Development of the Heart Flashcards
1
Q
when does vasculogenesis and hematopoiesis begin?
A
day 17
2
Q
where does vasculogenesis and hematopoiesis begin?
A
in the mesoderm adjacent to the endoderm of the yolk sac- the extraembryonic mesoderm
3
Q
what is the first step in the process of vasculogenesis and hematopoiesis?
A
aggregates of hemangioblasts differentiate and give rise to both hematopoietic progenitor cells and endothelial precursor cells (EPCs)
4
Q
what do the primitive hematopoietic precursor cells differentiate into?
A
early embryonic erythrocytes, macrophages, and megakaryocytes
5
Q
where do the early hematopoietic cells populate by day 23 and what is their function?
A
they populate the developing liver; they primarily function to meet the immediate need for blood cells
6
Q
what are the definitive hematopoietic stem cells programmed from?
A
hemogenic endothelial cells of the dorsal aorta in the aortic-gonadal-mesonephric (AGM) region
7
Q
when do AGM hemogenic endothelial cells appear and when do they seed the liver? and when do they disappear?
A
first appear: day 27
seed the liver: day 30
disappear: day 40
8
Q
where are the sites of eventual hematopoiesis?
A
yolk sac mesoderm, liver primordium, AGM region, liver, lymph organs, and bone marrow
9
Q
when and where does production of definitive HSCs begin?
A
~week 5 and continues until birth; occurs in the liver
10
Q
what is the difference between vasculogenesis and angiogenesis?
A
vasculogenesis is making new blood vessels de novo; angiogenesis is making new blood vessels when you already have a blood vessel
11
Q
what is intussusception?
A
splitting of blood vessels to make more
12
Q
what are angiomas caused by?
A
abnormal blood vessel and lymphatic growth via vasculogenesis likely stimulated by abnormal levels of vasculogenic factors
13
Q
what is a capillary hemangioma?
A
excessive formation of capillaries
14
Q
what is a cavernous hemangioma?
A
excessive formation of venous sinuses
15
Q
what are hemangiomas of infancy?
A
benign tumors made of mostly endothelial cells
16
Q
what are the first signs of the development of the first heart field?
A
first signs seen with the formation of EPC clusters that are arranged in a horseshoe shape within a cardiogenic area of intraembryonic splanchnic mesoderm
17
Q
where do the definitive HSCs eventually populate?
A
the lymph organs and bone marrow
18
Q
when does hematopoesis of the yolk sac mesoderm begin? and when is it finished?
A
starts day 17; finished by day 60
19
Q
when is the liver primordia colonized by primitive HSCs?
A
day 23
20
Q
when do the definitive HSCs seed lymph organs and bone marrow?
A
begins around week 10.5; bone marrow becomes eventual major hematopoietic organ
21
Q
inside the embryo we have vasculogenesis. What is this coupled with?
A
nothing (it is not coupled with any hematopoetic stem cells)
22
Q
when does intraembryonic vasculogenesis begin?
A
day 18
23
Q
the EPCs + the adjacent mesoderm (aka the intraembryonic splanchnic mesoderm) form what?
A
the first heart field (or cardiac crescent)
24
Q
what occurs to the primary heart field as the anterior/posterior body folding occurs?
A
the primary heart field and coelom become folded beneath the embryo- pulling some endoderm inside to form the foregut
25
what do the EPCs of the first heart field differentiate into? and what does this form?
they will differentiate into endothelial cells forming two primitive endocardial tubes
26
what occurs due to lateral folding?
the two forming heart tubes will fuse midline and together with the adjacent cardiogenic mesoderm, they form a simple tubular heart
27
what is the heart tube suspended by initially?
the dorsal mesocardium
28
when the dorsal mesocardium ruptures, what is created that can still be seen in the adult?
the transverse sinus
29
inflow of blood into the primitive heart is from 3 pairs of vessels. What are they?
the common cardinal veins, the vitelline veins, and the umbilical veins
30
what does the primary heart tube consist of?
endocardium, myocardium, and the cardiac jelly
31
what is the endocardium?
it is the inner epithelium that is continuous with the blood vessels
32
there are remnants of the ruptured dorsal mesocardium that remain caudally. What do they form?
proepicardial organ
33
what is the significance of the proepicardial organ?
they are going to be the progenitor cells for the epicardium (they will eventually migrate over the surface of the myocardium forming the epicardium)
34
What is the first major step required for cardiac septation?
cardiac looping
35
what do the three pairs of vessels- common cardinal veins, vitelline veins, and umbilical veins collectively form?
the left and right sinus horns
36
what does the combination of the sinus horns form?
the sinus venosus
37
before cardiac looping, what does the sinus venosus drain into?
the primitive atrium
38
What drives the cardiac looping?
