Sudden Death Flashcards
(213 cards)
1
Q
A
Splicing
2
Q
A
premature stop codon in exon 2 of a gene
3
Q
A
The variant is a deletion in the single base of the exon of a gene
4
Q
A
It allows more efficient analysis of multiple genes
5
Q
A
QT interval / square root of R-R interval
6
Q
A
Torsades de pointes
7
Q
A
put them on their back to go to sleep
8
Q
A
QRS complexes last longer than 120ms
9
Q
A
tachypneoic with resp rate of >22
10
Q
A
atenolol
11
Q
what is shock?
A
inadequate organ perfusion leading to inadequate oxygen delivery to tissues and eventually organ failure
12
Q
what are the 3 main origins of shock?
A
the heart
the blood vessels
flow of blood
13
Q
what are the 5 types of shock?
A
hypovolaemic
cardiogenic
septic
anaphylactic
neurogenic
14
Q
distributive shock is an umberella term for
A
septic
anaphylactic
neurogenic
15
Q
Explain hypovolaemic shock
A
16
Q
explain cardiogenic shock
A
17
Q
Explain septic shock
A
18
Q
Explain anaphylactic shock
A
19
Q
Explain neurogenic shock
A
20
Q
what is the meaning of cardiac arrest?
A
it does not necessarily mean the heart has stopped beating: it means that cardiac output is not sufficient for a palpable carotid pulse
21
Q
how does cpr work?
A
changes intra-thoracic pressure and creates a gradient for blood flow to continue
22
Q
reversible causes of cardiac arrest
A
hypovolaemia, hypoxia, hypothermia, metabolic causes (especially hyperkalaemia), tension pneumothorax, cardiac tamponade, toxins and thrombus (pulmonary embolus, atherosclerotic plaque & amniotic fluid)
23
Q
When do you defibrillate?
A
Ventricular Fibrillation and pulseless Ventricular Tachycardia
24
Q
Treat shock
A
Fluid resus
Blood
Vasopressin – vasoconstrictor
Warming – give calcium, ffp (run out of coagulation factors)
25
what are the basics of the frank starling mechanism?
increasing the heart rate increases the stroke volume
the higher the stroke volume the higher the cardiac output
26
vasoconstriction causes what
increase in bp
27
how do you calculate oxygen delivery?
Oxygen delivery (D02) = cardiac output (CO) x arterial oxygen content (CaO2)
28
how can you increase oxygen delivery?
give haemoglobin
29
mechanism of anaphylactic shock
Allergen binds to IgE releasing inflammatory mediators allows capillaries to become leaky, dilatation of lungs giving patients a wheeze, and prostaglandins lead to myocardial depression
30
basic treatment of anaphylaxis
Give adrenaline and iv fluids immediately. This stops the vessels from being leaky
high flow oxygen
chlorphenamine
hydrocortisone
31
basic mechanism of cardiogenic shock
heart becomes tired so not pumping all of the blood. So blood sits in the heart. This leads to pulmonary oedema
32
when do you not give fluids
when someone is in hf or cardiogenic shock as you worsen pulmonary oedema
33
what drug can you give in cardiogenic shock?
vasopressors
34
define sepsis
vascular dilatation and reflex tachycardia as a response to systemic infection
35
what is septic shock?
a patient with sepsis whos bp drops significantly
36
what does vasopressin do?
causes vascular constriction improving oxygen delivery to tissues
37
we can estimate how bad sepsis is by using
QSOFA
38
React very promptly with a young person who is even only a tad
confused
39
how does neurogenic shock differ from the others?
