Frank-Starling mechanism | Circulatory system physiology | NCLEX-RN | Khan Academy
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Frank-Starling mechanism | Circulatory system physiology | NCLEX-RN | Khan Academy


So a long time ago, there
were two gentlemen, one by the name of
Frank, and the other, his last name was Starling. So Frank and Starling coming
from two different countries. Frank was from Germany, and
Starling was from England. Came up with a set of ideas
that we still use today. And not just use,
but actually are pretty relevant to how we think
about how the heart works. And so these two guys, I just
want to give a little shout out to both of them because
they were leaders in their field 100
plus years ago. And their ideas are
still very, very relevant to how we think
about things today. So what they came
up with– and this is kind of the
content of the video– is related to
pressure and volume. Let’s start there. Let’s talk about both
pressure on this axis and volume on this axis. And you understand that P and
V are “Pressure” and “Volume.” So if you increase pressure
and volume over time– and let’s say the heart
is completely relaxed– you’re going to get a curve
that looks something like this. It’s going to kind
of go up near the end as you start really
packing in the fluid. And we call this the
“end-diastolic”– that’s where the
“ED” comes from– “pressure-volume
relationship.” “EDPVR.” This is kind of what
the curve looks like. And I could take different
points on this curve. I’m just going to kind of
choose some points arbitrarily. Let’s say 3, 4. Let’s choose one up here. 5 points on this curve. And you realize that, as
you go up from point 1 through point 5– let’s say
this is point 1, 2, 3, 4, and 5. And as you go from
point 1 through point 5, your preload is going up. Remember that preload
is related to pressure. And preload is really
a sense for– what is the stress on the walls? And of course, within
the walls, you’ve got these little heart cells. So what’s the stress
on these heart cells? We know that as,
the stress goes up, the heart cells themselves
begin to really stretch out. And so I’m going to
just kind of show that to you in this
little diagram. Let’s say this could be 1. This could be 3. And this could be 5. Right? So this is kind of what’s
happening with heart cells as you go up, up, up in
terms of the preload. They stretch out. So thinking about heart cells
stretching out– and of course, this is before they
contract– what does this mean for contraction? And this is something that Frank
and Starling thought about. And that’s what I want to
kind of jump into next. So just think about these
5 points– 1, 2, 3, 4, 5. And we’re going to
go kind of point by point through them each. So let’s start with point 1. And here in point 1, you’ve
got very little preload. Right? Very, very little preload. And maybe it’ll be useful to
kind of just draw some myosin. So this will be our myosin. And I’ll draw the myosin heads. I’m drawing, let’s say,
about 20 or so on the bottom and on the top. This is our myosin
molecule in purple. And I want you to keep an eye
on how many myosin heads are actually working, almost
as if you’re the taskmaster and you’ve got to make sure
that the myosin heads are all working. Make sure you keep an eye on
exactly how many are doing what we want them to do, which is
contract or pull in the actin. So let me actually just
take a little shortcut here so I don’t have to
keep redrawing this. I’m going to move this down
here, and I’ll do it again. And I’ll move it even lower. So we have our myosin there. Now, around the
myosin– in fact, let me label it
while I still can. This is our myosin. Right? Around our myosin, we
have, of course, actin. I’ll write it bigger just so
you can see it very clearly. We have actin, and actin
is we’ll do in red. But because we have
a very low preload– or almost no preload–
I’m going to show you what that means
for our molecules. You’re going to have
something like this where you have everything
kind of crowded together. And that’s kind
of the core issue I want to point out to you. You have lots of
crowding problems. And of course, the myosin–
on the ends of here– this is our Z-Disk. I’m going to write “Z-Disk.” And you have
another Z-Disk here. What I’m showing you is kind
of a part of the sarcomere. Remember, the sarcomere
is kind of the basic unit of contraction, and it usually
goes from Z-Disk to Z-Disk. So this is just a part
of it because you’d have many, many more
actins and myosins stacked up and below it. But this is just
to kind of give you a sense for what
we’re looking at. Right? And this is, of
course, our actin. The question is– and I
guess I should– sorry. Before the question,
let me throw in titin. This little green
molecule is titin. So the question is– how
would contraction occur? If you were to look
at this scenario and you’re kind of
an inspector, you’re just kind of assessing
for problems, would you expect that there
would be any problems? Would you expect
any problems here? And afterwards, I also want
you to think about force. What kind of force do
you expect to get out of this sort of arrangement? A lot of force,
or a little force? What do you think? Well, immediately, I
can see some problems. Right? I mean, you know
that the whole goal is to pull the Z-Disks
in closer to each other. That’s the whole point. The myosin is going to
yank on the actin ropes– you could think of it as a
rope– and yank the Z-Disks in. And if there’s really
almost no space here– see this right here,
there’s almost no space here. It’s all crowded. And this myosin is basically
almost touching the Z-Disk. Right? This guy right here is almost
touching the Z-Disk already. So close. Well, then, what do I
really expect to happen? There’s going to be almost no
force because the problem– and I’m going to write
it very clearly– is that the myosin is crowded. Meaning it’s right up
against the Z-Disk right from the beginning. And that’s a problem. Right? Because that means–
what can you really hope to achieve if you’ve already
gotten the myosin already against the Z-Disk? There’s really no space for
you to yank the actin in to bring the Z-Disk in closer. There’s no space there. It’s crowded. So I would say that’s
the biggest problem. And secondly, there’s
actually another problem here. And that’s around actin. Right? Because the actin has polarity,
and this is an important issue. These two actin molecules
that I’ve drawn arrows around are fundamentally
different because there’s a directionality to the way
those proteins are laid out. And we call that “polarity.” So actin has polarity. And what that means is that
then myosin can’t simply reach up and grab
the nearest actin. It has to grab
the correct actin. So for example, these
four right here– I’m going to draw a
little circle around them in yellow– these four really
