Control of Heart function Flashcards
What are the ways that cardiac function in the physiological setting is influenced?
Endogenous regulation (within the heart)
Exogenous regulation (outside the heart)
What are the exogenous regulations of cardiac function?
brain, kidneys, vessels
What can a prolonged or occasional acute imbalance in the mechanisms of control of cardiac function lead to?
pathophysiological consequences
The main anatomical components of the heart can be categorised broadly into what 3 categories?
- Muscle cells (cardio-myocytes): can contract and relax in response to electrical stimuli. Essential for pumping blood around the body
- Specialised electrical cells: cells that create spontaneous currents and those that transmit currents exist within the heart. Essential for regulating contraction of the cardio-myocytes
- Vessels: the major blood vessels are responsible for transporting blood in and out of the heart, whilst the coronary blood vessels are responsible for supplying blood to the heart
Which out of the three categories is the most prominent in controlling function?
specialised electrical cells
What are the nodes in the heart?
Sinoatrial node (SAN)
Atrioventricular node (AVN)
What are the tracts that connect the nodes?
Bundle of His and bundle branches
Purkinje fibres
What is the SAN?
Sinoatrial (SA) node
Pacemaker of the heart: 60-100 bpm
In the junction of crista terminalis; upper wall of right atrium & opening of superior vena cava
What is the AVN?
Atrioventricular (AV) node
Has pacemaker activity: slow calcium mediated action potential
Triangle of Koch at base of right atrium
What is the bundle of His and bundle branches?
Bundles of His & bundle branches
Specialised myocytes. AV node: His bundle -> branches at intraventricular septum -> apex
What are the purkinje fibres?
specialised conducting fibres
What are the 3 phases of the nodal cell action potential?
0, 3, and 4
4= pre-potential
0= upstroke
34=repolarisation
What is the upstroke due to in the nodal cell action potential?
due to Ca2+ influx
What is the repolarisation due to in the nodal cell action potential?
due to K+ efflux
What is the resting membrane potential of nodal cells?
Nodal cells do not have a resting membrane potential - only a pre-potential due to Na+ influx through a ‘funny’ channel
What are the action potential profiles?
Different parts of the heart have different action potential shapes
Why do the different parts of the heart have different action potential shapes?
it is caused by different ion currents flowing and different ion channel expression in cell membrane
What is the action potential profile of…
SAN
AVN
atrial myocardium
bundle of His
endocardium
myocardium
epicardium
What are the phases of a cardiac muscle action potential?
0= upstroke
1= early repolarisation
2= plateau
3= repolarisation
4= resting membrane potential
How long is a nerves AP and and how long is a cardiac AP?
200-300 ms= cardiac
2-3 ms= nerves
What does duration of AP control?
duration of contraction of the heart
What is required to produce an effective pump?
long, slow contraction
What is the absolute refractory period (ARP)?
time during which no AP can be initiated regardless of stimulus intensity
What is the relative refractory period (RRP)?
Period after ARP where an AP can be elicited but only with larger stimulus strength
What is the membrane potential (mV) to Time (ms) graph look like for a ventricular cell and what is the cell permeability to ions throughout it?
What is the membrane potential (mV) to Time (ms) graph look like for a SA node cell and what is the ell permeability to ions throughout it?
What connects the AVN and SAN?
Internodal tracts
What part, blue or green under the graph represents the absolute and the relative refractory period?
Blue= absolute
green= relative
What are the 3 major organs that control function of the heart?
brain/ central nervous system
kidneys
blood vessels
How does the brain control the heart?
it can effect immediate changes through nerve activity or slower changes through hormonal activity
How does the kidney control the heart?
the heart and kidneys share a bi-directional regulatory relationship usually through indirect mechanisms
How does the blood vessels control the heart?
by regulating the amount of blood that goes to and from the heart the blood vessels are able to influence cardiac activity
Where is the cardio-regulatory centre and vasomotor centre?
In the medulla
How is the nervous system divided in humans?
What division of the nervous is control of the heart?
autonomic nervous system
What does the parasympathetic nervous system do?
