regulation of the heartbeat. outline control of the heart beat intrinsic control of contractility ...

Regulation of the Regulation of the HeartbeatHeartbeat

OutlineOutline

Control of the heart beatControl of the heart beat Intrinsic control of contractilityIntrinsic control of contractility Extrinsic control of contractilityExtrinsic control of contractility

Control of the heartbeat Control of the heartbeat

Parasympathetic pathway Parasympathetic pathway Parasympathetic fibers originate in the nucleus Parasympathetic fibers originate in the nucleus

ambiguus.ambiguus. They pass through the mediastinum to synapse with They pass through the mediastinum to synapse with

postganglionic cells on the epicardial surface or within postganglionic cells on the epicardial surface or within the walls of the heart itself.the walls of the heart itself.

The right vagus nerve effects the SA node The right vagus nerve effects the SA node predominantly.predominantly.

The left vagus nerve mainly inhibits AV conduction.The left vagus nerve mainly inhibits AV conduction.

Control of the heartbeatControl of the heartbeat

Acetylcholine is rapidly hydrolyzed via nodal Acetylcholine is rapidly hydrolyzed via nodal cholinesterase so the effect is brief.cholinesterase so the effect is brief.

The muscarinic receptors are coupled directly to the The muscarinic receptors are coupled directly to the acetylcholine-regulated potassium channels by a G acetylcholine-regulated potassium channels by a G protein; this direct coupling allows a prompt responseprotein; this direct coupling allows a prompt response

Parasympathetic predominate over sympathetic Parasympathetic predominate over sympathetic effects at the SA node.effects at the SA node.

This is mediated by suppressing release of This is mediated by suppressing release of norepinephrine from the sympathetic nerve endings norepinephrine from the sympathetic nerve endings by acetylcholineby acetylcholine


Sympathetic pathwaySympathetic pathway The cardiac sympathetic fibers originate in the The cardiac sympathetic fibers originate in the

interomedial lateral columns of the T1-5 and C7-8 interomedial lateral columns of the T1-5 and C7-8 segments of the spinal cord.segments of the spinal cord.

Preganglionic and postganglionic neurons synapse Preganglionic and postganglionic neurons synapse mainly in the stellate and middle cervical ganglia.mainly in the stellate and middle cervical ganglia.

On reaching the base of the heart, these fibers are On reaching the base of the heart, these fibers are distributed to the various chambers as an extensive distributed to the various chambers as an extensive epicardial plexus.epicardial plexus.


The effects of sympathetic stimulation decay The effects of sympathetic stimulation decay very gradually after stimulation.very gradually after stimulation.

The response to sympathetic activity depends The response to sympathetic activity depends mainly on the intracellular production of mainly on the intracellular production of second messengers, mainly cAMPsecond messengers, mainly cAMP

Control of the heartbeatControl of the heartbeat Baroreceptor reflex Baroreceptor reflex

Acute changes in blood pressure elicit inverse changes in Acute changes in blood pressure elicit inverse changes in heart rate via the baroreceptors located in the aortic arch heart rate via the baroreceptors located in the aortic arch and carotid sinuses and carotid sinuses

Bainbridge reflexBainbridge reflex A fluid bolus accelerates the heart rate whether arterial A fluid bolus accelerates the heart rate whether arterial

blood pressure rise or notblood pressure rise or not Tachycardia occurs with CVP rises sufficient to distend the Tachycardia occurs with CVP rises sufficient to distend the

right heart.right heart. Increases in blood volume not only evoke the Bainbridge Increases in blood volume not only evoke the Bainbridge

reflex, but they also activate the baroreceptor reflex that reflex, but they also activate the baroreceptor reflex that tend to slow the heart rate.tend to slow the heart rate.

The actual change in heart rate evoked by an alteration of The actual change in heart rate evoked by an alteration of the blood volume is the results of these antagonistic reflex the blood volume is the results of these antagonistic reflex effects.effects.


