CP1 & CP2 - Cardio Embryology lecture notes Flashcards
how common are birth defects?
1% of live births have a heart defect
how many cells divisions does the zygote undergo
It can divide to form about 64-128 cells (6-7 divisions)
What is a morula
- from latin word for mulberry
- 32-64 cell stage
- Cells in the middle are at a disadvantage as far as getting nutrients in
what is a blastocyst?
why does it form?
- Group of cells that form a sphere with cavity on the inside.
- the cells need to be near the periphery to be able to access nutrients
inner cell mass becomes
most of the embryo
syncitium is a ____
It begins to invade the endometrium on what day?
-structure that has many nuclei due to the fact that the cells that have lost their cell membrane
5-6 days after fertilization
spotting may happen on what day?
why is this clinically relevant?
14-15 day, Woman may not know she is pregnant until “2nd missed period”
- This is clinically important because important developmental stages occur by this time.
when does uteroplacental circulation form
within the first 2 weeks
what happens on day 23
- heart cells begin to contract (heartbeat)
- there will be a lumen
- if any fluid there, it will be sloshing around
hypoblast cells induce what tissue early in development:
What does the induced part eventually become?
the tissues about it to become epiblast
-This becomes most of the embryo
What is the primitive streak
- it gives us an axis of right/left symmetry
- line where epiblast cells will ingress into to the other side and make the mesodermal cells
what does the mesoderm form?
-bone, muscle, heart, blood
what is the primitive node
- the anterior portion of the primitive streak
- some cells that will ingress through primitive node and will go directly anterior to the AVE
know difference between precordal plate and prochoradal plate
Prechordal plate - area between prochordal plate and notochord ( also helps induce primary migration cells)
Prochordal plate - orophraryngeal membrane.
- AVE is located in the orophraryngeal membrane and induces migrating cells (primary)
“a small area immediately rostral to the cephalic tip of the notochord where ectoderm and endoderm are in contact; when turned under the growing head, it forms the buccopharyngeal membrane.”
what does the region anterior to the primitive node produce?
retinoic acid
The anterior visceral endoderm gets its message to differentiate and then what happens?
-It is able to produce its own signals after this and induce the formation of the head and the heart
retinoic acid
- comes from the region anterior to the primitive node (continually made)
- diffusion leads to a gradient
what does different conc. of retinoic acid lead to
different fates for cells that ingress from different areas of the primitive streak (fate mapping)
How many migrations are there?
what is the first migration gives you___
There are more than one.
the anterior/primary heart field
what is the 2nd cell migration
These contribute to the atria
all models are wrong, but some modles are useful
where does the blood develop?
where?
- Primarily in the extraembryonic region
- It is primarily in the yolk sac
What is vasculogenesis?
What are these aggregation of cells called?
The development of blood vessels from a condensation of mesenchyme.
- mesoderm cells clump together
- angiogenic cells clusters (bad name!, because they occur in vasculogenensis)
What is angiogenesis?
In what pathological disorder does this take place?
The sprouting of new blood vessels from preexisting ones
-happens when you’re developing a tumor
splanchopleure
- involved with guts
- involved with the internal part of the body like the intestines, lungs, stomach and the heart
somatopleure
-involved with skin, connective tissue of the limbs (“…and all that stuff”)
heart develops where?
Why is this specific location important?
in the deep portion of the mesoderm
-This explains why teh e[ricardium is where it is
Do angiogenesis or vasculogenesis happen in the embryo?
Combination of the 2 happens in embryo
cephalocaudal folding
- curved area of heart tube folds forward to inferior ventral position
- The embryo begins to curl around the developing yolk sac
- Heart was anterior and vertebral column was posterior, but after this you wind up with a heart that is ventrally located and inferior to the head
what is the “hinge”
Oralpharyngeal membrane
dorsal aortas are associated with
vertebral column
folding lead to multiple aortas how?
folding and after you cut cross-section you see 4 aortas
lateral folding
brings curve to the midline where they fuse (Fusion of heart tubes)
Since the heart tube grows more rapidly that the rest of the embryo, what happens to it?
why does this happen?
How does this happen?
- bound by pericardial sac which joins everything posterior to the heart.
- it folds on itself
- Venous portion grows faster and appears that it is moving cephalically and to the right.
