Control of Heart Function

Question 1

What are the main components of the heart?

Answer 1

Consists of nodes and tracts. The sinoatrial node is the pacemaker of the heart, generating 60-100 bpm. Found in the junction of crista terminalis; upper wall of right atrium & opening of superior vena cava. Atrioventricular node also has pacemaker activity due to slow calcium mediated action potential production. Found in triangle of Koch at base of right atrium.
Important tract is Bundle of His, consisting of specialised myocytes. Runs from AV node, branches at intraventricular septum until apex. Purkinje fibres are specialised conducting fibres found in apex of heart.

Question 2

Describe nodal cell action potential at sinoatrial node

Answer 2

Nodal AP only has 3 phases (4, 0 & 3).
Pre-potential created due to Na+ influx through a ‘funny’ channel. Nodal cells don’t have a resting membrane potential. Goes from -40mV to approx -60mV.
Phase 0 is upstroke due to calcium ion influx. Goes up to 20mV.
Phase 3 is repolarisation due to potassium efflux. Decreases back down to -60mV.

Question 3

Compare nervous AP to cardiac muscle action potential

Answer 3

Compared to nerves, cardiac AP is long (200-300 ms vs. 2-3 ms). Duration of AP controls duration of contraction of heart and long, slow contraction is required to produce an effective pump.

Question 4

Why do different parts of the heart have different action potentials?

Answer 4

Different parts of the heart have different action potential shapes as caused by different ion currents flowing and different ion channel expression in cell membrane.

Question 5

Describe phases of cardiac muscle action potential

Answer 5

AP has 5 phases numbered 0-4
Phase 0 is the upstroke from -80mV to 30mV.
Phase 1 is early repolarisation where voltage reduces slightly to around 15/20mV.
Phase 2 is the plateau cell potential maintained at a level of depolarisation with only very slight, gradual decrease.
Phase 3 is where full repolarisation occurs and voltage drops back to -80mV.
Phase 4 is the resting membrane potential.

Question 6

What are the absolute and relative refractory periods?

Answer 6

Absolute refractory period (ARP) = time during which no AP can be initiated regardless of stimulus intensity. This lasts from upstroke till start of repolarisation.

Relative refractory period (RRP) = period after ARP where an AP can be elicited but only with larger stimulus strength. This runs through repolarisation period until resting membrane potential approached.

Question 7

Describe ion movement during ventricular cell action potential

Answer 7

Phase 0 occurs due to sodium ion influx causing depolarisation of cell. Potassium efflux causes phase 1 and plateau created through gradual calcium ion influx. Phase 3 occurs due to potassium ion efflux allowing repolarisation to occur.

Question 8

What major organ systems modulate the activity of the heart?

Answer 8

1. The brain/central nervous system: can effect immediate changes through nerve activity or slower changes through hormonal activity
2. The kidneys: the heart and kidneys share a bi-directional regulatory relationship usually through indirect mechanisms
3. The blood vessels: by regulating the amount of blood that goes to and from the heart the blood vessels are able to influence cardiac activity.

Question 9

What part of the brain controls heart activity?

Answer 9

Cardio-regulatory centre & vasomotor centres in medulla, parts of autonomic nervous system

Question 10

What are the actions of the parasympathetic nervous system and sympathetic nervous system on the heart?

Answer 10

PNS decreases heart rate by decreasing slope of phase 4. SNS increases heart rate (chronotropy) by increasing slope of phase 4 and there is an increased force of contraction (inotropy) which is not a result of nervous control but more to do with calcium ion dynamics.

Question 11

Describe parasympathetic pathway of cardiac innervation

Answer 11

Parasympathetic fibres arise from the cranial and sacral part of the spinal cord. Pre-ganglionic fibres use ACh as neurotransmitter and PNS post ganglionic NT = ACh. Post-ganglionic neurone has nicotinic receptors while target organ has muscarinic receptors. PNS important for controlling heart rate.

Question 12

Where do sympathetic fibres arise and what is their structure?

Answer 12

Sympathetic fibres arise from the thoracic and lumbar parts of the spine. Pre-ganglionic fibres use ACh as their neurotransmitter while post ganglionic NT is noradrenaline. Post-ganglionic neurone has nicotinic receptors at pre-synaptic terminal. SNS important for controlling circulation.

Question 13

Where is the vasomotor centre located and what is it composed of?

Answer 13

VMC located bilaterally in reticular substance of medulla & lower third of pons. Composed of:
Vasoconstrictor (pressor) area, Vasodilator (depressor) area and Cardio-regulatory inhibitory area. Transmits impulses distally through spinal cord to almost all blood vessels.

