Heart Development

Question 1

what is Vasculogenesis

Answer 1

Process of making blood vessels directly from mesenchyme

Question 2

Process of Extraembryonic vasculogenesis, what cells accomplish this and when does it begin

Answer 2

begins day 17 in mesoderm next to the endoderm yolk sac wall

this process is coupled with hematopoiesis (blood cell formation)

hemangioblasts differentiate to created Hematopoietic progenitor cells and endothelial precursor cells

these cells make blood islands that lengthen and connect to make vascular network

3rd week have vascularized yolk sac wall, connecting stalk, and chronic villi

Question 3

what are eventual sites of hematopoiesis

Answer 3

yolk sac, liver aortic gonadal mesonepheric (AGM) region, lymph organs, and bone marrow

Question 4

what do Embryonic hematopoietic cells do and when do they appear

Answer 4

appear day 17 and then populate the developing liver by dau 23 to make embryonic erythrocytes, macrophages, and megakaryocytes

Question 5

what do definitive hematopoietic stem cells do

Answer 5

programmed hemogenic endothelial cells of the dorsal aorta in the aortic-gonadal-mesonephric (AGM) region

these cells seed the liver day 30 and make myeloid (fetal and adult erythrocytes) and lymphoid cell lineages

then finally they go out to populate the lymph organs and bone marrow

Question 6

when does the AGM region appear and disappear

Answer 6

appears day 27 and then disappears by day 40 after seeding the liver

Question 7

Intraembryonic vasculogenesis

Answer 7

with the exception of the AGM region, blood vessel formation within the embryo is not coupled with hematopoiesis

starts by day 18, vessel formation occurs in the intraembryonic splanchopleuric mesoderm

subset of these cells differenticate into endothelial precursor cells to proliferate and differentiate into endothelial cells making the angioplastic plexus

this also occurs in the paraxial mesoderm as well due to migration of the EPCs

Question 8

what are the four ways the angioplastic plexus grows and spreads

Answer 8

1) continued proliferation of endothelial precursor cells
2) angiogenesis, the budding and sprouting of new vessesl from existing ones
3) intussusception: splitting of a existing vessel
4) recruitment of new mesodermal cells into walls of existing vessels

Question 9

what are Angiomas and how are they caused

Answer 9

benign tumors from vascular or lymphatic vessels

caused abnormal growth from the vasculogenic process stimulated by abnormal levels of angiogenic factors

Question 10

Capillary hemangioma

Answer 10

excessive growth from a small capillary network

Question 11

Cavernous hemangioma

Answer 11

excessive growth of a venous sinus

Question 12

Hemangiomas of infancy

Answer 12

benign tumors made mostly of endothelial cells

not immediate threats but deepending on the degree and site of growth can lead to clinical complications

can regress over the years though

Question 13

First Heart field

Answer 13

first seen with the formation of EPCs clusters that are arranged in a horseshoe shape within the cardiogenic area of intraembryonic splanchnic mesoderm

also called the cardiac crescent

intraembryonic coelom lies dorsal to the first heart field

Question 14

how does anterior/posterior folding affect the primary heart field

Answer 14

the primary heart field and coelom become folded beneath the embryo pulling in endoderm to help form the foregut

the limbs of the first heart field now lie ventral to the foregut and dosal to the coelom

Meanwhile the EPCs differentiate into endothelial cells making the primitive endocardial tubes

Question 15

How does the lateral folding affect the primary heart field

Answer 15

brings the two forming heart tubes together, thus the endocardial heart tubes fuse at the midline with the adjacent cardiogenic mesoderm to form a simble tubular heart

then the heart sinks into the pericardial cavity

the cranial ends of the developing dorsal aorta are dragged ventrally to make a loop making the first aortic arch

Question 16

what three blood vessels get blood to the primitive heart

Answer 16

Common cardinal veins
Vitelline veins
Umbilical veins

Question 17

What does the primary heart tube wall consist of

Answer 17

Endocardium (inner epithelium continuous with blood vessels)
Myocardium
Cardiac jelly (concentration of extracellular matrix between endocardium and myocardium)

Question 18

when does blood first flow through the primitive heart and when is the first rhythmic contraction

