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Title: 
[Events]
Format: Layer, Start, End, Style, Name, MarginL, MarginR, MarginV, Effect, Text
Dialogue: 0,0:00:07.07,0:00:10.28,Default,,0000,0000,0000,,The topic of our conference this afternoon
Dialogue: 0,0:00:10.28,0:00:12.41,Default,,0000,0000,0000,,is is a very important one
Dialogue: 0,0:00:12.41,0:00:13.79,Default,,0000,0000,0000,,namely, heart
Dialogue: 0,0:00:13.79,0:00:15.96,Default,,0000,0000,0000,,failure
Dialogue: 0,0:00:15.96,0:00:19.10,Default,,0000,0000,0000,,and its important, as you'll hear\Nfrom my colleagues,
Dialogue: 0,0:00:19.10,0:00:24.08,Default,,0000,0000,0000,,for a number of reasons. The sheer\Nprevalence of heart failure in our population
Dialogue: 0,0:00:24.08,0:00:25.01,Default,,0000,0000,0000,,says that
Dialogue: 0,0:00:25.01,0:00:29.08,Default,,0000,0000,0000,,you're going to deal with a tremendous numbers of patients having
Dialogue: 0,0:00:29.08,0:00:30.45,Default,,0000,0000,0000,,related problems.
Dialogue: 0,0:00:30.45,0:00:31.77,Default,,0000,0000,0000,,The associated
Dialogue: 0,0:00:31.77,0:00:36.06,Default,,0000,0000,0000,,morbidity and mortality is very significant and
Dialogue: 0,0:00:36.06,0:00:40.10,Default,,0000,0000,0000,,heart failure, one way or another,\Nconsumes a very, very significant
Dialogue: 0,0:00:40.10,0:00:43.06,Default,,0000,0000,0000,,fraction of our health care resources.
Dialogue: 0,0:00:43.06,0:00:46.06,Default,,0000,0000,0000,,So it's a problem that you're going to\Nbe dealing with
Dialogue: 0,0:00:46.06,0:00:48.09,Default,,0000,0000,0000,,a lot of the time.
Dialogue: 0,0:00:48.09,0:00:51.07,Default,,0000,0000,0000,,I will spend my time
Dialogue: 0,0:00:51.07,0:00:55.01,Default,,0000,0000,0000,,just introducing the\Ngeneral concept which we've had a little
Dialogue: 0,0:00:55.01,0:00:58.04,Default,,0000,0000,0000,,bit in lecture, but will try to embellish\Nthat
Dialogue: 0,0:00:58.04,0:01:02.01,Default,,0000,0000,0000,,and illustrate some of the\Npathologic anatomy associated with heart
Dialogue: 0,0:01:02.01,0:01:03.08,Default,,0000,0000,0000,,failure one way or another.
Dialogue: 0,0:01:03.08,0:01:07.03,Default,,0000,0000,0000,,Then I'll pass the baton to Dr Matthews
Dialogue: 0,0:01:07.03,0:01:11.10,Default,,0000,0000,0000,,who will make clinical reality out of\Nthis
Dialogue: 0,0:01:11.10,0:01:16.00,Default,,0000,0000,0000,,and translate all of this into signs and\Nsymptom that the patients manifest
Dialogue: 0,0:01:16.00,0:01:16.09,Default,,0000,0000,0000,,and
Dialogue: 0,0:01:16.09,0:01:19.09,Default,,0000,0000,0000,,appropriate strategies
Dialogue: 0,0:01:19.09,0:01:23.03,Default,,0000,0000,0000,,of medical therapy and then we\Nwill conclude the afternoon with
Dialogue: 0,0:01:23.03,0:01:25.03,Default,,0000,0000,0000,,Dr Jonathan Haft
Dialogue: 0,0:01:25.03,0:01:28.08,Default,,0000,0000,0000,,and with the participation of a\Npatient of his
Dialogue: 0,0:01:28.08,0:01:32.01,Default,,0000,0000,0000,,and discuss the treatment of\Nadvanced heart failure
Dialogue: 0,0:01:32.01,0:01:36.04,Default,,0000,0000,0000,,with mechanical support and\Ncardiac transplantation.
Dialogue: 0,0:01:36.04,0:01:37.04,Default,,0000,0000,0000,,So that's
Dialogue: 0,0:01:37.04,0:01:42.05,Default,,0000,0000,0000,,the agenda for this afternoon.
Dialogue: 0,0:01:42.05,0:01:43.03,Default,,0000,0000,0000,,Now in its
Dialogue: 0,0:01:43.03,0:01:47.10,Default,,0000,0000,0000,,very simple definition, and there are a\Nlot of ways to define it, the very simple
Dialogue: 0,0:01:47.10,0:01:50.02,Default,,0000,0000,0000,,definition of heart failure
Dialogue: 0,0:01:50.02,0:01:53.00,Default,,0000,0000,0000,,involves the inability of the heart
Dialogue: 0,0:01:53.00,0:01:55.73,Default,,0000,0000,0000,,to meet
Dialogue: 0,0:01:55.73,0:02:00.03,Default,,0000,0000,0000,,to really pump sufficient\Nblood to meet the metabolic needs of
Dialogue: 0,0:02:00.03,0:02:02.01,Default,,0000,0000,0000,,the body.
Dialogue: 0,0:02:02.01,0:02:06.06,Default,,0000,0000,0000,,Now this can happen in a in a variety of\Nways.
Dialogue: 0,0:02:06.06,0:02:10.59,Default,,0000,0000,0000,,It can come to pass, and this isn't as frequent, that the
Dialogue: 0,0:02:10.59,0:02:14.58,Default,,0000,0000,0000,,heart is putting out a normal or even an excessive amount of blood.
Dialogue: 0,0:02:14.58,0:02:16.66,Default,,0000,0000,0000,,It's really pumping it out there, but it's being
Dialogue: 0,0:02:16.66,0:02:18.05,Default,,0000,0000,0000,,driven by
Dialogue: 0,0:02:18.05,0:02:23.01,Default,,0000,0000,0000,,an increased demand in the peripheral\Ntissues that it just can't keep up with.
Dialogue: 0,0:02:23.01,0:02:26.44,Default,,0000,0000,0000,,This sort of thing we see in thyrotoxicosis.
Dialogue: 0,0:02:26.44,0:02:28.06,Default,,0000,0000,0000,,It used to be seen,
Dialogue: 0,0:02:28.06,0:02:31.79,Default,,0000,0000,0000,,we don't see it much any more thankfully, in beriberi - vitamin deficiency
Dialogue: 0,0:02:31.79,0:02:33.66,Default,,0000,0000,0000,,with vasodilatation
Dialogue: 0,0:02:33.66,0:02:36.41,Default,,0000,0000,0000,,all over the place and\Nthe heart just couldn't keep up with
Dialogue: 0,0:02:36.41,0:02:37.04,Default,,0000,0000,0000,,that volume
Dialogue: 0,0:02:37.04,0:02:38.14,Default,,0000,0000,0000,,of the
Dialogue: 0,0:02:38.14,0:02:40.21,Default,,0000,0000,0000,,cardiovascular system.
Dialogue: 0,0:02:40.21,0:02:45.84,Default,,0000,0000,0000,,It's seen occasionally with\Narteriovenous fistulas
Dialogue: 0,0:02:45.84,0:02:49.56,Default,,0000,0000,0000,,that dump a lot of blood\Ndirectly from arteries into the veins in the heart
Dialogue: 0,0:02:49.56,0:02:52.71,Default,,0000,0000,0000,,The heart just can't keep up. Or severe anemia.
Dialogue: 0,0:02:52.71,0:02:56.50,Default,,0000,0000,0000,,Those sorts of things will result in what we call a high output sort of failure,
Dialogue: 0,0:02:56.50,0:02:57.49,Default,,0000,0000,0000,,but much more
Dialogue: 0,0:02:57.49,0:02:59.12,Default,,0000,0000,0000,,often, we're dealing with
Dialogue: 0,0:02:59.12,0:03:00.08,Default,,0000,0000,0000,,the problem of
Dialogue: 0,0:03:00.08,0:03:03.80,Default,,0000,0000,0000,,not enough blood being ejected
Dialogue: 0,0:03:03.80,0:03:06.27,Default,,0000,0000,0000,,for one reason or another
Dialogue: 0,0:03:06.27,0:03:11.36,Default,,0000,0000,0000,,from the heart to support even normal\Ndemands
Dialogue: 0,0:03:11.36,0:03:15.04,Default,,0000,0000,0000,,and this is a combination really of
Dialogue: 0,0:03:15.04,0:03:18.49,Default,,0000,0000,0000,,the loss of systolic umph,
Dialogue: 0,0:03:18.49,0:03:22.07,Default,,0000,0000,0000,,in other words, the contracting\Nheart just can't get it out there
Dialogue: 0,0:03:22.07,0:03:23.06,Default,,0000,0000,0000,,in the way it should and
Dialogue: 0,0:03:23.06,0:03:27.05,Default,,0000,0000,0000,,often this can be accompanied by
Dialogue: 0,0:03:27.05,0:03:29.07,Default,,0000,0000,0000,,diastolic,
Dialogue: 0,0:03:29.07,0:03:34.28,Default,,0000,0000,0000,,i've listed it here as diastolic failure but\Nit's a difficulty in diastolic filling
Dialogue: 0,0:03:34.28,0:03:38.42,Default,,0000,0000,0000,,which can impair the heart action. If\Nthe heart muscle can't relax and is ineffective
Dialogue: 0,0:03:38.42,0:03:39.00,Default,,0000,0000,0000,,it's stiff
Dialogue: 0,0:03:39.00,0:03:40.46,Default,,0000,0000,0000,,it won't
Dialogue: 0,0:03:40.46,0:03:41.81,Default,,0000,0000,0000,,accept
Dialogue: 0,0:03:41.81,0:03:44.01,Default,,0000,0000,0000,,the right volume coming into it and\Nthat's going to lead
Dialogue: 0,0:03:44.01,0:03:46.99,Default,,0000,0000,0000,,also to failure.
