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Dialogue: 0,0:00:06.06,0:00:10.06,Default,,0000,0000,0000,,(From M1 Patients and Populations at University of Michigan Medical School. Lecture by Gerald Abrams, MD.)\NYou see the title is Disturbances of Growth in Neoplasia.
Dialogue: 0,0:00:10.06,0:00:11.77,Default,,0000,0000,0000,,This is one of the
Dialogue: 0,0:00:11.77,0:00:13.10,Default,,0000,0000,0000,,probably the only time
Dialogue: 0,0:00:13.10,0:00:18.00,Default,,0000,0000,0000,,in the sequence where pathology really\Nmeshes with what else is going on.
Dialogue: 0,0:00:18.00,0:00:18.83,Default,,0000,0000,0000,,
Dialogue: 0,0:00:18.83,0:00:21.04,Default,,0000,0000,0000,,We will spend
Dialogue: 0,0:00:21.04,0:00:25.01,Default,,0000,0000,0000,,much of the two hours today and\Nthen an hour Wednesday
Dialogue: 0,0:00:25.01,0:00:28.36,Default,,0000,0000,0000,,on the subject of neoplasms, that is\Ntumors
Dialogue: 0,0:00:28.36,0:00:33.40,Default,,0000,0000,0000,,this will feed into Dr Gruber's 11 o'clock lecture on Wednesday on the genetics
Dialogue: 0,0:00:33.40,0:00:34.04,Default,,0000,0000,0000,,
Dialogue: 0,0:00:34.04,0:00:38.07,Default,,0000,0000,0000,,aspects of neoplasia and\Nthen a very interesting MDC in the afternoon,
Dialogue: 0,0:00:38.07,0:00:39.09,Default,,0000,0000,0000,,
Dialogue: 0,0:00:39.09,0:00:44.07,Default,,0000,0000,0000,,dealing with some clinical aspects of\Nthose same things.
Dialogue: 0,0:00:44.07,0:00:46.03,Default,,0000,0000,0000,,But before we settle down
Dialogue: 0,0:00:46.03,0:00:49.09,Default,,0000,0000,0000,,to the subject of neoplasms, tumors and such,
Dialogue: 0,0:00:49.09,0:00:54.07,Default,,0000,0000,0000,,i want to spend a bit of time giving you\Na few notions and definitions in visual images
Dialogue: 0,0:00:54.07,0:00:55.06,Default,,0000,0000,0000,,images
Dialogue: 0,0:00:55.06,0:00:59.03,Default,,0000,0000,0000,,dealing with other
Dialogue: 0,0:00:59.03,0:01:03.04,Default,,0000,0000,0000,,abnormalities of growth short of\Nnew place, in other words there are some other
Dialogue: 0,0:01:03.04,0:01:04.08,Default,,0000,0000,0000,,some other
Dialogue: 0,0:01:04.08,0:01:08.03,Default,,0000,0000,0000,,disturbances in the size of cells\Ntissues and organs
Dialogue: 0,0:01:08.03,0:01:09.06,Default,,0000,0000,0000,,the
Dialogue: 0,0:01:09.06,0:01:13.04,Default,,0000,0000,0000,,mode of cellular proliferation and even
Dialogue: 0,0:01:13.04,0:01:16.01,Default,,0000,0000,0000,,lead the way that cells mature
Dialogue: 0,0:01:16.01,0:01:17.00,Default,,0000,0000,0000,,and
Dialogue: 0,0:01:17.00,0:01:20.01,Default,,0000,0000,0000,,look at a few of these\Nabnormalities first before we get onto the main
Dialogue: 0,0:01:20.01,0:01:21.08,Default,,0000,0000,0000,,subject
Dialogue: 0,0:01:21.08,0:01:23.00,Default,,0000,0000,0000,,let me begin
Dialogue: 0,0:01:23.00,0:01:25.03,Default,,0000,0000,0000,,very simply with
Dialogue: 0,0:01:25.03,0:01:26.06,Default,,0000,0000,0000,,situations
Dialogue: 0,0:01:26.06,0:01:28.08,Default,,0000,0000,0000,,in which you might
Dialogue: 0,0:01:28.08,0:01:32.08,Default,,0000,0000,0000,,encounter a bunch of cells, a tissue, an organ
Dialogue: 0,0:01:32.08,0:01:34.03,Default,,0000,0000,0000,,smaller than normal
Dialogue: 0,0:01:34.03,0:01:37.01,Default,,0000,0000,0000,,smaller than you expect
Dialogue: 0,0:01:37.01,0:01:38.36,Default,,0000,0000,0000,,and it runs
Dialogue: 0,0:01:38.36,0:01:40.03,Default,,0000,0000,0000,,something like this
Dialogue: 0,0:01:40.03,0:01:44.03,Default,,0000,0000,0000,,it makes pretty good sense that the one way\Nthat you could end up with a tissue
Dialogue: 0,0:01:44.03,0:01:46.08,Default,,0000,0000,0000,,that's abnormally small
Dialogue: 0,0:01:46.08,0:01:50.07,Default,,0000,0000,0000,,organized abnormally small is a\Ndevelopmental situation
Dialogue: 0,0:01:50.07,0:01:53.06,Default,,0000,0000,0000,,where it never grew up
Dialogue: 0,0:01:53.06,0:01:55.03,Default,,0000,0000,0000,,sort of a dwarfed tissue
Dialogue: 0,0:01:55.03,0:01:56.76,Default,,0000,0000,0000,,or organ
Dialogue: 0,0:01:56.76,0:01:58.00,Default,,0000,0000,0000,,and on the other hand
Dialogue: 0,0:01:58.00,0:01:59.08,Default,,0000,0000,0000,,there are situations
Dialogue: 0,0:01:59.08,0:02:03.04,Default,,0000,0000,0000,,as i think you're already familiar with
Dialogue: 0,0:02:03.04,0:02:08.80,Default,,0000,0000,0000,,when an organ or tissue reaches a\Ndefinitive adult size and then shrinks
Dialogue: 0,0:02:08.80,0:02:11.09,Default,,0000,0000,0000,,that process i think you know from\NRamsburgh's lecture we call
Dialogue: 0,0:02:11.09,0:02:13.63,Default,,0000,0000,0000,,atrophy
Dialogue: 0,0:02:13.63,0:02:15.04,Default,,0000,0000,0000,,so those are two kinds
Dialogue: 0,0:02:15.04,0:02:18.19,Default,,0000,0000,0000,,situations and i want to run\Nthrough first
Dialogue: 0,0:02:18.19,0:02:21.95,Default,,0000,0000,0000,,this list of developmental problems
Dialogue: 0,0:02:21.95,0:02:26.07,Default,,0000,0000,0000,,that we have encounter from time to time
Dialogue: 0,0:02:26.07,0:02:29.32,Default,,0000,0000,0000,,the most complete sort of defect
Dialogue: 0,0:02:29.32,0:02:33.29,Default,,0000,0000,0000,,you might encounter is when the\Nembryonic rudiment
Dialogue: 0,0:02:33.29,0:02:34.52,Default,,0000,0000,0000,,of an organ
Dialogue: 0,0:02:34.52,0:02:38.01,Default,,0000,0000,0000,,simply doesn't develop, it's a screw up in embryogenesis
Dialogue: 0,0:02:38.01,0:02:40.31,Default,,0000,0000,0000,,and then there is no organ
Dialogue: 0,0:02:40.31,0:02:41.04,Default,,0000,0000,0000,,laid down
Dialogue: 0,0:02:41.04,0:02:42.10,Default,,0000,0000,0000,,and we referred to that
Dialogue: 0,0:02:42.10,0:02:46.59,Default,,0000,0000,0000,,process as agenesis
Dialogue: 0,0:02:46.59,0:02:50.59,Default,,0000,0000,0000,,there's a slight variation on the theme\Nand that is where the rudiment of the organ
Dialogue: 0,0:02:50.59,0:02:51.36,Default,,0000,0000,0000,,may be
Dialogue: 0,0:02:51.36,0:02:53.38,Default,,0000,0000,0000,,laid down in the embryo, but
Dialogue: 0,0:02:53.38,0:02:56.18,Default,,0000,0000,0000,,the thing never grows
Dialogue: 0,0:02:56.18,0:02:58.93,Default,,0000,0000,0000,,non-descript nubbin' of nothing
Dialogue: 0,0:02:58.93,0:03:02.21,Default,,0000,0000,0000,,and that sometimes is referred to as aplasia
Dialogue: 0,0:03:02.21,0:03:05.89,Default,,0000,0000,0000,,those two terms are essentially\Nsynonymous
Dialogue: 0,0:03:05.89,0:03:07.69,Default,,0000,0000,0000,,it's an absence
Dialogue: 0,0:03:07.69,0:03:10.07,Default,,0000,0000,0000,,an absence of the tissue
Dialogue: 0,0:03:10.07,0:03:10.94,Default,,0000,0000,0000,,and I'll
Dialogue: 0,0:03:10.94,0:03:15.00,Default,,0000,0000,0000,,give you an example, a very striking example of this
Dialogue: 0,0:03:15.00,0:03:18.01,Default,,0000,0000,0000,,here's an autopsy specimen, let me orient you to it
Dialogue: 0,0:03:18.01,0:03:19.96,Default,,0000,0000,0000,,this is the urinary bladder down here
Dialogue: 0,0:03:19.96,0:03:21.24,Default,,0000,0000,0000,,here is
Dialogue: 0,0:03:21.24,0:03:29.82,Default,,0000,0000,0000,,a ureter on one side going up and connecting with a very respectable looking kidney
Dialogue: 0,0:03:29.82,0:03:32.60,Default,,0000,0000,0000,,here's the other ureter, boom!
Dialogue: 0,0:03:32.60,0:03:33.09,Default,,0000,0000,0000,,there was nothing outside the
Dialogue: 0,0:03:33.09,0:03:36.75,Default,,0000,0000,0000,,it's not a camera trick, there's nothing outside there, it just ended
Dialogue: 0,0:03:36.75,0:03:38.63,Default,,0000,0000,0000,,that way
Dialogue: 0,0:03:38.63,0:03:41.95,Default,,0000,0000,0000,,now that is an example of the unilateral renal
Dialogue: 0,0:03:41.95,0:03:42.100,Default,,0000,0000,0000,,agenesis
Dialogue: 0,0:03:42.100,0:03:47.38,Default,,0000,0000,0000,,or aplasia, i don't care which word you use
Dialogue: 0,0:03:47.38,0:03:50.99,Default,,0000,0000,0000,,this sort of thing is compatible with\Nlong happy life and this is strictly an incidental finding
Dialogue: 0,0:03:50.99,0:03:54.20,Default,,0000,0000,0000,,i don't remember anymore what this individual died of
Dialogue: 0,0:03:54.20,0:03:55.05,Default,,0000,0000,0000,,but it had nothing
Dialogue: 0,0:03:55.05,0:03:56.47,Default,,0000,0000,0000,,relating to the
Dialogue: 0,0:03:56.47,0:03:58.21,Default,,0000,0000,0000,,urinary tract
Dialogue: 0,0:03:58.21,0:04:02.29,Default,,0000,0000,0000,,so it's just a failure on one side for that
Dialogue: 0,0:04:02.29,0:04:05.45,Default,,0000,0000,0000,,kidney to develop. Agenesis or aplasia.
Dialogue: 0,0:04:05.45,0:04:07.44,Default,,0000,0000,0000,,sometimes we see this bilaterally. Both
Dialogue: 0,0:04:07.44,0:04:09.40,Default,,0000,0000,0000,,kidneys are not there
Dialogue: 0,0:04:09.40,0:04:11.03,Default,,0000,0000,0000,,and that
Dialogue: 0,0:04:11.03,0:04:16.02,Default,,0000,0000,0000,,of course is not compatible with life whereas this sort of thing is
Dialogue: 0,0:04:16.02,0:04:17.89,Default,,0000,0000,0000,,now
Dialogue: 0,0:04:17.89,0:04:20.82,Default,,0000,0000,0000,,the next step up from
Dialogue: 0,0:04:20.82,0:04:23.01,Default,,0000,0000,0000,,agenesis or aplasia
Dialogue: 0,0:04:23.01,0:04:25.06,Default,,0000,0000,0000,,is a situation where the
Dialogue: 0,0:04:25.06,0:04:28.06,Default,,0000,0000,0000,,the organ rudiment is laid down in the\Nembryo, and indeed
Dialogue: 0,0:04:28.06,0:04:31.23,Default,,0000,0000,0000,,grows but not
Dialogue: 0,0:04:31.23,0:04:33.06,Default,,0000,0000,0000,,as much as it should
Dialogue: 0,0:04:33.06,0:04:35.26,Default,,0000,0000,0000,,so you end up with something
Dialogue: 0,0:04:35.26,0:04:37.05,Default,,0000,0000,0000,,smaller than normal because of
Dialogue: 0,0:04:37.05,0:04:41.57,Default,,0000,0000,0000,,well we might call it loosely a growth failure, and that we call
Dialogue: 0,0:04:41.57,0:04:43.00,Default,,0000,0000,0000,,hypoplasia
Dialogue: 0,0:04:43.00,0:04:45.80,Default,,0000,0000,0000,,hypo meaning under or less than
Dialogue: 0,0:04:45.80,0:04:50.27,Default,,0000,0000,0000,,and there's an example, let me take you\Nthrough this one, it's a little bit confusing
Dialogue: 0,0:04:50.27,0:04:51.01,Default,,0000,0000,0000,,here's
Dialogue: 0,0:04:51.01,0:04:52.69,Default,,0000,0000,0000,,the bladder
Dialogue: 0,0:04:52.69,0:04:56.56,Default,,0000,0000,0000,,this happens to be the aorta, forget\Nabout that, here's the bladder
Dialogue: 0,0:04:56.56,0:04:57.76,Default,,0000,0000,0000,,the ureter
Dialogue: 0,0:04:57.76,0:05:00.50,Default,,0000,0000,0000,,on one side going up to a very decent looking
Dialogue: 0,0:05:00.50,0:05:03.02,Default,,0000,0000,0000,,kidney
Dialogue: 0,0:05:03.02,0:05:06.07,Default,,0000,0000,0000,,here is the ureter on the other side, sort\Nof stunted
Dialogue: 0,0:05:06.07,0:05:08.48,Default,,0000,0000,0000,,here's
Dialogue: 0,0:05:08.48,0:05:10.00,Default,,0000,0000,0000,,a little shrunken
Dialogue: 0,0:05:10.00,0:05:12.64,Default,,0000,0000,0000,,well, i shouldn't say shrunken, but a tiny, miniature
Dialogue: 0,0:05:12.64,0:05:14.90,Default,,0000,0000,0000,,kidney there
Dialogue: 0,0:05:14.90,0:05:16.01,Default,,0000,0000,0000,,that represents a unilateral
Dialogue: 0,0:05:16.01,0:05:22.02,Default,,0000,0000,0000,,renal hypoplasia
Dialogue: 0,0:05:22.02,0:05:25.17,Default,,0000,0000,0000,,again sort of an embryonic defect
Dialogue: 0,0:05:25.17,0:05:26.69,Default,,0000,0000,0000,,if you will
Dialogue: 0,0:05:26.69,0:05:29.01,Default,,0000,0000,0000,,sometimes we see this bilaterally
Dialogue: 0,0:05:29.01,0:05:32.09,Default,,0000,0000,0000,,and it could be all degrees, it could\Nbe something between this and this or something
Dialogue: 0,0:05:32.09,0:05:35.92,Default,,0000,0000,0000,,even less than this and as long as
Dialogue: 0,0:05:35.92,0:05:38.00,Default,,0000,0000,0000,,you put it under the microscope and you see
Dialogue: 0,0:05:38.00,0:05:41.65,Default,,0000,0000,0000,,the structure of kidney, but there's not enough of it, it's too small. that's hypoplasia.
