Full transcript
0:05Hello everybody and welcome to our
0:06module on cardiac physiology. On the
0:09screen is an echo cardiogram of the left
0:11ventricle of a patient's heart. You can
0:13see there are QRS complexes rolling
0:16along the bottom of the screen. And each
0:17time there's a QRS complex, the walls of
0:19the left ventricle thicken and move
0:21towards the middle. When this happens,
0:23it shrinks the volume inside the left
0:25ventricle and pushes blood out into the
0:27aorta. So in this module, we're going to
0:29talk about the changes in volume and the
0:30other physiological changes that occur
0:32as the heart goes through the cardiac
0:34cycle and moves blood out of the left
0:36ventricle. As we saw in the moving image
0:37on the last slide, the volume in the
0:39left ventricle is changing during the
0:41cardiac cycle. However, there are two
0:43important volumes when it comes to
0:44understanding cardiac physiology. The
0:46first one is the end diastolic volume or
0:49the EDV. This is the volume at the end
0:51of diastily. That's how it gets its
0:53name. This is the point in the cardiac
0:54cycle where filling of the left
0:56ventricle has completed. This is the
0:58largest volume of blood the left
0:59ventricle will hold. This is also the
1:01point where contraction is about to
1:03begin. The other important volume is the
1:05end systolic volume or the ESV. This is
1:08the volume at the end of cy. That's
1:09where it gets its name. This is the
1:11point in the cardiac cycle where
1:12emptying has been completed. This is the
1:15smallest volume that the left ventricle
1:16will hold. This is also the point in the
1:18cardiac cycle where relaxation is
1:20beginning. So now that we understand
1:22that we can understand some other
1:23important terms as related to cardiac
1:26physiology. And the first one is the
1:27stroke volume. This is the difference
1:29between the end diastolic volume and the
1:31endsctolic volume. It's the amount of
1:32blood pushed out of the left ventricle
1:34with each heartbeat. It's the difference
1:36between the largest volume the left
1:37ventricle holds and the smallest volume
1:39it holds. Another important term is the
1:41ejection fraction, sometimes called the
1:43EF. This is the stroke volume divided by
1:45the end diastolic volume. In other
1:47words, it is the percentage of blood
1:49pushed out of the left ventricle with
1:51each heartbeat. And a normal ejection
1:52fraction is about 55 to 60%. Our hearts
1:56don't normally eject 100% of the blood
1:58present in the left ventricle with each
2:00heartbeat. They only eject about 60%
2:01under normal circumstances. And then
2:04finally, the cardiac output is the
2:05stroke volume times the heart rate. This
2:07is the volume of blood pushed out with
2:09each heartbeat times the number of
2:11heartbeats per minute. When you multiply
2:12these two terms together, you get a
2:14number called the cardiac output, which
2:16has units of volume per time. For
2:18example, liters per minute is a common
2:20way to report the cardiac output.