Dialogue: 0,0:03:46.99,0:03:52.23,Default,,0000,0000,0000,,One way or another, these factors can lead to a constellation
Dialogue: 0,0:03:52.23,0:03:54.03,Default,,0000,0000,0000,,of signs and symptoms,
Dialogue: 0,0:03:54.03,0:03:57.01,Default,,0000,0000,0000,,we'll get to that at the end.
Dialogue: 0,0:03:57.01,0:04:00.69,Default,,0000,0000,0000,,It's really related on the one hand to\Ncongestion of organs which you know all
Dialogue: 0,0:04:00.69,0:04:02.44,Default,,0000,0000,0000,,about now after
Dialogue: 0,0:04:02.44,0:04:02.10,Default,,0000,0000,0000,,your
Dialogue: 0,0:04:02.10,0:04:08.03,Default,,0000,0000,0000,,lectures in pathology and\Nhypoprofusion of tissues which
Dialogue: 0,0:04:08.03,0:04:10.10,Default,,0000,0000,0000,,we haven't emphasized as much, but it's a
Dialogue: 0,0:04:10.10,0:04:13.07,Default,,0000,0000,0000,,very important point.
Dialogue: 0,0:04:13.07,0:04:18.66,Default,,0000,0000,0000,,Now, when we look at the causes of heart failure\Nand there are many, many of them, far more
Dialogue: 0,0:04:18.66,0:04:20.87,Default,,0000,0000,0000,,than we can talk about,
Dialogue: 0,0:04:20.87,0:04:22.32,Default,,0000,0000,0000,,but
Dialogue: 0,0:04:22.32,0:04:25.82,Default,,0000,0000,0000,,if we look at those\Nsituations where there is
Dialogue: 0,0:04:25.82,0:04:28.06,Default,,0000,0000,0000,,some unusual demand
Dialogue: 0,0:04:28.06,0:04:31.04,Default,,0000,0000,0000,,on the heart, and the heart just can't meet it, they
Dialogue: 0,0:04:31.04,0:04:33.23,Default,,0000,0000,0000,,fall into a number
Dialogue: 0,0:04:33.23,0:04:35.32,Default,,0000,0000,0000,,of categories, and I will
Dialogue: 0,0:04:35.32,0:04:37.92,Default,,0000,0000,0000,,illustrate each of these in a\Nmoment,
Dialogue: 0,0:04:37.92,0:04:41.03,Default,,0000,0000,0000,,but one very important\Ncategory is resistance
Dialogue: 0,0:04:41.03,0:04:42.76,Default,,0000,0000,0000,,to flow, in other words,
Dialogue: 0,0:04:42.76,0:04:46.77,Default,,0000,0000,0000,,if something is keeping the flow of blood from going so
Dialogue: 0,0:04:46.77,0:04:50.88,Default,,0000,0000,0000,,the heart has to work harder to push it\Npast that resistance
Dialogue: 0,0:04:50.88,0:04:55.63,Default,,0000,0000,0000,,it will come to the point where the\Nheart could no longer do it and it fails.
Dialogue: 0,0:04:55.63,0:04:59.01,Default,,0000,0000,0000,,Another problem is what we call regurgitant\Nflow, I mean you like to think of the
Dialogue: 0,0:04:59.01,0:05:03.98,Default,,0000,0000,0000,,blood flowing in one direction through\Nthe cardiovascular system, but
Dialogue: 0,0:05:03.98,0:05:05.77,Default,,0000,0000,0000,,sometimes it comes to pass where, at a point,
Dialogue: 0,0:05:05.77,0:05:06.01,Default,,0000,0000,0000,,there's
Dialogue: 0,0:05:06.01,0:05:09.09,Default,,0000,0000,0000,,regurgitation, instead of things pulsing forward, they slosh
Dialogue: 0,0:05:09.09,0:05:11.57,Default,,0000,0000,0000,,backward, and that
Dialogue: 0,0:05:11.57,0:05:16.44,Default,,0000,0000,0000,,imposes a strain on the heart\Nas you will see
Dialogue: 0,0:05:16.44,0:05:21.04,Default,,0000,0000,0000,,and thirdly and very importantly there is\Ndisease of various sorts, lots of sorts,
Dialogue: 0,0:05:21.04,0:05:25.44,Default,,0000,0000,0000,,targeting the myocardium itself
Dialogue: 0,0:05:25.44,0:05:29.02,Default,,0000,0000,0000,,so that there's no resistance to flow,\Nthere's no regurgitant flow
Dialogue: 0,0:05:29.02,0:05:29.100,Default,,0000,0000,0000,,perhaps, but the
Dialogue: 0,0:05:29.100,0:05:32.56,Default,,0000,0000,0000,,heart muscle is sick.
Dialogue: 0,0:05:32.56,0:05:34.02,Default,,0000,0000,0000,,And finally, we won't talk
Dialogue: 0,0:05:34.02,0:05:38.08,Default,,0000,0000,0000,,at all about this, I won't, about conduction abnormalities
Dialogue: 0,0:05:38.08,0:05:40.06,Default,,0000,0000,0000,,which can also lead to decompensation
Dialogue: 0,0:05:40.06,0:05:42.02,Default,,0000,0000,0000,,of the heart.
Dialogue: 0,0:05:42.02,0:05:43.37,Default,,0000,0000,0000,,Now, I'd like
Dialogue: 0,0:05:43.37,0:05:46.62,Default,,0000,0000,0000,,to illustrate some of these\Nvery quickly, don't get lost in the details,
Dialogue: 0,0:05:46.62,0:05:47.07,Default,,0000,0000,0000,,just
Dialogue: 0,0:05:47.07,0:05:51.05,Default,,0000,0000,0000,,let it flow over you, you're going\Nto get these details later on
Dialogue: 0,0:05:51.05,0:05:52.10,Default,,0000,0000,0000,,in the year
Dialogue: 0,0:05:52.10,0:05:57.51,Default,,0000,0000,0000,,later on in your careers, but just\Nfor a little orientation,
Dialogue: 0,0:05:57.51,0:06:03.01,Default,,0000,0000,0000,,I'll give you an example first of resistance to flow,
Dialogue: 0,0:06:03.01,0:06:04.71,Default,,0000,0000,0000,,there is a good hallmark for
Dialogue: 0,0:06:04.71,0:06:08.31,Default,,0000,0000,0000,,it, I can't show you\Nhypertension obviously
Dialogue: 0,0:06:08.31,0:06:09.18,Default,,0000,0000,0000,,but think of
Dialogue: 0,0:06:09.18,0:06:14.56,Default,,0000,0000,0000,,the situation when a patient\Nhas established significant hypertension,
Dialogue: 0,0:06:14.56,0:06:16.08,Default,,0000,0000,0000,,it means that 24/7
Dialogue: 0,0:06:16.08,0:06:19.76,Default,,0000,0000,0000,,every minute, every beat of the\Nheart
Dialogue: 0,0:06:19.76,0:06:24.22,Default,,0000,0000,0000,,that poor left ventricle is having to\Nforce against an increased resistance to flow,
Dialogue: 0,0:06:24.22,0:06:25.00,Default,,0000,0000,0000,,that's what hypertension
Dialogue: 0,0:06:25.00,0:06:27.51,Default,,0000,0000,0000,,is all about. The result
Dialogue: 0,0:06:27.51,0:06:28.01,Default,,0000,0000,0000,,
Dialogue: 0,0:06:28.01,0:06:32.03,Default,,0000,0000,0000,,one of the results you see here is\Nis this rather massive
Dialogue: 0,0:06:32.03,0:06:34.05,Default,,0000,0000,0000,,myocardial hypertrophy which i'm sure\Nyou all recognize,
Dialogue: 0,0:06:34.05,0:06:35.97,Default,,0000,0000,0000,,so that's one
Dialogue: 0,0:06:35.97,0:06:40.04,Default,,0000,0000,0000,,kind of resistance to flow. Here's another one, this takes a
Dialogue: 0,0:06:40.04,0:06:44.92,Default,,0000,0000,0000,,little explaining, it's an unusual plane of section of the heart,
Dialogue: 0,0:06:44.92,0:06:48.29,Default,,0000,0000,0000,,but what attracts your\Nattention right away is that the left ventricle
Dialogue: 0,0:06:48.29,0:06:51.01,Default,,0000,0000,0000,,is immensely hypertrophied, very thick
Dialogue: 0,0:06:51.01,0:06:52.82,Default,,0000,0000,0000,,and very heavy, and the reason
Dialogue: 0,0:06:52.82,0:06:56.48,Default,,0000,0000,0000,,for it is not terribly\Nwell shown here
Dialogue: 0,0:06:56.48,0:07:00.85,Default,,0000,0000,0000,,but here is the aortic outflow, this is the aorta here, and this would be the aortic valve
Dialogue: 0,0:07:00.85,0:07:03.00,Default,,0000,0000,0000,,which you can't get a good view\Nof, but
Dialogue: 0,0:07:03.00,0:07:08.04,Default,,0000,0000,0000,,a common lesion is stenosis of the aortic valve,
Dialogue: 0,0:07:08.04,0:07:13.02,Default,,0000,0000,0000,,and obviously, in that situation, it's very\Nanalogous to hypertension, every time
Dialogue: 0,0:07:13.02,0:07:16.16,Default,,0000,0000,0000,,the ventricle contracts, it's got to push that blood
Dialogue: 0,0:07:16.16,0:07:18.45,Default,,0000,0000,0000,,through a stenotic valve
Dialogue: 0,0:07:18.45,0:07:20.27,Default,,0000,0000,0000,,and it's a lot of work.