Dialogue: 0,0:05:41.65,0:05:44.04,Default,,0000,0000,0000,,
Dialogue: 0,0:05:44.04,0:05:49.48,Default,,0000,0000,0000,,i've shown you urinary tract here, these sorts of defects, agenesis and hypoplasia
Dialogue: 0,0:05:49.48,0:05:51.19,Default,,0000,0000,0000,,occur in
Dialogue: 0,0:05:51.19,0:05:52.45,Default,,0000,0000,0000,,other organs
Dialogue: 0,0:05:52.45,0:05:56.40,Default,,0000,0000,0000,,and organ systems as well, i just happen\Nto have these pictures on hand
Dialogue: 0,0:05:56.40,0:06:00.69,Default,,0000,0000,0000,,one of things you'll encounter when you\Nget over in the hospital because we're sort of
Dialogue: 0,0:06:00.69,0:06:03.09,Default,,0000,0000,0000,,a funnel for odd things
Dialogue: 0,0:06:03.09,0:06:05.13,Default,,0000,0000,0000,,is fairly often
Dialogue: 0,0:06:05.13,0:06:07.32,Default,,0000,0000,0000,,
Dialogue: 0,0:06:07.32,0:06:11.97,Default,,0000,0000,0000,,kids born with what we call hypoplastic left heart
Dialogue: 0,0:06:11.97,0:06:13.01,Default,,0000,0000,0000,,and that's the situation
Dialogue: 0,0:06:13.01,0:06:17.85,Default,,0000,0000,0000,,where the chambers of the left side\Nof the heart and even sometimes a portion
Dialogue: 0,0:06:17.85,0:06:19.03,Default,,0000,0000,0000,,of the aorta
Dialogue: 0,0:06:19.03,0:06:24.01,Default,,0000,0000,0000,,simply don't develop properly, and there are little tiny nubbin's on the heart
Dialogue: 0,0:06:24.01,0:06:28.01,Default,,0000,0000,0000,,and this hypoplastic left heart\Nsyndrome is lethal unless some pretty fancy
Dialogue: 0,0:06:28.01,0:06:32.01,Default,,0000,0000,0000,,surgery is done to intervene for a while
Dialogue: 0,0:06:32.01,0:06:36.35,Default,,0000,0000,0000,,so you will see that hypoplastic left heart
Dialogue: 0,0:06:36.35,0:06:40.01,Default,,0000,0000,0000,,one more term on that list that i gave\Nyou, i just defined it and i want to illustrate it
Dialogue: 0,0:06:40.01,0:06:42.67,Default,,0000,0000,0000,,and that is atresia
Dialogue: 0,0:06:42.67,0:06:44.84,Default,,0000,0000,0000,,a-t-r-e-s-i-a, atresia
Dialogue: 0,0:06:44.84,0:06:49.98,Default,,0000,0000,0000,,which is a situation and again it's a\Ndevelopmental failure where a channel
Dialogue: 0,0:06:49.98,0:06:53.03,Default,,0000,0000,0000,,a normal opening or channel fails
Dialogue: 0,0:06:53.03,0:06:55.54,Default,,0000,0000,0000,,to stay open
Dialogue: 0,0:06:55.54,0:06:59.07,Default,,0000,0000,0000,,fails to form properly so you end up with a closure where you should have
Dialogue: 0,0:06:59.07,0:07:02.03,Default,,0000,0000,0000,,a channel
Dialogue: 0,0:07:02.03,0:07:06.17,Default,,0000,0000,0000,,something let's say along the GI tract or along a duct
Dialogue: 0,0:07:06.17,0:07:10.17,Default,,0000,0000,0000,,where it simply disappears because it never\Nopened up properly. That's atresia.
Dialogue: 0,0:07:10.17,0:07:13.04,Default,,0000,0000,0000,,Now the second situation
Dialogue: 0,0:07:13.04,0:07:16.41,Default,,0000,0000,0000,,i mentioned back on that list
Dialogue: 0,0:07:16.41,0:07:19.01,Default,,0000,0000,0000,,other than developmental is a situation
Dialogue: 0,0:07:19.01,0:07:20.01,Default,,0000,0000,0000,,where the organ has reached
Dialogue: 0,0:07:20.01,0:07:25.30,Default,,0000,0000,0000,,a definitive size and undergoes a process of atrophy
Dialogue: 0,0:07:25.30,0:07:28.96,Default,,0000,0000,0000,,atrophy can come about really in in\Ntwo ways
Dialogue: 0,0:07:28.96,0:07:29.97,Default,,0000,0000,0000,,first of all
Dialogue: 0,0:07:29.97,0:07:34.00,Default,,0000,0000,0000,,every single cell in the tissue could shrink
Dialogue: 0,0:07:34.00,0:07:36.03,Default,,0000,0000,0000,,by some percentage
Dialogue: 0,0:07:36.03,0:07:39.35,Default,,0000,0000,0000,,and that would produce a smaller tissue, a smaller organ
Dialogue: 0,0:07:39.35,0:07:40.01,Default,,0000,0000,0000,,or
Dialogue: 0,0:07:40.01,0:07:43.70,Default,,0000,0000,0000,,a certain number of cells as they start out with a million cells in the population
Dialogue: 0,0:07:43.70,0:07:44.01,Default,,0000,0000,0000,,and
Dialogue: 0,0:07:44.01,0:07:47.91,Default,,0000,0000,0000,,some of them disappear by apoptosis
Dialogue: 0,0:07:47.91,0:07:49.79,Default,,0000,0000,0000,,and you end up
Dialogue: 0,0:07:49.79,0:07:53.02,Default,,0000,0000,0000,,with eight hundred thousand cells, that's going to be a shrunken tissue
Dialogue: 0,0:07:53.02,0:07:54.93,Default,,0000,0000,0000,,so a tissue can
Dialogue: 0,0:07:54.93,0:07:58.72,Default,,0000,0000,0000,,undergo atrophy with shrinkage of individual cells
Dialogue: 0,0:07:58.72,0:08:02.42,Default,,0000,0000,0000,,sometimes loss of cells or both
Dialogue: 0,0:08:02.42,0:08:06.88,Default,,0000,0000,0000,,but it's a secondary change after the\Nthe organ has reached its definitive size
Dialogue: 0,0:08:06.88,0:08:09.10,Default,,0000,0000,0000,,some
Dialogue: 0,0:08:09.10,0:08:12.81,Default,,0000,0000,0000,,examples of atrophy as some of you may know already
Dialogue: 0,0:08:12.81,0:08:17.14,Default,,0000,0000,0000,,is perfectly physiologic in the, let's say, fetus
Dialogue: 0,0:08:17.14,0:08:19.32,Default,,0000,0000,0000,,as various things form and come and go
Dialogue: 0,0:08:19.32,0:08:20.01,Default,,0000,0000,0000,,there's atrophy
Dialogue: 0,0:08:20.01,0:08:23.08,Default,,0000,0000,0000,,there's certainly atrophy of fetal structures
Dialogue: 0,0:08:23.08,0:08:25.08,Default,,0000,0000,0000,,in the neonatal period
Dialogue: 0,0:08:25.08,0:08:28.33,Default,,0000,0000,0000,,umbilical vessels and that sort of thing undergo
Dialogue: 0,0:08:28.33,0:08:30.44,Default,,0000,0000,0000,,atrophy
Dialogue: 0,0:08:30.44,0:08:31.06,Default,,0000,0000,0000,,there are examples
Dialogue: 0,0:08:31.06,0:08:34.01,Default,,0000,0000,0000,,of physiologic atrophy
Dialogue: 0,0:08:34.01,0:08:38.08,Default,,0000,0000,0000,,as one matures into adult life, the tonsils shrink
Dialogue: 0,0:08:38.08,0:08:40.17,Default,,0000,0000,0000,,the thymus shrinks
Dialogue: 0,0:08:40.17,0:08:41.01,Default,,0000,0000,0000,,and so forth
Dialogue: 0,0:08:41.01,0:08:44.01,Default,,0000,0000,0000,,there are these things which are expected and physiologic
Dialogue: 0,0:08:44.01,0:08:46.09,Default,,0000,0000,0000,,when
Dialogue: 0,0:08:46.09,0:08:52.00,Default,,0000,0000,0000,,it comes to pathologic forms of atrophy, there are many reasons why
Dialogue: 0,0:08:52.00,0:08:53.10,Default,,0000,0000,0000,,this can happen, one that Dr
Dialogue: 0,0:08:53.10,0:08:57.05,Default,,0000,0000,0000,,Ramsburgh may have mentioned is ischemia
Dialogue: 0,0:08:57.05,0:09:02.05,Default,,0000,0000,0000,,if you rob a tissue of its blood supply, let's say, not enough to kill it
Dialogue: 0,0:09:02.05,0:09:04.07,Default,,0000,0000,0000,,but really to cut it down, there's
Dialogue: 0,0:09:04.07,0:09:07.06,Default,,0000,0000,0000,,such a thing as ischemic atrophy
Dialogue: 0,0:09:07.06,0:09:10.03,Default,,0000,0000,0000,,and you'll see that in arteriosclerotic
Dialogue: 0,0:09:10.03,0:09:14.05,Default,,0000,0000,0000,,areas where the tissues tend to simply shrink
Dialogue: 0,0:09:14.05,0:09:16.03,Default,,0000,0000,0000,,starvation
Dialogue: 0,0:09:16.03,0:09:17.04,Default,,0000,0000,0000,,you don't
Dialogue: 0,0:09:17.04,0:09:20.08,Default,,0000,0000,0000,,feed a person enough calories, starvation will produce
Dialogue: 0,0:09:20.08,0:09:25.04,Default,,0000,0000,0000,,atrophy. there's a hierarchy of organs which i don't want to go into
Dialogue: 0,0:09:25.04,0:09:27.04,Default,,0000,0000,0000,,for instance, the brain doesn't atrophy
Dialogue: 0,0:09:27.04,0:09:28.71,Default,,0000,0000,0000,,in that situation
Dialogue: 0,0:09:28.71,0:09:32.30,Default,,0000,0000,0000,,but the adipose tissue does, the liver does, and so forth
Dialogue: 0,0:09:32.30,0:09:34.01,Default,,0000,0000,0000,,that's starvation atrophy
Dialogue: 0,0:09:34.01,0:09:37.06,Default,,0000,0000,0000,,in the case of muscular tissues
Dialogue: 0,0:09:37.06,0:09:38.07,Default,,0000,0000,0000,,disuse
Dialogue: 0,0:09:38.07,0:09:41.06,Default,,0000,0000,0000,,just plain old disuse will cause atrophy
Dialogue: 0,0:09:41.06,0:09:43.01,Default,,0000,0000,0000,,it could be very striking
Dialogue: 0,0:09:43.01,0:09:47.40,Default,,0000,0000,0000,,i don't know if any of you have been in this situation, but you have an acute injury
Dialogue: 0,0:09:47.40,0:09:48.08,Default,,0000,0000,0000,,like, oh let's say,
Dialogue: 0,0:09:48.08,0:09:53.08,Default,,0000,0000,0000,,a bad knee, for some reason, just self splinting
Dialogue: 0,0:09:53.08,0:09:56.03,Default,,0000,0000,0000,,not using that leg in the same way
Dialogue: 0,0:09:56.03,0:09:58.53,Default,,0000,0000,0000,,will cause a shrinkage within a few weeks
Dialogue: 0,0:09:58.53,0:10:04.03,Default,,0000,0000,0000,,you can get a loss in circumference of a thigh
Dialogue: 0,0:10:04.03,0:10:06.02,Default,,0000,0000,0000,,i don't know how many of you are skiiers
Dialogue: 0,0:10:06.02,0:10:07.10,Default,,0000,0000,0000,,that have gotten into
Dialogue: 0,0:10:07.10,0:10:12.03,Default,,0000,0000,0000,,trouble and ended up with let's say a cast on an extremity
Dialogue: 0,0:10:12.03,0:10:17.02,Default,,0000,0000,0000,,for a number of weeks and when that cast comes off, you've got a shriveled leg
Dialogue: 0,0:10:17.02,0:10:19.01,Default,,0000,0000,0000,,compared to the other one
Dialogue: 0,0:10:19.01,0:10:22.05,Default,,0000,0000,0000,,that is disuse atrophy
Dialogue: 0,0:10:22.05,0:10:26.02,Default,,0000,0000,0000,,an extreme example of that is something we call neurogenic atrophy, if you cut
Dialogue: 0,0:10:26.02,0:10:26.08,Default,,0000,0000,0000,,the motor
Dialogue: 0,0:10:26.08,0:10:29.03,Default,,0000,0000,0000,,nerve going to a muscle
Dialogue: 0,0:10:29.03,0:10:33.02,Default,,0000,0000,0000,,then that muscle can't work at all and is getting\Nno signals
Dialogue: 0,0:10:33.02,0:10:37.10,Default,,0000,0000,0000,,it'll really shrink, it's a tremendous sort of atrophy
Dialogue: 0,0:10:37.10,0:10:39.03,Default,,0000,0000,0000,,then
Dialogue: 0,0:10:39.03,0:10:42.01,Default,,0000,0000,0000,,well, i'll stop this list with one more
Dialogue: 0,0:10:42.01,0:10:45.04,Default,,0000,0000,0000,,many tissues in the body are
Dialogue: 0,0:10:45.04,0:10:48.06,Default,,0000,0000,0000,,the way they are because they have a\Ncertain endocrine support
Dialogue: 0,0:10:48.06,0:10:54.03,Default,,0000,0000,0000,,they depend on a certain level of a particular\Nhormone, and if you withdraw that hormone, the tissue
Dialogue: 0,0:10:54.03,0:10:58.07,Default,,0000,0000,0000,,will undergo atrophy. Morphologically
Dialogue: 0,0:10:58.07,0:10:59.05,Default,,0000,0000,0000,,it's pretty
Dialogue: 0,0:10:59.05,0:11:02.32,Default,,0000,0000,0000,,straight forward, i'm not going to show you much of this
Dialogue: 0,0:11:02.32,0:11:02.09,Default,,0000,0000,0000,,it's simply the tissue
Dialogue: 0,0:11:02.09,0:11:04.03,Default,,0000,0000,0000,,is smaller
Dialogue: 0,0:11:04.03,0:11:08.19,Default,,0000,0000,0000,,you look at it under the microscope and the\Nindividual cells are smaller
Dialogue: 0,0:11:08.19,0:11:11.10,Default,,0000,0000,0000,,the number of cells, that's a tougher thing to deal
