Congenital Heart Disease 1 and 2 Flashcards
What is the clinical importance of understanding fetal cardiodevelopment?
many fetal genes are turned on during heart failure/CV disease –> BMP, e.g. is an ER test for CHF
Embryogenesis of the heart
cardiac specificatino –> linear heart tube –> looping –> septation –> patterning of great vessels –> circulatory changes at birth
An epithelial layer of cardiac progenitors that forms early in development
cardiac crescent –> at anterior rim of embryonic disc
As an embryo grows, the heart assumes a position ventral/dorsal to the forming forebrain and foregut
ventral
When does blood flow begin (embryologically)?
when there is a linear heart tube –> intrinsic pacemaker caudal-rostral –> single circulation in series caudal-rostral
Where do most of the RV and OT cells come from?
secondary heart field –> migrate to heart tube and differentiate into muscle
How does lithium cause heart defects?
it is a Wnt agonist and messes up embryogenesis
11-18% of secondary heart field defects are attributable to genetic variation in ____
ISL1
What is cardiac looping?
linear heart tube bends to the right and anteriorly –> direction driven by regional differences in growth rate
*beginning of septation, myocardial trabeculation
How does atrial septation occur?
septum primum grows from dorsal wall of atrium towards AV cushions –> initially incomplete (passive) w/ residual vascular connection called ostium primum –> eventually completely close by fusion with cushions (active) –> ostium secundum opens and is closed passively by the septum secundum (parallel septum that still allows blood to still go through) –> closure at birth otherwise PFO
What causes PFO?
incomplete fusion of septum secundum with septum primum to block the ostium secundum –> small variant
Most common ASD
ostium secundum atrial septal defect- -> center of ceptum b/w right and left atria –> due to incomplete formation of septum or incomplete active closure of ostium secundum
*pfo is a variant that is small
What is an ostium primum ASD?
incomplete closure of the ostium primum –> at lower portion of atrial septum –> often associated with cleft/slit in the anterior leaflet of mitral valve
What is a sinus venosus ASD?
least common ASD –> upper portion of atrial septum due to defect in formation of septum primum –> associated w/ one pulmonary vein connected to RA instead of LA (anomalous pulmonary vein)
Nkx2.5 is….
a homeobox gene that is expressed as heart muscle precursors are specified –> heterozygous mutation in humans with CHD: ASD, conduction, tetralogy of fallot
Why might retinoic acid/vitamin A deficiency during pregnancy lead to CHD?
expression of homeobox is dependent on retinoic acid
How many pairs of symmetric aortic arch arteries exist initially and what happens to them?
5 –> some regress, others grow –>asymmetric adult vascular pattern –> requires signals from neural crest and pharyngeal endoderm for remodeling
What is DiGeorge Syndrome?
most common chr deletion syndrome –> CHD, parathyroid deficiency, thymus defect
- appears similar to neural crest ablation
- 22q11 - tbx1 (most common gene)
3 circulatory changes at birth
- closure of ductus arteriosus
- closure of ductus venosus
- closure of foramen ovale
What abnormality? mirror image
dextrocardia, situs inversus –> cilia mutation in early embryonic development
What abnormality? discordance between organs in mirror image
heterotaxy
How do valve leaflets form?
endothelial cells migrate into cardiac jelly (between endothelium/myocardium) –> phenotypic switch EMT (via ras)–> become the endocardial cushions that mature into valve leaflets
formation of new blood vessels from endothelial precursors/angioblasts
vasculogenesis
formation of new blood vessels from pre-existing blood vessels
angiogenesis
Which pathway determines artery vs vein and tip cells which mediate branching in vessel growth?
notch ligand/receptor
Which pathway is key in angiogenesis?
vegf
Which pathway mediates nerve and blood vessel patterning?
semaphorin (mediate repulsive signals in axon guidance/growth cone collapse) and plexin
What gives rise to the epicardium?
proepicardial organ (from septum transversum) –> EMT –> required for coronary artery development and myocardial maturation
Neural crest fate in heart
arterial smooth muscle in aorta –> divide aorta and pulmonary trunk