How does the Bainbridge reflex work?How does the Bainbridge reflex work? Atria have receptors that influence heart rate located Atria have receptors that influence heart rate located

in the venoatrial junction.in the venoatrial junction. Distention of these receptors send impulses centrally Distention of these receptors send impulses centrally

in the vagus nerve.in the vagus nerve. The efferent impulses are carried by fibers from both The efferent impulses are carried by fibers from both

autonomic divisions to the SA node.autonomic divisions to the SA node. The increase in sympathetic activity is restricted to The increase in sympathetic activity is restricted to

the heart rate; there is no increase of sympathetic the heart rate; there is no increase of sympathetic activity to the peripheral arterioles nor increase in activity to the peripheral arterioles nor increase in contractility.contractility.


Stimulation of atrial receptors also increases Stimulation of atrial receptors also increases urine volume.urine volume.

Atrial natriuretic peptide is released from atrial Atrial natriuretic peptide is released from atrial tissue in response to stretch of the atrial wall.tissue in response to stretch of the atrial wall.

It has potent diuretic and natriuretic effects on It has potent diuretic and natriuretic effects on the kidneys and dilates blood vessels.the kidneys and dilates blood vessels.


Respiratory variationRespiratory variation Heart rate accelerates during inspiration and Heart rate accelerates during inspiration and

decelerates during expiration.decelerates during expiration. Activity increases in the sympathetic nerve fibers Activity increases in the sympathetic nerve fibers

during inspiration, whereas activity in the vagal nerve during inspiration, whereas activity in the vagal nerve fibers increases during expiration.fibers increases during expiration.

Acetylcholine released at the vagal endings is Acetylcholine released at the vagal endings is hydrolyzed so rapidly that the rhythmic change in hydrolyzed so rapidly that the rhythmic change in activity are able to elicit rhythmic variations in heart activity are able to elicit rhythmic variations in heart rate.rate.

Conversely, norepinephrine is released at the Conversely, norepinephrine is released at the sympathetic endings is removed more slowly, thus sympathetic endings is removed more slowly, thus dampening out the effects of rhythmic variations in dampening out the effects of rhythmic variations in norepinephrine released on heart ratenorepinephrine released on heart rate


Hence, rhythmic changes in heart rate arise almost Hence, rhythmic changes in heart rate arise almost entirely from oscillations in vagal activity.entirely from oscillations in vagal activity.

During inspiration, venous return to the right side of During inspiration, venous return to the right side of the heart accelerated and elicits the Bainbridge reflex.the heart accelerated and elicits the Bainbridge reflex.

After the time delay required for the increased venous After the time delay required for the increased venous return to reach the left side of the heart, left return to reach the left side of the heart, left ventricular output increases and raises arterial blood ventricular output increases and raises arterial blood pressure. pressure.

This reduces heart rate reflexively through the This reduces heart rate reflexively through the baroreceptor stimulation.baroreceptor stimulation.

Intrinsic control of contractility Intrinsic control of contractility

Frank-Starling mechanism Frank-Starling mechanism When the load on the heart is When the load on the heart is

increased, it responds with a increased, it responds with a more forceful contraction.more forceful contraction.

In this experiment the right atrial In this experiment the right atrial pressure [preload] was increased.pressure [preload] was increased.

The width of the tracing reflects The width of the tracing reflects the stroke volume.the stroke volume.

For several beats after the rise in For several beats after the rise in preload, the ventricular volume preload, the ventricular volume progressively increased. progressively increased.

Intrinsic control of contractilityIntrinsic control of contractility

During a given systole, the volume of blood expelled During a given systole, the volume of blood expelled was not as great as the volume that had entered.was not as great as the volume that had entered.

This accumulation of blood dilated the ventricles and This accumulation of blood dilated the ventricles and lengthen the individual myocardial fibers in the wall of lengthen the individual myocardial fibers in the wall of the ventricle.the ventricle.

Increased fiber length alters cardiac performance Increased fiber length alters cardiac performance mainly by changing the calcium sensitivity of the mainly by changing the calcium sensitivity of the myofilaments and, in part, by changing the number of myofilaments and, in part, by changing the number of monofilament cross bridges that can interact.monofilament cross bridges that can interact.

