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EMBRIOLOGI JANTUNG DAN

MEKANISME DEFEK JANTUNG


Kuliah Anatomi Blok 2.3

dr. Zainuri Sabta Nugraha, M.Sc

Departemen Anatomi
Fakultas Kedokteran
Universitas Islam Indonesia

DEVELOPMENT OF THE HEART AND GREAT BLOOD VESSELS


LEARNING OUTCOMES
1.

menjelaskan perkembangan awal jantung dari mesoderm splanknik

2.

Menjelaskan fusi tabung endocardial untuk membentuk jantung linier sederhana dengan
atrium , ventrikel dan katup yang memompa darah ke dalam lengkungan aorta .

3.

menentukan tiga busur peredaran darah jantung yang memasok jaringan tubuh , yolk sac
( vitelline ) dan allantois dan menjelaskan fungsinya

4.

menjelaskan peran splanchnopleure yolk sac saat haematopoiesis awal

5.

Tunjukkan bagaimana pembentukan septum pada jantung linear primitif yang


memungkinkan memompa darah terpisah ke aorta dan truncus pulmonalis

6.

menggambarkan kelainan kongenital :defect septum , paten duktus arteriosus , dan arkus
aorta persisten

Introduction

Humanheartstartstodevelopduringthe3 rdweekofembryoniclife.Tillthentheneedsof
theembryoaremetthroughsimplediffusionofbloodbetweenthegermlayers.
Cardiogenesisinhumansisassociatedwithcomplexmorphogeneticevents

EarlyCardiacdevelopment
1.
2.
3.
4.
5.
6.
7.

Formationofthetrilaminarembryo
Originofcardiogeniccells
Formationofbilateralheartfields
Formationofthehearttube
Foldingofthehearttube
Loopingofthehearttube
Cardiacdevelopmentalabnormalities

Sequenceofevents

Occurstowardstheendofthe3 rdweek
DayI8cardiacprecursorcellsseenintheformofbloodislands
Day20firstintraembryonicbloodvesselsseen
Day21Folding,hearttubeformation,looping
Day22heartstartstobeat,ebbandflowinitially
Day28embryoniccirculationestablished

FORMATION OF THE MAMMALIAN GASTRULA - 9

MESODERM
TYPE

INTERMEDIATE
STRUCTURE

HEAD
CHORDA-

MESODERM
DERIVATIVE
HEAD MUSCLES, SKULL,
CARTILAGE

NOTOCHORD
LIMB MUSCLES
AXIAL SKELETON

PARAXIAL
ICM

EPIBLAST

SOMITES

MESODERM

TRUNK MUSCLES
DERMIS

INTERMEDIATE

PARTS OF KIDNEY
AND REPRODUCTIVE TRACT
LIMB SKELETON

LATERAL

HEART
BODY CAVITY DIVIDERS
BLOOD CELLS
AMNION
CHORION
YOLK SAC
ALLANTOIS

The developing blood vessels and heart tube can be seen in an embryo at
approximately 18 days .
When looking down at this early embryo you can see multiple blood islands
dispersed throughout the embryo.

The heart primordium arises


predominantly from the
mesoderm in the cardiogenic
region of the trilaminar embryo.

Cardiacprecursorcells

Firstheartfield(FHF)
Secondheartfield(SHF)
Proepicardium
Cardiacneuralcrestcells

FHF

SHF
CNC
Proepicardium

The cardiac tube folds under the gut tube

THE EARLY DEVELOPMENT OF THE HEART - 1


A

DORSAL AORTA

B
GUT TUBE

ENDODERM
CARDIAC TUBE
PERICARDIAL CAVITY
CARDIAC PRIMORDIUM
(SPLANCHNIC MESODERM)

The cardiac primordia are established in the


early gastrula as regions of splanchnic
mesoderm ahead of the embryo itself. As a
result of the head fold, this region ends up
beneath the pharynx.