- tube folds toward the left
what is the cavity that holds the developing heart called?
pericardial cavity
blood in heart tube travels
- comes from inferior up (through 5 pieces)
- blood comes from sinus venosus on 2 sides, then it goes through the embryonic atrium, tehn through the embryonic ventricle, then through the bulbus cordis, and teh out through the truncus arteriosus
what happens to venous return position
venous return and atria moves posteriorly and superiorly.
walls of the tube have what thickness and what substance
They are thick and have cardiac jelly (prevent kinks)
What does connective tissue have that prevents kinks?
- stuff in between the cells called brown substance or ECM material, etc
- This is usually composed of fibers like collagen and liquid
- liquid is in this molecule called hyaluronic acid
- HA is like a sponge and has the shape of a feather. and it holds things in shape.
what is the atrioventricular canal
connects atria to ventricles (before atrial and ventricular septums develop)
From where does the septum primum develop?
from the place where the outflow tract is
- 1st septa grows from what to what?
- what is it called?
- From posterior wall of the atrium down tot he anterior wall
- It looks like a half moon shape and will grow towards the floor
- Septum primum
what is the osteum primum
The opening in the septum primum located anteroinferiorly
- closes eventually as septum primum forms completely
bloodflow from what will be the inferior vena cava causes what
causes flimsy septuum (swiss cheese) to regular septum
Septum secundum
- more substancial, much thicker, forms on right side of septum primum
- grows from anterior to posterior
- has an opening on the growing part and never completes its closes on the posterior wall.
Ostium secondum
- Begins to form as swiss cheese like holes which are opened by blood flow from what will the the inferior vena cava.
osteum secundum of the 2 septa are offset.
what does that cause?
it causes the structure to act as flutter valve, pushing the flimsy septum out of the way.
which is the flimsy septum?
septum primum
at birth the septum primum :
is pushed against the septum secundum, closing the foramen ovale
What is the flutter valve called?
what is it called when is does not seal after birth?
What medical conditions ia probe-patent foramen ovale associated with?
- Foramen ovale
- probe-patent foramen ovale (funtionally closed, but tissues do not fuse)
- higher incidence of migraines, strokes and are more suceptable to altitude sickness
Heart is located where in an adult?
in the center
mostly behind the sternum
looks like a pyramid (4 sided):
- Base is just to the side of the sternum;
- Apex is to the left of it near the nipple and goes to the 4th intercostal space.
- It is asymmetric
what is the convention of how you section an embryo? how about and MRI/cadaver
- looking from head, down
- looking from feet up
what are the most common groups of malformations
cardivascular; many of which are heart malformations
Fertilization occurs where?
the ampullary region of the fallopian/uteran tube
what happens after fertilization?
cleavage divisions
what is released from the ovary
haploid egg
what are blastomeres
- a blastomere is a type of cell produced by cleavage (cell division) of the zygote after fertilization and is an essential part of blastula formation. -Wiki
what is particular about the size of the zygote
it is potentially visible to the naked eye
what does the extraembryonic tissue become?
the placenta, chorion, etc.
In the beginning how much of the embryonic tissue is the embryo proper?
very little of it.
most of it is extraembryonic.
When do lacunae begin to form?
During days 8-10
When do sinusoids begin to become eroded and leak into the lacunae
days 11-13
what does the evidence suggest about when does the strong uteroplacental circulation show up?
that it is not present until the 10th week of gestation
what is the first system to appear?
first to function?
Nervous system appears first
cardivascular system functions first.
what parts of the embryo become highly adherent to one another?
What will this eventually become?
what is this region of the hypoblast called?
The epiblast and hypoblast become very highly adherent to one another.
This will eventually become the oropharyngeal membreane.
The Anterior Visceral Endoderm (AVE)
What part of the hypoblast will induce the heart
The Anterior Visceral Endoderm (AVE)
As the AVE forms, what happens diametrically opposite from that?
the primitive streak forms
notochord helps to:
induce the neural tube…the neural plate, which will induce the central nervous system.
prechordal plate and oropharyngeal membrane (AVE)will induce what?
the heart
Epiblast cells will migrate in what orientation to the AVE?
What eventually happens to the AVE?
- They will migrate anterior to it and posterior to it but not directly to it.
- AVE will break down eventually
During cell migration after ingressing:
the first cells become
the Outflow tract
During cell migration after ingressing:
-middle cells become
the Ventricle
During cell migration after ingressing:
-most caudal cells become
The atrium
what do these migrating cells become as a whole?
the heart tube which eventually becomes the heart
The atria are the ends of the heart tube,
The ventricles are medial to that
The outflow tract is in the middle of the heart tube
Differentiation in these cells.