we are adding new muscle tissue to the anchored outflow and in flow ends
39
What is the final result of cardiac looping?
the atrium will move cranially and dorsally and the primitive ventricle will be pushed inferiorly
40
Cardiac looping requires and is driven by the lengthening of the cardiac tube at both ends; how is this accomplished/ what is driving this lengthening process?
by the development of the second heart field that forms at both ends of the rupturing dorsal mesocardium
41
how do NCCs contribute to heart development?
they are required for maintaining cardiogenic mesoderm proliferation and proper myocardial cell specification within the second heart field- if NCCs are not present you could shorten cardiac looping
42
normally, lengthening of the heart causes the primitive ventricle to?
move to the left
43
what is ventricular inversion?
anomaly-reverse cardiac lopping that results in a right-sided left ventricle; the primitive ventricle folds to the right and the outflow tract ends up on the left
44
what is heterotaxia and what are the different forms?
heterotaxia is any symmetry anomaly; there is situs inversus or situs ambiguous
45
what is situs inversus?
total reversal anomaly
46
what is situs ambiguous?
partial reversal anomaly
47
what is visceroatrial heterotaxia?
a form of situs ambiguous-right sided heart, but normal GI (aka it is a form of a situs ambiguous)
48
what effect does cardiac looping have on the sinus venosus?
it begins to shift towards the right atrium
49
what happens to the left vitelline vein and the left umbilical vein?
they eventually disappear
50
what does the remnants of the left sinus horn become?
the coronary sinus
51
as the left atrium enlarges, the sinus venosus now only opens into what?
the future right atrium (sinoatrial orifice)
52
what does the right common cardinal vein become?
the superior vena cava
53
what does the right vitelline vein eventually become?
part of the inferior vena cava
54
what happens to the right umbilical vein?
it is eventually lost
55
as the right atrium incorporates the developing superior and inferior vena cava and orifice of the coronary sinus, what develops on either side of the opening?
a pair of tissue flaps- the left and right atrial venous valves
56
What is the sinus venarum?
part of sinus venosus that is incorporated into the atria
57
what role does differential growth have on partition of the heart?
it makes the muscular interventricular septum and muscular atrial septum- never closes the lumen though
58
where is endocardial cushion tissue found?
in the AV region and the outflow tract
59
what does the endocardial cushion tissue make?
the fibrous (membranous) portions of the atrial and ventricular septum and the conotruncal ridges of the outflow tract
60
what do the specific molecules that are secreted into the cardiac jelly by the the endocardial cushion tissue induce?
the formation, migration, and proliferation of new mesenchymal cells derived from the endocardium
61
what is the atrioventricular septum and what is another name for it?
it separates the atrium from the ventricle; formed when the endocardial cushions in the AV region fuse at midline; aka the septum intermedium
62
what is the composition of the conotruncal ridges that are in the outflow tract?
part endocardial cushion tissue and part neural crest cells
63
what is a persistent AV canal?
when there is failure of AV septum fusion- there will be atrial septal defect and ventricular septal defect as cushion tissue from AV septum contributes to the fibrous portion of the septa
64
what is the effect of a persistent AV canal?
pulmonary hypertension; intolerance to exercise; shortness of breath; cardiac congestion
65
what is persistent AV canal linked with?
Down's syndrome
66
the oxygenated blood in the fetus is entering the right atrium and must bypass the pulmonary circuit and get the oxygenated blood into the systemic side(left side). How does it do this?
there is development of a one-way flutter valve between the atria - formation of two septa within the atrium
67
what is the first septa that is formed in the atrium?
the septum primum
68
what hole is found in the septum primum near the AV septum?
ostium I (or foramen primum)
69
as cushion tissue from the AV septum and dorsal mesenchymal protrusion begin to close the ostium I (or foramen primum), what forms?
a new hole in septum primum forms near the cranial end of the septum- called ostium secundum (aka foramen secondum)
70
as the atria are expanding, an additional sickle-shaped and much thicker septum forms. What is this new septum called?
septum secondum
71
what hole forms in the septum secondum?
foramen ovale
72
what 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
73
after birth and with the 1st breath, what happens to the blood pressure in the left atrium?
it increases
74
what happens to the RV and RA pressures at birth?
they decrease
75
what occurs due to the pressure always being higher on the left side of the heart compared to the right side?
this drives septum I up against septum II resulting in a functionally closed septum
76
at birth, what do most atrial septal defects (ASDs) result in?
an initial left to right shunting of blood
77
over time, what does the shunting to the right side that occurs with ASDs lead to?
abnormal increased blood flow to the lungs, which later causes the RV to hypertrophy and leads to CHF
78
what happens as the RV hypertrophies?
a right to left shunt begins and cyanosis appears
79
what is a high atrial septal defect?
