Basic cardiac embryology Nov2 M1 Flashcards
% of births with heart anomalies and one important origin of defects
0.7-0.8%
adaptations (shunt) developmental defects
why % of heart defects is greater than 0.7% or 0.8%
- many spontaneous defects abort prenatally
- some defects noticed later in life
2 leading causes of death in neonatal phase (1st month)
- Prematurity
2. Congenital heart disease
what causes congenital cardiac defects (2 categories)
genetic and environmental causes
ex of genetic causes of congenital heart disease
NKX2.5 mutation, Down syndrome, Edwards 18, Tuners, DiGeorge 22.
ex of environmental causes of congenital heart abnormalities
rubella virus, German measles, retinoic acid (vitamin A) disturbances, diabetes
first system formed in embryo
CVS
CVS origin (in the trilaminar embryo)
mesoderm
3 important cell types formed early in embryogenesis (day 14) important for the heart
- cardiogenic mesenchyme
- hemangioblasts
- neural crest cells
3 simultaneous events occuring in heart dev between day 17-22
- neurulation
- somite formation
- vasculogenesis and angiogenesis
time of first heart beat during embryogenesis
day 21
name of shunt in pulm artery during dev + name of remnant after birth
ductus arteriosus
ligamentum arteriosus
what ductus arteriosus does
shunts blood from pulm artery to aorta during embryo
most frequent congenital heart disease
Ventricular septum defect (VSD)
second most frequent congenital heart disease
Patent ductus arteriosus (stays open so venous blood goes to the body, cyanosis at birth)
third most frequent congenital heart disease
atrial septum defect
what structure forms cardiogenic mesenchyme and at what embryonic stage
primitive streak, at trilaminar embryo
what cardiogenic mesenchyme does once created in primitive streak
migrates in front of forming brain region
name of cardiogenic mesenchyme when still in primitive streak
mesenchyme. will say cardiogenic when has migrated
what structure cardiogenic mesenchyme lies on in front of brain + importance
will lie on the endoderm. Endoderm will induce cardiogenic mesenchyme to form heart
what mesenchymal stem cells also form in the primitive streak + importance
hemangioblasts. Most important stem cell forming the CVS
what hemangioblasts can give rise to
angioblasts and hematopoietic stem cells
how coelum forms
mesoderm forms somites and coelum forms in the somites
why coelum important in CVS embryology
will form the pericardial cavity
earliest shape of coelum and embryonic stage
U shape during trilaminar embryo phase
what cavity formed by the coelum is the most cranial + location
pericardial cavity. will be very close to the cardiogenic mesenchyme
hemangioblasts formed by the primitive streak: where they go (4)
go to extra embryonic tissues (yolk sac and placenta) and embryonic tissues and amnion
first hematopoietic organ of the embryo and 2 important cell types
yolk sac. mesenchyme and hemangioblasta
what anterior endoderm will stimulate other than the cardiogenic mesenchyme
will stimulate intra embryonic hemangioblasts to form endothelial tubes
hemangioblast in mesenchyme (in yolk sac for example): 3 markers at single cell stage
brachyury
Flk-1
endoglin
how hemangioblast develops in mesenchyme (in yolk sac for ex)
form a ball of cells: peripheral layer of angioblast and hematopoietic SCs in middle
marker of angioblasts
Flk-1
markers and charact. of endothelium surrounding angioblasts and hematopoietic SCs in middle
Flk-1, basement membrane, VE-CAD
name of phenomenon in middle of ball surrounded by angioblasts
intravascular hematopoiesis
name to hematopoiesis when happens outside an angioblast surrounding + example
extravascular hematopoiesis. ex. in bone marrow
name of structure formed by hematoipoietic stem cells within angioblasts circle
blood islet (or island)
what angioblasts and hematopoietic cells ball will do
angioblasts sprout and will form vessels
what is found in middle of cardiogenic mesenchyme before folding of trilaminar embryo
in center, endothelial vessels called endocardial tube (are the cavity of the future heart)
morphology of endothelial tube
two tubes paired
endothelial tubes (made of endothelial lining and cardiogenic mesenchyme) connect to what veins
vitelline vein in posterior region (from yolk sac) umbilical vein (from placenta)
most early CVS description
2 endocardial tubes, aorta coming out, vitelline vein and umbilical vein
first beating of heart occurs when in terms of embryonic phases and dev
before folding of trilaminar embryo, within the endocardial tubes
where heart goes after folding of trilaminar embryo
moves to thoracic region
where aorta (coming out of heart) goes