VITELLINE VEINS

The heart is a U-shaped tube at this stage and


the forming blood vessels are initially
unconnected

Formationoftheendocardialtube

Theheartinitiallyformsfromtwo
tubeslocatedbilaterally(oneither
side)ofthetrilaminarembryoin
thecranial(head)
Thisprimitive,bilateralheart
tubeseachcontainsaninner
layerofendocardium,amiddle
layerofcardiacjelly,andanouter
layerofmyocardiumregion

Formationoftheendocardialtube

Theprimitivehearttubes
thenfuseintheventral
midlinetoformthelinearor
straighthearttubeina
cranialtocaudaldirection

Simultaneouslytheheart
tubeshowsaseriesof
dilatations.
Fromcranialtocaudalthese
are:
1.
2.
3.
4.

Bulbouscordis
Ventricle
Atrium
Sinusvenosus

Thearterialtrunkwilldividetoseparatethepulmonaryandsystemicsupply.
Thebulbusandtheventriclewilllaterdifferentiateintotherightandleft
ventricle

and connects bilaterally with the dorsal aorta via the aortic arches

C
FUSED DORSAL AORTA

1ST AORTIC ARCH (R)

VENTRICLE

ORAL PLATE

The sides of the U-tube then fuse to


produce the atrial and ventricle regions
with valvular flaps to prevent back flow so
that the heart can function as a simple
peristaltic pump.

ATRIUM

VENOUS RETURN FROM


CARDINAL VEINS,
VITELLINE VEIN AND
ALLANTOIC (UMBILICAL)
VEIN

The dorsal aorta form independently and


then grow to meet the ventral output from the
heart in the aortic arches

This pattern of mammalian development


is a good example of recapitulation

D
PHARYNGEAL POUCHES
LUNG BUD

THIS STAGE RESEMBLES FISH

The diagram shows 6 aortic arches but, in mammals, 1 and


2 are regressing while the later arches are forming and
arches 5 never form

REMINDER:
The branchial arches and clefts and the juxtaposed pharyngeal
pouches are a recapitulation of the respiratory anatomy of fish
SEGMENTATION OF THE HEAD
THE BRANCHIAL ARCHES AND PHARYNGEAL POUCHES

THE FOUR PHARYNGEAL


POUCHES CORRESPOND
TO THE FOUR BRANCHIAL
CLEFTS LATERALLY
EACH BRANCHIAL ARCH
CONTAINS A CRANIAL NERVE
AND AN AORTIC ARCH

The embryonic circulation has three circulatory arcs


through which blood is pumped by a simple linear heart
Dorsal aorta

Cardinal veins

Mesonephros

Aortic arches

Vitelline vein
Vitelline artery
Allantoic artery
Allantoic vein
Deoxygenated blood
Mixed blood
Oxygenated blood

Yolk sac

Chorio-allantoic
placenta

Arterialendoftheheart

Bulbuscordisrepresentsthe
arterialendofheart.It
consistsof

proximalpartcalledtheconus
adistalpartcalledtruncus
arteriosus.
Thetruncuscontinuesdistally
withtheaorticsac.

VENOUSENDOFTHEHEARTTUBE

Thesinusvenosusrepresentsthe
venousendoftheheart.One
vitelline vein fromtheyolksac;
oneumbilical vein fromthe
placentaandonecommon
cardinal vein fromthe
bodywall,joinseachhornofthe
sinusvenosus.

Aftertheformationoftheheadfold,thistubeliesdorsalto
thepericardialcavityandventraltotheforegut.
Splanchnopleuricmesodermliningthedorsalsideofthe
pericardialcavityproliferatestoformathicklayercalledthe
myoepicardialmantle.
Whentheinvaginationiscomplete,themyoepicardialmantle
completelysurroundsthehearttube
Itgivesrisetothecardiacmuscle(MYOCARDIUM)and
alsototheviscerallayerofthepericardium(EPICARDIUM)

EXTERIOROFTHEHEART
Hearttubeissuspended
fromthedorsalwallofthe
pericardialcavityby2
layersofpericardiumthat
constitutesdorsal
mesocardium