Dialogue: 0,0:11:11.10,0:11:15.10,Default,,0000,0000,0000,,with, but basically it's a small tissue
Dialogue: 0,0:11:15.10,0:11:19.07,Default,,0000,0000,0000,,sometimes there's partial fibrous replacement as the tissues shrink
Dialogue: 0,0:11:19.07,0:11:23.03,Default,,0000,0000,0000,,we call that fibrous atrophy
Dialogue: 0,0:11:23.03,0:11:23.07,Default,,0000,0000,0000,,sometimes
Dialogue: 0,0:11:23.07,0:11:28.01,Default,,0000,0000,0000,,this seems to be an increase in adipose\Ntissue, marbling the tissue, we call that fatty atrophy
Dialogue: 0,0:11:28.01,0:11:31.00,Default,,0000,0000,0000,,but basically the business cells of the tissue
Dialogue: 0,0:11:31.00,0:11:32.07,Default,,0000,0000,0000,,are smaller
Dialogue: 0,0:11:32.07,0:11:35.01,Default,,0000,0000,0000,,there's one variation on this theme that
Dialogue: 0,0:11:35.01,0:11:40.03,Default,,0000,0000,0000,,Ramsburgh may have introduced you to and that's
Dialogue: 0,0:11:40.03,0:11:43.05,Default,,0000,0000,0000,,as a cell shrinks
Dialogue: 0,0:11:43.05,0:11:45.07,Default,,0000,0000,0000,,it basically
Dialogue: 0,0:11:45.07,0:11:50.04,Default,,0000,0000,0000,,is undergoing a process of autophagy, it's eating itself, it's digesting
Dialogue: 0,0:11:50.04,0:11:52.02,Default,,0000,0000,0000,,various of its
Dialogue: 0,0:11:52.02,0:11:55.00,Default,,0000,0000,0000,,organelles and so forth
Dialogue: 0,0:11:55.00,0:12:00.04,Default,,0000,0000,0000,,one of the things that happens\Nfrom this digestive process is that there
Dialogue: 0,0:12:00.04,0:12:02.37,Default,,0000,0000,0000,,may be residual products
Dialogue: 0,0:12:02.37,0:12:04.06,Default,,0000,0000,0000,,left afterwards and
Dialogue: 0,0:12:04.06,0:12:05.00,Default,,0000,0000,0000,,they
Dialogue: 0,0:12:05.00,0:12:07.08,Default,,0000,0000,0000,,tend to be pigmented products which we've
Dialogue: 0,0:12:07.08,0:12:10.09,Default,,0000,0000,0000,,we refer to as lipofuscin
Dialogue: 0,0:12:10.09,0:12:13.06,Default,,0000,0000,0000,,
Dialogue: 0,0:12:13.06,0:12:18.06,Default,,0000,0000,0000,,here's a liver where particularly in\Nthis area, the central area, the cells
Dialogue: 0,0:12:18.06,0:12:20.05,Default,,0000,0000,0000,,are shrunken and you'll
Dialogue: 0,0:12:20.05,0:12:23.08,Default,,0000,0000,0000,,notice this is not a particularly good photo, but you'll notice they are brown
Dialogue: 0,0:12:23.08,0:12:25.04,Default,,0000,0000,0000,,and that's
Dialogue: 0,0:12:25.04,0:12:28.01,Default,,0000,0000,0000,,because of a relative concentration of lipofuscin there
Dialogue: 0,0:12:28.01,0:12:29.83,Default,,0000,0000,0000,,they've been undergoing
Dialogue: 0,0:12:29.83,0:12:31.03,Default,,0000,0000,0000,,autophagy
Dialogue: 0,0:12:31.03,0:12:36.04,Default,,0000,0000,0000,,and the residual products are piling\Nup and sometimes we refer to this as pigment atrophy
Dialogue: 0,0:12:36.04,0:12:38.01,Default,,0000,0000,0000,,or brown atrophy
Dialogue: 0,0:12:38.01,0:12:42.04,Default,,0000,0000,0000,,and i've seen shrunken livers where there's perhaps half the mass of the usual liver
Dialogue: 0,0:12:42.04,0:12:43.00,Default,,0000,0000,0000,,and they're really
Dialogue: 0,0:12:43.00,0:12:44.64,Default,,0000,0000,0000,,definite
Dialogue: 0,0:12:44.64,0:12:46.04,Default,,0000,0000,0000,,brown
Dialogue: 0,0:12:46.04,0:12:47.70,Default,,0000,0000,0000,,rather than the ordinary
Dialogue: 0,0:12:47.70,0:12:48.65,Default,,0000,0000,0000,,liver color
Dialogue: 0,0:12:48.65,0:12:50.87,Default,,0000,0000,0000,,because of this sort of accumulation
Dialogue: 0,0:12:50.87,0:12:53.02,Default,,0000,0000,0000,,Okay so
Dialogue: 0,0:12:53.02,0:12:57.01,Default,,0000,0000,0000,,much for smaller than normal, let's go to the flip side
Dialogue: 0,0:12:57.01,0:13:00.96,Default,,0000,0000,0000,,and look at situations where the tissue\Nor the organ may be larger
Dialogue: 0,0:13:00.96,0:13:02.03,Default,,0000,0000,0000,,than normal
Dialogue: 0,0:13:02.03,0:13:03.05,Default,,0000,0000,0000,,and this
Dialogue: 0,0:13:03.05,0:13:07.00,Default,,0000,0000,0000,,can come about in two ways
Dialogue: 0,0:13:07.00,0:13:11.09,Default,,0000,0000,0000,,you can have an increase in the size of\Nthe cells in the tissue
Dialogue: 0,0:13:11.09,0:13:15.01,Default,,0000,0000,0000,,and we refer to that as hypertrophy
Dialogue: 0,0:13:15.01,0:13:19.02,Default,,0000,0000,0000,,you can have an increase in the number\Nof cells in the tissue, we call that hyperplasia
Dialogue: 0,0:13:19.02,0:13:21.01,Default,,0000,0000,0000,,Now let's go back
Dialogue: 0,0:13:21.01,0:13:23.07,Default,,0000,0000,0000,,up to hypertrophy
Dialogue: 0,0:13:23.07,0:13:28.02,Default,,0000,0000,0000,,let me point out that size increase isn't simply cell swelling, you know
Dialogue: 0,0:13:28.02,0:13:32.06,Default,,0000,0000,0000,,about the phenomenon of cell swelling, which involves a net accumulation of water
Dialogue: 0,0:13:32.06,0:13:35.06,Default,,0000,0000,0000,,that we wouldn't call hypertrophy
Dialogue: 0,0:13:35.06,0:13:39.06,Default,,0000,0000,0000,,in hypertrophy, the cells enlarge because of an increased
Dialogue: 0,0:13:39.06,0:13:41.01,Default,,0000,0000,0000,,synthesis
Dialogue: 0,0:13:41.01,0:13:43.05,Default,,0000,0000,0000,,of cellular components
Dialogue: 0,0:13:43.05,0:13:44.78,Default,,0000,0000,0000,,i'll show you that in a
Dialogue: 0,0:13:44.78,0:13:46.01,Default,,0000,0000,0000,,moment
Dialogue: 0,0:13:46.01,0:13:48.00,Default,,0000,0000,0000,,again hyperplasia
Dialogue: 0,0:13:48.00,0:13:51.07,Default,,0000,0000,0000,,involves an increase in cell number so you'd look
Dialogue: 0,0:13:51.07,0:13:55.01,Default,,0000,0000,0000,,for hyperplasia only in tissues that are capable of
Dialogue: 0,0:13:55.01,0:13:57.08,Default,,0000,0000,0000,,dividing in the adult state
Dialogue: 0,0:13:57.08,0:14:00.05,Default,,0000,0000,0000,,another was a permanent sort of tissue
Dialogue: 0,0:14:00.05,0:14:03.08,Default,,0000,0000,0000,,you're not going to get hyperplasia ordinarily in muscle
Dialogue: 0,0:14:03.08,0:14:05.01,Default,,0000,0000,0000,,you're not going to get
Dialogue: 0,0:14:05.01,0:14:11.03,Default,,0000,0000,0000,,hyperplasia, well muscle is probably the best example. but in other
Dialogue: 0,0:14:11.03,0:14:12.09,Default,,0000,0000,0000,,organs, you may
Dialogue: 0,0:14:12.09,0:14:16.05,Default,,0000,0000,0000,,get hyperplasia along with hypertrophy
Dialogue: 0,0:14:16.05,0:14:17.10,Default,,0000,0000,0000,,but conceptually hypertrophy
Dialogue: 0,0:14:17.10,0:14:22.40,Default,,0000,0000,0000,,is increase in cell size, hyperplasia is increase in cell
Dialogue: 0,0:14:22.40,0:14:24.25,Default,,0000,0000,0000,,number
Dialogue: 0,0:14:24.25,0:14:26.07,Default,,0000,0000,0000,,the
Dialogue: 0,0:14:26.07,0:14:33.07,Default,,0000,0000,0000,,best example of hypertrophy is in muscular tissues
Dialogue: 0,0:14:33.07,0:14:35.05,Default,,0000,0000,0000,,it's a response
Dialogue: 0,0:14:35.05,0:14:38.08,Default,,0000,0000,0000,,hypertrophy in muscle is a response to an overload
Dialogue: 0,0:14:38.08,0:14:42.06,Default,,0000,0000,0000,,or unusual workload or what not
Dialogue: 0,0:14:42.06,0:14:46.04,Default,,0000,0000,0000,,now you need a lot of imagination for this, but imagine i went in for bodybuilding
Dialogue: 0,0:14:46.04,0:14:48.03,Default,,0000,0000,0000,,which i never will
Dialogue: 0,0:14:48.03,0:14:51.07,Default,,0000,0000,0000,,and you know you you pump three hundred\Npounds like this
Dialogue: 0,0:14:51.07,0:14:53.02,Default,,0000,0000,0000,,and after a while couldn't
Dialogue: 0,0:14:53.02,0:14:55.08,Default,,0000,0000,0000,,get into the lab coat. Bulging
Dialogue: 0,0:14:55.08,0:14:59.03,Default,,0000,0000,0000,,muscles, i told you, imagination.
Dialogue: 0,0:14:59.03,0:15:00.04,Default,,0000,0000,0000,,the
Dialogue: 0,0:15:00.04,0:15:03.41,Default,,0000,0000,0000,,muscles of the bodybuilder
Dialogue: 0,0:15:03.41,0:15:06.43,Default,,0000,0000,0000,,you've all seen pictures of this and maybe some of you are into this sort of sport
Dialogue: 0,0:15:06.43,0:15:07.08,Default,,0000,0000,0000,,this
Dialogue: 0,0:15:07.08,0:15:09.69,Default,,0000,0000,0000,,represents
Dialogue: 0,0:15:09.69,0:15:10.05,Default,,0000,0000,0000,,hypertrophy
Dialogue: 0,0:15:10.05,0:15:15.00,Default,,0000,0000,0000,,of muscle, there isn't any real increase in the number of muscle cells
Dialogue: 0,0:15:15.00,0:15:18.08,Default,,0000,0000,0000,,but any individual muscle cells instead of being this big around is this big around
Dialogue: 0,0:15:18.08,0:15:20.01,Default,,0000,0000,0000,,and it
Dialogue: 0,0:15:20.01,0:15:23.00,Default,,0000,0000,0000,,represents actually a synthesis of more
Dialogue: 0,0:15:23.00,0:15:26.01,Default,,0000,0000,0000,,contractile machinery
Dialogue: 0,0:15:26.01,0:15:27.83,Default,,0000,0000,0000,,in the muscle, it's a response
Dialogue: 0,0:15:27.83,0:15:30.03,Default,,0000,0000,0000,,to the work
Dialogue: 0,0:15:30.03,0:15:33.08,Default,,0000,0000,0000,,now a place where we see this that isn't so trivial
Dialogue: 0,0:15:33.08,0:15:35.00,Default,,0000,0000,0000,,is
Dialogue: 0,0:15:35.00,0:15:37.02,Default,,0000,0000,0000,,is, for instance, heart muscle
Dialogue: 0,0:15:37.02,0:15:41.00,Default,,0000,0000,0000,,that is subjected to an abnormal load
Dialogue: 0,0:15:41.00,0:15:44.09,Default,,0000,0000,0000,,for instance, a left ventricle
Dialogue: 0,0:15:44.09,0:15:51.09,Default,,0000,0000,0000,,having to pump blood in a patient with uncontrolled hypertension
Dialogue: 0,0:15:51.09,0:15:55.01,Default,,0000,0000,0000,,in other words, the systemic blood pressure is elevated, the arteriolar resistance is elevated
Dialogue: 0,0:15:55.01,0:15:58.44,Default,,0000,0000,0000,,and every time that poor old left ventricle
Dialogue: 0,0:15:58.44,0:16:02.08,Default,,0000,0000,0000,,tries to eject blood, it's doing it against an increased head of pressure
Dialogue: 0,0:16:02.08,0:16:06.09,Default,,0000,0000,0000,,those muscles are going to undergo\Nhypertrophy
Dialogue: 0,0:16:06.09,0:16:07.10,Default,,0000,0000,0000,,or
Dialogue: 0,0:16:07.10,0:16:11.01,Default,,0000,0000,0000,,let's say the valve, the so-called\Naortic valve, which is a valve between
Dialogue: 0,0:16:11.01,0:16:17.05,Default,,0000,0000,0000,,the left ventricle and the aorta, as the blood flows out, if that valve gets narrowed
Dialogue: 0,0:16:17.05,0:16:20.01,Default,,0000,0000,0000,,the poor old ventricle has to squeeze harder to get
Dialogue: 0,0:16:20.01,0:16:23.00,Default,,0000,0000,0000,,the blood out to maintain life, it will\Nundergo hypertrophy
Dialogue: 0,0:16:23.00,0:16:24.14,Default,,0000,0000,0000,,not hyperplasia
Dialogue: 0,0:16:24.14,0:16:25.12,Default,,0000,0000,0000,,but hypertrophy
Dialogue: 0,0:16:25.12,0:16:26.06,Default,,0000,0000,0000,,and the
Dialogue: 0,0:16:26.06,0:16:29.04,Default,,0000,0000,0000,,heart gains weight
Dialogue: 0,0:16:29.04,0:16:31.03,Default,,0000,0000,0000,,the ventricle becomes thick
Dialogue: 0,0:16:31.03,0:16:35.09,Default,,0000,0000,0000,,and the cells become enlarged. I'll illustrate this for you.
