Cardiac Channelopathies Flashcards

1
Q

What are the main groupings of sudden cardiac death?

What are the causes of this?

A

Long or short QT syndrome

Changes to ventricular myocyte action potentials and ion channel mutations in the ventricles

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2
Q

What are the parts of the normal ECG?

What do these represent?

A

P wave - atrial depolarisation

QRS - ventricular depolarisation

T - ventricular REpolarisation

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3
Q

What is the QT interval?

A

From the START of the QRS to the END of the T

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4
Q

Why is atrial REpolarisation not shown on the ECG?

A

Happens at the SAME TIME as ventricular deoplarisation

So is MASKED by the QRS wave

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5
Q

What is long QT?

A

DELAY of the T wave
Defect in the ventricle REPOLARISATION

Prolonged QT interval

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6
Q

What is short QT?

A

SPEEDING up of the START of the T wave (happens too early)

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7
Q

What channels are involved in the QT interval?

A

Voltage gated Ca2+ channels
Na+ channels
K+ channels

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8
Q

What are the implications of altered QT intervals?

A

Increase risk of VENTRICULAR TACHYCARDIA

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9
Q

What is ventricular tachycardia?

What does increase the risk of?

A
  • Increase in the firing rate of action potentials
  • Increase in the number of CONTRACTIONS of the ventricles

Risk factor of going into VENTRICULAR FIBRILLATION

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10
Q

What is ventricular fibrillation?

A

Contraction of the ventricles in an UNCONTROLLED manner

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11
Q

What is triggered activity?

A

Changes in the electrical signals in the cells:
- Depolarisation in the cells reach threshold at a time point in the cardiac cycle that are NOT normally expected

  • EXTRA beat
  • VENTRICULAR TACHYCARDIA if the cells have many extra beats
  • At risk of VF
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12
Q

What is re-entrant excitation?

Why is it called ‘re-entrant’?

A

Seen in clusters of of myocytes (not all of them):

  • Electrical activity from the extra beat SPREADS from the effected cells to adjoining cells
  • Different LAYERS impacted
  • Causes FURTHER spread of contraction (effecting the normal spread)

Called re-entrant because the AP fired from the abnormal cells FEEDBACK onto the other cells, causing them to contract

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13
Q

What impacts does re-entrant excitation have?

A
  • Spatial (in space)

- Temporal (in time)

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14
Q

What happens after the abnormal cells fire what happens to them?

What does this mean?

A

They become REFRACTORY

Unable to respond to a NORMAL signal coming down from the node

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15
Q

What are the symptoms of long QT syndrome?

A
  • Syncope (fainting)

- Sudden death (Torsades de pointes - forms VT)

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16
Q

What is the inheritance of long-QT?

A
  • 12 different forms of gene changes

- Gain of function/loss of function

17
Q

What are the different types of long-QT?

How are they different?

A

1) Self-limiting episode
- ECG goes back to NORMAL
2) Episode leading to ventricular fibrillation
- ECG doesn’t go back to normal

18
Q

How many different mutations leading to LQT?

A

12 types

19
Q

What causes LQT1?

A

LOSS OF FUNCTION mutation in Kv7.1alpha channel (KCNQ1 gene):

  • K+ channel
  • In the alpha subunit
20
Q

What is LQT1?

A

Long QT type 1

21
Q

What is the Kv7.1 alpha channel associated with?

A

The Iks current

22
Q

What cause LQT3?

A

GAIN OF FUNCTION mutation in Nav1.5alpha channel (SCN5A gene):

23
Q

What is the Nav1.5alpha channel associated with?

A

Ina current

24
Q

What causes LQT5?

A

Mutation in MinK protein (KCNE1 gene)

25
Q

What is MinK protein?

A

Regulator of K+ Kv7.1alpha

26
Q

What causes LQT8?

A

GAIN OF FUNCTION mutation in Cav1.2alpha channel (CACNA1C)

27
Q

What is Cav1.2aplha involved with?

A

Ica current

28
Q

Why is it not a massive impact if there is a mutation in K+ channel?

A

Not a massive impact as there are many K+ channels

If a mutation in one channel, other channels can subserve the function

29
Q

What is the structure of the KVLQ1 channel?

A

4 subunits come together to form a functional K+ channel

30
Q

Why are the mutations that could be present in the KVLQ1 channel?

A
  • SOME are autosomal dominant and SOME are autosomal recessive
  • SOME mutations in the C terminus
  • MOST mutations in the membrane spanning domains
  • Loss of function in Q1 potassium channel or its regulator
31
Q

What is the Q1 potassium channel important in?

What happens if there is a mutation in this channel?

A

Repolarisation

  • Slows repolarisation
  • QT interval extends
32
Q

How are forms of LQT syndromes are associated with deafness?

A

K+ channels in the stria vascularis - concentrate endolymph

Through the Q1/E1 complex

33
Q

What mutations occur to Na+ and Ca2+ channels in LQT?

What does this cause?

Why?

A

Gain of function mutations

Causes:

  • Prolongation of the plateau phase
  • Delay of the repolarisation phase

As these channels are normally open and cause depolarisation - but stay open for LONGER

34
Q

What are the treatments for LQT?

Example?

A

Beta blockers

Example: atenolol