Development of the Heart and the foetal circulation

Question 1

When does the primordial heart and vascular system start to appear

Answer 1

About middle of week 3 = The first major system to function in the embryo

Question 2

Where do the cardiogenic progenitor cells ceom from and how do they get down

Answer 2

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.

Question 3

Outline how the cardiogenic field is formed

Answer 3

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

Question 4

How does the cephalocaudal and the lateral folds affect the cardiac progenitor tubes

Answer 4

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

Question 5

What sorrounds the heart once the 2 endocardial tubes have merged

Answer 5

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.

Question 6

What are the 4 regions of the endocardial tube, as well as the inflow and outflow

Answer 6

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.

Question 7

What vessels contribute to the sinus venosus of the endocardial tube

Answer 7

Contributes to the sinus venosus = Umbilica, vitelline, and cardinal veins = Which are from chorion, umbilical vesicle and embryo respectively.

Question 8

Describe how the endocardial tube bends

Answer 8

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.

Question 9

When does the heart looping finish|?

Answer 9

Finished by day 28.

Question 10

When does the partioning of the various chambre sof th eprimordial heart begin and finish?

Answer 10

Beings in middle of week 4

And finishes end of week 8

Question 11

Describe the partioning of the atrioventricular canal

Answer 11

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.

Question 12

Describe the partioning of the atrium

Answer 12

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

Question 13

What does the ostium primum allow and where is it

Answer 13

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.

Question 14

Describe the partioning of the sinus venosus

Answer 14

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).

Question 15

What is the sinus venarum

Answer 15

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.

Question 16

What vessels leave the LA

Answer 16

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>

Question 17

Describe the partioning of the ventricles

Answer 17

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.

Question 18

Describe the partioning of bulbis cordis and truncus arteriosis

Answer 18

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

Question 19

How does the conducting system of the heart develop and change through foetal development

Answer 19

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.

Question 20

Describe the genetic and chromosomal factors that are linked to congenital heart defects

Answer 20

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.

Question 21

Describe how environmental factors are related to congenital heart defects

Answer 21

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.

Question 22

Name 2 positional congenital heart anomalies

Answer 22

1) Dextrocardia

2) Extopia Cordis

Question 23

Outline what happens in dextrocardia and its relationship with situs inversus and heterotaxy

Answer 23

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

Question 24

Outline what happens in ectopia cordis, and what happens clinically.

Answer 24

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.

Question 25

Outline endocardiac cushion defects, and why they often occur with craniofacial defects at the same time

Answer 25

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

Question 26

Name the 5 types of ASD

Answer 26

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)

Question 27

What is the most common form of ASD, describe its incidence and significance

Answer 27

Patent foramen ovale = Can occur in 25% of population

Generally not significant = Unless forced open because of other cardiac defects

Question 28

Are ASDs more common in men or women

Answer 28

girls twice as likely to get ASD then boys.

Question 29

Describe a foramen secundum ASD, how it forms, and how it presents

Answer 29

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

Question 30

Describe endocardial cushion defects with foramen primum ASD

Answer 30

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.

Question 31

Describe a sinus venosus ASD

Answer 31

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.

Question 32

Describe common atrium (Cor triloculare biventriculare) ASD

Answer 32

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.

Question 33

Name the 4 subtypes of ventricular septal defects

Answer 33

1) Membranous VSD
2) Muscular VSD
3) Single ventricle (Cor triloculare bitriatum) VSD
4) Atrioventricular septic defect (AVSD)

Question 34

Describe the incidence of VSDs and if they are more common in boys or girls

Answer 34

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

Question 35

What are the general symptoms of a VSF

Answer 35

General symptoms of VSF = Dyspnoea, PHT, and cardiac failure.

But these depend on the VSD defect, and what associated conditions there are

Question 36

Outline what a membranous VSD is

Answer 36

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.

Question 37

Outline what a muscular VSF is

Answer 37

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’

Question 38

Outline what a single ventricle )Cor triloculare biatrium) VSD is

Answer 38

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

Question 39

Ourline what an atrioventricular septal defect or AVSD is

Answer 39

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

Question 40

Name the 4 most common abnormalities of the conotruncal region

Answer 40

1) Tetralogy of fallot
2) Persistent truncus arteriosus
3) Transposition of the great vessels
4) |Valvular stenoses

Question 41

Outline the changes in tetralogy of fallot

Answer 41

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.

Question 42

Outline what a presistent truncus arteriosus is

Answer 42

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

Question 43

Outline transposition of the great vessels

Answer 43

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.

Question 44

Outline vascular stenoses as a congenital heart lesion

Answer 44

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

Question 45

Outline what happens in tricuspid atresia

Answer 45

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.

Question 46

What is the most common cause of SIDS in developed countries?

Answer 46

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

Question 47

Describe how blood gets from placenta to foetal heart and then back to placenta

Answer 47

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.

Question 48

What is the source of the umbilical artery

Answer 48

It comes of the internal iliac artery.

Question 49

How many umbilicla arteries and veins are there

Answer 49

2 umbilical arteries

1 Umbilical vein

Question 50

What is the O2 sats of the blood in umbilical vein versus arteries

Answer 50

80% in vein

58% in arteries

Question 51

What are the 5 different areas where deoxygenated blood is mixed with the oxygenated blood that is coming through the umbilical vein?

Answer 51

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

Question 52

What is the course of the ductus venosus?

Answer 52

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

Question 53

How does the umbilical vein also supply some blood to the liver? and how is this supply regulated? Such as in labour

Answer 53

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.

Question 54

How does blood flow through the foetal heart

Answer 54

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.

Question 55

What are the 4 things that close in the circulatory system at birth

Answer 55

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

Question 56

Describe how the umbilical arteries close, and what the remnants are

Answer 56

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

Question 57

Describe how the umbilical vein and ductus venosus closes, and what the remnants are

Answer 57

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.

Question 58

Describe how the ductus arteriosus closes, including timelines and what the remnant is. Also what causes it to close

Answer 58

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.

Question 59

Describe the closure of the oval foramen

Answer 59

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.