Cardiac Arrythmias Flashcards
The electrical journey (6)
1) SAN
2) RA
3) AVN - junction point (rhythmically active - needs a poke = AP)
4) LA
5) Bundle of His
6) Pukinje fibres
What are the specialised conductive pathways?
pathways that take the electrical activity to LV + A
why does the AVN have a delay/ is a junction box?
allows for the filling of blood by the contraction of the ventricles
Where + what are the low resistance gap junctions? (3)
Heart is joined by them = heart is called syncytia
they are LR = pathway that does not impede the movement of electrical activity, membrane potential (made of connexons) = allows electrical activity to go through heart (sweeping motion)
connexons come together = connexins
what happens to the AP’s when you have myocardial ischaemia or myocardial infarction?
The non-decaying/decremental process of depolarisation + action potentials (sweeping motion) disappears.
what 3 things in the heart have inherent rhythmic system/pacemaker potential + what generates it? (4)
- SAN : 60-110bpm
- AVN: 40-55bpm
- Bundle of his/purkinje fibres: 25-40bpm
SAN generates/dominant one- fastest
But what happens if the SAN gets damaged?
different pacemaker takes over = but then there’s an imbalance b/w SAN + others
Nodal cells vs myocytes (5)
Nodal (SA/AV):
- cannot contract (because no myosin)
- small ca2+ store SR
- approx -55mV MPV
-unstable MPStability
-relatively slow AP dev
myocyte (atria/ventricle):
- can contract
- well dev SR
- approx -80-90 MPV
-stable MPstability
-fast AP dev
Ventricular action potential graph (5)
Phase 4: Baseline or resting membrane potential
Phase 0: Fast depolarisation
Phase 1: Notch or transient repolarisation.
Phase 2: Plateau depolarisation
Phase 3: Complete repolarisation
what is ion conductance/permeability?
Testing how open a channel is
Phase 4 - Baseline or resting membrane potential (3)
- Dominated by open k+ channels
-No other channels open (@rest)
-Pumps active to restore ionic balance
Phase 0- fast depolarisation (4)
- Depolarisation from adjacent cells produces depolarisation
- Opening of voltage sensitive sodium channels
[encoded by SCN5a gene] - Large influx of sodium {why?} = further depolarisation
- Channels inactivate leading to reduced conductance
Phase 1– Notch or transient repolarisation (3)
- Coincident with NaV1.5 channel inactivation =
Opening of potassium channels - Transiently open Kv channels
[Kv4.2 / 4.3 – why transient?]
Transient repolarisation
Phase 2- Maintained depolarisations (3)
- Voltage-gated calcium channels [CaV1.2] open
- Limited opposing Kv channels as Kv4.3 is transient
- Plateau phase determined by CaV
Phase 3: Complete repolarisation (5)
- CaV and NaV are inactivated
- Kv channels [Kv7.1 and Kv11.1] open to repolarise cell
- Kv7.1 is encoded by KCNQ1
-Kv11.1 is encoded by KCNH2 a.k.a ERG (ether-a-go-go related gene)
- Kv11.1 is susceptible to block by MANY drugs
[consequence?]
What drugs can induce cardiac arrythmias + ventricular fibrillation? (5)
Cardiac arrhythmia and ventricular fibrillation is
rare in the population
-astemizole (deworming)
-ketoconazole (antifungal)
- tefenadine (MOST POP ANTIHIST) = Vfib
- helopredole (psychotic disorders)
- Crisapride brouwer (bowel movements)
How do these drugs cause Arr + Vfib? - ECG (2)
they block the ERG channels
ECG = Vfib: Torsade de pointes (twisting of the points)
Ventricular Ion channel summary image
phase 0-3
Phase 0-3
Phase 1
Phase 3
Phase 3
Phase 4
Action potential of the atria vs ventricle - WHY??? (3)
images
ion channel complex in atria
- atria expresses more K+ = brings it back down into the negative
(IKur, IKAch, etc.)
