Heart Development Flashcards
1
Q
What is vasculogenesis?
A
Process of making blood vessels directly from mesenchyme
2
Q
What is angiogenesis?
A
Budding and sprouting of new vessels from existing ones
Helped by intussusception (splitting)
3
Q
When does extra embryonic vasculogenesis and early hematopoeisis occur?
A
Day 17
4
Q
What is hematopoiesis?
A
Blood cell formation
5
Q
Where does extraembryonic vasculogenesis begin?
A
Begins in mesoderm adjacent to endoderm of yolk sac wall
6
Q
What is the process of extraembryonic vasculogenesis?
A
Hemangioblasts —> Hematopoietic progenitor cells & Endothelial precursor cells (HPCs and EPCs)
HPCs & EPCs —> blood islands —> coalesce, lengthen and interconnect —> initial vascular network
7
Q
What has formed by the end of week 3 via vasculogenesis?
A
Vascularized yolk sac wall
Connecting stalk
Chorionic villi
8
Q
What are the sizes of eventual hematopoiesis?
A
Blood islands of yolk sac Liver Aortic gonadal mesonephric region (AGM) Lymph organs Bone marrow
9
Q
When do Embryonic hematopoietic stem cells appear?
A
Day 17 (When vasculogenesis starts)
10
Q
What do embryonic hematopoietic stem cells do by day 23?
A
Populate and reside in developing liver primordia
11
Q
What do Embryonic hematopoietic stem cells do in the liver primordia?
A
Generate embryonic erythrocytes, macrophages, and megakaryocytes
12
Q
What forms Definitive Hematopoietic stem cells?
A
Programmed from Homogenized endothelial cells of dorsal aorta in AGM region
13
Q
What do DHCs cells do?
A
Seed liver around day 30 allowing for cell-cell interaction to occur
Gives EHCs capacity to generate both myeloid and lymphoid stem cell lineages
14
Q
Where will Definitive heamtopoietic stem cells go after seeding the liver?
A
Go out to populate lymph organs and bone marrow
15
Q
When does the Aortic gonadal mesonephric region appear and disappear?
A
Appears around day 27
Disappears by day 40 after seeding the liver with DHCs
16
Q
When does intraembryonic vasculogenesis occur?
A
Day 18
17
Q
Is intraembryonic vasculogenesis coupled with heamtopoiesis?
A
NO
18
Q
Where does Intraembyronic vasculogenesis begin/
A
Vessel formation begins in the intraembyronic splanchnopleuric mesoderm
19
Q
What is the other name for ENdothelial precursor cells?
A
Angioblasts
20
Q
What is the embryonic origin of angioblasts?
A
Intraembyronic splanchnopleuric mesoderm
21
Q
What will Endothelial precursor cells turn into?
A
Endothelial cells
22
Q
What will endothelial cells organize into during intraembyronic vasculogenesis?
A
Endothelial cells
—> Vasculogenic cord
—> Long tube
—> angioplastic plexus
23
Q
How does the angioplastic plexus grow and spread?
A
- Continued proliferation of EPCs
- Angiogenesis
- Intussusception
- Recruitment of new mesodermal cells into walls of existing vessels
24
Q
Where else does intra-embryonic vasculogenesis also occur?
A
Paraxial mesoderm
25
What occurs during Intra-embryonic vasculogenesis in the Paraxial mesoderm?
EPCs differentiate, proliferate and then migrate out
Form blood vessels in areas outside splanchnic mesoderm
26
What are angiomas caused by?
Abnormal blood vessel and lymphatic growth via a vasculogenic process
(Likely Abnormal bc of abnormal levels of angiogenic factors
27
What is a capillary heamngioma?
Excess growth of small capillary network
28
What is a cavernous heamngioma?
Excess growth of venous sinuses
29
What is a hemangiomas of infancy?
How often does it occur?
Benign tumors made of mostly endothelial cells
Occurs in ~2.5% of neonates
(Not immediate threat and can regress over the years)
30
What creates the First heart field?