Intrinsic control of contractilityIntrinsic control of contractility Increased afterloadIncreased afterload

Changes in diastolic fiber length compensate for an Changes in diastolic fiber length compensate for an increase in afterload.increase in afterload.

When the afterload is first increased, the stroke When the afterload is first increased, the stroke volume ejected by the ventricles during systole is less volume ejected by the ventricles during systole is less than the filling volume.than the filling volume.

The consequent excess of volume in the ventricles The consequent excess of volume in the ventricles stretches the myocardial fibers in the ventricular stretches the myocardial fibers in the ventricular walls. walls.

This increase in myocardial fiber length enables the This increase in myocardial fiber length enables the ventricles to eject a given stroke volume against an ventricles to eject a given stroke volume against an increased afterload.increased afterload.


Heart rate effects Heart rate effects When the heart rate is suddenly increased, the force When the heart rate is suddenly increased, the force

increases over the next several beats.increases over the next several beats. This progressive increase in developed force induced This progressive increase in developed force induced

by changing contraction frequency is known as the by changing contraction frequency is known as the staircase phenomena.staircase phenomena.

The initial rise in developed force when the interval The initial rise in developed force when the interval between beats is suddenly decreased is achieved by between beats is suddenly decreased is achieved by a gradual increase in the intracellular calcium content.a gradual increase in the intracellular calcium content.


Two mechanisms for the rising calcium: Two mechanisms for the rising calcium: An increase in the number of depolarization per minute An increase in the number of depolarization per minute An increase in the inward calcium current per depolarizationAn increase in the inward calcium current per depolarization

As the interval between beats is suddenly diminished, As the interval between beats is suddenly diminished, the inward calcium current progressively increases the inward calcium current progressively increases with each successive beat until a new steady-state with each successive beat until a new steady-state level is attained at the new basic cycle length.level is attained at the new basic cycle length.


PVCs also affect the strength of contraction.PVCs also affect the strength of contraction. When a PVC occurs, the premature When a PVC occurs, the premature

contraction itself is feeble, whereas the beat contraction itself is feeble, whereas the beat after the subsequent pause is very strong.after the subsequent pause is very strong.

This response depends partly on the Frank This response depends partly on the Frank Starling mechanism.Starling mechanism.

Intrinsic control of contractilityIntrinsic control of contractility The beat is weak because not enough time has The beat is weak because not enough time has

elapsed to allow much of the calcium taken up by the elapsed to allow much of the calcium taken up by the sarcoplasmic reticulum during the preceding sarcoplasmic reticulum during the preceding relaxation to become available for release.relaxation to become available for release.

Conversely, the postextrasystolic beat is considerably Conversely, the postextrasystolic beat is considerably stronger than normal. stronger than normal.

The reason is that after the pause between beats, the The reason is that after the pause between beats, the sarcoplasmic reticulum had available for release the sarcoplasmic reticulum had available for release the calcium had been taken up during two heartbeats: the calcium had been taken up during two heartbeats: the extrasystole and the preceding normal beat.extrasystole and the preceding normal beat.

This effect is in addition to the increased preload from This effect is in addition to the increased preload from the PVC.the PVC.

Extrinsic control of contractilityExtrinsic control of contractility

SympatheticSympathetic Changes contractility can be evoked by stimulation of Changes contractility can be evoked by stimulation of

the left stellate ganglia.the left stellate ganglia. Neurally released norepinephrine or circulating Neurally released norepinephrine or circulating

catecholamines interact with beta adrenergic catecholamines interact with beta adrenergic receptors on the cardiac cell membrane.receptors on the cardiac cell membrane.

The peak pressure and the maximal rate of pressure The peak pressure and the maximal rate of pressure rise [dP/dt] during systole are markedly increased.rise [dP/dt] during systole are markedly increased.

The duration of systole is reduced and the rate of The duration of systole is reduced and the rate of ventricular relaxation is increased during the early ventricular relaxation is increased during the early phases of diastole.phases of diastole.

