S2: Heart - Preload and Afterload

Question 1

What is the equation of cardiac output?

Define the terms

Answer 1

CO = HR x SV

Cardiac output (CO) is the amount of blood ejected from the heart per minute

Heart rate (HR) is how often the heart beats per minute

Stroke volume (SV) is how much blood ejected from the heart per beat

Question 2

Compare CO from right side (via pulmonary artery) and left side (via aorta)

Answer 2

They are the same

Question 3

Compare CO at rest and excersize

Answer 3

Cardiac Output changes according to demand

Rest 70 bpm x 70 ml = 5 litres/min

Exercise 180 bpm x 120 ml = 22 litres/min

Question 4

What is the equation for blood pressure?

Answer 4

BP = CO x TPR

Question 5

What is the equation for blood flow?

Answer 5

Blood flow (CO) = BP/TPR

Question 6

What determines blood pressure and blood flow?

Answer 6

Cardiac Output

Question 7

What three things control stroke volume?

Answer 7

1. Preload - stretching the heart muscles at rest (starlings law)
2. Afterload - relationship between pressure, wall stress and radius. It reduces SV and opposes ejection (Laplace’s law)
3. Contractility which is the strength of contraction at given rest loading due to sympathetic nerves and circulating adrenaline increasing. Ca2+ concentration.

Question 8

If the heart was removed from the body, would it still obey Starlings law and Laplace’s law?

Answer 8

Yes

Both Starlings law and La Place’s law are based on intrinsic properties of the heart itself

Question 9

Explain how preload and afterload are related to each other and starlings law and Laplace’s law

How are they balanced for SV?

Answer 9

Starling's based on filling pressure which is linked to the idea of preload. Preload concerns the amount of blood in the ventricles that causes stretching of the heart muscle at rest so the more blood returning to heart from venous system, the more stretch the cardiac myocytes are under.
During relaxation (phase 1 of cardiac cycle) we have EDV which tell us how much stretch the cardiac myocytes are under. The stretch is controlling the energy of contraction and therefore how much we eject.

More volume –> More stretch = More preload –> More ejection

However there is also an opposing force which comes into play when the aortic/pulmonary valves open, this is afterload.
This afterload on the heart is caused by resting blood in the arteries pushing back on the heart, this afterload puts stress on the heart wall and opposes ejection.

In a healthy heart, preload “wins” so we get ejection of blood from the heart, but the important point is that this balance is going on between preload and afterload, governing stroke volume.

Question 10

Does preload and afterload encourage or discourage ejection?

Answer 10

Preload = Stretching heart, encouraging ejection
Afterload = Stressing heart wall, opposing ejection

Question 11

What is energy of contraction?

Answer 11

Energy of contraction is the amount of work required to generate stroke volume.

It depends on starlings law and contractility.

Question 12

What 2 important things does stroke work do in the cardiac cycle?

Why must they be balanced?

Answer 12

1. It increases the chamber pressure so it is greater than the aortic pressure i.e. isovolumetric contraction
2. It causes ejection

So the energy put into both isovolumetric contraction and ejection must be balanced, if too much is put into increasing the pressure so the semilunar valves open, there won’t be enough to be put into ejection to counteract the afterload. Therefore stroke volume would decrease.

Question 13

What is Starlings law of the heart?

Answer 13

The energy of contraction of cardiac muscle is proportional to the muscle fibre length at rest.

Meaning, the greater the fibre length at rest which is stretch (diastole), the greater the energy of contraction of the heart, therefore the greater they will overcome the afterload and stroke volume will be larger in systole (contracting muscle). This is an intrinsic property of the heart muscles so nerves, hormones etc are not involved.

Question 14

What is EDV and ESV? How can you calculate the SV from them?

Answer 14

EDV is end diastolic volume. It is the amount of blood in the ventricles at the end of diastole (before contraction).

ESV is the amount of blood left over in the ventricles at the end of contraction

EDV-ESV = SV (how much ejected per beat)

Question 15

Explain starlings experiment: Effect of CVP on stroke volume

Answer 15

Under normal levels of CVP, SV isn’t that great

When a large intravenous infusion (solution) is added, there is more blood volume going back to the heart.
There is an increase in EDV and ESV also goes up as there was more blood to start with.

Overall, we can see that the difference between the two has increased and this means stroke volume is larger.

Question 16

Describe starlings curve/ventricular function curve

Answer 16

As we can see, in a normal healthy person if we increase CVP we increase stroke volume. Eventually if you increase this pressure enough, the relationship begins to break down and it starts to plateau and if the pressure continues to go up it can actually begin to reduce stroke volume. This is because the heart is stretched to its full capacity so there is excess filling due to overstretched muscle.

