Week 3 Flashcards
What percent live births are affected by congential heart disease?
1%
Heart defects cause problems by what 2 things?
- Obstructing flow in heart or vessels near to it
2. Cause blood to take an abnormal route through the heart
Name 2 genetic conditions predisposing to congenital heart disease?
- Down’s syndrome
2. Turner’s syndrome
Name 3 pregnancy factors which may increase the chances of a congenital heart disease?
- maternal alcohol misuse
- maternal drug treatment and radiation
- maternal diabetes
What is the most common type of congenital lesion?
Ventricular septal defect
What 3 congential heart defects, with shunts, will present as acyanotic?
- Atrial septal defect
- ventricular septal defect
- patent ductus arteriosus
What 3 congenital heart defects, without shunts, will present as acyanotic?
- Coarctation of the aorta
- Pulmonary stenosis
- Aortic/left heart obstruction
What 3 congential heart defects, with shunts, will present as cyanotic?
- Fallots tetralogy
- Transposition of great vessels
- All but with PHT (Eisenmenger’s complex)
What 3 congenital heart defects, without shunts, will present as cyanotic?
- Severe pulmonary stenosis
- Tricuspid/Pulmonary atresia
- Hypoplastic left heart
What are possible symptoms of a congenital heart defect?
- Difficulty feeding in infancy
- Failure to thrive in infancy
- Shortness of breath
- Syncope
- Squatting in older children
- Symptoms of cardiac failure
What are the possible signs of a congenital heart defect?
- Murmur
- tachycardia
- tachypneoa
- central cyanosis
- clubbing
What are 4 possible complications of a congenital heart disease?
- Infective endocarditis
- Paradoxical embolism
- Polycythaemia
- Pulmoary hypertension
EIsenmenger’s syndrome?
When pulmonary pressure exceeds systemic and so shunt reverses to right to left, resulting in cyanosis
What Investigations would you do for congenital heart disease?
- History
- Echocardiography: non-invasive, cheap and quick
- Cardiac catheterisation: more serious cases
What are the 2 types of atrial spetal defect?
- Ostium primum defect- lower in atrial septum, riskier as closer to valves (15% of presentations)
2/ Ostium secundum defect- higher in atrial spetum, less serious (75%)
Describe the pathophysiology of an atrial septal defect?
Left to right shunt through defect in inter-atrial septum.
Results in dilation of pulmonary artery
Murmur due to increased flow over pulmonary valve
What is the presentation of an atrial septal defect?
Acyanotic, left to right shunt.
Adult with significant shunt may develop right heart overload/failure.
Parasternal heave/ pulmonary flow murmur
What is the clinical management for an atrial spetal defect?
- Primum defect: early closure recommended
- Secundum defect: closure for moderate to large defects only
Which type of ventricular septal defect is the more severe and why?
Membranous as closer to the valves (higher)
What is the pathophysiology of a ventricular defect?
When left ventrical contracts, some blood enters the aorta whilst some is shunted into the right ventricle to enter the pulmonary circulation. Resulting in pulmonary hypertension- eisenmengers complex for large shunts
What is the presentation of ventricular septal defects?
Acyanotic left to right shunt.
Large shunts may lead to symptoms of cardiac failure in young children and pulmonary hypertension/eisenmengers
Signs:
Pansystolic murmur (lasts for duration of systole)
What is the management for a ventricular septal defect?
Larger defects: management of cardiac failure
Surgical intervention may be required.
What is patent ductus arteriosus?
When the ductus arteriosus fails to close, resulting in a persistent connection from proximal left pulmonary artery to descending aorta
Which direction does blood flow in patent ductus arteriosus?
From descending aorta (due to higher pressure) down into pulmonary artery
What is the pathophysiology of patent ductus arteriosus?
Left to right shunt, acyanotic
Murmur produced by turbulent aortic/ pulmonary artery shunt.
May lead to left heart overload (due to increased pulmonary return), sometimes may cause pulmonary hypertension and eisenmengers
What is the presentation of patent ductus arteriosus?
Acyanotic,
with large defect, feeding difficulties in infancy and failure to thrive,
Continous machinery murmur below left clavicle +/- thrill
bounding pulse due to increase left stroke volume
What is the management of patent ductus arteriosus?
Prostaglandin synthesis inhibitor, closure of defect
What is coarctaion of the aorta?
Locallised constriction in the aortic diameter, usually distal to ductus arteriosus due to abnormalities in tunica media
What is the pathophysiology of coarctation of the aorta?
No shunt, severe obstruction of blood, instead aorta is perfused by collateral channels (subclavian, to vertebral arteries, to intercostal anastamosis, to aorta)
What are the symptoms of coarctation of the aorta?
May be asymptomatic, or headahces/nosebleeds/intermittent claudication of LL/ cold legs (due to BP difference between Upper and lower body
What are the signs of coarctation of the aorta?