The briefer systole allows more time for diastole and The briefer systole allows more time for diastole and hence for ventricular filling.hence for ventricular filling.


ParasympatheticParasympathetic Vagal stimulation decreases the peak left ventricular pressure, Vagal stimulation decreases the peak left ventricular pressure,

maximal rate of pressure development [dP/dt], and maximal rate maximal rate of pressure development [dP/dt], and maximal rate of pressure decline during diastole.of pressure decline during diastole.

The acetylcholine interact with muscarinic receptors which The acetylcholine interact with muscarinic receptors which inhibits adenyl cyclase.inhibits adenyl cyclase.

The consequent fall in cAMP diminishes the calcium conduction The consequent fall in cAMP diminishes the calcium conduction of the cardiac cell membrane, reduces phosphorylation of the of the cardiac cell membrane, reduces phosphorylation of the calcium channels, and hence decreases myocardial contractility.calcium channels, and hence decreases myocardial contractility.

The acetylcholine released from vagal endings can also inhibit The acetylcholine released from vagal endings can also inhibit norepinephrine release from neighboring sympathetic nerve norepinephrine release from neighboring sympathetic nerve endings.endings.


Other hormonesOther hormones CortisolCortisol

Hydrocortisone potentates the cardiotonic effects of Hydrocortisone potentates the cardiotonic effects of catecholamines. This may be mediated in part by inhibition catecholamines. This may be mediated in part by inhibition of the extraneuronal uptake of catecholamines.of the extraneuronal uptake of catecholamines.

Thyroid hormonesThyroid hormones The rate of calcium uptake and of ATP hydrolysis by the The rate of calcium uptake and of ATP hydrolysis by the

sarcoplasmic reticulum are increased in response to excess sarcoplasmic reticulum are increased in response to excess thyroid hormones.thyroid hormones.

Thyroid hormones increase protein synthesis in the heart Thyroid hormones increase protein synthesis in the heart which can lead to cardiac hypertrophy.which can lead to cardiac hypertrophy.

These hormones also affect the composition of myosin These hormones also affect the composition of myosin isoenzymes in cardiac muscle. They increase principally isoenzymes in cardiac muscle. They increase principally those isoenzymes with the greatest ATPase activity, and those isoenzymes with the greatest ATPase activity, and thereby enhance myocardial contractility thereby enhance myocardial contractility


InsulinInsulin Insulin has a predominant, direct, positive inotropic Insulin has a predominant, direct, positive inotropic

effect on the heart.effect on the heart.

GlucagonGlucagon Effect of glucagon on the heart closely resemble Effect of glucagon on the heart closely resemble

those of the catecholamines. Both glucagon and those of the catecholamines. Both glucagon and catecholamines activate adenyl cyclase to catecholamines activate adenyl cyclase to increase the myocardial tissue levels of cyclic increase the myocardial tissue levels of cyclic AMP. AMP.

Extrinsic control of contractilityExtrinsic control of contractility pH, PaO2, PaCO2pH, PaO2, PaCO2

Moderate degrees of hypoxia increase heart rate, cardiac Moderate degrees of hypoxia increase heart rate, cardiac output, and myocardial contractility via the sympathetic output, and myocardial contractility via the sympathetic nervous systemnervous system

Severe degrees of hypoxia depress myocardial contractility.Severe degrees of hypoxia depress myocardial contractility. Neither the PaCO2 nor blood pH is a primarily determinant of Neither the PaCO2 nor blood pH is a primarily determinant of

myocardial function, intracellular pH matters.myocardial function, intracellular pH matters. The reduced intracellular pH decreases the amount of The reduced intracellular pH decreases the amount of

calcium release from the sarcoplasmic reticulum in response calcium release from the sarcoplasmic reticulum in response to excitation.to excitation.

The diminished pH also decreases the sensitivity of the The diminished pH also decreases the sensitivity of the myofilaments to calcium.myofilaments to calcium.

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regulation of the heartbeat. outline control of the heart beat intrinsic control of contractility ...

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