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Heart Development Flashcards

1
Q

What is vasculogenesis?

A

Process of making blood vessels directly from mesenchyme

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2
Q

What is angiogenesis?

A

Budding and sprouting of new vessels from existing ones

Helped by intussusception (splitting)

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3
Q

When does extra embryonic vasculogenesis and early hematopoeisis occur?

A

Day 17

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4
Q

What is hematopoiesis?

A

Blood cell formation

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5
Q

Where does extraembryonic vasculogenesis begin?

A

Begins in mesoderm adjacent to endoderm of yolk sac wall

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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

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7
Q

What has formed by the end of week 3 via vasculogenesis?

A

Vascularized yolk sac wall

Connecting stalk

Chorionic villi

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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
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9
Q

When do Embryonic hematopoietic stem cells appear?

A

Day 17 (When vasculogenesis starts)

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10
Q

What do embryonic hematopoietic stem cells do by day 23?

A

Populate and reside in developing liver primordia

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11
Q

What do Embryonic hematopoietic stem cells do in the liver primordia?

A

Generate embryonic erythrocytes, macrophages, and megakaryocytes

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12
Q

What forms Definitive Hematopoietic stem cells?

A

Programmed from Homogenized endothelial cells of dorsal aorta in AGM region

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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

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14
Q

Where will Definitive heamtopoietic stem cells go after seeding the liver?

A

Go out to populate lymph organs and bone marrow

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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

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16
Q

When does intraembryonic vasculogenesis occur?

A

Day 18

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17
Q

Is intraembryonic vasculogenesis coupled with heamtopoiesis?

A

NO

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18
Q

Where does Intraembyronic vasculogenesis begin/

A

Vessel formation begins in the intraembyronic splanchnopleuric mesoderm

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19
Q

What is the other name for ENdothelial precursor cells?

A

Angioblasts

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20
Q

What is the embryonic origin of angioblasts?

A

Intraembyronic splanchnopleuric mesoderm

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21
Q

What will Endothelial precursor cells turn into?

A

Endothelial cells

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22
Q

What will endothelial cells organize into during intraembyronic vasculogenesis?

A

Endothelial cells
—> Vasculogenic cord
—> Long tube
—> angioplastic plexus

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23
Q

How does the angioplastic plexus grow and spread?

A
  1. Continued proliferation of EPCs
  2. Angiogenesis
  3. Intussusception
  4. Recruitment of new mesodermal cells into walls of existing vessels
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24
Q

Where else does intra-embryonic vasculogenesis also occur?

A

Paraxial mesoderm

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25
Q

What occurs during Intra-embryonic vasculogenesis in the Paraxial mesoderm?

A

EPCs differentiate, proliferate and then migrate out

Form blood vessels in areas outside splanchnic mesoderm

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26
Q

What are angiomas caused by?

A

Abnormal blood vessel and lymphatic growth via a vasculogenic process

(Likely Abnormal bc of abnormal levels of angiogenic factors

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27
Q

What is a capillary heamngioma?

A

Excess growth of small capillary network

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28
Q

What is a cavernous heamngioma?

A

Excess growth of venous sinuses

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29
Q

What is a hemangiomas of infancy?

How often does it occur?

A

Benign tumors made of mostly endothelial cells

Occurs in ~2.5% of neonates

(Not immediate threat and can regress over the years)

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30
Q

What creates the First heart field?

A

Clusters of Endothelial Precursor cellsa in horseshoe shape w/in Intraembryonic splanchnic mesoderm + adjacent mesoderm

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31
Q

What is the first heart field also called?

A

Cardiac crescent

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32
Q

What happens to the First heart field and intraembryonic coelom as anterior/posterior body folding occurs?

A

First heart field and coelom become folded beneath the embryo

And pulls some endoderm inside to form foregut

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33
Q

After the anterior/posterior body folding occurs, what is the position of the first heart field limbs?

A

Limbs lie ventral to foregut

And

Dorsal to coelom

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34
Q

What does the foregut come from embyrologically?

A

Endoderm

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35
Q

What forms the 2 primitive endocardium tubes?

A

EPCs differentiating into endothelial cells

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36
Q

What happens to the 2 primitive endocardium tubes as lateral folding occurs?