Dialogue: 0,0:07:20.27,0:07:23.84,Default,,0000,0000,0000,,I'll show you one of these valves from\Nabove, this is an interesting one,
Dialogue: 0,0:07:23.84,0:07:27.85,Default,,0000,0000,0000,,this is a pretty typical example of\Naortic stenosis,
Dialogue: 0,0:07:27.85,0:07:31.00,Default,,0000,0000,0000,,you're standing in the ascending\Naorta, looking back
Dialogue: 0,0:07:31.00,0:07:33.86,Default,,0000,0000,0000,,towards the left ventricle, and
Dialogue: 0,0:07:33.86,0:07:39.94,Default,,0000,0000,0000,,you're aware from your gross anatomy\Nthat this should be a three cusp valve
Dialogue: 0,0:07:39.94,0:07:42.03,Default,,0000,0000,0000,,and you're seeing a couple of things here,
Dialogue: 0,0:07:42.03,0:07:45.13,Default,,0000,0000,0000,,first of all this is only two cusps
Dialogue: 0,0:07:45.13,0:07:47.01,Default,,0000,0000,0000,,and that was a congenital problem
Dialogue: 0,0:07:47.01,0:07:50.28,Default,,0000,0000,0000,,and it's a fairly frequent one\Nin our population, there are probably a
Dialogue: 0,0:07:50.28,0:07:51.50,Default,,0000,0000,0000,,couple of so-called
Dialogue: 0,0:07:51.50,0:07:53.70,Default,,0000,0000,0000,,bicuspid valves in this room
Dialogue: 0,0:07:53.70,0:07:55.50,Default,,0000,0000,0000,,and
Dialogue: 0,0:07:55.50,0:07:57.01,Default,,0000,0000,0000,,whatever the case
Dialogue: 0,0:07:57.01,0:08:01.02,Default,,0000,0000,0000,,the aortic valve is very susceptible to calcification
Dialogue: 0,0:08:01.02,0:08:04.12,Default,,0000,0000,0000,,and stiffening with age, and if you
Dialogue: 0,0:08:04.12,0:08:07.97,Default,,0000,0000,0000,,plot it against the aging\Npopulation, we see an increasing
Dialogue: 0,0:08:07.97,0:08:09.41,Default,,0000,0000,0000,,incidence of stenotic
Dialogue: 0,0:08:09.41,0:08:11.32,Default,,0000,0000,0000,,aortic valves even if they're not
Dialogue: 0,0:08:11.32,0:08:15.41,Default,,0000,0000,0000,,bicuspid, if they're congenitally bicuspid like this they get wrecked
Dialogue: 0,0:08:15.41,0:08:16.69,Default,,0000,0000,0000,,very frequently
Dialogue: 0,0:08:16.69,0:08:18.61,Default,,0000,0000,0000,,earlier on so that
Dialogue: 0,0:08:18.61,0:08:21.96,Default,,0000,0000,0000,,instead of maybe in the\Nseventies or eighties, it might be in the
Dialogue: 0,0:08:21.96,0:08:24.05,Default,,0000,0000,0000,,fifties and sixties that the patient\Nwould suffer from such stenosis.
Dialogue: 0,0:08:24.05,0:08:25.01,Default,,0000,0000,0000,,But you can see
Dialogue: 0,0:08:25.01,0:08:26.92,Default,,0000,0000,0000,,that every time
Dialogue: 0,0:08:26.92,0:08:30.00,Default,,0000,0000,0000,,the ventricle is trying to push\Nblood through that orifice, and it's really like brick
Dialogue: 0,0:08:30.00,0:08:31.62,Default,,0000,0000,0000,,it doesn't move.
Dialogue: 0,0:08:31.62,0:08:32.08,Default,,0000,0000,0000,,It's going to be a
Dialogue: 0,0:08:32.08,0:08:37.02,Default,,0000,0000,0000,,tremendous load on\Nthe left ventricle.
Dialogue: 0,0:08:37.02,0:08:41.05,Default,,0000,0000,0000,,here's another valve stenosis for you,\Nwe don't see this as much anymore,
Dialogue: 0,0:08:41.05,0:08:45.09,Default,,0000,0000,0000,,it's a result usually of old rheumatic fever\Nin childhood, but the mitral valve
Dialogue: 0,0:08:45.09,0:08:50.00,Default,,0000,0000,0000,,here is reduced to\Na fish mouth, it's all puckered up
Dialogue: 0,0:08:50.00,0:08:54.04,Default,,0000,0000,0000,,and scarred, and frequently calcified,
Dialogue: 0,0:08:54.04,0:08:55.65,Default,,0000,0000,0000,,and the valve leaflets
Dialogue: 0,0:08:55.65,0:08:57.03,Default,,0000,0000,0000,,can't move at all,
Dialogue: 0,0:08:57.03,0:08:59.10,Default,,0000,0000,0000,,so that the blood coming out of the lungs into the
Dialogue: 0,0:08:59.10,0:09:01.06,Default,,0000,0000,0000,,into the left atrium trying to get through
Dialogue: 0,0:09:01.06,0:09:04.04,Default,,0000,0000,0000,,into the left ventricle, you're looking down towards the left ventricle,
Dialogue: 0,0:09:04.04,0:09:08.07,Default,,0000,0000,0000,,it's got to pass by that stenotic slit.
Dialogue: 0,0:09:08.07,0:09:10.01,Default,,0000,0000,0000,,The result is damming back,
Dialogue: 0,0:09:10.01,0:09:15.04,Default,,0000,0000,0000,,very obviously you know about passive\Ncongestion, you can see this immensely dilated
Dialogue: 0,0:09:15.04,0:09:16.02,Default,,0000,0000,0000,,left atrium
Dialogue: 0,0:09:16.02,0:09:17.00,Default,,0000,0000,0000,,and you can imagine
Dialogue: 0,0:09:17.00,0:09:20.01,Default,,0000,0000,0000,,what was happening in the\Nlungs
Dialogue: 0,0:09:20.01,0:09:21.67,Default,,0000,0000,0000,,behind that sort of obstruction.
Dialogue: 0,0:09:21.67,0:09:22.08,Default,,0000,0000,0000,,Now as far as
Dialogue: 0,0:09:22.08,0:09:25.09,Default,,0000,0000,0000,,regurgitant flow, hold on with me
Dialogue: 0,0:09:25.09,0:09:30.04,Default,,0000,0000,0000,,and i'll try to explain\Nit, here is another mitral valve, we've chopped off the
Dialogue: 0,0:09:30.04,0:09:32.00,Default,,0000,0000,0000,,the atrium and you're\Nlooking right at the
Dialogue: 0,0:09:32.00,0:09:34.09,Default,,0000,0000,0000,,mitral valve, and
Dialogue: 0,0:09:34.09,0:09:38.02,Default,,0000,0000,0000,,think about what you saw in gross anatomy, the\Nmitral valve leaflets usually come together
Dialogue: 0,0:09:38.02,0:09:41.00,Default,,0000,0000,0000,,like that and keep the blood, during systole,
Dialogue: 0,0:09:41.00,0:09:45.02,Default,,0000,0000,0000,,keep the blood from\Nflowing back into the atrium so all the blood goes out
Dialogue: 0,0:09:45.02,0:09:47.04,Default,,0000,0000,0000,,the aorta like it should.
Dialogue: 0,0:09:47.04,0:09:49.07,Default,,0000,0000,0000,,Here,
Dialogue: 0,0:09:49.07,0:09:54.08,Default,,0000,0000,0000,,and this happens for a variety of\Nreasons, but here this leaflet of the valve
Dialogue: 0,0:09:54.08,0:09:57.04,Default,,0000,0000,0000,,is sort of pooched up and
Dialogue: 0,0:09:57.04,0:10:02.07,Default,,0000,0000,0000,,and with every ventricular systole, blood is able to force its way back
Dialogue: 0,0:10:02.07,0:10:04.05,Default,,0000,0000,0000,,into the atrium, which means
Dialogue: 0,0:10:04.05,0:10:08.02,Default,,0000,0000,0000,,the poor old left ventricle is\Npumping some of that blood more than once
Dialogue: 0,0:10:08.02,0:10:11.06,Default,,0000,0000,0000,,in other words it's putting part of it out\Nthe aorta, part of it back up the atrium,
Dialogue: 0,0:10:11.06,0:10:12.04,Default,,0000,0000,0000,,and that comes
Dialogue: 0,0:10:12.04,0:10:14.05,Default,,0000,0000,0000,,sloshing down for the next
Dialogue: 0,0:10:14.05,0:10:16.03,Default,,0000,0000,0000,,beat of the heart
Dialogue: 0,0:10:16.03,0:10:18.08,Default,,0000,0000,0000,,and it consists,
Dialogue: 0,0:10:18.08,0:10:22.65,Default,,0000,0000,0000,,it induces a volume overload on the valve
Dialogue: 0,0:10:22.65,0:10:24.08,Default,,0000,0000,0000,,and
Dialogue: 0,0:10:24.08,0:10:26.06,Default,,0000,0000,0000,,on the ventricle
Dialogue: 0,0:10:26.06,0:10:29.02,Default,,0000,0000,0000,,and it may fail.
Dialogue: 0,0:10:29.02,0:10:33.03,Default,,0000,0000,0000,,Now when you get to the realm of myocardial\Nabnormality per se, in other words disease of the myocardium
Dialogue: 0,0:10:33.03,0:10:34.10,Default,,0000,0000,0000,,
Dialogue: 0,0:10:34.10,0:10:36.02,Default,,0000,0000,0000,,there are lots
Dialogue: 0,0:10:36.02,0:10:42.01,Default,,0000,0000,0000,,and lots of examples, and the most frequent one and most important one is myocardial ischemic disease
Dialogue: 0,0:10:42.01,0:10:46.10,Default,,0000,0000,0000,,in other words, the result of coronary artery disease, atherosclerosis
Dialogue: 0,0:10:46.10,0:10:50.06,Default,,0000,0000,0000,,and its complications, and what happens when the myocardium
Dialogue: 0,0:10:50.06,0:10:52.00,Default,,0000,0000,0000,,becomes ischemic.
