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DEVELOPMENT OF HEART- OVERVIEW
DR.D.SURESH
FIRST YEAR CARDIOLOGY RESIDENT
INTRODUCTION
• Cardiovascular system starts to develop by middle of 3rd week of
intrauterine life.
• Heart starts to beat by early 4th week (23 rd day).
• Entire process of heart development completes by 7th week.
• Crucial period for development of anomalies is 3 - 6 weeks.
PRIMARY HEART FIELDS
• Progenitor heart cells lie in
the epiblast, from they
migrate to splanchnic
mesoderm, which forms
primary heart fields.
• PHF
1. Atrium
2.Left ventricle
3. Parts of right ventricle.
.
SECONDARY HEART FIELDS
• Secondary heart fields(SHF)
develop in the splanchnic
mesoderm ventral to pharynx.
• SHF
1. Parts of Right ventricle
2. outflow tract ( conus cordis
and truncus arteriosus)
• SHF - Laterality of heart which
occurs on day 16
Molecular regulation- HEART FIELDS
• Induction of heart by NKX 2.5.
• BMP 2 & 4 Secreted by
endoderm and lateral plate
mesoderm.
• WNT INHIBITION by CRESCENT
and CEREBRUS -.
• RETINOIC ACID(RA) – contribute
to the venous portion of heart
tube.
LEFT SIDEDNESS
5 - HT - transcription factor
PITX2.
PITX2 - master gene for left
sidedness.
Laterality defects such as
dextrocardia, VSD, ASD, DORV,
OUTFLOW Defects occurs.
Tertogenicity of SSRI explains the
importance of 5 –HT Signaling
pathway.
Heart tube formation
• PHF are induced by the
endoderm to form cardiac
myoblasts and blood islands.
• Blood islands will forms blood
cells and vessels by
vasculogenesis.
• Blood islands unite and forms a
horseshoe shaped endothelial
tube , cardiogenic region.
• Pericardial cavity develops over
it
Formation and position of heart tube
• Cardiogenic area lie anterior to
oropharyngeal membrane.
• Growth of the brain and cephalic
folding of embryo pulls the
oropharyngeal membrane
cranialy ,while heart and
pericardial cavity moved first to
cervical region and then to
thorax.
• .
• As a embryo grows and bends
cephalocaudally, caudal regions
of the paired cardiac tube
merges except at the
caudalmost parts
• Central parts of the heart tube
expands to form the outflow
tract and ventricular regions
• Now the heart becomes a
continuous tube with an inner
endothelium and an outer
myocardial lining.
• Heart tube remains attached to
dorsal side of pericardium by the
dorsal messocardium.
• Middle section of dorsal
mesocardium disappears and
forms transverse pericardial sinus
which connects both sides of the
pericardial cavity.
• Myocardium thickens and secrete a
layer of ECM called cardiac jelly .
• Heart tube consists of three
layer
1.Endocardium – internal
endothelial lining of heart.
2. Myocardium – muscular wall
3. Epicardium – visceral
myocardium, formation of
coronary arteries
Cardiac looping
• Heart tube continues to elongate
as cells are added from SHF to its
cranial end.
• Lengthening process is essential
for normal formation of part of
right ventricle and outflow tract
region and looping process.
• Cardiac tube begins to bend on
day 23 and completes on day 28
• Cephalic portion of the tube
bends ventrally, caudally and to
the right.
• Caudal (atrial) portion shifts
dorsocranially and to the left.
Cardiac looping
• Conotruncal portion of heart tube
moves from the right side of
pericardium to the more medial
position,results from the formation
of two transverse dilations of
atrium.
• Trabeculae occurs in the primitive
ventricle becomes left ventricle.
• Bulboventricular sulcus – junction
between the ventricle and bulbus
cordis. Its called the primary
interventricular foramen.
Bulbus cordis
Proximal parts :
• Trabeculated parts of the right
ventricle
• Conus cordis :
Outflow tracts of both ventricle.
• Truncus arteriosus –
• Roots and proximal portion of aorta
and pulmonary artery.
Sinus venosus development
Each horns receives
• 1. viteline veins
• 2.. Umblical veins
• 3. common cardinal veins.
• During 4th and 5th week shifting
occurs predominantly to right -
obliteration of left vitelline veins
at 5th week and obliteration of
left common cardinal veins at
10th weeks
Cont..
• Only oblique vein of left atrium
and coronary sinus persists.
• Right sinus horns - smooth
walled part of right atrium.