A

Brings tubes together —> fuse in midline w/ adjacent cardiogenic mesoderm

Makes the simple, single tubular heart

Tube will sink to future pericardial cavity

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37
Q

How is the first aortic arch made?

A

By the cranial ends of develop dorsal aorta being dragged ventrally along heart

Thus forming loops

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38
Q

What 3 things allow inflow of blood into the primitive heart?

A

Common cardinal veins

Vitelline veins

Umbilical veins

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39
Q

What are the layer of the Simple single heart tube?

A
  1. Endocardium
  2. Myocardium
  3. Cardiac jelly
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40
Q

What is the endocardium of the primary heart tube wall?

A

Inner epithelium continuous w/ blood vessels

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41
Q

What is cardiac jelly?

A

Concentration of extracellular matrix b/w endocardium and myocardium

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42
Q

How is the simple tubular heart divided into regions?

A

Thru a series of constrictions and expansions

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43
Q

When doe the first they thymic contraction occur?

A

Day 22

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44
Q

When does blood flow thru the embryo heart occur?

A

Day 24

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45
Q

What is the direction of blood flow in the embryo heart?

A

Into sinus venosus and out the outflow tract

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46
Q

What are the regions of the simple tubular heart?

A
  1. Sinus venosus
  2. Primitive atrium
  3. AV region
  4. Primitive ventricle
  5. Outflow tract
  6. Aortic sac/root
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47
Q

What makes up the sinus venosus?

A

Partially confluent right and left sinus horns

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48
Q

What will drain into the sinus venosus’ horns?

A

Umbilical vein
Vitelline vein
Common cardinal vein

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49
Q

What blood is the umbilical vein carrying ?

A

Placental blood that is O2 rich

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50
Q

What blood is the Vitelline vein carrying ?

A

Blood from gut area that is O2 poor

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51
Q

What blood is the Common Cardinal vein carrying ?

A

Blood from head and trunk that is O2 poor

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52
Q

Where is the primitive atrium?

What will it receive blood from?

A

Region b/w sinus venosus and ventricle

Receives blood from sinus venosus

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53
Q

Where is the AV region located?

A

Region b/w primitive atrium and primitive ventricle

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54
Q

What is the lumen of the AV region called?

A

Atrioventricular canal/foramen

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55
Q

What will the primitive ventricle become?

A

Left ventricle

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56
Q

What separate the primitive ventricle from the right?

A

Interventricular sulcus

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57
Q

Where is the Outflow tract of the heart tube?

A

B/w primitive ventricle and aortic sac

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58
Q

What is the aortic sac of the heart tube?

A

Common confluence of pharyngeal arch blood vessels that contrives to great vessels

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59
Q

What is the role of the dorsal mesocardium?

A

Suspends heart

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60
Q

What will eventually happen to the dorsal mesocardium?

A

Ruptures and forms transverse sinus

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61
Q

What will the caudal remnants of the dorsal mesocardium form?

A

Pro-epicardium organ

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62
Q

What forms the epicardium of the heart?

A

Proepicardial organ cells that migrate over surface of myocardium

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63
Q

What is the first major step required for cardiac septation?

A

Cardiac looping

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64
Q

What does the Cardiac looping process do?

A

Reverses atrial and ventricular positions as the heart tube lengthens

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65
Q

How does the Cardiac looping move the atrium?

A

Atrium moves cranial and dorsally

Will be b/w outflow and dorsal pericardial wall now

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66
Q

How does Cardiac Looping move the Outflow tract?

A

Outflow tract will bend to the right, forward and down

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67
Q

What will the outflow tract form?

A

The future RV

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68
Q

How does the Conus Arteriosus form?

A

Thru the addition of myocardium at the cranial end of the outflow tract

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69
Q

What is the Conus arteriosus?

A

Proximal outflow tract that is the outflow portion of both ventricles

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70
Q

What will form at the distal end of the outflow tract?

A

Truncus arteriosus

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71
Q

What is the truncus arteriosus?

A

Distal outflow tract

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72
Q

What will the truncus arteriosus form?

A

Aorta and pulmonary a.

73
Q

How is the primitive ventricle (future LV) moved due to Cardiac Looping?

A

Bends to the left and superior-dorsal to outflow tract

74
Q

What does Cardiac Looping require?

How will is accomplish this?

A

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
Q

Where does the second heart field form?

