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BMS242 CVS Phys > L10 - Cardiac Channelopathies > Flashcards

L10 - Cardiac Channelopathies Flashcards

1
Q

How many sudden cardiac deaths per year in the UK

A

70000

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2
Q

What % of sudden cardiac deaths are caused by ischaemic heart disease

A

60%

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3
Q

What % of sudden cardiac deaths have no identifiable cause

A

40%

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4
Q

Long and Short QT syndromes are examples of __________ syndromes

A

Inherited

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5
Q

What is the main effect of long/short QT

A

Change to the action potentials of ventricular myocytes

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6
Q

P wave represents

A

Atrial depolarisation

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7
Q

QRS complex represents

A

Ventricular depolarisation

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8
Q

T wave represents

A

Ventricular repolarisation

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9
Q

Why is atrial repolasrisation not shown on an ECG

A

Because it is masked by the depolarisation of the ventricles

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10
Q

In long QT

A

Repolarisation is delayed

QT interval increases

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11
Q

In short QT

A

Repolarisation is accelerated

QT interval decreases

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12
Q

What is phase 0 of the ventricular AP

A

Depolarisation

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13
Q

What currents mediate depolarisation of the ventricles

A

Influx Ina

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14
Q

What is phase 1 of the ventricular AP

A

Partial repolarisation

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15
Q

What currents mediate the partial repolarisation of the ventricles

A

Ito influx

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16
Q

What is phase 2 of the ventricular AP

A

Plateau

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17
Q

What currents mediate the plateau phase

A

Influx Ina Ica

Efflux Iks Ikr Ikur

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18
Q

What is phase 3 of the ventricular AP

A

Repolarisation

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19
Q

What currents mediate repolarisation

A

Efflux: Iks Ikr Ikur IkATP IkACh

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20
Q

What is phase 4 of the ventricular AP

A

Resting

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21
Q

What currents mediate the resting state of the ventricular AP

A

Influx Ina Ica

Efflux Ik1 Ik2p

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22
Q

Normal QT interval is

A

0.36

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23
Q

Threshold for short QT is

A

0.34

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24
Q

Threshold for long QT is

A

0.45

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25
Q

Two main classes of implications of long and short QT, what can they lead to

A

Triggered activity
Re-entrant excitation
Lead to ventricular tachycardia and then to ventricular fibrilation

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26
Q

Describe triggered activity

A

Cells reach the threshold when they shouldn’t and fire action potentials
Leads to an additional beat - ectopic

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27
Q

Describe re-entrant excitation

A

Few layers of cells affected that include the extra beat
This can spread to other cells
Spatial and temporal distortion
AP propagation
When actual signal arrives cells are in refractory so can’t respond

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28
Q

What is spatial distortion

A

Electrical signals that can spread from one affected group of cells to another

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29
Q

What is temporal distortion

A

Where one cluster of cells fires an action potential - these then fire again at another point in time

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30
Q

Main symptom of Long QT

A

Syncope

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31
Q

What does syncope mean

A

Episodes of fainting

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32
Q

A twisting of the ECG trace is known as …

HINT: it is a form of VT

A

Torsade de pointes

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33
Q

LQT1 is caused by a muation in what gene

A

KCNQ1

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34
Q

LQT1 affects which ion channel

A

Kv7.1a

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35
Q

Kv7.1a is coded for by which gene

A

KCNQ1

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36
Q

LQT1 is caused by a _____ of function mutation in the gene ______ which codes for _______, affected the current _____

A

Loss
KCNQ1
Kv7.1a
Iks

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37
Q

Iks current is involved in

A

Repolarisation

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38
Q

What is the prevalence of LQT1

A

30-35%

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39
Q

LQT2 is caused by a mutation in what gene

A

KCNH2

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40
Q

Which ion channel is affected by LQT2

A

Kv11.1a

41
Q

Kv11.1a is mutated in which form of LQT

A

2

42
Q

Kv7.1a is mutated in which form of LQT

A

1

43
Q

LQT2 is caused by a _____ of function mutation in the gene ______ which codes for _______, affected the current _____

A

Loss
KCNH2
Kv11.1a
Ikr

44
Q

Ikr is involved in

A

Repolarisation

45
Q

LQT3 is caused by a mutation in which gene

A

SCN5A

46
Q

Prevalence of LQT2

A

25-30%

47
Q

Prevalence of LQT3`

A

5-10%

48
Q

What ion channel is mutated in LQT3

A

Nav1.5a

49
Q

LQT3 is caused by a _____ of function mutation in the gene ______ which codes for _______, affected the current _____

