Heart development embryo Flashcards
what is used to make blood vessels during vasculogenesis?
mesenchyme
what does vasculogenesis begin and what is it coupled with?
Day 17
hematopoiesis
where does vasculogenesis begin?
mesoderm adjacent to the endoderm of yolk sac wall.
how is the initial vascular network formed?
aggregates of hemangioblastsdifferentiate and give rise to both hematopoietic progenitor cells and endothelial precursor cells(EPCs)
These cells organize to form blood islands that then coalesce, lengthen and interconnect
what structures are visible by the end of week three?
you have a vascularized yolk sac wall, connecting stalk, and chorionic villi.
what are the sites of eventual hematopoiesis?
blood islands of the yolk sac, liver, aortic-gonadal-mesonephric region, lymph organs, and then bone marrow
when do Embryonic hematopoietic cells appear? what do they do?
day 17 and go on to populate and
reside in the developing liver primordia by day 23.
where do hematopoietic stem cells come from?
hemogenic endothelial cells of the dorsal aorta
in the aortic-gonadal-mesonephric (AGM) region
when can stem cells produce both lymphoid and and myeloid lineages?
how do they do it?
about day 30, in the liver
go out to populate lymph organs and bone marrow
how is vasculogenesis in embryos different from people?
blood vessel formation within the embryo is NOT coupled with hematopoiesis, except AGM region
when can you first see blood vessels in embryos? where?
By day 18,
one can begin to see vessel formation in the intraembryonic splanchnopleuric mesoderm
how is blood vessel formation done in embryos?
endothelial precursor cells (EPCs) proliferate and differentiate into endothelial cells that then organize into vasculogenic cords
form angioplastic plexus
how does angioplastic plexus in embryos grow and spread?
(1) continued proliferation of endothelial precursor cells,
(2) angiogenesis, the budding and sprouting of new vessels from existing ones
(3) intussusception(splitting),
(4) the recruitment of new mesodermal cells into walls of existing vessels
other than splanchnic mesoderm, where else can blood vessel development occur in embryos?
paraxial mesoderm
what are angiomas?
abnormal blood vessel and lymphatic growthvia a vasculogenic process, likely stimulated by abnormal levels of angiogenic factors
cavernous hemangiomas.
Excessive growth of venous sinuses
capillary hemangioma
Excessive growth of a small capillary network
Hemangiomas of infancy, what are they? are they important?
benign tumors made of mostly endothelial cells
can lead to clinical complications. However, most regress over the years
what forms the first heart field? where is it in comparison to intraembryonic coelom
formation of EPCsclusters
within a cardiogenic area of intraembryonic splanchnic mesoderm
with the adjacent mesoderm
intraembryonic coelom lies dorsal to this
what happens to first heart field and coelom with anterior/posterior body folding?
what is the consequence of this?
the primary heart field and coelom become folded beneath the embryo
pulling some endoderm inside to form the foregut
limbs of the first heart field now lie ventral the foregutand dorsal the coelom!!
EPCs differentiate into endothelial cells forming two primitive endocardial tubes.!!
what happens to first heart field with lateral folding?
the two forming heart tubes brought together
these heart tubes fuse with mesoderm to form simple tubular heart!
what does simple tubular heart link to? what happens to it as embryo continues to grow?
future pericardial cavity
his heart tube is pulled into the cervical and then the thoracic regions.
cranial ends of the developing dorsal aorta are also dragged ventrally along with the heart thereby forming a loop
FIRST AORTIC ARCH is formed!
how is first aortic arch formed?
cranial ends of the developing dorsal aorta are also dragged ventrally along with the heart thereby forming a loop
. Inflow of blood into the primitive heart is via what vessels?
common cardinal veins, vitelline veins, and umbilical veins.
primary heart tube wall consists of what?
Endocardium: blood vessels
myocardium
cardiac jelly: between the other two
when does the simple tubular heart have its first contraction? heart flow?
Day 22
Day 24
what are the initial parts of the simple heart?
