Lecture 3 Physiology of the Heart II

Question 1

What percentage of their volume do the ventricles expel per beat

Answer 1

55-60%

Question 2

What are the two methods of increasing cardiac output

Answer 2

Increasing the heart rate or increasing the stroke volume by increasing the volume of blood expelled by the ventricles in each beat

Question 3

What is the equation for cardiac output

Answer 3

Cardiac output = stroke volume x heart rate

Question 4

What are the units of cardiac output

Answer 4

Litres per minute

Question 5

What is the standard resting stroke volume

Answer 5

70ml

Question 6

What is the resting heart rate

Answer 6

70bpm

Question 7

What is the standard resting cardiac output

Answer 7

4.9L min-1

Question 8

What is the standard blood volume

Answer 8

5L

Question 9

How many times per minute does the entire blood volume circulate

Answer 9

Once per minute

Question 10

To what extent can cardiac output increase during exercise

Answer 10

Cardiac output can increase 7-fold to around 35L min-1

Question 11

What is meant by ejection fraction

Answer 11

The percentage of the ventricles volume ejected with each cardiac contraction

Question 12

What is the rough ejection fraction of patients in heart failure

Answer 12

Around 35%

Question 13

Cardiac output is controlled by heart rate and stroke volume. How can heart rate be regulated

Answer 13

Heart rate is mainly regulated by the autonomic nervous system. The sympathetic nervous system increases heart rate and contractility of the heart whole the parasympathetic nervous system decreases heart rate only. In addition circulating catecholamines such as noradrenaline also act although much slower to increase heart rate

Question 14

How does the action of the two divisions of the autonomic nervous system differ in terms of their effects on stroke volume

Answer 14

The sympathetic nervous system acts on both the SAN and the cardiac myocytes themselves hence increasing the rate of impulse generation and the contractility of the muscle itself. In contrast the parasympathetic nervous system has very little effect on the ventricles themselves and mainly just decreases heart rate

Question 15

How is stroke volume intrinsically regulated

Answer 15

Intrinsic regulation of stroke volume occurs due to changes in contractility of the muscle itself. This is determined by the availability of intracellular Ca2+ oxygen free fatty acids and ATP.

Question 16

How is stroke volume regulated by extrinsic factors

Answer 16

Extrinsic regulation of stroke volume occurs due to changes in the preload or filling pressure and afterload as well as a contribution by the sympathetic nervous system

Question 17

What is meant by preload

Answer 17

The preload is referred to as the filling pressure or the pressure created during diastole when the venous return brings blood back to the heart setting the stretch or tension in the muscle. It is also referred to as LV end diastolic pressure

Question 18

What is meant by afterload

Answer 18

The afterload is the pressure against which the heart needs to contract. This is essentially the resistance of the circulation

Question 19

How can the sympathetic nervous system extrinsically regulate the stroke volume

Answer 19

Due to its positive inotropic effects increasing the force of contraction

Question 20

Describe the role of Ca2+ in the contraction of cardiac muscle

Answer 20

Depolarisation of the membrane of the cardiac myocyte spreads down T-tubules allowing it to get closer to the sarcoplasmic reticulum. During depolarisation there is an activation of voltage-gated L-type Ca2+ channels in the membrane of the cardiac myocyte which causes Ca2+ influx. This results in a rise in intracellular concentrations of Ca2+ specially during the plateau phase (100nM to 1-10μm). This Ca2+ entry from outside the cell leads to activation of the ryanodine receptor in the membrane of the sarcoplasmic reticulum. This in turn causes store calcium release of Ca2+ (CICR) by SR which acts to enhance the increase in intracellular Ca2+ as part of a positive feedback system. The massive increase in intracellular Ca2+ leads to it binding to and displacing the troponin/tropomyosin complex from actin. This allows myosin to contact actin and filament sliding to occur

Question 21

What is the significance of the intercalated discs

Answer 21

The intercalated discs are crosslinkages in the cardiac myocytes that help electrical conduction between cells

Question 22

Define the Frank-Starling law

Answer 22

Changing the preload changes the resting tension and the tension that the heart can generate when it actively contracts

Question 23

What is the relationship between changing the filling pressure/preload and the force of contraction in the heart. How does this relate to stroke volume and cardiac output

Answer 23

Increases in filling pressure (LVEDP/myocardial fibre stretching) increase the force of contraction. This in turn increases stroke volume and cardiac output

Question 24

Draw a diagram of the typical healthy Frank-Starling curve

Answer 24

See completed diagram below

Question 25

What can be said about the gradient of the Frank-Starling curve in healthy patients