What is going inside of them and what affects them as they migrate?
Probably hoc genes and the retinoic acid gradients they migrate through.
What happens to the migrating cells destined to be heart cells after migrate?
Migrating cells become the horshoe area that surrounds the region where the oropharyngeal membrane breaks down.
What type of cells will become blood cells?
When is this happening?
Pockets of extraembryonic mesodermal cells
there will also be some in that will become the umbilical chord and eventually some inside the embryo , as well.
This is happening on the 20,21,22,23rd days of gestation
What happens within a couple of days of the emergence of blood cells
Within a couple of days, some of the cells forming vessels begin to contract
angiogenic cell clusters form ______
where are these located?
a tube (blood vessels)
-located in a position in the mesechyme that will be associated with the endoderm
the space above where the heart is gonna develop is called ________
How does this get to its position in a developed embryo?
the pericardial sac
cephalocaudal folding
All septums that divide the atria
are considered to be in the right atrium
Explain prenatal circulation within the heart
as blood comes into the right ventricle, there is high pressure because the lungs have high resistance.
This makes the blood travel from the right atrium to the left atrium through the foramen ovale
Describe what happens to the circulation after the baby is born
the pressure in the left side exceeds that in the right and functionally closes the foramen ovale
why do the atria have a smooth wall?
what process is involved?
The embryonic atrium become the auricles in the adult heart
- they are little pieces that hang of teh top of the adult atrium
- The tissue from the nearby veins are absorbed by the growing atria.
- Intussusception leads to absorption of veins into the atria
What veins come into the embryonic heart?
- veins from the yolk sac
- veins that come from the umbilical chord
- Veins that come back from the body (head and body regions)
on the right side, the sinus venosus becomes incoorporated into the ____
right atrium
on the left side, sinus venosus becomes the ____
coronary sinus and the oblique vein of the left atrium
what is intussuception?
When you have a tube and for some reason you can shove the proximal end of the tube into the one behind it. (also referred to as telescoping)
When this happens the parts that overlap can be expanded, thereby incorporating it into the wall of the the structure absorbing it (the atrium wall, in this case)
look up what veins come into left side of heart and what veins come to the right side of heart
4 Pulmonary veins enters the left ventricle
vena cava enters the right ventricle
how do the 4 openings from the pulmonary wall into the left atrium form?
intussusception: branched wall is absorbed into the atrium and the resulting 4 openings are formed from the branches of a single vessel that was absorbed.
does intussusception happen in both atria?
intussusception happens in both atria, but is more dramatic in the left one
what is the process of separating the atria from the ventricles called?
atrioventricular separation
what is the endocardial cushing
does this form before or after atrial separation?
does it happen before or after ventricular separation?
- It is in between the 2 epithelial layers of the heart
- tissue that closes in on the primitive atrioventricular canal forming a dumbell or H that will eventually separate it into the left and right atrioventricular canals.
- this happens prior to formation of the ventricular septum, but after the atrial septums have formed.
the opening between the embryonic atrium and the ventricle called?
primitive atrioventricular canal
what are adherons
- molecules that are released by the myocardial cells which induce endocardial cells to migrate and populate the endocardial cushing.
- Have signal molecules ( it is uncertain which ones, so don’t memorize them!!)
The primitive interventricular septum is what?
what does it become and how does it become that?
- a bump in the bottom of the embryonic ventricle is the beginning of the interventricular septum.
- What will become the 2 ventricles is an out-pouching of the tube.
- This area becomes stabilized while the sides of the ventricles begin to bulge out.
- On the outiside of this area, there are molecules that are very sticky. As the walls grow out, the stickiness causes them to stick together and you whind with a area that becomes the septum as the side baloon out. The parts of the “baloons” that are stuck together form the interventricular septum. (the muscular part)
Besides the formation via aposition of adjacent walls, what else is involved in the formation of the ventricular septum?
some mitotic divisions takes place as well
The interventricular septum has 2 parts.
what are they called?
The muscular and a membranous septum
neural crest cells from the hind brain migrate to __
what do they help form?
area of the outflow tract of the heart and they help to separate it and form the aorticopulmonary septum AKA the spiral septum.
Describe the membranous part of the ventricular septum
- Goes through a clockwise location
- There are ridges on either side,
- Two ridges come together and form a spiraling septum.