A

At both ends of rupturing dorsal mesocardium (which ruptures and forms transverse sinus/proepicardial organ)

76
Q

What happens if there is a failure of splanchnic mesoderm to proliferate?

A

Cardiac defects could develop

77
Q

How is cardiogenic mesoderm proliferation and proper myocardial cells peicification maintained in the 2nd heart field?

A

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
Q

How does ventricular inversion occur?

What is the outcome of this?

A

Primitive ventricles goes to RIGHT

Outflow tract goes to LEFT

Outcome: Left ventricle on right side

79
Q

What is Heterotaxia?

Occurrence?

A

Any abnormal lef-right development of some or all organs

Occurs in 3:20,000

80
Q

What syndromes is Heterotaxia often seen in?

A

Immobile cilia syndrome

Kartagener syndrome

81
Q

What is Sinus inversus?

Assoc. problems?

A

Complete reverse symmetry of heart and GI organs

A subset of heterotaxia

Generally unproblematic/asymptomatic

82
Q

What is Sinus Ambiguous?

Assoc. problems?

A

Reversal of some organs

Is problematic

Subset of heterotaxia

83
Q

What is Visceroatrial heterotaxia?

What problems does this cause?

A

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
Q

Due to cardiac looping, how will the sinus venosus opening into the primitive atrium move?

A

Will begin to shift toward the RIght atrium

85
Q

What happens to the Left vitelline veins, left umbilical cord, and left common cardinal vein?

A

Eventually disappears

86
Q

What happens to the Left Sinus Venosus and Sinus horn after Cardiac looping?

A

They merge connections to the RIght half of the common atrium

87
Q

What will the remnants of the Left SInus horn form?

A

Coronary sinus and valve of coronary sinus

88
Q

What is the opening from the Sinus venosus to the RA called?

When does it form?

A

Sinoatrial orifice

As atrium enlarges

89
Q

What happens to the Right sinus horns and it’s branches as the R. Atrium expands?

A

Incorporated into the Posterior wall of expanding RA

90
Q

What will the Right Common cardinal v. Become ?

A

Superior vena cava

91
Q

What willl the RIght Vitelline v. Become?

A

Inferior vena cava

92
Q

What happens to the Right Umbilical cord?

A

Disappears

93
Q

What is incorporated into the Right atrium?

A

Developing superior and inferior vena cava and orifice of coronary sinus

94
Q

What will the Left atrial venous valve become?

A

Interatrial septum

95
Q

What will the superior right venous valve become?

A

Disappears

96
Q

What will the inferior right venous valve become?

A

Valve of inferior vena cava

97
Q

What is the Crista terminal

A

Junction between the

Pectinate of RA
&
Sinus Venarum

98
Q

What is the Pectinate of RA?

A

Rough wall of RA

99
Q

What is the SInus Venarum?

A

Smooth wall of RA

100
Q

What is the sinus venarum from?

A

Part of sinus venosus incorporated into atria

101
Q

What forms the SA node?

A

Portion of Right sinus horn and right common cardinal v.

102
Q

What forms the AV node?

A

Root of left sinus horn

103
Q

How is the heart partitioned?

A

Into 4 chambers by the septa formation in atria, ventricles and outflow tract

104
Q

What are the 2 mechanisms of partitioning?

A
  1. Differential growth

2. Endocardium cushion tissue

105
Q

What will differential growth due in the partitioning of the heart?

A

Makes the

muscular interventricular septum
&
muscular atrial septum

106
Q

What will differential growth never be able to do in the partitioning of the heart?

A

Will never fully close a lumen

Needs new tissue for that to happen

107
Q

What is endocardium cushion tissue in the partitioning of the heart?

A

Formation of New CT that occurs in the

AV region
&
Outflow tract

108
Q

What will the endocardium cushion tissue form in the partitioning of the hart?

A

Makes

FIBROUS (membranous) portions of atrial and ventricular septum
and
conotruncal ridges of outflow tract

109
Q

What is fibrous septa formed by?

A

By myocardial synthesis and secretion of molecules into cardiac jelly that induces the formation, migration and proliferation of new mesenchymal cells

110
Q

What are the new mesenchymal cells derived from and what will they make?

A

From endocardium to make Endocardial cushion tissue

111
Q

Wha is the Role of the Endocardial Cushion tissue in the AV region?

How?