2:22Another important term is the Venus
2:24return. This is the amount of blood
2:26returned to the left ventricle via the
2:27Venus system. It should be equal to the
2:29cardiac output. The amount of blood that
2:31is returned to the heart from the body
2:33should be equal to the amount that goes
2:34out. And then another important term is
2:36the total peripheral resistance. This is
2:38the resistance to blood flow out of the
2:40left ventricle that comes from
2:42peripheral structures. For example, the
2:44organs of the body and the arteries of
2:45the body. Importantly, vasoc
2:47constriction of peripheral arterials
2:49leads to a rise in the total peripheral
2:51resistance. When those vessels
2:52constrict, it's harder to push blood
2:54through them and there's greater
2:55resistance to flow. And when the
2:57peripheral arterials vasoddilate, this
2:59leads to a fall in total peripheral
3:01resistance. There are some blood
3:03pressure terms that are important for
3:05understanding cardiac physiology. You
3:06may know that we all have a systolic and
3:08a diastolic blood pressure. And a normal
3:10systolic blood pressure is about 120
3:12millimeters of mercury. A normal
3:13diastolic blood pressure is about 80
3:15millimeters of mercury. You should also
3:17know that the systolic pressure is
3:19largely determined by the stroke volume
3:21and the diastolic blood pressure is
3:22largely determined by the total
3:24peripheral resistance. To understand
3:25this, let's imagine that we're tracking
3:27the blood pressure as the left ventricle
3:28begins to contract and push blood out
3:30into the arterial system. What we'll see
3:33is that the blood pressure will rise and
3:35the height of that rise will be
3:36determined by the stroke volume. In
3:38other words, when the left ventricle
3:39stops contracting and stops pushing
3:41blood into the arterial system, the
3:43blood pressure will peak and that peak
3:45will be determined by how much blood is
3:46pushed out by the left ventricle. The
3:48blood pressure will then begin to fall
3:50steadily and the depth to which it falls
3:52will be determined by the peripheral
3:54resistance. If peripheral vessels are
3:56very vasoddilated, then the pressure
3:57will fall greatly so that there'll be a
3:59very low diastolic blood pressure. On
4:01the other hand, if the peripheral
4:02vessels are relatively vasoc
4:04constricted, then it will only fall to a
4:05lesser degree and thus we will have a
4:07higher diastolic blood pressure. So in
4:09this manner, the peak of the blood
4:11pressure meaning the systolic blood
4:12pressure is largely determined by the
4:13stroke volume and the depth or the nater
4:16of the blood pressure is largely
4:17determined by the total peripheral
4:19resistance. One other important blood
4:21pressure term is the pulse pressure.
4:22This is the difference between the
4:23systolic and diastolic pressure. So for
4:25example, for a patient with a normal
4:27blood pressure of 120 over 80, the pulse
4:29pressure would be 40. And this is also
4:31proportional to the stroke volume.
4:33Remember what I told you before, the
4:34height of the blood pressure, meaning
4:36the maximum value or the systolic
4:38pressure is determined by the stroke
4:39volume. This means that the difference
4:41between these two numbers or the pulse
4:43pressure is also determined by the
4:44stroke volume. Another important blood
4:46pressure term is the mean arterial
4:48pressure or MAP. This is equal to the
4:50diastolic pressure plus 1/3 of the
4:52difference between the systolic and
4:54diastolic pressures, which you may
4:55recall is called the pulse pressure. The
4:57reason it's not halfway between the two
4:59pressures is because our blood pressure
5:01spends more of its time in the diastolic
5:03range. If you chart the blood pressure,
5:05you will find that it briefly goes up to
5:06the systolic peak, then falls down to
5:08the diastolic range and stays down there
5:10for a much longer period of time before
5:12it climbs again. This means that in
5:14order to calculate the mean, you don't
5:16simply take the midway point between the
5:18bottom and the top. You take onethird of
5:20the way from the bottom coming closer
5:22down to the bottom number because you
5:23spend more time down in this range here
5:25at the bottom. So for example, if a
5:27person had a normal blood pressure of
5:29120 over 80, the mean arterial pressure
5:30would be 80 plus 1/3 of the difference
5:33between those two, which is 40. And that
5:34would work out to 93.3.
5:37Of the cardiac physiology variables
5:38we've been discussing, one of the most
5:40important is the cardiac output. That's
5:42because the cardiac output must rise to
5:44meet the demands placed upon the heart
5:46by the body. And in many disease states,
5:48the disease is caused because the
5:50cardiac output is insufficient. Also
5:52remember that the more cardiac output
5:54the heart produces, the more work it
5:55must do and the more oxygen that is
5:57required. The cardiac output is equal to
5:59the heart rate times the stroke volume.
6:01So when the heart rate goes up, there
6:02are more beats per minute and this is
6:04more work the heart must do. In
6:06addition, when the stroke volume goes
6:07up, there's more volume per beat that
6:09the heart must pump and that also means
6:11more work that the heart must do. These
6:12are very important principles of cardiac
6:14physiology for you to understand. So the
6:17four classic determinants of the cardiac
6:19output are the preload, the afterload,
6:21the contractility, and the heart rate.