- cells know how to take up origin in the right place in the conotruncal (Bulbus cordis) ridge. As they grow out towards lumen, they are on diff places and wind up making a septum that spins.
-
left truncoconal ridge and right truncoconal ridge
ridges from where the spiral septum forms
***doublecheck
how do the atrioventriclar valves form?
- TBX genes involved
- As ventricluar walls get thicker, there will be some cell death that will form trabeculae.
- At the same time and under same control there is a laying down of collagen fibers on the top edges of the ventricle. This also happens partially along the lumen of the ventricle.
- Dense areas have been carved out and the connective tissue connect to structure called papillary muscle. These strings, called chordi tendinae, are like a parachute and prevent valve leaflets from prolapsing into the atria as a result of the force of contraction of the ventricles.The stabilize valves.
what are trabeculae
- Trabeculae are 3D structures that are present in wall of heart. Areas of cell death.
What are the names of the aortae leaving the heart?
what about the ones by the vertebrae?
What comes out of the heart is aortic sac or ventral aorta.
the part by the vertabrae are called the dorsal aortae
How many braches of aortae form?
There are 5 aortic arches (1,2,3,4 and 6th), but 5th is vestigeal and probably does not develop in humans.
describe the chronology of how the aortic arches develop.
they develop in sequence: by time 3rd is forming, the 1st is disappearing, so they are not all present at the same time.
what does the Aortic Arch I become?
it becomes the Maxillary artery on both sides
what does the Aortic Arch II become?
- It becomes the hyoid artery on both sides
- it becomes the stapedial artery on both sides (they disappear)
what does the Aortic Arch III become?
- It becomes the Proximal Arch: common carotid artery on both sides
- It becomes the Distal Arch : Internal Carotid artery on both sides
what does the Aortic Arch IV become?
- ON THE RIGHT: Proximal right subclavian artery
- ON THE LEFT: Arch of the Aorta (medial portion)
what does the Aortic Arch VI become?
- ON THE RIGHT: Right pulmonary artery
- ON THE LEFT: Left pulmonary artery AND Ductus arteriosus
Ventral Aorta becomes
- Cranial to Arch III: External Carotid Artery on bothe sides
- Between Arch III & IV: Common Carotid Artery on both sides
- Between Arch IV & VI:
- ON THE RIGHT: Brachiocephalic Artery
- ON THE LEFT: Ascending Aorta
Dorsal Aorta becomes
- Cranial to Arch III: Internal Carotid Artery on both sides
- Between Arch III & IV: Disappears with growth of neck on both sides
- Between Arch IV & VI:
- ON HE RIGHT SIDE: Central Right Subclavian Artery- ON THE LEFT SIDE: Descending Aorta
Caudal to Arch VI
- ON THE RIGHT SIDE: Disappears - ON THE LEFT SIDE: Decending aorta
Vitelline Veins bring blood from
from yolk sac and eventually from intestine
Umbilical veins bring blood from
from placenta
Cardinal veins bring blood from
from body (head or trunk)
Subcardinal veins bring blood from
mesonephric Kidneys plus the gonads (which take up a large percentage in the abdominal cavity.)
supracardinal veins bring blood from:
they become_____
- Body wall
- either of two veins in the mammalian embryo and various adult lower vertebrate forms located in the thoracic and abdominal regions dorsolateral to and on either side of the descending aorta and giving rise to the azygous and hemiazygous veins and a part of the inferior vena cava
- become the azygous and the hemiazygous system
What does Dr. Desseso want us to remember about the Vena Cava?
- is complex
- some veins drop out
- Don’t know that 7 parts of the inferior vena cava
- In the lab, supracardinal veins become the azygos and the hemiazygous system (supposed to find)
- Seen a cadaver that had no inferior vena cava (went through azygous system)
umbilical arteries return blood to the placenta by way of the
iliac veins
Why doesn’t the blood pressure in the baby drop at birth?`
what is a clinical correlate related birth
The blood in the placenta is pumped into the embryo
-Dont immediately tie off umbilical chord at birth or will have a problem with hypovolemia
6th aortic arch gives rise to ductus arteriosus. What does this structure do before birth and what happens after birth.
what does it become?
how does it know how to close?
- before birth it shunts oxygenated blood to the aorta.
- after birth, it needs to close. It becomes the ligamentum arteriosus.
- The prostaglandins coming from placenta begin to drop, and oxygen tension tends to drop. This causes that piece of smooth muscle in the ductus arteriosum to constrict and functionally close.in 24-48 hours. and permanently close (fibrous material) within about 6 weeks.
