intrinsic and extrinsic control of the heart

Question 1

cardiac output definition

Answer 1

the volume of blood ejected by the heart per minute

Question 2

what determines the CO?

Answer 2

stroke volume, the volume of blood ejected per beat

heart rate, number of beats per minute

Question 3

normal resting CO

Answer 3

5L/min

Question 4

two different types of control of CO

Answer 4

intrinsic control- cardiac regulation in response to the volume of blood entering the heart, the Frank Starling mechanism

extrinsic control- regulation of contractility and heart rate by autonomic nerves and circulating factors such as hormones

Question 5

two types of intrinsic auto regulation + definition

Answer 5

heterometric autoregulation- function of diastolic fibre length, independent of innervation and other extrinsic influences, a length-tension relationship as dictated by Starling’s law of the heart

homometric autoregulation- the intrinsic mechanisms controlling the ventricular contraction strength that don’t depend upon the length of myocardial fibres at the end of diastole, due to agents such as pH and intracellular Na+

Question 6

preload definition

Answer 6

the initial stretching go cardiac myocytes prior to contraction

Question 7

What determines preload?

Answer 7

increased cardiac filling pressure caused by an increased blood volume or vasoconstriction which increases ventricular end diastolic volume, which is determined by central venous pressure

Question 8

what does increased preload lead to?

Answer 8

increased stroke volume and cardiac output via the Frank Starling mechanism

Question 9

afterload definition

Answer 9

the load that the heart must eject blood against, determined by arterial pressure as a result of peripheral resistance and compliance

Question 10

what increases afterload?

Answer 10

arteriole and arterial vasoconstriction

Question 11

explain an increased afterload’s impact on preload stages

Answer 11

1. after load briefly decreases the velocity of fibre shorting, EDV is initially unchanged
2. constant stroke work in the face of increased resistance decreases stroke volume
3. end systolic volume increases as there is more blood left in the ventricle after systole. This causes an increased left ventricular diastolic pressure
4. the increased residual volume left in the heart after ejection is added to the venous return of the ventricle, increasing pressure and EDV
5. this increase in preload increases stroke work until a steady state is reestablished with increased EDV and the same cardiac output as before

Question 12

Starling’s law definition

Answer 12

states that cardiac output increases proportionally to the increase in diastolic stretch of the myocardial fibres. The increased stroke volume following an increase in central venous pressure is known as starling’s law of the heart.

Question 13

explain how increased preload leads to a stronger contraction

Answer 13

1. increased preload increases the volume of blood pumped into the right atrium and then the right ventricle
2. this increases loading into the left atrium and left ventricle
3. these leads to an increase in end diastolic volume, which is associated with an increase in developed pressure during systole, resulting in an increased stroke volume
4. increased volume of blood stretches the myocytes in the walls of the cardiac chambers, which increases the strength of contraction

Question 14

what does the Frank-Starling mechanism allow?

Answer 14

Ensures that the output volume is equal to the input volume, and thus synchronises the blood serially through the four chambers

Question 15

what is the optimal length of the sarcomere for maximal force?

Answer 15

2.2-2.3 microns

Question 16

2 ways the Frank-Starling mechanism increase the strength of the contraction?

Answer 16

there is no transient increase in calcium ions, stretch produces an immediate response instead

1. as the sarcomere increases in length, the stretch reduces the overlap of actin and interference of sarcomeres
2. increases sensitivity to calcium

Question 17

explain interference

Answer 17

when less than 2 microns, the actin filaments extend past the midline into the wrong half of the sarcomere, causing some cross bridges to pull in the opposite direction to the majority, reducing net tension generated

when less than 1.6 microns the myosin filaments reach the Z lines, causing interference with other sarcomeres

Question 18

explain increasing the sensitivity to calcium

Answer 18

stretch increases the fraction of cross bridges activated by a given calcium level, as stretched myocytes need less to become activated

lattice spacing hypothesis is a possible explanation, where an increase in length of a myocyte decreases the diameter due to having a fixed volume, which reduces the side to side separation of the actin and myosin

longitudinal stretch also increases calcium binding affinity of troponin C

Question 19

what happens some time after the Frank-Starling mechanism?

Answer 19

Anrep effect

Question 20

explain the Anrep effect

Answer 20

sustained stretch to myocytes occurs over around 5 minutes

stretch activated calcium channels are opened in the myocyte sarcolemma, permitting calcium, increasing CICR meaning an increase in inotropy

Question 21

inotropy definition

Answer 21

contraction force

Question 22

factors which increase preload,

Answer 22

increased central venous pressure, from decreased venous compliance (contraction of vessels)

increased ventricular compliance- greater expansion of chamber

increased atrial force of contraction from sympathetic activation or stretch

reduced heart rate, increases ventricular filling time

increasing aortic pressure- increases afterload on the ventricle, reduces stroke volume by increasing end systolic volume, eventually leads to increased preload

Question 23

Frank-Starling function

Answer 23

increased stroke volume during exercise

maintains postural hypotension

mediates hypovolaemic hypotension

balances the output of the right and left ventricle, prevents pulmonary oedema or congestion

Question 24

what is hypovolaemic hypotension?

Answer 24

low blood pressure due to a fall in blood volume, from haemorrhage or dehydration which lowers central venous pressure

loss of blood volume detected by Starling’s law, which leads to the heart pumping more slowly to reduce stroke volume and blood loss

Question 25

determinants of cardiac output

Answer 25

stroke volume and heart rate

Question 26

how can cardiac output be measured?

Answer 26

Fick principle

Question 27

explain the fick principle

Answer 27

VO2= (CO x Ca) - (CO x Cv)

VO2- oxygen consumption per minute, measured using. a spirometer

Ca= oxygen content of arterial blood, taken from the pulmonary vein

Cv= oxygen content of venous blood, taken from an intravenous cannula

CO= cardiac output

Question 28

chronotropy definition

Answer 28

changes in heart rate

Question 29

chemical factors affecting the isotropy and chronotropy of the heart

Answer 29

adrenaline + other beta agonists, secreted by adrenal medulla

angiotensin II- AT1 receptors on sympathetic nerve terminals facilitate NA release and also act directly on cardiac myocyte receptors to increase iCa

hormones, thyroxine, insulin, glucagon have a long term positive inotropic effect

Question 30

When is sympathetic regulation active?

Answer 30

exercise, stress haemorrhage and orthostasis

Question 31

what do the cardiac sympathetic fibres innervate?

Answer 31

right fibres innervate SAN

left fibres innervate atrial and ventricular myocardium

Question 32

explain sympathetic chronotropy

Answer 32

1. noradrenaline rebased from terminal varicosities
2. binds to beta1 receptors, which are a Gs GPCR
3. activates adenyl cyclase to make cAMP which activates protein kinase A
4. PKA phosphorylates L type calcium channels and increases their open state probability and duration
5. This increases the calcium current into the SAN which accelerates the pacemaker decay contributing to the chronotropic effect

Question 33

explain sympathetic inotropy

Answer 33

as previously, increase calcium ions move into ventricular and atrial myocytes which increases their contractile force

1. PKA also phosphorylates phospholamban which reduces its inhibitory effect of SERCA
2. boosts calcium ion re-uptake from the sarcoplasmic reticulum
3. increases the calcium store so will increase the inward calcium current when triggered by an action potential

Question 34

long term effect of B activation

Answer 34

calmodulin dependent kinase II becomes activated

phosphorylates phospholamban, so more inhibition of SERCA, more calcium ions available for sliding filament mechanism which allows for a longer contraction, maintaining the isotropic effect