low bp low hr
40
in neurogenic shock:
sympathetic NS is
parasympathetic NS is
sympathetic - cut
parasympathetic - slows hr down
41
only shock in vt and vfib if they
have a pulse
42
diagnose and treat cardiac tamponade
diagnose on echo; needle pericardiocentesis in heart to allow pressure to release or resuscitative thoracotomy
43
treat a thrombus
PCI or thrombolysis; if fibrinolytic therapy given continue CPR for up to 60-90min
44
treat tension pneumo
thoracostomy or needle compression in 2nd ICS to equalise the pressure; check tube position if intubated
45
treat hypoxia
oxygen
46
treat hypovolaemia
give fluids and control haemorrhage
47
treat hypothermia
active rewarming techniques and consider cardiopulmonary bypass
48
irreversible causes of cardiac arrest
decapitation; cryogenic freezing; thermally burned by a volcano (denature enzymes); paraquat poisoning (cellular toxin which prevents oxygen delivery in the mitochondria).
49
treat hypercalcaemia
Calcium resonium and calcium gluconate
50
what is clinical death?
the period of respiratory, circulatory and brain arrest during which initiation of resuscitation can lead to recovery with prearrest central nervous system function. Clinical death is a reversible state. The duration of clinical death depends on the length of time the cerebral cortex survives in the absence of circulation and respiration. Under normal temperature from clinical death to biologic death the period does not exceed 3-6min.
51
define sudden cardiac arrest
death resulting from an abrupt loss of heart function. In most victims if its treated in a few minutes with defibrillation the heart may be restored to an organised rhythm
52
define biologic death
sets in after clinical death and is an irreversible state of cellular destruction
53
in cpr give adrenaline
every 3-5mins
54
in cpr give amiodarone
every 5 mins
55
depth of compressions
5-6cm
56
what is recoil?
release all pressure without removing hands from chest
57
rate of cpr
100-120 (2 per second)
58
ratio of compressions to breaths
30:2
59
rate within breaths
2 within 10s
60
what is shockable?
VF (bizarre irregular chaotic) / pulseless VT (broad constant QRS with torsade de pointes)
61
what is non shockable?
PEA (activity but no pulse – adrenaline 1mg IV then every 3-5mins) / asystole (no QRS wavy straight line – give adrenaline 1mg iv then every 3-5 mins)
62
give adrenaline after
3rd shock
63
pr interval shows
AV nodal delay
64
how do you read a rhythm strip?
65
how do you calculate hr on ecg?
Count the number of large squares present within one R-R interval then divide 300 by this number to calculate the heart rate
If the rhythm is irregular – count the number of complexes on the rhythm strip and multiply by 6
66
how do you assess the heart rhythm?
The heart rhythm can be regular or irregular.
Irregular rhythms can be either:
· Regularly irregular (i.e. a recurrent pattern of irregularity)
· Irregularly irregular (i.e. completely disorganised)
Cardiac axis – look at leads I, II, and III
67
describe the normal cardiac axis
68
describe right axis deviation
69
describe left axis deviation
70
how do you analyse p wave and pr interval?
P waves – are they present?; is each followed by a qrs?; do they look normal; saw tooth/ flutter/ chaotic?
PR should be between 120-200ms (3-5 small squares) – prolonged would be \>0.2s
71
what does the delta wave look like and what is it associated with?
wpw
72
how do you analyse the QRS?
narrow (\<0.12s) or broad (\>0.12s); small (as \< 5mm in the limb leads or \< 10 mm in the chest leads) or tall (imply ventricular hypertrophy); delta wave; pathological q wave (\> 2mm in height and \> 40ms in width).
73
st depression a sign of
ischaemia
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tall t waves
hyperkalaemia
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hyperkalaemia
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treat AF
control rate with beta blocker and diltiazem
if heart failure consider digoxin or amiodarone
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control atrial flutter with
beta blocker
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which leads link to which arteries of the heart?
79
define sudden death
An event that is no traumatic non-violent unexpected and resulting in cardiac arrest within 6 hours of being completely healthy.
80
causes of sudden cardiac death
· Inherited arrhythmia syndrome
· Inherited cardiomyopathy
· Inherited multiple system diseases with CVS involvement
· Myotonic Dystrophy
81
what is a channelopathies?
arrhythmia related to ion channel imbalance
82
what are the main channelopathies?