What are 6 mechanisms that drive cardiovascular development and an example of each
Ed Clark (university of rochester)
- Cellular migration - spiral septum neural crest cells
- Extracellular matrix - issues with interatrial septa
- Hemodynamics - how blood travels through heart
- Targeted growth- Muscular septum
- Cell death- has to occur in some places for septa
- Visceral Situs- whether heart looped to the right or not
Congenitall malformations incidence
Overall (Major and minor): 7 %
Heart Malformations:
- Among liveborn: 1%
- Among Stillbirth: 10%
Extracellular ECM defects
- Osteum primum septal defect-
- Wide open foramen ovale or perforations
- Probe-patent foramen ovale (not malformation, just an anotomical difference)
- Foramen Ovale not sealed
Spiral septum
joins with the muscular part of the interventricular septum
Membranous Ventricular septal defect
- spiral septum does not form correctly and so interventricular septum is not completely closed
- 85-90% of these close spontaneously during the first week of life
- May be considered a developmental delay
- Sometimes is a small hole that is not functionally significant
- Related to the cell migration??
Malformations related to abnormal blood flow:
Coarctation of aorta
- when smooth muscles collapse around ductus arteriosus, the muscles cells involved sometimes spill over to the aorta. They respond the same as the ductus arteriosus and constrict a part of the aorta.
- Preductal and postductal (before or after ductus arteriosus)
- Postductal can be fixed surgically quite easily
-Goes from large lumen to small lumen to large lumen again
Malformations related to abnormal blood flow:
How does the body adjust when the is coarctation of aorta?
Anastomotic channels shunt blood through another path
Malformations related to abnormal blood flow:
Atresia of valves
give 2 examples
valves not present (both pulmonary and aortic)
- Pulmonary valve atresia
- Aortic Valve Atresia
Malformations related to abnormal blood flow:
Stenosis of valves
give example of one
- Small valves
- ie. Aortic Valvular Stenosis
aberrant cellular migration defects
- persistent truncus arteriosus: interventricular septum does not fully form. Blood mixes
- transposition of great vessels: Spiral septum forms in wrong direction. Blood never mixes. normally incompatible with life except when accompanied by an interventricular septal defect. Surgery can fix this at birth
- Tetralogy of falllot: spiral septum divides aortic pulmonary trunk unevenly leading to the formation of large overriding opening to the aorta and one that is stenotic for the pulmonary artery.
- Accompanied by interventricular ventral septum
- Because of energy required to force blood into the pulmonary artery you end up with hypertrophy of teh right ventricle.
- Radiography looks like Coeur en Sabot (wooden shoe)
- babies tend to crouch because they have difficulty getting blood to lungs and this position compresses the femoral vessels, ameliorates the dyspnea, increasing the left ventricular pressure. TOGETHER THIS REDUCES THE RIGHT TO LEFT SHUNT.
How can patients planning to have children reduce the risk of TOF
- Lower incidence of TOF by taking multivitamin in periconceptual times
- it is associted with decreased amount of VEGF
Malformation caused by Aberrant Cell death
Muscular ventricular septal defect
Visceral Situs causes what?
Dextrocardia
- Heart loops in the wrong direction: right sided heart (Left looping)
- Normal looping is Right looping and it leads to left sided heart - May or may not be a problem, depending on what else hasn’t looped at the same time.
What are the 3 most common Cardiac Malformations
Ventricular Septal defect (39%)
Atrial septal defect (10%)
Persistent Ductus Arteriosus (8%)
One-cell zygote timeline
1
Blastocyst timeline
5
Implantation
7.5
Cardiogenic plate timeline
19-20
First contractions timeline
21-24
Aortic arch 1 timeline
22
Sinus venosus
24-27
Cardiac looping timeline
25-27
Circulation begins timeline
26
Aortic arch 2 timeline
30
Aortic arch 3 timeline
28-31
Aortic arch 4 (AA 1 regressing)
31-34
Endocardial cushions timeline
26-28
Aortic arch 6 timeline
32-35
Interventricular septum begins
29-35
Septum primum timeline
28-37
Endocardial cushions fused timeline
35-40
Spiral septum begins
32-35
Ostium secundum timeline
40
Septum secundum timeline
40
Foramen ovale
41-44
Interventricular septum complete timeline
43-46
Spiral septum complete timeline
35-46