there is a hole in the atrial septum caused by either excessive absorption of septum I that forms an overly large ostium II or an inadequate development of septum II
80
what is a low atrial septal defect?
an ostium I defect; failure of up-growth of AV cushion tissue from the AV septum to fill in ostium primum
81
how is cyanosis also manifested visually?
clubbing of fingers, bluish fingernail beds and lips; easy fatique
82
what is the fetal cardiac blood flow?
pattern is such that the bulk of the blood entering from the IVC is shuttled through the foramen ovale into the left atrium
83
how is ventricular septation accomplished?
by the formation of the interventricular septum
84
why must you shift the AV canal toward the right side?
to separate the ventricle into a right and left side and still get blood from the atrium into both ventricular sides
85
how does shifting of the AV canal occur?
differential expansions of the right ventricle, remodeling of the AV canal, and through cardiac looping (shifts the out flow track to the left)
86
what happens if the AV shift fails or cardiac looping is insufficient?
mal-alignment defects can form such as a double outlet right ventricle
87
what occurs during a double outlet right ventricle?
both aorta and pulmonary artery exit via the right ventricle accompanied by a ventricular septal defect
88
what are the symptoms like in a patient with a double outlet right ventricle?
symptoms show within days including cyanosis, breathlessness, murmur and later poor weight gain
89
what does complete ventricular septation require?
fusion of the conotruncal ridges with each other and then with the interventricular septum
90
what is the difference between extraembryonic vasculogenesis and intraembryonic vasculogenesis?
extraembryonic vasculogenesis is coupled with hematopoiesis; intraembryonic vasculogenesis is not
91
when does vessel formation in the intraembryonic splanchnopleuric mesoderm occur?
day 18
92
a subset of cells in the intraembryonic splanchnic mesoderm differentiates directly into what?
endothelial precursor cells
93
what do the endothelial precursor cells proliferate and differentiate into?
endothelial cells that then organize into small-vesicle like structures (vasculogenic cords)
94
what is the proximal outflow tract and becomes the outflow portion of both ventricles?
the conus arteriosus
95
what is the distal-most end of the outflow tract that forms the aorta and the pulmonary artery?
truncus arteriosus
96
what forms the SA node?
a portion of the right sinus horn and right common cardinal vein
97
before we separate the atrium into right and left halves, we need to somehow get all the blood coming back to the heart to be coming back to the right side of the common atrium. What are the two major drivers of this?
differential growth of the left side causes the sinus venosus opening (aka the sinuatrial junction) to shift to the right; and changes in hemodynamics
98
what are the changes in hemodynamics that occur that allow the returning blood to the return to the right side of the heart?
we lose the left umbilical vein, left vitelline vein, and the right umbilical vein
99
as the heart enlarges, the right sinus horn becomes incorporated into the posterior wall of the right atrium. What will this eventually be known as?
the sinus venarum
100
what are some of the most common congenital heart defects?
ventricular septal defects
101
what do ventricular heart defects initally start out as?
acyanotic (left-to-right) but become cyanotic sometime after birth
102
what is persistent truncus arteriosus?
the conotruncal ridges do not form at all
103
what are the clinical signs of persistent truncus arteriosus?
mild cyanosis that develops into severe cyanosis
104
What are the four hallmarks associated with Tetralogy of Fallot?
VSD, overriding aorta, pulmonary stenosis, right ventricular hypertrophy
105
what happens in tetraology of fallot?
as the spiraling septa forms, instead of diving the outflow track in half equally, it cheats the pulmonary side- there is unequal division
106
what will we see at birth in patients with tetralogy of fallot?
a right to left shunt and cyanosis
107
what happens with cases of transportation of the great vessels?
the fused conotruncal ridges do not spiral
108
what are the connections of the heart in patients with transportation of the great vessels?
the right ventricle gets connected with the aorta and the left ventricle gets connected with the pulmonary artery
109
how can you survive transposition of the great vessels?
keep the ductus arteriosus open
110
what is pulmonary valvular atresia?
the pulmonary semi lunar valves do not form at all
111
in order to get blood anywhere in patients with pulmonary valvular atresia, what must happen?
the foramen ovale must stay open
112
what happens to the right ventricle in patients with pulmonary valvular atresia?
the right ventricle will be hypoplastic
113
what happens to the left ventricle in patients with pulmonary valvular atresia?
it will be hypertrophied
114
what is aortic valvular stenosis and what does it cause?
narrowing of the semi lunar valves of the aorta- causes left ventricular hypertrophy
115
what is aortic valvular atresia?
complete closure of the aortic outlet- the left ventricle does not develop at all
116
how do we get blood to the systemic circulation in patients with aortic valvular atresia?
they have a very large ductus arteriosus
117
what does a bicuspid aortic valve cause?
left ventricular hypertrophy- since the two valves don't close off the outlet very well- you can get regurgitation