Clusters of Endothelial Precursor cellsa in horseshoe shape w/in Intraembryonic splanchnic mesoderm + adjacent mesoderm
31
What is the first heart field also called?
Cardiac crescent
32
What happens to the First heart field and intraembryonic coelom as anterior/posterior body folding occurs?
First heart field and coelom become folded beneath the embryo
And pulls some endoderm inside to form foregut
33
After the anterior/posterior body folding occurs, what is the position of the first heart field limbs?
Limbs lie ventral to foregut
And
Dorsal to coelom
34
What does the foregut come from embyrologically?
Endoderm
35
What forms the 2 primitive endocardium tubes?
EPCs differentiating into endothelial cells
36
What happens to the 2 primitive endocardium tubes as lateral folding occurs?
Brings tubes together —> fuse in midline w/ adjacent cardiogenic mesoderm
Makes the simple, single tubular heart
Tube will sink to future pericardial cavity
37
How is the first aortic arch made?
By the cranial ends of develop dorsal aorta being dragged ventrally along heart
Thus forming loops
38
What 3 things allow inflow of blood into the primitive heart?
Common cardinal veins
Vitelline veins
Umbilical veins
39
What are the layer of the Simple single heart tube?
1. Endocardium
2. Myocardium
3. Cardiac jelly
40
What is the endocardium of the primary heart tube wall?
Inner epithelium continuous w/ blood vessels
41
What is cardiac jelly?
Concentration of extracellular matrix b/w endocardium and myocardium
42
How is the simple tubular heart divided into regions?
Thru a series of constrictions and expansions
43
When doe the first they thymic contraction occur?
Day 22
44
When does blood flow thru the embryo heart occur?
Day 24
45
What is the direction of blood flow in the embryo heart?
Into sinus venosus and out the outflow tract
46
What are the regions of the simple tubular heart?
1. Sinus venosus
2. Primitive atrium
3. AV region
4. Primitive ventricle
5. Outflow tract
6. Aortic sac/root
47
What makes up the sinus venosus?
Partially confluent right and left sinus horns
48
What will drain into the sinus venosus’ horns?
Umbilical vein
Vitelline vein
Common cardinal vein
49
What blood is the umbilical vein carrying ?
Placental blood that is O2 rich
50
What blood is the Vitelline vein carrying ?
Blood from gut area that is O2 poor
51
What blood is the Common Cardinal vein carrying ?
Blood from head and trunk that is O2 poor
52
Where is the primitive atrium?
What will it receive blood from?
Region b/w sinus venosus and ventricle
Receives blood from sinus venosus
53
Where is the AV region located?
Region b/w primitive atrium and primitive ventricle
54
What is the lumen of the AV region called?
Atrioventricular canal/foramen
55
What will the primitive ventricle become?
Left ventricle
56
What separate the primitive ventricle from the right?
Interventricular sulcus
57
Where is the Outflow tract of the heart tube?
B/w primitive ventricle and aortic sac
58
What is the aortic sac of the heart tube?
Common confluence of pharyngeal arch blood vessels that contrives to great vessels
59
What is the role of the dorsal mesocardium?
Suspends heart
60
What will eventually happen to the dorsal mesocardium?
Ruptures and forms transverse sinus
61
What will the caudal remnants of the dorsal mesocardium form?
Pro-epicardium organ
62
What forms the epicardium of the heart?
Proepicardial organ cells that migrate over surface of myocardium
63
What is the first major step required for cardiac septation?
Cardiac looping
64
What does the Cardiac looping process do?
Reverses atrial and ventricular positions as the heart tube lengthens
65
How does the Cardiac looping move the atrium?
Atrium moves cranial and dorsally
Will be b/w outflow and dorsal pericardial wall now
66
How does Cardiac Looping move the Outflow tract?
Outflow tract will bend to the right, forward and down
67
What will the outflow tract form?
