Sudden death Flashcards
In the central dogma, which process is most likely to be affected by a mutation changing the first base in an intron
Splicing
What is a motif
short DNA sequences that indicate where splicing should happen in the RNA strand, the most important parts are the 2 bases in the intron just before and just after the exon
what type of genetic sequence variant is most likely to cause long QT syndrome
A premature stop codon in the exon 2 of a gene
what is the effect of deleting a single base in an exon of the gene
Frameshift mutation
changes all the following amino acids as the base pairs change
what is a missense mutation
single base pair substitution altering genetic code
what is a nonsense mutation?
where a stop codon is encoded for, creating short chains
what is next generation sequencing?
high throughput method used to determine portion of nucleotide sequence of a genome
what is the most common arrhythmia associated with long QT
torsades de pointes
What advice should you give to reduce risk of sudden infant death
put baby on their back to go to sleep
what is a feature of an ECG seen in Ventricular tachycardia?
The QRS complexes last longer than 120s
what are clinical signs of sepsis
rapid breathing and HR shortness of breath low BP confusion feverish and clammy
what drug is used to treat a patient with long QT syndrome
Atenolol
Avoid QT prolonging drugs
flecainide, haloperidol, furosemide
What are the reversible causes of cardiac arrest
4 H’s
- hypoxia
- hypovolaemia
- hypo/hyperkalaemia
- hypothermia
4 T’s
- thrombosis (coronary or pul)
- Tamponade
- toxins
- Tension pneumothorax
Name the non - suspicious and suspicious causes of hypoxia
Non suspicious
- asthma
- pneumothorax
- respiratory obstruction (epiglottitis, choking)
- Respiratory depression (drug related, overdose)
- Aspiration
Suspicious
- Respiratory obstruction
- Drug related - overdose, negligence, poisoning
- Drowning
Name the non - suspicious and suspicious causes of hypovolaemia
Non - suspicious
- upper GI haemorrhage
- lower GI haemorrhage
- Haemoperitoneum - liver/spleen laceration
- Trauma
- Abdominal aortic aneurysm
Suspicious
- trauma
- stabbings
- shootings
Name the non - suspicious and suspicious causes of hyper/hypokalaemia?
Non - suspicious
- DKA
- Alcoholic ketoacidosis
- Toxins
Suspicious
- toxins
Name some non suspicious and suspicious causes of hypothermia
Non - suspicious
- exposure to cold
- alcoholic
- drugs
- underlying medical disease
Suspicious
- cold exposure
- water
- neglect
- forced outside
Define shock
condition of inadequate perfusion to sustain normal organ perfusion
what are the 5 main classes of shock
Hypovolaemic - loss of circulating volume, reduced preload and CO
Cardiogenic - myocardial dysfunction causing reduction in systolic function and CO
Obstructive - physical obstruction to filling of the heart, reduced preload and CO
Distributive - significant reduction in SVR
Cytotoxic - uncoupling of tissue oxygen delivery and mitochondrial oxygen uptake
Give examples of causes for the different types of shock
Hypovolaemic
- bleeding (most common), third space losses, severe dehydration
Cardiogenic
- MI, myocarditis, acute valve lesion
Obstructive
- Tamponade, PE, Tension pneumothorax
Distributive
- septic shock, anaphylaxis, neurogenic
Cytotoxic
- CO/CN poisoning
Describe hypovolaemic shock
where there is insufficient circulating volume to fill the circuit and maintain BP
Leads to hypoperfusion and hypoxia of end organs
Features of hypovolaemic shock
Initially people compensate very well and may just have tachycardia
- sweaty
- anxious
- tachycardia
- narrowing pulse pressure
- increasing resp rate
- hypotension is a late sign in haemorrhage
- confusion
Compensatory mechanisms in hypovolaemia
Baroreceptor reflexes - stretch sensitive receptors in carotid sinus and aortic arch, decreased stretch = enhanced symp. output
Sympathetic mediated neurohormonal response - release of adrenergic vasoconstrictors (adrenaline and noradrenaline), redirection of fluids, leads to lactic acidosis driving chemoreceptors, circulating vasodilators also increase
Capillary absorption of interstitial fluid - reduced capillary pressure, net inward filtration
Renal and hypothalamo - pituitary adrenal response - renin release enhancing vasoconstriction and secretion of aldosterone/vasopressin
what are the 3 ways that the heart can increase its cardiac output
Increase HR
increase SV (inotropy)
Increase both
In the Frank starling relationship, if the heart is failing what will happen to the curve
It will shift down
What does inotropy do to the frank starling curve?
shifts the curve up
what is cardiogenic shock
where the heart as a pump cannot meet circulatory demands
What are clinical signs of cardiogenic shock?
