CHD Module 1 - Embryology

Where is the cardiogenic region of the early embryo?

Angiogenic cell clusters within the mesoderm

How is the early embryo nourished?

Yolk sac

What is the gestational age that the heart begins and completes its development?

Begins: Day 18

Completes: Day 22

What is the gestational age the heart begins to beat?

Day 22

Describe cardiac looping, including timing of the events.

Day 18: angiogenic cells develop into 2 lateral endocardial tubes located cephalad to the developing brain

Day 21: lateral folding of the disks and cranial folding of the head region

Day 22: heart tube anchors to arteries at cephalic and and veins at caudal ends

Describe apex pivoting.

After looping is complete, the apex pivots leftward

Levocardia, mesocardia, dextrocardia.

Levocardia: apex directed leftward (normal)

Mesocardia: apex directed to midline

Dextrocardia: apex directed rightward

Describe lateral heart tube merging.

Lateral (endocardial) heart tubes merge and myocardium and epicardium layers form the pericardial cavity surrounding.

Describe differentiation of the heart tube.

The heart tube elongates, developing dilations and constrictions.

Describe how the heart tube come to be in the thoracic region.

Cranial folding of the head moves the oropharyngeal membrane and developing forebrain dorsal/cephalad to the heart tube and the septum transversum posterior/caudal to the heart tube. 

Describe how the heart tube anchors itself within the pericardium.

Cephalic/atrial end - bilateral dorsal aortas and it’s developing arch system

Caudal/venous end - bilateral developing umbilical venous sytem

Aortic sac becomes

• aortic arch

• aortic head and neck branches

• pulmonary artery branches

Truncus arteriosus becomes

• aortic valve and trunk

• pulmonary valve and trunk

Conus cordis becomes

Outflow tracts of both ventricles

Bulbus cordis becomes

Right ventricle

Primitive ventricle becomes

• Left ventricle

• Inflow of right ventricle

Primitive atrium becomes

Rough portions of right and left atriums (including atrial appendages)

Sinus venosus becomes

Right horn - smooth portion of right atrium

Left horn - coronary sinus

Name the 3 paired sets of veins returning blood to the sinus venosus and where they perfuse.

Cardinal veins from the embryo

Umbilical veins from the placenta

Vitelline veins from the yolk sac

Paired sets of veins becomes

Mature veins

Primary foramen becomes

Closed with IVS formation

Atrioventricular canal becomes

Mitral and tricuspid valve

Sinoatrial junction becomes 

Eustachian valve

Draw the pericardial cavity at approximately 28 days in a coronal cut. Include the yolk sac, umbilical cord, and placenta.

Why does dextroventricular looping occur?

Bulbus cordis and primitive ventricle grow faster than the rest of the tube, causing the tube to form a U-shaped bend (bulboventricular loop)

Describe the movement of the heart tube components during dextroventricular looping.

Bulbus cordis and primitive ventricle move caudal and anterior

Primitive atrium and sinus venosus move cephalad and posterior

Describe what part of development went atypical to result in an L-looped heart and how it differentiates from a D-looped heart.

Instead of dextroventricular looping, the heart loops to the left. This causes the ventricles to switch positions and the aorta to arise to the left of the pulmonary artery.

Describe AV canal migration.

Occurs after looping

Rightward expansion of the AV canal to bring blood flow into the bubus cordis

Now the primitive atrium brings blood into the primitive ventricle (future LV) and bulbus cordis (future RV)

Explain what heart defects may occur when AV canal migration is abnormal.

Double inlet left ventricle (DILV)

Both AV valves supply the LV

The vitelline veins become

Portal and hepatic veins

The umbilical veins become

Right disappears

Left brings oxygenated blood to the fetus throughout the pregnancy

The cardinal veins become

Left and right anterior anastomos → left brachiocephalic vein

Right anterior →  SVC

Left anterior → regresses

Posterior → IVC, azygous and hemiazygous veins

Explain how pulmonary veins develop.

Explain the common anomalies that may result if venous development is abnormal.

Persistent left superior vena cava (LSVC)

• Drains to coronary sinus, causing dilation due to increased flow

Intrahepatic portion of the IVC fails to develop

• Interruption of the IVC with azygous continuation (IVC→azygous→SVC)

Total anomalous pulmonary venous drainage (TAPVD)

• Failure of the confluence to be absorbed to the LA

• LA is very small and only has rough walls

Cor-triatriatum

• Incomplete absorption of the pulmonary confluence creates a “third atria”

• obstruction of flow from the wall between smooth and rough portions of LA

If the IVC is blocked, how does blood from the lower body return to the heart?

Azygous and hemiazygous veins are accessory pathways that drain to the SVC and can dilate if necessary.

Describe the changes in the sinus venosus as it matures.

Right horn enlarges and becomes the posterior wall of the RA (smooth wall)

Left horn regresses, becomes coronary sinus

SA junction migrates rightward, closer to the RA

What are crista terminalis?

Line of demarcation between smooth and rough portions of the artias.

Describe the development of the pulmonary veins.

Pulmonary venous plexus drains into cardinal and vitelline veins

4 distinct veins form and join a confluence

Common pulmonary vein connects to the LA, primitive venous connections regress

Confluence is absorbed to the posterior wall of the LA

Describe the formation of the atrial septum and understand the importance of the foramen ovale.