The future RV
68
How does the Conus Arteriosus form?
Thru the addition of myocardium at the cranial end of the outflow tract
69
What is the Conus arteriosus?
Proximal outflow tract that is the outflow portion of both ventricles
70
What will form at the distal end of the outflow tract?
Truncus arteriosus
71
What is the truncus arteriosus?
Distal outflow tract
72
What will the truncus arteriosus form?
Aorta and pulmonary a.
73
How is the primitive ventricle (future LV) moved due to Cardiac Looping?
Bends to the left and superior-dorsal to outflow tract
74
What does Cardiac Looping require?
How will is accomplish this?
Lengthening of the cardiac tube at both ends but especially the cranial outflow end (where conus arteriosus forms)
Accomplished via development of the 2nd heart field
75
Where does the second heart field form?
At both ends of rupturing dorsal mesocardium (which ruptures and forms transverse sinus/proepicardial organ)
76
What happens if there is a failure of splanchnic mesoderm to proliferate?
Cardiac defects could develop
77
How is cardiogenic mesoderm proliferation and proper myocardial cells peicification maintained in the 2nd heart field?
Neural crest cells w/in future pharyngeal arch region
bc they help tissue-tissue interactions b/w neural crest,PA mesoderm and PA endoderm
78
How does ventricular inversion occur?
What is the outcome of this?
Primitive ventricles goes to RIGHT
Outflow tract goes to LEFT
Outcome: Left ventricle on right side
79
What is Heterotaxia?
Occurrence?
Any abnormal lef-right development of some or all organs
Occurs in 3:20,000
80
What syndromes is Heterotaxia often seen in?
Immobile cilia syndrome
Kartagener syndrome
81
What is Sinus inversus?
Assoc. problems?
Complete reverse symmetry of heart and GI organs
A subset of heterotaxia
Generally unproblematic/asymptomatic
82
What is Sinus Ambiguous?
Assoc. problems?
Reversal of some organs
Is problematic
Subset of heterotaxia
83
What is Visceroatrial heterotaxia?
What problems does this cause?
Form of Sinus Ambiuous wher Heart and GI tract are asymmetric
(R heart w/ normal GI)
Or
(L heart w/ right GI)
Problems w/ inflow and outflow tract development and can be life threatening
84
Due to cardiac looping, how will the sinus venosus opening into the primitive atrium move?
Will begin to shift toward the RIght atrium
85
What happens to the Left vitelline veins, left umbilical cord, and left common cardinal vein?
Eventually disappears
86
What happens to the Left Sinus Venosus and Sinus horn after Cardiac looping?
They merge connections to the RIght half of the common atrium
87
What will the remnants of the Left SInus horn form?
Coronary sinus and valve of coronary sinus
88
What is the opening from the Sinus venosus to the RA called?
When does it form?
Sinoatrial orifice
As atrium enlarges
89
What happens to the Right sinus horns and it’s branches as the R. Atrium expands?
Incorporated into the Posterior wall of expanding RA
90
What will the Right Common cardinal v. Become ?
Superior vena cava
91
What willl the RIght Vitelline v. Become?
Inferior vena cava
92
What happens to the Right Umbilical cord?
Disappears
93
What is incorporated into the Right atrium?
Developing superior and inferior vena cava and orifice of coronary sinus
94
What will the Left atrial venous valve become?
Interatrial septum
95
What will the superior right venous valve become?
Disappears
96
What will the inferior right venous valve become?
Valve of inferior vena cava
97
What is the Crista terminal
Junction between the
Pectinate of RA
&
Sinus Venarum
98
What is the Pectinate of RA?
Rough wall of RA
99
What is the SInus Venarum?
Smooth wall of RA
100
What is the sinus venarum from?
Part of sinus venosus incorporated into atria
101
What forms the SA node?
Portion of Right sinus horn and right common cardinal v.
102
What forms the AV node?
Root of left sinus horn
103
How is the heart partitioned?