Poor forward flow - hypotension, shock, fatigue, syncope
Back pressure - pulmonary oedema, elevated JVP, hepatic congestion
what is inotropy
A measure of the contractile state for any given preload
Positive inotropy is an increase in force of cardiac contraction
How is positive inotropy achieved
The sympathetic nervous system
Can be replicated with drugs
- Dopaminergic stimulation using dobutamine, adrenaline
What is obstructive shock
Involves a physical obstruction to either the heart or great vessels, mainly affects the cardiac filling rather than cardiac ejection
Treatment of obstructive shock
Remove underlying cause:
PE - anticoagulation +/- thrombolysis
Cardiac tamponade - pericardial drainage
Tension pneumothorax - decompression and chest drain
what is distributive shock?
The circuit is too big
caused by excessive vasodilation resulting in inadequate oxygen delivery and perfusion to organs
What are the 3 subtypes of distributive shock?
Septic - bacterial endotoxin mediated capillary dysfunction
Anaphylactic shock - mast cell release of vasodilators
Neurogenic shock - loss of thoracic sympathetic outflow following spinal injury
what do a rise in lactate levels suggest?
a marker of tissue hypoperfusion and shock
What are the 2 shockable cardiac arrest rhythms
Ventricular fibrillation
Pulseless Ventricular tachycardia
what are the 2 non - shockable cardiac arrest rhythms
Pulseless electrical activity
Asystole
what two categories can you split inherited cardiac conditions into?
Channelopathies
carddiomyopathies
Give some examples of channelopathies
Congenital long QT syndrome Brugada Catecholaminergic polymorphic ventricular tachycardia short QT familial Wolf parkinsons white Familial AF
Give some examples of cardiomyopathies
Hypertrophic cardiomyopathy
Dilated cardiomyopathy
Arrhythmogenic right ventricular cardiomyopathy
what is a channelopathy and a cardiomyopathy
Channelopathy - problem in the conduction system, usually associated with proteins, ion current imbalances
Cardiomyopathy - problem with the heart muscle, can be caused by scarring
what are after depolarisations
Abnormal depolarisation of cardiac myocytes that interrupt the cardiac action potentials and can lead to triggered activity, occur in phase 2, 3, 4
What are early after depolarisations?
What can they result in?
Abnormal depolarisations which occur in phase 2 or 3 caused by an increase in frequency of AP
Torsades de pointes
what arrhythmia is commonly seen in long QT syndrome
Torsades de pointes
what are delayed after depolarisations
These are depolarisations that begin during phase 4 after repolarisation has completed but before another action potential would normally occur.
what can cause delayed after depolarisations
elevated calcium concentrations
seen in digoxin toxicity
where is calcium ions stored and released from?
sarcoplasmic reticulum
what is a classic feature of delayed after depolarisations and what condition is it usually seen in?
Bidirectional ventricular tachy
Catecholaminergic polymorphic ventricular tachycardia
what is the commonest (autosomal dominant) long QT syndrome?
