Mechanism of arrhythmias Flashcards
Two subtypes of tachycardia and parts of heart they involve
1) Supraventricular tachy: inviolve SA or AV node
2) Ventricular tachy: Originate from His-Purkinje system or ventricles
What are the components of the conducting system of the heart and how are they unique from the rest of the cells of the myocardium?
They are unique becasue they display automaticity, ability to spontaneously generate an AP.
Types:
1) SA node: 60-100 depolarizations/mine
2) AV node: 40-60 depolarizations/ min
3) Ventricular system: 20-40 depolarizations/ min
What currents are active in phase 4 depolarization of pacemaker cells, and how are the channels that carry ions activated?
During phase 4 depolarization, If channels are activated by hyperpolarization. These conduct mainly inward Na+ current and outward K+ current. Inward flow of Na+ current depolarizes membrane toward threshold.
Difference between Na+ channels involved in phase 4 of pacemaker potential and phase 0 of regular atrial/cardiac cells
In phase 4 of pacemaker potentials, there is a slow depolarization due to slow Na+ channels (HCN channels) which generate the If current. In phase 0 of cardiac potentials, the fast Na+ channels are responsible for rapid depolarization.
Why are phase 0 upstroke of SA and AV nodes much slower than that of regular cardiac myocardium?
This is because the number of available (resting-state) fast Na+ channels decreases (more are inactivated) as resting membrane potential becomes less negative. Sinus and AV nodes have a less negative maximum diastolic (resting) membrane voltage (-50 to -60 mV) compared to myocardial resting membrane potential (-90 mV); as a result, majority of fast Na+ channels are inactivated in SA/AV nodal cells. Upstroke in these cells is determined by a Calcium current, via relatively slower opening of L-type Ca2+ channels.
What determines the proportion of fast sodium channels that are available (resting state) compared to inactivated state?
The resting membrane (diastolic) potential. AV and SA nodal cells have a less negative membrane potential (-50 to -60 mV) than that of myocardial cells; thus, most fast Na+ channels are inactivated and rely on Ca2+ channels for the upstroke.
What current is involved in repolarization of pacemaker cells and what activates this?
K+ efflux via opening of VG K+ channels; activated by inactivation of Ca2+ channels
What affects the automatic rates of firing in pacemaker cells (3)? How does each affect the rate?
1) The rate (e.g.) of phase 4 spontaneous depolarization
2) The maximum diastolic potential
3) Threshold potential
How does If affect the rate of firing of pacemaker cells?
Greater the If, the steeper the slope of phase 4 depolarization and faster the cell will reach the threshold potential ⇒ increase in rate.
Smaller the If, the more shallow the slope of phase 4 depolarization and slower the cell will reach the threshold potential ⇒ decrease in rate.
How does the threshold potential affect the pacemaker cells’ rates of firing?
More negative the threshold potential, the time to threshold potential from maximal diastolic potential is decreased ⇒ increased firing rate.
Less negative the threshold potential, the time to threshold potential from maximal diastolic potential is increased ⇒ decrease in firing rate.
How does maximal diastolic potential affect the firing rate of pacemaker cells?
More negative the maximal diastolic potential, the longer time it will take to reach threshold potential ⇒ decrease in firing rate.
Less negative the maximal diastolic potential, the shorter time it will take to reach threshold potential ⇒ incrase in firing rate.
Overdrive suppression
Phenomenon in which the fastest intrinsic rhythm cells (e.g. SA node) suppresses slower automaticity cell’s activity. This is because the Na+/K+ pump, which maintains the normal ion distributions, moves 3 Na+ out while moving 2K+ in, meaning that the inside keeps getting more negative and therefore becomes more hyperpolarized. This is increased when a cell is caused to fire more frqeuently than its intrinsic automaticity rate because the more often it is depolarized via If current from a faster cell, the greater the quantity of Na+ ions that enter the cell per time. Thus, as a result of more Na+ coming in, the Na+/K+ pump becomes more active to restore the Na+ gradient ⇒ larger hyperpolarizing current ⇒ decreases spontaneous depolarization.
How is overdrive suppression related to the various pacemaker cells?
Since the SA node is has the fastest rates of firing, it makes AV nodes and ventricular myocytes fire than their intrinsic automaticity rates, making them more hyperpolarized via the Na+/K+ ATPase. As a result, their rate of spontaneous depolarization is decreased, which decreases their automaticity and making it less likey for them to fire alone.
