Development of the Heart and the foetal circulation Flashcards
When does the primordial heart and vascular system start to appear
About middle of week 3 = The first major system to function in the embryo
Where do the cardiogenic progenitor cells ceom from and how do they get down
Cardiac progenitor cells lie in the epiblast = Immediately lateral to the primitive streak
These then migrate through the steak towards the cranium and lie in the splanchnic layer of the lateral plate mesoderm. SO THEY ARE MESODERM
Here they are then induced into cardiac myoblasts.
Outline how the cardiogenic field is formed
First blood islands start to also appear in the splanchnic layer of lateral plate (meosderm) This is same place the progenior cardiac cells go.
These form blood cells and vessels by vasculogenesis.
These islands then unite to form a horsehoe-shaped and endothelial-lined tube sorrounded by myoblasts. Think of this as a horshoe, with the cranial ends of tube joined, and a cardiac tube running down each side of the embryo.
The intra-embryonic cavity around this then forms the pericardial cavity
How does the cephalocaudal and the lateral folds affect the cardiac progenitor tubes
The cephalocaudal folding and rapid growth of the brain = Causes cardiogenic area to move caudally to the thorax
As a result of lateral folding = The caudal regions of the paried cardiac primordia merge, except at the most caudal end.
This means 2 entries at top, merged tube in the middle, and 2 outracks at the bottom
What sorrounds the heart once the 2 endocardial tubes have merged
The tube is sorroudned by a gelatinous connective tissue = Cardiac jelly.
Pericardium = Formed of mesothelial cells that sorround it. This outer layer is repsonsibel for formation of coronary arteries.
What are the 4 regions of the endocardial tube, as well as the inflow and outflow
Outfflow at top = Aortic roots and aortic sac 1) Truncus arteriosus 2) Bulbis cordis 3) Primitive ventricle 4) Primitive atria Inflow at bottom = Sinus venosus.
What vessels contribute to the sinus venosus of the endocardial tube
Contributes to the sinus venosus = Umbilica, vitelline, and cardinal veins = Which are from chorion, umbilical vesicle and embryo respectively.
Describe how the endocardial tube bends
The bulbis cordis and ventricle = Grow faster then other regions, which means heart bends on itself in a S-shaped look. Known as cardiac loop or bulboventricular loop
This means that the bulbis cordis and primitive ventricles come anteriorly and become the Right and Left ventricle repsectively.
Eventually heart fills the entire pericardial cavity, suspended there. Only attached at cranial and caudal ends by blood vessels.
When does the heart looping finish|?
Finished by day 28.
When does the partioning of the various chambre sof th eprimordial heart begin and finish?
Beings in middle of week 4
And finishes end of week 8
Describe the partioning of the atrioventricular canal
During week 4 = Endocardial cushions form on dorsal and ventral wall of the atrioventricular canal.
These then approach and fuse eachother dividing the atrioventricular canal down the middle into the right and left sided atrioventricular canals.
These canals = Seperate the primordial atrium from primordial ventricle.
Describe the partioning of the atrium
Occurs = Between day 27 and 37 meaning between week 4 and 6.
Septum primum = Grows first down from roof of primordial atrium to endocardial cushion. This has the osium primum. But this quickly becomes smaller and dissapears.
Before ostium primum dissapears = The septum secondum grows and the foramen secondum opens, which then allows blood flow.
Thick muscular fold = This when grows down from roof of right atrium and forms a flap like valve called the foramen ovale. This then allows R to L atrial blood flow during foetal life
What does the ostium primum allow and where is it
In the septum primum that is between the 2 atria = Allows oxygenated blood to flow from R to L atria.
After this closes = Ostium secondum opens.
Describe the partioning of the sinus venosus
This occurs between = Week 4 and week 10
Remember that the sinus venosus has 2 horns (or vessels that feed into it).
During weeks 4-5 there are many L to R shunts in the venous system. The vessels that supply the L horn, the right umbilical vein, and Left vitelline vein also obliterate in week 5 = This causes the R sinus horn to enlarge, while left sinus horn rapidly shrinks
At week 10 = Left common cardial vein also obliterates. All that is left feeding left sinus horn is the oblique vein of the left atrium and the coronary sinus.
This means the right sinus horn now receives all of the bloods body via the SVC and IVC. These then get incorporated into wall of RA, the sinus venarum (most posterior part of RA).
