Cardiovascular PhysiologyQiang XIA (), MD & PhDDepartment of PhysiologyRoom C518, Block C, Research Building, School of MedicineTel: 88208252Email: xiaqiang@zju.edu.cn

Components of the cardiovascular system:HeartVascular systemBloodSystem Overview

Plasma includes water, ions, proteins, nutrients, hormones, wastes, etc.

The heart is the pumpthat propels theblood through the systemic and pulmonary circuits.

Red color indicates blood that isfully oxygenated.

Blue color representsblood that is only partially oxygenated.

The distribution of blood in a comfortable, restingperson is shown here.

Dynamic adjustments inblood delivery allow aperson to respond to widely varying circumstances, including emergencies.

Functions of the heartPumpingEndocrineAtrial natriuretic peptide (ANP)Brain natriuretic peptide (BNP)Other bioactivators

The major external andinternal parts of the heart areshown in thisdiagram.

The black arrowsindicate the routetaken by theblood as it ispumped along.The Heart

Valves of the heart

The general route of the blood through the body is shown, including passage through the heart (colored box).

The major types of cardiac muscle:Atrial muscleVentricular muscleSpecialized excitatory and conductive muscleContractile cellsAutorhythmic cells

Conducting system of the heart

Cardiac muscle

The sinoatrial node is the hearts pacemaker because it initiates each wave of excitation with atrial contraction. The Bundle of His and other parts of the conducting system deliver the excitation to the apex of the heart so that ventricular contraction occurs in an upward sweep. Sequence of cardiac excitation

General process of excitation and contraction of cardiac muscleInitiation of action potentials in sinoatrial nodeConduction of action potentials along specialized conductive systemExcitation-contraction couplingMuscle contraction

(250-300 bpm)(350-600 bpm)

Transmembrane potentials recorded in different heart regions

Transmembrane potentials in epicardium and endocardium

Transmembrane potential of ventricular cells and its ionic mechanismsResting Potential: -90 mVAction PotentialPhase 0: Depolarization Phase 1: Early phase of rapid repolarization Phase 2: PlateauPhase 3: Late phase of rapid repolarization Phase 4: Resting phase

Resting potentialK+ equilibrium potential Na+-inward background currentElectrogenic Na+-K+ pumpIonic mechanisms

Phase 0Threshold potential (-70mV)Opening of fast Na+ channel Regenerative cycleThe action potential of a myocardial pumping cell.

Phase 1Transient outward current, Ito K+ current activated at 20 mVopening for 5~10 ms Phase 2Inward currentOutward current(Ca2+ & Na+) (K+ current)

Ca2+ channelsDuration of currentlong-lastingtransientActivation kineticsslowerfasterInactivation kineticsslowerfasterThresholdhigh (-35mV)Low (-60mV)cAMP/cGMP-regulatedYesNoPhosphorylation-regulatedYesNoOpenersBay-K-8644-BlockersvarapamilTetramethrinnifedipine, diltiazemNi2+ Inactivation by [Ca2+]iYesslightPatch-clamp recordingrun-downrelatively stableL-type T-typeTypes of Ca2+ channels in cardiac cells: (1) L-type (long-lasting) (Nowycky, 1985) (2) T-type (transient) (Nowycky, 1985)

Outward current (K+ current): (1) inward rectifier K+ current (IK1)(2) delayed rectifier K+ current (IK)

Phase 3Inactivation of Ca2+ channelOutward K+ current dominates IK: Progressively increased IK1: Regenerative K+ Outward Current

Phase 4Na+-Ca2+ exchange Sarcolemmal Ca2+ pump SR Ca2+ pump Na+-K+ pump

a, The key ion channels (and an electrogenic transporter) in cardiac cells. K+ channels (green) mediate K+ efflux from the cell; Na+ channels (purple) and Ca2+ channels (yellow) mediate Na+ and Ca2+ influx, respectively. The Na+/Ca2+ exchanger (red) is electrogenic, as it transports three Na+ ions for each Ca2+ ion across the surface membrane. b, Ionic currents and genes underlying the cardiac action potential. Top, depolarizing currents as functions of time, and their corresponding genes; centre, a ventricular action potential; bottom, repolarizing currents and their corresponding genes.From the following article:Cardiac channelopathiesEduardo MarbnNature 415, 213-218(10 January 2002)doi:10.1038/415213a