Aholeformsinthedorsal
mesocardiumwhichincreases
insize.
GraduallyMesocardium
disappearsandthehearttube
liesfreewithinthepericardial
cavity
Mesocardiumdisappearsto
formthetransversesinusofthe
pericardium

Cardiaclooping
Loopingofthehearttubeallowsthestraighthearttubetoform
amorecomplexstructurereminiscentoftheadultheart.Most
cardiacloopingoccursduringthefourthweekandcompletes
duringthefifthweekofdevelopment

Thelinearhearttubedevelopsdifferentialgrowthoftheheart
tubeincomparisonwiththeforegut
Thedirectionofcardiacloopingisdeterminedbyanasymmetric
signallingsystemwhichaffectsthepositionofboththoracic
andabdominalcontents
Inallvertebrates,thereisdifferentialgrowthwithintheheart
tubeitselfresultinginposterior,leftward,slowergrowthand
anterior,rightward,fastergrowthresultinginrightward
looping.Thispositioningresultsinthefuturerightventricle
takingananteriorandrightwardlocationwithreferencetothe
futureleftventricle

Furtherdisproportionategrowthofthehearttubein
comparisontotheforegutresultsinbendingoftheheart
tubeattheinflowaswellaswithintheventricularsegment
eventuallypositioningtheinflowandfutureleft
ventricularsegmentsposteriorlyandtotheleft,withthe
futurerightventricleandoutflowsegmentsanteriorlyand
totheright

Thestraighthearttubebeginsto
elongatewithsimultaneousgrowthin
thebulbuscordisandprimitive
ventricle

Thisforcesthehearttobendventrally
androtatetotheright,formingaC
shapedloopwithconvexsidesituated
ontheright.

Theventricularbendmovescaudally
andthedistancebetweentheoutflow
andinflowtractsdiminishes.

Theatrialandoutflowpolesconverge
andmyocardialcellsareadded,
formingthetruncusarteriosus

HenceanSshapeisformedwiththefirstbendofthe'S'
beingthelargeventricularbendwhilethebendatthe
junctionoftheatriumandsinusvenosusformsthesecond
'S'bend

The cardiac tube grows at a greater


longitudinal rate then the rest of the
embryo, causing it to fold. As it does
this
it falls to the right. This is known as
d-looping. It may fall to the left in an
l-loop: this will lead to a malformed
heart.
Below are chick embryo dissections
showing
the two types of loop.

normal d-loop

l-loop

The fold of the loop is principally at the junction of bulbus cordis and
ventricle. Note in panel C that the two end up side by side.
The left ventricle will develop from the ventricle, and the right ventricle
will develop from the bulbus cordis. (And an l-loop will
result in ventricular inversion with the left ventricle on the right.
Note also that the arterial trunk is above the developing right ventricle.

Abnormalitiesoflooping
VentricularInversionwithTranspositionof
theGreatArteries

Defectivemigrationofcells

HYPOPLASIAOFRVOT/MPATOF
ABSENCEOFRVOT/MPATA
ABSENCEOFAORTOPULMONARYSEPTUMTA
MALALINGMENTOFAORTAANDLVABNORMAL
WEDGINGTOF
ABNORMALMYOCARDIALTRABECULATIONLV/RVNON
COMPACTION

DEVELOPMENT
ABNORMALITIES

Timelineofcardiogenesis

Pathophysiology

Abnormalleftrightsignalling

Loopingdefects

Defectsduetoabnormalmigrationofcellsofprimaryandsecondary
heartfieldsandofcardiacneuralcrest

Onediseaseseveralmechanismsseveral
genes

THE CIRCULATORY ARCS OF THE EMBRYONIC BLOOD SUPPLY

1.

BODY CIRCULATION

TRANSPORT OF O2 /FOOD MATERIALS TO TISSUES


TRANSPORT OF WASTE MATERIALS AWAY

2.

VITELLINE CIRCULATION

CARRIES MOBILISED FOOD MATERIALS FROM THE YOLK SAC


LOST FUNCTION IN MAMMALS BECAUSE SAC EMPTY
CARRIES FIRST BLOOD CELLS FROM YOLK SAC
SPLANCHNOPLEURE

3.