Dialogue: 0,0:10:52.00,0:10:55.08,Default,,0000,0000,0000,,Clearly many patients who have a\Nmyocardial infarct, an acute heart attack
Dialogue: 0,0:10:55.08,0:10:56.10,Default,,0000,0000,0000,,will go into
Dialogue: 0,0:10:56.10,0:11:01.01,Default,,0000,0000,0000,,acute failure if enough of\Nthe myocardium is involved right then and there in the
Dialogue: 0,0:11:01.01,0:11:04.02,Default,,0000,0000,0000,,emergency room.
Dialogue: 0,0:11:04.02,0:11:06.10,Default,,0000,0000,0000,,But chronically it can become a big problem\Neven when the
Dialogue: 0,0:11:06.10,0:11:11.06,Default,,0000,0000,0000,,situation heals. Here, for example,
Dialogue: 0,0:11:11.06,0:11:15.04,Default,,0000,0000,0000,,a slice of a heart, this is left ventricle over here,
Dialogue: 0,0:11:15.04,0:11:19.01,Default,,0000,0000,0000,,and this individual sustained a\Nmyocardial infarct, I don't know how long ago,
Dialogue: 0,0:11:19.01,0:11:20.09,Default,,0000,0000,0000,,it could be years ago,
Dialogue: 0,0:11:20.09,0:11:25.01,Default,,0000,0000,0000,,months ago, and you see a lot of scar
Dialogue: 0,0:11:25.01,0:11:28.02,Default,,0000,0000,0000,,throughout the ventricular wall, a little\Nbit back there, a little bit in the septum,
Dialogue: 0,0:11:28.02,0:11:31.00,Default,,0000,0000,0000,,but a tremendous scar here
Dialogue: 0,0:11:31.00,0:11:36.40,Default,,0000,0000,0000,,and when this involves enough of the\Nventricular myocardium, it puts a strain
Dialogue: 0,0:11:36.40,0:11:39.06,Default,,0000,0000,0000,,on what's left of viable myocardium, because this
Dialogue: 0,0:11:39.06,0:11:43.00,Default,,0000,0000,0000,,obviously doesn't contract.
Dialogue: 0,0:11:43.00,0:11:47.00,Default,,0000,0000,0000,,Patients can sustain a lot of myocardial infarcts,
Dialogue: 0,0:11:47.00,0:11:52.02,Default,,0000,0000,0000,,here's serial sections of the same heart,\Nand you can see at least a couple of infarcts
Dialogue: 0,0:11:52.02,0:11:52.81,Default,,0000,0000,0000,,that involve
Dialogue: 0,0:11:52.81,0:11:54.02,Default,,0000,0000,0000,,a tremendous
Dialogue: 0,0:11:54.02,0:11:55.07,Default,,0000,0000,0000,,fraction of the
Dialogue: 0,0:11:55.07,0:11:56.02,Default,,0000,0000,0000,,left ventricle
Dialogue: 0,0:11:56.02,0:11:57.09,Default,,0000,0000,0000,,and again when
Dialogue: 0,0:11:57.09,0:11:59.64,Default,,0000,0000,0000,,that happens, the rest of
Dialogue: 0,0:11:59.64,0:12:02.05,Default,,0000,0000,0000,,this can't keep up with it, and the left
Dialogue: 0,0:12:02.05,0:12:04.08,Default,,0000,0000,0000,,ventricle fails.
Dialogue: 0,0:12:04.08,0:12:06.06,Default,,0000,0000,0000,,Here is a heart that was
Dialogue: 0,0:12:06.06,0:12:09.09,Default,,0000,0000,0000,,was removed from a patient\Nwho was still alive
Dialogue: 0,0:12:09.09,0:12:12.07,Default,,0000,0000,0000,,happy and well as far as i know
Dialogue: 0,0:12:12.07,0:12:15.07,Default,,0000,0000,0000,,This is an explant to the heart, in\Nother words, taken out of the time of transplantation
Dialogue: 0,0:12:15.07,0:12:16.89,Default,,0000,0000,0000,,and this was also
Dialogue: 0,0:12:16.89,0:12:19.24,Default,,0000,0000,0000,,ischemic disease, and this
Dialogue: 0,0:12:19.24,0:12:22.46,Default,,0000,0000,0000,,individual had scraped through
Dialogue: 0,0:12:22.46,0:12:26.08,Default,,0000,0000,0000,,with this much of the heart converted into
Dialogue: 0,0:12:26.08,0:12:29.08,Default,,0000,0000,0000,,what amounted to a fibrous sack, totally
Dialogue: 0,0:12:29.08,0:12:32.02,Default,,0000,0000,0000,,non-contractile
Dialogue: 0,0:12:32.02,0:12:36.01,Default,,0000,0000,0000,,and you can see there's even a clot in there because it wasn't moving
Dialogue: 0,0:12:36.01,0:12:37.00,Default,,0000,0000,0000,,and that had
Dialogue: 0,0:12:37.00,0:12:41.02,Default,,0000,0000,0000,,produced failure of the remaining myocardium.
Dialogue: 0,0:12:41.02,0:12:42.09,Default,,0000,0000,0000,,So that's a
Dialogue: 0,0:12:42.09,0:12:45.00,Default,,0000,0000,0000,,good sample of
Dialogue: 0,0:12:45.00,0:12:46.01,Default,,0000,0000,0000,,ischemic
Dialogue: 0,0:12:46.01,0:12:49.02,Default,,0000,0000,0000,,disease leading to chronic failure of the left ventricle.
Dialogue: 0,0:12:49.02,0:12:49.68,Default,,0000,0000,0000,,
Dialogue: 0,0:12:49.68,0:12:51.08,Default,,0000,0000,0000,,Now, beyond
Dialogue: 0,0:12:51.08,0:12:55.02,Default,,0000,0000,0000,,ischemic disease there are a whole lot of them,\Ndon't worry about the details
Dialogue: 0,0:12:55.02,0:12:58.09,Default,,0000,0000,0000,,I'll show you this as an example\Nof an inflammatory process targeted at
Dialogue: 0,0:12:58.09,0:13:01.01,Default,,0000,0000,0000,,the myocardium. We see this
Dialogue: 0,0:13:01.01,0:13:05.05,Default,,0000,0000,0000,,with certain viral infections, certain protozoan infections,
Dialogue: 0,0:13:05.05,0:13:06.07,Default,,0000,0000,0000,,with bacterial
Dialogue: 0,0:13:06.07,0:13:11.00,Default,,0000,0000,0000,,infections, but you can\Nget inflammation of the myocardium
Dialogue: 0,0:13:11.00,0:13:13.08,Default,,0000,0000,0000,,and you can almost literally hear
Dialogue: 0,0:13:13.08,0:13:16.02,Default,,0000,0000,0000,,these cells chewing at the myocytes
Dialogue: 0,0:13:16.02,0:13:18.02,Default,,0000,0000,0000,,and obviously
Dialogue: 0,0:13:18.02,0:13:22.06,Default,,0000,0000,0000,,obviously that can produce failure.
Dialogue: 0,0:13:22.06,0:13:25.05,Default,,0000,0000,0000,,We see that not infrequently,
Dialogue: 0,0:13:25.05,0:13:29.05,Default,,0000,0000,0000,,then the heart can be involved in a\Nvariety of systemic diseases, in other words
Dialogue: 0,0:13:29.05,0:13:32.10,Default,,0000,0000,0000,,you can have something\Ngoing on affecting many tissues in
Dialogue: 0,0:13:32.10,0:13:36.04,Default,,0000,0000,0000,,the body, but that something may affect the heart and produce
Dialogue: 0,0:13:36.04,0:13:37.67,Default,,0000,0000,0000,,failure. Here's an example
Dialogue: 0,0:13:37.67,0:13:39.09,Default,,0000,0000,0000,,now I don't know
Dialogue: 0,0:13:39.09,0:13:44.02,Default,,0000,0000,0000,,if I want to dart in the\Nauditorium completely to show you this
Dialogue: 0,0:13:44.02,0:13:49.09,Default,,0000,0000,0000,,did you discuss hemochromatosis in genetics? Yes? Not a complete blank.
Dialogue: 0,0:13:49.09,0:13:52.02,Default,,0000,0000,0000,,
Dialogue: 0,0:13:52.02,0:13:56.02,Default,,0000,0000,0000,,It's an ineffective storage\Ndisease because the body absorbs too much iron
Dialogue: 0,0:13:56.02,0:13:56.08,Default,,0000,0000,0000,,from the gut,
Dialogue: 0,0:13:56.08,0:13:58.00,Default,,0000,0000,0000,,and the iron
Dialogue: 0,0:13:58.00,0:14:01.09,Default,,0000,0000,0000,,gets stored in a variety of\Nissues and one of the tissues it gets stored in
Dialogue: 0,0:14:01.09,0:14:03.07,Default,,0000,0000,0000,,is the heart,
Dialogue: 0,0:14:03.07,0:14:07.02,Default,,0000,0000,0000,,and you recognize instantly that this is myocardium
Dialogue: 0,0:14:07.02,0:14:11.02,Default,,0000,0000,0000,,and as you stare at it a little bit, you'll pick out some nice golden brown pigment
Dialogue: 0,0:14:11.02,0:14:16.04,Default,,0000,0000,0000,,there and there and there, you see a little\Nmore over there, and little bit down there and over there.
Dialogue: 0,0:14:16.04,0:14:18.07,Default,,0000,0000,0000,,and one of the pigments
Dialogue: 0,0:14:18.07,0:14:21.09,Default,,0000,0000,0000,,you'd think of in the heart, someone asked me a question about this last week,
Dialogue: 0,0:14:21.09,0:14:25.05,Default,,0000,0000,0000,,it would be lipofuscin (wear and tear pigment)
Dialogue: 0,0:14:25.05,0:14:30.07,Default,,0000,0000,0000,,but another pigment you got to think about is iron, and this is stored iron
Dialogue: 0,0:14:30.07,0:14:31.99,Default,,0000,0000,0000,,in this myocardium. Here is
Dialogue: 0,0:14:31.99,0:14:33.04,Default,,0000,0000,0000,,that blue
Dialogue: 0,0:14:33.04,0:14:37.10,Default,,0000,0000,0000,,Prussian blue iron stain, tremendous iron
Dialogue: 0,0:14:37.10,0:14:38.10,Default,,0000,0000,0000,,load, iron is bad for you
Dialogue: 0,0:14:38.10,0:14:44.02,Default,,0000,0000,0000,,if it gets deposited in certain tissues. This can produce myocardial failure.