Congenital long qt
Brugada syndrome
Catecholaminergic polymorphic ventricular tachycardia
Short qt syndrome
Progressive familial conduction disease
Familial AF
Familial WPW
83
what are the most common inherited cardiac conditions?
o Familial Arrhythmia Syndromes
§ Structurally sound hearts but risk of malignant ventricular arrhythmia and sudden arrhythmic death
§ Associated with ECG abnormalities
§ E.g. Long QT Syndrome
o Cardiomyopathies
§ E.g. Hypertrophic Cardiomyopathy
84
how do you screen family of a relative who has died of a sudden cardiac death under 40yo?
cascade screening
85
what type of inheritance is familial hypercholesterolaemia?
multifactorial
86
mutations associated with familial hypercholesterolaemia
in LDLR, APOB or PCSK9
87
what is a cardiomyopathy and what are the main types?
arrhythmia related to scar/ electrical barrier formation and subsequent re entry
Hypertrophic cardiomyopathy
Arrhythmogenic right ventricular cardiomyopathy
Dilated cardiomyopathy
88
what are after depolarisations?
After depolarisations are abnormal depolarisation of cardiac myocytes that interrupt phase 2, 3 or 4 of the cardiac AP in the cardiac conduction system of the heart. After depolarisation ca lead to triggered activity seen as sustained cardiac arrhythmia (All cells doing other things).
89
what are early after depolarisations?
Early after depolarisations occur with abnormal depolarisation during phase 2 or phase 3, and are caused by an increase in the frequency of abortive action potentials before normal repolarisation is completed.Phase 2 may be interrupted due to augmented opening of calcium channels, while phase 3 interruptions are due to the opening of sodium channels.Early after depolarisations can result in torsades de pointes.EADs can be potentiated by hypokalaemia and drugs that prolong the ST interval, including class Ia and III antiarrhythmic drugs.
90
what do early after depolarisations look like?
91
what are delayed after depolarisations?
Delayed after depolarisations occur in late phase 3 or early phase 4 when the action potential is nearly or fully repolarized. The mechanism is poorly understood; however, this type of arrhythmia is found to be associated with high intracellular Ca++ concentrations as occurs with digitalis toxicity or excessive catecholamine stimulation. The triggered impulse can lead to a series of rapid depolarizations (i.e., a tachyarrhythmia).
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what do delayed after depolarisations look like?
93
torsades de pointes associated with
long qt
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describe congenital long qt syndrome
Common. Polymorphic VT (torsades de pointes – constant change in depolarisatioon some high some low points on ecg) triggered by adrenergic stimulation (so caused by adrenaline). Associated with syncope or sudden cardiac death. Risk associated with severity of qt prolongation.
13 subtypes od LQTS.
95
treat long qt
beta blockers and ICD
96
Isolated LQT
romano ward syndrome (autosomal dominant)
97
Deafness and long qt
jervell and lange Nielsen syndrome (autosomal recessive)
98
diagnose long qt
Diagnosis – QT\>480ms in repeated ecgs or when there is a LQTS risk score \>3 ; if you have a known mutation you can make a diagnosis irrespective of ecg
Schwarts score is used for diagnosis of long qt
99
manage long qt
avoid prolong QT prolonging drugs (clarithromycin, anaesthetic drugs etc), correction of electrolyte abnormalities, minimal exercise
100
How do you correct the QT interval for heart rate?
(QT interval) / (Square root of R-R interval)
101
short qt caused by a mutation in
K channels
102
describe short qt syndrome
QT \<300ms at heart rate \<80bpm
May be associated with AF may present in young children and often a cause of young infant sudden death
103
what are the ecg changes in brugada syndrome?
ST elevation and RBBB in V1-3
104
diagnose brugada
Diagnostic ECG changes may seen only with provocative testing with flecainide or ajmaline (drugs that block that cardiac sodium channel)
105
treat brugada
. Treat – ICD; avoid drugs; genetic testing; ajmaline test (provokes arrhythmia and cardiovert)
106
what drugs need to be avoided in long qt?