Into 4 chambers by the septa formation in atria, ventricles and outflow tract
104
What are the 2 mechanisms of partitioning?
1. Differential growth
| 2. Endocardium cushion tissue
105
What will differential growth due in the partitioning of the heart?
Makes the
muscular interventricular septum
&
muscular atrial septum
106
What will differential growth never be able to do in the partitioning of the heart?
Will never fully close a lumen
Needs new tissue for that to happen
107
What is endocardium cushion tissue in the partitioning of the heart?
Formation of New CT that occurs in the
AV region
&
Outflow tract
108
What will the endocardium cushion tissue form in the partitioning of the hart?
Makes
FIBROUS (membranous) portions of atrial and ventricular septum
and
conotruncal ridges of outflow tract
109
What is fibrous septa formed by?
By myocardial synthesis and secretion of molecules into cardiac jelly that induces the formation, migration and proliferation of new mesenchymal cells
110
What are the new mesenchymal cells derived from and what will they make?
From endocardium to make Endocardial cushion tissue
111
Wha is the Role of the Endocardial Cushion tissue in the AV region?
How?
Separates atrium from ventricle
Superior and inferior ECTS fuse at middle and form Atrioventricular septum
112
How does Endocardial Cushion tissue helps formation of HEart valves?
Provides mesenchyme
needed to anchor heart valves and contribute to cardiac skeleton
113
How are Tricuspid and bicuspid valves formed?
From ECT w/ contribution from Epicardial derived cells
114
How is Chordae tendinae and Papillary Ms. formed?
By freed leaflets from walls
115
How are leaflets freed from walls in order to make chordae tendinae and papillary ms. ?
Via cavitation and remodeling of the ventricular myocardium
116
What will the Conotruncal ridges do to the outflow tract?
A. Conus arteriosus
B. RV
C. Truncus Arteriosus
A. Divides conus arteriosus so that blood from LV and RV goes out different vessels
B. Forms Interventricular septum so that the RV and LV are separated
C. Divides Truncus arteriosus into aorticopulmonary septum
117
What will the aorticopulmonary septum form?
Aorta
Pulmonary a.
118
Why do we need a leaky barrier between atria in the embryo?
Bc lungs are not developed/un-inflated so we cannot use them to get to left side
119
How do you get O2 rich blood from placenta to enter future RA and get to left side?
Thru formation of two septa w/in the atria
120
How is the formation of the Septum Primum induced?
When the outflow tract touches the atrium during cardiac looping
121
Where is the Septum Primum?
From atrial wall toward AV septum
122
What contributes to the formation of te Septum Primum?
Dorsal mesenchymal protrusions (DMP)
| Or spina vestibuli
123
What is spina vestibuli?
Mesodermal projections coming from caudal dorsal mesocardium
Can contribute for septum primum
124
What is the Ostium Primum?
Hole near AV septum within the Septum primum
125
What closes the Ostium Primum?
Cushion tissue from AV septum and DMP
126
What will form in place of Ostium Primum?
New hole forms in Septum primum toward the cranial end = ostium secundum (foramen secundum)
127
What will overlap the ostium secundum?
Septum secundum - a thicker septum growing toward AV region
128
What does the Septum secundum allow for?
The septum never completely separates the 2 sides of common atrium and alllows for blood flow
129
What is the opening that remains between the 2 sides of the common atrium called?
Foramen ovalis
130
Where is the foramen ovalis located?
Above and dorsal to AV septum and is overlapped by the septum primum
131
What does the septum primum allow for w/ the foramen ovalis?
Acts as one way flutter valve that allows for RA blood —> LA without flowing backwards
132
What happens to pulmonary circulation after birth and w/ 1st breath?
What does this do to the BP?
Will open and increase blood flow thru lungs and return it to LA
Decreases BP in RA and RV
Increases BP in LA
133
What will close the septum secundum and primum connection?
When does this connection fully seal?
