L10 - Cardiac Channelopathies Flashcards
(98 cards)
1
Q
How many sudden cardiac deaths per year in the UK
A
70000
2
Q
What % of sudden cardiac deaths are caused by ischaemic heart disease
A
60%
3
Q
What % of sudden cardiac deaths have no identifiable cause
A
40%
4
Q
Long and Short QT syndromes are examples of __________ syndromes
A
Inherited
5
Q
What is the main effect of long/short QT
A
Change to the action potentials of ventricular myocytes
6
Q
P wave represents
A
Atrial depolarisation
7
Q
QRS complex represents
A
Ventricular depolarisation
8
Q
T wave represents
A
Ventricular repolarisation
9
Q
Why is atrial repolasrisation not shown on an ECG
A
Because it is masked by the depolarisation of the ventricles
10
Q
In long QT
A
Repolarisation is delayed
QT interval increases
11
Q
In short QT
A
Repolarisation is accelerated
QT interval decreases
12
Q
What is phase 0 of the ventricular AP
A
Depolarisation
13
Q
What currents mediate depolarisation of the ventricles
A
Influx Ina
14
Q
What is phase 1 of the ventricular AP
A
Partial repolarisation
15
Q
What currents mediate the partial repolarisation of the ventricles
A
Ito influx
16
Q
What is phase 2 of the ventricular AP
A
Plateau
17
Q
What currents mediate the plateau phase
A
Influx Ina Ica
Efflux Iks Ikr Ikur
18
Q
What is phase 3 of the ventricular AP
A
Repolarisation
19
Q
What currents mediate repolarisation
A
Efflux: Iks Ikr Ikur IkATP IkACh
20
Q
What is phase 4 of the ventricular AP
A
Resting
21
Q
What currents mediate the resting state of the ventricular AP
A
Influx Ina Ica
Efflux Ik1 Ik2p
22
Q
Normal QT interval is
A
0.36
23
Q
Threshold for short QT is
A
0.34
24
Q
Threshold for long QT is
A
0.45
25
Two main classes of implications of long and short QT, what can they lead to
Triggered activity
Re-entrant excitation
Lead to ventricular tachycardia and then to ventricular fibrilation
26
Describe triggered activity
Cells reach the threshold when they shouldn't and fire action potentials
Leads to an additional beat - ectopic
27
Describe re-entrant excitation
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
28
What is spatial distortion
Electrical signals that can spread from one affected group of cells to another
29
What is temporal distortion
Where one cluster of cells fires an action potential - these then fire again at another point in time
30
Main symptom of Long QT
Syncope
31
What does syncope mean
Episodes of fainting
32
A twisting of the ECG trace is known as ...
| HINT: it is a form of VT
Torsade de pointes
33
LQT1 is caused by a muation in what gene
KCNQ1
34
LQT1 affects which ion channel
Kv7.1a
35
Kv7.1a is coded for by which gene
KCNQ1
36
LQT1 is caused by a _____ of function mutation in the gene ______ which codes for _______, affected the current _____
Loss
KCNQ1
Kv7.1a
Iks
37
Iks current is involved in
Repolarisation
38
What is the prevalence of LQT1
30-35%
39
LQT2 is caused by a mutation in what gene
KCNH2
40
Which ion channel is affected by LQT2
Kv11.1a
41
Kv11.1a is mutated in which form of LQT
2
42
Kv7.1a is mutated in which form of LQT
1
43
LQT2 is caused by a _____ of function mutation in the gene ______ which codes for _______, affected the current _____
Loss
KCNH2
Kv11.1a
Ikr
44
Ikr is involved in
Repolarisation
45
LQT3 is caused by a mutation in which gene
SCN5A
46
Prevalence of LQT2
25-30%
47
Prevalence of LQT3`
5-10%
48
What ion channel is mutated in LQT3
Nav1.5a
49
LQT3 is caused by a _____ of function mutation in the gene ______ which codes for _______, affected the current _____
Gain
SCN5A
Nav1.5
Ina
50
what is Ina involved in
Depolarisation and the plateau