Answer 18

rhythmic contraction begins day 22
blood flow starts about day 24

goes from sinus venosus to the outflow tract

Question 19

Morphologically the heart consists of what 5 structures when first beginning contraction

Answer 19

Sinus venosus: right and left sinus horns, draining into each horn is umbilical horn, vitelline vein (blood from gut), and common cardinal vein (venous blood from head and trunk)

Primitive atrium: region between vsinus venosus and ventricle

Atrioventricular region: area seperating primitive atrium and primitive ventricle

Primitive ventricle: early left ventricle, delineated from future right ventricle by construction of interventricular sulcus

Outflow tract: portion between primtive ventricle and aortic sac

Aortic sac or root: eventually become the great vessels.

Question 20

what is the function of the Dorsal mesocardium and what does it become as an adult

Answer 20

suspends the heart tube but eventually ruptures forming the transverse sinus as an adult

remenants are the proepicardial organ

Question 21

Cardiac Looping

Answer 21

reverses the atrial and ventricle positions as the heart tube lengthens

atrium moves cranially and dorsally now locatedbetween outflow tract and dorsal pericardial wall

ventricle bends left and superior and dorsally to the outflow tract

Question 22

what does the initial outflow tract form, what does myocardium at the cranial end form, and what does the distal most end of the outflow tract form

Answer 22

initial outflow: right ventricle

cranial end myocardium: conus arteriosus (outflow portion of both ventricles)

distal end outflow: forms the truncus arteriosus (aorta and pulmonary artery)

Question 23

how does the lengtheining of the cardiac tube occur during cardiac looping

Answer 23

accomplished by the development of a second heart field that forms at both ends of the rupturing dorsal mesocardium

Neural crest cells, pharyngeal arch mesoderm, and pharyngeal arch endoderm help maintain the cardiogenic mesoderm proliferation and proper myocardial cell specification

Question 24

Looping anomalies: Ventricular inversion

Answer 24

primitive ventricle folds to the right and the outflow tract ends up on the left generating a rightsided left ventricle

Question 25

Looping anomalies: two forms of Heterotaxia

Answer 25

any abnormal left right development of either some or all organs (often seen in immobile cilia syndrome and Kartagener syndrome Situs inversus: complete reverse symmetry of the heart and GI organs that is often asymptomatic Situs ambiguous: reversal of some organs.. can be problematic -Visceroatrial hererotaxia: heart and GI tract are asymetrically arranged from one other. this affects the inflow and outflow tract development which can be life threatening

Question 26

what happenss to the left side of the embryonic vessels and sinuses as the heart grows and loops

Answer 26

sinus venosus opening into the primitive atrium begins shifting to the right due to the looping, growth, and hemodynamics left vitelline vein and left umbilical vein disappear left sinus venosus and left horn shift their connection to the right half of the common atrium (since atria expansion bigger on the left side of common sinus opening) this helps with net shifit in amount of blood return to right side left common cardinal vein then disappears left sinus horn becomes the coronary sinus

Question 27

what happens as the atrium enlarges on the right side?

Answer 27

sinus venosus now only opens to the future right atrim via the sinoatrial orifice right sinus horn and right common cardinal veins are incorporated into the posterior wall of the expanding right atrium right common cardinal vein becomes the superior vena cava Right vitelline vein becomes part of the inferior vena cava Right umbilical vein is lost pair of tissue flaps develop on either side of the developing opening of the coronary sinus (left and right atrial venous valves)

Question 28

what happens to the left and right valvular folds

Answer 28

Left valvular fold becomes incorporated into the interarterial septum Superior right vavlular fold disappears inferior part of right valvular fold becomes valve of inferior vena cava small fold of left sinus horn makes valve of the coronary sinus

Question 29

What is the crista terminalis

Answer 29

junction between the pectinate (rough) part of the right atrium and the smoothed wall (sinus venarum- part of sinus venosus incorporated into atria)

Question 30

what does the SA node and AV node come from

Answer 30

SA node comes from a portion of the right sinus horn and right common cardinal vein AV node comes from the similar tissue in the root of the left sinus horn

