Sudden Death Flashcards by Jenny Lee

What is penetrance?

The likelihood of developing a disease if you have a gene mutation

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Are Mendelian disorders high or low penetrance?

High

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What is a promoter region?

Base sequence which starts transcription

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What is a stop codon? What will an error cause?

Sequence of bases which stops transcription.
Premature stop - smaller mutant protein
Late stop - larger mutant protein

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What is splicing?

Removal of introns from mRNA

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What is the effect of a deletion or insertion mutation?

Frameshift mutation

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How is Next Generation Sequencing done?

gDNA
Parallel sequencing - broken into pieces then sequenced
Alignment - lined up against reference
Sequence

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What is coverage in NGS?

Number of times one part of a gene is sequenced

98% coverage is good

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What can genetic changes found in NGS be?

Disease-causing mutation
Polymorphism (3 million in genome)
Variant of Unknown Significance

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How do you calculate QR interval?

QT interval/square root R-R interval

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What does long-QT increase the risk of?

Torsades de pointes

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Name signs of hypovolaemic shock

What is the management?

Tachycardia
Skin cool and pale
Mx - fluid and blood replacement

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Name signs of cardiogenic shock

What is the management?

Swollen, oedematous skin

Mx - careful fluid management, inotropes (dobutamine), vasopressors (adrenaline)

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Name signs of septic shock

What is the management?

Skin flushed and warm then cool and pale
Pyrexia
Mx - SEPSIS 6, vasopressor (NA) if unresponsive to fluid

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Name signs of anaphylactic shock

What is the management?

Urticarial rash

Mx - adrenaline, IV fluids

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Name signs of neurogenic shock

What is the management?

Skin vasodilatated below lesion

Mx - vasopressors

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Name reversible causes of cardiac arrest

Hypoxia
Hypothermia
Hypovolaemia
Hyperkalaemia/metabolic
Thrombosis (PE)
Tamponade
Tension pneumothorax
Toxins

In which rhythms can defibrillation be used?

What is the management?

VF
Pulseless VT
Shock, CPR 2 mins, 2nd shock, CPR 2 mins, 3rd shock, CPR 2 mins AND adrenaline 1mg, amiodarome 300mg IV

Which rhythms are non-shockable?

What is the management?

Asystole
Pulseless electrical activity
CPR with 1mg adrenaline IV every 3-5 mins

What are mechanisms of congenital long-QT syndrome?

Isolated LQT Roman-Ward Syndrome - most common

K+ channel mutation

How is LQTS diagnosed?

QT>/480ms in repeated ECGS
OR LQTS risk score >3
OR pathogenic mutation

What is the management of Long QT Syndrome?

B-blockers
Avoid QT-prolonging drugs
Correct electrolyte abnormalities
Avoid genotype-specific triggers
- LQTS1 - strenuous swimming
- LQTS2 - loud noises

List QT-prolonging drugs

Clarythromycin, azithromycin, erythromycin
Anaesthetic drugs
Tricyclic antidepressants
Neuroleptics

How is short QT syndrome diagnosed?

What is the pathogenesis?

QT interval <300ms
K+ channel mutation
Young children - very malignant

What are ECG features of Brugada syndrome?

ST elevation and RBBB in V1-3

What are people with Brugada syndrome at risk of?

AF Polymorphic VT VF

What are triggers of decompensation in Brugada syndrome?

Sleep Fever Excess alcohol Large meals

How is Brugada syndrome managed?

Avoid drugs causing ST elevation - Na blockers, anaesthetics Hospital admission if fever High risk ECG - ICD

What is the pathogenesis in Brugada syndrome?

Often AD mutation in Na channel | Inefficient depolarisation predisposes to arrhythmias

What is the mutation in Catecholaminergic Polymorphic VT? (CPVT)

Ryanodine receptor mutation - RyR2 | AD

What are features of catecholaminergic polymorphic VT?

``` Normal resting ECG Adrenaline trigger (emotional stress, strenuous exercise, competitive sport) --> bidirectional VT ```

What is the management of CPVT?

B-blocker. avoidance of triggers | In VT - anaesthetise and defibrillate

What is the pathogenesis of Wolf-Parkinson-White syndrome? (WPW)

Accessory pathway --> ventricular re-excitiation | AV re-entrant tachycardia - SVT, AF

What are ECG signs of WPW?

Delta sign

What is the gene mutation in Hypertrophic Cardiomyopathy? (HOCM)

Mutation in sarcomeric genes

What are ECG features of LVH?

>7 big boxes positive deflection in V5 plus negative deflection in V2

How do people with HOCM present?

Sudden death Heart failure AF

What is the management of HOCM?

Hx cardiac arrest or VT - ICD FHx SCD, LV>3cm, unexplained recent syncope - ICD 5y risk SCD >5% - ICD Avoid competitive sports

What is the gene mutation in arrhythmogenic right ventricular cardiomyopathy? (ARVC)

AD mutation in desmosomal genes | Structural problem with RV --> replacement myocytes with fibrofatty tissue --> scar --> re-entrant tachycardia

What increases risk in ARVC?

FHx SCD Severity RV and LV function Frequent non-sustained VT Younger age

How is ARVC managed?

Avoid competitive sports B-blockers - sotalol Hx poorly tolerated VD/cardiac death - ICD

What are complications of an ICD?

``` Endocarditis Perforation Haemothorax Pneumothorax Thrombolic event Vascular complications Lead - fractures, extraction complications, dislodgement ```