CVS: Development of the Heart and its Conduction System Flashcards
Describe early heart development
- Tube formation - muscle wrapped around endothelium
- Tube attached to arteries at one end, veins at the other
- Tube elongates by addition at each end of cells from the SHF
- Tube bends, loops + coils
- Neural crest cells migrate into outflow region to make outflow cushions
- Epicardium cells come from proepicardial organ
- Tube divided by partitioning into chamber
When does the heart begin to develop?
Weeks 3-10 post conception
First recognisable as a crescent-shaped tube of myocardium, lumen of tube lined by endocardium
Heart is first organ to develop and function
What is the cardiac crescent derived from?
Mesodermal cells
Describe the expansion of the primary heart tube
Medial part of crescent expands - later becomes left ventricle
Endocardial tube attaches to developing aortic arches cranially (outflow) and systemic veins caudally (inflow)
Describe the elongation of the heart tube
Cells from 2nd heart field added at both outflow and inflow
Ends of tube fixed, so heart must bend as it elongates
Direction of looping is genetically controlled (leftward)
What are the primitive chambers formed by?
Expansion (ballooning) of tube
How is the heart tube divided?
Dividing heart tube = Septation
Divided into:
- Atrioventricular septation
- Divides atria from ventricles
- Divided by AV cushions
- Atrial septation
- Divides LA + RA
- Divided by interatrial septum
- Ventricular septation
- Divided LV + RV
- Divided by interventricular septum
- Outflow tract septation
- Divides pulmonary artery from aorta
- Divided by OFT cushions
What 2 types of septation divide the heart tube?
Cushions:
- AV and OFT cushions
- Valve formation, stenosis and atresia defects if goes wrong
- Form when cardiac jelly (ECM) secreted by myocardium endocardial cells undergo epithelial-mesenchymal transition and populate the jelly. Neural crest cells contribute significantly to OFT cushions
Muscular walls:
- 1° and 2° interatrial septa, interventricular septum
- Defects give rise to holes
What are the FHF and SHF?
FHF - First Heart Field
SHF - Second Heart Field
What does the FHF form in heart embryology?
Forms primary heart tube, mostly left ventricle, parts of RA and LA
What does the SHF form in heart embryology?
Forms cells of outflow tract, RV + portions of RA and LA
What is the process called by which the heart tube is divided into 4 chambers?
Elongation
Explain the process by which the 4 chambers form
- Tubes (made from mesodermal cells) from either side midline fused
- Medial side expands (forming LV primarily)
- Arterial + venous sides need to move so they are on same side, done via twisting and looping
- Endocardial tubes attach to developing aortic arch (cranially, i.e. outflow) and systemic veins (caudally i.e. inflow)
- Cardiac crest and initial heart tube formed
- Cells from SHF add more tissue at outflow and inflow ends
- Outflow and inflow ends (anterior + posterior) are fixed so as tissue added, heart tube starts to bend as it elongates
- Bending = looping
- Direction of looping genetically controlled (humans → LHS)
What is dextrocardia?
Right hand side looping
This isn’t problematic as long as everything else is correctly reversed
Explain the later stages and actual forming of the chambers of the heart
- Tube elongates + loops
- Ballooning out of certain areas, mapping out chambers, specifically ventricles
- Interventricular groove on external surface that begins to separate the LV from RV on outside
- Venous region wrapped behind heart so LA and RA have been position on cranial region of heart
- Process of ballooning and folding continues until appendages of heart tube fuse to side of heart in adult position
What is the characterical difference between atria and ventricles in development?
Coronal section:
- On RHS - ballooning chamber
- Atria - smooth
- Ventricles - Honeycomb, trubecular layers
Discuss the formation of the aortic arch arteries
- Form sequentially with looping + ballooning of chamber
- Initially → Aortic arch I, until aortic arch VI
- As each forms the earlier forms will degenerate so that adult structures formed from 2, 4, 6
- When 4th forms, 1st degenerates
- When 5th forms, 2nd degenerates
- Remodelled at later stages, giving rise to structures in aortic arch
- Symmetrical
- In embryo - called pharyngeal arteries (transient)
- Form in sequence from anterior → posterior
Outline the remodelling of the aortic arch vessels and how it links to outflow tract separation
Makes the great vessels
- Cells responsible for separation of outflow tract are neural crest cells (from neural tube)
- Cells migrate from dorsal aspect of neural tube down pharyngeal arteries towards outflow tract
- Neural crest cells migrate to outflow tract and populate it + divide into aorta and pulmonary artery
- Causes change in BF in the R+L side of common trunk
- This BF is what causes degeneration of aortic arch arteries
Describe CHD effects
Acyanotic - Left to Right shunt
- VSD
- ASD
- AVSD
- Persistent Ductus Arteriosus
Cyanotic - Right to Left shunt
- Transposition of great arteries
- ToF
- Truncus arteriosus
- TAPVC (Total anomalous pulmonary venous connection)
Holes in septums are usually acyanotic (pressure is higher on left than right)
What are the 2 different types of septation that divide the heart tube?
