519
and actually invade as clumps of cells,
00:48:39.519 --> 00:48:43.069
lines of cells, individual cells,
00:48:43.069 --> 00:48:44.349
Invasion is one
00:48:44.349 --> 00:48:47.042
of the defining
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.
00:48:55.289 --> 00:49:03.709
They have to be invasive to be malignant.
00:49:03.709 --> 00:49:05.075
One other, well this sums it up,
00:49:05.075 --> 00:49:08.519
cohesive, expansile, circumscribed, localized
00:49:08.519 --> 00:49:13.119
that's benign. Malignant is poorly circumscribed, invasive, metastasizing.
00:49:13.119 --> 00:49:13.659
That means
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
00:49:21.099 --> 00:49:32.399
and metastasis that define malignancy. Benign neoplasms do not metastasize.
00:49:32.399 --> 00:49:37.579
Here's a uterus
00:49:37.579 --> 00:49:41.429
cut sort of in
00:49:41.429 --> 00:49:43.769
sagittal sections, this is the cervix
00:49:43.769 --> 00:49:47.013
down here, this is a normal one half
00:49:47.013 --> 00:49:48.919
this is the cavity here, here is a
00:49:48.919 --> 00:49:52.729
neoplasm.
00:49:52.729 --> 00:49:57.379
Benign or malignant? See, it works.
00:49:57.379 --> 00:49:58.031
This is what you
00:49:58.031 --> 00:49:59.619
probably grew up hearing, a fibroid.
00:49:59.619 --> 00:50:01.088
Uterine fibroid.
00:50:01.088 --> 00:50:04.809
That's a misnomer, because it isn't
00:50:04.809 --> 00:50:08.779
a fibrous tumor, it's a muscular tumor
00:50:08.779 --> 00:50:10.459
one we call a leiomyoma.
00:50:10.459 --> 00:50:13.629
But you can see it's got, just like the cartoon, pushing at the edges.
00:50:13.629 --> 00:50:15.719
You look at that microscopically,
00:50:15.719 --> 00:50:16.619
same sort of thing
00:50:16.619 --> 00:50:18.159
here's a
00:50:18.159 --> 00:50:20.059
tumor, here's the
00:50:20.059 --> 00:50:24.179
edge along here, no invasion.
00:50:24.179 --> 00:50:28.089
Can see it just pushing, pressing along that adjacent line.
00:50:28.089 --> 00:50:31.329
Here's a breast
00:50:31.329 --> 00:50:32.989
that's been
00:50:32.989 --> 00:50:33.819
taken off
00:50:33.819 --> 00:50:37.549
a mastectomy specimen and it's been cut in this plane,
00:50:37.549 --> 00:50:39.539
a section where you can see
00:50:39.539 --> 00:50:41.669
the skin out here, and this is the neoplasm
00:50:41.669 --> 00:50:43.039
very very hard
00:50:43.039 --> 00:50:45.008
to define and circumscribe.
00:50:45.008 --> 00:50:47.209
It's going out in little
00:50:47.209 --> 00:50:48.669
sites in the adjacent
00:50:48.669 --> 00:50:49.589
tissue, even
00:50:49.589 --> 00:50:51.051
way beyond this microscopically
00:50:51.051 --> 00:50:54.013
there are lines of cells that you couldn't see here.
00:50:54.013 --> 00:50:57.229
That's invasion. A benign neoplasm
00:50:57.229 --> 00:50:59.559
wouldn't look like that.
00:50:59.559 --> 00:51:01.419
Here's one that's a little deceptive at first.
00:51:01.419 --> 00:51:02.004
This is a colon cancer,
00:51:02.004 --> 00:51:06.009
we've opened the colon and washed it off. You might
00:51:06.009 --> 00:51:08.519
say, at first, gee that's circumscribed,
00:51:08.519 --> 00:51:10.989
isn't it? Well, not exactly.
00:51:10.989 --> 00:51:13.179
What I did here is
00:51:13.179 --> 00:51:14.093
fix this in formaldehyde
00:51:14.093 --> 00:51:17.539
and then made a cut
00:51:17.539 --> 00:51:21.069
across it, and it looks like
00:51:21.069 --> 00:51:23.269
this. Now this doesn't look so
00:51:23.269 --> 00:51:25.599
awful, but it really is.
00:51:25.599 --> 00:51:30.067
Here's the normal mucous membrane up here, this layer we call sub-mucosa,
00:51:30.067 --> 00:51:33.569
this is the muscular wall of the colon here.
00:51:33.569 --> 00:51:36.509
Here is that mushroom
00:51:36.509 --> 00:51:39.679
and you can see this whitish tissue, this is neoplasm, invade
00:51:39.679 --> 00:51:41.349
all the way through that muscular layer.
00:51:41.349 --> 00:51:44.729
This is invasion.
00:51:44.729 --> 00:51:49.919
This is what it looks
00:51:49.919 --> 00:51:52.639
like microscopically, don't worry about this.
00:51:52.639 --> 00:51:55.269
duct cells, hyperchromatic, pleomorphic nuclei,
00:51:55.269 --> 00:51:58.529
and so forth.
00:51:58.529 --> 00:52:03.459
These cancer cells are cutting right through the colonic wall, it's not that simple,
00:52:03.459 --> 00:52:05.579
but they're cutting right through that colonic wall
00:52:05.579 --> 00:52:08.729
and invading. That constitutes
00:52:08.729 --> 00:52:13.015
the evidence
00:52:13.015 --> 00:52:18.369
that this is a malignant neoplasm.
00:52:18.369 --> 99:59:59.999
Let's take a break.