High pressure on left side drives septum’s against each other (even during diastole)
W/in 3 months of birth
134
What happens if the Foramen ovalis does not close?
How often does this occur? What is this known as ?
A patent Foramen ovalis could cause problems
15-25% fail to close - Probe Latency
135
What is the flow of Fetal Cardaic blood?
Bulk of blood from IVC —> Foramen ovalis —> LA —> LV —-> Fetal systemic arterial side
Other blood from SVA and coronary sinus —> RA—> RV —> Ductus Arteriosus —> re-enter systemic arterial side
136
In the fetus, how much blood goes from RV to pulmonary arteries to reach lungs?
11-13%
137
How is the Primordial Ventricle partitioned?
Thru the formation of the interventricular septum
138
What are the 2 parts of the interventricular septum?
What are they formed from?
1. Muscular par from ventricular wall
2. Fibrous part
From fusion tissue of AV cushion and proximal conotruncal ridges
139
What does the partitioning of theOutflow tract accomplish?
Connects
Future aorta to LV
Pulmonary a. To RV
140
What connects the RV to the lungs?
Aortic arch 6
141
What connects LV to the rest of the body?
Aortic arch 3 and 4
142
How is the outflow tract partitioned?
Via myocardializaton that shifts AV canal to the right
143
What does shifting the AV canal to the right do?
Makes the fusing AV cushions meet near region of forming muscular interventricular septum
Separate ventricles into r and l sides
But allows for blood from atrium to still get to both side
144
What is myocardializatoin?
Outer myocardial wall is thinned
as myocardial cells are replaced by cushion cells and
As remodeling occurs via apoptosis
145
What happens if there is a failure to shift the AV canal or insufficient cardiac looping?
Ex.?
Can cause mal-alignment defects
Double outlet right ventricle
146
What is a double outlet right ventricle?
Sxs?
Both aort and pulmonary a. Exit via the RV w/ accompanying Ventricular septal defects
```
Will show w/in days
Cyanosis
Breathlessness
Murmur
Poor weight gain
```
147
What will formation of Conotruncal ridges do?
Connect Pulmonary a. W/ RV
Connect aorta w/ LV
148
How are conotruncal ridges formed?
Endocardial derived cushion tissue and NCC forms in outflow tract
Ridges spiral toward ventricular septum and fuse
Creates conotruncal septum
149
What does the conotruncal septum do?
How?
Divides the outflow tract
Will come from upper truncus and turn 180 degrees to become parallel to the interventricular septum
150
How is ventricular septation completed?
Conotruncal ridges fuse w/ each other and then w/ interventricular septum and coincide w/ downgroth of cushion tissue from AV septum
151
What are the cells o the spiraling conotruncal ridges derived from?
From migrated neural crest cells and from the Endocardial-derived cushion tissue
152
What becomes the smooth part of each ventricle?
Conus arteriosus
| is incorporated as ventricle overgrows it
153
What do the spiraling ridges at truncus/conus junction provide?
Provide primordia for semilunar valves of aorta and pulmonary trunk
154
What is the most common life threatening congenital defect?
Heart defects account for 20% of all congenital defects
155
What are the causes for congenital heart defects?
* 4% - single gene mutations
* 6% - chromosomal anomalies
* 5% - teratogens
* 85% - multifactorial
156
What is the first functioning organ?
Heart
157
Who is an Atrial Spetal Defect more common in?
2x more common in females
158
What does an Atrial Septal Defect result in?
Initial L—> R shunting bc of increased returning blood flow from lungs and decreased pulmonary resistance after lungs expands
```
—> increased pulmonary resistance
—> hypertrophy of RV
—> (R—> L) shunting
—> Cyanosis
—> COngestive heart failure
```
159
What are the 3 types of Atrial Septa defects?
1. Ostium II or HIgh atrial septal defect
2. Common atria
3. Ostium I or Low atrial septal defect
160
What is a Ostium II or High atrial septal defect?