What is the sinus venarum
The smooth most posterior area of the RA. Which is the part of the R sinus horn of the sinus venosus that joins the RA to become part of the heart.
What vessels leave the LA
Well at this piont blood is entering the LA through 4 pulmonary veins.
These join the wall of the LA, just like R sinus horn of sinus venosus joins the RA>
Describe the partioning of the ventricles
A muscular septum grows up from floor of primordial ventricle.
It has a crescent shaped interventricular foramen, which allows communication. This closes at week 7.
After it closes = The pulmonary trunk is linked with RV, and aorta linked with LV.
Describe the partioning of bulbis cordis and truncus arteriosis
During week 5 = There are mesenchymal cells in the walls of the bulbis cordis and truncus arteriosus. These form ridges called conotruncal ridges.
These then rotate 18- degrees resulting in the formation of a spiral aorticopulmonary septum when the ridges fuse.
This divides bulbis cordis and truncus arteriosus into the future ascending aorta and the pulmonary trunk.
Because of spiraling septum = The aorta and pulmonary trunk twist around eachother
How does the conducting system of the heart develop and change through foetal development
Early stages = Pacemaker is done by atrium
Later = Done by sinus venosus
As sinus venosus is incorporated into the RA = The pacemaker joins the RA near opening of the SVA. This becomes the SAN at week 5.
AVN + bundle of His = Comes fom cells in the left wall of sinus venosus and the atrioventricular canal.
Describe the genetic and chromosomal factors that are linked to congenital heart defects
About 8% of cardiac malformations are due to genetic factors.
Example genetic syndromes = DiGeorge, Goldenhar, and Down syndromes.
Of children with chromosomal abnormalities = 33% have congenital heart defects. With an incidence of nearly 100% with trisomy 18 (Edwards syndrome.
Describe how environmental factors are related to congenital heart defects
A small amount 2% of congenital heart defects are due to environmental factors.
Classic examples of cardiovascular teratogens = Alcohol, rubella virus, drugs like thalidomide, and isotretinoin (Vit A).
Raised first-trimester blood glucose, and hypertension = Also been linked.
Name 2 positional congenital heart anomalies
1) Dextrocardia
2) Extopia Cordis
Outline what happens in dextrocardia and its relationship with situs inversus and heterotaxy
Features = Heart lies on right side of thorax. Most common positional anomaly of heart
Cause = When the heart loops to the left instead of the right.
Associations = Can also occur with situs invertus, where all organs are also inverted. Or with heterotaxy where positions of some organs are reversed
Generally these conditions have normal physiology, but can be associated with heart defects
Outline what happens in ectopia cordis, and what happens clinically.
Feature = Heart in wrong place, most commonly partly or completely exposed on surface of thorax. Can also protrude through diaphragm into abdo.
Cause = Faulty development of sternum and pericardium
Death = Comes from infection, cardiac failure, hypoxaemia in most cases in first few days of life.
Management = Surgery. Some patients survive to adulthood.
Outline endocardiac cushion defects, and why they often occur with craniofacial defects at the same time
Endocardial cushions are in key locations = So can lead to various cardiac malformations.
Neural crest cells = Are present in conotruncal cushions, but also contirbute to development of the head and neck. So often get cardiac and craniofacial defects at the same time
Name the 5 types of ASD
1) Patient foramen ovale
2) Foramen secundum ASD
3) Endocardial cushion defects with foramen primum ASD
4) Sinus venosus ASD
5) Common atrium (Cor triloculare biventriculare)
What is the most common form of ASD, describe its incidence and significance
Patent foramen ovale = Can occur in 25% of population
Generally not significant = Unless forced open because of other cardiac defects
Are ASDs more common in men or women
girls twice as likely to get ASD then boys.
Describe a foramen secundum ASD, how it forms, and how it presents
This is generally considered a alrge opening between the atria.
Cause = Excessive cell death and resorption of the septum primum, or inadequate development of the septum secundum.
Presentation = Well tolerated in childhood, presenting with PHT in 3rd decade of life
Describe endocardial cushion defects with foramen primum ASD
This is actually group of disorders all with same cause below.
Cause = Deficiency of the endocardial cushions and the atrioventricular septum. The septum primum did not fuse with endocardial cushions.
Describe a sinus venosus ASD
Rarest type of ASD
Cause = Incomplete incorporation of the sinus venosus into RA or abnormal development of the septum secondum.
