Embryological Development of Cardiovascular system Dr. Cole Flashcards
Timeline: cardiovascular plan begin week ___ and present by week _____
3 and present by week 4
first system to develop
embryo can no longer meet nutritional or oxygen needs by diffusion
Development of CVS begins with the migration of _____ cells toward the _____
epiblast cells toward the primary heart field
cardiac progenitor cells = epiblast cells
where is the primary heart field?
surrounding the cranial neural folds
PHF cell migration
during migration they are specified to form left AND right sides:
this includes atria, left ventricle and some of the right ventricles
PHF forms the
atria, left ventricle and some of the right ventricle
SHG
secondary heart field, responsible for forming outflow tract
consisting of conus cordis amd truncus arteriosus
patterning of cardiac progenitor cells
occurs at the same time patterning of the rest of the embryo does
PITX2 programs heart cells in the primary and SHFs
gene/transcription factor PW that leads to development of PHF and SHF
5HT –> FGF8 –> Nodal/Lefty –> PitX2
PITX2 master gene for left sidedness
PITX2 problems —> (causes and outcomes)
SSRIs taken by new mothers —> interrupt PITX2 leding to heart defects
“a horseshoe shaped endothelial lined tube surrounded by myoblasts”
cardiogenic center formed when blood islands merge
this process begins when PHF progenitor cells are induced to form blood islands and cardiac myoblasts.
_____ tubes fuse to form a single primitive heart tube
endocardial
Embryonic circuit
series of aortic arches that connect to dorsal aortae
Cardinal veins
anterior and posterior cardinal veins drain developing embryo
“nursery for blood cells”
yolk sac
vitelline: supply and drain yolk sac “nursery for blood cells”
what veins drain into the sinus venosus
the anterior and posterior cardinal veins –> common cardinal vein –> sinus venosus
umbilical veins —> sinus venosus
vitelline —> sinus venosus
the embryonic vascular circuit is converted into
system and pulmonary portions
Embryonic structure and adult derivative
Truncus arteriosus —>
aorta, pulmonary trunk
Embryonic structure and adult derivative
Bulbus cordis —>
smooth part of right ventricle (conus cordis)
smooth part of the left ventricle (aortic vestibule (arotic vestibule)
Embryonic structure and adult derivative
Primitive ventricle
trabeculated part of left and right ventricles
Embryonic structure and adult derivative
Primitive atrium
Trabeculated part of right and left atria (auricles)
Embryonic structure and adult derivative
Sinus venosus
smooth part of the right atrium (sinus venarum), coronary sinus, oblique vein of left atrium
Blood flow through embryo
1 —> sinus venosus –> 2 —> 3 —-> 4
umbilical veins (from placenta) common cardinal vein (embryo) vitelline veins (yolk sac)
endocardial tube formation
Venous end is specified by
RA
endocardial tube formation
lower concentrations of RA specify
more anterior structures; ventricles amd outflow tract
by day 22, the fastest growing structures are
the truncus arteriosis
bulbus cordis
primitive ventricle
endocardial tube formation
what is it, and what does it become and how does it relate to the heart
it’s a primitive tube that arises out of blood islands combining
Day 23: the day the
endocardial tube begins to loop under the influecne of PITX2
the primitive ventricle and aorta bend around one another in which directions?
the ventricle bends inferiorly and the aorta bends superiorly making an S shape
the “shape” of the cardiac looping goes from ___ to ___
C to S
where is the fulcrum of bending in the primitive heart occur?
