Lecture 5 - Congential Heart Defects Flashcards
What are congenital heart defects?
Structural abnormalities of the heart that are normally present at birth and affect the blood flow through the heart and to the rest of the body
When do congenital heart defects occur?
During embryogenesis and foetal growth
What is the septa?
Separates the chambers and great vessels
What do valves allow?
Unidirectional flow of blood through the heart and vessels
What are the great veins?
Vena cava and pulmonary veins
What are the ventricles?
Pumping chambers
What is the atria?
The collecting chambers
What is the left ventricle connected to?
Aorta
What is the right ventricle connected to?
Pulmonary trunk
Where does deoxygenated blood enter?
Right atrium
Where does oxygenated blood enter?
Left atrium
What does most congenital heart defects result in mixing?
Deoxygenated blood with oxygenated blood
What is the heart composed of?
A thick layer of cardiac muscle called myocardium
What are individual cells in the myocardium called?
Cardiomyocytes
What is the layer of cells called inside the heart?
Endocardium
What structures does the endocardium form?
Cushions which are precursors of the valves and the septa
What are the great arteries coated in?
Smooth muscle for muscular support
What are neural crest cells essential for?
Outflow tract cushions - come from outside the heart and migrate down into the heart and contribute to its development
What is the heart coated with?
A single cell layer called epicardium
What is the heart enclosed in?
The pericardium - a sac
What is cardiovascular development divided into?
Embryonic stage and foetal stage
What happens in the embryonic stage?
All organs are forming and cells are differentiating, in humans this lasts 8 weeks
What is the foetal stage?
Is mostly growth lasts 32 weeks, maturing of certain structures
What happens mid way through the embryonic stage?
The heart starts it form
What cells are formed in them formation of the heart in the embryonic stage?
The progenitor cells
What are progenitor cells?
They come together and form the linear heart tube - where they have the ventricle at the top and the atria at the bottom as this is the way through blood comes through
Describe looping
Rearranging the heart tube so you end up with the atria at the top and ventricles at the bottom
How are the chambers formed in the heart?
By ballooning
What is septation?
Where the heart is formed and divided into each chamber
What is the cardiac mesoderm?
Original progenitors of the heart - form in early development
What does the formation of the foregut do?
Brings the two arms of cardiac crescent together
What is the cardiac crescent?
Cell progenitors migrate out to the anterior lateral plate
What is gastrolation?
The stage you start to get condensing of the cells into layers
What does gastrolation form?
The distinct tissue layers that will then go onto to differentiate into vital organs
What is gastrolation portrayed as?
A single sheet which has an ectoderm
What happens to the ectoderm as development continues?
There is infolding of the ectoderm cells which forms the neural tube
What happens after formation of the neural tube?
Fusion of the neural tube and the mesoderm is pushed into a cardiac crescent and forms the heart
What are the two distinct progenitor cells that form the heart?
Primary heart and secondary heart fields
What does the primary heart field form?
The left ventricle and part of the atria
What does the secondary heart field do?
Adds cells to ends of the heart tube as looping occurs and forms the right ventricle and outflow tract and most of the atria
What happens during the looping phase?
The heart tube detaches from the body wall region
When is the heart joined to the body wall at outflow and inflow tract?
After breakdown of dorsal mesocardium
What are some inherited cardiac malformations?
Atrioventricular defects and gapes between the atria and the ventricles
What happens if the vessels are transposed?
It could be disastrous
What are inherited cardiac malformations associated with?
Syndromes or single gene mutations - or could be syndromes linked with single gene mutations
What is the process for septation important?
Because it is how you separate the two blood streams
What is the outflow track separated into?
The aorta and the pulmonary trunk
What is the atria separated by?
The atrial septum
What does the ventricular septum separate?
The right and the left ventricle
What are the atria and the ventricle separated by?
By valves, left = bicuspid, right = tricuspid
How is the outflow tract septated?
Has the aorta coming off the left ventricle and the pulmonary trunk going to the arteries off the right ventricle
What is the septum that separates the atria?
The interatrial septum
What are the two parts of the interatrial septum?
Prime and the secondum
What is different about the atria septum?
Don’t form a complete barrier
What is a cardiac shunt?
When blood follows a pattern that deviates from the systemic circulation
What is a cardiac malformation in shunts?
Left - to right shunt is bad
Describe left to right shunts
Allows oxygenated blood to return directly to the lungs rather than going to the rest of the body
Describe the right to left shunt
Allows deoxygenated blood to bypass the lungs and return to the body without becoming oxygenated - better shunt when you are foetus
What are two types of shunts used in the foetus?
Arterial duct and foramen ovale (part of the atrial septum)
In foetus what does the arterial duct do?
Acts as a shunt to divert blood away from the non-functioning lungs
When does the arterial duct close?
1-2 days after birth
Where is the arterial duct found?
Connects to the pulmonary trunk and goes straight to the aorta
What does the foreman ovale allow?
Allows blood to be pumped across from the right atrium into the left atrium then to the left ventricle to be pumped around the body - bypassing the lungs
What does the right to left shunts allow?
Allows the foetus to have a pumping heart
What is a patent arterial duct?
The arterial duct remains open, this means that oxygenated blood can be pushed back into the aorta down the channel into the pulmonary circulation. Putting stress on the heart and can cause left ventricular overload and increased circulation in the lungs
What are the symptoms of patent arterial duct?
Fast breathing, shortness of breath, lack of appetite, failure to gain weight and sweating with exertion
What are prostaglandins and how are they derived?