• Sinus venosus also gives rise to
the visceral pericardium of the
heart.
• Some of sinus venosus cells
infiltrate into the heart and forms
the conducting system of the
heart.
• Its entrance sinuatrial orifice
flanked on each side by rt and lt
venous valves.
• Dorsocranially valves fuses and
forms a sputum spurium.
• Lt venous valve and sputum
spurium helps in the development
of atrial septum
• Rt venous valve develops into
• 1.valve of IVC
• 2. valve of coronary sinus
Abnormalities of cardiac looping
• Dextrocardia : the location of the heart in the right hemithorax with
the base to apex axis to the right
• Mesocardia : cardiac base to apex axis directed to the midline of the
thorax or with ventricular apices equally directed to both right and
left sides
Cardiac septa formation
1.Endocardial cushions-
septum formation by two
actively growing ridges
2. septum formation by single
actively growing cell mass,
such as septum primum and
septum secundum.
3.IVS - septum formation by
merging two expanding
portions of the walls of heart.
Formation of interatrial septum
• Septum primum –
• End of 4th week
• Sickle shaped crest grows from
the roof of common atrium
towards endocardial cushions.
• Opening between the lower rim
of septum primum and
endocardial cushions – ostium
primum.
Cont..
• Superior and inferior
endocardial cushions grows
along the edge of septum
primum and closes the ostium
primum.
• Before closure , cell death occurs
in the upper portion of septum
primum and forms the ostium
secundum
• New crescent shaped fold called
septum secundum appears .
• Left venous valve and septum
spurium fuse with the right side
of the septum secundum .
• It overlap the ostium secundum
• The opening left by ostium
secundum is called oval foramen
(foramen ovale)
• Remaining parts of septum
primum becomes the valve of
the oval foramen.
Formation of left atrium and pulmonary veins
Dorsal mesenchymal
protrusion(DMP) - the
proliferating mesenchyme of
the dorsal mesocardium.
This tissues grows with the
septum primum towards the
atriventricular canal.
• Pulmonary veins is positioned.
• Remaining parts of DMP
contributes to endocardial
cushion formation.
Clinical correlates:
TAPVR
AV CANAL SEPTUM FORMATION
• FOUR endocardial cushions
appears at the end of 4 weeks.
• AV CANAL access only to
primitive left ventricle and is
separated by bulbo ventricular
flange.
• At the end of fifth
week,posterior extremity of
flange terminates midway along
the base of dorsal endocardial
cushions.
• AV canal enlarges to right -
direct access to rt and lt
ventricle.
• Two lateral endocardial cushions
appear on the right and left
borders of canal.results into rt
and left av valves
• Each AV Orifices is surrounded
by local proliferations of
mesenchymal tissues
• Blood flows hollows out,
mesenchymal tissue becomes
fibrous and forms the AV
VALVES.
• AV valves remain attached to the ventricular wall by the muscular
cords.
• Muscular cords degenerates and is replaced by dense connective
tissues to become chordae tendinae.
• AV Valves are connected to the papillary muscles by means of
chordae tendinae.
Septum formation in the truncus arteriosus
and conus cordis
• Right superior truncus swelling
grow distally and to the left and
on
the left inferior truncus grow
distally and on the right.
• Swelling twisted around each
other and forms the
aorticopulmonary septum
divides the truncus into an aortic
and pulmonary channel.
Cont..
• Similar swellings appear on the
dorsal and ventral walls of conus
cordis ,grows towards each
other and distally to unite with
the truncus septum.
• Septum divides the conus into
an anterolateral portion
(outflow tract of RV) AND
POSTEROMEDIAL
portion(outflow tract of LV)
INTERVENTRICLUAR SEPTUM- MUSCULAR
PART
• By the end of 4TH week ,two
primitive ventricles begin to
expand.
• Medial walls of the expanding
ventricles become apposed and
gradually merge – muscular
ventricular septum.
• Interventricular foramen – space
between the free rim of muscular
ventricular septum and fused
endocardial cushions.
• Interventricular foramen closes by
completion of conus septum and
outgrowth of tissue from the
anterior endocardial cushions
along the top of muscular
interventricular septum.
BULBAR PARTS
• Right and left bulbar ridges arise
in bulboventricular cavity
• These ridges grows towards each
other to form bulbar septum
• Grows downwards towards
muscular part of IVS but does
not reach it
MEMBRANOUS PARTS
• Proliferation of tissue from
inferior A-V endocardial
cushions fills the gap between
muscular and bulbar parts of IVS
• TWO parts :
• INTERVENTRIULCAR
• ATRIOVENTRICULAR – separates LV
& RA
Semilunar valves
• Semilunar valves visible as small tubercles found on the main truncus
swellings.