Answer 25

It is relatively steep

Question 26

In healthy patients what would be the effect of changes in the preload on the cardiac output

Answer 26

Changes in venous return would have a massive effect on stroke volume

Question 27

Normally venous return is continually fluctuating to maintain cardiac output T or F

Answer 27

F – its remains relatively unchanged as small changes in preload will have a massive effect on cardiac output

Question 28

The main regulation of cardiac output in healthy patients in the Frank-Starling mechanism T or F

Answer 28

F – the sympathetic nervous system takes over

Question 29

In what situation(s) is the heart reliant on the Frank-Starling relationship

Answer 29

Heart transplant patients do not have a nerve supply to the heart so their cardiac output is controlled entirely by circulating catecholamines and the Frank-Starling mechanism

Question 30

What is the effect of denervating the heart what does this tell us about its autonomic nervous system regulation

Answer 30

Denervation of the heart causes an increase in heart rate this implies that the parasympathetic nervous system is dominant and that vagal stimulation is occurring under rest conditions

Question 31

What is the first response of the autonomic nervous system to exercise

Answer 31

The first response to exercise is to decrease vagal activity which acts to increase heart rate

Question 32

What is the effect of changes in the afterload and contractility on the Frank-Starling curve

Answer 32

Increasing the afterload decreases the contractility of the heart and decreases the gradient of the Frank-Starling curve

Question 33

What causes a decrease in cardiac contractility how does this impact stroke volume

Answer 33

Cardiac contractility can be decreased in heart attacks whereby the loss of heart muscle decreases the ability of the heart to contract. This decreases the stroke volume of the patient and decreases the gradient of the Frank-Starling curve

Question 34

Describe the effects of changes in the preload and afterload on the Frank-Starling curve

Answer 34

Changes in the preload changes the point on the curve at which a particular stroke volume is achieved. Meanwhile changes in the afterload change the gradient of the curve itself

Question 35

Increasing preload increases the stroke volume and cardiac output T or F

Answer 35

T

Question 36

Increasing afterload increases the stroke volume and cardiac output T or F

Answer 36

F – it decreases it

Question 37

The effects of sympathetic nervous system stimulation of the heart occur independently of preload and afterload T or F

Answer 37

T

Question 38

What is the effect of sympathetic nervous system stimulation on the Frank-Starling curve

Answer 38

Sympathetic nervous system stimulation of the heart results in an increase in the gradient of the Frank-Starling curve. This means that the same stimulus in the presence of background sympathetic nervous system stimulation will result in a much larger response.

Question 39

Sympathetic nervous system stimulation changes contractility T or F

Answer 39

T

Question 40

Draw a diagram to depict what happens to the Frank-Starling relationship in patients in heart failure relative to healthy individuals

Answer 40

See completed diagram below

Question 41

What is the problem in raising stroke volume and cardiac output in patients in heart failure

Answer 41

Because the gradient of their Frank-Starling curve is so shallow massive increases in preload/venous return will have very little effect on cardiac output

Question 42

As a compensatory mechanism in heart failure patients will often have massively increased venous return what are the problems associated with this

Answer 42

Increased preload/venous return increases the filling pressure of the ventricles. This in turn increases the pressure in the atria and in the connected veins as there aren’t valves to regulate the pressure. In the left side of the heart increases in venous pressure causes pulmonary congestion and pulmonary oedema. In the right side of the heart this causes venous congestion and peripheral oedema.

Question 43

What are the symptoms associated with high preload/LVEDP

Answer 43

Venous and pulmonary oedema

Question 44

What are the symptoms associates with low cardiac output

Answer 44

Fatigue exercise intolerance

Question 45

What is the benefit of diuretics in the treatment of heart failure

Answer 45

Diuretics lower the venous return and bring patients back down the Frank-Starling curve without significantly decreasing cardiac output (due to the fact that the curve is shallow)

Question 46

What do patients with the most severe heart failure show

Answer 46

Low cardiac output and venous/pulmonary congestion

Question 47

What combination of treatments are extremely effective in the treatment of heart failure and how do these act on the Frank-Starling curve

Answer 47

Diuretics shift them down the curve alleviating the symptoms of high end diastolic pressure. Meanwhile ACE inhibits decrease afterload and increase the gradient of the curve alleviating the symptoms of low cardiac output

Question 48

What is the effect of digoxin on the Frank-Starling curve

Answer 48

As digoxin is a positive inotrope it increases the contractility of the heart muscle hence increasing the gradient of the Frank-Starling curve