9- Heart Development Flashcards
These are the most common life-threatening birth defects. They comprise 20% of all congenital defects in live births. Causes include:
- 4% single gene mutations
- 6% chromosomal anomalies
- 5% teratogens
- 85% multifactorial
Heart Defects
This is the process of making blood vessels directly from mesenchyme.
Vasculogenesis
***Remember, mesenchyme is embryonic CT derived from neural crest and mesoderm!
At day 17, vasculogenesis starts at the mesoderm that is adjacent to the endoderm of the yolk sac wall and is coupled with ________, which is blood cell formation
hematopoiesis
Describe how a blood island is formed
Hemangioblasts will differentiate and give rise to hematopoietic progenitor cells and endothelial precursor cells
These cells all organize together to form a blood island
How do blood islands form an initial vascular network?
They coalesce, lengthen, and interconnect
By the end of the ____ week, you have a vascularized yolk sac wall, connecting stalk, and chorionic villi
3rd
What are the sites of hematopoiesis?
Blood islands of the yolk sac
liver
aortic-gonadal-mesonephric region
lymph organs
bone marrow
Embryonic hematopoietic cells appear about day ____ and go on to populate and reside in the developing liver primordia by day _____.
17
populate liver by 23
What do embryonic hematopoietic stem cells go on to be?
embryonic erythrocytes
macrophages
megakaryocytes
Where are the definitive hematopoietic stem cells programmed?
hemogenic endothelial cells of the dorsal aorta in the aortic-gonadal-mesonephric region (AGM)
Describe hematopoietic stem cells…
- When do they “seed” the liver
- What do they do when they get there?
- day 30
- They give rise to the myeloid and the lymphoid stem cell lineages that are able to go and populate the lymph nodes and the bone marrow
The AGM regions appears on day ____ and disappears by ____
27
40
T/F: blood vessel formation in the embryo is NOT coupled with hematopoiesis
TRUE
Where does the initial blood vessel formation occur (in what embryonic layer)?
What is another place that intraembryonic vasculogeneis can occur? (migrate to form vessels outside the splanchnic mesoderm)
Intraembryonic splanchnopleure mesoderm
Paraxial mesoderm
Describe the overall process of intraembryonic vasculogenesis
- intraembryonic splanchnic mesoderm differentiates into endothelial precursor cells
- these can proliferate and differentiate into endothelial cells
- endothelial cells organize into small cords and coalesce to form long tubes
- angiogenic plexus continues to grow
What are the steps that an angioplasties plexus is able to grow and spread?
- continued proliferation of the endothelial precursor cells
- angiogenesis (forming new vessels)
- intusseption
- recruiting new mesodermal cells into the wall of existing vessels
_______ is the splitting of a blood vessel
intussusception
_______ is the budding and sprouting of new vessels from existing ones
angiogenesis
________ are caused by abnormal blood vessel and lymphatic growth
Angiomas
What are angiomas stimulated by?
abnormal levels of angiogenic factors
_______ is the excessive growth of a small capillary network
Capillary hemangioma
______ is the excessive growth of the venous sinus
Cavernous hemangioma
the ______ ______ ______ is the EPC clusters that are arranged in a horseshoe shape within the cariogenic area of the intraembryonic splanchnic mesoderm and the adjacent mesoderm
first heart field
Where does the intraembryonic coelom lie in relation to the first heart field?
Dorsal
As the anterior/posterior body folding occurs, the _______ _______ ______ and _____ become folded beneath the embryo, pulling some endoderm inside to form the foregut.
Primary heart field
coelom
After the anterior/posterior folding, where do the limbs of the heart field lie?
Ventral to the foregut and dorsal to the coelom
Describe the formation of the simple tubular heart
During anterior/posterior folding, the EPCs differentiate into endothelial cells and produce two primitive endocardial tubes
While this is happening, the lateral sides of the embryo start to move together and the two tubes will merge and fuse midline and also fuse with the cardiogenic mesoderm
** tubes–> merge–>fuse to cardiogenic–> boom tubular heart
What are the three pairs of vessels that allow the inflow of blood into the primitive heart?
- common cardinal veins
- Vitelline veins
- umbilical veins
Primary heart tube wall consists of:
1.