6:23And we'll talk about these one at a time
6:25in the next few slides. But I just want
6:26to make a general point here that
6:28changes in these four factors affect the
6:30cardiac output. And that means that
6:32these four factors also affect how much
6:34work the heart has to perform. The
6:36preload is the amount of blood loaded
6:38into the left ventricle prior to each
6:40contraction. That's how it gets its
6:42name, the preload. If you've watched the
6:44video on the stling curve, you're aware
6:46that the more preload that goes into the
6:47left ventricle, the harder it will
6:49contract. And for that reason, when
6:51there is more preload, there's more
6:52cardiac output. In addition, when
6:54there's more preload, there's more work
6:55the heart must do and more oxygen that
6:57is required. And because of the stling
6:59mechanism, preload is sometimes referred
7:01to in textbooks as the amount of stretch
7:03on the fibers prior to contraction. Some
7:05books say length instead of stretch. But
7:06all these are ways of referring to the
7:08preload and the fact that the sterling
7:10mechanism dictates that the more the
7:12left ventricle is loaded and the fibers
7:14are stretched, the more vigorously the
7:16left ventricle will contract. And if you
7:18find the concept of preload confusing, a
7:20way I've always explained it to students
7:21is to think of a room full of people and
7:24the left ventricle's job is to push all
7:26those people out into the hallway
7:27through a small door. The preload is the
7:29amount of people put into the room. And
7:31you can imagine that if there are more
7:33people in the room, then there's more
7:34work that must be done in order to shove
7:36them all through the door and into the
7:37hallway outside. So if preload is the
7:40amount of blood preloaded into the left
7:42ventricle to be pumped, how could you
7:44increase the preload to the left
7:46ventricle? Well, the easiest way is to
7:47add volume to the body. Patients who
7:49receive a blood transfusion or
7:51introvenous fluids will have increased
7:53preloads. These two interventions
7:55deliver more fluid to the venus system
7:57of the body which goes to the left
7:59ventricle. This preloads the left
8:01ventricle with more fluid that must be
8:02pumped and thus they increase the
8:03preload. This means that both of these
8:05things will raise the cardiac output.
8:07They will also raise the amount of work
8:08that the heart must perform. Another way
8:11that's not so obvious is to slow the
8:13heart rate. When you slow the heart
8:14rate, there's more time for filling of
8:16the left ventricle. Thus, it fills with
8:18more volume and therefore there is more
8:19preload. And then a final way which is
8:21very important physiologically is to
8:23constrict the veins. The veins are like
8:25large storage basins for fluid inside
8:28the body. They contain a significant
8:30amount of fluid that can be pushed into
8:31the left ventricle if needed. So when
8:34the sympathetic nervous system is
8:35stimulated, alpha 1 receptors in the
8:37veins will react and constrict and they
8:39will push lots of blood into the left
8:42ventricle. This is very important for
8:43the response to blood loss. Venus
8:45constriction increases the amount of
8:47volume available to the heart and helps
8:48to maintain the cardiac output in the
8:50setting of blood loss. To decrease the
8:52preload, you do the opposite of the
8:54three mechanisms I just discussed. You
8:56can remove volume. Patients who are
8:58bleeding or dehydrated have decreased
8:59preload on the left ventricle. You can
9:02raise the heart rate. This allows less
9:03time for filling. The opposite mechanism
9:05we talked about before. In addition, you
9:07can pull blood in the veins. And this is
9:09the mechanism of action of drugs called
9:11nitrates which are sometimes used in
9:13heart failure and in anga. They dilate
9:15the veins and they pull blood in the
9:17venus system. This pulls blood away from
9:19the heart. This lowers the preload.