Dialogue: 0,0:16:35.09,0:16:37.05,Default,,0000,0000,0000,,here is
Dialogue: 0,0:16:37.05,0:16:41.04,Default,,0000,0000,0000,,don't pay attention to the color, there have been\Nsome post-mortem changes here but
Dialogue: 0,0:16:41.04,0:16:43.74,Default,,0000,0000,0000,,this is a bread loaf slice
Dialogue: 0,0:16:43.74,0:16:45.04,Default,,0000,0000,0000,,of a normal heart
Dialogue: 0,0:16:45.04,0:16:47.92,Default,,0000,0000,0000,,you're looking at the right ventricle\Nover here
Dialogue: 0,0:16:47.92,0:16:52.21,Default,,0000,0000,0000,,left ventricle over here ordinarily, this is normal, the right ventricle is very thin
Dialogue: 0,0:16:52.21,0:16:57.01,Default,,0000,0000,0000,,because it pumps against a lesser head of pressure in the pulmonary circuit. The left ventricle
Dialogue: 0,0:16:57.01,0:16:59.56,Default,,0000,0000,0000,,,that's about normal thickness,
Dialogue: 0,0:16:59.56,0:17:01.00,Default,,0000,0000,0000,,now the next slide
Dialogue: 0,0:17:01.00,0:17:05.04,Default,,0000,0000,0000,,is not a photo trick and again\Ndon't worry about the colors, but the next
Dialogue: 0,0:17:05.04,0:17:12.02,Default,,0000,0000,0000,,slide is taken from an individual with high blood pressure
Dialogue: 0,0:17:12.02,0:17:15.02,Default,,0000,0000,0000,,now that first heart probably weighed
Dialogue: 0,0:17:15.02,0:17:18.82,Default,,0000,0000,0000,,oh in the neighborhood of three hundred, three hundred and twenty five grams
Dialogue: 0,0:17:18.82,0:17:20.04,Default,,0000,0000,0000,,this heart weighed closer
Dialogue: 0,0:17:20.04,0:17:24.02,Default,,0000,0000,0000,,to the six or seven hundred grams, i don't remember precisely, but
Dialogue: 0,0:17:24.02,0:17:28.00,Default,,0000,0000,0000,,it kind of speaks for itself, there is more muscle\Nthere
Dialogue: 0,0:17:28.00,0:17:31.10,Default,,0000,0000,0000,,and again this is not hyperplasia, this is\Nhypertrophy
Dialogue: 0,0:17:31.10,0:17:36.04,Default,,0000,0000,0000,,and it looks something like this. i know you don't know much of this histology
Dialogue: 0,0:17:36.04,0:17:37.09,Default,,0000,0000,0000,,but just
Dialogue: 0,0:17:37.09,0:17:41.05,Default,,0000,0000,0000,,think of these as cross-sections of these cylindrical muscle cells
Dialogue: 0,0:17:41.05,0:17:42.09,Default,,0000,0000,0000,,and this is
Dialogue: 0,0:17:42.09,0:17:44.09,Default,,0000,0000,0000,,a normal myocardium
Dialogue: 0,0:17:44.09,0:17:45.06,Default,,0000,0000,0000,,and
Dialogue: 0,0:17:45.06,0:17:50.05,Default,,0000,0000,0000,,let's just cast your eyeballs around and look at the approximate
Dialogue: 0,0:17:50.05,0:17:54.08,Default,,0000,0000,0000,,average diameter
Dialogue: 0,0:17:54.08,0:17:55.06,Default,,0000,0000,0000,,the next slide
Dialogue: 0,0:17:55.06,0:17:58.06,Default,,0000,0000,0000,,is taken with the same optics in the microscope
Dialogue: 0,0:17:58.06,0:18:04.01,Default,,0000,0000,0000,,from a hypertrophic heart, now you got this?
Dialogue: 0,0:18:04.01,0:18:04.07,Default,,0000,0000,0000,,The point
Dialogue: 0,0:18:04.07,0:18:08.81,Default,,0000,0000,0000,,those cells are really increased in diameter, don't worry about this, I don't expect you to
Dialogue: 0,0:18:08.81,0:18:11.05,Default,,0000,0000,0000,,pick this up on the quiz
Dialogue: 0,0:18:11.05,0:18:13.01,Default,,0000,0000,0000,,but just to show you
Dialogue: 0,0:18:13.01,0:18:14.00,Default,,0000,0000,0000,,the increase
Dialogue: 0,0:18:14.00,0:18:19.02,Default,,0000,0000,0000,,and what this represents really is an increase, a very striking increase
Dialogue: 0,0:18:19.02,0:18:21.06,Default,,0000,0000,0000,,in the myofibrillar contractile machinery
Dialogue: 0,0:18:21.06,0:18:24.08,Default,,0000,0000,0000,,of these cells
Dialogue: 0,0:18:24.08,0:18:28.68,Default,,0000,0000,0000,,so this is clearly an adaptive
Dialogue: 0,0:18:28.68,0:18:30.05,Default,,0000,0000,0000,,phenomenon
Dialogue: 0,0:18:30.05,0:18:33.06,Default,,0000,0000,0000,,and it works very well up to a point
Dialogue: 0,0:18:33.06,0:18:38.09,Default,,0000,0000,0000,,the heart can't keep getting more and more and more hypertrophic
Dialogue: 0,0:18:38.09,0:18:40.07,Default,,0000,0000,0000,,i've never seen a heart
Dialogue: 0,0:18:40.07,0:18:42.08,Default,,0000,0000,0000,,weigh much more than a kilogram
Dialogue: 0,0:18:42.08,0:18:44.31,Default,,0000,0000,0000,,and that's rare
Dialogue: 0,0:18:44.31,0:18:45.05,Default,,0000,0000,0000,,but beyond that
Dialogue: 0,0:18:45.05,0:18:46.81,Default,,0000,0000,0000,,it doesn't work
Dialogue: 0,0:18:46.81,0:18:51.30,Default,,0000,0000,0000,,and one of the reasons that it doesn't work\Nis that the vascularity of the blood supply
Dialogue: 0,0:18:51.30,0:18:53.01,Default,,0000,0000,0000,,of the heart
Dialogue: 0,0:18:53.01,0:18:56.02,Default,,0000,0000,0000,,muscle doesn't keep up
Dialogue: 0,0:18:56.02,0:18:59.04,Default,,0000,0000,0000,,with too much hypertrophy and pretty soon
Dialogue: 0,0:18:59.04,0:19:03.07,Default,,0000,0000,0000,,the muscle to capillary ratio is unfavorable
Dialogue: 0,0:19:03.07,0:19:06.10,Default,,0000,0000,0000,,and it plateaus, it can't go any further
Dialogue: 0,0:19:06.10,0:19:12.01,Default,,0000,0000,0000,,and then what you get is the onset of apoptosis in cells and actually some
Dialogue: 0,0:19:12.01,0:19:17.00,Default,,0000,0000,0000,,fibrous replacement of the myocardium so it doesn't work indefinitely
Dialogue: 0,0:19:17.00,0:19:17.06,Default,,0000,0000,0000,,actually some
Dialogue: 0,0:19:17.06,0:19:19.08,Default,,0000,0000,0000,,of the proteins that are formed
Dialogue: 0,0:19:19.08,0:19:22.08,Default,,0000,0000,0000,,are not necessarily normal either
Dialogue: 0,0:19:22.08,0:19:23.09,Default,,0000,0000,0000,,so hypertrophy
Dialogue: 0,0:19:23.09,0:19:30.04,Default,,0000,0000,0000,,is nice and adaptive up to a point, but beyond that
Dialogue: 0,0:19:30.04,0:19:33.09,Default,,0000,0000,0000,,i might mention that before we leave hypertrophy that this also goes on in other types of
Dialogue: 0,0:19:33.09,0:19:35.07,Default,,0000,0000,0000,,of muscle
Dialogue: 0,0:19:35.07,0:19:36.01,Default,,0000,0000,0000,,as you may
Dialogue: 0,0:19:36.01,0:19:40.04,Default,,0000,0000,0000,,know for instance, the wall of the urinary bladder is muscle but
Dialogue: 0,0:19:40.04,0:19:43.06,Default,,0000,0000,0000,,this kind of muscle is what we call smooth muscle
Dialogue: 0,0:19:43.06,0:19:46.05,Default,,0000,0000,0000,,but if there is a chronic obstruction to\Nbladder outflow
Dialogue: 0,0:19:46.05,0:19:48.07,Default,,0000,0000,0000,,you get a very thick muscular bladder
Dialogue: 0,0:19:48.07,0:19:51.07,Default,,0000,0000,0000,,the same kind of response
Dialogue: 0,0:19:51.07,0:19:55.05,Default,,0000,0000,0000,,hypertrophy of the muscle cells
Dialogue: 0,0:19:55.05,0:19:57.08,Default,,0000,0000,0000,,we return to hyperplasia
Dialogue: 0,0:19:57.08,0:19:59.92,Default,,0000,0000,0000,,lots of examples i can give you
Dialogue: 0,0:19:59.92,0:20:00.04,Default,,0000,0000,0000,,of increased
Dialogue: 0,0:20:00.04,0:20:02.00,Default,,0000,0000,0000,,in
Dialogue: 0,0:20:02.00,0:20:02.10,Default,,0000,0000,0000,,the number of cells
Dialogue: 0,0:20:02.10,0:20:05.00,Default,,0000,0000,0000,,in the tissue
Dialogue: 0,0:20:05.00,0:20:07.10,Default,,0000,0000,0000,,and a nice example i think you've all\Nbeen there
Dialogue: 0,0:20:07.10,0:20:09.01,Default,,0000,0000,0000,,one way or another
Dialogue: 0,0:20:09.01,0:20:11.02,Default,,0000,0000,0000,,there's a callus that forms
Dialogue: 0,0:20:11.02,0:20:13.00,Default,,0000,0000,0000,,in the skin
Dialogue: 0,0:20:13.00,0:20:14.06,Default,,0000,0000,0000,,if you have a
Dialogue: 0,0:20:14.06,0:20:17.02,Default,,0000,0000,0000,,ill-fitting pair of shoes and something is rubbing
Dialogue: 0,0:20:17.02,0:20:18.02,Default,,0000,0000,0000,,on the spot
Dialogue: 0,0:20:18.02,0:20:21.08,Default,,0000,0000,0000,,or God forbid if you have to do manual\Nlabor
Dialogue: 0,0:20:21.08,0:20:26.02,Default,,0000,0000,0000,,some concerted length of time
Dialogue: 0,0:20:26.02,0:20:29.66,Default,,0000,0000,0000,,you develop calluses. You've all had this happen. This is an example of
Dialogue: 0,0:20:29.66,0:20:31.06,Default,,0000,0000,0000,,hyperplasia
Dialogue: 0,0:20:31.06,0:20:33.02,Default,,0000,0000,0000,,It's a response to this overwork stimulus
Dialogue: 0,0:20:33.02,0:20:35.08,Default,,0000,0000,0000,,which increases
Dialogue: 0,0:20:35.08,0:20:40.05,Default,,0000,0000,0000,,or leads to an increase in number of cells in the system
Dialogue: 0,0:20:40.05,0:20:42.00,Default,,0000,0000,0000,,let me illustrate this
Dialogue: 0,0:20:42.00,0:20:44.08,Default,,0000,0000,0000,,give you a little histology
Dialogue: 0,0:20:44.08,0:20:47.08,Default,,0000,0000,0000,,this is basically normal skin
Dialogue: 0,0:20:47.08,0:20:49.01,Default,,0000,0000,0000,,on the palmar surface of the hand
Dialogue: 0,0:20:49.01,0:20:50.08,Default,,0000,0000,0000,,this is the dermis, the connective tissue part
Dialogue: 0,0:20:50.08,0:20:51.09,Default,,0000,0000,0000,,this is the
Dialogue: 0,0:20:51.09,0:20:56.04,Default,,0000,0000,0000,,epidermis, the epithelial portion
Dialogue: 0,0:20:56.04,0:20:58.06,Default,,0000,0000,0000,,now this is a renewing
Dialogue: 0,0:20:58.06,0:21:00.66,Default,,0000,0000,0000,,cell system
Dialogue: 0,0:21:00.66,0:21:01.02,Default,,0000,0000,0000,,normally
Dialogue: 0,0:21:01.02,0:21:06.02,Default,,0000,0000,0000,,a certain number of cells are mitosing down here in the basal layer
Dialogue: 0,0:21:06.02,0:21:08.09,Default,,0000,0000,0000,,and daughter cells are moving out and maturing
Dialogue: 0,0:21:08.09,0:21:13.01,Default,,0000,0000,0000,,as they move on out
Dialogue: 0,0:21:13.01,0:21:16.02,Default,,0000,0000,0000,,and this upper layer where you see no nuclei is the
Dialogue: 0,0:21:16.02,0:21:18.04,Default,,0000,0000,0000,,so-called stratum corneum
Dialogue: 0,0:21:18.04,0:21:20.00,Default,,0000,0000,0000,,it's like a layer of shingles on the roof
Dialogue: 0,0:21:20.00,0:21:23.06,Default,,0000,0000,0000,,these cells undergo progressive changes
Dialogue: 0,0:21:23.06,0:21:26.05,Default,,0000,0000,0000,,in armor plate there
Dialogue: 0,0:21:26.05,0:21:30.02,Default,,0000,0000,0000,,so the normal palmar skin is set with a certain cell population
Dialogue: 0,0:21:30.02,0:21:31.42,Default,,0000,0000,0000,,and a certain
Dialogue: 0,0:21:31.42,0:21:36.02,Default,,0000,0000,0000,,balance where certain cells come and go
Dialogue: 0,0:21:36.02,0:21:38.08,Default,,0000,0000,0000,,i'll show you the callus
Dialogue: 0,0:21:38.08,0:21:41.05,Default,,0000,0000,0000,,keep this picture in mind
Dialogue: 0,0:21:41.05,0:21:44.01,Default,,0000,0000,0000,,and this represents the hyperplasia of the callus
Dialogue: 0,0:21:44.01,0:21:47.00,Default,,0000,0000,0000,,now you've got
Dialogue: 0,0:21:47.00,0:21:49.01,Default,,0000,0000,0000,,a much thicker cell population
Dialogue: 0,0:21:49.01,0:21:51.06,Default,,0000,0000,0000,,it's still a very orderly cell population
Dialogue: 0,0:21:51.06,0:21:55.01,Default,,0000,0000,0000,,the cells are being born down here and are maturing up here
Dialogue: 0,0:21:55.01,0:21:56.06,Default,,0000,0000,0000,,there's actually
Dialogue: 0,0:21:56.06,0:21:58.10,Default,,0000,0000,0000,,so much thickening going on here that I couldn't
Dialogue: 0,0:21:58.10,0:22:00.03,Default,,0000,0000,0000,,get it all on one picture
Dialogue: 0,0:22:00.03,0:22:02.06,Default,,0000,0000,0000,,at the same magnification
Dialogue: 0,0:22:02.06,0:22:03.10,Default,,0000,0000,0000,,here is the beginning of the stratum
Dialogue: 0,0:22:03.10,0:22:05.01,Default,,0000,0000,0000,,corneum
Dialogue: 0,0:22:05.01,0:22:07.93,Default,,0000,0000,0000,,there's the rest of it
Dialogue: 0,0:22:07.93,0:22:10.08,Default,,0000,0000,0000,,and that is a callus
Dialogue: 0,0:22:10.08,0:22:12.02,Default,,0000,0000,0000,,So you see there is a tremendous
Dialogue: 0,0:22:12.02,0:22:16.03,Default,,0000,0000,0000,,hyperplasia here in response to this mechanical stimulus
Dialogue: 0,0:22:16.03,0:22:18.07,Default,,0000,0000,0000,,Now the nice thing
Dialogue: 0,0:22:18.07,0:22:25.00,Default,,0000,0000,0000,,about hyperplasia, and also applies to hypertrophy, if you get rid of
Dialogue: 0,0:22:25.00,0:22:28.01,Default,,0000,0000,0000,,the noxious stimulus,
Dialogue: 0,0:22:28.01,0:22:29.42,Default,,0000,0000,0000,,things pretty much
Dialogue: 0,0:22:29.42,0:22:32.07,Default,,0000,0000,0000,,wind back to normal. You can't always do that, but
Dialogue: 0,0:22:32.07,0:22:34.03,Default,,0000,0000,0000,,if you can, if you quit
Dialogue: 0,0:22:34.03,0:22:37.07,Default,,0000,0000,0000,,raking the ground or whatever you're doing,
Dialogue: 0,0:22:37.07,0:22:39.09,Default,,0000,0000,0000,,pretty soon those hands will be the ones you know and love.