What happens when pacemaker cells and nonpacemaker cells are connected via gap junctions?
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When a pacemaker an nonpacemaker cells are connected via gap junctions, this affecst their electric potential due to the electrotonic current flow between the cells. Pacemaker cells have a maximum diatsolic potential of about -60 mV while myocardial cells in ventricle have resting potential of about -90 mV. This connection causes relative hyperpolarization of the pacemaker cells, while causing relative depolarization of the nonpacemaker cells. Because the pacemaker cells are hyperpolarized, this makes the diastolic potential more negative, slowing the heart rate.
How do gap junctions with nonpacemaker cells affect AV nodes, SA nodes, and Purkinje fibers?
AV nodal cells are connected to atrial myocytes, while Purkinje fibers are coupled to ventricular myocardial cells, both via gap junctions. This hyperpolarizes the pacemaker cells, suppressing the automaticity of these cells. In contrast, SA nodal cells are less tightly connected to their neighboring atrial myocytes via gap junctions; as a result, their automaticity is less suppressed.
What would happen to automaticity if nonpacemaker cells connected to AV nodal cells/ Purkinje fibers were impaired (e.g. ischemic damage)?
The pacemaker cells wouldn’t get hyperpolarized as much without the nonpacemaker cells’ influence in electric potential; thus, they would be more likely to fire ectopic rhythms since their automaticity isn’t as suppressed.
What is abnormal impulse generation and what are the different mechanisms that cause this (3)
Abnormal impulse generation is arrhythmia arising from one area of the heart. Main mechanisms:
1) Altered automaticity (of SA or latent pacemakers)
2) Abnormal automaticity in atrial or ventricular myocytes
3) Triggered activity
What is the most important modulator of normal SA node automatcitiy?
Autonomic nervous system
How does SNS affect the SA node automaticity?
SNS activates beta-1 receptors ⇒ increase in HR (e.g. exercise, stress). It does this by:
SNS (e.g. epinephrine) stimulation increases probability of opening pacemaker channels (HCN channels) for If current for any level of membrane voltage. By increasing If flow, the slope of phase 4 depolarization is steeper, and SA node will reach threshold potential faster and earlier than normal ⇒ tachycardia.
How does parasympathetic nervous system affect SA node automaticity?
Normal decreases in SA node automaticity are mediated by this (e.g. at rest). Cholinergic (parasympathetic) stimulation via vagus nerve acts on the SA node in 3 ways:
1) Reduced If: reduces probability of pacemaker channels (HCN channels) being open at any given membrane potential, decreasing the slope of phase 4 depolarization ⇒ slower HR
2) Less negative threshold potential: probability of Ca2+ channel being open is decreased (Phase 0)
3) More negative maximum diastolic potential: increase probability of ACh-sensitive K+ channels being open at rest ⇒ K+ ions exit at rest.
Types of arrhythmias due to abnormal automaticity of atrial/ventricular cells (4)
1) Ventricular Premature Complexes
2) Ventricular Tachycardia
3) Atrial Premature Complexes
4) Atrial Tachycardia
How does abnormal automaticity in non-pacemaker cells occur?
Cardiac tissue injury may lead to pathologic changes in myocardial cells outside of specialized conduction system acquires automaticity that normally do not possess it. If rate of depolarization of cells exceeds sinus node, they can take over pacemaker function. This occurs bc when cardiac tissue becomes injuerd, they become “leaky” and the resting membrane potential becomes less negative (cell partially depolarizes) and can have gradual phase 4 depolarization.
What are examples of arrhythmias due to enhanced automaticity of latent pacemakers? (2)
1) Junctional premature complexes
2) Junctional tachycardia
What are the two different ways in which “triggered activity” can lead to arrhythmias?
1) Early afterdepolarizations
2) Delayed afterdepolarizations
When do early afterdepolarizations occur and in what type of action potentials (long vs. short) is this usually seen?
They occur during repolarization phase- either during plateau phase (phase 2) or during rapid repolarization (phase 3). They are more likely to occur in situations in which action potentials are prolonged (prolonged QT interval) e.g. during therpay with certain drugs such as antiarrhythmics that block K+ currents or congenital long QT syndromes.