Sinus venosus
Primitive atrium
Atrioventricular (AV) region
Primitive ventricle
Outflow tract
Aortic sac
what does the Sinus venosus do?
made of partially confluent right & left sinus horns
umbilical vein(placental blood–O2enriched),
vitelline vein(blood from gut area–venous blood),
and common cardinal vein
drain into each horn
where is the Primitive atrium?
region between sinus venosus and ventricle
what is the Atrioventricular (AV) region?
region of heart separating theprimitive atrium from primitive ventricle
what is the Outflow tract?
portion between primitive ventricle and aortic sac.
what is the aortic sac?
common confluens of pharyngeal arch blood vessels. These will contribute to the great vessels
what is the Dorsal mesocardium?
suspends the heart tube but eventually ruptures forming the transverse sinus
remnants form the proepicardial organ
what is the Epicardium?
future visceral pericardium
what is the primitive ventricle?
early left ventricle.
Delineated from future right ventricle
by a constriction called theinterventricular sulcus
what is the first major step in cardiac septation? what happens?
Cardiac looping , reverses atrial and ventricular positions as the heart tube lengthen
atrium moves cranially and dorsally
outflow tract initially bends to right, ventrally and inferiorly
primitive ventricle bends left and superior-dorsal to the proximal outflow tract.
what forms future right ventricle?
initial outflow tract
outflow tract forms what two structures?
conus arteriosus at cranial end
truncus arteriosus at distal end
why is second heart field developed?
what does it require?
lengthening of the cardiac tube to allow for cardiac looping
NCC within pharyngeal arches, interaction with pharyngeal arch mesoderm and pharyngeal arch endoderm are required to maintain proliferation
how does Failure of proliferation of splanchnic mesoderm affect looping?
results in several cardiac defects including looping anomalies (discussed below) and
outflow tract defects
what are the two looping anomalies?
Ventricular inversion
Heterotaxia
what is ventricular inversion?
the primitive ventricle folds to the right
and the outflow tract ends up on the left with the outcome being a
right-sided, left ventricle
what is heterotaxia?
any abnormal left-right development ofeither some or all organs
two types of heterotaxia?
Situs inversus
Situs ambiguous
what is Situs inversus?
complete reverse symmetry of the heart and GI organs that is not fatal and may be asymptomatic
what is Situs ambiguous?
reversal of some organs
“Visceroatrial heterotaxia”:condition whereby the heart and GI tract are asymmetrically arranged from one another
problems with inflow and outflow tract development, life threatening
what eventually happens to Left vitelline vein and left umbilical vein ?
eventually disappear
what happens to left sinus venosus and left horn?
what does this cause?
shift their connection to the right half of the common atrium
because the expansion of the atria is more pronounced
on the left side of the common sinus opening.
net shift in the amount of blood returning to the right side of the common atrium
what disappears from left sinus horn and what does it become?
Left vitelline vein and left umbilical vein
left common cardinal vein disappears
eventually remains of the left sinus horn becomes
the coronary sinus
what happens to sinus venosus as atrium enlarges?
only opens into the future right atrium (sinoatrial orifice)
what is incorporated into posterior wall of the expanding right atrium?
. Right sinus horn
and proximal parts of the right vitelline
and right common cardinal veins
right common cardinal vein becomes what as atrium enlarges?
superior vena cava
right vitelline vein becomes what as atrium enlarges?
inferior vena cava
when do venous valves develop?
As the right atrium incorporates the developing superior and inferior vena cava and orifice of the coronary sinus,
what become valve of inferior vena cava?
Inferior part of right valvular fold
what forms SA node?