Question 31

what are the two aspects important in septa formation

Answer 31

Differential growth (however this does not fully close off a lumen) Endocardial cushion tissue: connective tissue in the AV region that makes the fibrous portions of atrial and ventricular septa and conotruncial ridges

Question 32

How does the Atrioventricular septum develop

Answer 32

superior and inferior endocardial cushions fuse at the midline to form the atrioventricular septum subsequent growth up and down from the AV septum contributes to the atrial and ventricular septa as well cushion cells also provide mesenchyme needed for anchoring the heart valves and contribute to the cardiac skeleton leflets are freed fromthe walls by cavitation and remodeling of the ventricular myocardium and remnants help form the chordae tendinae and papillary muscles

Question 33

what are the conotruncal ridges and what do they contribute to

Answer 33

found in the outflow tract that are part ECT and neural crest cell derived they divide the conus arteriosus so blood from the LV and RV go out different vessels also contributes to the fibrous portion of the interventricular septum also divides the truncus arteriosus to make aorta and pulmonary arteries via formation of the aorticpulmonary septum

Question 34

What is critical about the septum between the atrium and how is this problem solved

Answer 34

must be leaky since the left side of the atrium needs the blood so that the left side of the heart doesnt become hypoplastic also since the lungs have not developed or uninflated the heart can push all the blood through the lungs therefore create two septum in the atria

Question 35

Septum Primum and its other contributers and the holes it has

Answer 35

touching of the outflow tract to the atrium during cardiac looping that induces septum I formation sickle shaped extends from the atrial wall toward the AV septum also recieves contribution from the dorsal mesenchymal protrusion (DMP) or spina vestibuli (a mesodermal projection emanating from the caudal dorsal mesocardium the hole in the septum primum near the AV septum called the ostium primum however cushion tissue and DMP forms near the AV and blocks this hole a new hole will form in septum primum toward the cranial end of the septum called the ostium secundum

Question 36

Septum secundum

Answer 36

as the atria contiunues to expand a additional sickle shaped and much thicker septum grows toward the AV region this will overlap the ostium secundum but as the septa secundum grows it never fully covers the lumen and leaves an opening called the foramen ovalis (ovale) this makes the septuum primum act as a one way flutter valve allowing for right atrial blood to enter the left atrium but not let the flow go in the opposite direction

Question 37

what happens to septum I and II after a baby takes their first breath

Answer 37

pulmonary circulation opens up and increases blood flow to the lungs, this process increases pressure in the left atrium and decreases pressure in RV and RA the higher pressure on the left vs the right side drives septum I against septum II resulting in a functionally closed septum and eventually seals shut within 3 months of birth if it does not fuse the patent foramen ovalis (ovale) may cause issues in the future

Question 38

Three types of Atrial septal defects

Answer 38

Ostium II or high atrial septal defect: hole in atrial septum caused by either excessive absoprtion of septum I forms an overly large ostium II or Inadequate development of septum II Common atria: no septa are formed Ostium I defect or low atrial septal defect: failure of up growth of AV cushion tissue from AV septum and DMP to fill ostium primum initial left to right shunting because of increased blood flow returning from the lungs and decreased pulmonary resistance however as time leads on an increased blood flow to lungs leads to pulmonary damage and resistance (pulmonary congestion) RV hypertorphy and eventually congestive heart failure as the RV hypertrophies a right to left shunt begins and cyanosis appears can go many years unnoticed depending on degree of severity because of the lower atria pressures

Question 39

cyanosis

Answer 39

refers to bluish coloration of skin due to the presence of deoxygenated blood mixing with oxygenated blood can be seen via clobbing of fingers and bluish fingernail beds and lips individual also fatigues easily patients have an oxygen saturation of below 90 percent

Question 40

how much blood actually goes through to the pulmonary circulation in a fetus

Answer 40

11-13 percent this is due to the foramen ovale and the ductus arteriosus

Question 41

how is the ventricular septation created

Answer 41

formation of the interventricular septum is made of a muscular part (ventricular wall) and a fibrous part (from cushion tissue of AV cushion and proximal conotruncal ridges

