intrinsic and extrinsic control of the heart Flashcards
cardiac output definition
the volume of blood ejected by the heart per minute
what determines the CO?
stroke volume, the volume of blood ejected per beat
heart rate, number of beats per minute
normal resting CO
5L/min
two different types of control of CO
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
two types of intrinsic auto regulation + definition
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+
preload definition
the initial stretching go cardiac myocytes prior to contraction
What determines preload?
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
what does increased preload lead to?
increased stroke volume and cardiac output via the Frank Starling mechanism
afterload definition
the load that the heart must eject blood against, determined by arterial pressure as a result of peripheral resistance and compliance
what increases afterload?
arteriole and arterial vasoconstriction
explain an increased afterload’s impact on preload stages
- after load briefly decreases the velocity of fibre shorting, EDV is initially unchanged
- constant stroke work in the face of increased resistance decreases stroke volume
- end systolic volume increases as there is more blood left in the ventricle after systole. This causes an increased left ventricular diastolic pressure
- the increased residual volume left in the heart after ejection is added to the venous return of the ventricle, increasing pressure and EDV
- this increase in preload increases stroke work until a steady state is reestablished with increased EDV and the same cardiac output as before
Starling’s law definition
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.
explain how increased preload leads to a stronger contraction
- increased preload increases the volume of blood pumped into the right atrium and then the right ventricle
- this increases loading into the left atrium and left ventricle
- 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
- increased volume of blood stretches the myocytes in the walls of the cardiac chambers, which increases the strength of contraction
what does the Frank-Starling mechanism allow?
Ensures that the output volume is equal to the input volume, and thus synchronises the blood serially through the four chambers
what is the optimal length of the sarcomere for maximal force?
2.2-2.3 microns
2 ways the Frank-Starling mechanism increase the strength of the contraction?
there is no transient increase in calcium ions, stretch produces an immediate response instead
- as the sarcomere increases in length, the stretch reduces the overlap of actin and interference of sarcomeres
- increases sensitivity to calcium
explain interference
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
explain increasing the sensitivity to calcium
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
what happens some time after the Frank-Starling mechanism?
Anrep effect
explain the Anrep effect
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
inotropy definition
contraction force
factors which increase preload,
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
Frank-Starling function
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
what is hypovolaemic hypotension?
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
determinants of cardiac output
stroke volume and heart rate
how can cardiac output be measured?
Fick principle
explain the fick principle
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
chronotropy definition
changes in heart rate
chemical factors affecting the isotropy and chronotropy of the heart
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
When is sympathetic regulation active?
exercise, stress haemorrhage and orthostasis
what do the cardiac sympathetic fibres innervate?
right fibres innervate SAN
left fibres innervate atrial and ventricular myocardium
explain sympathetic chronotropy
- noradrenaline rebased from terminal varicosities
- binds to beta1 receptors, which are a Gs GPCR
- activates adenyl cyclase to make cAMP which activates protein kinase A
- PKA phosphorylates L type calcium channels and increases their open state probability and duration
- This increases the calcium current into the SAN which accelerates the pacemaker decay contributing to the chronotropic effect
explain sympathetic inotropy
as previously, increase calcium ions move into ventricular and atrial myocytes which increases their contractile force
- PKA also phosphorylates phospholamban which reduces its inhibitory effect of SERCA
- boosts calcium ion re-uptake from the sarcoplasmic reticulum
- increases the calcium store so will increase the inward calcium current when triggered by an action potential
long term effect of B activation
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