They are physiologically active compounds and are derived from arachidonic acid
What do prostaglandins do?
They interact with specific receptors and the interactions allowed for the specific vessel to be maintained in a dilated state (open)
What happens after birth - to prostaglandins?
Prostaglandins and ligands are reduces because they are not signalling anymore - the dilation factor is taken away and the duct starts to close off
How long can it take for the duct to close?
24-48 hours
What do prostaglandins interact with?
EP4 and EP2
What happens to prostaglandins with babies that have CHD (congenital heart defects)
Prostaglandins are given to the baby to keep the duct open so there is time to prep for surgery - allows the duct to be open so that some oxygenated blood can be delivered around the body
What are intra cardiac malformations?
Defects inside the heart
Where are the most common intra-cardiac malformations found?
In the atria or the ventricles
What is an example of a intra-cardiac malformation in the atria?
Atrial septal defect (ASD) which causes a left-to right shift and volume overload of the right atrium and right ventricle
Describe the atrial septal defect
An opening in the interatrial septum
How does atrial septal defect affect individuals?
Children are rarely symptomatic but it can lead to later life problems e.g. hypertension, heart failure or atrial arrhythmias
What does the ventricular septal defect (VSD) cause?
Left to right shunt - communications between the ventricles
What direction will shifting normally go in?
From the left to the right because of the higher pressures in the left heart
What are the 4 other common congenital heart defects known as the tetralogy of fallout?
- VSD, overriding aorta, pulmonary stenosis and right ventricular hyper trophy
Describe the overriding aorta
Aorta sits on top of the VSD, instead of being on the left ventricle - means that it can receive blood from the left AND the right
Describe pulmonary stenosis
Narrower, thinner then normal - the right side of the heart has to pump hoarder to try and get blood to the lungs and the extra work required by the ventricles makes it bigger which is hypertrophy
ASD = atrial septal defect symptoms
Heart murmur, shortness of breath, fatigue, swelling of legs, feet or abdomen
VSD symptoms
Shortness of breath, fast heart rate, paleness, failure to gain weight and sweating while feeding
Tetralogy of fallout (FOT) symptoms
Shortness of breath, blue colouration of the skin
What is the outflow tract?
The region of the heart through which blood passes to enter the great arteries
What happens to the outflow tract during development?
Goes from a single tube to having cushions that then remodel to form valves (aortic and pulmonary valve)
3 cushions =
Tricuspid valve
2 cushions =
Bicuspid valve
What is septation of the outflow tract caused by?
Neural crest cells
What do the neural crest cells do?
Separates the common trunk into two vessels
What are cardiac neural crest cells known as?
A migratory cell population that stem from the neural tube
What transition to neural crest cells undergo?
Epithelial to mesenchymal transition - means that can now migrate down to the fragile arches
What can neural crest cells also differentiate into?
Smooth muscle which coat the forming arch arteries
Where do neural crest cells originate from?
The dorsal region in the occipital neural tube
What can the pax3 gene do in mouse models?
Can separate the aorta and the pulmonary trunk
What are outflow tract malformations?
Double outlet right ventricle - aorta remains in the right ventricle it hasn’t been twisted, there is no aorta to take blood away so within a couple of cycles the ventricle will swell and pop
What is a consequence of the double outlet phenotype?
Double outlet is always associated with the ventricle septal defect
What is another more severe phenotype associated with the doublet outlet?
Common arterial trunk (CAT), septation has failed and you end up with one big vessel
Symptoms for outflow tract malformations
Blue colouration, shortness of breath, lack of appetite and failure to fain weight
How long into birth can mothers know what is wrong with their baby?
20 weeks
What is the most common congenital defect?
The bicuspid aortic valve, normally the valve has 3 leaflets but it only has 2 which means there is abnormal fusion between the 2 cusps. Affects 1-2% of the population
What are the sympotoms for bicuspid aortic valve defect?
Some people can be asymptomatic, later life problems include calcification (get stiff), stenosis and aortic valve regurgitation where the valve can let blood out but it doesn’t close properly
Describe hypoplastic left heart syndrome
Very serious affects 4 per 10,000 births, effects the structure of the left side of the heart, get a very small left ventricle - the capacity to deliver oxygenated blood around the body is reduced
Describe charge syndrome
It is a multifactorial condition
C = Colomboma of the eye
H = heart defects
A = arteries of nasal choanea (bones at the back of the nose)
R = retardation of growth
G = genital and or urinary abnormality
E = ear problems
What gene is the majority of patients that have charge syndrome found to have a mutation on?
Mutations in CHD7 on chromosome 8
What is CHD7 involved in?
DNA binding and chromatin remodelling
What is Down syndrome known as?
Trisomy 21
What do 50% of downsyndromes have?
A congenital heart defect - mostly commonly atrioventricular septal defect (VSD)
Describe holt syndrome
Caused by a mutation in TBX5, all patients have at least one abnormality, affects carpal bones of wrist - 75% of patients have heart defects
Describe noonan syndrome
Mutations in of 5 different genes account for 60-80% of cases, craniofacial features, growth related or chest deformalites including cardiac abnormalities
What are the 5 genes in Noonan syndrome?
PTPN11, KRAS, SOS1, RAF1, NAF1
What are examples of single gene mutations?
NKX2-5 and NOTCH
What is hypertrophic cardiomyopathy?
Is one of the most frequently occurring inherited cardiac disorder - it is the disease of the sarcomere caused by mutations of contractile protein genes