Question 14

What do different parts of the vasomotor centre do and how is its activity modulated?

Answer 14

Lateral portions of VMC controls heart activity by influencing heart rate and contractility. Medial portion of VMC transmits signals via vagus nerve to heart that tend to decrease heart rate. Many higher centers of the brain such as the hypothalamus can exert powerful excitatory or inhibitory effects on the VMC.

Question 15

Describe parasympathetic cardiac innervation based on what receptor it acts on

Answer 15

Parasympathetic impulses transmitted to heart cause release of acetylcholine which binds to the M2 muscarinic receptors in sinoatrial nodal cell. This is a G-protein coupled receptor and so acts through G1 type protein which inhibits adenyl cyclase action, so protein kinase A not formed.

Question 16

Describe sympathetic cardiac innervation based on what receptor it acts on

Answer 16

Sympathetic impulses transmitted to heart cause release of noradrenaline which binds to a beta-1 receptor in sinoatrial nodal cell. Also G-protein coupled to a G2 protein which stimulates adenyl cyclase and protein kinase A formation potentiated.

Question 17

How do parasympathetic and sympathetic innervation impact heart rate?

Answer 17

Exist in dynamic equilibrium as when a parasympathetic nerve is cut, increase in heart rate seen even if sympathetic not stimulated. Hence, both exist to maintain basal control but parasympathetic has a bigger role in this.

Question 18

What is the impact on sympathetic innervation of kidney on blood volume?

Answer 18

Sympathetic nerve fibres innervate afferent & efferent arterioles of the glomerulus (& nephron tubule cells). The afferent arteriole is the primary site of sympathetic activity. alpha1-adrenoceptor is stimulated by noradrenaline, causing vasoconstriction and a decrease in glomerular filtration rate, meaning less sodium leaves the bloodstream. Simultaneously, noradrenaline stimulates the juxtaglomerular cells via the beta1-receptors. Juxtaglomerular cells are responsible for synthesis, storage & release of renin so when stimulated they secrete renin. Renin increases aldosterone secretion which also increases blood volume.

Question 19

How does the cardiopulmonary circuit impact heart control?

Answer 19

Volume sensors are found in the large pulmonary vessels, atria and right ventricle. These send signals though glossopharyngeal & vagus nerves. When they detect a decrease in filling, there is a decrease in baroreceptor firing which results in an increase in sympathetic nervous system activity. Distension occurs when there is an increase in filling which increases baroreceptor firing and hence decreases SNS activity.

Question 20

How does the arterial circuit impact heart control?

Answer 20

Pressure sensors are found in the aortic arch, carotid sinus & afferent arterioles of kidneys. These send signals though glossopharyngeal & vagus nerves. When there is a decrease in pressure, there is a decrease in baroreceptor firing and a subsequent increase in sympathetic activity. When there is an increase in pressure, the opposite occurs.

Question 21

Describe distribution in volumes of blood

Answer 21

61% of blood is in the veins, 9% in heart, 17% in pulmonary circulation, 11% in arteries and 7% in arterioles and capillaries.

Question 22

What determines stroke volume?

Answer 22

Venous volume distribution affected by peripheral venous tone, gravity, skeletal muscle pump & breathing. Central venous pressure (mean pressure in the right atrium) determines amount of blood flowing back to heart. Amount of blood flowing back to the heart determines stroke volume.

Question 23

What is the impact of constriction in veins and arterioles?

Answer 23

In veins, constriction reduces compliance and increases venous return. In arterioles, constriction determines:
Blood flow to downstream organs
Mean arterial blood pressure
The pattern of blood flow to organs

Question 24

How can atrial pressure be increased?

Answer 24

An increase in blood volume, SNS activation of veins, increased skeletal muscle pump and increased respiratory movement can all cause increased venous return. Increased venous return leads to increased venous pressure which leads to increased atrial pressure.

Question 25

What are local mechanisms of regulating blood flow?

Answer 25

Endothelium-derived mediators are intrinsic to the smooth muscle (or closely associated) and important for reflex local blood flow regulation within an organ. Include:
Nitric oxide (NO): potent vasodilator, which diffuses into vascular smooth muscle cells.
Prostacylin: 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

Question 26

What are systemic mechanisms of regulating blood flow?

Answer 26

Non-endothelium-derived mediators are extrinsic to the smooth muscle and include the autonomic nervous system & circulating hormones. 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.