Heart Development

Question 1

Primitive hematopoietic stem cells

Answer 1

Make erythrocytes, megakaryocytes and macrophages

Meet immediate needs of the early embryo

Question 2

Definitive hematopoietic stem cells

Answer 2

Programmed from hemogenic endothelial cells found in the aortic-gonadal-mesonephric (AGM) region
Appear at day 27, seed the liver at day 30
Generate full spectrum of myeloid and lymphoid cell lineages
Without AGM, you never get definitive hematopoietic stem cells

Question 3

Sites of hematopoiesis

Answer 3

Yolk sac mesoderm- day 17-60: source of early RBCs and macrophages
Liver primordia: beginning day 23, continues to birth
AGM dorsal aorta: colonizes liver
Lymph organs
Bone marrow

Question 4

AGM region vasculogenesis

Answer 4

Hematopoiesis is coupled to vasculogenesis, which is different from the rest of the embryo
Mesodermal cells directly turn into endothelial cells and form blood vessels in most other areas

Question 5

Angiogenesis vs vasculogenesis

Answer 5

Vasculogenesis is de novo formation of blood vessels, while angiogenesis is the sprouting of new vessels from existing ones

Question 6

Intussusception

Answer 6

Taking an existing blood vessel and splitting it in half

Question 7

Angioma

Answer 7

Abnormal blood vessel and lymphatic capillary growth via vasculogenesis
Capillary hemangioma- excessive formation of capillaries
Cavernous hemangioma- excessive formation of venous sinuses

Question 8

Primary heart field

Answer 8

Splanchnic mesoderm- precardiomyocytes
Endoderm
Endothelial precursor cells form angiogenic clusters (all though this is a vasculogenic process) which form cardiac crescent and two endocardial tubes

Question 9

Endocardial tube formation

Answer 9

Splanchnic mesoderm consisting of precardomyocytes continue with the process of body folding and bring the two tubes towards the midline
Fuse into one single tube formed from endocardium and myocardium, and the tube dangles from dorsal mesocardium
Dorsal mesocardium must rupture so the tube can loop

Question 10

Proepicardial organ

Answer 10

Remnants of dorsal mesocardium that are responsible for forming the epicardium- cardiovasculature, CT and visceral layer of pericardium

Question 11

Primitive ventricle and proximal portion of outflow

Answer 11

Primitive ventricle forms left ventricle

Proximal portion of outflow forms the right ventricle

Question 12

Sinus horns

Answer 12

Two horns come together to form sinus venosus, which expands into atrium

Question 13

Lengthening of the heart tube is due to

Answer 13

Growth of the second heart field

Question 14

Neural crest cells

Answer 14

Do not add to heart
Regulate GF that comes from endoderm to drive proliferation of precardiac mesenchyme/mesoderm
If NCCs do not migrate to correct place there will be problems with cardiac looping

Question 15

Heterotaxia

Answer 15

Any symmetry anomaly
Situs inversus- total side reversal of organs
Situs ambiguous- partial reversal of organs
Visceroatrial heterotaxia - right sided heart, normal GI
Ventricular inversion- reverse cardiac looping, right sided left ventricle

Question 16

Right vitelline vein and Right common cardinal vein

Answer 16

Right vitelline becomes inferior vena cava, right common cardinal becomes superior vena cava

Question 17

Cushion tissue and separating atria and ventricles

Answer 17

Myocardial cells produce more extracellular matrix which pushes endocardial cells from both sides towards eachother
Endocardial cells are signaled by myocardium to undergo epithelial–>mesenchymal/mesodermal cell transition so the two sides can fuse
This is how AV septum is formed

Question 18

Valves derived from what tissue

Answer 18

Endocardium which is derived from intraembryonic splanchnic mesoderm

Question 19

Cushion tissue in outflow tract is derived from

Answer 19

Both endocardium (intraembryonic splanchnic mesoderm) and neural crest cells (ectoderm)

Question 20

Persistent AV canal

Answer 20

Failure of AV septum fusion
Results in atrial septal defect and ventricular septal defect
Abnormal or agenesis of AV valves
Pulmonary hypertension, exercise intolerance, shortness of breath
Linked with downs syndrome

Question 21

How does O2 rich blood entering right atrium bypass the pulmonary circuit and get into the systemic side

Answer 21

One-way flutter valve between atria formed by dorsal mesenchymal protrusion
Ductus arteriosus allows blood entering right atrium to travel to left atrium

Question 22

Early blood flow into right atrium flows through

Answer 22

Goes through foramen ovale, then displaces septum primum from septum secundum and through foramen secundum

Question 23

Fibrous CT of AV septum is derived from

Answer 23

Endocardium

Question 24

Foramen primum is filled in by

Answer 24

Cushion tissue

Question 25

AV septal defects

Answer 25

Excessive erosion of septum primum or inadequate development of septum secundum
Causes high atrial septal defect
Low hole septal defect caused by foramen primum defect

Question 26

Septation of outflow tract

Answer 26

To form complete interventricular septum, there must be spiraling of the conotruncal swellings that align with the muscular portion of the IV septum as well as the AV septum

Question 27

Shifting of AV canal

Answer 27

AV canal must shift towards the midline during development
If it does not, both the aorta and pulmonary artery exit via the right ventricle, accompanied by a ventricular septal defect
Can be caused by insufficient cardiac looping
Symptoms include cyanosis, breathlessness, murmur, poor weight gain

Question 28

Cardiac NC cells

Answer 28

Important for sprouting of secondary heart field, lengthening/looping of the heart tube, septation of the outflow tract

Question 29

Ventricular septal defects

Answer 29

Most common congenital heart defect
Initially there will be blood flow from left to right side, increasing blood flow to pulmonary circuit
Later after development there will be blood flow from right to left side

Question 30

Persistent truncus arteriosus

Answer 30

There will be a ventricular septal defect involved
Cyanosis
Look into this more- not well described

Question 31

Tetralogy of fallout

Answer 31

Small pulmonary artery
VSD
Right ventricle must work harder and hypertrophies
Over-riding aorta
(those are the four symptoms- tetra)
Causes right to left shunt at birth, causing cyanosis

Question 32

Transposition of great vessels

Answer 32

Conotruncal ridges formed and fused but did not spiral
Right ventricle connected to the aorta, left connected to the pulmonary artery
Ductus arteriosus allows oxygenated blood to get to embryo

Question 33

Pulmonary valvular atresia

Answer 33

Blood comes into right atria but cannot be pumped out pulmonary artery
Left ventricle does all the work and hypertrophies
Only way to get oxygenated blood is to have blood flow through foramen ovale and back through the ductus arteriosus

Question 34

Aortic valvular stenosis

Answer 34

Left ventricle has to work harder causing hypertrophy

Question 35

Aortic valvular atresia

Answer 35

Left ventricle has no workload so it is much smaller

Right ventricle does all the work so it hypertrophies

Question 36

Bicuspid aortic valve

Answer 36

Initially asymptomatic but can develop left ventricular hypertrophy over time
Associated with development of aortic aneurysms

Question 37

Tricuspid atresia

Answer 37

Tricuspid valve has no opening
No blood can enter right ventricle, so it is hypoplastic
There is a patent foramen ovale that persists and ductus arteriosus so that oxygenated blood can be distributed
Usually involves a VSD

Question 38

Hypoplastic left ventricle

Answer 38

Mitral valve is not formed or very small
Aortic valve is not formed or very small
Ascending portion of aorta is underdeveloped
Patent ductus arteriosus and foramen ovale (or ASD)
Heart works as a uni-ventricular heart with right ventricle doing all the work