15lecture Cardiovascular System

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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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15lecture Cardiovascular System

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