Dialogue: 0,0:22:39.09,0:22:41.06,Default,,0000,0000,0000,,The calloused thins out
Dialogue: 0,0:22:41.06,0:22:45.07,Default,,0000,0000,0000,,and you go back to normal. Now
Dialogue: 0,0:22:45.07,0:22:46.08,Default,,0000,0000,0000,,I could give you
Dialogue: 0,0:22:46.08,0:22:52.02,Default,,0000,0000,0000,,other happier examples, maybe, I'll give you one.
Dialogue: 0,0:22:52.02,0:22:53.09,Default,,0000,0000,0000,,In a hormone sensitive
Dialogue: 0,0:22:53.09,0:22:55.07,Default,,0000,0000,0000,,tissue that responds
Dialogue: 0,0:22:55.07,0:22:58.03,Default,,0000,0000,0000,,that response with hyperplasia
Dialogue: 0,0:22:58.03,0:23:00.07,Default,,0000,0000,0000,,here is a normal
Dialogue: 0,0:23:00.07,0:23:03.04,Default,,0000,0000,0000,,lobule. This is kind of a potential
Dialogue: 0,0:23:03.04,0:23:04.10,Default,,0000,0000,0000,,secretory unit,
Dialogue: 0,0:23:04.10,0:23:07.08,Default,,0000,0000,0000,,a normal lobule of an adult female breast.
Dialogue: 0,0:23:07.08,0:23:08.10,Default,,0000,0000,0000,,I don't want to go into detail, but
Dialogue: 0,0:23:08.10,0:23:11.05,Default,,0000,0000,0000,,just to show you the little terminal
Dialogue: 0,0:23:11.05,0:23:15.01,Default,,0000,0000,0000,,units forming this lobule. During pregnancy
Dialogue: 0,0:23:15.01,0:23:16.80,Default,,0000,0000,0000,,and lactation,
Dialogue: 0,0:23:16.80,0:23:17.00,Default,,0000,0000,0000,,this tremendous
Dialogue: 0,0:23:17.00,0:23:19.09,Default,,0000,0000,0000,,hormonal stimulus to these cells
Dialogue: 0,0:23:19.09,0:23:20.10,Default,,0000,0000,0000,,makes them undergo
Dialogue: 0,0:23:20.10,0:23:22.03,Default,,0000,0000,0000,,hyperplasia
Dialogue: 0,0:23:22.03,0:23:23.42,Default,,0000,0000,0000,,and that lobule
Dialogue: 0,0:23:23.42,0:23:24.06,Default,,0000,0000,0000,,, take a look
Dialogue: 0,0:23:24.06,0:23:26.04,Default,,0000,0000,0000,,at the size there
Dialogue: 0,0:23:26.04,0:23:27.05,Default,,0000,0000,0000,,enlarged
Dialogue: 0,0:23:27.05,0:23:30.01,Default,,0000,0000,0000,,couldn't even get the whole lobule on the screen there
Dialogue: 0,0:23:30.01,0:23:33.00,Default,,0000,0000,0000,,This is a lactating mammary gland
Dialogue: 0,0:23:33.00,0:23:34.06,Default,,0000,0000,0000,,there's a tremendous
Dialogue: 0,0:23:34.06,0:23:38.01,Default,,0000,0000,0000,,increase in the number of cells, actually some hypertrophy
Dialogue: 0,0:23:38.01,0:23:40.04,Default,,0000,0000,0000,,in individual cells, but basically
Dialogue: 0,0:23:40.04,0:23:41.09,Default,,0000,0000,0000,,a whole lot of hyperplasia
Dialogue: 0,0:23:41.09,0:23:44.03,Default,,0000,0000,0000,,there, and it responds to
Dialogue: 0,0:23:44.03,0:23:46.07,Default,,0000,0000,0000,,the hormone.
Dialogue: 0,0:23:46.07,0:23:51.06,Default,,0000,0000,0000,,When the hormonal stimulus is withdrawn at the end of lactation, things pretty much
Dialogue: 0,0:23:51.06,0:23:55.00,Default,,0000,0000,0000,,go back to normal, plus or minus a little stretching of the connective tissue
Dialogue: 0,0:23:55.00,0:23:57.00,Default,,0000,0000,0000,,but the epithelial
Dialogue: 0,0:23:57.00,0:24:02.30,Default,,0000,0000,0000,,population goes back to normal.
Dialogue: 0,0:24:02.30,0:24:06.01,Default,,0000,0000,0000,,That's hyperplasia, tends to be reversible
Dialogue: 0,0:24:06.01,0:24:09.07,Default,,0000,0000,0000,,under very nice elegant control
Dialogue: 0,0:24:09.07,0:24:11.09,Default,,0000,0000,0000,,in some situations
Dialogue: 0,0:24:11.09,0:24:13.08,Default,,0000,0000,0000,,got to throw this in. Not all good news.
Dialogue: 0,0:24:13.08,0:24:15.09,Default,,0000,0000,0000,,In some situations, the hyperplasia
Dialogue: 0,0:24:15.09,0:24:17.04,Default,,0000,0000,0000,,
Dialogue: 0,0:24:17.04,0:24:18.07,Default,,0000,0000,0000,,isn't necessarily
Dialogue: 0,0:24:18.07,0:24:22.05,Default,,0000,0000,0000,,adaptive and good. We see
Dialogue: 0,0:24:22.05,0:24:25.05,Default,,0000,0000,0000,,examples of hyperplasia, I'll show two of them.
Dialogue: 0,0:24:25.05,0:24:28.01,Default,,0000,0000,0000,,
Dialogue: 0,0:24:28.01,0:24:29.06,Default,,0000,0000,0000,,They're probably responses
Dialogue: 0,0:24:29.06,0:24:34.08,Default,,0000,0000,0000,,to the subtly abnormal endocrine stimulation, somehow
Dialogue: 0,0:24:34.08,0:24:36.04,Default,,0000,0000,0000,,we don't exactly know.
Dialogue: 0,0:24:36.04,0:24:40.06,Default,,0000,0000,0000,,but, i think one for the guys, one for the girls
Dialogue: 0,0:24:40.06,0:24:43.06,Default,,0000,0000,0000,,this is something that is going to afflict about
Dialogue: 0,0:24:43.06,0:24:46.07,Default,,0000,0000,0000,,forty nine percent of us in the room, one way or the other.
Dialogue: 0,0:24:46.07,0:24:48.00,Default,,0000,0000,0000,,and this is
Dialogue: 0,0:24:48.00,0:24:50.08,Default,,0000,0000,0000,,a cross cut of the prostate
Dialogue: 0,0:24:50.08,0:24:51.06,Default,,0000,0000,0000,,and the
Dialogue: 0,0:24:51.06,0:24:54.04,Default,,0000,0000,0000,,prostate normally is about the size
Dialogue: 0,0:24:54.04,0:24:56.01,Default,,0000,0000,0000,,of a golf
Dialogue: 0,0:24:56.01,0:24:59.05,Default,,0000,0000,0000,,ball, a walnut, a good sized walnut
Dialogue: 0,0:24:59.05,0:25:00.08,Default,,0000,0000,0000,,and it's right at the base
Dialogue: 0,0:25:00.08,0:25:08.00,Default,,0000,0000,0000,,the bladder and the urethra. The outflow tract goes through the prostate.
Dialogue: 0,0:25:08.00,0:25:08.03,Default,,0000,0000,0000,,You're looking at a cross-section there
Dialogue: 0,0:25:08.03,0:25:10.05,Default,,0000,0000,0000,,and you see the urethra there.
Dialogue: 0,0:25:10.05,0:25:11.10,Default,,0000,0000,0000,,The normal prostate would be
Dialogue: 0,0:25:11.10,0:25:15.02,Default,,0000,0000,0000,,nice and smooth across the cut surface.
Dialogue: 0,0:25:15.02,0:25:15.10,Default,,0000,0000,0000,,Here you see
Dialogue: 0,0:25:15.10,0:25:21.00,Default,,0000,0000,0000,,a bunch of lumps and this represents
Dialogue: 0,0:25:21.00,0:25:23.00,Default,,0000,0000,0000,,hyperplasia of
Dialogue: 0,0:25:23.00,0:25:26.03,Default,,0000,0000,0000,,glandular and muscular tissue, glandular tissue undergoes tremendous hyperplasia.
Dialogue: 0,0:25:26.03,0:25:29.04,Default,,0000,0000,0000,,we don't know why, and the
Dialogue: 0,0:25:29.04,0:25:31.04,Default,,0000,0000,0000,,problem with
Dialogue: 0,0:25:31.04,0:25:33.06,Default,,0000,0000,0000,,is not simply walk around with a tennis ball
Dialogue: 0,0:25:33.06,0:25:39.02,Default,,0000,0000,0000,,there instead of a walnut, but it rests on the base of the bladder
Dialogue: 0,0:25:39.02,0:25:41.07,Default,,0000,0000,0000,,and urethra and can cause outflow problems.
Dialogue: 0,0:25:41.07,0:25:46.03,Default,,0000,0000,0000,,and also urinary tract problems.
Dialogue: 0,0:25:46.03,0:25:49.05,Default,,0000,0000,0000,,I'll give you a little tidbit that's absolutely useless.
Dialogue: 0,0:25:49.05,0:25:53.04,Default,,0000,0000,0000,,Eunuchs don't get prostatic hyperplasia,
Dialogue: 0,0:25:53.04,0:25:58.05,Default,,0000,0000,0000,,but it's not a very popular preventative measure.
Dialogue: 0,0:25:58.05,0:26:02.10,Default,,0000,0000,0000,,so there's an example, it's not a neoplasm, it's strictly hyperplasia, but it's out of
Dialogue: 0,0:26:02.10,0:26:05.04,Default,,0000,0000,0000,,kilter and not good.
Dialogue: 0,0:26:05.04,0:26:07.01,Default,,0000,0000,0000,,for
Dialogue: 0,0:26:07.01,0:26:07.10,Default,,0000,0000,0000,,the rest of you
Dialogue: 0,0:26:07.10,0:26:09.04,Default,,0000,0000,0000,,we'll talk about
Dialogue: 0,0:26:09.04,0:26:11.04,Default,,0000,0000,0000,,a very common condition
Dialogue: 0,0:26:11.04,0:26:13.08,Default,,0000,0000,0000,,called fibrocystic change in the breast
Dialogue: 0,0:26:13.08,0:26:15.03,Default,,0000,0000,0000,,now this is
Dialogue: 0,0:26:15.03,0:26:18.06,Default,,0000,0000,0000,,a non-descript looking piece of tissue
Dialogue: 0,0:26:18.06,0:26:19.05,Default,,0000,0000,0000,,but if it were perfectly normal
Dialogue: 0,0:26:19.05,0:26:20.09,Default,,0000,0000,0000,,mostly
Dialogue: 0,0:26:20.09,0:26:23.06,Default,,0000,0000,0000,,it would be a yellowish background
Dialogue: 0,0:26:23.06,0:26:25.06,Default,,0000,0000,0000,,because the breast is largely fatty tissue
Dialogue: 0,0:26:25.06,0:26:27.02,Default,,0000,0000,0000,,and not
Dialogue: 0,0:26:27.02,0:26:30.07,Default,,0000,0000,0000,,those big yawning things there. So what's happened in this breast
Dialogue: 0,0:26:30.07,0:26:34.03,Default,,0000,0000,0000,,it's, first of all, increase in fibroblast
Dialogue: 0,0:26:34.03,0:26:38.04,Default,,0000,0000,0000,,fibrous connective tissue, see these white streaks
Dialogue: 0,0:26:38.04,0:26:39.10,Default,,0000,0000,0000,,and this represents part of the duct system.
Dialogue: 0,0:26:39.10,0:26:42.00,Default,,0000,0000,0000,,where the cells increase in number
Dialogue: 0,0:26:42.00,0:26:44.56,Default,,0000,0000,0000,,and fluid is accumulated in
Dialogue: 0,0:26:44.56,0:26:45.10,Default,,0000,0000,0000,,what we call cysts,
Dialogue: 0,0:26:45.10,0:26:46.08,Default,,0000,0000,0000,,a cyst
Dialogue: 0,0:26:46.08,0:26:48.06,Default,,0000,0000,0000,,is a hollow space filled with fluid
Dialogue: 0,0:26:48.06,0:26:51.09,Default,,0000,0000,0000,,lined with epithelium
Dialogue: 0,0:26:51.09,0:26:54.08,Default,,0000,0000,0000,,and so we call this fibrocystic change.
Dialogue: 0,0:26:54.08,0:26:56.06,Default,,0000,0000,0000,,In and of itself, it's very
Dialogue: 0,0:26:56.06,0:27:00.02,Default,,0000,0000,0000,,common, in and of itself it's no big deal.
Dialogue: 0,0:27:00.02,0:27:01.05,Default,,0000,0000,0000,,I'll show you
Dialogue: 0,0:27:01.05,0:27:04.09,Default,,0000,0000,0000,,what happens conceptually, here again here's the
Dialogue: 0,0:27:04.09,0:27:09.03,Default,,0000,0000,0000,,normal breast, this is a lobule like I showed you before and this is
Dialogue: 0,0:27:09.03,0:27:15.05,Default,,0000,0000,0000,,part of the duct system leading to that lobule. That's normal. Now in a fibrocystic
Dialogue: 0,0:27:15.05,0:27:17.01,Default,,0000,0000,0000,,change, what you see
Dialogue: 0,0:27:17.01,0:27:17.04,Default,,0000,0000,0000,,is
Dialogue: 0,0:27:17.04,0:27:19.56,Default,,0000,0000,0000,,this little {\i1}garbled{\i0}
Dialogue: 0,0:27:19.56,0:27:20.10,Default,,0000,0000,0000,,Here's a lobule
Dialogue: 0,0:27:20.10,0:27:22.06,Default,,0000,0000,0000,,that has undergone
Dialogue: 0,0:27:22.06,0:27:26.10,Default,,0000,0000,0000,,hyperplasia, pretty evident
Dialogue: 0,0:27:26.10,0:27:28.56,Default,,0000,0000,0000,,and the duct system, the lining is also
Dialogue: 0,0:27:28.56,0:27:35.08,Default,,0000,0000,0000,,undergone hyperplasia, the ducts are dilating and eventually form cysts.