Question 42

mechanism of partitioning outflow tract

Answer 42

Aortic arch VI ataches RV to lungs Aortic arch III and IV connects LV to rest of body 1) shift of AV canal toward right side so that the fusing of the AV cushions meet near the region of the forming interventricular septum.. done via myocardialization (outer myocardial wall is thinned and replaced by cushion cells and futrther apoptosis for remodeling) 2) new cushion tissue forms in outfow tract called conotruncal ridges that spiral down the ventricular septum and fuse to form the conotruncal septum as this spirals down it makes a 180 degree turn and become parallel with the interventricular septum (these are derived from migrating neural crest cells and endocardial derived cushion tissue. the resut is pulmonary artery connected with RV and aorta connected with LV 3) complete ventricular septation requires fusion of the conotruncal ridges with each other and then with the interventricuar septum and coincident with downgrowth of cushion tissue from the AV septum 4) Proximal root of the outflow tract is eventually incorporated into each ventricle s the ventricle overgrows the conus . spiraling ridges at the truncus/conus junction provide primordia for semilunar valves or aorta and pulmonary trunk

Question 43

Ventricular septal Defects

Answer 43

failuure of proper closure by abnormal or inadequate fibrous tissue starts as a left to right shunt but becomes cyanotic sometime after birth RV hypertrophies enough so RV pressure builds up and exceeds the left side thus needing a right to left shunt to develop will die of cardiac failure if not addressed

Question 44

how does double outlet right ventricle occur

Answer 44

shift fails of the AV canal both aorta and pulmonary artery exit the right ventricle lead to cyanosis and breathlessness and murmur

Question 45

Persistent truncus Arteriosus

Answer 45

failure of contruncial ridge formation and fusion, pulmonary artery arises some distance away above the undivided truncus and causes a VSD due to the fibrousportion mixing of left and right ventricle contents giving rise to low degree cyanosis RV hypertrophy and increased right ventricular pressure and eventual more severe cyanotic condition

Question 46

Tetralogy of Fallot

Answer 46

Conotruncal ridges form off center leading to unequal division of pulmonary and aorta VSD (missing fibrous portion) Pulmonary infundibular stenosis Overriding aorta RV hypertrophies in the fetus due to the small pulmonary opening increases RV pressure over LV resulting in right to left shunting of blood and leads to cyanosis

Question 47

Transposition of great vessels

Answer 47

Conotruncal ridges fail to spiral pulmonary artery is connected to the LV and the aorta to the Right survival due to shunts such as VSD, ASD, patent ductus arteriosus life expectency is 3 years without surgery

Question 48

Pulmonary valvular atresia

Answer 48

Semilunar valves are fused leading to RV hypoplasia Patent foramen ovale then forms as the only outlet for blood on right side to get to left Patent ductus arteriosus to get blood to lungs need surgery to open pulmonary valve if the RV is not too weak can have a VSD and become a univentricular heart

Question 49

Aortic Vavlular stenosis

Answer 49

leads to hypertrophy of the LV and eventually cardiac failure and pulmonary hypertension, can be congenital, due to a fever, or degenerative

Question 50

Bicuspid aortic valve

Answer 50

only two leaflets rather than 3 are formed or three formed but two are fused leads to regurgitation or later to form a stenosis starts asymptomatic but eventual leads to LV hypertrophy associated with aortic aneurysm

Question 51

Aortic Valvular atresia

Answer 51

valves are completely fused the LV is underdeveloped (hypoplastic) wide ductus arteriosus forms to get oxygen rich blood to the left side RV hypertrophy and blood must go back through a ASD to the right side from the left needs surgery for survival

Question 52

Tricuspid Atrestia

Answer 52

Obliteration of the right AV orifice and fusion of the tricuspid vavles associated with a patent foramen ovale VSD, and underdeveloped right ventricle and a hypertrophy left ventricle and patent ductust arterisus can be corrected based on the RV weakness most likely transplant

Question 53

Hypoplastic keft ventrice

Answer 53

LV is underdeveloped with absent or small bicuspid and aortic valve ascending portion of aorta is underdeveloped and there is a patent ductus arteriosus and foramen ovale univentricular heart with the right ventricle need surgery