Na channel blockers, psychotropics, analgesics, anti arrhythmics and anaesthetics
107
what is catecholaminergic polymorphic VT?
Adrenergic induced bidirectional and polymorphic VT, SVTS triggered by emotional stress or physical activity (autosomal dominant)
Alarm clocks and diving contraindicated.
108
Catecholaminergic polymorphic ventricular tachycardia
109
Catecholaminergic polymorphic ventricular tachycardia treat
given beta blockers; flecainide is considered but not always given
110
describe wpw
Very common. Short PR interval with delta wave.
Ventricular preexcitation
AVRT most common arrhythmia
AF more common and may be pre-excited
Small risk of sudden death
Ablate the patient and its sorted
111
mutations in what genes cause hypertrophic cardiomyopathy
sarcomeres
112
what would you look for on ecg to show hypertrophic cardiomyopathy
left ventricular hypertrophy
113
clinical signs and how you treat hypertrophic cardiomyopathy
Clinical profiles – sudden death; heart failure; end stage HF; atrial fibrillation
Treat – give ICD (HOCM: SCD risk calculator); avoid competitive sports
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genes associated with dilated cardiomyopathy
Sarcomere and desmosomal genes laminA/C and desmin if there is conduction disease, dystrophin if x linked
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genes and description of arrhythmogenic rv cardiomyopathy
Fibro fatty replacement of cardiomyocytes LV involvement in \>50 % of vases. Autosomal dominant and associated with desmosomal genes.
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describe management of inherited cardiac conditions
clinical and genetic testing while managing risks (lifestyle (reduce exercise); pharmacological management (beta blockers); non pharmacological management (ICD). Also make sure to do family screening after genetic testing of patient.
If sudden collapse and clinical death with no internal defibrillator, early CPR is necessary.
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complications associated with transvenous leads
· Endocarditis
· Perforation
· Haemothorax
· Pneumothorax
· Thromboembolic events
· Vascular complications
· Lead fractures
· Lead extraction complications
· Lead dislodgement
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chemical pathologist
study of bodily fluids
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microbiologist
study of bacetria
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haematologist
stidy of blood components
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immunologist
study of allergens
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virologist
stidy of viruses
123
why would a pathology specimen be abnormal?
inflammation; infection; metaplasia; dysplasia; invasive malignancy.
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metaplasia
is the transformation of one differentiated cell type to another differentiated cell type e.g. Barretts oesophagus
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dysplasia
presence of cells of an abnormal type within a tissue, which may signify a stage preceding the development of cancer (pre-invasive) e.g. tubular adenoma with high grade dysplasia, cervical intraepithelial neoplasia (CIN)
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differentiation
refers to the extent at which a tumour looks like its tissue of origin
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penetrance
the likelihood of having a disease if you have a gene mutation (100% penetrance means that you will always get the disease if you have the mutation)
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mendelian disorders
diseases that segregate in families in a manner predicted by mendels laws essentially a disease that predominantly caused by a single change in a single gene so has to be high penetrance
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aut dom children risk
autosomal dominant (50% risk of affected child – may have low penetrance)
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aut rec children risk
1 in 4 risk of affected child if parents are carriers
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x linked children risk
female carrier - half of the male children will be affected; half of the female children will be carriers. Affected male – all male children will be normal; all female children will be carriers
132
In x linked diseases, a female carrier may show features of the disease due to
In x linked diseases, a female carrier may show features of the disease due to x inactivation
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G1/ S/ G2/ M are each controlled by a series of ..... that activate each other and other enzymes in a step-wise fashion. Each .... is activated by a specific .......
G1/ S/ G2/ M are each controlled by a series of cyclin dependent kinases (CDKs) that activate each other and other enzymes in a step-wise fashion. Each CDK is activated by a specific “cyclin”.
