Harrison: principles of electrophysiology Flashcards
pathway of cardiac impulse
Pacemaker cells in SA node generate impulse –> atria –> AV node–> bundle of His –> L and R BB –> purkinje –> activation of ventricles
What is the only connection between the atria and ventricles?
AV node
cardiac action potnetial time vs. skeletal muscle cell AP time
Cardiac myocyte action potential time >> skeletal muscle cells
Cardiac: 200-400 ms
Skeletal: 1-5 ms
Think of ventricular AP vs. Atrial AP. Describe difference in the AP curve, and associated channels
Most common ion channel in the heart
voltage gated
Four homogenous subunits (e.g. K channels) or four internally homologous domains (Na and Ca channels)
What is responsible for opening the channel in response to depolarization?
S4- 4th transmembrane segment in the voltage-dependent ion channels
Cardiac arrhythmias result from abnormalities of _____
electrical impulse generation, conduction, or both
What distrubances usually cause bradyarrhythmias?
- impulse formation at level of SA node
- impulse propagation at any level: exit block from sinus node, conduction block in AV node
- impaired conduction in His-Purkinje system
Different mechanisms for Tachyarrhythmias
- Enhanced automaticity (spontaneous depolarization)
- Reentry (circus propagation)
- Triggered arrhythmias (initiated by afterdepolarizations, occur during or immediately after cardiac repolarization, phase 3 or 4 of AP)
Mechanism of ANS on rate of phase 4 depolarization
- PNS: negative chronotropic effect
- release of Ach
- binds Muscarinic receptors
- activate IKACh in nodal and atrial cells
- increases K+ conductance, opposes depolarization, slowing rate of rise of phase 4 AP
- SNS:
- catecholamine release
- activate α– and β–adrenergic receptors
- β1: predominates in pacemaking cells
- both L-type Ca current (ICa-L) and If
- increases the slope of phase 4
Hypokalemia - effect on action potential
- reduces activity of Na/K-ATPase
- Lower potassium levels in the extracellular space
- cause hyperpolarization of the resting membrane potential due to altered K+ gradient
- greater than normal stimulus is required for depolarization of the membrane to initiate an action potential
- reduces repolarizing current
- enhance phase 4 diastolic depolarization
- increase in spontaneous firing
Definition of afterdepolarization, EAD vs. DAD, and difference in mechanisms
Afterdepolarization: spontaneous depolarization
EADs: occur before end of AP (phase 2 and 3)
- enhance of L-type Ca current, inward current
- prolongs AP
- intracellular Ca loading may enhance chance of DAD
DAD: occur during phase 4 after repolarization completion
- increase Ca load in cyotosol and SR
- digitalis glycoside toxicity, catecholamines, and ischemia and nehance Ca loading
Why are pts with ischemia or CHF likely to develop arrhythmias, especially on exposure to AP-prolonging drugs?
- messes with intracellular [Ca2+]
- calcium loading can lead to EADs and DADs
What conditions can predispose generation of EADs and why?
Any condition causing a prolonged AP and QT
-hypokalemia, hypomagnesemia, bradycardia, and drugs (Antiarrhythmics with class IA and III action)
Explain the paradox: decreased [K+]o may decrease membrane potassium currents in the ventricular myocyte
- the reduced extracellular potassium (paradoxically) inhibits the delayed rectifier current IKr
- delays ventricular repolarization
- may promote reentrant arrhythmias,
- Most common arrhythmia mechanism
- definition
- requirements
- reentry
- circulation of an acitvation wave around an inexcitable obstacle
- a premature impulse blocks in the fast pathway and conducts over the slow pathway
- fast pathway can recover, activation wave can reenter fast pathway from retrograde direction
Treatment for bradyarrhythmias due either to primary sinus node dysunfction or atrioventricular conduction defects
permanent pacemaker
ventricular tachyarrhythmias treatment
- antiarrhythmic drugs
- catheter ablation
- implantation of internal cardioverter-defibrillator (ICD)