A

Separates atrium from ventricle

Superior and inferior ECTS fuse at middle and form Atrioventricular septum

112
Q

How does Endocardial Cushion tissue helps formation of HEart valves?

A

Provides mesenchyme

needed to anchor heart valves and contribute to cardiac skeleton

113
Q

How are Tricuspid and bicuspid valves formed?

A

From ECT w/ contribution from Epicardial derived cells

114
Q

How is Chordae tendinae and Papillary Ms. formed?

A

By freed leaflets from walls

115
Q

How are leaflets freed from walls in order to make chordae tendinae and papillary ms. ?

A

Via cavitation and remodeling of the ventricular myocardium

116
Q

What will the Conotruncal ridges do to the outflow tract?

A. Conus arteriosus
B. RV
C. Truncus Arteriosus

A

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
Q

What will the aorticopulmonary septum form?

A

Aorta

Pulmonary a.

118
Q

Why do we need a leaky barrier between atria in the embryo?

A

Bc lungs are not developed/un-inflated so we cannot use them to get to left side

119
Q

How do you get O2 rich blood from placenta to enter future RA and get to left side?

A

Thru formation of two septa w/in the atria

120
Q

How is the formation of the Septum Primum induced?

A

When the outflow tract touches the atrium during cardiac looping

121
Q

Where is the Septum Primum?

A

From atrial wall toward AV septum

122
Q

What contributes to the formation of te Septum Primum?

A

Dorsal mesenchymal protrusions (DMP)

Or spina vestibuli

123
Q

What is spina vestibuli?

A

Mesodermal projections coming from caudal dorsal mesocardium

Can contribute for septum primum

124
Q

What is the Ostium Primum?

A

Hole near AV septum within the Septum primum

125
Q

What closes the Ostium Primum?

A

Cushion tissue from AV septum and DMP

126
Q

What will form in place of Ostium Primum?

A

New hole forms in Septum primum toward the cranial end = ostium secundum (foramen secundum)

127
Q

What will overlap the ostium secundum?

A

Septum secundum - a thicker septum growing toward AV region

128
Q

What does the Septum secundum allow for?

A

The septum never completely separates the 2 sides of common atrium and alllows for blood flow

129
Q

What is the opening that remains between the 2 sides of the common atrium called?

A

Foramen ovalis

130
Q

Where is the foramen ovalis located?

A

Above and dorsal to AV septum and is overlapped by the septum primum

131
Q

What does the septum primum allow for w/ the foramen ovalis?

A

Acts as one way flutter valve that allows for RA blood —> LA without flowing backwards

132
Q

What happens to pulmonary circulation after birth and w/ 1st breath?

What does this do to the BP?

A

Will open and increase blood flow thru lungs and return it to LA

Decreases BP in RA and RV
Increases BP in LA

133
Q

What will close the septum secundum and primum connection?

When does this connection fully seal?

A

High pressure on left side drives septum’s against each other (even during diastole)

W/in 3 months of birth

134
Q

What happens if the Foramen ovalis does not close?

How often does this occur? What is this known as ?

A

A patent Foramen ovalis could cause problems

15-25% fail to close - Probe Latency

135
Q

What is the flow of Fetal Cardaic blood?

A

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
Q

In the fetus, how much blood goes from RV to pulmonary arteries to reach lungs?

A

11-13%

137
Q

How is the Primordial Ventricle partitioned?

A

Thru the formation of the interventricular septum

138
Q

What are the 2 parts of the interventricular septum?

What are they formed from?

A
  1. Muscular par from ventricular wall
  2. Fibrous part
    From fusion tissue of AV cushion and proximal conotruncal ridges
139
Q

What does the partitioning of theOutflow tract accomplish?

A

Connects

Future aorta to LV
Pulmonary a. To RV

140
Q

What connects the RV to the lungs?

A

Aortic arch 6

141
Q

What connects LV to the rest of the body?

A

Aortic arch 3 and 4

142
Q

How is the outflow tract partitioned?

A

Via myocardializaton that shifts AV canal to the right

143
Q

What does shifting the AV canal to the right do?

A

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
Q

What is myocardializatoin?

A

Outer myocardial wall is thinned
as myocardial cells are replaced by cushion cells and
As remodeling occurs via apoptosis

145
Q

What happens if there is a failure to shift the AV canal or insufficient cardiac looping?