2.
3.
- Endocardium–inner epithelium continuous with blood vessels.
- Myocardium.
- Cardiac jelly– concentration of extracellular matrix between endocardium and
myocardium.
First rhythmic contraction begins about day ____
22
blood flow starts about day ____
24
What are the 5 things that make up the heart tube?
- Sinus venous
- Primitive atrium
3 AV region - Primitive ventricle
- Aortic sac or root
________ is made of partially confluent right & left sinus horns. Draining into each horn is an umbilical vein (placental blood–O2 enriched), vitelline vein (blood from gut area– venous blood), and common cardinal vein (venous blood from head and trunk) in the tubular heart.
Sinus venous
________ is region between sinus venosus and ventricle. Receives blood from sinus venous in the tubular heart.
Primitive atrium
_____________ is the region of heart separating the primitive atrium from primitive ventricle. Lumen of this region is called the atrioventricular canal or foramen in the tubular heart.
AV region
the _____ ______ is the portion between primitive ventricle and aortic sac in the tubular heart.
outflow tract
______ _____ is the common confluens of pharyngeal arch blood vessels. These will contribute to the great vessels. Present in the heart tube
Aortic sac or root
________ ________suspends the heart tube but eventually ruptures forming the transverse sinus seen in the adult
Dorsal mesocardium
What do the caudal remnants of the dorsal mesocardium form?
The proepicardial organ
Proepicardial cells eventual migrate over the surface of the myocardium forming the______
epicardium
epicardium is also known as the future ______
Visceral pericardium
_____ _____ is the first major step required for cardiac septation
cardiac looping
Prior to cardiac looping, describe the positioning of the atria and the ventricles
The ventricles are above the atria; the looping reverses these positions
Atrium moves _______ and ______ so it becomes located between outflow tract and dorsal pericardial wall while it enlarges.
cranially and dorsally
The initial outflow tract forms the future ____ ______
right ventricle
The outflow tract initially bends to ______, _______, and _______ during cardiac looping
right
ventrally and inferiorly
the _____ ______ bends left and somewhat superior-dorsal to the proximal outflow tract during cardiac looping
primitive ventricle
Myocardium is added at the cranial end of the heart tube to form the ______ _______ which is the proximal outflow tract; becomes the outflow portion of both ventricles
conus arteriosus
The distal end of the heart tube forms the ______ _______ which is the distal outflow tract; forms the aorta and pulmonary artery
truncus arteriosus
What are the steps of cardiac looping
- tube lengthens and reverses the atria and the ventricle–
a. atrium moves cranially and dorsally and is located between the outflow tract and the pericardial wall
b. outflow tract moves to the right, ventrally and inferiorly
c. ventricle moves left and superior/dorsal to the outflow tract - Myocardium is added to the proximal end forming the conus arteriosus
- distal end of the tube forms the truncus arteriosus
Cardiac looping requires lengthening of the cardiac tube at both ends, predominantly at the _____ ______ _____
cranial outflow end
How is the heart tube able to lengthen in the way that it needs to?
Creates the second heart field
Describe where the second heart field forms
At both ends of the tube at the site of the rupturing dorsal mesocardium
Tissue- tissue interactions between _____ ______ , pharyngeal arch ______ and pharyngeal arch _____ are necessary for maintaining cardiogenic mesoderm proliferation and proper myocardial cell specification within the second heart field.
Neural crest
pharyngeal arch endoderm
pharyngeal arch mesoderm
This is an anomaly where 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.
Ventricular inversion
_______ is any abnormal left-right development of either some or all
organs. Often seen in immobile cilia syndrome and Kartagener syndrome.
Heterotaxia
_____ _______ is the complete reverse symmetry of the heart and GI organs that is not
fatal and may be asymptomatic.
situs inversus
_____ _______ is the reversal of some organs
Situs ambiguous
_______ _______ is a condition whereby the heart and GI tract are asymmetrically arranged from one another
Visceroatrial heterotaxia
What is the fate of the left vitelline artery and the left umbilical artery?