During heart failure the curve changes

Question 17

Explain the molecular basis of Starling’s law

Answer 17

Actin is connected to the z band and myosin in the middle

Unstretched fibre:

• actin and myosin fibres overlap
• not much room for myosin to row actin across so limited movement due to mechanical interference between myosin and actin
• leads to less cross bridge formation available for contraction

Stretched fibre:

• less overlapping between the actin and myosin
• less mechanical interference
• much greater area to row actin across
• potential for more cross bridge formation
• in stretched fibre and much greater energy for contraction
• in stretched fibre, there is also increased sensitivity to calcium (works at lower conc)

Question 18

Why does stretching cardiac myocytes lead to greater contraction?

Answer 18

The difference in un-stretched muscle fibres compared to stretched muscle fibres.

Question 19

Roles of starlings law

Answer 19

• Starlings law balances the outputs of the RV and LV
• Starlings law is also responsible for the fall in CO during a drop in blood volume. This is because there is less blood returning to the heart hence less preload and less ejection
• However, we can use Starlings law to restore CO by giving intravenous fluid transfusions which increases blood volume returning to the heart. CO goes up, hence BP goes up.
• Responsible for the fall in CO during orthostasis causing postural hypertension and dizziness
• It also contributes to increased stroke volume during upright exercise, as sympathetic system makes more blood return to the heart, stretching the heart more increasing SV so more is pumped out.

Question 20

Explain how starlings law balances outputs of the RV and LV

Answer 20

If more blood is returning to the heart, the RV will be stretched more first leading to greater energy of contraction so more blood will go to the lungs.

Therefore more blood volume will come back to the heart into the left atria which will push more blood into the ventricles which in turn now filled with more blood will push more blood out to the systemic circulation.

This shows, the increase first seen in the great veins has been transferred to the systemic circulation, so there is transferring of increase/decrease in blood volume.
If this wasn’t done properly it would lead to congestion.

Question 21

Explain how Starlings law is responsible for the fall in CO during orthostasis (standing)

Answer 21

This is because blood goes to the legs when we stand up, so less is returning to the heart (less stretch), so CO is reduced which can lead to less perfusion of the brain, causing someone to faint. The sympathetic system can compensate for this by increasing Co, and increasing BP subsequently.

Question 22

Describe afterload

Answer 22

• Afterload opposes ejection of blood from the heart

Afterload is determined by wall stress directed through the heart which reduces contractility of the heart (low afterload is good)

More energy of contraction is needed to overcome wall stress to produce ejection and heart doesn’t function efficiently

When the semilunar valves open, there is a backpressure produced by blood in the arteries, this pressure produces a wall stress that is directed through the walls. This is the afterload as it opposes contraction.
It is the force within the chamber wall that opposes contraction.
Hence we talk about afterload reducing ejection, thus decreasing stroke volume and cardiac output.

Question 23

What is Laplace’s law?

Answer 23

• Can be good or bad
  The law states how effectively wall tension is converted into pressure within the ventricles.

Laplaces law describes parameters that determine Afterload: Wall Tension (T), Pressure (P), and Radius (r) in a chamber (ventricle)

P= 2T/r
(2 becomes tension can move both ways and chamber has 2 directions of curvature)

Question 24

What is wall tension?

What is it determined by?

Answer 24

Wall tension is a force.

It is determined by wall stress and wall thickness.

Wall tension (T) = Wall stress (S) x Wall thickness (w)

T=SW

Question 25

What is the equation of Laplace’s law with wall tension equation added?

Rearrange this to give the equation for after load (s)

Answer 25

P = 2sw/r

or

S= Pr/2w

Question 26

What increases and decreases afterload using the equation?

Answer 26

S= Pr/2w

Increasing pressure and radius increases afterload

Increasing wall thickness decreases afterload

Question 27

Describe the relationship between radius and wall stress (afterload)

Answer 27

Small radius:
If a chamber has small radius it has large curvature. This causes more wall stress
directed towards the centre of the chamber. Hence there is greater wall tension converted into pressure causing ejection.

Large radius:
A chamber with a larger radius has smaller curvature which causes less wall stress to be directed into centre of the chamber. The stress gets dispersed throughout the wall then less pressure is developed causing less ejection.

Question 28

When ventricles are full at EDV, explain how starlings law and laplace’s law are balanced

Answer 28

When ventricles are full at EDV:
Starlings law would mean there would be more stretch, more increased force of contraction and ejection but La Place’s law would mean there would be less pressure so decreased ejection.