ALLANTOIC CIRCULATION

IN MAMMALS TAKES OVER THE FUNCTIONS OF THE


VITELLINE ARC IN BIRDS
SUPPLIES FOOD MATERIALS FROM MATERNAL
CIRCULATION
RETAINS AVIAN FUNCTION OF REMOVAL OF WASTE
AND GAS EXCHANGE

MESENCHYME IN
SPLANCHNOPLEURE
OF YOLK SAC

Haematopoiesis begins in the


splanchnopleure of the yolk sac
before transferring to the embryo
itself later in development

CELL CLUSTERS

ENDOTHELIUM
BLOOD ISLAND

ENDOTHELIAL CELLS

HAEMATOPOIETIC
CELLS

From Noden and La Hunta p 211

FORMATION OF BLOOD
VESSEL

AGGREGATION OF FURTHER
MESENCHYME TO FORM
MUSCULAR AND CONNECTIVE
TISSUE WALL

1. The first blood cells arise in the


splanchnic mesoderm on the
endodermal wall of the yolk sac.
2. Cells in the outer zone of these
blood islands become vascular
endothelium and enclose
haematopoietic stem cells.
3. The function of
haematopoiesis is transferred
during foetal development from
yolk sac to liver to bone marrow.

The simple tubular heart twists to prepare for septum formation and the creation of a fourchambered organ. The aortic arches are selectively modifed to give rise to the great arteries
THE HEART AND THE AORTIC ARCHES - FORMATION OF THE GREAT BLOOD VESSELS

CAROTIDS
(from L and RIII)
AORTA
(from LIV)

I
II
III
IV
V
VI

III
IV
VI
TA

RIGHT
SUBCLAVIAN
(from RIV)

DUCTUS
ARTERIOSUS
(LVI to LIV)

RA

LA

PULMONARY
TRUNK
(from LVI)
SEPTA

RV
VENOUS RETURN
NOTES:
1. View from ventral surface
2. RA - Right atrium, LA - Left atrium, RV - right ventricle,
LV - left ventricle, TA = truncus arteriosus

LV

After birth venous return is from


vena cava (blue arrows) and
pulmonary veins (red arrows)

1. The diagram shows 6 aortic arches but this does not occur at the one time
except in fish. Also in mammals. the 5th aortic arch does not form
2. The twisting of the heart tube leads to the atrium behind and slightly rostral
to the ventricle. This sets the scene for septum formation which divides
the heart vertically to separate the left and right sides and horizontally to
separate atria from ventricles
3. To coincide with these change, the truncus arteriosus divides within itself
into a pulmonary artery leading from the right ventricle and the aorta itself
leading from the left ventricle
4. The connection between the dorsal roots of the 3rd and 4th aortic arches
are lost and the 3rd arch persiste as the brachiocephalic trunk which
divides into the external and internal carotid arteries and the right and left
subclavian arteries
5. The key changes are
a)
b)

the regression of the right 4th aortic arch and the development of the left 4th into the
dorsal aorta
the regression of the right 6th aortic arch and the development of the left 6th into the
pulmonary trunk dividing into the left and right pulmonary arteries but remaining
connected via the ductus arteriosus to the aorta (this is the original 4th to 6th aortic arch
connection in the dorsal root). The ductus arteriosus closes at birth in response to the
changing blood pressures and oxygenation.