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next generation sequencing
Next generation is more expensive but you get a much greater amount of info on genes. (large number of genes it looks at. The more genes you test the more variants you find the more difficult it gets)
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polymorphism
Any variation in the human genome that has a population frequency of greater than 1% (every person has about 3 million)
136
a mutation is a
DNA variant which causes or predisposes to a specific disease
137
what are balanced and unbalanced chromosomes?
Balanced chromosome rearrangement
All the chromosomal material is present, even though may be arranged in a different way
Unbalanced chromosome rearrangement
Extra or missing chromosomal material. Usually 1 or 3 copies of some of the genome.
Having 1 or 3 copies of a part of your genome is developmentally bad news.
138
acrocentric
Defined as a chromosome in which the centromere is located very near the end of the chromosome
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aneuploidy
whole extra or missing chromosome
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translocation
rearrangement of chromosomes
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what are the 4 non mendellian disorders?
multifactorial
imprinting
mitochondrial
mosaicism
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multifactorial
mutations in multiple genes combine with environmental factors to cause disease
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imprinting
Differences in gene expression depending on whether a gene is maternally or paternally inherited
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mitochondrial
Inherited almost exclusively from the mother; contains important genes for mitochondrial metabolic pathways and ribosomal RNAs
145
what is mocaisicm and what are the two types?
· Defined as the presence of two or more populations of cells with different genotypes in one individual (Somatic Mosaicism – derived from a post-zygotic mutation, may affect only a portion of the body and are not transmitted to progeny; Gonadal Mosaicism - When a person has two populations of cells in the gonads, one population of cells containing a DNA mutation or chromosome anomaly)
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name and describe the 6 different types of mutations
147
frameshift mutation
single base pair deletion
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DNA repair pathways
Base Excision Repair Pathway - Removes damaged bases
Nucleotide Excision Repair Pathway - Removes dimerize bases (caused by UV Damage)
Mismatch Repair Pathway - Removes mismatched Watson and Crick bases
Homologous Recombination - Copying DNA sequences from the sister chromatid to fill a double strand break
Non-homologous End Joining - Joining the two ends of a DSB
149
...... is done when you know which gene the patient is predisposed to so you are only targeting/ looking for that one gene mutation.
PCR
150
HOW DO YOU CALCULATE BABIES RISK OF GETTING CF?
151
The bonds between the bases and various other interactions allow the DNA to curl into a helix, which then wraps around proteins called
histones
152
RNA
Single stranded
Ribose rather than deoxyribose
Uracil instead of Adenine
153
¢ After transcription, you’re left with ......
¢ ..... must occur to get mature mRNA
¢ Splicing removes introns from the RNA transcript
¢ Only exons, which contain coding DNA, remain
pre-mRNA
Splicing
154
Each .... correspond with an amino acids
codon (triplet of bases)
155
describe dna synthesis
¢ DNA Helicase unzips the DNA; DNA polymerase copies the 5’-3’ strand
¢ DNA polymerase copies the 3’-5’ strand in Okazaki fragments which DNA ligase joins
156
mitosis
Gives 2 identical daughter cells; Occurs in the M stage of the Cell Cycle
157
meiosis
Gives 4 daughter cells; Daughter cells display genetic variation; Crossing-over
158
describe FISH
¢ Involves attached a fluorescent probe to a gene
One colour for one gene
¢ Can recognise aneuploidy, translocations etc.
These probes are complementary to certain regions of DNA in the target chromosomes, for example. This can therefore be used to identify aneuploidy, translocations etc.
