Regulation of Cardiac Output (Flipped)

Question 1

What is the equation for cardiac output?

Answer 1

Cardiac output = heart rate * stroke volume.

or

Cardiac output = heart rate * (EDV - ESV).

Question 2

List the average end diastolic and end systolic volumes.

Answer 2

• End diastolic volume: 120ml.

- End systolic volume: 50ml.

Question 3

What must happen in order to allow myosin heads to bind to the myosin binding sites on actin?

Answer 3

Troponin C must undergo a conformational change to expose the binding site.

Question 4

Through which channels is Ca2+ released before entering a myocyte’s t tubules?

Answer 4

L type channels

Question 5

What is the effect of Ca2+ influx into a myocyte?

What is this effect known as?

Answer 5

• Ca2+ stimulates further Ca2+ release from the sarcoplasmic reticulum via ryanodine receptors.
• Known as calcium-induced calcium release.

Question 6

What are ryanodine receptors?

Answer 6

The calcium release channels in the sarcoplasmic reticulum.

Question 7

What is the effect of Ca2+ released from the sarcoplasmic reticulum on the myocyte?

Answer 7

• Calcium binds to troponin C.
• This causes troponin C to undergo a conformational change.
• This exposes the myosin binding site on actin.

Question 8

How does calcium affect the force of a muscle contraction?

Answer 8

• Greater calcium release results in more exposed myosin binding sites on actin.
• This results in the formation of more crossbridges between actin and myosin.

Question 9

List 2 ways by which the force of muscle contraction can be increased by altering the activity of calcium.

Answer 9

1 - By increasing intracellular concentration of Ca2+.

2 - By increasing the Ca2+ sensitivity of the contractile apparatus.

Question 10

What happens when Ca2+ is pumped back into the sarcoplasmic reticulum from the contractile apparatus?

Answer 10

Muscle relaxation occurs.

Question 11

Via which pump is Ca2+ returned to the sarcoplasm from the contractile apparatus?

Answer 11

Sarco-endoplasmic reticulum calcium ATPase (SERCA).

Question 12

What is the function of phospho-lamban?

Answer 12

To regulate SERCA.

Question 13

What is Starling’s law?

Why is this true physiologically?

Answer 13

• When sarcomere length increases, force of contraction also increases.
• This is because more crossbridges are formed between actin and myosin in longer sarcomeres.

Question 14

Why does increasing end diastolic volume result in a greater stroke volume?

By what proportion does stroke volume change with respect to end diastolic volume?

Answer 14

• Due to the property of the cardiac muscle that causes contractile force to increase when ventricular muscle is stretched.
• Stroke volume increases by the same amount as end diastolic volume; ESV does not change as a result of EDV change (the reserve / ESV is regulated separately).

Question 15

List 2 factors that affect end diastolic volume.

Answer 15

1 - Venous return.

2 - Venous pressure.

Question 16

What is the risk associated with a mismatch in right and left cardiac output?

Answer 16

Blood would accumulate in and congest the pulmonary circulation.

Question 17

List 7 factors that affect venous return (and therefore preload) to the right ventricle.

Answer 17

1 - Blood volume.

2 - Skeletal muscle pump.

3 - Respiratory pump.

4 - Venous tone.

5 - Gravity.

6 - Atrial contraction.

7 - Heart rate (EDV decreases above 180bpm as diastole becomes short enough).

Question 18

What proportion of blood is held in systemic veins?

Answer 18

60-70%.

Question 19

Explain how the skeletal muscle pump helps pump venous blood to the heart.

Answer 19

• At each end of a vein surrounded by skeletal muscle, there is a distal and proximal valve.
• When the skeletal muscle contracts and compresses the vein, the distal valve closes (preventing backflow), and the proximal valve opens (forcing venous blood towards the heart).
• When the skeletal muscle relaxes, the proximal valve closes and the distal valve opens, allowing blood to enter the vein.

Question 20

Explain how the respiratory pump helps pump venous blood to the heart.

Answer 20

• During inhalation, the diaphragm flattens and presses against the abdomen.
• This decreases pressure in the thorax and increases pressure in the abdomen.
• This pressure gradient moves venous blood from the abdomen back to the thorax, and into the heart.

Question 21

What effect will an increase in sympathetic activity have on the veins?

Answer 21

Venoconstriction.

Question 22

How does compliance change with venoconstriction?

What is the equation for compliance?

Answer 22

• It decreases.

- Compliance = volume / pressure.

Question 23

What is central venous pressure?

Answer 23

The pressure in the thoracic vena cava.

Question 24

Define pre-load.

Answer 24

Any factor which influences the stretch of cardiac muscle at diastole.

Question 25

What is the mechanism by which the sympathetic nervous system changes heart contractility / inotropy?

How will this affect EDV, ESV and stroke volume?

Answer 25

• The sympathetic fibres innervating the heart release noradrenaline, and sympathetic activity also leads to an increase in circulating adrenaline and noradrenaline.
• Noradrenaline binds to and stimulates beta 1 GPCRs on ventricular myocytes, triggering the PKA and PKC pathways.
• PKA increases opening of L-type calcium channels, increasing influx of Ca2+ into the myocyte.
• This results in increased calcium-induced calcium release, resulting in greater contractile force.
• IP3 increases Ca2+ release from the sarcoplasmic reticulum directly, resulting in greater contractile force.
• This will result in a decreased ESV but will not change EDV. Stroke volume therefore increases by the same amount ESV decreases.

Question 26

Define after-load.

What is the primary determinant of after-load?

Answer 26

• The load against which the heart must contract to eject the stroke volume.
• Primarily determined by aortic / pulmonary artery pressure.

Question 27

What is the main determinant of aortic pressure (other than increased ventricular contractile force)?

Answer 27

Total peripheral resistance.

Question 28

How does the heart maintain stroke volume when total peripheral resistance increases?

Answer 28

• An increase in total peripheral resistance will increase aortic pressure.
• This will result in a higher end systolic volume and, after one or two contractions, a higher end diastolic volume, too.
• According to Starling’s law, the ventricles will contract with a greater force due to a greater end diastolic volume.