51
LQT5 is caused by a _____ of function mutation in the gene ______ which codes for _______, affected the current _____
Loss
KCNE1
MinK (regulatory)
Iks
52
Iks current involved in
Repolarisation
53
Prevalence of LQT5
1%
54
What protein is mutated in LQT5
MinK
55
What gene is mutated in LQT5
KCNE1
56
What gene is mutated in LQT1
KCNQ1
57
What gene is mutated in LQT2
KCNH2
58
What gene is mutated in LQT3
SCN5A
59
What gene is mutated in LQT5
KCNE1
60
What type of mutation LQT1
Loss
61
What type of mutation LQT2
Loss
62
What type of mutation LQT3
Gain
63
What type of mutation LQT5
Loss
64
What protein mutated LQT1
Kv7.1a
65
What protein mutated LQT2
Kv11.1a
66
What protein mutated LQT3
Nav1.5a
67
What protein mutated LQT5
MinK
68
What current affected LQT1
Iks - repolarising
69
What current affected LQT2
Ikr - repolarising
70
What current affected LQT3
Ina - plateau
71
What current affected LQT4
Iks - repolarising
72
What type of channelopathy is LQT1
k channelopathy
73
How many subunits must come togehter to form the fucntional channel Kv7.1
4
74
Where are a few of the mutation sites found in Kir7.1
At the carboxy terminus
| Intracelluar loops
75
Where are the majority of mutations found in Kir7.1
Tm spannig omains
76
Why does the loss of function in Kv7.1 cause the long QT
repolarisation is delayed as you can't get the K+ into the cell as quickly
77
Explain why LQT1 also causes deafness
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
Explain how a gain of function in a Ca channel would lead to long QT syndrome
Open normally but stay open for longer, would delay the start of the repolarisation
79
Explain how a gain of function mutation in a Na channel would lead to long QT syndrome
Na channels don't close as quickly so plateau is delayed which would delay the start of repolarisation
80
What class of beta blockers would be used to treat long QT
Class two antidysrhythmic drugs
81
What would an example of a beta blocker be
What is it linked to
What actions would it have on the heart
Atenolol
cAMP linked
Negative chrondotropic and ionotropic actions
82
What group of patients may not be suitable for treatment with atenolol, why?
People with an obstructive lung disease
| Atenolol may cause bronchoconstrcition
83
What is atenolo
B1 adrenoreceptor antagonist
84
Short QT syndrome calssified by
A shortened QT interval
85
What other symptoms of SQT syndrome
Arrhymthmias, palpitations, syncope
86
How many forms of Lqt
12
87
How many forms of SQT
5
88
What is syncope
Fainting episodes
89
What percentage of males are effected by SQT
75%
90
What other aspects of an ECG trace are characteristic of SQT
Short/absent ST
Tall/peaked T wave
QT interval fixed - doesn't move
91
A mutatation in what gene causes SQT1
| Is this a gain or loss of function mutation
KCNH2
| GAIN
92
KCNH2 codes for what ion channel and is mutated in which form of SQT
Kv11.1a (gain of function)
| 1
93
What current is Kv11.1a involved in
Ikr
94
Explain how a loss of function mutation in a Ca channel may cause SQt
Dont open normally or close early
| Less Ca influx into the cell - reduced plateau and repolarisation would be initiated earlier
95
Explain how a gain of function mutation in a K Ch would cause SQT
More channels in membrane//may open sooner
More K+ efflux from the cell
Repolarisation would occur soon
96
Two treatments for SQT
Implant defib
| Quinidine
97
What is the mechanism for quinidine action
Block K channels and delay repolarisation
98
What is the issue with using quinine for the treatment of SQT
Blocks other K channels throughout the body