9:21There's less work for the heart to
9:22perform and for this reason it can
9:23relieve anga. A couple of important
9:26terms regarding preload. Preload is
9:28often not called preload. It's usually
9:29referred to by one of the two terms I've
9:31shown on the screen here. The first one
9:33is the LVEDv. That's the left
9:35ventricular end diastolic volume. This
9:38is the volume I talked about at the
9:39beginning of this module. It's the
9:40volume of blood in the left ventricle
9:42when it's completed its filling phase.
9:44It's the largest volume of blood that
9:46the left ventricle will hold during the
9:47cardiac cycle. That is an indication of
9:50how much the left ventricle has been
9:52preloaded and thus the LVEDv is usually
9:54used to represent the preload. Now in
9:57clinical practice, it's very hard to
9:58measure the LVED. However, it's much
10:00easier to measure the pressure at the
10:03end of diastilly, the left ventricle or
10:04end diastolic pressure. So instead of
10:07using the volume, we often use the
10:08pressure clinically because it's simply
10:10an easier number to obtain. This is the
10:12pressure in the left ventricle when
10:13filling is completed. This is also a
10:15measurement of the preload on the left
10:17ventricle. The afterload are the forces
10:20resisting flow out of the left
10:21ventricle. Remember that the heart must
10:23squeeze in order to raise the pressure
10:24in the left ventricle. It needs to raise
10:26the pressure enough to pop open the
10:28aortic valve so that blood can be pushed
10:30into the aorta. This is harder to do if
10:32for example the blood pressure is high.
10:34that blood pressure is one of the
10:35determinants of afterload. This is also
10:37harder to do if the aortic valve is
10:39stiff. Aortic stenosis is a classic
10:41condition where the afterload increases.
10:43There are also some rare forms of high
10:45afterload such as when things are in the
10:47way of blood moving out of the left
10:49ventricle. This can occur in
10:50hypertrophic cardiopathy. It can also
10:52occur in rare conditions like when
10:54patients have a subaortic membrane
10:55obstructing the outflow of blood. But
10:57all of these things raise the amount of
10:59work that the heart must do in order to
11:01move blood out of the left ventricle.
11:03And just like with preload, an easy
11:05analogy to understand afterload is to
11:07think of a bunch of people in a room and
11:09it's the left ventricle's job to push
11:10them through a doorway into the hallway
11:12outside. The afterload is high if there
11:15are already a lot of people in the
11:17hallway outside. It's obviously going to
11:18be harder to move those people out of
11:19the room and into the hallway. That's
11:21what happens when your blood pressure is
11:22high. There's already a lot of high
11:24pressure and molecules outside of the
11:26heart and therefore it's harder to move
11:27blood out of the way. It's also harder
11:29to move those people out of the room and
11:30into the hallway if the door is stiff
11:32and won't open. And that's what happens
11:34in aortic stenosis. So these are ways
11:36you can think of the concept of
11:37afterload. So just like we did with
11:39preload, let's talk about ways we could
11:42increase or decrease the afterload. So
11:44one of the ways to increase the
11:46afterload is to raise the mean blood
11:48pressure. The mean blood pressure is one
11:50major determinant of the afterload of
11:52the left ventricle. Another way to
11:53increase the afterload is to obstruct
11:55the outflow of the left ventricle in
11:57some manner. This is what happens when
11:58patients have aortic stenosis or
12:00hypertrophic cardiopathy. To decrease
12:02the afterload, we could do the opposite
12:04of the two things I mentioned on the
12:05last slide. We could lower the mean
12:07blood pressure. We could treat the
12:08aortic valve disease or the hypertrophic
12:10cardiopathy. And the principle here is
12:12that more afterload means more work the
12:14heart must do and therefore more oxygen
12:16that is required. Now let's talk about
12:18the third determinant of cardiac output
12:20and that is the contractility. This is
12:22how hard the heart muscle squeezes. And
12:24the ejection fraction is one potential
12:26measurement of contractility. When the
12:28ejection fraction goes up, it means that
12:30the left ventricle is contracting more
12:32vigorously and pushing more blood out of
12:34the left ventricle with each heartbeat.