‘Rest & digest’
decrease heart rate (HR) – decreases the slope of phase 4
What does the sympathetic nervous system do?
‘fight or flight’
increase HR (chronotropy) – increases the slope of phase 4
increase force of contraction (inotropy) – increases Ca2+ dynamics
What nerve connects the medulla to the heart for parasympathetic nervous system innervation?
Vagus
What nerve connects the medulla to the heart for sympathetic nervous system innervation?
sympathetic nerves
How do the graphs of membrane potential to time differ between para and sympathetic stimulation?
What is the parasympathetic nervous system particularly important for?
controlling the heart rate
What is the sympathetic nervous system particularly important for?
controlling the circulation
What are the neurotransmitters used in the parasympathetic NS?
Pre-ganglionic fibres use ACh as neurotransmitter
post ganglionic NT = ACh
What are the neurotransmitters used in the sympathetic NS?
Pre-ganglionic fibres use ACh as their neurotransmitter
Post ganglionic NT = NA
Where do parasympathetic and sympathetic nerves arise from
Para= cranial part of spinal cord and sacral part of spinal cord
Sympathetic= thoracic vertebra, lumbar vertebra
What are the receptors for the neurotransmitters in parasympathetic fibres?
Nicotinic receptors (preganglionic) and Muscarinic receptors (post ganglionic)
What are the receptors for the neurotransmitters in sympathetic fibres?
Nicotinic receptors (preganglionic) noradrenaline receptors (post ganglionic)
What is the vasomotor centre composed of?
Composed of:
Vasoconstrictor (pressor) area
Vasodilator (depressor) area
Cardio-regulatory inhibitory area
Where is the vasomotor centre located?
VMC located bilaterally in reticular substance of medulla & lower third of pons
What does the vasomotor centre do?
Transmits impulses distally through spinal cord to almost all blood vessels
What can exert excitatory/ inhibitory effects on the vasomotor centre?
Many higher centers of the brain such as the hypothalamus can exert powerful excitatory or inhibitory effects on the VMC.
What do the lateral portions of the vasomotor centre control?
Lateral portions of VMC controls heart activity by influencing heart rate and contractility
What does the medial portion of the vasomotor centre do?
Medial portion of VMC transmits signals via vagus nerve to heart that tend to decrease heart rate.
How does parasympathetic and sympathetic cardiac innervation change heart rate, shown in a graph?
In the parasympathetic nervous system, is the preganglionic or postganglionic fibre longer?
preganglionic is longer
In the sympathetic nervous system, is the preganglionic or postganglionic fibre longer?
postganglionic fibre is longer
Where do the sympathetic nerve fibres tend to synapse?
sympathetic ganglia/ paravertebral ganglia
How does parasympathetic cardiac innervation work?
1) Acetylcholine acts on M2-receptors (muscarinic receptors) on cell membrane of a SAN cell
2) Gi protein causes inhibition of adenylyl cyclase
3) prevents conversion of ATP-> cAMP-> PKA
Inhibition of the secondary messenger
How does sympathetic cardiac innervation work?
1) noradrenaline acts on B1-receptors
2) Gs protein promotion causing the promoting of adenylyl cyclase
3) promoting ATP-> cAMP-> PKA
Opposite of parasympathetic
What does angiotensin II also cause to be secreted?
aldosterone from adrenal glands
What happens to the renal system with afferent sympathetic nerve innervation?
Decrease glomerular filtration-> decrease Na+ excretion:
increase in blood volume
(aldosterone also plays a role in increasing blood volume)
What detects changes in blood volume?
venous volume receptors
What caused renin secretion, and what does renin secretion cause?
Sympathetic nerves
Increased renin secretion-> increased angiotensin-II production:
leading to vasoconstriction & increased blood pressure
What detects changes in blood pressure?
arterial baroreceptors
How does the sympathetic nerves, blood volume and blood pressure all link to cause a change in blood pressure?
What innervates afferent and efferent arterioles of the glomerulus (and nephron tubule cells)?
sympathetic nerve fibres
What happens at the afferent arterioles?
