Generation of action potential and its conduction in heart ... · • early after-depolarisation...

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Electro(patho)physiology Generation of action potential and its conduction in heart Abnormalities of the heart rhythm Cardiac output – CO = SV x f Resting membrane potential – One ion • Nernst equation – Several ions • Goldmann equation • Determined by: – fixed intracellular anions – membrane permeability • i.e. density and channel gating – Na + /K + -ATP-ase Cardiac automacy • Due to physiologic instability of membrane potential of P cells of the SA node time (s) 0 -40 -80 threshold potential time (s) 0 -50 -90 absolute refractory phase cell of the SA node contractile myocyte cationt channels (mainly Na + ) Ca 2+ channels relative refractory phase 250ms resting potential action potential Na + channels Ca 2+ channels K + channels Na+/K+ ATP-ase Na+/K+ ATP-ase Temporal and spatial coordination of potential changes Conductory system of the heart • SA node – internodal atrial tracts • Bachmann, Thorel, Wenckebach • Atrioventricular (AV) junction – AV node – AV bundle • Right and left bundle branch • anterior and posterior fasciculus • Pukrynje fibres

Transcript of Generation of action potential and its conduction in heart ... · • early after-depolarisation...

Page 1: Generation of action potential and its conduction in heart ... · • early after-depolarisation – manifests as a ventricular tachyarrhythmia • late after-depolarisation – manifests

Electro(patho)physiologyGeneration of action potential and

its conduction in heart

Abnormalities of the heart rhythm

Cardiac output – CO = SV x f

Resting membrane potential

– One ion

• Nernst equation

– Several ions

• Goldmann equation

• Determined by:

– fixed intracellular anions

– membranepermeability

• i.e. density and channel gating

– Na+/K+-ATP-ase

Cardiac automacy

• Due to physiologicinstability of membranepotential of P cells of the SA node

time (s)

0

-40

-80

threshold potential

time (s)

0

-50

-90

absolute refractory phase

cell of the SA node

contractile myocyte

cationtchannels

(mainly Na+)

Ca2+ channels

relative refractory phase

250ms

resting potential

action potential

Na+ channels

Ca2+

channels

K+ channels

Na+/K+ ATP-ase

Na+/K+ ATP-ase

Temporal and spatial coordination of potential changes

Conductory system of the heart • SA node

– internodal atrialtracts• Bachmann, Thorel,

Wenckebach

• Atrioventricular (AV)junction– AV node

– AV bundle

• Right and left bundle branch

• anterior and posterior fasciculus

• Pukrynje fibres

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Connection between cardiocytes

• gap junctions

– intercellular channels (d=1.5 - 2nm)

– transport of ions and small molecules (<1kDa)

– 4 – 6 connexinsubunits

Dominant and auxiliary pacemakers

Excitation – contractioncoupling

Excitation – contractioncoupling

Ion channels

• Voltage gated

–Na+ channels

–K+ channels (Kv, Kir)

–T-Ca2+ channels, L-Ca2+ channels (DHP)

• Ligand gated (G-protein)

–K+ channel sensitive to acetylcholine

–K+ channel sensitive to adenosine

• Ligand gated (without G-protein)

–K+ channel sensitive to ATP

• Mechanically gated (stretch)

Contractile apparatus

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Classification of heart rhythm abnormalities = arrhythmias• (1) according to effect

– tachycardia (>100/min, regular), tachyarrhythmia (irregular)– bradycardia (<60/min, irregular), bradyarrhythmia (irregular)

• (2) according to origin– supraventricular– ventricular

• (3) according to pathogenesis– pathologic site of excitation

• homotopic• heterotopic (ectopy)• chaotic (flutter, fibrillation)

– pathologic conduction• blockade• preexcitation

• (4) according to aetiology– cardial

• ischemia, remodelation in heart failure and valve disorders (hypertrophy,dilatation), CMP

– extracardial• electrolyte dysbalance, hypoxia, ABB disorders

Abnormal heart conduction• Homotopic automacy =

from SA node

– physiologic

• sinus tachy-/bradycardiaas a consequence of autonomic nervous system activation

• athlete’s bradycardia

• respiratory arrhythmia

– pathologic

• sinus arrest

– periodical arrest followed by escaped excitation

• sick sinus syndrome (SSS)

– paroxysmal bradycardiaevent. alternated by paroxysmal tachycardia

Abnormal automacy

• Heterotopic automacy =not from SA node

• automacy generated I different part of conductive system or event. contractile myocytes

– pasive = escaped rhythm

• compensates missing activity of SA node

– sinus arrest or AV blockades

– causes bradycardia

– active

• extrasystoles

• triggered activity

– follows

Extrasystoles• Atrial• Junctional

– no effect on hemodynamics

– partial compensatory pause

– caused by microreentry

• Ventricular– originates distally from AV

bundle• monotopic vs. polytopic

– complete compensatory pause

– caused by microreentry orby “triggered activity”

