Heart development

Question 1

When does hematopoesis and blood vessel formation begin and where?

Answer 1

• Day 17 blood islands in the yolk sac form
  
  • hemangioblasts differentiatte forming hematopoietic progenitor and endothelial precursor cells which organize to orm blood islands

Question 2

What do hematopoietic stem cells differentiate into and populate?

Answer 2

• embryonic erythrocytes and macrophages
• early hematopoietic cells populate the liver at day 23

Question 3

What are definitive hematopoietic stem cells and where are they found

Answer 3

• 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

Question 4

Where does programming of the HSCs occur and what do they generate and populate?

Answer 4

• Liver and this allows them to generate the full all of the myeloid and lymphoid cell lineages
• Populate lymph organs and bone marrow

Question 5

Sites of hematopoesis in order from beginning to end?

Answer 5

• 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

Question 6

when does intraembryonic vasculogenesis start?

Answer 6

day 18

Question 7

what is an angioma? What are capillary hemangiomas and cavernous hemangiomas?

Answer 7

• Abnormal BV and lymphatic capillary growth via vasculogenesis
• Capilllary hemangioma
  
  • excessive form of capillaries
• Cavernous hemangioma
  
  • excessive formation of venouos sinuses
    *

Question 8

What are the first signs of first heart field formation?

Answer 8

• Formation of EPCs clusters arranged in a horse shoe shape within a cardiogenic area of intraembryonic splanchnic mesoderm

Question 9

How are primitive endocardial tubes formed?

Answer 9

• 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

Question 10

What does the primary heart tube wall consist of?

Answer 10

• Endocardium: inner epi continuous with blood vessels
• Myocardium
• Cardiac jelly: concentration of ECM btw endocardium and myocardium

Question 11

What is the sinus venosus?

Answer 11

• made of partially confluent right and left sinus horns that receives blood from umbilical vein, vitelline vein, and common cardial vein

Question 12

Where does the primitive atrium receive blood from?

Answer 12

Sinus venous

Question 13

what separates the primitive right and left ventricles?

Answer 13

interventricular sulcus

Question 14

What is the aortic sac or root?

Answer 14

• common confluens of pharyngeal arch blood vessels that contributes to great vessels

Question 15

What is the first major step required for cardiac septation?

Answer 15

• 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

Question 16

What is necessary for cardiac looping to occur?

Answer 16

• Secondary heart field which is found at both ends of rupturing dorsal mesocardium

Question 17

What i heterotaxia?

Answer 17

• 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

Question 18

What are two major drives of getting the blood to return to the right atrium to prepare for separation?

Answer 18

• 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

Question 19

What is the coronary sinus a remnant of?

Answer 19

remnant of left sinus horn

Question 20

what does the right common cardinal vein become?

Answer 20

SVC

Question 21

What embryological vein becomes the IVC?

Answer 21

Right vitelline vein

Question 22

What makes the muscular interventricular septum and muscular atrial septum?

Answer 22

Differential growth

Question 23

What is endocardial cushion tissue?

Answer 23

• 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

Question 24

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 ____.

Answer 24

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.

Question 25

What is persistent AV canal?

Answer 25

* 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

Question 26

How is blood shunted to skip the lungs?

Answer 26

* 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

Question 27

How does septum I and II between the atria close?

Answer 27

* 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

Question 28

What causes a high atrial septal defect?

Answer 28

* 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)*

Question 29

What is foramen (ostium) primum defect? (low atrial septal defect)

Answer 29

* failure of up growth of AV cushion tissue from AV septum and DMP to fill in ostium primum

Question 30

What is a double outlet right ventricle?

Answer 30

* 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

Question 31

What are NCC's important for in heart development?

Answer 31

* driving continual growth of secodary heart field * important for septation * Primary cell type responsible for semi lunar valve cusps * vagal nerves and PSNS derived

Question 32

Most common congenital heart defect and describe it?

Answer 32

* 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

Question 33

What is persistenet truncus arteriosus?

Answer 33

* 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

Question 34

What is Tetralogy of Fallot?

Answer 34

* 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

Question 35

Transposition of great vessels?

Answer 35

* 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

Question 36

Pulmonary valvular atresia?

Answer 36

* 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

Question 37

Aortic Valvular stenosis?

Answer 37

* Hypertrophy of LV and eventually cardiac failure and pulmonary htn * Can be due to congenital defect, infection, or degenerative * 4:1 in males

Question 38

Bicuspid aortic valve?

Answer 38

* 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

Question 39

Aortic valvular atresia?

Answer 39

* 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

Question 40

Tricuspid atresia?

Answer 40

* 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

Question 41

Hypoplastic LV

Answer 41

* 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%