want this actin on this side. And these four down
here, they really want the actin on this side. But both of those
groups of myosins are blocked by the other actin. So for example,
these four at the top are blocked by this
segment right here, and these bottom four
are being blocked by– I could actually change it. I could say these. Or this segment right there. So there’s actually some
actin-blocking going on. So I call that “actin
overlap” or “actin blocking.” Overlap. Let’s call it
“overlap” because I think that makes a
little bit more sense. So you’ve got some
actin overlap, but that’s kind of
a secondary point here because the main issue
is that myosin, frankly, is just crowded. So in terms of force,
would I expect any? I would say no. I wouldn’t really expect
any because there’s really nothing for the myosin
to really get done. There’s just no space. Now, let’s say we
stretch things out. This is scenario two. So things are a little
bit stretched out now. You’re looking at
our graph up above. Now, things are stretched
out– meaning that here, instead of the way it was drawn
before– let me, actually, kind of correct it and
draw it like this. You still have to consider
the polarity issue, but things are a little
bit more spaced out now. Right? You’ve got something like that. And going on the
other side, you’ve got something like,
let’s say, that. So look at this, and now
tell me what you think. You’ve got a couple of myosins
that are still blocked. Right? You still have a little
bit of blockage here. These ones are blocked,
and these ones are blocked. The main reason, again,
for the blockage is that there’s a polarity
issue here and here, meaning that those myosins
cannot simply bind whatever is closer. And they’re really not able
to get over to the side where the actin is,
where they need to bind. So those 4 out of
20 myosin heads are not going to
be able to work. But the rest of it is
actually looking a lot better than before. Right? We have some improvement. So here, you’ve got some
actin overlap issues. So in terms of
problems, I would say actin overlap is still
kind of an issue. In terms of force,
I wouldn’t say no anymore because now, at least,
the “myosin is crowded” problem has gone away. It’s not as crowded, and
there is room to move. So I would say I would
expect some force. So when there’s contraction, I
would expect some force here. So things are definitely
getting better. Right? The stretching is
helping things out because it’s basically moving
the actin so that it’s not congesting the area. And the myosin is similarly
moving away from the Z-Disk. Let me make a few more of these. I’ll make one more,
and we’ll keep going. So now, let’s go to
the third picture. Well, here, let’s keep it up. Let’s see what we can do if
we keep the stretch going. Now, I can say, well, gosh. I’ve got lots and lots of
space for the myosin to work. The very first point
we talked about, that’s completely non-issue
now because look at the titin. Watch as I draw the titin. Look at this. All those coils, all that
space for the myosin to move. The Z-Disks here–
remember, these are our Z-Disks–
have a lot of room. If we really want to
tank them in, we could. We could really yank them in
because the myosin is not right up against them anymore. And we’ve actually solved
the other problem– the actin overlap problem. Because there is no
overlap at this point. Now, you’ve really
got nice spacing, and the actin isn’t
blocking the myosin from binding to
another actin molecule. So in terms of problems, I
would say no problems here. And in terms of force, I
would say lots of force. Because really, I’ve got 20
myosin heads all ready to go. Right? They’re all pumped up and
ready to do their thing– to bind the actin and
to yank the Z-Disks in. So that was scenario three. Scenario four is going to
be really, really similar– a lot of the same
kinds of issues– because now I’m just kind of
pulling it a little bit further apart. And again, all those myosins
are going to be able to work. They’re going to have
no problems of crowding. I’ve, in fact, even made
more space out by the titin so the Z-Disks are
even further apart. So certainly, all 20 myosins
are going to be working, and I would expect
no problems again. Really, no problems here either. So in scenario three and four,
things are looking really good. And so of course, I would
expect lots of force. I would expect lots of
force on this one as well. It seems like, well, the
more we stretch things out, the better things get. So let’s just keep stretching. Let’s just see how it goes. And let me just really stretch
things out to the point where it looks almost like that. So you’re thinking,
well, wait a second. Wait a second, Rishi.I got a
little too carried away here. And now, how the heck is
this even going to stay put? Well, remember the
titin is definitely going to keep my myosin
attached to the Z-Disk. So that’s good. They won’t just float away. It’ll stay attached. But in terms of
actually doing work, would I expect this
to be a good setup? Well, I’ve really
stretched things out. So there’s no crowding issue. That’s true. But I have a new issue. Right? Really, I have
actin out of reach. If actin is out of reach of my
myosin, then how the heck am I supposed to get work done? If they can’t even attach
themselves to the actin, then would I expect any force? I would say no. I would expect really no force
because it’s just too stretched out. This is the overall
look and feel of what happens as
the preload goes up. As you get more and
more stretched out, things seem to be
getting better initially. But then, they get a little
bit too stretched out at the very end. In the optimal
situation– this is pretty important– the
optimal situation is really– out of these 5,
these 5 scenarios– would basically be
one of these two. Situation three and four
are looking really good, where we got lots of
force, no crowding issues, no “actin out of reach” issues,
no myosin-actin-overlap issues. Nothing. Right? Three and four are really
our golden situations. Just keep this in mind when
you look a preload curve. It really does start
affecting how well the myosin and actin are able
to create force. And this idea of stretch
relating to force is something that Frank and
Starling thought of a long time ago.

About James Carlton

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6 thoughts on “Frank-Starling mechanism | Circulatory system physiology | NCLEX-RN | Khan Academy

  1. This is the basis of heart failure, I learned this back in pathophysiology and then forgot. Came back to remember this stuff and holy fuck it clears things up, thanks.

  2. Overall poor example of Frank Starling, should use a Frank Starling curve to explain this, not a pressure volume graph. Try looking at a book on Cardiac Physiology

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