Hypertension in the upper limbs,
weak/delayed pulses in the legs,
may have systolic murmur over upper back (due to turbulence through narrowed section)
What is the medical management of coarctation of the aorta?
Surgical repair, baloon dilatation and stenting
What is fallot’s tetralogy?
- Ventricular septal defect
- Pulmonary stenosis
- Hypertrophy of right ventricle
- Overrinding aorta
(although only 3 of them need to be present)
resulting in cyanotic right to left shunt
What is transposition of the great arteries?
Cyanotic, usually aorta drains the right ventricle and pulmonary artery drains the left ventricle, resulting in 2 seperate circulations
What is peripheral cyanosis?
Blue tinge of the skin. Not as worrying as central cyanosis. Can be due to cardiac failure, shock or pathology.
What would you look for on a patients fingers?
- Tar staining (indicating smoking)
- Nail clubbing (abnormality in soft tissue)
- Splinter haemorrhage (due to circulating immune complexes or trauma)
- Osler’s Nodes (RARE)
- Janeway lesions (abcesses from septic emboli. RARE)
What is central cyanosis?
Blueish colour in lips. Very concerning - needs urgent medical assistance.
What is Malar flush?
- Discolouration over patients cheeks, dusky pink and bilateral
- Due to pulmonary hypotension due to mitral stenosis
What are Xanthoma(ta)?
- Fatty deposits under the skin, can be over tendons or knees or elbows
- Hallmark of hypercholestoleamia
What are Xanthelasma?
- Yellowish plaques around the eyes.
- Concerning in a young person you need to check cholesterol and blood liver profile
What is Corneal Arcus?
- Discolouration around the iris.
- Due to cholesterol crystals.
- May be normal in older patients but could be due to hypercholestaemia
What is a normal heartrate?
60-100 bpm
How long should you record an irregular pulse?
1 minute
What is the character of a pulse?
The rise and fall of a pulse.
What might cause a fast and regular pulse?
Exercise, anxiety, pain, fever, medication, hyperthyroidism
What might cause a fast and irregular pulse?
Uncontrolled atrial fibrillation, hyperthyroidism (but also predisposes to AF)
What might cause a slow and regular pulse?
Athletic training, hypothyroidism, medication
What might cause a slow and irregular pulse?
Sick sinus syndrome, second degree heart block, complete heart block
What causes low volume?
Hypovolaemia, left ventricular failure
What causes increased volume?
Anaemia, fever, thyotoxicosis
What changes character?
slow rising pulse - aortic stenosis
collapsing pulse - aortic regurgitation
What is the jugular venous pulse?
- Measured by the right internal jugular vein.
- Pulsation reflects changes in pressure within the right atrium
How do you measure the JVP?
- Position the patient at 45 degrees.
- Ensure neck relaxed/turned to left.
- Measure vertical height from sternal angle to top of jugular venous pulsation.
- Should be less than 4 cm.
- JVP can be obliterated by gently occluding vein.
What you can feel on praecodium?
Find apex beat then check its position
Heaves - left sternal edge, right ventricular enlargement (due to right ventricular hypertrophy) as hand is pushed off right chest wall.
Thrills - Palpable murmur as you put your hand on someones chest, and you feel a vibration (apex, upper praecordium, sternal notch)
What happens during Ascultation?
Tell patient what you are doing.
Palpate carotid pulse initially and distinguish 1st and 2nd heart sounds. Listen for heart sounds, added sounds and murmurs (turbulent blood flow)
Use bell (higher frequency sounds) and diaphragm (lower frequency sounds)
Manoeuvres to accentuate diastolic murmurs (get patient to lie on left side to bring heart closer to chest wall / make them hold in their breath / make them to lean forwards)
Remember carotids (patient must hold breath)
What are the other components of the cardiovascular exam?
- Auscultate lung bases
- Sacral oedema
- Peripheral vascular examination
- BP
- Fundoscopy
- Urinalysis
- Offer abdominal examination
What is the first and second heart sound due to?
First heart sound - mitral and tricuspid valves closing
Second heart sound - pulmonary and aortic valves closing
Both listened to with a diaphragm
What proportion of people with down’s syndrome also have a heart defect?
~50%
What are the 4 common heart defects associated with down’s syndrome
- atrial septal defect
- ventricular septal defect
- atrioventricular canal defect
- patent ductus arteriosus
Which chromosome is tripicated in down’s syndrome?
Trisomy 21
How can we establish which genes on chromosome 21 are related to the heart defects associated with down’s syndrome in human cases?
Often there is only segments of triplicated 21, or there is a large rearrangement of the tripicated 21 chromosome. See which genes are triplicated most frequently in the individuals with heart defects
What technique is used to view the loci of specific genes?
Fluorescent in situ hybridisation (FISH)
What are the 2 genes when triplicated that are associated with down’s syndrome studied in transgenic mice?
DSCAM (down’s syndrome cell adhesion molecule)
COL6A2 (collagen alpha 2 (VI) chain)
What role does the DSCAM gene play in development?