So at rest these two forces are opposing and in a normal healthy heart, Starlings law “wins”.
In a failing heart, the chambers are often dilated, this increase the radius, La Place’s law means this will cause a reduction in ejection. This is because as the radius is larger there is not enough Wall Stress converted into pressure.

Question 29

Importance of Laplace’s law

Answer 29

• It facilitates ejection
• It opposes starlings law at rest
• It contributes to a failing heart

Question 30

How does Laplace’s law facilitate ejection?

Answer 30

Ventricular contraction will be increased if there is decreased chamber radius and increased curvature - Laplace law states that this will reduce afterload in emptying chamber. This is due to there being greater conversion of wall stress (into centre of chamber) into pressure of “emptying” the chamber, this aids expulsion = increased stroke volume

Question 31

How does Laplace’s law oppose starlings law at rest?

Answer 31

Increased preload = increased stretch of chamber = increased chamber radius/curvature. Laplace’s law states that this will increase afterload. This means there will be reduced conversion of wall stress to pressure in the chamber. La Place’s law opposes ejection of blood from a “full” chamber. In an healthy heart, Starling law overcomes Laplaces which maintains ejection.

Question 32

How does Laplace’s law contribute to a failing heart?

Answer 32

In a healthy heart, Starlings law overcomes La Place’s leading to good ejection. In a failing heart, the chambers are often dilated, this increase the radius, La Place’s law means this will cause a reduction in ejection. This is because as the radius is larger there is not enough wall stress converted into pressure

Question 33

Explain how Laplace’s law can be beneficial

Answer 33

Laplace’s law is beneficial will a small radius but bad with large radius

During ejection, we start off with Starlings law encouraging ejecting and La Place’s opposing. But once we start ejecting and blood volume decreases in the heart you begin to get a smaller radius. So now La Place’s law will be converting more of that wall stress into the centre and thus pressure to aid ejection, while Starlings law starts to fade away. So La Place’s law helps during the ejection.

Question 34

Describe the relationship between pressure and wall stress (afterload)

Answer 34

Laplaces law states that increased arterial blood pressure leads to Increased Wall Stress – Increased Afterload – Reduced ejection (decreased SV)

Question 35

What 3 things offset acute rises in blood pressure?

Answer 35

1. Starlings law

Increased stretch leads to increased contraction and increased SV

2. Intrinsic increase in contractility

Anrep response (autoregulation), local positive ionotropes

3. Baroreflex

Decreased sympathetic nervous system, decreased TPR, decreased BP

Question 36

Consequences of a chronic increased arterial blood pressure

Answer 36

• Increased energy expenditure to maintain SV
• Ultimately decreased SV/CO - poor blood flow to end organs
• High blood pressure is bad for the heart

This is an important reason why blood pressure needs to be kept fairly constant during exercise or else CO will decrease when we need it to increase

Question 37

Why is there increased radius and pressure during heart failure (laplace’s law)?

Answer 37

Increased radius:
Volume overload heart failure occurs because the heart can’t contract properly to expel all the blood so the volume remains high in the heart.
This increased volume would naturally cause a larger radius meaning more stress dissipated through the walls and less in the centre causing less pressure and less SV.

Increased pressure:
If arterial pressure increases (e.g. hypertension, aortic stenosis), then there is more back pressure on the heart causing more wall stress through the walls, not the centre. This would also lead to less ejection and less stroke volume.

Question 38

What is hypertrophy?

Answer 38

Same number of cells but more sarcomeres

Question 39

What does the heart do to compensate for heart failure?

What is the problem with this?

Answer 39

The heart increases its wall thickness (w), this is ventricular hypertrophy. This decreases the afterload, because the radius of the chamber is being decreased, hence more wall stress is directed towards the centre (OR same wall stress is now being dissipated over a greater area, so more is directed into the centre – less wall stress per sarcomere). This aids contractility, to overcome afterload and maintain SV as well as CO.

However, in the long term, thicker muscle requires more energy consumption. Hence greater O2 is needed to be used and if you’re unable to supply this increased level of O2, then ultimately there will be a decrease in contractility and heart failure will get worse.

Question 40

Effect of Starlings law (preload) on ventricular pressure-volume loop

Answer 40

• Increased venous return e.g. during exercise, IV fluids
• Increased EDV
• Increased starlings law
• Increased SV for little increase in energy used

Question 41

Effect of afterload on ventricular pressure volume loop

Answer 41

• increase arterial blood pressure
• Greater isovolumetric contraction to get over the threshold and open valve (EDV same)
• Less energy for ejection and decreased SV
• More energy used to eject less blood

Opposite for decrease in arterial blood pressure