Dialogue: 0,0:14:44.02,0:14:46.09,Default,,0000,0000,0000,,This was from a relatively young man who presented with
Dialogue: 0,0:14:46.09,0:14:49.00,Default,,0000,0000,0000,,very advanced heart failure
Dialogue: 0,0:14:49.00,0:14:51.01,Default,,0000,0000,0000,,because of his unrecognized
Dialogue: 0,0:14:51.01,0:14:52.00,Default,,0000,0000,0000,,hemochromatosis.
Dialogue: 0,0:14:52.00,0:14:54.06,Default,,0000,0000,0000,,
Dialogue: 0,0:14:54.06,0:14:55.01,Default,,0000,0000,0000,,One other that you will hear about
Dialogue: 0,0:14:55.01,0:14:58.04,Default,,0000,0000,0000,,probably next year
Dialogue: 0,0:14:58.04,0:15:01.03,Default,,0000,0000,0000,,is amyloidosis. Amyloid
Dialogue: 0,0:15:01.03,0:15:02.11,Default,,0000,0000,0000,,
Dialogue: 0,0:15:02.11,0:15:06.06,Default,,0000,0000,0000,,is an abnormal protein that could\Nget deposited in a number of tissues
Dialogue: 0,0:15:06.06,0:15:08.08,Default,,0000,0000,0000,,for a number of reasons, which I won't go into.
Dialogue: 0,0:15:08.08,0:15:10.15,Default,,0000,0000,0000,,But all of this
Dialogue: 0,0:15:10.15,0:15:15.00,Default,,0000,0000,0000,,sort of translucent, gray stuff surrounding the
Dialogue: 0,0:15:15.00,0:15:19.07,Default,,0000,0000,0000,,myocytes, you're looking at a cross-sectional view of myocardium,
Dialogue: 0,0:15:19.07,0:15:23.05,Default,,0000,0000,0000,,and you can see that each myocyte is enveloped in this
Dialogue: 0,0:15:23.05,0:15:24.06,Default,,0000,0000,0000,,casing
Dialogue: 0,0:15:24.06,0:15:26.04,Default,,0000,0000,0000,,of amyloid.
Dialogue: 0,0:15:26.04,0:15:27.06,Default,,0000,0000,0000,,And this is
Dialogue: 0,0:15:27.06,0:15:31.01,Default,,0000,0000,0000,,a marvelous example of\Nsomething that renders the heart rigid
Dialogue: 0,0:15:31.01,0:15:31.09,Default,,0000,0000,0000,,and unable to
Dialogue: 0,0:15:31.09,0:15:34.07,Default,,0000,0000,0000,,expand diastolically, and it can be
Dialogue: 0,0:15:34.07,0:15:36.06,Default,,0000,0000,0000,,a cause of heart failure.
Dialogue: 0,0:15:36.06,0:15:38.09,Default,,0000,0000,0000,,Finally,
Dialogue: 0,0:15:38.09,0:15:41.06,Default,,0000,0000,0000,,this is not a complete list, I'm just showing
Dialogue: 0,0:15:41.06,0:15:43.01,Default,,0000,0000,0000,,the examples, there are
Dialogue: 0,0:15:43.01,0:15:47.08,Default,,0000,0000,0000,,a number of genetic diseases\Nof the heart muscle itself, where from
Dialogue: 0,0:15:47.08,0:15:49.08,Default,,0000,0000,0000,,the get go, because of
Dialogue: 0,0:15:49.08,0:15:51.09,Default,,0000,0000,0000,,abnormal genetic endowment
Dialogue: 0,0:15:51.09,0:15:52.05,Default,,0000,0000,0000,,
Dialogue: 0,0:15:52.05,0:15:53.08,Default,,0000,0000,0000,,the heart is
Dialogue: 0,0:15:53.08,0:15:56.00,Default,,0000,0000,0000,,made wrong. Here's an example
Dialogue: 0,0:15:56.00,0:16:00.02,Default,,0000,0000,0000,,of something we call hypertrophic cardiomyopathy.
Dialogue: 0,0:16:00.02,0:16:06.01,Default,,0000,0000,0000,,Cardiomyopathy means\Nheart muscle disease.
Dialogue: 0,0:16:06.01,0:16:09.08,Default,,0000,0000,0000,,This particular heart was immensely\Nhypertrophic, you can see that left ventricle
Dialogue: 0,0:16:09.08,0:16:11.09,Default,,0000,0000,0000,,it's really tremendous with no
Dialogue: 0,0:16:11.09,0:16:14.01,Default,,0000,0000,0000,,valve disease, no hypertension to explain that,
Dialogue: 0,0:16:14.01,0:16:17.00,Default,,0000,0000,0000,,but look at the
Dialogue: 0,0:16:17.00,0:16:19.06,Default,,0000,0000,0000,,goofy muscle, you know
Dialogue: 0,0:16:19.06,0:16:23.03,Default,,0000,0000,0000,,what myocardium is supposed to look like, and the histology people never show you
Dialogue: 0,0:16:23.03,0:16:24.00,Default,,0000,0000,0000,,the kind of
Dialogue: 0,0:16:24.00,0:16:27.06,Default,,0000,0000,0000,,disarray and criss-crossing of\Nfibers like that.
Dialogue: 0,0:16:27.06,0:16:33.06,Default,,0000,0000,0000,,This is the result of the genetic\Nabnormality of this myocardium.
Dialogue: 0,0:16:33.06,0:16:37.00,Default,,0000,0000,0000,,All right, these are just a few examples\Nof the things that can go wrong
Dialogue: 0,0:16:37.00,0:16:40.01,Default,,0000,0000,0000,,
Dialogue: 0,0:16:40.01,0:16:41.09,Default,,0000,0000,0000,,and most frequently,
Dialogue: 0,0:16:41.09,0:16:46.00,Default,,0000,0000,0000,,if I had to pick from this whole list, I'd say hypertension and
Dialogue: 0,0:16:46.00,0:16:47.06,Default,,0000,0000,0000,,ischemic disease
Dialogue: 0,0:16:47.06,0:16:52.06,Default,,0000,0000,0000,,are the big actors at least in our population.
Dialogue: 0,0:16:52.06,0:16:55.05,Default,,0000,0000,0000,,Whatever the cause, as the heart is
Dialogue: 0,0:16:55.05,0:16:56.09,Default,,0000,0000,0000,,overburdened,
Dialogue: 0,0:16:56.09,0:17:00.00,Default,,0000,0000,0000,,there are certain compensatory\Nmechanisms that kick in
Dialogue: 0,0:17:00.00,0:17:02.09,Default,,0000,0000,0000,,for a while, in other words, enable\Nthe heart to keep up
Dialogue: 0,0:17:02.09,0:17:05.04,Default,,0000,0000,0000,,with the abnormal strain,
Dialogue: 0,0:17:05.04,0:17:08.08,Default,,0000,0000,0000,,and some of these you know about, you've\Nheard about I'm sure about the Frank Starling
Dialogue: 0,0:17:08.08,0:17:10.18,Default,,0000,0000,0000,,mechanism,
Dialogue: 0,0:17:10.18,0:17:11.00,Default,,0000,0000,0000,,
Dialogue: 0,0:17:11.00,0:17:11.07,Default,,0000,0000,0000,,
Dialogue: 0,0:17:11.07,0:17:17.00,Default,,0000,0000,0000,,where the myocyte is stretched by\Nincreased filling pressure, it's stretched
Dialogue: 0,0:17:17.00,0:17:19.00,Default,,0000,0000,0000,,and contracts then
Dialogue: 0,0:17:19.00,0:17:20.09,Default,,0000,0000,0000,,with greater vigor,
Dialogue: 0,0:17:20.09,0:17:23.43,Default,,0000,0000,0000,,in other words, it can put out more UMPH
Dialogue: 0,0:17:23.43,0:17:27.07,Default,,0000,0000,0000,,if it starts from a slight stretch. The\Ntrouble with that mechanism is that it fails.
Dialogue: 0,0:17:27.07,0:17:28.21,Default,,0000,0000,0000,,In other words, for a while
Dialogue: 0,0:17:28.21,0:17:31.08,Default,,0000,0000,0000,,it's adaptive, you get more and more UMPH for each
Dialogue: 0,0:17:31.08,0:17:34.02,Default,,0000,0000,0000,,contraction and then it peters out
Dialogue: 0,0:17:34.02,0:17:37.00,Default,,0000,0000,0000,,for a variety of reasons.
Dialogue: 0,0:17:37.00,0:17:40.04,Default,,0000,0000,0000,,A second compensation is hypertrophy,
Dialogue: 0,0:17:40.04,0:17:44.05,Default,,0000,0000,0000,,and you know about this, we talked about\Nit last summer I guess.
Dialogue: 0,0:17:44.05,0:17:46.16,Default,,0000,0000,0000,,It's a situation where the same number
Dialogue: 0,0:17:46.16,0:17:49.15,Default,,0000,0000,0000,,of muscle cells are there
Dialogue: 0,0:17:49.15,0:17:51.07,Default,,0000,0000,0000,,but more sarcomeres are added
Dialogue: 0,0:17:51.07,0:17:54.09,Default,,0000,0000,0000,,and the muscle cells enlarge the whole
Dialogue: 0,0:17:54.09,0:17:56.07,Default,,0000,0000,0000,,tissue grossly
Dialogue: 0,0:17:56.07,0:17:59.00,Default,,0000,0000,0000,,enlarges and there's more UMPH.