Primary site of sympathetic activity:
a1-adrenoceptor -> vasoconstriction
decreases glomerular filtration rate -> decrease Na+ filtered
How do sympathetic nerves affect juxtaglomerular cells?
Juxtaglomerular cells are the site of synthesis, storage & release of renin
B1-adrenoceptor-> renin secretion
subsequently increasing aldosterone secretion
which increases blood volume
What happens with a1-receptors in the glomerular afferent arterioles?
noradrenaline acts on a1-receptor
causes Gq to activate PLC
leading to…
PIP2–> DAG–> PKC
PIP2-> IP3-> Ca2+
WHat happens to B1 receptors in juxtaglomerular cells?
noradrenaline acts on B1-receptors
causes Gs to activate AC
leading to ATP-> cAMP-> PKA
What is the cardiopulmonary circuit made of?
Large pulmonary vessels
How does the cardiopulmonary circuit work?
Volume sensors (also atria & right ventricle): send signals through glossopharyngeal & vagus nerves
Decrease in filling -> decreased baroreceptor firing -> increased sympathetic nerve (SNS) activity
Distention -> increased baroreceptor firing -> decreased SNS activity
What is the arterial circuit made of?
Aortic arch, carotid sinus & afferent arterioles of kidneys
How does the arterial circuit work?
Pressure sensors: send signals through glossopharyngeal & vagus nerves
Decrease in pressure -> decreased baroreceptor firing -> increased SNS activity
Increase in pressure -> increased baroreceptor firing -> decreased ISNS activity
What are the 2 circulation of the heart?
pulmonary and systemic
What is the order of circulation?
right heart-> lungs-> left heart-> body
What is venous volume distribution affected by?
peripheral venous tone, gravity, skeletal muscle pump and breathing
What is central venous pressure?
Mean pressure in the right atrium
It determines amount of blood flowing back to heart
What does the amount of blood flowing back to the heart determine?
stroke volume (using starling’s law of the heart)
What does constriction in veins lead to?
reduces compliance and increases venous return
In arterioles what does constriction determine?
Blood flow to downstream organs
Mean arterial blood pressure
The pattern of blood flow to organs
What is the blood distribution around the heart?
What is the control of venous return like?
What are the local mechanisms of regulating blood flow? (4)
Intrinsic to the smooth muscle (or closely associated)
Important for reflex local blood flow regulation within an organ
Endothelium-derived mediators include:
- Nitric oxide (NO): potent vasodilator, which diffuses into vascular smooth muscle cells.
- Prostacyclin: vasodilator that also has antiplatelet & anticoagulant effects
- Thromboxane A2 (TXA2): vasoconstrictor that is also heavily synthesised in platelets
- Endothelins (ET): vasoconstrictors generated from nucleus of endothelial cells
What are the systemic mechanism for regulating blood flow? (5)
Extrinsic to the smooth muscle
These include the autonomic nervous system & circulating hormones
Non-endothelium-derived mediators include:
- Kinins: bind to receptors on endothelial cells & stimulate NO synthesis – vasodilator effects
- Atrial natriuretic peptide (ANP): secreted from the atria in response to stretch – vasodilator effects to reduce BP
- Vasopressin (ADH): secreted from pituitary gland. Binds to V1 receptors on smooth muscle to cause vasoconstriction
- Noradrenaline/Adrenaline: secreted from adrenal gland (& SNS); causes vasoconstriction
- Angiotensin II: potent vasoconstrictor from the renin-angiotensin-aldosterone axis. Also stimulates ADH secretion.
What is inotropy and chronotropy?
inotropy= muscle contraction
chronotropy= heart rate
What effect will activation of renal arteriole alpha-1 receptor eventually have on the heart, chronotropy and inotropy wise?
Reduced chronotropy & increased inotropy
This is most likely to happen if we are only taking into account the Starling forces on the heart (increased volume –> increased force of contraction) and the effects on the baroreceptors (increased volume and pressure –> reduced SNS activity)
When does baroreceptor firing increase?
When pressure increases