1. septum primum grows towards the dorsal endocardial cushions

2. perforations in septum primum become foramen secumdum

3. foramen primum closes, blood flow from RA to LA persists through foramen secundum

4. septum secundum starts growing superior and to the right of septum primum

5. septum secundum grows inferiorly until it covers foramen secundum

6. as foramen secundum does not allow blood flow through, foramen ovale allows blood flow through the valve of foramen ovale (inferior aspect of septum primum)

7. after birth, Pr LA > Pr RA, causing the valve to close (no blood flow from RA to LA)

Describe the embryological origin of the atriums.

RA smooth - right horn of sinus venosus

LA smooth - confluence of pulmonary veins

Rough - primitive atrium

What is the defect that could occur if the foramen ovale is restrictive during development?

• enlarged RA

• high Pr LA

• small LV

• pulmonary hypertension at birth (large RA)

Describe the different types of atrial septum defects and how they occur.

Primum ASD - ostium near the MV

Secundum ASD - ostium in the middle of the IAS

Sinus venosus ASD - ostium at the junction between the SVC and RA

Describe how the AV canal develops into two separate orifices and what structure the division creates.

Superior and inferior endocardial cushions grow towards each other and fuse, creating 2 separate orifices separated by the inlet ventricular septum

Describe how the AV leaflets are formed.

1. mesenchymal tissue near the AV canal is reshaped to form leaflets

2. ventricular tissue is undermined (degenerating myocardium) to form chordae tendineae

Define Ebstein’s Anomaly.

Incomplete undermining of the TV leaflet, leaving the TV leaflet tethered to the RV wall (no chordae tendineae).

Name the common anomalies that may result if AV canal development is abnormal.

Single AV Orifice Persists

• single AV valve

Primum ASD

• atrial septal defect at the MV

Inlet VSD

• ventricular septal defect

Define complete AV canal defect

All 3 AV canal defects:

• Single AV Orifice Persists

• Primum ASD

• Inlet ASD

Name the 4 sections of the IVS.

• membranous septum

• outlet septum

• inlet septum

• trabecular septum

Describe the formation of the trabecular septum.

• grows towards the endocardial cushions and eventually fuses

• muscular ridge on the floor between the PV and BC, elongates as the ventricles expand

Describe the formation of the inlet septum.

• formed from endocardial cushions as the AV canal divides

• wall between the AV valves

Describe the formation of the outlet/conal/infundibular septum.

1. ridges develop on opposing sides of the conus cordis

2. ridges grow towards each other and fuse to form the conal septum, with the subpulmonic cordis closer to the BC and the subaortic conus closer to the PV

3. the subaortic conus regresses and twisting occurs to bring the aorta in close proximity to the PV

4. twisting aligns the conal septum with the inlet and trabecular septum

Describe the formation of the membranous septum.

• endocardial tissue that grows between the conal, trabecular, and inlet septum

• last and smallest part of the IVS

• only part that is not muscular (very thin)

Ventricular growth is stimulated by:

Inflow from the TV and MV

No flow, no grow

Name the defect that can cause the RV and LV respectively to be very small.

Tricuspid Valve Atresia

• TV completely blocked, no flow to RV, no growth of RV

Mitral Valve Atresia

• very small MV, little flow to LV, little growth of LV

Describe 4 IVS defects.

Double Outlet RV

• failure of the subaortic conus to regress

• both pulmonary trunk and aorta come off the RV

Trabecular VSD

Inlet VSD

Outlet/Conal/Infundibular VSD

 Membranous VSD

Describe the development of the aorta and pulmonary trunks and their valves.

1. Ridges in the truncus arteriosus and conus cordis grow towards each other in a spiral fashion (aorticopulmonary septum)

2. Tissue a the orifice of each vessel remodel to form aortic and pulmonary valves

Errors in truncal septation result in:

Truncus Arteriosus

• absent septum, single outlet leaving the heart (IVS does not close, no membranous septum)

Aortopulmonary Window

• ostium in septum

Transposition of the Great Arteries

• division is not spiral, PA does not develop anterior to the Ao

Describe the embryonic myocardium.

• spongelike with deep trabecular recesses

• lined with endothelium for direct gas exchange (no coronary circulation)

Describe how embryonic myocardium differs in the RV and LV.

• spongelike myocardium is compacted more in the LV than RV

  • LV has fine trabeculations, RV has coarse trabeculations

What is expected if compaction of trabeculations is arrested?

Non-compaction LV or Spongey Myocardium

• deep recesses in the LV, increasing the risk of thromboembolism 

Describe the development of the aortic arch.

Left 4th aortic arch forms the definitive aortic arch

Describe the development of the branch pulmonary arteries and ductus arteriosus.

Right and left 6th arches

List the aortic arches and their mature structures.

Right 3rd aortic arch → right common carotid artery

Left 3rd aortic arch → left common carotid artery

Left 4th aortic arch → aortic arch

Left and right 6th aortic arches → pulmonary arteries and ductus arteriosus

Dorsal aortas → internal carotid arteries, right subclavian artery, and descending aorta

Describe the result if the right 4th aortic arch persists .

Double arch

Arches on either side of the trachea and esophagus squeeze the structures

Name the common anomalies that of incorrect great vessel development.

Double Aortic Arch

Truncus arteriosus

Aortopulmonary Window

Transposition of Great Vessels

Explain the importance of the neural crest tissue in cardiac development.

Cells in the developing hindbrain migrate to the conus cordis, truncus arteriosus, and aortic arch vessels and are critical for normal development

When is major embryological development of the heart compete?

Day 49