Romano ward syndrome
Physiology of LQT syndrome
Defect in a channel protein Reduced or dysfunctional ionic current Prolonged cardiac repolarisation QT interval prolongation Polymorphic ventricular tachycardia (torsades)
what can trigger sudden cardiac death in someone with long QT
Exercise
Emotional stress
Sleep
what are some examples of QT prolonging drugs
amiodarone
erythromycin
haloperidol
what are the main arrythmias associated with brugada syndrome
polymorphic VT
VF
AF
what are ECG findings in brugadas
ST elevation
RBBB in V1 - V3
often intermittent ECG findings and so can use provocative testing using flecainide (sodium blocker)
what inheritance pattern does brugada follow
Autosomal dominant (mainly men)
Brugada syndrome VF triggers
rest or sleep
fever
excessive alcohol, large meals
What drugs should be avoided in brugada
Anti - arrhythmics - sodium channel blockers Psychotropics Analgesics Anaesthetics
what is catecholaminergic polymorphic ventricular tachycardia
sensitivity of cardiac muscle to adrenaline which can be triggered by emotional stress or exercise
what will an ECG look like in someone with CPVT
normal at rest
Can cause bidirectional tachycardia and polymorphic VT
Treatment in CPVT
beta blockers lifestyle changes (avoid competitive sports, stress) ICD implantation (who have had cardiac arrest)
what will be seen on an ECG in wolff parkinson white syndrome
Short PR interval
Delta waves
AF (maybe)
what causes Hypertrophic cardiomyopathy
mutation in sarcomeric genes
investigations for hypertrophic cardiomyopathy
doppler echo
48hr ambulatory ECG
what is dilated cardiomyopathy
a type of heart muscle disease that causes the heart chambers to thin and stretch, growing larger
treatment of dilated cardiomyopathy
lower BP
flecainide - rhythm control drug
what is arrhythmogenic right ventricular cardiomyopathy
it is where cardiomyocytes is replaced by fibro fatty tissue
what inheritance pattern is arrhythmic right ventricular cardiomyopathy
Autosomal dominant - for desmosomal proteins
Autosomal recessive - for nondesmosomal proteins
Treatment of arrhythmogenic right ventricular cardiomyopathy
Avoidance of competitive sports
Beta blockers
ICD implantation
Amiodarone if not beta blockers
Diagnosis of inherited cardiac conditions
Clinical testing
genetic testing
family screening
what is the only known treatment for ventricular fibrillation, how does it work?
Defibrillation
Resets all the cardiac myocytes to enable normal electrical activation to recommence
Causes all cardiac myocytes to fully depolarise
what is a polymorphism
a variant that is prevalent in the general population. Often used to imply benign
how do you classify a variant
Class 1: definitely benign Class 2: probably benign Class 3: Variant of uncertain significance Class 4: Probably pathogenic Class 5: Definitely pathogenic
When would you use FISH
for translocation mutations
When would you use microarray CGH
To detect any missing or duplicated pieces of chromosome
This is first line chromosome test
what is PCR used for
allows you to select one small piece of the human genome and amplify it
what is NGS
a high throughput method used to determine a portion of the nucleotide sequence of an individual genome
what pattern of inheritance causes dissecting aortic aneurysm
autosomal dominant
what is an aortic dissection
a condition in which a tear occurs into he inner layer of the aorta, blood rushes through the tear causing the inner/middle layers of the aorta to split
what is marfans syndrome caused by
fillibrin mutation
A disorder of the body’s connective tissues
what is classed as a stillbirth
When a baby dies after 24 weeks of pregnancy and before or during birth
what is classed as a miscarriage
Loss of a baby before 24 weeks of pregnancy
Risk factors for stillbirths
Congenital abnormalities Cord prolapse maternal infections extremes of ages multiple pregnancies Medical complications - pre eclampsia ect.
What is some advice you should give to women to prevent the likelihood of a stillbirth
Sleep on side in third trimester
Quitting smoking
Staying healthy weight
Avoid alcohol and drugs
Take folic acid until end of first trimester
Report any leaking fluid/discharge in pregnancy
In what instances should immediate delivery of baby be strongly advised?
Sepsis
Eclampsia
Placental abruption
Membrane rupture
what is SUDI?
All infant deaths which happen suddenly for which there is no apparent reason, are unexpected
At what age do SUDI’s mainly occur?
2 - 6 months
Risk factors for SUDI
Acute illness (URTI/otitis media) Preterm birth before 37 weeks Congenital anomaly Multiple birth Previous unexplained infant death Small for gestational age Male Sleeping prone or on side Co - sleeping sleeping with pillows Substance misuse in parents
What are the 5 stages of grief
Denial Anger Depression Bargaining Acceptance