IKach: opened by the vagus releasing ACh = activating M2r = HR reduces
Myocytes vs Nodal cells - SAN + V’s (3)
images
SAN:
-Low resting K permeability
low/no Kir2.1 expression
-Funny current present High HCN expression
- No NaV low SCN5a expression = sluggish
Ventricles:
- High resting K permeability High Kir2.1 expression
- Negligible funny current Low HCN expression
- Prominent NaV High SCN5a expression = high energy
Regional differences
created by the expression of different ion channels
Q’s to ask: (6)
What are the phases of
an action potential and
what is the main
characteristics ?
What determines
the AP in nodal v
myocyte cells?
What might cause
the cardiac rhythm
alter?
What is a funny
current and why is it
called that?
What is the order of
depolarisation in a
healthy heart?
What would you
target if rhythm is
altered?
2 types of arrthmias:
bradycardia - slow
tachycardia - fast
AHA arrythmia def’s (4)
The term “arrhythmia” refers to any change
from the normal sequence of electrical impulses.
The electrical impulses may happen too fast, too
slowly, or erratically – causing the heart to beat
too fast, too slowly, or erratically.
When the heart doesn’t beat properly, it can’t
pump blood effectively.
When the heart doesn’t pump blood effectively,
the lungs, brain and all other organs can’t work
properly and may shut down or be damaged”
Atrial (a.k.a supra-ventricular) arrhythmias (2)
Atrial flutter (Aflut)
Afib
Ventricular arrhythmias
(2)
ventricular tachycardia (Vtach)
Vfib =killer (pumping no blood)
Vfib =killer = why? (3)
not pumping blood
- because of contractions being too fast
no blood to brain = fainting
no blood to itself
Normal process of electrical pathway (5)
1) APs generated in nodal cells
2) Propagate through gap
junctions to myocytes
3) Activation and
inactivation of sodium
channels = upstoke
4) Balance of calcium and
potassium channels
=plateau
5) Repolarisation and
sodium channels
available
Effective refractory period (2)
3) Activation and
inactivation of sodium
channels = upstoke
4) Balance of calcium and
potassium channels
=plateau
- cannot be stimulated in this specific time frame - don’t respond (dictated by ion channel properties)
- tells you when the cell can be reactivated again
Relative Refractory period
images
some ion channels have started to recover and they’re able to respond to another input ( just before full recovery)
what are arrythmias caused by? + why (4)
Cardiac arrhythmias are generated by abnormal
impulse formation or impulse propagation.
- Changes in the repetitive SAN activity, depending on its pacemaker currents.
- Creation of subsidiary pacemaker formation
in specialized conducting AVN or Purkinje fibres. - Ectopic activity in normally nonautomatic
atrial and ventricular cardiomyocytes when they
are depolarized by some pathological processes (- assuming heart disease)
-usually as a consequence of defective ion channels,
exchangers or ion handling
images of cardiac arrythmia causes images (3)
Exaggeration of normal cellular capacity to fire.
Increase in funny current = faster SAN depolarisation
Failure to repolarise results in an EARLY after depolarisation that
stimulates adjacent cell
DELAYED after depolarisation induces AP sooner than expected.
Calcium release = NCX current = depolarisation
Maintenance of arrhythmias (3)
Heterogeneities generate obstacles to AP conduction,
around which the AP circulates with slowed conduction velocities.
May reflect altered ion channel or myocardial tissue electric properties
Re-entrant excitation is also facilitated by abnormalities leading to heterogeneities in AP recovery
Re-entrant or circus activity 1 (3)
- Abnormal impulse formation or abnormal
automaticity - Pathological conduction
images:
1) Normal wave of propagation
2) Injury - region of slow conduction
3) Re-entry: Slow retrograde
conduction , Wave split
Re-entrant or circus activity 2 (3)
1) Normal wave of propagation
2) Unidirectional block: Ragged wave front
3) Re-entry
Focal activity def
an abnormal site is generating impulses (WHY?). This site is
often called “ectopic”, which
really means outside the
normal location (i.e. the sinus node)
circus movement def
In re-entry, the impulse
turns around in a loop or a
circuit (a.k.a circus
movement). These can also
occur in the atria or in the
ventricles.
