MECHANISMS OF CARDIAC ARRYTHMIAS

Disorders of heart rhythm result from alterations of impulse formation, impulse

conduction, or both.

Normal Impulse Formation

Secara umum, electrical impulse itu dihasilkan oleh specialized cardiac cells yang
memiliki intrinsic automaticity (cell’s ability to depolarize itself to a threshold
voltage to generate spontaneous action potential) e.g. SA node, AV node and
ventricular conducting system (bundle of His, bundle branches, Purkinje fibers) 
pacemaker cells
1. Ionic Basis of Automaticity
 Cells with natural automaticity do not have a static resting voltage 
they display gradual depolarization during phase 4 of AP (due to the
pacemaker current)
 Threshold pacemaker cells before opening the Na+ channels itu
biasanya around -60mV
 Gradual depolarization (beda sama myocyte cell contraction yang
rapid), due to: (1) slow inward Ca2+ current, (2) progressive decline of
an outward K+ current, and (3) additional Na+ current via activation of
Na-Ca exchanger from sarcoplasmic reticulum (“calcium clock”)
  Kenapa depolarization pacemaker cells lebih lambat dibandingkan
myocyte? Because membrane potential determines the proportion
of fast Na+ channels capable of depolarization, semakin negatif
membrane voltagenya, semakin banyak fast Na+ channels yang
available for ion exchange.

 Repolarization phase of pacemaker cells depends on inactivation of the

Ca2+ channels and the opening of voltage-gated K+ channels for K+
efflux.
2. Native and Latent Pacemakers
 The pacemaker cells with the fastest rate of depolarization set the
heart rate.
 Dominant pacemaker in the normal heart: SA node (rate: 60-100bpm)
 Native pacemakers: SA node (because it sets the heart rate)
 Latent pacemakers (ectopic pacemakers): other cells within the
specialized conduction system that has the same potential to act as a
pacemaker (if necessary) e.g. AV node & Purkinje system (firing rate:
30-40 bpm)  these latent pacemakers may initiate and take over the
pacemaking function if SA node slows/fails to fire/conduction
abnormalities block the normal wave of depolarization.
3. Overdrive Suppression
 The cells preempt all other automatic cells from spontaneously firing
but also directly suppresses their automaticity  overdrive
suppression
  Overdrive suppression decreases cell’s automaticity when that cell is
driven to depolarize faster than its intrinsic discharge rate.
 Hyperpolarization: 3 Na+ keluar, K+ masuk. Ada 1 positive ion diluar to
create the membrane to be more negative  cell potential (inside the
membrane) becomes more negative  additional time is required for
spontaneous phase 4 (depolarization) to reach the threshold.
 Hyperpolarizaton current meningkat apabila cells ini dipaksa untuk
meningkatkan firing rate mereka (lebih dari normal)  overdrive
suppression  decreases firing rate.
4. Electronic Interactions
 Gangerti

Altered Impulse Formation

1. Alterations in SA Node Automaticity
They are regulated primarily by neurohormonal factors.
A. Increased SA Node Automaticity
- Important modulator of normal SA automaticity: ANS
- Sympathetic stimulation (beta-adrenergic receptors): increases
the open probability of the pacemaker channels  increase of
pacemaker current  steeper slope in phase 4 depolarization 
SA node reaches threshold and fire earlier than normal  HR
increases.
- Sympathetic activity increases the rate of pacemaker
depolarization via pacemaker current and by causing the action
potential threshold to become more negative.
- E.g: exercise, emotional stress.
B. Decreased SA Node Automaticity
- Caused by PNS
- Cholinergic stimulation via vagus nerve  reduce the
probability of pacemaker channels to be opened  reduced
pacemaker current and reduced slope of phase 4 depolarization
 slowed intrinsic firing rate  decreased HR
 - Reduced pacemaker current, more negative maximum diastolic
potential, and less negative threshold level  slows the intrinsic
firings  reduced heart rate
2. Escape Rhythms
 Sinus node becomes suppressed  fires less frequently  site of
impulse formationnya berubah jadi latent pacemaker
 Impulse initiated by latent pacemaker = escape beat.
 Persistent impairment of SA node will allow a continued series of
escape beats = escape rhythm (they are actually protective, to
prevent the HR becomes pathologically slow)
 Decreased HR usually caused by the activation of PNS. Bagian
jantung itu beda-beda sensitivitynya sama PNS stimulation. Yang
paling sensitive SA-AV node  atrial tissue  ventricular conducting
system
 Moderate parasympathetic stimulation: slows SA node  pacemaker
shifts to AV node
 Strong parasympathetic stimulation: SA&AV node becomes
suppressed  ventricular escape pacemaker
 The beat is usually late and terminates a pause caused by slowed
sinus rhythm.
3. Enhanced Automaticity of Latent Pacemakers
 Latent pacemaker develops an intrinsic rate of depolarization faster
than SA node = ectopic beat
 The impulse is premature (lebih cepet daripada sinus rhythm)
 Sequence of similar ectopic beats = ectopic rhythm
 Usually caused by: high catecholamine concentration, hypoxemia,
ischemia, electrolyte disturbances, drug toxicities (digoxin intoxication)
4. Abnormal Automaticity
 Cardiac tissue injury  pathologic changes in impulse formation 
myocardial cells diluar specialized conduction system acquire
automaticity & spontaneously depolarize
  Injured myocyte  membrane nya jadi “leaky” atau bocor  unable to
maintain concentration gradient of ion  resting potential jadi lebih gak
negatif
Triggered Activity
 Action potential can trigger abnormal depolarization  extra heart beat
or rapid arrythmias
 This type of automaticity is stimulated by a preceeding acton potential
 Early after depolarization (EAD): menganggu repolarisasi  may
initiate TdP
 Delayed after depolarization (DAD): terjadi setelah repolarisasi 
biasanya terjadi karena calcium intracellular nya tinggi, biasanya ada di
kondisi intoksiasi digitalis  atrial & ventricular tachycardias associated
with digitalis toxicity

Altered Impulse Conduction

1. Conduction Block
 Propagating impulse is blocked karena ada bagian dari jatung yang
udh electrically unexcitable
 Can be transient or permanent
 Caused by ischemia, fibrosis, inflammation, and certain drugs
 Functional block: conduction block occurs waktu ada electrical impulse
yang dateng ke cardiac cells yang lagi “rest” (masih di dalam RF period
setelah depolarisasi) (e.g. antiarrythmic drugs)
 Fixed block: karena ada barrier yang disebabkan oleh fibrosis/scarring
2. Undirectional Block and Reentry