Dialogue: 0,0:17:59.00,0:18:00.09,Default,,0000,0000,0000,,I mean it's very definitely
Dialogue: 0,0:18:00.09,0:18:03.10,Default,,0000,0000,0000,,a compensatory mechanism.
Dialogue: 0,0:18:03.10,0:18:05.00,Default,,0000,0000,0000,,A third compensation
Dialogue: 0,0:18:05.00,0:18:08.02,Default,,0000,0000,0000,,mechanism I've listed
Dialogue: 0,0:18:08.02,0:18:11.06,Default,,0000,0000,0000,,is activation of neuro-humoral systems and we're not going to go into that
Dialogue: 0,0:18:11.06,0:18:13.65,Default,,0000,0000,0000,,in much detail, just enough detail
Dialogue: 0,0:18:13.65,0:18:15.00,Default,,0000,0000,0000,,so you know that
Dialogue: 0,0:18:15.00,0:18:17.01,Default,,0000,0000,0000,,they are there.
Dialogue: 0,0:18:17.01,0:18:19.08,Default,,0000,0000,0000,,Now here's hypertrophy!
Dialogue: 0,0:18:19.08,0:18:22.05,Default,,0000,0000,0000,,Normal size myocytes you see over here
Dialogue: 0,0:18:22.05,0:18:25.09,Default,,0000,0000,0000,,and each one is on the average just a\Nlittle bit thicker
Dialogue: 0,0:18:25.09,0:18:27.01,Default,,0000,0000,0000,,than the normal
Dialogue: 0,0:18:27.01,0:18:28.04,Default,,0000,0000,0000,,
Dialogue: 0,0:18:28.04,0:18:32.05,Default,,0000,0000,0000,,That's because of addition of sarcomeres, not much change in the number of cells
Dialogue: 0,0:18:32.05,0:18:36.00,Default,,0000,0000,0000,,and you can imagine these cells having\Nmore UMPH like a weight lifter,
Dialogue: 0,0:18:36.00,0:18:41.10,Default,,0000,0000,0000,,imagine that, like a weight lifters arm
Dialogue: 0,0:18:41.10,0:18:44.39,Default,,0000,0000,0000,,This is maybe what we see
Dialogue: 0,0:18:44.39,0:18:48.79,Default,,0000,0000,0000,,grossly, there's an increase in\Nthe muscle, increase in the weight of the heart,
Dialogue: 0,0:18:48.79,0:18:49.07,Default,,0000,0000,0000,,and sometimes
Dialogue: 0,0:18:49.07,0:18:53.09,Default,,0000,0000,0000,,we see concentric hypertrophy, meaning
Dialogue: 0,0:18:53.09,0:18:58.04,Default,,0000,0000,0000,,the chamber is not enlarged, it may even be a\Nlittle smaller, gross thickening of the walls
Dialogue: 0,0:18:58.04,0:18:59.10,Default,,0000,0000,0000,,and its
Dialogue: 0,0:18:59.10,0:19:00.08,Default,,0000,0000,0000,,concentric.
Dialogue: 0,0:19:00.08,0:19:03.05,Default,,0000,0000,0000,,We see that usually with\Npressure overload.
Dialogue: 0,0:19:03.05,0:19:06.04,Default,,0000,0000,0000,,With a volume overload, we may see
Dialogue: 0,0:19:06.04,0:19:07.05,Default,,0000,0000,0000,,what looks like no hypertrophy
Dialogue: 0,0:19:07.05,0:19:10.06,Default,,0000,0000,0000,,at all except that's a lot more muscle
Dialogue: 0,0:19:10.06,0:19:13.05,Default,,0000,0000,0000,,than there is normal, it's just that it's\Ndilated.
Dialogue: 0,0:19:13.05,0:19:16.02,Default,,0000,0000,0000,,That also happens in very advanced\Nfailure
Dialogue: 0,0:19:16.02,0:19:19.00,Default,,0000,0000,0000,,from any cause, you see this sort of\Neccentric picture.
Dialogue: 0,0:19:19.00,0:19:20.04,Default,,0000,0000,0000,,
Dialogue: 0,0:19:20.04,0:19:24.01,Default,,0000,0000,0000,,When it comes to the neuro-humoral\Nmechanisms, I'm just going to race through these now,
Dialogue: 0,0:19:24.01,0:19:25.05,Default,,0000,0000,0000,,there is
Dialogue: 0,0:19:25.05,0:19:28.02,Default,,0000,0000,0000,,first of all
Dialogue: 0,0:19:28.02,0:19:30.00,Default,,0000,0000,0000,,
Dialogue: 0,0:19:30.00,0:19:32.08,Default,,0000,0000,0000,,all of these things tend to be triggered\Nby pressure and
Dialogue: 0,0:19:32.08,0:19:36.41,Default,,0000,0000,0000,,stretch receptors that are\Nscattered through the heart
Dialogue: 0,0:19:36.41,0:19:38.79,Default,,0000,0000,0000,,the aorta, the carotids,
Dialogue: 0,0:19:38.79,0:19:41.03,Default,,0000,0000,0000,,and the kidney even there is such sensing.
Dialogue: 0,0:19:41.03,0:19:45.07,Default,,0000,0000,0000,,When the cardiac output\Nbegins to drop, these receptors say UH OH
Dialogue: 0,0:19:45.07,0:19:50.02,Default,,0000,0000,0000,,and they trigger a number of things, one of the things they trigger is
Dialogue: 0,0:19:50.02,0:19:51.09,Default,,0000,0000,0000,,a central nervous system,
Dialogue: 0,0:19:51.09,0:19:54.04,Default,,0000,0000,0000,,i'm sorry, the sympathetic nervous\Nsystem
Dialogue: 0,0:19:54.04,0:19:57.56,Default,,0000,0000,0000,,with release of norepinephrine
Dialogue: 0,0:19:57.56,0:19:59.00,Default,,0000,0000,0000,,and this can produce
Dialogue: 0,0:19:59.00,0:20:02.06,Default,,0000,0000,0000,,a contractile boost for the heart
Dialogue: 0,0:20:02.06,0:20:04.03,Default,,0000,0000,0000,,
Dialogue: 0,0:20:04.03,0:20:07.09,Default,,0000,0000,0000,,this can produce an increased heart\Nrate
Dialogue: 0,0:20:07.09,0:20:11.09,Default,,0000,0000,0000,,these things will help meet\Nan abnormal load
Dialogue: 0,0:20:11.09,0:20:16.00,Default,,0000,0000,0000,,and also this will produce vasoconstriction peripherally.
Dialogue: 0,0:20:16.00,0:20:18.06,Default,,0000,0000,0000,,This is designed,
Dialogue: 0,0:20:18.06,0:20:20.05,Default,,0000,0000,0000,,this evolved this way presumably to
Dialogue: 0,0:20:20.05,0:20:26.01,Default,,0000,0000,0000,,to make sure that\Nblood gets shunted to essential organs
Dialogue: 0,0:20:26.01,0:20:29.03,Default,,0000,0000,0000,,so there's peripheral\Nvasoconstriction
Dialogue: 0,0:20:29.03,0:20:33.55,Default,,0000,0000,0000,,which increase, well we'll talk about\Nwhat the bad things it does.
Dialogue: 0,0:20:33.55,0:20:35.22,Default,,0000,0000,0000,,Vasopressin is released
Dialogue: 0,0:20:35.22,0:20:38.09,Default,,0000,0000,0000,,from the hypothalamus, that's also a vasoconstrictor,
Dialogue: 0,0:20:38.09,0:20:41.02,Default,,0000,0000,0000,,and we talked in class previously about
Dialogue: 0,0:20:41.02,0:20:44.09,Default,,0000,0000,0000,,the renin-angiotension-aldosterone system.
Dialogue: 0,0:20:44.09,0:20:45.10,Default,,0000,0000,0000,,
Dialogue: 0,0:20:45.10,0:20:51.55,Default,,0000,0000,0000,,The kidney senses the decreased flow\Nthat's coming to it, secretes renin which
Dialogue: 0,0:20:51.55,0:20:56.00,Default,,0000,0000,0000,,acts on angiotensinogen which is\Ncirculating protein
Dialogue: 0,0:20:56.00,0:20:56.10,Default,,0000,0000,0000,,
Dialogue: 0,0:20:56.10,0:20:58.09,Default,,0000,0000,0000,,forms angiotensin I
Dialogue: 0,0:20:58.09,0:21:02.00,Default,,0000,0000,0000,,and then there's angiotensin\Nconverting enzyme which takes angiotensin II
Dialogue: 0,0:21:02.00,0:21:03.04,Default,,0000,0000,0000,,that in turn
Dialogue: 0,0:21:03.04,0:21:05.00,Default,,0000,0000,0000,,stimulates the production
Dialogue: 0,0:21:05.00,0:21:10.02,Default,,0000,0000,0000,,in the adrenals of aldosterone.
Dialogue: 0,0:21:10.02,0:21:11.00,Default,,0000,0000,0000,,
Dialogue: 0,0:21:11.00,0:21:14.86,Default,,0000,0000,0000,,The importance of all of this is first of all angiotensin II
Dialogue: 0,0:21:14.86,0:21:18.06,Default,,0000,0000,0000,,is also a vasoconstrictor
Dialogue: 0,0:21:18.06,0:21:20.05,Default,,0000,0000,0000,,and
Dialogue: 0,0:21:20.05,0:21:24.08,Default,,0000,0000,0000,,between angiotensin II and aldosterone, there is
Dialogue: 0,0:21:24.08,0:21:29.04,Default,,0000,0000,0000,,sodium retention, salt\Nretention, sodium retention and water retention
Dialogue: 0,0:21:29.04,0:21:30.07,Default,,0000,0000,0000,,and that has
Dialogue: 0,0:21:30.07,0:21:33.08,Default,,0000,0000,0000,,some important consequences.