12:36And the major regulator of contractility
12:38is the sympathetic nervous system. This
12:40is the major regulator under physiologic
12:42conditions of both contractility and
12:44also heart rate which we'll talk about
12:45in a minute. The main physiologic
12:47mechanism by which contractility is
12:49increased is via sympathetic nervous
12:51system activity. There are two
12:53mechanisms by which the sympathetic
12:55nervous system can increase
12:56contractility. First of all, the
12:58sympathetic nervous system directly
12:59intervates the heart. In addition, the
13:01sympathetic nervous system can stimulate
13:03the release of catakolamines from the
13:05adrenal gland. Those can circulate and
13:07reach the heart. Those include
13:08substances like epinephrine and
13:09norepinephrine. When either of these
13:12mechanisms activates the heart, there's
13:14increased calcium release from the
13:15cycloplasmic reticulum and this will
13:17increase the contractility. So some
13:19classic triggers are stress, also
13:21exercise, which we'll talk about later,
13:23anything that increases sympathetic
13:24nervous system activity. A
13:27non-physiologic way by which
13:28contractility can be increased is via
13:30the use of sympathomimedic drugs. These
13:33are drugs like dopamine, dobutamine,
13:35epinephrine, and norepinephrine. They
13:37all stimulate sympathetic nervous system
13:39receptors in the heart and they exert
13:41the same effects that the sympathetic
13:42nervous system normally does under
13:44physiologic conditions. And then finally
13:46the drug deoxin which I talk about in
13:48some of the other cardiology modules
13:50inhibits the sodium potassium ATPA's
13:52pump. This leads to an increased calcium
13:54level inside of myioytes. And this is
13:56another non-physiologic way to increase
13:58contractility. The main way that
14:00contractility is decreased is by dialing
14:03back the sympathetic nervous system.
14:04This can occur naturally when patients
14:06enter states where there's less
14:08sympathetic activity. It can also occur
14:10via the use of drugs. So the main
14:12mechanism of sympathetic nervous system
14:14blocking drugs like beta blockers on the
14:15heart is to decrease contractility and
14:18also heart rate which we'll talk about
14:19in a minute. Some calcium channel
14:21blockers especially veramil and
14:23deltayazm also affect contractility.
14:25They lead to less calcium being pulled
14:28into myasytes and therefore there's less
14:29calcium available for muscle contraction
14:31and decreased contractility. And then
14:34finally, heart failure, especially
14:35systolic heart failure, is a disease of
14:37myioytes that results in decreased
14:39contractility. That's the defining
14:41characteristic of the disease. Our
14:43fourth determinant of cardiac output and
14:45the work of the heart is the heart rate.
14:47When the heart rate goes up, this
14:48increases the cardiac output under
14:50physiologic conditions. And the main
14:52regulators of heart rate, the factors
14:54that cause it to increase or decrease
14:56are the same ones that affect
14:57contractility. In general, heart rate
14:59and contractility go together. They are
15:01both mainly regulated by the sympathetic
15:03nervous system and they are both also
15:05affected by sympathomimetic drugs and
15:07blocked by drugs like beta blockers.