. A portion of the right sinus horn and right common cardinal vein
valve of the coronary sinus is formed by what?
a small fold of the remaining left sinus horn
what does Differential growth make?
muscular interventricular septum and muscular atrial septum
Never fully closes a lumen,
Endocardial cushion tissue makes what?
fibrous (membranous) portions of atrial and
ventricular septum and conotruncal ridges of the outflow tract
formation of new connective tissue that occurs in the AV region and outflow tract
How is AV septum formed?
superior (dorsal) and inferior (ventral) endocardial cushions
fuse at midline
what do cushion cells do?
provide mesenchyme needed for anchoring the heart valves and also contribute to the cardiac skeleton
what are Conotruncal ridges made of?
part ECT and part neural crest cell-derived.
Conus arteriosus is divided how?
divided so blood from LV and RV go out different vessels
Truncus arteriosus is divided to make what and how?
will be divided to make aorta and pulmonary arteries
by formation of an aorticopulmonary (AP) septum
where are two septa produced in the atrium?
want O2-rich blood from the placenta (entering the future RA) to get to the left side with most of it skipping the lungs.
what induces Septum 1 formation?
touching of outflow tract to atrium during cardiac looping
how does Septum 1 form, what contributes to its formation as well?
extends from atrial wall toward the AV septum.
eceives a contribution from the dorsal mesenchymal protrusion(DMP) or spina vestibuli (mesodermal)
what is the ostium primum?
Septum primum has a hole in it near the AV septum
how is ostium secundum formed?
As cushion tissue from the AV septum and DMP begins to close this hole, a new hole forms in septum primum toward cranial (superior) end , this is ostium secundum
how is septum secundum formed? what does it overlap?
As the atria are expanding, septum secundum grows toward the AV region.
As it grows, it overlaps the ostium secundum.
what is the opening left by septum secundum? what overlaps it
foramen ovale, overlapped by septum primum, blood cant flow back to left atrium
when can a patent foramen ovale cause problems?
if it doesnt close within one year
What happens after first breathe?
pulmonary circulation increases blood flow and return to right atrium
drives septum 1 against septum 2, seals septum
what happens with atrial septal defects in the beginning?
initial left to right shunting because of increased blood flow returning from the lungs
leads to pulmonary resistance over time
what does increased pulmonary resistance cause?
causes the RV to hypertrophy and over time this leads to congestive heart failure
cyanosis due to right to left shunt
what happens with a high atrial septal defect?
hole in atrial septum
inadequate development of septum 2
what happens with a low atrial septal defect?
failure of up-growth of AV cushion tissue from AV septum and DMP to fill in ostium primum
what is cyanosis?
bluish coloration of the skin due to the presence of deoxygenated blood mixing with oxygenated blood to the point that
it lowers the overall oxygen content and is insufficient for normal tissue physiology.
describe the Fetal cardiac blood flow pattern from TV?
Blood entering the RV from the RA includes less oxygenated blood from SVA and coronary sinus but also a portion of the blood from the IVC.
Blood exiting the RV re-enters the systemic arterial side via the ductus arteriosus with only about 11-13%actually going through the pulmonary arteries to reach the developing lungs
how does blood enter heart from IVC?
bulk of the blood entering from the IVC is shuttled through the foramen ovale into the left atrium.
the LA receives the oxygenated blood that is transferred to the LV and out into fetal systemic arterial side
ventricular septation is accomplished by what? what are the parts
formation of the interventricular septum
septum is made of a muscular part and a fibrous part
partitioning of outflow tract accomplishes what?
must be divided into two tubes in such a way that it connects the future aorta to the LV and the pulmonary artery to the RV
what arch connects RV to lungs?
Aortic arch VI
what arch connects LV to the body?
aortic arch III & IV
what is myocardialization?
outer myocardial wall is thinned as some myocardial cells begin to be replaced by cushion cells in specific areas and there is further remodeling through apoptosis
what is double-outlet right ventricle? what does it happen from?
both aorta and pulmonary artery exit via the right ventricle with an accompanyingventricular septal defec
symptoms showwithin days including cyanosis, breathlessness, murmur and later,
cardiac looping is insufficient,
what divides outflow tract, what is made from?
conotruncal septum, made from conotruncal ridges
made from neural crest cells and from the endocardial-derived cushion tissue
Complete ventricular septation is completed how?
fusion of the conotruncal ridges with each other and then
with the interventricular septum and coincident with a
downgrowth of cushion tissue from the AV septum
what provides primordia for semilunar valves of aorta and pulmonary trunk
Spiraling ridges at the truncus/conus junction
what are ventricular septal defects caused by?
what happens?