159
DESCRIBE ARRAY CGH
¢ Patient DNA is mixed with red fluorescent dye and the control DNA with green; these two are mixed together and placed in wells
¢ These wells contain DNA probes to which specific regions of the patient and control DNA can bind
¢ If there is more control than patient DNA for that specific region, the well will be predominantly green
160
AUT DOM
161
AUT REC
162
X LINKED
163
EXPRESSION
the process by which information from a gene is used in the synthesis of a functional gene product
164
DE NOVO
An alteration in a gene that is present for the first time in a family
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INHERITED MUTATION
An alteration in a gene which is present in other family members
166
A GENETIC CHANGE IN DNA COULD BE DUE TO
· A disease causing mutation (would be pathogenic if symptomatic with rare mutation of gene known to cause disease)
· A polymorphism
A variant of unknown significance
167
WHAT ARE THE REASONS FOR HAVING A VARIANT OF UNKNOWN SUGNIFICANCE?
o Missence – causes a damage of one amino acid
o Trunkating – stop the sequence part of the way through
o Splicing – +/- exons; +/- introns in the final protein
168
DIAGNOSTIC
NGS
169
PRESYMPTOMMATIC
PCR TO LOOK FOR SPECIFIC GENE
170
SMAD4:p.Met157Thr
The Methionine in the peptide sequence of SMAD4 at position 157 has mutated to an threonine
Position 1 is the first amino acid of the peptide sequence
171
SMAD4:p.Cys162Ter
The Cystine in the peptide sequence of SMAD4 at position 162 has mutated to a stop codon
172
SMAD4:c.471A\>T
The Adenine in position 471 in the cDNA sequence has mutated to a thymine.
cDNA sequence is essentially the mature mRNA sequence with the introns removed, referenced to the first base of the first codon.
173
SMAD4:p.Arg157Ile
The arginine in the peptide sequence of SMAD4 at position 157 has mutated to an Isoleuine
Position 1 is the start Methionine of the peptide sequence
(we need a Database reference to tell us which sequence we are looking at)
174
INHERITANCE OF DISSCETING AA
AUT DOM
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CAUSES OF DISSECTING AA
changes in the TGF-beta1 pathway are associated with this; marfans sydnorme is associated with fibrillin mutations which has something to do with TGF-beta1
176
wide spread eyes; increased vascular tortuosity; bifid uvula
Loeys dietz syndrome
177
Loeys dietz syndrome associated with which mutations
TBR1/ TBR2
178
IS LONG QT LOW OR HIGH PENETRANCE USUALLY?
LOW - MAY HAVE MUTATION BUT MAY NOT HAVE DISEASE (EXPLAIN TO PATIENT ON GENETIC TESTING)
179
GENES CAUSING LONG QT
. LQTS1/ SCN5A – need to sequence a lot of genes as there are a lot of things that can cause it
NGS
180
tendon xanthomas and corneal arcus in a young person is a clue for
FAMILIAL HYPERCHOLESTEROLAEMIA
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TREAT FAMILIAL HYPERCHOLESTEROLAEMIA
statins to reduce their cardiovascular risk (young MI? – genetic screening for mutations) do their cholesterol levels, bp and cardiovascular risks
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INHERITANCE PATTERN OF FAMILIAL HYPERCHOLESTEROLAEMIA
MULTIFACTORIAL
183
MOST CARDIOVASCULAR GENETIC DISEASES ARE
MULTIFACTORIAL
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DESCRIBE THE GENETICS PF HUNTINGTONS
autosomal dominant; huntington gene; within 1 exon there is a trinucleotide repeat within the CAG; anticipation occurs (number of repeats increases with each generation); anyone with \>36 repeats may be affected and \>40 repeats = full penetrance
185
DESCRIBE GENETICS OF ALZHEIMERS
ApoE; presenilin 1 and 2 and APP; genetic testing can be predictive; consider these if the patient has a rare phenotype/ affected at young age; multifactorial
186
GENETICS OF BIPOLAR
twins play a large role in this disease; always check family history as is a risk factor in its self
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DESCRIBE THE GENETICS OF DUCHENNES MUSCULAR DYSTROPHY
x linked recessive; males; female carriers may have mild symptoms; mutation in dystrophin leading to a dystrophin deficiency (large scale deletions). Dystrophin is a key part of the Dystrophin-associated glycoprotein complex which links the internal cytoskeletal system of individual myofibers to structural proteins within the extracellular matrix