Dialogue: 0,0:21:33.08,0:21:38.06,Default,,0000,0000,0000,,I just listed, I don't have time to go into it, the natriuretic peptides
Dialogue: 0,0:21:38.06,0:21:42.08,Default,,0000,0000,0000,,secreted by the heart which\Ntend to counteract the renin-angiotensin-aldosterone
Dialogue: 0,0:21:42.08,0:21:45.09,Default,,0000,0000,0000,,system to some extent.
Dialogue: 0,0:21:45.09,0:21:49.06,Default,,0000,0000,0000,,Unfortunately, all of these
Dialogue: 0,0:21:49.06,0:21:52.04,Default,,0000,0000,0000,,mechanisms
Dialogue: 0,0:21:52.04,0:21:56.00,Default,,0000,0000,0000,,are limited in how much help they can provide and there's a downside
Dialogue: 0,0:21:56.00,0:21:57.03,Default,,0000,0000,0000,,to a lot of them.
Dialogue: 0,0:21:57.03,0:21:58.07,Default,,0000,0000,0000,,Now
Dialogue: 0,0:21:58.07,0:22:02.03,Default,,0000,0000,0000,,problems with hypertrophy, it just gets bigger and
Dialogue: 0,0:22:02.03,0:22:04.00,Default,,0000,0000,0000,,bigger and bigger muscle,
Dialogue: 0,0:22:04.00,0:22:08.05,Default,,0000,0000,0000,,it doesn't work out that way because\Nthe capillary network in the muscle
Dialogue: 0,0:22:08.05,0:22:11.27,Default,,0000,0000,0000,,does not increase in parallel and you
Dialogue: 0,0:22:11.27,0:22:15.26,Default,,0000,0000,0000,,end up with perfusion problems\Nso there's a limit to how much hypertrophy
Dialogue: 0,0:22:15.26,0:22:18.04,Default,,0000,0000,0000,,the tissue can stand.
Dialogue: 0,0:22:18.04,0:22:21.06,Default,,0000,0000,0000,,Same is true for the ratio between mitochondria and
Dialogue: 0,0:22:21.06,0:22:27.03,Default,,0000,0000,0000,,and contractile protein, so to speak,\Nthe mitochondria-to-meat ratio
Dialogue: 0,0:22:27.03,0:22:31.04,Default,,0000,0000,0000,,does not keep up to what it should be so\Nthe energy is a problem.
Dialogue: 0,0:22:31.04,0:22:33.04,Default,,0000,0000,0000,,Then very importantly
Dialogue: 0,0:22:33.04,0:22:38.07,Default,,0000,0000,0000,,we're learning that there is altered\Ngene expression
Dialogue: 0,0:22:38.07,0:22:40.04,Default,,0000,0000,0000,,and alteration in the
Dialogue: 0,0:22:40.04,0:22:43.07,Default,,0000,0000,0000,,proteins that are produced, and these may involve
Dialogue: 0,0:22:43.07,0:22:45.67,Default,,0000,0000,0000,,contractile proteins,
Dialogue: 0,0:22:45.67,0:22:46.07,Default,,0000,0000,0000,,segmentation
Dialogue: 0,0:22:46.07,0:22:50.07,Default,,0000,0000,0000,,contraction coupling them, they may involve energy utilization,
Dialogue: 0,0:22:50.07,0:22:53.09,Default,,0000,0000,0000,,but some abnormal proteins are made
Dialogue: 0,0:22:53.09,0:22:57.05,Default,,0000,0000,0000,,there's an increase in apoptosis
Dialogue: 0,0:22:57.05,0:23:00.00,Default,,0000,0000,0000,,in a hypertrophic myocardium
Dialogue: 0,0:23:00.00,0:23:01.52,Default,,0000,0000,0000,,and, under the influence
Dialogue: 0,0:23:01.52,0:23:06.97,Default,,0000,0000,0000,,of all of this is actually driven by the various hormonal
Dialogue: 0,0:23:06.97,0:23:09.10,Default,,0000,0000,0000,,things that i've mentioned
Dialogue: 0,0:23:09.10,0:23:11.47,Default,,0000,0000,0000,,and with something
Dialogue: 0,0:23:11.47,0:23:15.10,Default,,0000,0000,0000,,we call remodeling occurs, there's a\Nchange in geometry of the ventricle
Dialogue: 0,0:23:15.10,0:23:19.08,Default,,0000,0000,0000,,which can have implications of tugs on the chordae tendinae of the mitral valve
Dialogue: 0,0:23:19.08,0:23:23.01,Default,,0000,0000,0000,,the wrong valve, you can get mitral regurgitation,
Dialogue: 0,0:23:23.01,0:23:26.02,Default,,0000,0000,0000,,it's a disadvantageous thing
Dialogue: 0,0:23:26.02,0:23:30.00,Default,,0000,0000,0000,,often associated with a lot of fibrosis, that blue-green tissue racing through the myocardium
Dialogue: 0,0:23:30.00,0:23:31.04,Default,,0000,0000,0000,,
Dialogue: 0,0:23:31.04,0:23:35.00,Default,,0000,0000,0000,,is a fibrosis in the remodeled ventricle
Dialogue: 0,0:23:35.00,0:23:39.01,Default,,0000,0000,0000,,which causes problems of its own as you\Ncan imagine, I don't have to go into any detail
Dialogue: 0,0:23:39.01,0:23:40.02,Default,,0000,0000,0000,,
Dialogue: 0,0:23:40.02,0:23:42.08,Default,,0000,0000,0000,,So that's a problem
Dialogue: 0,0:23:42.08,0:23:44.08,Default,,0000,0000,0000,,and there's a problem
Dialogue: 0,0:23:44.08,0:23:48.09,Default,,0000,0000,0000,,with neurohumoral activation,
Dialogue: 0,0:23:48.09,0:23:50.08,Default,,0000,0000,0000,,vasoconstriction increases the
Dialogue: 0,0:23:50.08,0:23:54.08,Default,,0000,0000,0000,,afterload that this poor\Nold failing heart has to pump against.
Dialogue: 0,0:23:54.08,0:23:56.02,Default,,0000,0000,0000,,It sounds like
Dialogue: 0,0:23:56.02,0:23:59.00,Default,,0000,0000,0000,,a nice mechanism, but it
Dialogue: 0,0:23:59.00,0:24:00.03,Default,,0000,0000,0000,,bites the heart
Dialogue: 0,0:24:00.03,0:24:04.07,Default,,0000,0000,0000,,Various of these humoral\Nsubstances are
Dialogue: 0,0:24:04.07,0:24:06.00,Default,,0000,0000,0000,,cardiotoxic
Dialogue: 0,0:24:06.00,0:24:07.03,Default,,0000,0000,0000,,chronically
Dialogue: 0,0:24:07.03,0:24:09.10,Default,,0000,0000,0000,,in other words, they are\Nresponsible for the increase in apoptosis
Dialogue: 0,0:24:09.10,0:24:14.07,Default,,0000,0000,0000,,they drive the remodeling and it's a bad thing for the heart
Dialogue: 0,0:24:14.07,0:24:16.00,Default,,0000,0000,0000,,in the long run,
Dialogue: 0,0:24:16.00,0:24:17.21,Default,,0000,0000,0000,,and we know about the
Dialogue: 0,0:24:17.21,0:24:21.53,Default,,0000,0000,0000,,implications of sodium and\Nwater retention and how that
Dialogue: 0,0:24:21.53,0:24:24.04,Default,,0000,0000,0000,,overloads the heart.
Dialogue: 0,0:24:24.04,0:24:26.03,Default,,0000,0000,0000,,All of these things
Dialogue: 0,0:24:26.03,0:24:26.07,Default,,0000,0000,0000,,contribute to the downward spiral
Dialogue: 0,0:24:26.07,0:24:29.07,Default,,0000,0000,0000,,
Dialogue: 0,0:24:29.07,0:24:33.05,Default,,0000,0000,0000,,and I've simplified a very\Ncomplex business, but
Dialogue: 0,0:24:33.05,0:24:35.02,Default,,0000,0000,0000,,there are many
Dialogue: 0,0:24:35.02,0:24:38.05,Default,,0000,0000,0000,,consequences for the\Nperipheral tissues and that's what we're
Dialogue: 0,0:24:38.05,0:24:41.86,Default,,0000,0000,0000,,really talking about when we talk about\Nheart failure, what's going on
Dialogue: 0,0:24:41.86,0:24:44.30,Default,,0000,0000,0000,,in the peripheral tissues.
Dialogue: 0,0:24:44.30,0:24:48.01,Default,,0000,0000,0000,,These consequences we can\Ntalk about in a number of ways, we talk
Dialogue: 0,0:24:48.01,0:24:51.06,Default,,0000,0000,0000,,about sometimes forward failure and backward failure.
Dialogue: 0,0:24:51.06,0:24:53.51,Default,,0000,0000,0000,,Forward failure being the idea that
Dialogue: 0,0:24:53.51,0:24:58.07,Default,,0000,0000,0000,,the failing heart does not perfuse the\Ntissues well enough, and
Dialogue: 0,0:24:58.07,0:24:59.67,Default,,0000,0000,0000,,backward failure you're familiar
Dialogue: 0,0:24:59.67,0:25:03.04,Default,,0000,0000,0000,,with the idea of passive\Ncongestion and we talked about that in class
Dialogue: 0,0:25:03.04,0:25:05.07,Default,,0000,0000,0000,,so you have a good image of that.
Dialogue: 0,0:25:05.07,0:25:08.93,Default,,0000,0000,0000,,We speak of left heart failure and\Nright heart failure,
Dialogue: 0,0:25:08.93,0:25:10.03,Default,,0000,0000,0000,,most processes that cause
Dialogue: 0,0:25:10.03,0:25:12.00,Default,,0000,0000,0000,,heart failure start out on the left
Dialogue: 0,0:25:12.00,0:25:15.00,Default,,0000,0000,0000,,but it's a closed plumbing system
Dialogue: 0,0:25:15.00,0:25:20.01,Default,,0000,0000,0000,,so as the left heart fails, the right heart is going to fail.