to placenta
what structure will envelop the endocardial tubes as they fuse
pericardium (has parietal and visceral layer). Visceral layer goes over tube
morphology of vessels entering the single endocardial tube after folding an d location
are paired. enter the tube at the caudal region at septum transversum
septum transversum origin
mesenchyme
consequence of defects in lateral folding of the body (that didn’t meet in the midline)
incomplete sternum, heart exposed to outside
how heart chambers number will evolve and what this reminds of
initially one chamber after folding. then 2 like fish. then 3 like amphibians. then 4
most important gene in cardiogenic mesenchyme + 2nd name
Nkx2-5 (Tin Man gene)
function of Nkx2-5
orchestrates cardiac transcription pathway (all other TFs that go form the chambers)
Nkx2-5 gene haplosufficient or haploinsufficient so we say that the condition is _____
haploinsufficient. dominant
what happened when Nkx2-5 knocked out in drosophila
no heart developped
defects of one Nkx2-5 mutation
ventricular septum defects, atrial septum defects, cardiac defects, conduction anomalies
cardinal veins gross def
primitive embryonic veins
where common cardinal veins drain in the heart exactly
in sinus venosus. posterior
where common cardinal veins drain tissue from
cranial and caudal embryonic tissues
sinus venosus def
is the inflow chamber of the primitive heart tube
what drains into the sinus venosus + origin
paired cardinals (from embryo), umbilical vein (from placenta), vitelline vein (from yolk sac)
name of outflow trunk in the primitive heart tube and what it does
truncus arteriosus. empties in aortic sac which empties in paired aortic arches to the two dorsal aortae
how primitive heart tube will start to form the heart chambers + initial structures obtained
primitive dilations
- primitive common atrium
- primitive common ventricle
- bulbus cordis
oxygenation of blood from cardinal, umbilical and vitelline veins
cardinal veins: deox
umbilical: highly oxyg
vitelline veins (yolk sac): hematopoeitic stem cells within the islands (yolk sac embryonic blood)
3 walls of the heart (layers)
inside: endothelium (primitive wall = endocardium)
2nd layer: myocardium
3rd region: epicardium
what myocardium gives rise to
myoblasts
what lines epicardium
mesothelium
epicardialization def
process by which the visceral pericardium forms the epicardium
inside the heart, what accompanies the endocardium (endothelium)
primitive mesenchyme in a cardiac jelly
what mesenchyme cardiac jelly does
plays role in valve formation, septation of the heart, formation of the fiber skeleton, molding into heart shape
3 myoblast lineages formed by the myocardium + name these have in common (not important)
3 types of myocytes*:
- contractile striated myocytes
- Myo-conducting myocites (Purkinje cells)
- Myo-endocrine cells that produce ANF
important component of epicardium around the heart tube
coronary vessel precursors
description of event changing paired symmetrical system to asymmetrical system
bulbo-ventricular looping of the single heart within the pericardial cavity
asymmetrical drainage into the heart: components
IVC, SVC, coronary sinus
location of venous inflow and arterial outflow prior to heart folding
venous inflow is caudal (bottom)
arterial outflow is cranial (top)
what happens to endocardial tube after folding in thoracic cavity
they fuse together
normal positioning of the heart and abnormal: names
levocardia is normal
dextrocardia is abnormal
in levocardia, event initiating bulbo-vent looping
Pitx2 expressed on left side. and also in SA region
Pitx2 type of gene
TF
other TF expressed at looping + origin
retinoic acid (vitamin A): by mesenchyme
what region becomes the sinoatrial node
sinus venosus
location of atrium after looping (in levocardia)
in the back.
orientation of looping in levocardia and what happens
counterclockwise. truncus arteriosus, bulbus cordis, pV and pA fold to the left and stay in that order from top to bottom
dextrocardial situs inversus def and what happens
inversion of heart in situs inversus where other organs inverted too. Pitx2 expressed on the right
isolated dextrocardia def
only heart inverted
isolated dextrocardia: what is normal and what is abnormal
RA and RV are normal.
Apex is to the right (abnormal)
transposition of great vessels: position of aorta and pulm trunk + connection
aorta in front (connects to RV) and pulm trunk in the back (connects to LV)
problem of transposition of great vessels
hypoxia at birth
why transposition of great vessels is viable (2)
Ventricular septum defects + open ductus arteriosis allow mixing of the blood (correction surrgically at birth)