Dialogue: 0,0:27:35.08,0:27:38.05,Default,,0000,0000,0000,,and again we don't know exactly why
Dialogue: 0,0:27:38.05,0:27:43.02,Default,,0000,0000,0000,,this happens, but it represents hyperplasia
Dialogue: 0,0:27:43.02,0:27:48.06,Default,,0000,0000,0000,,gone wrong.
Dialogue: 0,0:27:48.06,0:27:59.04,Default,,0000,0000,0000,,All right, moving right along, what I'm doing is just ticking off these concepts. You can follow this in your reading too.
Dialogue: 0,0:27:59.04,0:28:09.04,Default,,0000,0000,0000,,I want to move on to proliferation and maturation of cells within a population.
Dialogue: 0,0:28:09.04,0:28:12.00,Default,,0000,0000,0000,,I'm talking about two particular situations here
Dialogue: 0,0:28:12.00,0:28:13.04,Default,,0000,0000,0000,,we'll talk first about
Dialogue: 0,0:28:13.04,0:28:17.08,Default,,0000,0000,0000,,metaplasia and then dysplasia.
Dialogue: 0,0:28:17.08,0:28:23.02,Default,,0000,0000,0000,,all right, what about metaplasia? We define this as
Dialogue: 0,0:28:23.02,0:28:30.09,Default,,0000,0000,0000,,a change in the cell population, in which one normal mature special
Dialogue: 0,0:28:30.09,0:28:34.07,Default,,0000,0000,0000,,cell, I'll clarify this in a moment, but one
Dialogue: 0,0:28:34.07,0:28:37.80,Default,,0000,0000,0000,,cell type is replaced by another
Dialogue: 0,0:28:37.80,0:28:39.02,Default,,0000,0000,0000,,normal cell type,
Dialogue: 0,0:28:39.02,0:28:41.01,Default,,0000,0000,0000,,except it doesn't belong
Dialogue: 0,0:28:41.01,0:28:43.10,Default,,0000,0000,0000,,there, in other words, it's changed
Dialogue: 0,0:28:43.10,0:28:52.06,Default,,0000,0000,0000,,that particular location. Now this isn't just a substitution, where this cell
Dialogue: 0,0:28:52.06,0:28:54.00,Default,,0000,0000,0000,,changes into another cell
Dialogue: 0,0:28:54.00,0:28:56.07,Default,,0000,0000,0000,,what this is, rather,
Dialogue: 0,0:28:56.07,0:29:02.06,Default,,0000,0000,0000,,is change in the maturation of stem cells in the population. We've got a proliferating cell population
Dialogue: 0,0:29:02.06,0:29:09.08,Default,,0000,0000,0000,,where ordinarily the cells mature in this direction, and metaplasia represents
Dialogue: 0,0:29:09.08,0:29:30.06,Default,,0000,0000,0000,,a switch, under some influence, where they mature in that direction.
Dialogue: 0,0:29:30.06,0:29:36.07,Default,,0000,0000,0000,,They become more resistant than the normal one and that represents metaplasia.
Dialogue: 0,0:29:36.07,0:29:40.81,Default,,0000,0000,0000,,Let me illustrate this, try to make sense out of it.
Dialogue: 0,0:29:40.81,0:29:43.06,Default,,0000,0000,0000,,Here is the lining
Dialogue: 0,0:29:43.06,0:29:45.02,Default,,0000,0000,0000,,of the
Dialogue: 0,0:29:45.02,0:29:46.02,Default,,0000,0000,0000,,what we call
Dialogue: 0,0:29:46.02,0:29:49.03,Default,,0000,0000,0000,,the endocervical canal
Dialogue: 0,0:29:49.03,0:29:54.54,Default,,0000,0000,0000,,this is the canal that goes up into the uterus. Now normally
Dialogue: 0,0:29:54.54,0:29:56.02,Default,,0000,0000,0000,,what's going on
Dialogue: 0,0:29:56.02,0:30:00.30,Default,,0000,0000,0000,,here is that there are certain number of, well, call them stem cells
Dialogue: 0,0:30:00.30,0:30:02.05,Default,,0000,0000,0000,,or reserved cells that are proliferating
Dialogue: 0,0:30:02.05,0:30:02.05,Default,,0000,0000,0000,,all the
Dialogue: 0,0:30:02.05,0:30:05.00,Default,,0000,0000,0000,,time, but they mature
Dialogue: 0,0:30:05.00,0:30:06.04,Default,,0000,0000,0000,,into these tall
Dialogue: 0,0:30:06.04,0:30:07.04,Default,,0000,0000,0000,,what we call columnar
Dialogue: 0,0:30:07.04,0:30:09.06,Default,,0000,0000,0000,,cells, they are
Dialogue: 0,0:30:09.06,0:30:11.09,Default,,0000,0000,0000,,tall and columnar and they've got
Dialogue: 0,0:30:11.09,0:30:15.08,Default,,0000,0000,0000,,very pale cytoplasm because they're full of mucus.
Dialogue: 0,0:30:15.08,0:30:22.00,Default,,0000,0000,0000,,So normally this endocervical canal is lined by this mucus secreting epithelium, very
Dialogue: 0,0:30:22.00,0:30:23.03,Default,,0000,0000,0000,,slight stimulus
Dialogue: 0,0:30:23.03,0:30:24.06,Default,,0000,0000,0000,,is all it takes
Dialogue: 0,0:30:24.06,0:30:26.02,Default,,0000,0000,0000,,and there may be a change
Dialogue: 0,0:30:26.02,0:30:29.00,Default,,0000,0000,0000,,here you see the normal, here you see a plaque
Dialogue: 0,0:30:29.00,0:30:31.15,Default,,0000,0000,0000,,of cells that looks a little bit different
Dialogue: 0,0:30:31.15,0:30:33.09,Default,,0000,0000,0000,,and these cells
Dialogue: 0,0:30:33.09,0:30:35.02,Default,,0000,0000,0000,,are, well, they're
Dialogue: 0,0:30:35.02,0:30:39.05,Default,,0000,0000,0000,,odd shapes here, they're maturing into these
Dialogue: 0,0:30:39.05,0:30:43.01,Default,,0000,0000,0000,,flat cells that we saw on top of the epidermis, and we call this
Dialogue: 0,0:30:43.01,0:30:44.05,Default,,0000,0000,0000,,these are columnar
Dialogue: 0,0:30:44.05,0:30:47.10,Default,,0000,0000,0000,,cells, these are squamous cells, we call this squamous
Dialogue: 0,0:30:47.10,0:30:48.08,Default,,0000,0000,0000,,metaplasia
Dialogue: 0,0:30:48.08,0:30:51.03,Default,,0000,0000,0000,,very very
Dialogue: 0,0:30:51.03,0:30:52.76,Default,,0000,0000,0000,,common, some of you
Dialogue: 0,0:30:52.76,0:30:54.54,Default,,0000,0000,0000,,in this room have this, it's a trivial change
Dialogue: 0,0:30:54.54,0:30:56.02,Default,,0000,0000,0000,,practically
Dialogue: 0,0:30:56.02,0:31:00.02,Default,,0000,0000,0000,,ubiquitous in the adult females in the
Dialogue: 0,0:31:00.02,0:31:01.07,Default,,0000,0000,0000,,endocervix
Dialogue: 0,0:31:01.07,0:31:06.04,Default,,0000,0000,0000,,it can become quite extreme. Look at this.
Dialogue: 0,0:31:06.04,0:31:14.09,Default,,0000,0000,0000,,this whole area should be lined by these columnar cells that look this, and instead what we've got here is squamous
Dialogue: 0,0:31:14.09,0:31:20.03,Default,,0000,0000,0000,,epithelium, looks a lot like the epidermis, doesn't it?
Dialogue: 0,0:31:20.03,0:31:24.02,Default,,0000,0000,0000,,I would emphasize a couple things
Dialogue: 0,0:31:24.02,0:31:27.07,Default,,0000,0000,0000,,this is perfectly orderly, you look at this
Dialogue: 0,0:31:27.07,0:31:32.02,Default,,0000,0000,0000,,and I know you haven't become histologic experts yet
Dialogue: 0,0:31:32.02,0:31:33.01,Default,,0000,0000,0000,,but that is a perfectly orderly
Dialogue: 0,0:31:33.01,0:31:37.15,Default,,0000,0000,0000,,squamous epithelium, nothing unusual about it except
Dialogue: 0,0:31:37.15,0:31:38.10,Default,,0000,0000,0000,,it doesn't belong there.
Dialogue: 0,0:31:38.10,0:31:41.03,Default,,0000,0000,0000,,So that's an example
Dialogue: 0,0:31:41.03,0:31:43.03,Default,,0000,0000,0000,,of metaplasia
Dialogue: 0,0:31:43.03,0:31:44.16,Default,,0000,0000,0000,,in and of itself
Dialogue: 0,0:31:44.16,0:31:45.09,Default,,0000,0000,0000,,trivial
Dialogue: 0,0:31:45.09,0:31:47.04,Default,,0000,0000,0000,,or even protective.
Dialogue: 0,0:31:47.04,0:31:49.02,Default,,0000,0000,0000,,Let's say
Dialogue: 0,0:31:49.02,0:31:52.08,Default,,0000,0000,0000,,chemical workers were exposed to fumes might develop
Dialogue: 0,0:31:52.08,0:31:53.01,Default,,0000,0000,0000,,this kind of
Dialogue: 0,0:31:53.01,0:31:59.03,Default,,0000,0000,0000,,metaplasia in the lining of their trachea and bronchi, that makes them more resistant to whatever they're
Dialogue: 0,0:31:59.03,0:32:02.01,Default,,0000,0000,0000,,inhaling, smokers develop
Dialogue: 0,0:32:02.01,0:32:03.08,Default,,0000,0000,0000,,this sort of thing. Now, this could go on
Dialogue: 0,0:32:03.08,0:32:05.05,Default,,0000,0000,0000,,and something
Dialogue: 0,0:32:05.05,0:32:07.07,Default,,0000,0000,0000,,else might happen, and this might
Dialogue: 0,0:32:07.07,0:32:09.01,Default,,0000,0000,0000,,lead to bad
Dialogue: 0,0:32:09.01,0:32:10.07,Default,,0000,0000,0000,,things, but
Dialogue: 0,0:32:10.07,0:32:12.07,Default,,0000,0000,0000,,in and of itself, metaplasia
Dialogue: 0,0:32:12.07,0:32:14.06,Default,,0000,0000,0000,,is perfectly innocent.
Dialogue: 0,0:32:14.06,0:32:16.00,Default,,0000,0000,0000,,Not so
Dialogue: 0,0:32:16.00,0:32:17.06,Default,,0000,0000,0000,,with dysplasia.
Dialogue: 0,0:32:17.06,0:32:19.05,Default,,0000,0000,0000,,D-y-s-p-l-a-s-i-a
Dialogue: 0,0:32:19.05,0:32:23.08,Default,,0000,0000,0000,,Now morphologically,
Dialogue: 0,0:32:23.08,0:32:42.10,Default,,0000,0000,0000,,dysplasia is a
Dialogue: 0,0:32:42.10,0:32:45.06,Default,,0000,0000,0000,,variation, abnormal variation
Dialogue: 0,0:32:45.06,0:32:48.06,Default,,0000,0000,0000,,in
Dialogue: 0,0:32:48.06,0:32:50.01,Default,,0000,0000,0000,,the size
Dialogue: 0,0:32:50.01,0:32:51.01,Default,,0000,0000,0000,,of the cells, the shape of the cells
Dialogue: 0,0:32:51.01,0:32:53.09,Default,,0000,0000,0000,,the arrangement of the
Dialogue: 0,0:32:53.09,0:32:54.06,Default,,0000,0000,0000,,cells
Dialogue: 0,0:32:54.06,0:32:57.02,Default,,0000,0000,0000,,and the maturation of the cells
Dialogue: 0,0:32:57.02,0:32:59.04,Default,,0000,0000,0000,,too much variation
Dialogue: 0,0:32:59.04,0:33:01.01,Default,,0000,0000,0000,,in other words
Dialogue: 0,0:33:01.01,0:33:04.03,Default,,0000,0000,0000,,something very well controlled like this
Dialogue: 0,0:33:04.03,0:33:06.06,Default,,0000,0000,0000,,this epithelium is very well controlled
Dialogue: 0,0:33:06.06,0:33:08.01,Default,,0000,0000,0000,,with all the cells down here proliferating
Dialogue: 0,0:33:08.01,0:33:10.06,Default,,0000,0000,0000,,at a certain rate and maturing gradually
Dialogue: 0,0:33:10.06,0:33:12.00,Default,,0000,0000,0000,,and so forth
Dialogue: 0,0:33:12.00,0:33:19.02,Default,,0000,0000,0000,,all of this gets screwed up in dysplasia.
Dialogue: 0,0:33:19.02,0:33:21.03,Default,,0000,0000,0000,,Here again is a normal squamous
Dialogue: 0,0:33:21.03,0:33:23.03,Default,,0000,0000,0000,,epithelium, this isn't palmar
Dialogue: 0,0:33:23.03,0:33:28.02,Default,,0000,0000,0000,,or skin now, this is let's say the lining of the vagina or
Dialogue: 0,0:33:28.02,0:33:32.02,Default,,0000,0000,0000,,covering of the cervix, one of those, this happens to be cervix
Dialogue: 0,0:33:32.02,0:33:35.03,Default,,0000,0000,0000,,perfectly normal squamous epithelium, notice how orderly
Dialogue: 0,0:33:35.03,0:33:36.08,Default,,0000,0000,0000,,it is, it's like a
Dialogue: 0,0:33:36.08,0:33:37.08,Default,,0000,0000,0000,,kind of like
Dialogue: 0,0:33:37.08,0:33:41.06,Default,,0000,0000,0000,,a parade where you have cells in
Dialogue: 0,0:33:41.06,0:33:44.01,Default,,0000,0000,0000,,a certain type down here, they all resemble one another
Dialogue: 0,0:33:44.01,0:33:46.03,Default,,0000,0000,0000,,in this layer, cells here
Dialogue: 0,0:33:46.03,0:33:49.09,Default,,0000,0000,0000,,resemble one another, and then there's this maturation
Dialogue: 0,0:33:49.09,0:33:53.05,Default,,0000,0000,0000,,these flattened out cells, that's occurring in a very orderly
Dialogue: 0,0:33:53.05,0:33:57.09,Default,,0000,0000,0000,,step fashion. In dysplasia
Dialogue: 0,0:33:57.09,0:34:00.10,Default,,0000,0000,0000,,of the epithelium, everything gets
Dialogue: 0,0:34:00.10,0:34:08.41,Default,,0000,0000,0000,,screwed up. All right,
Dialogue: 0,0:34:08.41,0:34:10.33,Default,,0000,0000,0000,,this is dysplasia.