Cell adhesion
What role does COL6A2 play in development?
Cell migration
What are the 2 other terms used to describe DiGeorge syndnrome?
- 22q11.2 deletion syndrome
- CATCH-22
How can a deletion be shown on a chromosome?
Using FISH
What are the 5 phenotypes associated with DiGeorge/22q11.2 deletion syndome?
Cardiac abnormalities Abnormal facies Thymic aplasia Cleft palate Hypothyroidism
What are the three cardiac abnomalities associated with DiGeorge syndrome?
- Interruption of the aortic arch
- Tetralogy of fallot
- Ventricular septal defect
Why do the deletions arise?
Misalign, resulting in chromosome breakage and rearrangement- the region may be duplicated or deleted.
How does a patient aquire the deletion?
Either de novo OR inherited if not detected in the parent
How does DiGeorge syndrome arise without deletion?
Instead of being missing, there is a mutation of the gene
Which gene, if mutated would result in DiGeorge syndrome?
TBX1 gene
What possible mutations could occur in the TBX1 gene?
- Deletion, resulting in a frameshift/nonesense mutation
- Base pair substitution, resulting in an amino acid change, missense mutation
How would you describe a patient with one base at a position on 1 chromosome but another at the same position on another chromosome?
Heterozygous at that position
What is TBX1?
- Transcription factor
- Regulated transcription from a particular set of genes on the DNA sequence.
- Located at the 22q11.2 loci
What is the effect of the TBX1 gene being increased or decreased?
Abnormal development of 4th pharyngeal arch arteries
What is hypertrophic cardiomyopathy?
- Either pathological or due to athlete being highly trained.
- Wells of heart are thickened including the septum, most commonly on the left side
What is the phenotype of hypertrophic cardiomyopathy?
- increased muscle thickness,
- disorganised myocytes
- fibrosis
In what fashion is the genetic defect for hypertrophic cardiomyopathy passed on?
Autosomal dominant
What is the name given to a phenotype that can be caused by a defect in more than one gene?
Locus heterogeneity
How is a “long QT” patient defined?
Exceeds the 99th percentile value in a population
What causes the long QT signal?
Delay in the repolarisation of the ventricles
What causes the delay in repolarisation due to loss of function?
- Channelopathy, loss of function mutation in the K+ ion channel, meaning K+ can’t flood out to repolarise myocyte.
- Mutations occur on cytoplasmic side of the channel.
- Inability to repolarise
What is the name given to a phenotype that may be produced due to lots of different mutations to the same gene?
Allelic heterogeneity
What causes a delay in repolarisation due to a gain in function?
SCN5A sodium channel stays open, due to mutation. This extents depolarisation, making it harder to repolarise.
In what fashion are mutations for long QT inherited?
AUTOSOMAL DOMINANT
What is penetrance?
The likelyhood that a molecular diagnosis (presence of mutation) will give rise to a clinical diagnosis (phenotype)
Will people with c loop, v.s. non-c loop long QT mutations respond well or poorly to beta blockers
C loop mutations responds well to beta-blocker
What is familial hypercholesterolaemia?
Inherited predisposition to high concentrations of serum LDL cholesterol (total >7.5mM)
What clinical signs may you see with someone with hypercholesteraemia?
Xanthoma, atherosclerosis
What possible consequences are there due to the high frequency of familial hypercholesterolaemia?
- Possibility that offspring of two parents with different mutations for hypercholesterolaemia will aquire 2 separate genes contributing to the condition.
- Resulting in a severe phenotype
What is the name given to a genotype with two seperate mutations, on from maternal and one from paternal chromosome, contributing to a condition?
COMPOUND HETEROZYGOTE (severe phenotype)
What sort of things can happen as a result of mutation in the LDL pathway to cause hypercholesterolaemia?
- receptor not sythesized
- cholesterol not transported properly into the cell membrane
- receptor doesn’t bind to LDL well
- Receptor isn’t internalised properly
- receptor is not recycled properly
What treatment is effective at treating people with familial hypercholesterolamia?
Statins
What are the strategies of treatment for treating heart failure?
- Increase cardiac contractility
- Decrease preload and/or afterload to decrease cardiac work demand
- Inhibiting RAAS
- Preventing inappropriate increase in heart rate
How would you decrease preload an afterload
Relax vascular smooth muscle (vasodilation) and decrease blood volume
What is the acronym for drugs used in heart failure?
DAB (diuretic, ace inhibitor, beta blocker)
What are the signs and symptoms of heart failure?
- Shortness of breath
- Swelling of feet and legs
- Chronic lack of energy
- Difficulty sleeping due to breathing problems
- Swollen or tender abdomen with loss of apetite
- Cough with frothy sputum
- Increased urination at night
- Confusion and/or imparied memory
What is class 1 New York Heart Association Classification of Heart Failure (NYHA)?
No limitation of physical activity