• Third tubercle appear in both channels opposite the fused truncus
swellings.
• Tubercles hollow out at their upper surface forming semilunar valves.
• Neural crest cells contribute to the formation of semilunar valves.
Aortic Arch
• Each pharyngeal arch has own
cranial nerve and arteries.
• Aortic arches arise from the aortic
sac ,the most distal part of truncus
arteriosus.
• .
• By day 27,most parts of 1st and 2nd
arch disappears.
• First arch artery is represented by
maxillary artery.
• Second arch artery is represented
by stapedial artery.
• 3rd arch
• Common carotid artery
• Part of internal carotid artery
• External carotid atery arises as
sprout from 3rd arch
5th arch fails to form
FOURTH ARCH
4th arch on right
• Proximal segment of
subclavian artery
• Distal segment - 7th
intersegmental and Rt dorsal
aorta.
4th arch on left
Arch of aorta
• 6th arch on right
• Right pulmonary artery
• Distal segment regress
6th arch on left
• Left pulmonary artery
• Distal segment as ductus
arteriosus
• .
Venous system
Inferior vena cava
• Rt Vitelline veins –
hepatocardiac portion of ivc
• Rt subcardinal veins – renal
segment of ivc
• Rt sacrocardinal veins.
Superior venae cava
ANASTOMOSIS of rt common
cardinal veins and proximal
portion of right anterior cardinal
veins.
Conducting system of heart
• Pacemaker for the heart lies in the caudal part of the left cardiac
tube.
• AFTER cardiac looping ,sinus venosus assumes this function’
• Pacemaker lies near the opening of svc into the right atrium ,thus
sinoatrial node is formed.
• Av node and bundle of his are derived from two sources:
1.myocardial cells in the left wall of sinus venosus.
2.myocardial cells from AV Canal.
NEURAL CREST CELLS
• Cardiac neural crest cells - the
formation endocardial formation in
both conus and truncus arteriosus.
• Neural crest cells - the smooth
muscle and connective tissues of
the arch vessels.
• Heart defects caused by this
mechanism include TOF,PS,PTA
AND TGA.
THANK YOU

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Development of heart.pptx

  • 1. DEVELOPMENT OF HEART- OVERVIEW DR.D.SURESH FIRST YEAR CARDIOLOGY RESIDENT
  • 2. INTRODUCTION • Cardiovascular system starts to develop by middle of 3rd week of intrauterine life. • Heart starts to beat by early 4th week (23 rd day). • Entire process of heart development completes by 7th week. • Crucial period for development of anomalies is 3 - 6 weeks.
  • 3. PRIMARY HEART FIELDS • Progenitor heart cells lie in the epiblast, from they migrate to splanchnic mesoderm, which forms primary heart fields. • PHF 1. Atrium 2.Left ventricle 3. Parts of right ventricle. .
  • 4. SECONDARY HEART FIELDS • Secondary heart fields(SHF) develop in the splanchnic mesoderm ventral to pharynx. • SHF 1. Parts of Right ventricle 2. outflow tract ( conus cordis and truncus arteriosus) • SHF - Laterality of heart which occurs on day 16
  • 5. Molecular regulation- HEART FIELDS • Induction of heart by NKX 2.5. • BMP 2 & 4 Secreted by endoderm and lateral plate mesoderm. • WNT INHIBITION by CRESCENT and CEREBRUS -. • RETINOIC ACID(RA) – contribute to the venous portion of heart tube.
  • 6. LEFT SIDEDNESS 5 - HT - transcription factor PITX2. PITX2 - master gene for left sidedness. Laterality defects such as dextrocardia, VSD, ASD, DORV, OUTFLOW Defects occurs. Tertogenicity of SSRI explains the importance of 5 –HT Signaling pathway.
  • 7. Heart tube formation • PHF are induced by the endoderm to form cardiac myoblasts and blood islands. • Blood islands will forms blood cells and vessels by vasculogenesis. • Blood islands unite and forms a horseshoe shaped endothelial tube , cardiogenic region. • Pericardial cavity develops over it
  • 8. Formation and position of heart tube • Cardiogenic area lie anterior to oropharyngeal membrane. • Growth of the brain and cephalic folding of embryo pulls the oropharyngeal membrane cranialy ,while heart and pericardial cavity moved first to cervical region and then to thorax. • .