Failure of proper closure by abnormal or inadequate fibrous tissue is the cause 95% of the time
becomes cyanotic sometime after birth
as the RV hypertrophies due to increased work load
what is the usual outcome of ventricular septal defects?
RV hypertrophies enough so that the RV pressure builds and exceeds the left side, so now a right to left shunt develops
Eventually die of cardiac failure if not addressed.
Persistent truncus arteriosus is caused by what?
failure of contruncal ridge formation and fusion
pulmonary artery arises some distance away above the undivided truncus.
VSD because of the ridges contribution to the fibrous portion.
Undivided truncus overrides bothright & left ventricle. There is mixing of oxygenated and deoxygenated blood within truncus so it can present with low degree of cyanosi
Persistent truncus arteriosus can lead to what?
pulmonary congestion, RV hypertrophy, increased right ventricular pressure
Tetralogy of Fallot is caused by what?
Conotruncal ridges form off-center leading to unequal division of pulmonary trunk and aorta.
consequences of Tetralogy of Fallot ?
- VSD (missing fibrous portion).
- Pulmonary infundibular stenosis.
- Overriding aorta
- RV hypertrophies in the fetus , right to left shunting of blood even at the time of birth
Transposition of great vessels is caused by what?
what happens?
Conotruncal ridges fail to spiral.
pulmonary artery is connected to the LV and the aorta to RV
Even with shunts, a life expectancy may be only 3 years without surgery.
Pulmonary valvular atresia is due to what?
Semilunar valves are fused leading to RV hypoplasia
Patent foramen ovale then forms the only outlet for blood on right side to get to the left side
Ductus arteriosus is always patent and is only route for blood to get to lungs
how can a person stay alive with Pulmonary valvular atresia
Surgically can open the pulmonary valve and if the RV is not too weak, the person can live
If there is an accompanying VSD,blood can enter the left ventricle and be pumped out the aorta, univentricular heart
Aortic valvular stenosis, what happens? why? to who?
leads to hypertrophy of LV and eventually to cardiac failure and pulmonary hypertension
Can be congenital , due to disease, or generation
4:1 in males
Bicuspid aortic valve, what happens?
2 leaflets rather than 3 are formed
Results in regurgitation or later, to a form of stenosis
eventual leads to LV hypertrophy.
“leads to aortic aneurysms”
Aortic valvular atresia, what happens? how can it be resolved
valves are completely fused the LV is underdeveloped
wide ductus arteriosus forms because it is the only way O2-enriched blood from placenta can get into left side
Leads to RV hypertrophy during fetal period
after birth, O2-enriched blood must enter right atrium by way of an atrial septal defect and then enter the systemic circulation by passing through a patent ductus arteriosus.
Tricuspid atresia, what happens?
obliteration of right AV orifice
fusion of tricuspid valves always associated with patency of foramen ovale, ventricular septal defect, underdeveloped right ventricle, hypertrophy of left ventricle, and patent ductus arteriosus
how can Tricuspid atresia be treated?
Can be corrected surgically if RV is not too under developed, or surgery
Hypoplastic left ventricle, what happens?
the LV is underdeveloped with absent or small bicuspid and aortic valves
The ascending portion of the aorta is underdeveloped and there’s a patent ductus arteriosus and/or foramen ovale
heart is basically working as a univentricular heart with the RV doing all the work
Hypoplastic left ventricle, how to treat it?
Surgical and medical interventions improve outcomes
how is conus arteriosus and truncus arteriosus formed?
initial outflow tract +myocardium
truncus arteriosus forms what?
aorta +pulmonary artery
