PBL 4 - cardiac embryology Flashcards
what is gastrulation?
the formation of 3 germ layers — endoderm, mesoderm and ectoderm
what does gastrulation enable through cell movements?
gets tissues and organs in correct orientation
what germ layer does the heart form from?
mesoderm
what happens in the 1st stage of cardiac development?
- cardiac cell fate acquired
- angiotensin cells located in cardiogenic plate — cranial and lateral to neural plate
how many days post fertilisation do heart fields form?
15
how many heart fields are there?
primary and secondary heart fields
where does the cardiac crescent fuse and what does it form?
cardiac crescent fuses at mid-line to form cardiac tube
what do the cells in the cardiac crescent do?
come together and elongate a bit at the midline of the embryo, so that those regions of the cardiac crescent will fuse into a single developing heart tube (primary heart tube)
after how many days does the linear heart tube form?
21
where is the heart tube formed?
mid-line
what cells are incorporated in the linear heart tube?
primary and secondary heart field derived cells
where are the developing heart tubes situated in relation to the developing atria?
more cranial to the developing atria
when does cardiac looping occur?
23-24 days
why does the linear heart tube loop?
must loop to acquire correct anatomy to enable the adult heart to function
where does the looping bring the atria?
brings atria more upwards and behind the presumptive ventricles
in what direction does cardiac looping occur?
dextral (rightward) — C-shape loop
anti-clockwise
cardiac looping is the first event to establish what?
left-right asymmetry
what is the name for defects in cardiac looping?
heterotaxy
what causes Situs Inversus (SI)?
complete looping in wrong direction of all organs
what causes Left Atrial Isomerism Syndrome (LAI) and RAI?
disruption of the left-right axis orientation during early embryonic development
list 4 heterotaxy syndromes
what is cardiac chamber development?
when atria and ventricles move into position and acquire specific identity
when does septation occur?
weeks 4-9 post fertilisation
atrial septation occurs in what 2 steps?
septum primum and septum secundum
when does atrial septation occur?
occurs end of 6th-8th week post fertilisation
what is the most common CHD to present in adulthood?
atrial septal defects — often asymptomatic
where is the foramen ovale in the developing heart?
between atria
what does the foramen ovale allow? what causes it to close?
- allows transmission of blood between RA to LA
- allows blood to bypass the lungs
- pressure changes following birth pressure promotes closure
what is a patent foramen ovale?
- birth defect
- common 10-20% of adults
- often asymptomatic
when does ventricular septation occur?
end of 7th - mid 9th week
what accounts for up to 40% of congenital cardiac malformations?
ventricular septal defects
when does AV valve formation occur?
mid 7th-8th week
what are the precursors of valves?
endocardial cushions
label this linear heart tube
when does outflow tract (truncus arteriosus) septation occur?
mid 7th-8th week
what does outflow tract (truncus arteriosus) septation do?
divides the truncus arteriosus into the aorta and pulmonary trunk
what is the ridge formed down the mid-line of truncus arteriosus by?
truncal cushions (similar in morphology to the cushions that give rise to the valves)
what is persistent truncus arteriosus?
- brith defect
- results from failure of septation of aorta and pulmonary artery
- single artery arising from both ventricles
- rare congenital defect
- causes complex circulatory problems
what is the name of the precursor of the epicardium?
proepicardium
describe epicardium formation and how it leads to coronary vessel formation
- cells from proepicardial organ (just below heart in embryo) migrate onto the developing heart tube and migrate on to form an epithelial layer on the top surface of the heart
- they further progress during development to differentiate and move deeper into the myocardium to give rise to the coronary vessels
what do EPDCs (epicardial derived cells) do? characteristics?
- move from epicardium into myocardium
- differentiate into other cardiac cell types
- coronary smooth muscle, myocardial fibroblasts, vascular endothelial cells (some debate over the latter)
- pluripotent — source of stem cells for vessel regeneration?
by what week have major heart chambers and vessels formed by?
8th week
where and what are the 3 main foetal adaptations of foetal circulation?
what does the ductus arteriosus connect?
the pulmonary artery to aortic arch
what does blood bypass due to the ductus arteriosus?
lungs
what is formed when the ductus arteriosus closes after brith?
ligamentum arteriosum
what promotes the closure of ductus arteriosus after birth?
increase in neonatal blood O2 content and withdrawal of maternal prostaglandins
how common is a patent ductus arteriosus?
occurs 8/1000 premature births and 2/1000 full-term births
why is a patent ductus arteriosus bad?
mixing of blood between aorta and pulmonary artery remains —result in abnormalities of the oxygenation of the blood due to mixing of oxygenated and deoxygenated blood
CHD occur in how many live births (1:_)?
1:125
what is the most common deletion syndrome that is an example of a CHD associated with a syndrome? 1/___ births?
22q11.2 deletion syndrome — 1/4000 births
explain 22q11.2 deletion syndromes
- genetic cause — TBX1 loss contributes to cardiac defect phenotypes
- spectrum of outflow tract defects
- TBX1, expressed in secondary heart field which gives rise to outflow tract (aorta, pulmonary artery, right ventricle)
- animals models reveal TBX1 is needed for proliferation in secondary heart field
- loss of TBX1 causes shorter outflow tract lacking septation
PFO (patent foramen ovale) increases the risk of what?
a stroke — blood clot forms in one of vessels retuning to heart and can travel up to brain
what % of CHD patients survive into adulthood?
90%
what does the primary heart field give rise to?
LA, RA, LV
what does the secondary heart field give rise to?
RV + outflow tract