Associated = Commonly with partial anomalous pulmonary venous connections.
Describe common atrium (Cor triloculare biventriculare) ASD
This is the complete absence of the atrial septum, and is therefore a combination of all the other ASDs.
The others being = Foramen secundum ASD, foramen primum ASD, sinus venosus ASD.
Name the 4 subtypes of ventricular septal defects
1) Membranous VSD
2) Muscular VSD
3) Single ventricle (Cor triloculare bitriatum) VSD
4) Atrioventricular septic defect (AVSD)
Describe the incidence of VSDs and if they are more common in boys or girls
VSDs are most common congenital heart defect, about 25% of all cardiac defects.
More common in boys then girls.
Can be isolated lesion, or associated with others, esp abnormalities in partioning of the conotruncal region
What are the general symptoms of a VSF
General symptoms of VSF = Dyspnoea, PHT, and cardiac failure.
But these depend on the VSD defect, and what associated conditions there are
Outline what a membranous VSD is
Cause = Failure of membranous part of interventricular septum to form.
Incidence = This is most common form of VSD, at about 12 in 10,000 births. 30-50% of these should close in first year of life.
Outline what a muscular VSF is
Can occur anywhere in muscular part of the interventricular septum. Less common the membranous VSDs
Sometimes = Can multiple small defects, producing a ‘swiss cheese VSD’
Outline what a single ventricle )Cor triloculare biatrium) VSD is
This is a complete absence of the interventricular septum. Extremely rare, but results in a 3 chambered heart. IN this case both aorta and pulmonary trunk will arise from this single common ventricle
Ourline what an atrioventricular septal defect or AVSD is
Failure of the endocardial cushions to fuse.
Results in a large defect in the centre of the heart.
It is rare, but occurs in 20% of children with Down’s syndrome
Name the 4 most common abnormalities of the conotruncal region
1) Tetralogy of fallot
2) Persistent truncus arteriosus
3) Transposition of the great vessels
4) |Valvular stenoses
Outline the changes in tetralogy of fallot
Incidence = This is the most common abnormality of the conotruncal region occuring in 9.6 in 10,000 births.
Cause = There is anterior displacement of the conotruncal septum. This causes an unequal division o fthe conus and therefore produces 4 alterations
1) Pulmonary stenosis
2) Causing RV hypertrophy
3) VSD
4) Dextroposition of the aorta (overiding aorta)
Presentation = Cyanosis, but this may not be present at birth.
Treatment = Primary surgical repair in early infancy.
Outline what a presistent truncus arteriosus is
Incidence = Occurs in 0.8 in 10,000 births.
Cause = truncal ridges and aorticopulmonary septum fail to develop normally. This means truncus arteriosus cannot divide into aorta and pulmonary trunk.
The undivided truncus overides both ventricles and recieveds mixed blood.
Can also result in VSD because ridges participate in development of the interventricuar septum also
Outline transposition of the great vessels
Incidence = Occurs in 4.8 in 10,000 biths. Most common cyanotic heart disease in newborn infants.
Cause = Conotruncal septum runs straight down instead of spiral course. Means aorta overides RV, and PT overides LV.
Often associated with membranous VSD or patent ductus arteriosus.
Death occurs in a few months if not surgically corrected.
Outline vascular stenoses as a congenital heart lesion
Can occur in pulmonary artery or aorta.
Cause = Due to fusion of the semilunar valves. The stenoses can occur over varying distances, so it can either be a mild narrowing or complete atresia.
Pulmonary artery stenosis = In this case a patent foramen ovale is the only way for blood to get out from the right side. And a patient ductus arteriosus is only way for blood to get to the lungs.
Aortic valve stenosis = Aorta is usually normal size, but LV and LA are markedly underdeveloped. In this case the PDA delivers blood into aorta
Outline what happens in tricuspid atresia
This is absence or fusion of the tricuspid valve = Results in obliteration of the right atrioventricular orifice.
Associated with patent foramen ovale, a VSD, an underdeveloped RV, and a hypertrophied LV.
What is the most common cause of SIDS in developed countries?
Abnormalities of the hearts conducting system.
We dont really know the mechanism. But it is thought to be related to abnormalities in the autonomic nervous system
Describe how blood gets from placenta to foetal heart and then back to placenta
Remember umbilical vein goes to heart form placenta. SO this carries 80% oxygen saturated blood from the placenta.
