Heart development Flashcards
1
Q
When does hematopoesis and blood vessel formation begin and where?
A
- Day 17 blood islands in the yolk sac form
- hemangioblasts differentiatte forming hematopoietic progenitor and endothelial precursor cells which organize to orm blood islands
2
Q
What do hematopoietic stem cells differentiate into and populate?
A
- embryonic erythrocytes and macrophages
- early hematopoietic cells populate the liver at day 23
3
Q
What are definitive hematopoietic stem cells and where are they found
A
- They are programmed from hemogenic endothelial cells
- found in aortic gonadal mesonephric region (AGM)
- AGM hemogenic endothelial cells appear at day 27 and appear in liver by 30 and dissapear from AGM by day 40
4
Q
Where does programming of the HSCs occur and what do they generate and populate?
A
- Liver and this allows them to generate the full all of the myeloid and lymphoid cell lineages
- Populate lymph organs and bone marrow
5
Q
Sites of hematopoesis in order from beginning to end?
A
- Yolk sac mesoderm starts day 17 finishes 60, source early RBC and macro
- Liver primordia colonized by primitive HSCs day 23
- AGM dorsal aorta begins forming hemogenic endothelial cells days 27-40 to populate liver
- Liver produces definitive HSC begining 5 weeks and goes until birth
- Definitive HSCs seed lymph organs and bone marrow beginning at 10.5 weeks bone marrow becomes the major hematopoetic organ
6
Q
when does intraembryonic vasculogenesis start?
A
day 18
7
Q
what is an angioma? What are capillary hemangiomas and cavernous hemangiomas?
A
- Abnormal BV and lymphatic capillary growth via vasculogenesis
- Capilllary hemangioma
- excessive form of capillaries
- Cavernous hemangioma
- excessive formation of venouos sinuses
*
- excessive formation of venouos sinuses
8
Q
What are the first signs of first heart field formation?
A
- Formation of EPCs clusters arranged in a horse shoe shape within a cardiogenic area of intraembryonic splanchnic mesoderm
9
Q
How are primitive endocardial tubes formed?
A
- Anterior and posterior body folding occurs the primary heart field and coelom get folded under the embryo which pulls endoderm inside forergut
- The EPCs differentiate into endothelial cells forming primitive endocardial tubes
10
Q
What does the primary heart tube wall consist of?
A
- Endocardium: inner epi continuous with blood vessels
- Myocardium
- Cardiac jelly: concentration of ECM btw endocardium and myocardium
11
Q
What is the sinus venosus?
A
- made of partially confluent right and left sinus horns that receives blood from umbilical vein, vitelline vein, and common cardial vein
12
Q
Where does the primitive atrium receive blood from?
A
Sinus venous
13
Q
what separates the primitive right and left ventricles?
A
interventricular sulcus
14
Q
What is the aortic sac or root?
A
- common confluens of pharyngeal arch blood vessels that contributes to great vessels
15
Q
What is the first major step required for cardiac septation?
A
- Cardiac looping
- the atrium moves cranially and dorsally, outflow tract bends right, and ventricle bends left and superior dorsal to outflow tract.
- Initial outflow tract forms right vent
16
Q
What is necessary for cardiac looping to occur?
A
- Secondary heart field which is found at both ends of rupturing dorsal mesocardium
17
Q
What i heterotaxia?
A
- any type of abnormal left right development of some or all organs
- Situs inversus: total reversal
- Situs ambiguous: partial reversal
- visceroatrial heterotaxia: right heart, normal GI
- Ventricullar inversion: reverse cardiac looping, right sided left ventricle
18
Q
What are two major drives of getting the blood to return to the right atrium to prepare for separation?
A
- differential expansion of the atrium to the left shifts the opening (sinuatrial jxn) to the right half of the atrium
- Changes in hemodynamics, vitelline and umbilical veins dissapear
19
Q
What is the coronary sinus a remnant of?
A
remnant of left sinus horn
20
Q
what does the right common cardinal vein become?
A
SVC
21
Q
What embryological vein becomes the IVC?
A
Right vitelline vein
22
Q
What makes the muscular interventricular septum and muscular atrial septum?
A
Differential growth
23
Q
What is endocardial cushion tissue?
A
- Formation of new connective tissue that occurs in the AV region and Conotruncal ridges in the outflow tract
- makes fibrous portions of atrial and ventricular septa
24
Q
In the outflow portion of the heart the cushion tissue is made of ___. In the AV portion of the heart cushion tissue is made of ____.
A
In the outflow portion of the heart the cushion tissue is made of endocardial and NCC derived cushion cells. In the AV portion of the heart cushion tissue is made of endocardial derived.
25
What is persistent AV canal?