Causes (8)
Acute myocardial infarction (AMI) (no blood = cells ischaemic or die)
Heart failure (chamber remodelling = structural changes = easy to dev + main arrth)
Therapeutic (e.g. digitalis) and abuse drugs (xs na+ drive)
Inherited mutations of cardiac ion channels
Hyperthyroidism
Hypokalemia (especially in anorexia nervosa)
Autonomic dysfunction
Fever
Anti-Arrhythmic mechanism (5)
Target the abnormal automaticity
Target the ectopic activity
Directly:
- Na channel blockers
- Ca channel blockers
Indirectly:
- K channel blockers
Vaughan‐Williams Classification (VWC) (5) BKG
class I – Sodium Channel blockers
Class II – beta adrenoceptor blockers
Class III‐ Potassium channel blockers
Class IV‐ Calcium channel blockers
Others adenosine / digoxin
Class I - function (3)BKG
Reduce ectopic ventricular/atrial automaticity
Reduce DAD‐induced triggered activity
Reduce re‐entrant tendency by converting unidirectional
to bidirectional block
Class 1 - 3 drug types - dw about names (3) BKG
Block NaV1.5 Na+ channel
1a (Dissociation rate: quickly) : Quinidine, dysopyramide, procainamide, ajmaline:
Open channel block, APD duration prolonged due to K block
1b (Dissociation rate: not so quickly): Lidocaine, mexiletine
Rapid onset and dissoc mean little accumulated block, Fast depolarizing tissue or ischemic tissues - affected, Bind to inactive channel state
1c (Dissociation rate: slowly)
flecainide, propafenone
Depression of phase 0 by accumulated block
Problems of Class I (3) BKG
Do not target the damaged tissues
Effectively make healthy tissue like ischaemic
Can stop conduction = asystole
Class Ia also affect K channels = increased risk of torsade de pointes
Class II (3) BKG
Target the abnormal automaticity
Abnormal automaticity may be due to high β adrenergic drive (sympathetic).
β adrenoceptor blockers eg Atenolol or metoprolol
Class II VWC
Class III (5) BKG
Potassium channel blockers
E.G Amiodarone, dronedarone, vernakalant, D‐sotalol,
Achieved by delaying repolarization anywhere in re‐ entrant pathway including healthy regions
This is because cells are inexcitable during AP (refractory to any arrhythmic wavefront)
Prolonging refractory period indirectly blocks Na channels and conduction
Increase in AP recovery time = increased refractory time =decreased re‐entrant tendency
Problems of Class III (3) BKG
Possibility to precipitate LQT prolongation and TdP
Eg SWORD trial (Survival With ORal D‐sotalol) showed:
‐ increased one year mortality with D‐sotalol
Amiodarone decreases thyroid function
Spectrum of class I and class III antiarrhythmics:
relationship with Na and K channel blocking (4) BKG
image
so Na+ and K+ block - work together (opposite levels)
Class1b = neurotoxicity
Class1C + a = good
Class III = tosardes de pointes
Class IV (5) BKG
Reduce conduction in AV node by blocking Ca++
channels
Reduce DADs leading to ectopic activity in atria
/ventricle
Eg verapamil or diltiazem
Not dihydropyridines like nifedipine
Bolus i.v. converts re‐entry in the AV node to sinus
rhythm
High concentration arrives at AV node blocking
conduction in damaged section
Caveats (5) BKG
Reduction inexcitability and prolongation of refractoriness are also
pro‐arrhythmic.pro‐arrhythmic.
Na+ channel block slows conduction thereby promoting re‐entry
β‐AR blockers and Ca2+ channel blockers cause bradycardia and
atrioventricular (AV) block
Extensive APD prolongation especially by selective hERG (K+) channel blockers increases the risk for early afterdepolarizations.
Torsade de pointes, a polymorphic ventricular tachyarrhythmia that
can easily turn into ventricular fibrillation
Modified Vaughan Williams Classification (8)
Class O-rhythm generation
Class Id – late Sodium Channel blockers
Class II- Adenosine
Class III – Atria specific blockers
Class IV- Calcium-release modifiers
Class V- Stretched activated channels
Class VI-Gap junctions
Class VII-environmental remodelling