Here it becomes the ductus venosus around the liver, then becomes the IVC and enters the heart
In total it mixes with deoxygenated blood from 5 different sources and enters the heart.
Blood form the descneding aorta goes back to the placenta from two umbilical arteries.
What is the source of the umbilical artery
It comes of the internal iliac artery.
How many umbilicla arteries and veins are there
2 umbilical arteries
1 Umbilical vein
What is the O2 sats of the blood in umbilical vein versus arteries
80% in vein
58% in arteries
What are the 5 different areas where deoxygenated blood is mixed with the oxygenated blood that is coming through the umbilical vein?
1) Liver = This is blood that is coming back from the portal system
2) IVC = This is blood coming from lower extremities, pelvis, and kidneys
3) Right atrium = This is blood coming from head and upper extremities that comes through SVA
4) Left atrium = Blood returning from the lungs via the pulmonary veins. Remember this is deoxygenated blood as it is returning form the lungs in feotus
5) Junction of ductus arteriosus and descending aorta = This allows the oxygenated blood from pulmonary trunks to travel into the aorta so it can supply the blood around body. But also some deoxygenated blood from proximal aorta mixes into the PT
What is the course of the ductus venosus?
The umbilical vein becomes the ductus venosus. This allows the oxygenated blood to mainly bypass the liver and go straight into RA via the IVC
How does the umbilical vein also supply some blood to the liver? and how is this supply regulated? Such as in labour
Most umbilicla vein blood bypasses liver via ductus venosus. But some does enter liver through the liver sinusoids.
This flow is regulated through a sphincter mechanism which is in the ductus venosus close to the entrance of the umbilical vein.
During uterine contract = This can cause the venous return to the heart to be very high, and can cause overload of the heart. So in uterine contraction the sphincter closes stopping this.
How does blood flow through the foetal heart
IVC into RA = The blood from the IVC points up and therefore goes more into the foramen ovale to the LA. But a small amount of the blood stays in the RA and mixes with deoxygenated blood from the SVC.
SVC to RA = Points down so goes down into RV and then into the PT. Pulmonary resistance is high in foetus, therefore blood passes into descending arota through ductus arteriosus.
LA to LV = And then enters the ascending aorta. The coronary and carotid arteries are the first branches of the ascending aorta. This means heart and brain are well supplied first.
What are the 4 things that close in the circulatory system at birth
1) Closure of umbilical arteries
2) Closure of the umbilical vein and ductus venosus
3) Closure of the ductus arteriosus
4) Closure of the oval foramen
Describe how the umbilical arteries close, and what the remnants are
Trigger = Thermal and mechanical stimuli, along with change in oxygen tension causes SM in umbilicla arteries to contract
When = Functional closure of the arteries occurs in a few minutes. Complete obliteration of the lumen with fibrous proliferation takes 2-3 months.
Proximal portions of the arteries = Remain open as the superior vesical arteries.
Distal portions = Form the medial umbilical ligaments
Describe how the umbilical vein and ductus venosus closes, and what the remnants are
When = These both close shortly after umbilical arteries.
Remnant = After obliteration, the umbilical vein forms the ligamentum teres hepatis, or the round ligament of the liver. This is the lower margin of the falciform ligament
And the ductus venosus = Forms the ligamentum venosum which courses from the round ligament to the IVC.
Describe how the ductus arteriosus closes, including timelines and what the remnant is. Also what causes it to close
Cause = Mediated by bradykinin. This is released by lungs during initial inflation.
Closure = Immediately after birth the muscular walls contract. But complete obliteration takes 1-3 months.
What happens = Causes massive increase in blood supply to lungs. This increases pressure in the LA (blood returning). This shuts the foramen ovale.
Remnant = Forms the ligamentum arteriosum.
Describe the closure of the oval foramen
Cause = Closure of the ductus arteriosus means opening of the pulmonary system means increased LA pressure and reduced RA pressure.
When first breath is taken = Septum primum presses against septum secondum. This causes functional closure of the foramen ovale.
Reversible = This closure is actually reversible in the first days of life, when the baby cries it opens the R to L shunt again, and accounts for the cyanotic periods in the newborn.
Eventually = Constant apposition causes the 2 septa to fuse at about 1 year of age.