* Failure of AV septum to fuse
* ASD and VSD as cushion tissue from AV septum contributes to the fibrous portion of the septa
* This results in:
* pulmonary htn
* intolerance to exercise
* SOA
* cardiac congestion
* Increase risk of endocarditis
* Linked with down syndrome
26
How is blood shunted to skip the lungs?
* Septum primum (#1) due to differential growth forms the foaramen primum (gets filled by cushion tissue from AV septum)
* **foramen secundum** forms high in septum primum
* Septum Secundum (#2) grows so it overlaps foramen secundum and grows to posterior atrial wall
* **foramen ovale** is within septum secundum
27
How does septum I and II between the atria close?
* With the first breath the lungs inflate and blood now flows to them
* Results in right atrium and ventricle pressure decreasing and increasing on the left
* This pushes the septa together and non functional, eventually they fuse shut within 3 months of birth
28
What causes a high atrial septal defect?
* Excessive absorption of septum I forms an overly large foramen II
* Inadequate development of septum II
## Footnote
*Eventually right ventricular hypertrophy, and mixing of de ox and ox blood occurs, can lead to cyanosis and CHF (takes long time to see sx)*
29
What is foramen (ostium) primum defect? (low atrial septal defect)
* failure of up growth of AV cushion tissue from AV septum and DMP to fill in ostium primum
30
What is a double outlet right ventricle?
* Insufficient shifting of AV septum or cardiac looping resulting in a mal-alignment defect
* Borth the aorta and pulmonary artery exit via the right ventricle accompanied by a VSD
* Sx are seen within days
* cyanosis
* breathlessness
* murmur
* poor weight gain
31
What are NCC's important for in heart development?
* driving continual growth of secodary heart field
* important for septation
* Primary cell type responsible for semi lunar valve cusps
* vagal nerves and PSNS derived
32
Most common congenital heart defect and describe it?
* VSD
* Starts acyanotic (L to R shunt) but becomes cyanotic months after birth as RV hypertrophies
* RV hypertrophies enough to where RV pressure exceeds the left and shunt becomes R to L and cyanosis occurs
33
What is persistenet truncus arteriosus?
* Contruncal ridge formation and fusion fails
* Pulm artery is above the undivided truncus causing a VSD bc of the ridges contribution to fiborus portion
* Undivided truncus will override both R and L ventricle so mixing of blood occurs
* low degree of cyanosis
* pulmonary congestion
* RV hypertrophy
* increased R vent pressure and more severe cyanosis
34
What is Tetralogy of Fallot?
* Conotruncal ridges form off center leading to unequal division of pulm trunk and aorta resulting in:
* VSD missing fibrous portion
* Pulm infundibular stenosis
* Overriding aorta
* RV hypertrophies increasing RV pressure so it exceeds LV resulting in right to left shunt
* Most cyanotic presenting heart defect in newborns
35
Transposition of great vessels?
* conotruncal ridges fail to spiral resulting in:
* pulm art connectted to LV and aorta to RV
* 1/3 die w/n first year or months if not treated
* corrective surgery allows long term survival
36
Pulmonary valvular atresia?
* semilunar valves are fused leading to RV hypoplasia
* Patent formen ovale forms the only outlet for blood on right side to get to left
* Ductus arteriosus is always batent and onnly way for blood to get to lungs
* May need a transplant depending on hypoplasia
37
Aortic Valvular stenosis?
* Hypertrophy of LV and eventually cardiac failure and pulmonary htn
* Can be due to congenital defect, infection, or degenerative
* 4:1 in males
38
Bicuspid aortic valve?
* only 2 functional leaflets not 3 (2 fuse)
* Results in regurgitation or stenosis
* Initally asymptomatic but leads to LV hypertrophy eventually
* assoc with aortic aneurysm
39
Aortic valvular atresia?
* Valves are completely fused the LV is hypoplastic
* Wide ductus arteriosus forms bc its only way to get ox right blood from placenta to systemic system
* Leads to RV hypertrophy
* After birth ox rich blood enters by way of ASD and enters systemic via patent ductus arteriosus
* Needs transplant but new surgeries have 5 yr survival rate
40
Tricuspid atresia?
* Obliteration of right AV orifiace, fusion of tricuspid valves assoc with patency of foramen ovale, ventricular septal defect, underdev right vent, hypertrophy of left vent and patent ductus arteriosus
* Can be corrected surically if RV is not too underdeveloped otherwsie transplant
41
Hypoplastic LV
* LV is underdev with absent or small bicuspid and aortic valves
* Ascending portion of aorta is under dev and there's a patent ductus arteriosus &/or foramen ovale
* Heart is working as univentricular heart with RV doing alll work
* Surgery improves outcome but 5 yr survival rate is 65%