  • 9. • As a embryo grows and bends cephalocaudally, caudal regions of the paired cardiac tube merges except at the caudalmost parts • Central parts of the heart tube expands to form the outflow tract and ventricular regions
  • 10. • Now the heart becomes a continuous tube with an inner endothelium and an outer myocardial lining. • Heart tube remains attached to dorsal side of pericardium by the dorsal messocardium. • Middle section of dorsal mesocardium disappears and forms transverse pericardial sinus which connects both sides of the pericardial cavity. • Myocardium thickens and secrete a layer of ECM called cardiac jelly .
  • 11. • Heart tube consists of three layer 1.Endocardium – internal endothelial lining of heart. 2. Myocardium – muscular wall 3. Epicardium – visceral myocardium, formation of coronary arteries
  • 12. Cardiac looping • Heart tube continues to elongate as cells are added from SHF to its cranial end. • Lengthening process is essential for normal formation of part of right ventricle and outflow tract region and looping process.
  • 13. • Cardiac tube begins to bend on day 23 and completes on day 28 • Cephalic portion of the tube bends ventrally, caudally and to the right. • Caudal (atrial) portion shifts dorsocranially and to the left.
  • 14. Cardiac looping • Conotruncal portion of heart tube moves from the right side of pericardium to the more medial position,results from the formation of two transverse dilations of atrium. • Trabeculae occurs in the primitive ventricle becomes left ventricle. • Bulboventricular sulcus – junction between the ventricle and bulbus cordis. Its called the primary interventricular foramen.
  • 15. Bulbus cordis Proximal parts : • Trabeculated parts of the right ventricle • Conus cordis : Outflow tracts of both ventricle. • Truncus arteriosus – • Roots and proximal portion of aorta and pulmonary artery.
  • 16. Sinus venosus development Each horns receives • 1. viteline veins • 2.. Umblical veins • 3. common cardinal veins. • During 4th and 5th week shifting occurs predominantly to right - obliteration of left vitelline veins at 5th week and obliteration of left common cardinal veins at 10th weeks
  • 17. Cont.. • Only oblique vein of left atrium and coronary sinus persists. • Right sinus horns - smooth walled part of right atrium. • Sinus venosus also gives rise to the visceral pericardium of the heart. • Some of sinus venosus cells infiltrate into the heart and forms the conducting system of the heart.
  • 18. • Its entrance sinuatrial orifice flanked on each side by rt and lt venous valves. • Dorsocranially valves fuses and forms a sputum spurium. • Lt venous valve and sputum spurium helps in the development of atrial septum • Rt venous valve develops into • 1.valve of IVC • 2. valve of coronary sinus
  • 19. Abnormalities of cardiac looping • Dextrocardia : the location of the heart in the right hemithorax with the base to apex axis to the right • Mesocardia : cardiac base to apex axis directed to the midline of the thorax or with ventricular apices equally directed to both right and left sides
  • 20. Cardiac septa formation 1.Endocardial cushions- septum formation by two actively growing ridges 2. septum formation by single actively growing cell mass, such as septum primum and septum secundum. 3.IVS - septum formation by merging two expanding portions of the walls of heart.
  • 21. Formation of interatrial septum • Septum primum – • End of 4th week • Sickle shaped crest grows from the roof of common atrium towards endocardial cushions. • Opening between the lower rim of septum primum and endocardial cushions – ostium primum.
  • 22. Cont.. • Superior and inferior endocardial cushions grows along the edge of septum primum and closes the ostium primum. • Before closure , cell death occurs in the upper portion of septum primum and forms the ostium secundum
  • 23. • New crescent shaped fold called septum secundum appears . • Left venous valve and septum spurium fuse with the right side of the septum secundum . • It overlap the ostium secundum • The opening left by ostium secundum is called oval foramen (foramen ovale) • Remaining parts of septum primum becomes the valve of the oval foramen.
  • 24. Formation of left atrium and pulmonary veins Dorsal mesenchymal protrusion(DMP) - the proliferating mesenchyme of the dorsal mesocardium. This tissues grows with the septum primum towards the atriventricular canal.
  • 25. • Pulmonary veins is positioned. • Remaining parts of DMP contributes to endocardial cushion formation. Clinical correlates: TAPVR
  • 26. AV CANAL SEPTUM FORMATION • FOUR endocardial cushions appears at the end of 4 weeks. • AV CANAL access only to primitive left ventricle and is separated by bulbo ventricular flange. • At the end of fifth week,posterior extremity of flange terminates midway along the base of dorsal endocardial cushions.