– often followed byventricular tachycardia

Triggered activity

• Pathologic spontaneous periodical depolarisation of the part of myocardium

• without impulse from conductive system

– due to instability of membrane potential

– leads to tachyarrhythmia due to:

• early after-depolarisation

– manifests as a ventricular tachyarrhythmia

• late after-depolarisation

– manifests as a extrasystoleor tachyarrhythmia

Long QT syndrome (LQTS)• Disorder of repolarisation

– prolonged influx of Na+ or Ca2+

– prolonged efflux of K+

• (1) inherited form (LQTS1 - 7)• mutation in Na+, Kv

+ and L-Ca2+

channels– Jervell/Lange-Nielsen syndrome

– Romano-Ward syndrome

• (2) acquired form– drugs (antibiotics, diuretics,

antidepressants, statins, ……..)

• genetic disposition???

• Manifestation– ECG abnormality, syncope,

convulsions, arrhythmias(“torsades de points”), sudden death

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Abnormal conduction• Spreading of excitation

via accessory bundle = pre-excitation

• accessory bundles– Kent , James , Mahaim

• acceleration of AV conduction (short PQ interval)

• event. broader QRS ( -wave)

– constant ECG anomaly• Wolf-Parkinson-White

syndrome (WPW)• Lown-Gannong-Levine

syndrome (LGL)

– re-entrant SVT tachycardia• atrial, junctional,

atrioventricular

Re-entry phenomenon

Supraventricular tachycardia Ventricular tachycardia

Abnormal conduction

• Blockades

– SA blockade

• 1. – 3. dg.

• symptoms

– no

– bradycardia,bradyarrhythmia

– AV blockade

• 1. – 3. dg.

• symptoms

– no (1. dg.)

– bradycardia,bradyarrhythmia

– bundle branch blockade

• symptoms

– no

Atrial fibrillation and flutter– depolarisation without obvious

pacemaker• chaotic spreading in fibrillation

– does not generate any pressure

– etiologic factors:• dilatation, hypoxia, changes of

[K+], [Ca2+] or [H+]

• Atrial fibrillation

– fibrillation waves (350-600/min)

– CO ~15%

– frequency irregular, rate normal or tachyarrhythmia

– caused most often by atrialdilatation, could be complicated by thrombus in atria

• Atrial flutter– frequency 250–350-min, regular,

constant AV conduction x:1

– caused by re-entry or early after-depolarisation

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Ventricular fibrillation and flutter• Fibrillation

– f. waves >300/min

– could follow ventricular extrasystole, tachycardia or flutter

– fatal if not terminated soon enough

• unconsciousness (10s), brain death (4-5min)

• Flutter

– waves 250-300/min

– CO (diastolic filling) !!

Vegetative stimulation of heart

Hyper- a hypocalemia• 98% K+ in ICF

• 35x more than in ECF (3.8 –5.5 mmol/l)

• Na+/K+ ATP-ase

• High membrane permeability for K+

• contribution to resting membrane potential

• changes of calemia in ECF quickly reflected in ICF

• Regulation of [K+] in ECF –excretion by kidneys

• aldosterone, [K+], insulin, adrenalin

• Hypercalemia

– slows down depolarisation, accelerates repolarisation

• Hypocalemia

– accelerates depolarisation, slows down repolarisation

ECG signs of [K+] alteration

Hypo- a hypercalcemia• Balance of calcium

– resorbtion form food in intestine(vitamine D)

– excretion by kidneys (parathormon)– resorption vs. formation of bone

(parathormon, kalcitonin)

• total plasma level Ca (2.0 - 2.7mmol/l)– 45 – 50% ionised Ca– Ca bound to proteins (albumin)– complexes with bicarbonate,

phosphate etc.• ionisation of calcium is dependent on

pH• drop of pH leads to increased

neuromuscular excitability– spasms or tetny in resp. alcalosis

• Plasma [Ca2+] influenced also by phosphates– product of concentration of calcium

and phosphates is roughly constant

• Hypercalcemia– accelerates repolarisation

• Hypocalcemia slows down

HYPOCALCEMIA

HYPERCALCEMIA

prolongation of QTinterval

shortening of QT interval

Manifestation and consequences of arrhythmia• Benign

• Manifest

– hemodynamicallysignificant -influencing cardiac output!!!

– sudden death risk

– Subjective

• palpitation

• skip of heart beat

• dyspnoe

• fatigue

– Objective

• irregular frequency

• syncope

• symptoms of heart failure

• cardiac arrest

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The most common arrhythmia Summary of consequences of arrhythmias

origin tachyarrhythmia bradyarrhythmia

SA node sin. tachycardia sin. bradycardia

atria extrasystols, flutter, fibrillatin, paroxysmal and non-paroxysmal SVT

sick sinus syndrome,escaped rhythms

AV junction paroxysmal SVT blockade of 2nd and 3rddg.

chambers extrasystols, tachycardia, (incl. “torsade de pointes”), flutter, fibrillation

Practicals