Muscular walls:
- Primary and Secondary interatrial septa, interventricular septum
- Defects give rise to holes
Cushions:
- AV and OFT cushions - also give rise to valves
- Valve formation, stenosis and atresia defects if this goes wrong
Explain how the AV septum is formed
- AV cushion growing from dorsal wall towards midline of heart and also growing from medial wall towards midline
- Ventral + dorsal cushion meet in midline and fuse
- On either side of AV cushion are narrow channels which go on to form tricuspid + mitral valve, allowing flow of blood b/w LA + LV and RA + RV
H hole - 2 vertical lines which are the narrow channels
In what condition is an AV septum defect more common?
AVSD - Common AV junction, common in Down’s syndrome
What is the first step in interatrial septum formation?
- LA with the orifice of the pulmonary vein (broken arrow)
- RA with orifice of the systemic venous sinus (star)
- Primary interatrial septum (arrow) is growing to dive L-R
- First to form to separate atria
- Grows downwards
- Will grow down, meet AV cushion + fuse
Explain how interatrial septum is formed
- Primary interatrial septum grows down + fuses with AV cushion
- Trailing edge of septum that starts breaking down - allows blood to flow b/w LA and RA
- This hole is the foramen ovale and it exists to allow blood to flow around the lungs.
- Secondary interatrial septum is forming and that grows down, adjacent to primary
- As it grows it covers the foramen ovale
- Trailing edge of primary can move and allows shunting of blood
Outline statistical evidence that shows the severity of congenital heart disease and which types are more common and which lead to more infant death
CHD - Most common causes of infant mortality due to birth defects (30-50%)
Describe the origins of the cardiac conduction system
- Conduction tissue is specialised myocardium, not nerves (they come from neural crest cells)
- Variations in conduction properties caused by differences in ion channel and connexin (gap junctions) expression
- Conduction system differentiates by progressive, localised recruitment from heart tube myocardium
- Electrical insulation layers:
- Fibro-fatty layer at AV junction (ex cushions)
- Ventricular bundle branches wrapped in fibrous sheath
What is the hole between the atria called?
Ostium secundum or foramen ovale
Explain how the atrial septum is formed
- Primary interatrial septum grows down, fuses with AV cushions
- Trailing edge primary septum break down, allows blood to continue flowing from RA → LA
- Septum secundum grows down to form flap valve
- LA pressure increases after birth, closes valve, eventually seals
Describe the different ASDs
Atrial septal defects:
- Persistent foramen ovale
- Flap valve doesn’t completely seal
- Common (10% population) seen as probe patency
- Possible risk factor for stroke and in divers
- Ostium primum defect - Located near lower portion of atrial septum, may be associated with defects in mitral and tricuspid
- Ostium secundum defect - Located in centre of atrial septum
Explain how the interventricular septum is formed
IVS grows from wall, towards AV cushions, initially as thickened trabeculum
Describe ventricular septal defects
- 75% perimembranous
- 25% muscular
- Small
- Small L→ R shunt
- Medium
- Moderate L→ R shunt
- Large
- Large L→ R sunt
- Surgically repaired in childhood
Explain how the outflow tract is separated
- Single tube separated into aorta and pulmonary artery
- Must be attached to L + R ventricles respectively
- 2 cushions spiral through truncus arteriousus
- Complex remodelling at each end
Explain how the outflow tract is formed
- Spiralling cushions separate aorta + pulmonary artery
- Neural crest cells contribute to AP septum
- Complex remodelling of aortic arches
- Proximal cushions fuse with the IVS and AVS
What are the effects of OFT defects?
Several types of OFT defect:
- Different types that result in a common truncus
- OFT defects associated with neural crest defects
- Unequal division of OFT can lead to aortic or pulmonary stenosis
Describe transposition of the great arteries (TGA)
- Aorta connected to RV
- Pulmonary trunk connected to LV
- Arterial trunks usually side-by-side
- Probably caused by abnormal OFT cushions
- Lethal without VSD, ASD or PDA
- Cyanotic
- Can be surgically correct
Describe Tetralogy of Fallot
4 characteristic features:
- VSD (large)
- Pulmonary stenosis
- RV hypertrophy
- Overriding aorta
Right → Left shunt
Cyanotic
Complex phenotype may result from abnormal looping, leading to malalignment of segments
