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The vascularsystem appearsin the middle of
the third week,The entirecardiovascular
system,heart,bloodvessels,and bloodcell,originates fromthe mesodermal germlayer.
Cardiac progenitor cellslie in the epiblast,(immediately lateral to
the primitive streak.).1
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cardiogenic
fieldBy the union of blood
islands units andform a tube
surrounded by
myoblasts.
later develops into the
pericardial cavity
As a result of cephalic
folding the heart and
pericardial cavity
move first to thecervical region and
finally to the thorax.
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Although initiallypaired, tubesformed,
by the 22nd day ofdevelopment, thetwo tubes fusesand form a single,
slightly bent hearttube consisting ofan
1. inner endocardialtube
2. and asurroundingmyocardialmantle.
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, the tube remains attachedby the dorsalmesocardium Withfurther development itdisappears, creating thetransverse pericardialsinus, which connectsboth sides of thepericardial cavity.
The heart is nowsuspended in the cavity
by blood vessels at itscranial and caudal poles
the heart tube consists ofthree layers:
(a) the endocardium,
(b) the myocardium,
(c) the epicardium orvisceral pericardium
This outer layer isresponsible forformation of thecoronary arteries
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The caudal end will form atrialstructures by highconcentrations of retinoicacid (RA).
During these events, themyocardium
thickens and separates fromthe endothelium
Epicardium:is derived from mesothelial
cells
1-cells on the septumtransversum form most ofthe epicardium.
2-The remainder cellsoriginating in the outflowtract region.
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Bulbus Cordis refers to the outflow
tract in early embryo
3 parts1) distal - forms
truncus
arteriosus (aorta
and pulmonaryartery)
2) middle - conus
arteriosus
ventricularoutflow tract
3) proximal - right
ventricle
trabeculate part6
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cardiac loopThe heart tube
continues to
elongate and bendon day 23.The cephalic portion
of the tube bendsventrocaudally, andto the right
and the atrial (caudal)portion shiftsdorsocranially andto the left
This bending, whichmay be due to cell
shape changes,creates the cardiacloop.
It is completeby day 28.
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During the 4th to 7th weeks,the heart undergoes loopingfollowed by septation into a typical four chambered structure
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Clinical CorrelatesAbno rmal it ies o f Cardiac Looping
Dextrocardia,in which the heart lies on the right sidebecause the heart loops to the leftinstead of the right.
Dextrocardia may coincide with situs
inversus, a complete reversal ofasymmetry in all organs.
Situs inversus,
1. which occurs in 1/7,000 individuals,usually is associated with normal
physiology& a slight risk of heartdefects.
In other cases, sidedness is random,such that some organs are reversedand others are not; this is
heterotaxy. These cases areclassified as laterality sequences.9
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laterality sequenceslaterality sequences.
1. Patients with these conditions appear to bepredominantly left-sided bilaterally or right-sidedbilaterally.
2. The spleen reflects the differences: those with left-sided
bilaterality have polysplenia;
3. those with right-sided bilaterality have asplenia orhypoplastic spleen.
4. They have increased incidences of other malformations,especially heart defects.
5. Genes regulating sidedness are expressed duringgastrulation.
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DEVELOPMENT OF THESINUS VENOSUS
In the middle of the4th week,
the sinus venosusreceives venousblood from theright and leftsinus horns
Each horn receivesblood from threeimportant veins:
(a) the vitelline or
omphalomesenteric vein,
(b) the umbilicalvein,
(c) the common
cardinal vein.11
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At first, communication between the sinus and the atrium is wide.
Soon, the entrance of the sinus shifts to the right
This shift is caused primarily by left-to-right shunts of blood, which occur in thevenous system during the fourth and fifth weeks of development
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Septumformation inthe heart inpart arisesfrom
1. development ofendocardialcushion tissue in
theatrioventricularcanal(atrioventricularcushions)
2. and in theconotruncalregion(conotruncal
swellings).13
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Septum Formation in the Atrium.The septum primum,
a sickle-shaped crest descending from the roof of the atrium, begins to
divide the atrium into two but leaves a lumen, the ostium primum, for
communication between the two sides
Later, when the ostium primum is obliterated by fusion of the septum
primum with the endocardial cushions, the ostium secundum is formed
by cell death with an interatrial opening left, the oval foramen, which
persists.