A

Gain
SCN5A
Nav1.5
Ina

50
Q

what is Ina involved in

A

Depolarisation and the plateau

51
Q

LQT5 is caused by a _____ of function mutation in the gene ______ which codes for _______, affected the current _____

A

Loss
KCNE1
MinK (regulatory)
Iks

52
Q

Iks current involved in

A

Repolarisation

53
Q

Prevalence of LQT5

A

1%

54
Q

What protein is mutated in LQT5

A

MinK

55
Q

What gene is mutated in LQT5

A

KCNE1

56
Q

What gene is mutated in LQT1

A

KCNQ1

57
Q

What gene is mutated in LQT2

A

KCNH2

58
Q

What gene is mutated in LQT3

A

SCN5A

59
Q

What gene is mutated in LQT5

A

KCNE1

60
Q

What type of mutation LQT1

A

Loss

61
Q

What type of mutation LQT2

A

Loss

62
Q

What type of mutation LQT3

A

Gain

63
Q

What type of mutation LQT5

A

Loss

64
Q

What protein mutated LQT1

A

Kv7.1a

65
Q

What protein mutated LQT2

A

Kv11.1a

66
Q

What protein mutated LQT3

A

Nav1.5a

67
Q

What protein mutated LQT5

A

MinK

68
Q

What current affected LQT1

A

Iks - repolarising

69
Q

What current affected LQT2

A

Ikr - repolarising

70
Q

What current affected LQT3

A

Ina - plateau

71
Q

What current affected LQT4

A

Iks - repolarising

72
Q

What type of channelopathy is LQT1

A

k channelopathy

73
Q

How many subunits must come togehter to form the fucntional channel Kv7.1

A

4

74
Q

Where are a few of the mutation sites found in Kir7.1

A

At the carboxy terminus

Intracelluar loops

75
Q

Where are the majority of mutations found in Kir7.1

A

Tm spannig omains

76
Q

Why does the loss of function in Kv7.1 cause the long QT

A

repolarisation is delayed as you can’t get the K+ into the cell as quickly

77
Q

Explain why LQT1 also causes deafness

A

Kv7.1 (Q1/E1) also found in the stria vascualris (pump K+ to form the endolymph) of the ear. When mutated endolymph doesnt form so where hair cells move and K+ channels open there is no K+ to move in and depolarise

78
Q

Explain how a gain of function in a Ca channel would lead to long QT syndrome

A

Open normally but stay open for longer, would delay the start of the repolarisation

79
Q

Explain how a gain of function mutation in a Na channel would lead to long QT syndrome

A

Na channels don’t close as quickly so plateau is delayed which would delay the start of repolarisation

80
Q

What class of beta blockers would be used to treat long QT

A

Class two antidysrhythmic drugs

81
Q

What would an example of a beta blocker be
What is it linked to
What actions would it have on the heart

A

Atenolol
cAMP linked
Negative chrondotropic and ionotropic actions

82
Q

What group of patients may not be suitable for treatment with atenolol, why?

A

People with an obstructive lung disease

Atenolol may cause bronchoconstrcition

83
Q

What is atenolo

A

B1 adrenoreceptor antagonist

84
Q

Short QT syndrome calssified by

A

A shortened QT interval

85
Q

What other symptoms of SQT syndrome

A

Arrhymthmias, palpitations, syncope

86
Q

How many forms of Lqt

A

12

87
Q

How many forms of SQT

A

5

88
Q

What is syncope

A

Fainting episodes

89
Q

What percentage of males are effected by SQT

A

75%

90
Q

What other aspects of an ECG trace are characteristic of SQT

A

Short/absent ST
Tall/peaked T wave
QT interval fixed - doesn’t move

91
Q

A mutatation in what gene causes SQT1

Is this a gain or loss of function mutation

A

KCNH2

GAIN

92
Q

KCNH2 codes for what ion channel and is mutated in which form of SQT

A

Kv11.1a (gain of function)

1

93
Q

What current is Kv11.1a involved in

A

Ikr

94
Q

Explain how a loss of function mutation in a Ca channel may cause SQt

A

Dont open normally or close early

Less Ca influx into the cell - reduced plateau and repolarisation would be initiated earlier

95
Q

Explain how a gain of function mutation in a K Ch would cause SQT

A

More channels in membrane//may open sooner
More K+ efflux from the cell
Repolarisation would occur soon

96
Q

Two treatments for SQT

A

Implant defib

Quinidine

97
Q

What is the mechanism for quinidine action

A

Block K channels and delay repolarisation

98
Q

What is the issue with using quinine for the treatment of SQT

A

Blocks other K channels throughout the body

BMS242 CVS Phys (12 decks)

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