The separation between atria and between ventricles and between


atria and ventricles occurs by means of septum formation
1. The septa of the heart form simultaneously
2. Remarkably the heart continues to function through these remodelling changes

SEPTUM FORMATION
Vena cava

ATRIAL
SEPTATION

Pulmonary
veins

Foramen
ovale

Vena cava

ATRIOVENTRICULAR
SEPTATION
VENTRICULAR
SEPTATION

RV

LV

PRIOR TO SEPTATION
(SURFACE VIEW)

INCOMPLETE SEPTATION
(SECTION)

Mouse, 12 days,
section of truncus arteriosus

Mouse, 10 days, frontal section

Blood from the atrium passes


to the ventricle by means of a
channel. The beginnings of
interatrial septum formation
can be seen (A)

Cushions form within the truncus


arteriosus and will fuse to form the
aortico-pulmonary septum
separating the aortic and
pulmonary flows

http://www.med.unc.edu/embryo_images/

FOETAL CIRCULATION
25
14

To
lungs

Brachycephalic vessels
19

DA

From lungs

FO
25

19

25

14 Liver
30
Trunk

Placenta

22

Hindlimb

There is a split between deoxygenated


blood returning from the rostral end of
the foetus and oxygenated blood
returning from the placenta. This spit
is achieved by directed flow through
the foramen ovale

CHANGES IN THE CIRCULATION AT BIRTH


Contraction of allantoic artery and veins to force placental blood
into main circulation. Rupture of umbilical cord
Contraction of Ductus arteriosus and closure of Foramen ovale so that
right side blood is directed to lungs

The changes at birth are as follows


Umbilical (allantoic) arteries contract. Allantoic veins contract forcing blood into
circulation (may be 30% total blood). Cord ruptures.
Ductus arteriosus contracts so that all right side blood goes to the lungs and all
left side blood to the body
Prior to birth most blood coming through the caudal vena cava (which is
relatively oxygen-rich because of placental exchange), is directed through the
foramen ovale and hence via the dorsal aorta to prefernential cranial offshoots
(the carotids). The foramen ovale closes at birth and all venous return is then
directed to the right ventricle and hence the lungs, while the only blood entering
the left atrium is oxygen-rich blood from the lungs

DEFECTIVE SEPTUM FORMATION

INTER-ATRIAL SEPTAL DEFECT


(persistent Foramen ovale)

INTER-VENTRICULAR SEPTAL DEFECT


(Tetralogy of Fallot is variation on this)

DEFECTIVE SEPTUM FORMATION


There is a relatively high incidence of developmental abnormalities at birth
(about 1% in dogs) and this may be because of the relatively complex
remodelling that occurs.
1.Inter-atrial septal defects. Failure of closure of foramen ovale leading to
mixing of blood in the two atria
2. Interventricular septal defects. Blood passes from left ventricle to right
leading to increased pulmonary pressure
3.Tetralogy of Fallot. Defective aortic/pulmonary septum formation associated
with a ventricular septal defect. Blood from right ventricle enters aorta leading
to right ventricular hypertrophy to compensate

PERSISTENCE OF AORTIC ARCHES AND VASCULAR RING ANOMALIES

Right 4

Left 6

Oesophagus
PATENT DUCTUS
ARTERIOSUS

PERSISTENT RIGHT AORTIC


ARCH IV

Patent Ductus arteriosus and Persistent aortic arch


1. In patent Ductus arteriosus, blood is forced from dorsal aorta into
pulmonary artery and sometimes back into right ventricle. Cardiac output is
increased to maintain body circulation
2. Persistent right aortic arch 4 forms the arch of the aorta while the left arch 6
forms a patent ductus arteriosus with a persistnet segment of the left dorsal
aorta
Other defects
1. Pulmonary stenosis is a narrowing of the pulmonary artery impeding blood
flow to the lungs
2. Aortic stenosis is a narrowing of the aorta leading to left ventricular
hypertrophy
3. Ectopic heart is a result of interference with the normal descent into the
thoracic cavity. In cattle, an ectopic heart in the neck can be compatible with
a normal life
4. Congenital venous shunts include persistence of the normal foetal liver
shunt which takes a proportion of blood by-passing the liver. If this persists
after birth, there is a build-up of toxic wastes in the blood

REFERENCES
Carlson BM (2003) Patten's Foundations of Embryology
Noden DM, de Lahunta (1985) A Embryology of domestic animals
McGeady TA, Quinn PJ, Fitzpatrick ES, Ryan MT (2006) Veterinary embryology
University of North Carolina web site: http://www.med.unc.edu/embryo_images/