Dialogue: 0,0:34:10.33,0:34:14.38,Default,,0000,0000,0000,,and we can see where
Dialogue: 0,0:34:14.38,0:34:18.62,Default,,0000,0000,0000,,there's a shadow of what you looked at in the preceding slide, but now some things have
Dialogue: 0,0:34:18.62,0:34:20.07,Default,,0000,0000,0000,,happened, there's more
Dialogue: 0,0:34:20.07,0:34:22.83,Default,,0000,0000,0000,,variation in any
Dialogue: 0,0:34:22.83,0:34:23.08,Default,,0000,0000,0000,,layer. In other words,
Dialogue: 0,0:34:23.08,0:34:24.05,Default,,0000,0000,0000,,
Dialogue: 0,0:34:24.05,0:34:29.22,Default,,0000,0000,0000,,if you look down here, these cells are more variable than those cells were in the basal layer
Dialogue: 0,0:34:29.22,0:34:31.36,Default,,0000,0000,0000,,in the normal. You look here
Dialogue: 0,0:34:31.36,0:34:33.34,Default,,0000,0000,0000,,where in the
Dialogue: 0,0:34:33.34,0:34:36.95,Default,,0000,0000,0000,,preceding slide, every cell in the intermediate zone is perfectly
Dialogue: 0,0:34:36.95,0:34:38.98,Default,,0000,0000,0000,,like every other cell, there's variation
Dialogue: 0,0:34:38.98,0:34:43.42,Default,,0000,0000,0000,,here, there's big cells and small cells, round cells and elongated cells
Dialogue: 0,0:34:43.42,0:34:45.01,Default,,0000,0000,0000,,cells with
Dialogue: 0,0:34:45.01,0:34:48.64,Default,,0000,0000,0000,,very dark nuclei, cells with lighter nuclei
Dialogue: 0,0:34:48.64,0:34:50.95,Default,,0000,0000,0000,,and so forth
Dialogue: 0,0:34:50.95,0:34:51.08,Default,,0000,0000,0000,,and gradually, though, despite
Dialogue: 0,0:34:51.08,0:34:53.54,Default,,0000,0000,0000,,this mess, there is
Dialogue: 0,0:34:53.54,0:34:54.100,Default,,0000,0000,0000,,slight
Dialogue: 0,0:34:54.100,0:34:56.01,Default,,0000,0000,0000,,maturation
Dialogue: 0,0:34:56.01,0:35:01.96,Default,,0000,0000,0000,,you can see here how this jumble of cells gradually becomes organized
Dialogue: 0,0:35:01.96,0:35:04.69,Default,,0000,0000,0000,,up here, so what have we got
Dialogue: 0,0:35:04.69,0:35:07.08,Default,,0000,0000,0000,,we've got abnormal
Dialogue: 0,0:35:07.08,0:35:07.94,Default,,0000,0000,0000,,variations
Dialogue: 0,0:35:07.94,0:35:11.58,Default,,0000,0000,0000,,in the size of the cells, the shape of the cells, the arrangement
Dialogue: 0,0:35:11.58,0:35:15.71,Default,,0000,0000,0000,,of the cells, this is out of order. It's not in a nice, neat, locked set.
Dialogue: 0,0:35:15.71,0:35:16.10,Default,,0000,0000,0000,,And it's not
Dialogue: 0,0:35:16.10,0:35:21.22,Default,,0000,0000,0000,,maturing quite properly until it gets to the very top.
Dialogue: 0,0:35:21.22,0:35:23.44,Default,,0000,0000,0000,,Actually,
Dialogue: 0,0:35:23.44,0:35:28.80,Default,,0000,0000,0000,,this is trivial for you now, but we grade dysplasia as slight, moderate, severe depending on how much
Dialogue: 0,0:35:28.80,0:35:30.37,Default,,0000,0000,0000,,normal
Dialogue: 0,0:35:30.37,0:35:32.81,Default,,0000,0000,0000,,there might be there. But when you see
Dialogue: 0,0:35:32.81,0:35:36.27,Default,,0000,0000,0000,,this degree of variation, that's a very
Dialogue: 0,0:35:36.27,0:35:39.02,Default,,0000,0000,0000,,bad thing. There's one other thing
Dialogue: 0,0:35:39.02,0:35:42.50,Default,,0000,0000,0000,,that's abnormal here, it's a little more subtle, ordinarily
Dialogue: 0,0:35:42.50,0:35:44.97,Default,,0000,0000,0000,,mitosis occurs only down in this
Dialogue: 0,0:35:44.97,0:35:47.06,Default,,0000,0000,0000,,basal layer. But these cells
Dialogue: 0,0:35:47.06,0:35:51.52,Default,,0000,0000,0000,,are goofy enough that they forget about that and they do something very impolite.
Dialogue: 0,0:35:51.52,0:35:53.49,Default,,0000,0000,0000,,They reproduce out
Dialogue: 0,0:35:53.49,0:35:59.04,Default,,0000,0000,0000,,in public and you find mitotic figures at all levels of such an epithelium.
Dialogue: 0,0:35:59.04,0:36:00.80,Default,,0000,0000,0000,,So morphologically,
Dialogue: 0,0:36:00.80,0:36:07.38,Default,,0000,0000,0000,,this represents a lot of variation.
Dialogue: 0,0:36:07.38,0:36:13.96,Default,,0000,0000,0000,,This is a serious change because these cells
Dialogue: 0,0:36:13.96,0:36:26.75,Default,,0000,0000,0000,,are in a sense losing control. They're losing control of proliferation and maturation.
Dialogue: 0,0:36:26.75,0:36:28.07,Default,,0000,0000,0000,,Any number of mutations
Dialogue: 0,0:36:28.07,0:36:38.81,Default,,0000,0000,0000,,that occur in the cell population, this reflects genetic change in the cell, somatic cell
Dialogue: 0,0:36:38.81,0:36:56.07,Default,,0000,0000,0000,,any number of these mutations and this happens. This I want you to remember for the rest of your lives, dysplasia
Dialogue: 0,0:36:56.07,0:36:58.42,Default,,0000,0000,0000,,in other words, I can't tell you
Dialogue: 0,0:36:58.42,0:37:12.73,Default,,0000,0000,0000,,that epithelium absolutely for sure will become cancer, it depends I suppose on the last {\i1}garbled{\i0}
Dialogue: 0,0:37:12.73,0:37:38.11,Default,,0000,0000,0000,,mild degree of dysplasia sometimes don't necessarily progress, while very severe degrees of dysplasia can.
Dialogue: 0,0:37:38.11,0:37:39.04,Default,,0000,0000,0000,,Here is a squamous epithelium
Dialogue: 0,0:37:39.04,0:37:40.89,Default,,0000,0000,0000,,with what we call severe
Dialogue: 0,0:37:40.89,0:37:42.86,Default,,0000,0000,0000,,dysplasia, and you can see close
Dialogue: 0,0:37:42.86,0:37:45.14,Default,,0000,0000,0000,,up what's going on here
Dialogue: 0,0:37:45.14,0:37:48.58,Default,,0000,0000,0000,,This basal layer is increased in thickness, a lot of variation
Dialogue: 0,0:37:48.58,0:37:49.49,Default,,0000,0000,0000,,in these cells,
Dialogue: 0,0:37:49.49,0:37:51.30,Default,,0000,0000,0000,,here is
Dialogue: 0,0:37:51.30,0:37:56.05,Default,,0000,0000,0000,,a cell dividing, as they say, out in public and there is an absolute total
Dialogue: 0,0:37:56.05,0:37:57.86,Default,,0000,0000,0000,,jumble
Dialogue: 0,0:37:57.86,0:38:01.38,Default,,0000,0000,0000,,in terms of how these cells are arranged with respect to one another.
Dialogue: 0,0:38:01.38,0:38:03.09,Default,,0000,0000,0000,,We call that a loss of polarity.
Dialogue: 0,0:38:03.09,0:38:05.31,Default,,0000,0000,0000,,And in this instance
Dialogue: 0,0:38:05.31,0:38:16.25,Default,,0000,0000,0000,,it occurred all the way, full thickness of this epithelium.
Dialogue: 0,0:38:16.25,0:38:20.15,Default,,0000,0000,0000,,and we now know, from a lot of experience, severe dysplasia
Dialogue: 0,0:38:20.15,0:38:22.09,Default,,0000,0000,0000,,really is
Dialogue: 0,0:38:22.09,0:38:23.99,Default,,0000,0000,0000,,tantamount to cancer
Dialogue: 0,0:38:23.99,0:38:27.03,Default,,0000,0000,0000,,that perhaps hasn't
Dialogue: 0,0:38:27.03,0:38:28.01,Default,,0000,0000,0000,,yet invaded. Now that'll
Dialogue: 0,0:38:28.01,0:38:34.46,Default,,0000,0000,0000,,make sense when we talk about what cancer really is. Without
Dialogue: 0,0:38:34.46,0:38:40.18,Default,,0000,0000,0000,,any evidence of invasion or anything else that cancers usually do
Dialogue: 0,0:38:40.18,0:38:43.85,Default,,0000,0000,0000,,when dysplasia is this severe, we can say this is like carcinoma-in-situ
Dialogue: 0,0:38:43.85,0:38:46.60,Default,,0000,0000,0000,,which means an 'in-place' cancer
Dialogue: 0,0:38:46.60,0:38:48.24,Default,,0000,0000,0000,,pre-invasive
Dialogue: 0,0:38:48.24,0:38:51.07,Default,,0000,0000,0000,,cancer because we know
Dialogue: 0,0:38:51.07,0:38:51.81,Default,,0000,0000,0000,,if this sort of
Dialogue: 0,0:38:51.81,0:38:54.65,Default,,0000,0000,0000,,dysplasia is left alone, probably close
Dialogue: 0,0:38:54.65,0:38:56.23,Default,,0000,0000,0000,,to 100% will
Dialogue: 0,0:38:56.23,0:39:02.05,Default,,0000,0000,0000,,evolve into a cancer if the patient lives long enough.
Dialogue: 0,0:39:02.05,0:39:07.61,Default,,0000,0000,0000,,While I've got this on the screen, I'll point out some cytologic changes that are very important in making
Dialogue: 0,0:39:07.61,0:39:09.02,Default,,0000,0000,0000,,this decision. First of all
Dialogue: 0,0:39:09.02,0:39:09.10,Default,,0000,0000,0000,,you'll notice
Dialogue: 0,0:39:09.10,0:39:13.01,Default,,0000,0000,0000,,there's a lot of variation in size of nuclei. We call that
Dialogue: 0,0:39:13.01,0:39:15.21,Default,,0000,0000,0000,,nuclear pleomorphism.
Dialogue: 0,0:39:15.21,0:39:16.47,Default,,0000,0000,0000,,p-l-e-o
Dialogue: 0,0:39:16.47,0:39:18.77,Default,,0000,0000,0000,,that's a bad sign
Dialogue: 0,0:39:18.77,0:39:19.54,Default,,0000,0000,0000,,and none of these
Dialogue: 0,0:39:19.54,0:39:23.34,Default,,0000,0000,0000,,is absolute, but it's a bad sign.
Dialogue: 0,0:39:23.34,0:39:28.67,Default,,0000,0000,0000,,Some of the nuclei are very dark as you cast your eye around here.
Dialogue: 0,0:39:28.67,0:39:32.89,Default,,0000,0000,0000,,We would call that nuclear hyperchromatism. Too much
Dialogue: 0,0:39:32.89,0:39:36.75,Default,,0000,0000,0000,,colored material in the nucleus.
Dialogue: 0,0:39:36.75,0:39:37.12,Default,,0000,0000,0000,,The nuclei
Dialogue: 0,0:39:37.12,0:39:43.76,Default,,0000,0000,0000,,are very unusually shaped and sometimes
Dialogue: 0,0:39:43.76,0:39:44.99,Default,,0000,0000,0000,,you can't see it, but
Dialogue: 0,0:39:44.99,0:39:47.96,Default,,0000,0000,0000,,sometimes the mitotic figures are themselves
Dialogue: 0,0:39:47.96,0:39:51.32,Default,,0000,0000,0000,,are even abnormal, may see a tripolar mitotic figure
Dialogue: 0,0:39:51.32,0:39:53.27,Default,,0000,0000,0000,,or something like that.
Dialogue: 0,0:39:53.27,0:40:01.58,Default,,0000,0000,0000,,These are all signs of badness in a cell population.
Dialogue: 0,0:40:01.58,0:40:13.32,Default,,0000,0000,0000,,If something like this is left alone, it will proceed to an invasive cancer. Instead of carcinoma-in-situ, we call it invasive.
Dialogue: 0,0:40:13.32,0:40:18.04,Default,,0000,0000,0000,,Put a line underneath all of this and now we turn to the main topic -- Neoplasia.
Dialogue: 0,0:40:18.04,0:40:47.56,Default,,0000,0000,0000,,Spend the rest of this morning and Wednesday morning on this topic. It's ultimately
Dialogue: 0,0:40:47.56,0:40:49.34,Default,,0000,0000,0000,,more cells than there ought to be, it's an increase in cells
Dialogue: 0,0:40:49.34,0:40:52.19,Default,,0000,0000,0000,,it's a lump basically
Dialogue: 0,0:40:52.19,0:40:56.22,Default,,0000,0000,0000,,and these are proliferating cells, they're not just sitting there, they're
Dialogue: 0,0:40:56.22,0:41:01.80,Default,,0000,0000,0000,,they're dividing and making new cells. And, they're cells that have somehow
Dialogue: 0,0:41:01.80,0:41:23.22,Default,,0000,0000,0000,,become autonomous
Dialogue: 0,0:41:23.22,0:41:25.28,Default,,0000,0000,0000,,they don't obey the same start and stop signals
Dialogue: 0,0:41:25.28,0:41:28.16,Default,,0000,0000,0000,,that normal cells do. Their growth
Dialogue: 0,0:41:28.16,0:41:34.33,Default,,0000,0000,0000,,tends to be excessive and uncoordinated with the needs of the host.
Dialogue: 0,0:41:34.33,0:41:37.23,Default,,0000,0000,0000,,In other words, this thing is taking off on its own!
Dialogue: 0,0:41:37.23,0:41:45.90,Default,,0000,0000,0000,,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.
Dialogue: 0,0:41:45.90,0:41:59.73,Default,,0000,0000,0000,,You want to think teleologically, serves no useful purpose, it's not adaptive.
Dialogue: 0,0:41:59.73,0:42:04.46,Default,,0000,0000,0000,,Once the neoplasm is formed, it's off and running,
Dialogue: 0,0:42:04.46,0:42:22.85,Default,,0000,0000,0000,,which is different from hypertrophy and hyperplasia, where once you remove the stimulus, it goes back to normal.
Dialogue: 0,0:42:22.85,0:42:31.29,Default,,0000,0000,0000,,In some countries, it's the word tumor, which now is practically synonymous with neoplasm.
Dialogue: 0,0:42:31.29,0:42:38.04,Default,,0000,0000,0000,,It's also one of the cardinal signs of inflammation, the old meaning of tumor simply means swelling. But
Dialogue: 0,0:42:38.04,0:42:48.85,Default,,0000,0000,0000,,when you say a patient has a tumor, you don't mean swelling, you mean neoplasm. So tumor, neoplasm, same thing.
Dialogue: 0,0:42:48.85,0:43:04.09,Default,,0000,0000,0000,,'oma' usually denotes a neoplasm of some sort, there are exceptions, hematoma is a lump of blood.
Dialogue: 0,0:43:04.09,0:43:07.77,Default,,0000,0000,0000,,Different types of neoplasms are distinguished by their behavior,
Dialogue: 0,0:43:07.77,0:43:21.36,Default,,0000,0000,0000,,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
Dialogue: 0,0:43:21.36,0:43:30.71,Default,,0000,0000,0000,,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.