in the primitive ventricle: makes a V around an invisible fulcrum
Dextrocardia
heart is supposed to bend toward the left but in this condition the heart bends to the right and there is transposition of the great vessels
most common positional abnormality
Dextrocardia can occur at two times
during gastrulation or cardiac looping
Endocardial cushions
after folding, there is a narrow passage between PA and PV
dorsal and ventral blocks of tissue grow together
development of the tricuspid and bicuspid valves
the narrow AV cannel is formed after looping. dorsal and ventral masses fuse and separate Left and Right AV canals
“endocardial cushions” are the masses that
the critical “first step” in the formation of the 4 chambered heart
atrioventricular communis: fusion of endocardial cushions
Atrioventricular communis:
defect that occurs when the endocardial cushions fail to fuse, limits amount of blood that reaches the lungs
the effects of a common AV canal
enlargened pulmonary artery, decreased pulmonary resistance than in systemic circulation
Interventricular septum formation
Two parts: muscular portion devleoping in the midline of the floor of the primitive ventricle
grows upward towards endocardial cushions and down toward bulbar ridges
what defect results when the muscular midline of the interventricular septum fails to fuse
the r and l ventricles are not separated
most ventricular septal defects occur in the
the muscular portion (which are supposed to spontaneously close)
what kind of ventricular septum defect is most often correct by surgery?
membranous defect
VSD
ventricular septal defect
VSD causes
left to right ventricular shunting
acyanotic
(left to right shunting)
VSD pressure causes
increased blood flow to heart causes LF to fill —>
pressure causes blood to go into R ventricle —> R ventricle compensates by having to work harder and hypertrophying
Conduction effects associated with VSD
VSD doesnt effect the ventricular bundle branches almost at all. it is very rare.
Atrial septum formation: primums
foramen primum is the duct connecting the early atrias
the septum primum is the outgrowing walling superior to the atria
Atrial septum formation: secundum
the second event is a mass in the middle of the atria primum creating two new openings between the atria
foramen secundum and foramen primum
Atrial septum formation: endocardial cushion
grow up to merge with the primum, leaving a secundum
sequence of foramen formation
foramen primum —> foramen primum + foramen secundum —> foramen secundum + outgrowing septum primum —> foramen ovale + upper and lower septum secundum
what structures make up the formane ovale?
the upper and lower arms of the septum secundum
Before birth there’s a foramen ovale. describe the pressure differentials allowing it to work
Right atrium has greater pressure causing the foramen ovale shunt to open to the left atrium, which has a lower pressure
What is the “valve” between the atria that opens and closes before birth? What are the walls?
the arm of the septum primum = valve
upper/lower arms of septum secundum = walls of shunt
Foramen ovale —> adult structure
fossa ovalis
adult heart, LIMBUS =
septum secundum
adult heart, Fossa ovale =
septum primum, the floor
valve of the fossa ovale is the ____ while the floor of the fossa ovale is the
septum primum
septum secundum
atrial septal defects (ASD) : 3 kinds
defect in the foramen primum “ostium primum”
defect is similar to one in endocardial cushion
defect in secundum: foramen ovael and septum primum
defect in sinus venosus, usually near openings of SVC
Mutations in TBX5 cause
thumb anomaly and atrial septal defects. can also impact VSD
Sinus Venosus: the changes, and components
initially opens dorsally into the primitive atrium, L/R equl
then the R gets bigger L –> R
Shunts involve “nutritional” and embryonic circuits
nutritional circuits include
vitelline and umbilical
embryonic circuit includes
cardinal veins
Shunt 1 Vitelline Veins
liver develops in septum transversum, and is flanked on both sides by vitelline veins
veins grow into liver initially as hepatic sinusoids, veins, IVC, and some GI
Shunt 2 Umbilical
no direct connection with the heart by converting its liver connection into the ligamentum teres heptis
Umbilical vein —> ______ —> ______
ductus venosus —> IVC
bypasses liver and directs blood to heart
ductus venosus
connects umbilical vein with IVC
which horn of the sinus venosus enlargens
Right horn
what primitive structure does the “future superior vena cava” grow into?
right horn of the sinus venosum
what happens to the sinus venosus?
vitelline veins are absorbed into the GI system
umbilical veins are re-routed to utilize the ductus venosus to bypass the liver without having a direct connection to the right atrium
what happens to the cardinal veins?