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Only at birth, when pressure in the left
atrium increases, do the two septa
press against each other and close thecommunication between the two.
Abnormalities in the atrial septum may
vary from total absence to a smallopening known as probe patency of the
oval foramen
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Septum Formation in the AtrioventricularCanal.
Fourendocardial cushions surround the atrioventricular canal.Fusion of theopposing superior and inferior cushions divides the orifice into right and left atrioventricular
canals. Cushion tissue then becomes fibrous and forms the mitral (bicuspid) valve on the
left and the tricuspid valve on the right).
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Septum Formation in the Ventricles.The interventricular septum consists of a thick muscular part and a thin
membranous portion formed by
(a) an inferior endocardial atrioventricular cushion,
(b) the right conus swelling, and(c) the left conus swelling
In many cases, these three components fail to fuse, resulting in an open
interventricular foramen.
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Formation of the atrioventricular valves and chordae tendineae. The valvesare hollowed out from the ventricular side but remain attached to the
ventricular wall by the chordae tendineae.19
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Clinical Correlates
Heart Defects
Heart and vascular abnormalities account for 1% ofmalformations among live-born infants. And itis 10 timeshigher among stillborns
Causes:
1) 8% of cardiac malformations (genetic factors),
2) 2% (environmental agents),3) mostly (genetic and environmental influences)=
(multifactorial).
Classic examples of cardiovascular teratogens include
1) rubella virus
2) thalidomide.3) retinoic acid
4) alcohol.
5) Maternal diabetes& or hypertension.
6) Chromosomal abnormalities
7) genetic syndromes, including craniofacial abnormalities,20
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E.g.:
1) DiGeorge syndrome.
2) Goldenhar syndrome.
3) Down syndrome.
Genes regulating cardiac development are beingidentified and mapped, and mutations that resultin heart defects are being discovered.
gene result5TBXMutations in thebysyndrome,characterizedOram-n Holti
1) preaxial (radial) limb abnormalities
2) atrial septal defects.
3) Defects in the interventricular septum may also occur.
4) .Holt-Oram syndrome is inherited as an autosomal dominant trait5) with a frequency of 1/100,000 live births.
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hypertrophic cardiomyopathy1) Mutations in a number of genes regulating production of
sarcomere proteins
2) result in sudden death in athletes&general population.
3) autosomal dominant
Atrial septal defect (ASD)A. is a congenital heart abnormality
B. with an incidence of 6.4/10,000 births
C. 2:1 prevalence in female to male infants
D. caused byi. excessive resorption of the septum primum.
ii. failure of development of the septum secundum.
iii. complete failure of the septum primum and septum
secundum to form.
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Figure 12.19
A. Normal atrial septum formation. B,C. Ostium secundum defect caused byexcessive resorption of the septum primum.
D,E. Similar defect caused by failure of development of the septum secundum.
F. Common atrium, or cor triloculare biventriculare, resulting from complete failure ofthe septum primum and septum secundum to form.23
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Tricuspidatresia,
involves obliteration ofthe right atrioventricularorifice
characterized by theabsence or fusion of thetricuspid valves.
Tricuspid atresia isalways associated with
(a) patency of the ovalforamen,
(b) ventricular septal
defect,
(c) underdevelopment ofthe right ventricle, and (d)hypertrophy of the leftventricle
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BulbusSeptum Formation in the
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.BulbusSeptum Formation in the
The truncus region is divided bythe spiral aorticopulmonaryseptum into the two main arteriesThe conus swellings +the inferiorendocardial cushion, close theinterventricular foramen.Many vascular abnormalities, such
as
1) transposition of the greatvessels
2) pulmonary valvular atresia,
result from abnormal division of theconotruncal region;
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A. Persistent common
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A. Persistent commonatrioventricularcanal. Thisabnormality isalwaysaccompanied by a
septum defect inthe atrial as well asin the ventricularportion of thecardiac partitions.
B. Valves in theatrioventricularorifices undernormal conditions.
C. Split valves in apersistentatrioventricularcanal.
D,E. Ostium primumdefect caused byincomplete fusionof theatrioventricular
endocardialcushions
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