They disappear
The left sinus venosus and left horn shift their connection to the _____ _____ of the common atrium because the expansion of the atria is more pronounced on the _____ side of the common sinus opening
right half
left
*** shifts the amount of blood that is returning to the right side of the common atrium
The remaining left sinus horn after certain veins have disappeared turns into the ______ _____
coronary sinus
(in atrial enlargement) Right sinus horn and proximal parts of the right vitelline and right common cardinal veins are incorporated into the _____ _____ of the expanding right atrium.
posterior wall
The _______ ______ ______ _____ becomes the superior vena cava while the ______ _____ _____ eventually becomes part of the inferior vena cava
right common cardinal vein
right vitelline vein
The left valvular fold of the sinuses and horns becomes incorporated into the _____ ______
interatrial septum
Small fold that is remaining of the left sinus horn becomes the valve of the _____ _____
coronary sinus
What happens to the right valvular fold? (superior and inferior)
Superior disappears
Inferior becomes the valve of the inferior venal cava
What forms the SA node?
A portion of the right sinus horn and the right common cardinal vein
Describe the partitioning of the chambers of the heart
Differential growth occurs and then the endocardial cushion tissues comes in and fills the gaps
Where does the formation of endocardial tissue occur?
In the AV region and the outflow tract
Where are the endocardial cushion cells derived from?
endocardium
Besides fibrous septa formation, what else do the cushion cells do?
provide the mesenchyme that is needed for anchoring the heart valves and contribute to the cardiac skeleton
Most of the tricuspid and bicuspid valves themselves appear to form from the ____ with possible contributions from the epicardial-derived cells
ECT(endocardial cushion tissue)
What are conotruncal ridges made up of?
Part ECT and part neural crest cell derived
_____ ______ (proximal outflow tract) is divided so blood from LV and RV go out different vessels
Conus arteriosus
______ ______ (distal outflow tract) will be divided to make aorta and pulmonary arteries by formation of an aorticopulmonary (AP) septum.
Truncus arteriosus
Why do you need a hole to be present in the atria of an embryo?
Because the lungs are not getting air, so BOTH side of the heart needs to get the oxygen rich blood from the placenta
- **if this does not happen, one side of the heart becomes hypoplastic
- **SO you form TWO septa in the atria with a little hole in between
touching of the ____ _____ to _____ during cardiac looping induces septum I formation.
outflow tract
atrium
Sickle-shaped, this septum extends from atrial wall toward the AV septum.
Septum primum
Septum primum has a hole in it near the AV septum called _____ ______
ostium primum
As cushion tissue from the AV septum and DMP begins to close this hole (osmium primum), a new hole forms in septum primum toward cranial (superior) end of the septum called _____ ______
ostium secundum
Describe septum secundum
Thicker than septum primum and grows to overlap the ostium second; separates the atrium but leaves a hole in between called the foramen oval
Where is the foramen oval located?
just above and dorsal to the AV septum and is overlapped by septum primum.
______ _____ acts as a one-way flutter valve allowing right atrial blood to enter the left atrium but not flow in the opposite direction.
Septum primum
With the first breath, describe what happens to the pressures of the…
left atrium
right atrium
right ventricle
left atrium pressure increases because blood flow is increased from the lungs
right atria and ventricle pressures decrease
Because the left pressure is always greater on the left than the right, describe what happens to the septum 1 and septum 2?
They merge closer together by force and are eventually fused by month 3
What is a patent foramen ovale?
The hole that is present from the septum 1 and 2 does not shut and can cause issues
At birth, most ASDs (atrial septal defects) result in an initial _____ to _____ shunting because of increased blood flow returning from the lungs and decreased pulmonary resistance after the lungs expand.
left to right
What happens to the body when there is prolonged shunting to the right side like seen with an atrial septal defect?
There is an abnormal increased blood flow to the lungs (with deoxygenated blood) which leads to pulmonary damage, and increased pulmonary resistance
The pulmonary resistance will increase the workload and the RV hypertrophies which can lead to CHF
Describe an ostium II septal defect
High septal defect
caused by
- Excessive absorption of septum I forms an overly large ostium II.
- Inadequate development of septum II.
A ______ _______ is when no septa are formed
Common atria
Describe an ostium I septal defect
low atrial septal defect
failure of up-growth of AV
cushion tissue from AV septum and DMP to fill in ostium primum.