◦ 90% of ASDs
◦ Hole in atrial septum bc
‣ 1. Excessive absorption of septum I forms an overly large ostium II
‣ 2. Inadequate development of septum II
161
What is a Common Atria Atrial Septal defect?
No septa formed
162
What is a OStium I or Low Atrial Septal Defect?
Failure of up-growth of AV cushion tissue from AV septum and DMP to fill in ostium primum
163
What is cyanosis?
* Bluish coloration of the skin due to the presence of deoxygenated blood mixing w/ oxygenated blood
* Continues tot he point that is lowers the overall oxygen content and is insufficient for normal tissue physiology.
164
What are the Sxs of cyanosis?
◦ Clubbing of fingers
◦ blue fingernail beds and lip
◦ Fatigues easily
◦ seen in patients w/ O2 sats below 90%
165
What does a Ventricular Septal Defect result from?
Failure of proper closure by abnormal or inadequate fibrous tissue (95% of time)
166
What are the symptoms of Ventricular Septal Defects?
- begins acyanotic (L—> R shunt)
- becomes Cyanotic as RV hypertrophies bc of its increased work load
- RV hypertropies
- R—> L side shunt = cyanosis
167
What does complete closure of the vetnricular septum require?
Downgrowth of AV septum
Proper formation of conotruncal ridges
Interventricular muscular septum formation
168
What is persistent truncus arteriosus result from?
Failure of conotruncal ridge formation and fusion leaving Truncus undivided
(Truncus becomes aorticopulmonary septum—> aorta and pulmonary a.)
If left undivided, O2 rich and poor blood mix
169
What is the Tetralogy of Fallot result from?
What are the consequences?
Conotruncal ridges form off-center causing unequal divisions of pulmonary trunk and aorta
◦ VSD - no fibrous portion
◦ Pulmonary infundibular stenosis
◦ Overriding aorta
◦ RV hypertrophies in fetus bc of small pulmonary opening
‣ RV hypertrophy —> R—>L shunting —> cyanosis
170
What is the most common cyanotic presenting heart defect in newborns?
Tetralogy of Fallot
171
What does the Transposition of Great Vessles caused from?
Consequences?
Txs?
Failure of Conotruncal ridges to spiral
Consequences:
PA - LV
Aorta - RV
Shunts but prognosis is poor
172
What is Pulmonary Valvular Atresia?
How does blood travel?
Fused semilunar valves that causes RV hypoplasia
Blood goes thru patent foramen ovale to left side and then Ductus arteriosus allows blood to get to lungs
Or w/ VSD blood can get to LV and be pumped out of aorta (even if blood is mixed)
173
What is Aortic Valvular Stenosis?
Narrowing of aortic valve leading to hypertrophy of LV and eventual cardiac failures
174
What can cause aortic valvular stenosis?
Congenital
Due to infection (rheumatic fever)
Due to degeneration (aging, calcification)
175
Who is aortic valvular stenosis more commonly seen in?
4x more frequent in males
176
What is a bicuspid aortic valve?
What are the consequences?
What can this lead to?
Only 2 leaflets (either only 2 formed, or all 3 formed but 2 fused)
Regurgitation or stenosis
Can lead to LV hypertrophy and development of aortic aneurysm
177
What is Aortic valvular Atreisa?
Complete fusion of valves that leads to LV hypoplasia
Ductus arteriosus will form as only way O2 blood can get out to body
RV will hypertrophy
178
What is Tricuspid Atresia?
What does this cause?
No right AV orifice and fused tricuspid valves
Patency of foramen ovale w/ a VSD
Underdeveloped RV (bc no blood going to it)
LV hypertrophy (all blood going to it)
Patent ductus arteriosus
179
What is a hypoplastic left ventricle?
How does a heart work with this?
LV is underdeveloped w/ small or absent bicuspid and aortic valves
(causes blood to flow back into RV thru foramen ovale and be sent out to body via patent ductus arteriosus)
Heart works as univentricular Heart with RV doing all the work