Anterior cardinal veins become connected,
anastomosis becomes left brachiocephalic vein
right anterior cardinal and common cardinal become SVC
why does the right horn of the sinus venosus get larger?
because there’s shunting of the blood to the right atrium
Coronary sinus =
remnant of Left Horn of sinus venosus
sinus venosus becomes the
smooth part of the right atrium
left horn of sinus venosus
becomes coronary sinus, oblique vein of the left atrium
Crista terminalis marks the
division between sinus venosus and embryonic primitive atrium and auricles
truncus arteriosus becomes partitioned to become
the aortic and pulmonary semilunar valves
partition of the AV canal will form the
bicuspid and tricuspid valves
neural crest cells migrate to ridges of truncus arteriosus
here they contribute to formation of truncus ateriosus
and bulbis cordis
Aorticopulmonary septum
it twists like a pretzl, making the twisting arrangement of the pulmonic trunk and the aorta
the distal aspect of the aorticopulmonary septum has to connect to the
endocardial cushions and interventricular septum
Eisenmenger’s Syndrome
incomplete fusions of bulbar ridges —> inferior VSD
there’s a proliferation in intima and media that narrows the lumen in
eisenmenger’s syndrome, causes increased pulmonary resistance, causes R–>L shunt cyanosis
Tetralogy of Fallot
Pulmonary stenosis,
VSD
overriding aorta
Rt. Ventricular hypertrophy
ventricular defect that causes septal in R atrium to remain unfused, so blood is shunted directly into the aorta
Arterial System: aortic arches
6 pairs of aortic arches
connect the aortic sac and truncus arteriosus to the dorsal aortae
pharyngeal arches organize development of head and neck
Aortic Arche 1
Contribute to maxillary arteries
Aortic Arche 2
produce stapedial and hyoid arteries
Aortic Arche 3
Common Carotid arteries and proximal portion of the internal carotid arteries
Aortic Arche 4
persists after birth to connect dorsal aorta to ventral aorta = aortic arch
on the right it forms the proximal portion of the right subclavian artery
Aortic Arch 5
lost, does not develop into anything known
Aortic Arch 6
Proximal portions develop into pulmonary arteries; distal portion develops into the ductus arteriosus
Ductus Arteriosus: what compound is required to sustain it during development?
PGE2, prostaglandin 2 by the ductus
what kind of medication would a pregnant woman avoid in order to prevent the ductus arteriosus from closing off?
NSAIDs: they interfere with prostaglandins
Patent Ductus Arteriosus
failure of ductus arteriosus to close after birth
Branches of the Aorta
cervical intersegmentals —>
vertebral arteries
Branches of the Aorta
seventh intersegmentals —>
subclavian arteries
Branches of the Aorta
thoracic intersegmentals —>
intercostal arteries
Branches of the Aorta
lumbar intercostals —>
iliac arteries
Branches of the Aorta
lateral segmental branches —>
adrenals, renal, gonadal arteries
Branches of the Aorta
ventral segmental branches (vitelline and allantoic) —->
vitelline —> GI, celiac, superior and inferior mesenteric arteries
allantoic —> umbilical arteries
Vitellin veins become the
part of IVC, hepatic veins/sinusoids, ductus venosus, portal, superior/inferior mesenteric ans splenic veins
TAPVR
Total Anomalous Pulmonary Return
TAPVR: supracardiac
pulmonary veins drain to the right atrium via superior vena cava
TAPVR: Cardiac
pulmonary veins come together behind heart, drain into right atrium via coronary sinus
TAPVR: Infracardiac
pulmonary veins drain to the right atrium via hepatic liver veins and IVC
All TAPVRs have AT LEAST an
ASD
what happens to an embryo with a TAPVR who lacks an ASD?
baby will die because blood cant be shunted to left side of the heart
Right Aortic Arch malformation
persistence of right 4th arch distal to the right subclavian
left segment is caudal to left subclavian disappears
isolated
situs inversus complex
Doubt Aortic Arch
4th aortic arch caudal to right subclavian persists ,creating a vascular ring around trachea and esophagus
Coarctation of Aorta
Aorta narrows right near ductus arteriosus
once PHF cells are established, what happens
underlying pharyngeal endoderm induces the cells to form cardiac myoblasts and blood islands through the process of vasculogenesis
why do blood islands unite?
to form the horseshoe shaped endothelial lined tune surrounded by myocytes called the “cardiogenic region”
