Arryhthmia mechanism

Question 1

Cardiac arrhythmias are more commonly acquired or inherited?

Answer 1

acquired

Question 2

Common causes of arrhythmias

Answer 2

myocardial infarction, ischemia, acidosis, alkalosis, electrolyte abnormalities, or excessive catecholamine exposure, drug toxicity (glycosides, antihistamines, antibiotics)

Question 3

Which drugs are the only ones that have demonstrated reduced incidence of sudden cardiac death?

Answer 3

beta blockers

Question 4

Generally, what is long QT syndrome?

Answer 4

prolongation of the duration of the cardiac action potential (QT interval) that can lead to ventricular arrhythmia and sudden death

Question 5

Which phase of cardiac cycle is prolonged in long QT syndrome? What type of AP’s are affected, in what type of cells, and what is the result?

Answer 5

In this disease, prolongation of the plateau phase (phase 2) of the fast response action potential in ventricular myocytes initiates a polymorphic ventricular tachycardia called torsades de pointes

Question 6

Torsades de pointes can degenerate into what?

Answer 6

ventricular fibrillation followed by syncope and sudden cardiac death.

Question 7

What are common triggers of Torsades de pointes?

Answer 7

an abrupt increase in sympathetic tone as occurs with emotional excitement, fright, or physical activity, causes enhanced Ca influx. This is why we treat long QT with Beta blockers

Question 8

What is the genetic cause of long QT syndrome?

Answer 8

Mutations in cardiac ion channels

Question 9

Describe the different genetic forms of long QT syndrome

Answer 9

Romano-Ward syndrome: autosomal dominant mutations mostly in Ks, Kr or Na channels. Jervell-Lange-Nielson syndrome: autosomal recessive mutations mostly in Ks. Homozygotes suffer from additonal congenital deafness. Heterozygotes are asymptomatic

Question 10

Differentiate between the mutations in K channels vs Na channels in long QT syndrome

Answer 10

K channel mutations are loss of function mutations that reduce the number of K channels. Na channel mutations are gain of function mutations that prevent Na channels from inactivating completely.

Question 11

What are the ion channel effects for the specific long QT types?

Answer 11

1. LQT3- incomplete Na inactivation. (increased inward Na) 2.LQT8- incomplete Ca-L inactivation 3. LQT2, LQT6 (alpha, beta subunits)- decreased Kr current.4. LQT1, LQT5 (alpha, beta)- decreased Ks current. 5. LQT7-decreased K1 current during diastole

Question 12

What type of drug should be used for LQT3 mutation? LQT1/LQT2?

Answer 12

LQT3- drugs that block Na channels. LQT2/1- drugs that open K channels

Question 13

What are other types of congenital arrhythmias?

Answer 13

Brugada syndrome reduces peak inward Na current. Yotiao mutations allow for upregulated Ca channel activity but not K channels.

Question 14

Name two mechanisms for arrhythmia generation

Answer 14

(1) inappropriate impulse initiation in SA node or elsewhere (ectopic focus), and (2) disturbed impulse conduction in nodes, conduction cells (Purkinje cells) or myocytes

Question 15

What causes an innapropriate impulse initiation?

Answer 15

a.) ectopic foci: because normal SA nodal pacemaker is abnormally slow, or ectopic focus is abnormally fast OR infarct causes membrane to depolarize (decrease in [K+]i occurs as Na/K-ATPase fails). B.) triggered afterdepolarizations: triggered by action potential

Question 16

What are the types of afterdepolarizations?

Answer 16

1. Early afterdepolarizations (EADs): appear during late phase 2 and phase 3. Largely dependent upon re-activation of RyR Ca2+ channels in response to elevated [Ca2+]in. Prolongation of phase 2 (long QT) contributes to elevated [Ca2+]in. 2. delayed afterdepolarizations (DADs): during early phase 4. Initiated by elevated [Ca2+]in and, consequently, elevated Na+/Ca2+ exchange which pumps 3 Na into the cell for every 1 Ca removed causing depolarization

Question 17

Describe the Na/Ca exchanger

Answer 17

“the Na+/Ca2+ exchanger is electrogenic: 3 Na+ move in for 1 Ca2+ moved out. Net increase in positive charge inside myocytes corresponds to depolarization
this exchanger is called NCX, and the current it generates is INCX”

Question 18

What causes a disturbed impulse conduction?

Answer 18

a.) conduction block: 1°: long P-R interval, 2°: some P waves not followed by QRS, 3°: no relationship between timing of P and QRS (called “complete heart block” requires pacemaker). B.) re-entry: means loop current flowing – also called “circus rhythm”. Can occur in every type of cell in heart and can be small, large, atrial and/or ventricular.

Question 19

re-entrant arrhythmias require what two conditions?

Answer 19

(i) uni-directional conduction block in a functional circuit. (ii) conduction time around the circuit is longer than the refractory period

Question 20

Arrhythmia is usually triggered by _____________ but maintained by _______________

Answer 20

Triggered by afterdepolarizations, maintained by re-entry