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
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
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
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
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
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