Molecular Mechanisms of Arrhythmias Flashcards

1
Q

Almost all arrhythmias are ________.

A

acquired, such as from myocardial infarctions, ischemias, acidoses, alkaloses, drug toxicities, catecholamine exposure, or electrolyte abnormalities

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2
Q

Prolonged QT intervals correspond to ___________.

A

increased action potential duration, such as from blocked Ik channels or sodium channels that fail to inactivate

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3
Q

Mutations that lengthen the QT interval include those that ____________.

A

impair current amplitude through K channels and prevent the sodium channels from closing completely

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4
Q

Explain the pathophysiology of Brugada syndrome.

A

Mutations in sodium channels reduce peak sodium current; ventricular fibrillation results in 40% mortality by age 5.

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5
Q

What are two broad categories of arrhytmia origin?

A

Inappropriate impulse initiation in sinoatrial node or ectopic foci; disturbed impulse conduction in nodes, conduction cells, or myocytes

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6
Q

Only ________ have been shown to reduce the incidence of sudden cardiac death.

A

ß-blockers

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7
Q

Familial long QT syndrome results from a defect in ____________.

A

the phase 2 of fast contractile muscles

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8
Q

Familial long QT syndrome is __________.

A

polymorphic and autosomal dominant

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9
Q

There is another kind of congenital arrhythmia in which cardiac myocytes can upregulate CaL but not _________.

A

Iks, thus, the cell cannot repolarize effectively

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10
Q

Delayed afterdepolarizations occur because __________.

A

the NCX is electrogenic and depolarizes the membrane

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11
Q

A 1° conduction block will lead to a _________ on an ECG.

A

lengthend P-R time

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12
Q

A 2° conduction block will lead to ________ on an ECG.

A

some P waves not followed by QRS waves

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13
Q

A 3° conduction block will lead to _________ on an ECG.

A

no coordination between P waves and QRS waves

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14
Q

What drugs can cause arrhythmias?

A

Sulfamethoxazole, astemizole, terfenadine, and cardiac glycosides

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15
Q

What causes torsades de pointes?

A

Prolonged phase 2

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16
Q

Explain the pathophysiology of Finnish long QT / yotiao syndrome.

A

Yotiao is a protein that binds PKA, CaL, and Ikr, thus activating them. Mutations in Ikr prevent yotiao from chaperoning PKA, and thus Ikr channels do not get up-regulated in response to ß-adrenergic stimulation.

17
Q

What causes early afterdepolarizations?

A

Prolonged QT leads to increased [Ca] and thus reactivated SR [Ca] channels