_______ refers to the bluish coloration of the skin due to the presence of deoxygenated blood mixing with oxygenated blood
Cyanosis
What are sx that can be seen because of cyanosis
clubbing of fingers
bluish fingernail beds and lips
fatigue
Describe the fetal cardiac blood flow
- bulk of blood from IVC is shuttled through the foramen oval into the left atrium
- Goes to LV and out to the body
- RA blood has LESS oxygen from SVA and coronary sinus but some from IVC
- blood goes to RV
- RV blood re-enters the systemic arterial side via the ductus arteriosus
Aortic arch___ will connect the RV with the lungs and aortic arch ___ and ____ connects the LV to rest of body.
VI
III & IV
________ is a process where the 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
Myocardialization
______ ______ _____ _______ is when both the pulmonary artery and the aorta exit from the right ventricle with an accompanying ventral septal defect
Double outlet right ventricle
Describe the steps that occur in order to create a ventricular septa.
- myocardialization–> starts to separate everything by adding cushion tissue and shifting the blood flow
- New cushion tissue (conotruncal ridges) is added to form the spiraling ridges which makes it to where the pulmonary artery is on the right ventricle and the aorta is on the left ventricle
- conotruncal ridges fuse and there is a downward cushion tissue growth
- spiraling ridges help to form the valves of the aorta and the pulmonary artery
Cells of the spiraling ridges are derived from migrating _____ _____ _____ and from the endocardial-derived cushion tissue
neural crest cells
Complete ventricular septation requires fusion of the _____ ______ with each other and then with the interventricular septum and coincident with a downgrowth of cushion tissue from the AV septum
conotruncal ridges
Complete ventricular closure requires…
- down growth of the AV septum
- proper formation of the conotruncal ridges
- interventricular muscular septum formation
______ _____ ______ are one of the most common congenital heart defects
Ventricular defects
Describe the sx of a VSD
starts out as
acyanotic (left-to-right shunt) but becomes cyanotic
sometime after birth
RV hypertrophies due to
increased work load.
Eventually the RV hypertrophies
enough so that the RV pressure builds and exceeds the left
side, so now a right to left shunt develops (cyanosis)
______ ______ ______ is due to the failure of contruncal ridge formation and fusion
Persistent truncus arteriosus
Describe a persistent truncus arteriosus
Causes a VSD and the undivided truncus allows for the mixing of blood in the right and left ventricles, atria, and aorta and pulmonary artery
** look at the pictures int he both packet these help
What is tetralogy of Fallot?
There is unequal distribution of the pulmonary trunk and the aorta
The following symptoms are indicative of what disease?
- VSD (missing fibrous portion).
- Pulmonary infundibular stenosis.
- Overriding aorta.
- RV hypertrophies in the fetus because of the
small pulmonary opening. This increases RV pressure to point it will eventually exceed LV pressure thereby resulting in right to left shunting of blood even at the time of birth. It is the most common cyanotic-presenting heart defect in newborns.
Tetraology of FAllot
What causes the transposition of the great vessels?
Conotruncal
ridges fail to spiral
Describe the transposition of the great vessels
pulmonary artery is
connected to the LV and the aorta to RV.
_____ ______ _____ is where the Semilunar valves are fused leading to RV hypoplasia.
Pulmonary valvular atresia
What are the consequences of aortic valvular stenosis?
leads to hypertrophy of LV and eventually to cardiac failure and pulmonary hypertension
Describe a bicuspid aortic valve
2 leaflets rather than 3 are formed or two of the leaflets fuse and leave one hanging
What happens as a result of a bicuspid aortic valve?
Regurgitation
LV hypertrophy
aortic aneurysm
What is the result of an aortic valvular atresia?
wide ductus arteriosus
RV hypertrophy
patent ductus arteriosus
What disease/defect is being described?
obliteration of right AV orifice– fusion of tricuspid valves always
associated with patency (keep open) of foramen ovale, ventricular septal defect (probably because of abnormal AV septum development), underdeveloped right ventricle, hypertrophy of left ventricle, and patent ductus arteriosus.
Tricupsid atresia
What is a hypoplastic left ventricle?
LV is underdeveloped and there is a small bicuspid valve (or absent)
patent ductus arterioles or foramen ovale
heart is basically univentricular