Transmembrane potential of autorhythmic cells and its ionic mechanisms

Transmembrane potentials recorded in different heart regions

Contractile cellsAutorhythmic cells Phase 4 stable potentialPhase 4 spontaneous depolarization4

Resting potentialMaximal repolarization potential

Purkinje cells: Fast response autorhythmic cells 4

Ionic mechanismPhase 0~3similar to ventricular cellsPhase 4(1) If Funny current, Pacemaker current (2) Ik Decay

Characteristics of If channelNa+, K+Voltage- & time-dependent Activation Repolarized to -60mV Full activation Hyperpolarized to -100mV Inactivation Depolarized to -50mVBlocked by Cesium (Cs), not by TTX

Sinoatrial cells

Maximal repolarization potential -60mVThreshold potential -40mVPhase 0, 3, 4Sinoatrial cells: Slow response autorhythmic cells

Ionic mechanismPhase 0: ICa (ICa,L) Phase 3: Inactivation of L-type Ca2+ channelOutward K+ current (Ik)

The action potential of an autorhythmic cardiac cell.Phase 4Ik decayInactivated when repolarized to -60mVICa,TActivated when depolarized to -50mVIf

During which phase of the ventricular action potential is the membrane potential closest to the K+ equilibrium potential?(A) Phase 0(B) Phase 1(C) Phase 2(D) Phase 3(E) Phase 4

During which phase of the ventricular action potential is the conductance to Ca2+ highest?(A) Phase 0(B) Phase 1(C) Phase 2(D) Phase 3(E) Phase 4

Which phase of the ventricular action potential coincides with diastole?(A) Phase 0(B) Phase 1(C) Phase 2(D) Phase 3(E) Phase 4

The low-resistance pathways between myocardial cells that allow for the spread of action potentials are the(A) gap junctions(B) T tubules(C) sarcoplasmic reticulum (SR)(D) intercalated disks(E) mitochondria

Electrocardiogram (ECG)The electrocardiogram (ECG) measures changes in skin electrical voltage/potential caused by electrical currents generated by the heart

The relationship between the electrocardiogram (ECG), recorded as the difference between currents at the left and right wrists,

and

an action potential typical of ventricular myocardial cells. Electrocardiogram (ECG)

The standard 12 lead ECG Einthovens Triangle

Limb leads (Bipolar) (I, II, III)Augmented limb leads (Unipolar) (aVR, aVL, aVF)Chest leads (Unipolar) (V1, V2, V3, V4, V5, V6) Willem Einthoven: Dutch physiologist. He won a 1924 Nobel Prize for his contributions to electrocardiography.

Placement of electrodes in electrocardiography

Normal ECG

Animation of a normal ECG wave

P wave: the sequential depolarization of the right and left atriaQRS complex: right and left ventricular depolarizationST-T wave: ventricular repolarizationU wave: origin for this wave is not clear - but probably represents "afterdepolarizations" in the ventricles

PR interval: time interval from onset of atrial depolarization (P wave) to onset of ventricular depolarization (QRS complex)QT interval: duration of ventricular depolarization and repolarizationST segment: the time period between the end of the QRS complex and the beginning of the T wave, during which each myocyte is in the plateau phase (phase 2) of the action potential

NormalPartial blockComplete block

ExcitabilityAutorhythmicity ConductivityContractilityElectrophysiological propertiesMechanical propertyPhysiological properties of cardiac cells

Factors affecting excitabilityResting potentialThreshold potentialStatus of Na+ or Ca2+ channelsExcitability

HyperkalemiaThe QRS complexes may widen so that they merge with the T waves, resulting in a sine wave appearance. The ST segments disappear when the serum potassium level reaches 6 mEq/L and the T waves typically become tall and peaked at this same range. The P waves begin to flatten out and widen when a patients serum potassium level reaches about 6.5 mEq/L; this effect tends to disappear when levels reach 7-9 mEq/L. Sinus arrest may occur when the serum potassium level reaches about 7.5 mEq/L, and cardiac standstill or ventricular fibrillation may occur when serum levels reach 10 to 12 mEq/L.