188
GENETIC OF MS
multifactorial; more common in individuals with certain MHC haplotypes
189
CHORIONIC VILLOUS SAMPLING
Involves sampling the Chorionic Villi
Complete at approx. 11.5 weeks
190
AMNIOCENTESIS
Involves sampling the amniotic fluid
Complete at 15 weeks +
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FOETAL BLOOD SAMPLING
Involves inserting a needle directly a foetal blood vessel
Complete at 18+ weeks
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MATERNAL BLOOD SAMPLING
Involves extracting free foetal DNA from the mother’s blood
Complete at 8+ weeks
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WHAT IS CONFINED PLACENTAL MOCAISISM
¢ Placenta is a highly proliferative tissue
¢ High proliferation = high number of mutations
DIFFERENCES IN THE CELLS GENETIC MAKE UP IN THE PLACENTA
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CURRENT PRENATAL SCREENING FOR DOWNS SYNDROME
¢ Dating Ultrasound Scan with Serum Biochemistry
Performed at approx. 12 weeks
Looks for increased Nuchal thickness
¢ Serum Screening
Performed at approx. 16 weeks
¢ Detailed Ultrasound Scan
Performed at approx. 20 weeks
Looks for other foetal abnormalities
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WHAT IS PREIMPLANTATION GENETIC DIAGNOSIS?
FINDING MUTATION AND ENSURING FOETUS IMPLANTED DOES NOT HAVE IT BY ONLY PLANTING SPECIFIC EMBRYOS
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GENETIC OF CHRONIC MYELOID LEUKAEMIA
Associated with the Philadelphia Chromosome
Reciprocal translocation of Chromosomes 9 and 22
Allows the formation of a tyrosine kinase
Transfers a phosphate group from ATP to a protein causing it to turn on
Codes for a protein that is continuously activated resulting in unregulated cell division
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GENETICS OF POLYCYTHAEMIA RUBRA VERA
Commonly a mutation in JAK2
Results in the formation of a kinase
Kinase allows activation of erythropoiesis in the absence of erythropoietin
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MUTATIONS INVOLVED IN ESSENTIAL THROMBOCYTHAENIA
Associated with CALR or MPL mutations
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MUTATIONS INVOLVED IN MYELOFIBROSIS
Associated with JAK2 and CALR mutations
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MISCARRIAGES WHICH ARE REFERRED TO COUNSELLING
\>14 WEEKS GESTATION
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STILL BIRTH
\>24 WEEKS TO TERM
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COT DEATH NOW CALLED
sudden unexpected death in infancy (SUDI).
203
WHAT IS AN APNOEA MONITOR?
ALARM GOES OFF WHEN BABY STOPS BREATHING
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DO NOT LET BABY SLEEP
WITH YOU
IN A CAR SEAT
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HOW WOULD YOU ASSESS A BABY IF THE APNOEA ALARM GOES OFF
look at baby not alarm; check if baby is breathing; give baby a pat on the nappy as may just need stimulation; check airway; check breathing; check circulation; carry on as routine
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TRANSCRIPTION
dna acts a template to make pre mrna
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SPLICING
mrna spices out introns to make mature mrna
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TRANSLATION
mrna used as template to make polypeptide
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RNA MODIFICATION
edit or remove pathological mRNA
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WHAT ARE THE STAGES OF DEVELOPING A NEW MEDICINE?
Idea and disease target
Phase one – give it to a human
Phase two – give it to a patient with the disease
Phase three – study to see if it helps with a cohort of patients (clinical efficacy)
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SPINOMUSCULAR ATROPHY GENETICS
sma type 1 (nusinersin)
One child with SMA – 1 in 4 risk of another affected child
In some testing there is prenatal testing for sma, but this does not come with guaranteed treatment
212
DRUG USED IN LONG QT
LONG ACTING BETA BLOCKERS
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