Ex.?

A

Can cause mal-alignment defects

Double outlet right ventricle

146
Q

What is a double outlet right ventricle?

Sxs?

A

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
Q

What will formation of Conotruncal ridges do?

A

Connect Pulmonary a. W/ RV

Connect aorta w/ LV

148
Q

How are conotruncal ridges formed?

A

Endocardial derived cushion tissue and NCC forms in outflow tract

Ridges spiral toward ventricular septum and fuse

Creates conotruncal septum

149
Q

What does the conotruncal septum do?

How?

A

Divides the outflow tract

Will come from upper truncus and turn 180 degrees to become parallel to the interventricular septum

150
Q

How is ventricular septation completed?

A

Conotruncal ridges fuse w/ each other and then w/ interventricular septum and coincide w/ downgroth of cushion tissue from AV septum

151
Q

What are the cells o the spiraling conotruncal ridges derived from?

A

From migrated neural crest cells and from the Endocardial-derived cushion tissue

152
Q

What becomes the smooth part of each ventricle?

A

Conus arteriosus

is incorporated as ventricle overgrows it

153
Q

What do the spiraling ridges at truncus/conus junction provide?

A

Provide primordia for semilunar valves of aorta and pulmonary trunk

154
Q

What is the most common life threatening congenital defect?

A

Heart defects account for 20% of all congenital defects

155
Q

What are the causes for congenital heart defects?

A
  • 4% - single gene mutations
    * 6% - chromosomal anomalies
    * 5% - teratogens
    * 85% - multifactorial
156
Q

What is the first functioning organ?

A

Heart

157
Q

Who is an Atrial Spetal Defect more common in?

A

2x more common in females

158
Q

What does an Atrial Septal Defect result in?

A

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
Q

What are the 3 types of Atrial Septa defects?

A
  1. Ostium II or HIgh atrial septal defect
  2. Common atria
  3. Ostium I or Low atrial septal defect
160
Q

What is a Ostium II or High atrial septal defect?

A

◦ 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
Q

What is a Common Atria Atrial Septal defect?

A

No septa formed

162
Q

What is a OStium I or Low Atrial Septal Defect?

A

Failure of up-growth of AV cushion tissue from AV septum and DMP to fill in ostium primum

163
Q

What is cyanosis?

A
  • 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
Q

What are the Sxs of cyanosis?

A

◦ Clubbing of fingers
◦ blue fingernail beds and lip
◦ Fatigues easily
◦ seen in patients w/ O2 sats below 90%

165
Q

What does a Ventricular Septal Defect result from?

A

Failure of proper closure by abnormal or inadequate fibrous tissue (95% of time)

166
Q

What are the symptoms of Ventricular Septal Defects?

A
  • begins acyanotic (L—> R shunt)
  • becomes Cyanotic as RV hypertrophies bc of its increased work load
  • RV hypertropies
  • R—> L side shunt = cyanosis
167
Q

What does complete closure of the vetnricular septum require?

A

Downgrowth of AV septum

Proper formation of conotruncal ridges

Interventricular muscular septum formation

168
Q

What is persistent truncus arteriosus result from?

A

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
Q

What is the Tetralogy of Fallot result from?

What are the consequences?

A

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
Q

What is the most common cyanotic presenting heart defect in newborns?

A

Tetralogy of Fallot

171
Q

What does the Transposition of Great Vessles caused from?

Consequences?

Txs?

A

Failure of Conotruncal ridges to spiral

Consequences:
PA - LV
Aorta - RV

Shunts but prognosis is poor

172
Q

What is Pulmonary Valvular Atresia?

How does blood travel?

A

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
Q

What is Aortic Valvular Stenosis?

A

Narrowing of aortic valve leading to hypertrophy of LV and eventual cardiac failures

174
Q

What can cause aortic valvular stenosis?

A

Congenital
Due to infection (rheumatic fever)
Due to degeneration (aging, calcification)

175
Q

Who is aortic valvular stenosis more commonly seen in?

A

4x more frequent in males

176
Q

What is a bicuspid aortic valve?

What are the consequences?

What can this lead to?

A

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
Q

What is Aortic valvular Atreisa?

A

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
Q

What is Tricuspid Atresia?

What does this cause?

A

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
Q

What is a hypoplastic left ventricle?

How does a heart work with this?

A

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

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