Periodic changes in excitability

Premature systole & compensatory pause(extrasystole)

A 39-year-old lady presenting with frequent palpitations lasting a few months

A 39-year-old lady presents to you with frequent palpitations lasting a few months, which are not associated with dizziness, syncope or angina. She has enjoyed good health and is not on any medication or herbal medicine. She is a non-smoker and has no known diabetes, hypertension or hypercholesterolaemia. Her menses is regular and physical examination is unremarkable other than a few premature beats. This is her ECG.

Answers:Ventricular premature beats are noted.

Premature ventricular contractions unmask the P waves

Autorhythmicity

Autorhythmicity SA node100 times/minAV node 50 times/minBundle of His 40 times/minPurkinje fibers 25 times/min

Normal pacemakerSA nodeLatent pacemaker (Ectopic pacemaker [] under pathophysiological conditions) AV node Bundle of HisPurkinje fibers

The possible mechanisms of SA node to control latent pacemakersCaptureOverdrive suppression

Factors Affecting AutorhythmicityMaximal repolarization potentialThreshold potential The rate of phase 4 spontaneous depolarization

Sinus Bradycardia

Pacemaker

Conductivity

Gap junction

SA nodeAtriaA-V node 0.05 m/s0.4 m/s0.02~0.05 m/s

His bundlePurkinje fiber Ventricle1.2~2.0 m/s2.0~4.0 m/s1.0 m/s Conducting velocityAtrioventricular delay: Asynchronization of atrial and ventricular depolarization to provide adequate cardiac output

Factors Affecting ConductivityStructural factorsDiameter of cardiac cellsGap junctions at Intercalated diskPhysiological factorsThe velocity and amplitude of phase 0 depolarizationExcitability of adjacent region

First Degree AV BlockDefinition: 1AVB is a rhythm in which the electrical impulse which leaves the SA node and travels through the atria, AV node, Bundle of His to purkininjie fibers is slowed down and takes longer than normal to arrive at its destination. The normal PR interval is 0.12- 0.20 seconds. A 1AVBT is greater than 0.20 seconds. The cause ranges from coronary heart disease, inferior wall MI's, hyperkalemia, congenital abnormalities, and medications such as quinidine, digitalis, beta blockers, and calcium channel blockers.

Second degree AV Block type 1 (Mobitz)Definition: Second degree AV block is also known as Second Degree Type I, Mobitz I, or Wenckelbach. This arrhythmia is characterized by a progressive delay of the conduction at the AV node, until the conduction is completely blocked. This occurs because the impulse arrives during the absolute refractory period, resulting in an absence of conduction, and no QRS. The next P wave occurs and the cycle begins again. Possible causes are acute inferior wall myocardial infraction, digitalis, beta blockers, calcium channel blockers, rheumatic fever, myocarditis, or excessive vagal tone.

Mobitz II is characterized by 2-4 P waves before each QRS. The PR of the conducted P wave will be constant for each QRS. It is usually associated with acute anterior or anteroseptal myocardial infarction. Other causes are cardiomyopathy, rheumatic heart disease, coronary artery disease, digitalis, beta blockers, and calcium channel blockers. Mobitz II has the potential of progressing into a third degree heart block or ventricular standstill.

Second degree AV Block Type II

A third degree atrial ventricular block is also know as a complete heart block artrioventricular block of 3degree AV block. It is a problem with electrical conduction. All electrical conduction from the atria are blocked at the AV junction, therefore, the atria and the ventricles beat independently from each other. This arrhythmia is dangerous because it significantly decreases cardiac output, and could lead to asystole. Possible causes: acute inferior and anterior myocardic infraction, coronary heart disease, excessive vagal tone, myocarditis, endocarditis, age, edema from heart surgery, and meditation toxicity from digitalis, beta blockers, calcium channel blockers.

Third Degree -- Complete Block

Q-T interval recorded on an ECG primarily corresponds to: A Ventricular repolarization B Ventricular depolarization plus ventricular repolarization C Ventricular depolarization and atrial repolarization D Atrial depolarization and conduction through AV node E Purkinje fibers repolarization

The resting membrane potential of a sinus nodal fiber is A -124 mV B -91 mV C -85 mV D -55 mV E -25 mV

You see a 55-year-old, white female for a routine check-up. On the ECG you see a prolonged PQ interval suggesting a first-degree atrioventricular block. What is the primary pacemaker of the heart? A Sinoatrial node B Atrioventricular node C Atrioventricular bundle D Right and left bundle branches E Purkinje fibers

The End.

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