Dialogue: 0,0:25:20.01,0:25:21.03,Default,,0000,0000,0000,,The commonest
Dialogue: 0,0:25:21.03,0:25:25.10,Default,,0000,0000,0000,,cause of right heart failure then is left heart failure.
Dialogue: 0,0:25:25.10,0:25:29.05,Default,,0000,0000,0000,,There are some of the examples where the\Nright heart fails primarily and it has to do
Dialogue: 0,0:25:29.05,0:25:31.04,Default,,0000,0000,0000,,with things happening in the lungs,
Dialogue: 0,0:25:31.04,0:25:37.02,Default,,0000,0000,0000,,they're relatively less common and you'll\Nhear more about them some other time,
Dialogue: 0,0:25:37.02,0:25:41.04,Default,,0000,0000,0000,,but the backward consequences\Nof left and right heart failure are very
Dialogue: 0,0:25:41.04,0:25:45.08,Default,,0000,0000,0000,,familiar to you already, we know that when the left heart fails you get
Dialogue: 0,0:25:45.08,0:25:47.51,Default,,0000,0000,0000,,pulmonary congestion and edema,
Dialogue: 0,0:25:47.51,0:25:50.05,Default,,0000,0000,0000,,when the right heart fails, you get
Dialogue: 0,0:25:50.05,0:25:52.07,Default,,0000,0000,0000,,elevation of hydrostatic
Dialogue: 0,0:25:52.07,0:25:55.03,Default,,0000,0000,0000,,pressure in a variety of\Ntissues
Dialogue: 0,0:25:55.03,0:25:56.42,Default,,0000,0000,0000,,with associated
Dialogue: 0,0:25:56.42,0:26:00.39,Default,,0000,0000,0000,,congestive changes in\Norgans and accumulation of edema
Dialogue: 0,0:26:00.39,0:26:02.01,Default,,0000,0000,0000,,fluid and this
Dialogue: 0,0:26:02.01,0:26:05.00,Default,,0000,0000,0000,,is when we start to speak of congestive heart failure.
Dialogue: 0,0:26:05.00,0:26:08.06,Default,,0000,0000,0000,,We're throwing that adjective very frequently
Dialogue: 0,0:26:08.06,0:26:10.02,Default,,0000,0000,0000,,
Dialogue: 0,0:26:10.02,0:26:14.02,Default,,0000,0000,0000,,What we're not emphasizing, and I'll just conclude by mentioning this,
Dialogue: 0,0:26:14.02,0:26:15.08,Default,,0000,0000,0000,,are the forward changes
Dialogue: 0,0:26:15.08,0:26:18.08,Default,,0000,0000,0000,,associated with left heart\Nfailure, in other words, when the left
Dialogue: 0,0:26:18.08,0:26:20.10,Default,,0000,0000,0000,,heart fails, things begin to
Dialogue: 0,0:26:20.10,0:26:25.56,Default,,0000,0000,0000,,happen because tissues\Nin a variety of places simply aren't being perfused.
Dialogue: 0,0:26:25.56,0:26:27.03,Default,,0000,0000,0000,,And you're familiar already with
Dialogue: 0,0:26:27.03,0:26:30.09,Default,,0000,0000,0000,,the activation of the
Dialogue: 0,0:26:30.09,0:26:32.06,Default,,0000,0000,0000,,renin-angiotensin-aldosterone system
Dialogue: 0,0:26:32.06,0:26:37.02,Default,,0000,0000,0000,,from forward failure to
Dialogue: 0,0:26:37.02,0:26:39.10,Default,,0000,0000,0000,,supply enough blood to the kidney,
Dialogue: 0,0:26:39.10,0:26:45.27,Default,,0000,0000,0000,,I would point out that as the\Nperfusion drops more and more,
Dialogue: 0,0:26:45.27,0:26:49.10,Default,,0000,0000,0000,,the kidney can really shut down as far as\Nits excretory function and nitrogenous
Dialogue: 0,0:26:49.10,0:26:52.09,Default,,0000,0000,0000,,waste can pile up.
Dialogue: 0,0:26:52.09,0:26:54.04,Default,,0000,0000,0000,,Sometimes they speak,
Dialogue: 0,0:26:54.04,0:26:58.04,Default,,0000,0000,0000,,people speak, of a cardio-renal syndrome because of this.
Dialogue: 0,0:26:58.04,0:26:59.05,Default,,0000,0000,0000,,Well many other
Dialogue: 0,0:26:59.05,0:27:04.08,Default,,0000,0000,0000,,tissues suffer from this lack of perfusion in the same way.
Dialogue: 0,0:27:04.08,0:27:07.08,Default,,0000,0000,0000,,We've shown you for instance the liver,
Dialogue: 0,0:27:07.08,0:27:11.01,Default,,0000,0000,0000,,and the liver gets caught in a one-two punch,
Dialogue: 0,0:27:11.01,0:27:12.92,Default,,0000,0000,0000,,there's resistance to outflow from the liver
Dialogue: 0,0:27:12.92,0:27:16.00,Default,,0000,0000,0000,,the fact is that the poor old failing left\Nventricle isn't delivering enough blood
Dialogue: 0,0:27:16.00,0:27:17.00,Default,,0000,0000,0000,,to this, the central
Dialogue: 0,0:27:17.00,0:27:19.08,Default,,0000,0000,0000,,lobular area,
Dialogue: 0,0:27:19.08,0:27:22.00,Default,,0000,0000,0000,,and it undergoes a sort of hemorrhagic
Dialogue: 0,0:27:22.00,0:27:24.01,Default,,0000,0000,0000,,necrosis which you remember that, you never forget
Dialogue: 0,0:27:24.01,0:27:26.08,Default,,0000,0000,0000,,that kind of a picture.
Dialogue: 0,0:27:26.08,0:27:31.01,Default,,0000,0000,0000,,Now something, a little wrinkle that I'll point out here,
Dialogue: 0,0:27:31.01,0:27:31.08,Default,,0000,0000,0000,,is that the aldosterone
Dialogue: 0,0:27:31.08,0:27:35.31,Default,,0000,0000,0000,,levels in patients in\Nfailure are way way up there
Dialogue: 0,0:27:35.31,0:27:36.10,Default,,0000,0000,0000,,and part of it
Dialogue: 0,0:27:36.10,0:27:40.02,Default,,0000,0000,0000,,obviously is because it's been\Ntriggered by the production of angiotensin II
Dialogue: 0,0:27:40.02,0:27:42.05,Default,,0000,0000,0000,,and so forth, but the liver
Dialogue: 0,0:27:42.05,0:27:44.08,Default,,0000,0000,0000,,when it's in that kind of a state,
Dialogue: 0,0:27:44.08,0:27:48.08,Default,,0000,0000,0000,,does not catabolize aldosterone the way it should,
Dialogue: 0,0:27:48.08,0:27:52.56,Default,,0000,0000,0000,,and the patient may end up with a twenty fold increase in aldosterone level partly because
Dialogue: 0,0:27:52.56,0:27:55.04,Default,,0000,0000,0000,,of synthesis and partly because of
Dialogue: 0,0:27:55.04,0:27:57.03,Default,,0000,0000,0000,,"non tearing down"
Dialogue: 0,0:27:57.03,0:27:58.06,Default,,0000,0000,0000,,
Dialogue: 0,0:27:58.06,0:27:59.05,Default,,0000,0000,0000,,by the liver
Dialogue: 0,0:27:59.05,0:28:01.01,Default,,0000,0000,0000,,
Dialogue: 0,0:28:01.01,0:28:02.04,Default,,0000,0000,0000,,One more example, the gut
Dialogue: 0,0:28:02.04,0:28:04.05,Default,,0000,0000,0000,,may suffer in very advanced cardiac
Dialogue: 0,0:28:04.05,0:28:06.52,Default,,0000,0000,0000,,failure, patches of mucosa
Dialogue: 0,0:28:06.52,0:28:09.00,Default,,0000,0000,0000,,in the bowel may undergo
Dialogue: 0,0:28:09.00,0:28:13.01,Default,,0000,0000,0000,,necrosis because they're furthest from the blood supply
Dialogue: 0,0:28:13.01,0:28:17.00,Default,,0000,0000,0000,,and we speak of ischemic colitis, a bit\Nof a misnomer as it is an inflammatory condition,
Dialogue: 0,0:28:17.00,0:28:17.10,Default,,0000,0000,0000,,
Dialogue: 0,0:28:17.10,0:28:18.10,Default,,0000,0000,0000,,but actually that sort of thing
Dialogue: 0,0:28:18.10,0:28:21.05,Default,,0000,0000,0000,,can be a problem.
Dialogue: 0,0:28:21.05,0:28:24.93,Default,,0000,0000,0000,,Other organs and in fact even the\Ncentral nervous system in very advanced failure
Dialogue: 0,0:28:24.93,0:28:26.02,Default,,0000,0000,0000,,we see problems
Dialogue: 0,0:28:26.02,0:28:29.00,Default,,0000,0000,0000,,with CNS function.
Dialogue: 0,0:28:29.00,0:28:32.05,Default,,0000,0000,0000,,Well I turn the baton over
Dialogue: 0,0:28:32.05,0:28:34.26,Default,,0000,0000,0000,,to Dr. Matthews
Dialogue: 0,0:28:34.26,0:28:38.01,Default,,0000,0000,0000,,you just keep some of\Nthese images in mind and she will flesh them out,
Dialogue: 0,0:28:38.01,0:28:38.07,Default,,0000,0000,0000,,
Dialogue: 0,0:28:38.07,0:28:40.08,Default,,0000,0000,0000,,as they say, with the clinical realities
Dialogue: 0,0:28:40.08,0:28:43.03,Default,,0000,0000,0000,,and with some of the
Dialogue: 0,0:28:43.03,0:28:44.08,Default,,0000,0000,0000,,therapeutic strategies
Dialogue: 0,0:28:44.08,9:59:59.99,Default,,0000,0000,0000,,that make sense I hope.