Dialogue: 0,0:43:30.71,0:43:51.02,Default,,0000,0000,0000,,Looking at all of these characteristics, they are very different from hyperplasia and hypertrophy, which are generally adaptive.
Dialogue: 0,0:43:51.02,0:44:20.28,Default,,0000,0000,0000,,A neoplasm is a living, proliferating cell and
Dialogue: 0,0:44:20.28,0:44:27.13,Default,,0000,0000,0000,,we call this neoplastic transformation, basically, and when speaking of transformed cells, we speak of cells that have acquired
Dialogue: 0,0:44:27.13,0:44:30.48,Default,,0000,0000,0000,,a set of these new characteristics
Dialogue: 0,0:44:30.48,0:44:45.02,Default,,0000,0000,0000,,that define them as neoplastic and, as you will hear, usually
Dialogue: 0,0:44:45.02,0:44:48.08,Default,,0000,0000,0000,,the wrong mutations. We talk about the clonal origin
Dialogue: 0,0:44:48.08,0:45:00.30,Default,,0000,0000,0000,,of neoplasms, in other words, a neoplasm is a clonal proliferation of a transformed cell.
Dialogue: 0,0:45:00.30,0:45:03.89,Default,,0000,0000,0000,,This transformed cell has a lot of characteristics
Dialogue: 0,0:45:03.89,0:45:11.50,Default,,0000,0000,0000,,and behaviors that are quite abnormal and we can see this in vitro when we culture it.
Dialogue: 0,0:45:11.50,0:45:13.70,Default,,0000,0000,0000,,Malignant cells, for instance,
Dialogue: 0,0:45:13.70,0:45:31.94,Default,,0000,0000,0000,,they've often lost control of movement that they display on the surface of a plate. There's
Dialogue: 0,0:45:31.94,0:45:55.43,Default,,0000,0000,0000,,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
Dialogue: 0,0:45:55.43,0:46:11.45,Default,,0000,0000,0000,,in vitro and in vivo, in the host, it manifests a non-equilibrium growth, at some point, and keeps on growing.
Dialogue: 0,0:46:11.45,0:46:28.68,Default,,0000,0000,0000,,You will learn that
Dialogue: 0,0:46:28.68,0:46:42.15,Default,,0000,0000,0000,,there's a difference between benign and malignant. I think this cartoon sums it up well.
Dialogue: 0,0:46:42.15,0:46:52.58,Default,,0000,0000,0000,,As the neoplasm grows, the number of cells gradually increases, they tend to be cohesive
Dialogue: 0,0:46:52.58,0:46:58.00,Default,,0000,0000,0000,,there's not any reason for this, just they tend to be cohesive, so as the neoplasm
Dialogue: 0,0:46:58.00,0:47:00.64,Default,,0000,0000,0000,,grows, and it may grow to a very large
Dialogue: 0,0:47:00.64,0:47:02.49,Default,,0000,0000,0000,,size, it tends to grow
Dialogue: 0,0:47:02.49,0:47:07.55,Default,,0000,0000,0000,,by a centrifugal expansion. Now it's not a perfect circle, but
Dialogue: 0,0:47:07.55,0:47:13.04,Default,,0000,0000,0000,,it tends to grow by expansion. As it expands,
Dialogue: 0,0:47:13.04,0:47:14.91,Default,,0000,0000,0000,,it frequently will pick up
Dialogue: 0,0:47:14.91,0:47:15.50,Default,,0000,0000,0000,,a
Dialogue: 0,0:47:15.50,0:47:18.08,Default,,0000,0000,0000,,condensed capsule of connective tissue as it pushes out
Dialogue: 0,0:47:18.08,0:47:20.17,Default,,0000,0000,0000,,causes atrophy of surrounding tissues
Dialogue: 0,0:47:20.17,0:47:25.58,Default,,0000,0000,0000,,and will accumulate a kind of capsule almost and anyway
Dialogue: 0,0:47:25.58,0:47:26.22,Default,,0000,0000,0000,,at any rate
Dialogue: 0,0:47:26.22,0:47:32.72,Default,,0000,0000,0000,,it stays local, its size, and it doesn't invade
Dialogue: 0,0:47:32.72,0:47:38.04,Default,,0000,0000,0000,,adjacent tissues, just pushes them out of the way, or it may press up, but it's like blowing up a
Dialogue: 0,0:47:38.04,0:48:04.48,Default,,0000,0000,0000,,balloon in the thing. On the average,
Dialogue: 0,0:48:04.48,0:48:07.03,Default,,0000,0000,0000,,this is not as cohesive as this suggests
Dialogue: 0,0:48:07.03,0:48:11.62,Default,,0000,0000,0000,,it grows, the cells have a great tendency of invading
Dialogue: 0,0:48:11.62,0:48:12.83,Default,,0000,0000,0000,,what we call the primary,
Dialogue: 0,0:48:12.83,0:48:16.66,Default,,0000,0000,0000,,they tend to drift
Dialogue: 0,0:48:16.66,0:48:20.94,Default,,0000,0000,0000,,away and don't obey the stop and start signals.
Dialogue: 0,0:48:20.94,0:48:22.05,Default,,0000,0000,0000,,They have a very different relationship
Dialogue: 0,0:48:22.05,0:48:25.09,Default,,0000,0000,0000,,with the cellular matrix and basically
Dialogue: 0,0:48:25.09,0:48:27.04,Default,,0000,0000,0000,,they have
Dialogue: 0,0:48:27.04,0:48:32.91,Default,,0000,0000,0000,,the ability, this is the primary difference, to cut their way
Dialogue: 0,0:48:32.91,0:48:35.52,Default,,0000,0000,0000,,through
Dialogue: 0,0:48:35.52,0:48:36.07,Default,,0000,0000,0000,,the adjacent stroma
Dialogue: 0,0:48:36.07,0:48:39.52,Default,,0000,0000,0000,,and actually invade as clumps of cells,
Dialogue: 0,0:48:39.52,0:48:43.07,Default,,0000,0000,0000,,lines of cells, individual cells,
Dialogue: 0,0:48:43.07,0:48:44.35,Default,,0000,0000,0000,,Invasion is one
Dialogue: 0,0:48:44.35,0:48:47.04,Default,,0000,0000,0000,,of the defining
Dialogue: 0,0:48:47.04,0:48:55.29,Default,,0000,0000,0000,,characteristics of malignancy. When I said the malignant ones tend to grow faster than benign ones, that's not a defining difference.
Dialogue: 0,0:48:55.29,0:49:03.71,Default,,0000,0000,0000,,They have to be invasive to be malignant.
Dialogue: 0,0:49:03.71,0:49:05.08,Default,,0000,0000,0000,,One other, well this sums it up,
Dialogue: 0,0:49:05.08,0:49:08.52,Default,,0000,0000,0000,,cohesive, expansile, circumscribed, localized
Dialogue: 0,0:49:08.52,0:49:13.12,Default,,0000,0000,0000,,that's benign. Malignant is poorly circumscribed, invasive, metastasizing.
Dialogue: 0,0:49:13.12,0:49:13.66,Default,,0000,0000,0000,,That means
Dialogue: 0,0:49:13.66,0:49:21.10,Default,,0000,0000,0000,,it can spread to distant foci, we'll talk about that in just a moment. But it's invasion
Dialogue: 0,0:49:21.10,0:49:32.40,Default,,0000,0000,0000,,and metastasis that define malignancy. Benign neoplasms do not metastasize.
Dialogue: 0,0:49:32.40,0:49:37.58,Default,,0000,0000,0000,,Here's a uterus
Dialogue: 0,0:49:37.58,0:49:41.43,Default,,0000,0000,0000,,cut sort of in
Dialogue: 0,0:49:41.43,0:49:43.77,Default,,0000,0000,0000,,sagittal sections, this is the cervix
Dialogue: 0,0:49:43.77,0:49:47.01,Default,,0000,0000,0000,,down here, this is a normal one half
Dialogue: 0,0:49:47.01,0:49:48.92,Default,,0000,0000,0000,,this is the cavity here, here is a
Dialogue: 0,0:49:48.92,0:49:52.73,Default,,0000,0000,0000,,neoplasm.
Dialogue: 0,0:49:52.73,0:49:57.38,Default,,0000,0000,0000,,Benign or malignant? See, it works.
Dialogue: 0,0:49:57.38,0:49:58.03,Default,,0000,0000,0000,,This is what you
Dialogue: 0,0:49:58.03,0:49:59.62,Default,,0000,0000,0000,,probably grew up hearing, a fibroid.
Dialogue: 0,0:49:59.62,0:50:01.09,Default,,0000,0000,0000,,Uterine fibroid.
Dialogue: 0,0:50:01.09,0:50:04.81,Default,,0000,0000,0000,,That's a misnomer, because it isn't
Dialogue: 0,0:50:04.81,0:50:08.78,Default,,0000,0000,0000,,a fibrous tumor, it's a muscular tumor
Dialogue: 0,0:50:08.78,0:50:10.46,Default,,0000,0000,0000,,one we call a leiomyoma.
Dialogue: 0,0:50:10.46,0:50:13.63,Default,,0000,0000,0000,,But you can see it's got, just like the cartoon, pushing at the edges.
Dialogue: 0,0:50:13.63,0:50:15.72,Default,,0000,0000,0000,,You look at that microscopically,
Dialogue: 0,0:50:15.72,0:50:16.62,Default,,0000,0000,0000,,same sort of thing
Dialogue: 0,0:50:16.62,0:50:18.16,Default,,0000,0000,0000,,here's a
Dialogue: 0,0:50:18.16,0:50:20.06,Default,,0000,0000,0000,,tumor, here's the
Dialogue: 0,0:50:20.06,0:50:24.18,Default,,0000,0000,0000,,edge along here, no invasion.
Dialogue: 0,0:50:24.18,0:50:28.09,Default,,0000,0000,0000,,Can see it just pushing, pressing along that adjacent line.
Dialogue: 0,0:50:28.09,0:50:31.33,Default,,0000,0000,0000,,Here's a breast
Dialogue: 0,0:50:31.33,0:50:32.99,Default,,0000,0000,0000,,that's been
Dialogue: 0,0:50:32.99,0:50:33.82,Default,,0000,0000,0000,,taken off
Dialogue: 0,0:50:33.82,0:50:37.55,Default,,0000,0000,0000,,a mastectomy specimen and it's been cut in this plane,
Dialogue: 0,0:50:37.55,0:50:39.54,Default,,0000,0000,0000,,a section where you can see
Dialogue: 0,0:50:39.54,0:50:41.67,Default,,0000,0000,0000,,the skin out here, and this is the neoplasm
Dialogue: 0,0:50:41.67,0:50:43.04,Default,,0000,0000,0000,,very very hard
Dialogue: 0,0:50:43.04,0:50:45.01,Default,,0000,0000,0000,,to define and circumscribe.
Dialogue: 0,0:50:45.01,0:50:47.21,Default,,0000,0000,0000,,It's going out in little
Dialogue: 0,0:50:47.21,0:50:48.67,Default,,0000,0000,0000,,sites in the adjacent
Dialogue: 0,0:50:48.67,0:50:49.59,Default,,0000,0000,0000,,tissue, even
Dialogue: 0,0:50:49.59,0:50:51.05,Default,,0000,0000,0000,,way beyond this microscopically
Dialogue: 0,0:50:51.05,0:50:54.01,Default,,0000,0000,0000,,there are lines of cells that you couldn't see here.
Dialogue: 0,0:50:54.01,0:50:57.23,Default,,0000,0000,0000,,That's invasion. A benign neoplasm
Dialogue: 0,0:50:57.23,0:50:59.56,Default,,0000,0000,0000,,wouldn't look like that.
Dialogue: 0,0:50:59.56,0:51:01.42,Default,,0000,0000,0000,,Here's one that's a little deceptive at first.
Dialogue: 0,0:51:01.42,0:51:02.00,Default,,0000,0000,0000,,This is a colon cancer,
Dialogue: 0,0:51:02.00,0:51:06.01,Default,,0000,0000,0000,,we've opened the colon and washed it off. You might
Dialogue: 0,0:51:06.01,0:51:08.52,Default,,0000,0000,0000,,say, at first, gee that's circumscribed,
Dialogue: 0,0:51:08.52,0:51:10.99,Default,,0000,0000,0000,,isn't it? Well, not exactly.
Dialogue: 0,0:51:10.99,0:51:13.18,Default,,0000,0000,0000,,What I did here is
Dialogue: 0,0:51:13.18,0:51:14.09,Default,,0000,0000,0000,,fix this in formaldehyde
Dialogue: 0,0:51:14.09,0:51:17.54,Default,,0000,0000,0000,,and then made a cut
Dialogue: 0,0:51:17.54,0:51:21.07,Default,,0000,0000,0000,,across it, and it looks like
Dialogue: 0,0:51:21.07,0:51:23.27,Default,,0000,0000,0000,,this. Now this doesn't look so
Dialogue: 0,0:51:23.27,0:51:25.60,Default,,0000,0000,0000,,awful, but it really is.
Dialogue: 0,0:51:25.60,0:51:30.07,Default,,0000,0000,0000,,Here's the normal mucous membrane up here, this layer we call sub-mucosa,
Dialogue: 0,0:51:30.07,0:51:33.57,Default,,0000,0000,0000,,this is the muscular wall of the colon here.
Dialogue: 0,0:51:33.57,0:51:36.51,Default,,0000,0000,0000,,Here is that mushroom
Dialogue: 0,0:51:36.51,0:51:39.68,Default,,0000,0000,0000,,and you can see this whitish tissue, this is neoplasm, invade
Dialogue: 0,0:51:39.68,0:51:41.35,Default,,0000,0000,0000,,all the way through that muscular layer.
Dialogue: 0,0:51:41.35,0:51:44.73,Default,,0000,0000,0000,,This is invasion.
Dialogue: 0,0:51:44.73,0:51:49.92,Default,,0000,0000,0000,,This is what it looks
Dialogue: 0,0:51:49.92,0:51:52.64,Default,,0000,0000,0000,,like microscopically, don't worry about this.
Dialogue: 0,0:51:52.64,0:51:55.27,Default,,0000,0000,0000,,duct cells, hyperchromatic, pleomorphic nuclei,
Dialogue: 0,0:51:55.27,0:51:58.53,Default,,0000,0000,0000,,and so forth.
Dialogue: 0,0:51:58.53,0:52:03.46,Default,,0000,0000,0000,,These cancer cells are cutting right through the colonic wall, it's not that simple,
Dialogue: 0,0:52:03.46,0:52:05.58,Default,,0000,0000,0000,,but they're cutting right through that colonic wall
Dialogue: 0,0:52:05.58,0:52:08.73,Default,,0000,0000,0000,,and invading. That constitutes
Dialogue: 0,0:52:08.73,0:52:13.02,Default,,0000,0000,0000,,the evidence
Dialogue: 0,0:52:13.02,0:52:18.37,Default,,0000,0000,0000,,that this is a malignant neoplasm.
Dialogue: 0,0:52:18.37,9:59:59.99,Default,,0000,0000,0000,,Let's take a break.