  • 27. • AV canal enlarges to right - direct access to rt and lt ventricle. • Two lateral endocardial cushions appear on the right and left borders of canal.results into rt and left av valves • Each AV Orifices is surrounded by local proliferations of mesenchymal tissues • Blood flows hollows out, mesenchymal tissue becomes fibrous and forms the AV VALVES.
  • 28. • AV valves remain attached to the ventricular wall by the muscular cords. • Muscular cords degenerates and is replaced by dense connective tissues to become chordae tendinae. • AV Valves are connected to the papillary muscles by means of chordae tendinae.
  • 29. Septum formation in the truncus arteriosus and conus cordis • Right superior truncus swelling grow distally and to the left and on the left inferior truncus grow distally and on the right. • Swelling twisted around each other and forms the aorticopulmonary septum divides the truncus into an aortic and pulmonary channel.
  • 30. Cont.. • Similar swellings appear on the dorsal and ventral walls of conus cordis ,grows towards each other and distally to unite with the truncus septum. • Septum divides the conus into an anterolateral portion (outflow tract of RV) AND POSTEROMEDIAL portion(outflow tract of LV)
  • 31. INTERVENTRICLUAR SEPTUM- MUSCULAR PART • By the end of 4TH week ,two primitive ventricles begin to expand. • Medial walls of the expanding ventricles become apposed and gradually merge – muscular ventricular septum.
  • 32. • Interventricular foramen – space between the free rim of muscular ventricular septum and fused endocardial cushions. • Interventricular foramen closes by completion of conus septum and outgrowth of tissue from the anterior endocardial cushions along the top of muscular interventricular septum.
  • 33. BULBAR PARTS • Right and left bulbar ridges arise in bulboventricular cavity • These ridges grows towards each other to form bulbar septum • Grows downwards towards muscular part of IVS but does not reach it
  • 34. MEMBRANOUS PARTS • Proliferation of tissue from inferior A-V endocardial cushions fills the gap between muscular and bulbar parts of IVS • TWO parts : • INTERVENTRIULCAR • ATRIOVENTRICULAR – separates LV & RA
  • 35. Semilunar valves • Semilunar valves visible as small tubercles found on the main truncus swellings. • Third tubercle appear in both channels opposite the fused truncus swellings. • Tubercles hollow out at their upper surface forming semilunar valves. • Neural crest cells contribute to the formation of semilunar valves.
  • 36. Aortic Arch • Each pharyngeal arch has own cranial nerve and arteries. • Aortic arches arise from the aortic sac ,the most distal part of truncus arteriosus. • . • By day 27,most parts of 1st and 2nd arch disappears. • First arch artery is represented by maxillary artery. • Second arch artery is represented by stapedial artery.
  • 37. • 3rd arch • Common carotid artery • Part of internal carotid artery • External carotid atery arises as sprout from 3rd arch 5th arch fails to form
  • 38. FOURTH ARCH 4th arch on right • Proximal segment of subclavian artery • Distal segment - 7th intersegmental and Rt dorsal aorta. 4th arch on left Arch of aorta
  • 39. • 6th arch on right • Right pulmonary artery • Distal segment regress 6th arch on left • Left pulmonary artery • Distal segment as ductus arteriosus • .
  • 40. Venous system Inferior vena cava • Rt Vitelline veins – hepatocardiac portion of ivc • Rt subcardinal veins – renal segment of ivc • Rt sacrocardinal veins. Superior venae cava ANASTOMOSIS of rt common cardinal veins and proximal portion of right anterior cardinal veins.
  • 41. Conducting system of heart • Pacemaker for the heart lies in the caudal part of the left cardiac tube. • AFTER cardiac looping ,sinus venosus assumes this function’ • Pacemaker lies near the opening of svc into the right atrium ,thus sinoatrial node is formed.
  • 42. • Av node and bundle of his are derived from two sources: 1.myocardial cells in the left wall of sinus venosus. 2.myocardial cells from AV Canal.
  • 43. NEURAL CREST CELLS • Cardiac neural crest cells - the formation endocardial formation in both conus and truncus arteriosus. • Neural crest cells - the smooth muscle and connective tissues of the arch vessels. • Heart defects caused by this mechanism include TOF,PS,PTA AND TGA.
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