15:10There is a confusing concept about heart
15:12rate and stroke volume that's shown in
15:14many cardiac physiology textbooks and
15:16I'll explain this to you in the next few
15:17slides in a way that hopefully makes
15:18sense. So in laboratory settings when
15:21you insert pacemakers into the hearts of
15:23animals like dogs and you artificially
15:25increase the heart rate you see a fall
15:27in stroke volume. This is because
15:29there's less time for filling of the
15:30left ventricle. So the relationship
15:32between heart rate and stroke volume
15:34experimentally is like what I've shown
15:35on the screen. Now this is very
15:37counterintuitive. Most of us think of
15:39our output of our heart going up when
15:41our heart rate rises. And this slide
15:43indicates the opposite. But keep in mind
15:45this is under artificial settings in the
15:47laboratory when you're increasing the
15:49heart rate without also raising the
15:51contractility. Even in artificial
15:53settings like the laboratory where
15:55you're pacing the heart of a dog, an
15:57increase in heart rate over physiologic
15:59ranges of heart rates still leads to a
16:01rise in cardiac output. That's because
16:03even though the stroke volume falls when
16:05the heart rate goes up, like I showed
16:06you on the last slide, the heart rate
16:08rises to a greater degree. And remember,
16:10cardiac output is equal to the product
16:12of stroke volume times heart rate. Thus,
16:13if you have a small drop in stroke
16:15volume but a greater rise in heart rate,
16:17the net effect will be to increase
16:19cardiac output. So thus even in the
16:21laboratory when you're studying animals
16:22and you're pacing their heart as you
16:24increase the heart rate you still see a
16:26rise in cardiac output even though the
16:28stroke volume is going down as you raise
16:30the heart rate. And that's a confusing
16:31concept to make sure you understand
16:33that. All of those relationships I just
16:35showed you however are artificial
16:37because under physiologic circumstances
16:39the sympathetic nervous system controls
16:40heart rate and contractility and it
16:43never raises the heart rate alone
16:44without also raising the contractility.
16:47What this means is when the sympathetic
16:49nervous system raises the heart rate,
16:51the stroke volume goes up. Even though
16:53there's less time for filling, there's
16:54more contractility such that overall
16:57there is a rise in the stroke volume
16:58under physiologic conditions when the
17:00sympathetic nervous system raises the
17:02heart rate. The one clinical situation
17:04where a rise in heart rate can lead to a
17:06fall in cardiac output is under
17:08pathologic conditions in the setting of
17:09some cardiac arrhythmias. There are some
17:12cardiac arhythmias where the heart rate
17:13can get very very high, sometimes as
17:15high as 300 beats per minute. In this
17:17setting, there isn't enough time for the
17:19left ventricle to fill and thus the
17:20stroke volume falls and the cardiac
17:22output falls. In other words, at these
17:24very high heart rates, even though the
17:25heart rate is increased, the stroke
17:27volume has dropped dramatically. Thus,
17:29the product of stroke volume times heart
17:31rate begins to fall. That means the
17:33cardiac output gets low. What this means
17:35is that some patients with cardiac
17:37arhythmias can develop hypotension and
17:39shock. And this usually happens when the
17:40arrhythmia results in a very rapid heart
17:42rate. What this means is the true
17:45relationship between cardiac output and
17:46heart rate is like what I've shown on
17:48the screen here. Under the physiologic
17:50range of heart rates when the
17:51sympathetic nervous system drives an
17:53increase in the heart rate, there is an
17:55increase in cardiac output. This is
17:57because the sympathetic nervous system
17:58is increasing contractility in addition
18:00to heart rate and thus the cardiac
18:02output is going up. However, if the
18:04heart rate gets very very high, for
18:06example, in the setting of arrhythmia,
18:08you can reach a point where the cardiac
18:10output begins to fall and that's because
18:12of the dramatic drop in stroke volume
18:14seen when the heart rate gets very very
18:15high. So to summarize, the work of the
18:18heart is determined by four key
18:19components. The first is the preload
18:21which we often estimate by the left
18:23ventricular endtolic volume or pressure.
18:25The second is the afterload which is
18:27often estimated by the mean arterial
18:29blood pressure. The third variable is
18:31the contractility which is often
18:33estimated by the ejection fraction. And
18:34the fourth is the heart rate. And this
18:36will be important when we talk about
18:38disease states because hearts that are
18:39starved for oxygen need to have these
18:42factors modified so that there's reduced
18:44oxygen demand. In addition, hearts that
18:46are generating a low cardiac output need
18:48to have these factors modified so that
18:50they increase the work of the heart and
18:52increase the cardiac output. And that
18:54concludes our video on cardiac
18:56physiology.