STATE BUDGETARY EDUCATIONAL
ESTABLISHMENT OF HIGHER PROFESSIONAL
MINISTRY OF PUBLC HEALTH OF RUSSIAN
KURSK STATE MEDICAL UNIVERSITY
DEPARTMENT OF HISTOLOGY, EMBRYOLOGY&
Development of the Heart
Name : Jean Vitor Alves Guimaraes
The Human development
Normal development of the heart
Pathology in the heart development
Persistent Truncus Arteriosus (PTA)
Dextro Transposition of the great arteries (d-TGA)
Levo- transposition of the great arterie( L-TGA )
Teatralogy of fallot 13
Probe patency of the foramen ovale ( PFO )
Premature Closure of the Foramen Oval
Common atrium ( cortrilocularebiventriculare )
Persistent Common AV Canal
Fertilization: a process by which the male and female merge and forms a zygote. Is required capacitation
and acrosomal reactions
The human life is divided into developmental process by which the body passes though. Basically we
may divide it into 2 parts:
1. Intrauterine life: is all process of development of the body after the Zygoteformation until start the
extra uterine life. In others words, is a set of developmental process that the human being pass within
the uterus. It may be divided into three parts:
Conceptus: This occurs when the male and female gametes are uniting, and forms the Zygote. It
takes at least 21 days.
Embryonic period: isthe perfect product of conception from implantation of the gametes until the
8th week of development.
Fetal Period: Is a process that leads with growth and differentiation of tissues and organs that
began to develop in the embryonic period. It takes from 9th until the birth.
2. Extra uterine life: is all process of development of the body after intrauterine life, which is
characterized by Neonatal (from birth until 4 weeks ), Infancy ( 1st year of life ), Childhood ( from 1 year
of life till 12 to 13 year old ), Adolescence (from 12 to 13 until 17 ), adult hood ( from 18 to 21 until 25 ),
middle age, old age and consequently the death.
The Human development in the intrauterine life is accompanied and marked into a chronologic time in
weeks. A normal human being takes 38 weeks or 266 daysto develop fully. If the birth be less than 37th
week we use to say that is apreterm birth.
All weeks together may be divided into three parts or trimesters, which each one have 12.6 weeks.
Critical Period: all weeks are very important because they covers important development of a different
organ or even a set of organs, but the 1st trimester takes special attention because the embryo may be
more affected, the heart critical period, normally starts at 3th week and finish at the 6th week. The
sensitive weeks are marked by the strong action of chemical products, mechanic shocks on the embryo.
It starts from 3th week till 8th(this text was adapted from USMLE : Falcon Online –Anatomy review).
The human development
Embryology: Is a the science which search study the embryo and it development.
Embryogenesis: Is the process by which the embryo is formed develops, until it develops into a fetus.
The human embryology of the human beings may be divided into the following parts:
1. Zygote: After the fecundation the first cell of a future human being will be formed, this cell is
named zygote that is the initial cell which is formed by means of sexual reproduction. It got 46
chromosomes, 23 from the father ( spermatozoid) and 23 from the mother (ovule). It contains a
full complement of genetic material and develops into the embryo. It takes place from the 1st day
until the 3th day.
2. Cleavage: the zygote pass through several mitotic divisions, which leads directly with a increase of
cell number, they are big in size cell, but according to the cell divisions it starts to decrease in size.
It takes 1 week of intrauterine life. In humans the cleavage is hotoblastic, in other words,
3. Morula: is the first state of embryonic development after the zygote begins to divide to form a
sphere with 64 cells. The name Morula mean mulberry.
4. Blastula: this stage is characterized by the formation of a central cavity filed with fluid named
Blastocoel and a inner wall named Blastoderm.
5. Gastrulation: During gastrulation, cell movements result in a massive reorganization of the embryo
from a simple spherical ball of cells, the blastula, into a multi-layered organism. During gastrulation,
many of the cells at or near the surface of the embryo move to a new, more interior location. It
have three layers:
Endoderm:the most internal germ layer, forms the lining of the gut and other internal organs.
Ectoderm: the most exterior germ layer, forms skin, brain, the nervous system, and other
Mesoderm: the middle germ layer, forms muscle, the skeletal system, and the circulatory ( This
part was adapted from http://biology.kenyon.edu/courses/biol114/Chap14/Chapter_14.htm l)
Invagination: a sheet of cells (called an epithelial sheet) bends inward.
6. Neurulation: in all vertebrates results in the formation of the neural tube, which gives rise to both
the spinal cord and the brain. Neural crest cells also created during neurulation. Neural crest cells
migrate away from the neural tube and give rise to a variety of cell types, including pigment cells
and neurons. It begins with the formation of a neural plate, a thickening of the ectoderm caused
when cuboidal epithelial cells become columnar. Changes in cell shape and cell adhesion cause the
edges of the plate fold and rise, meeting in the midline to form a tube. The cells at the tips of
the neural folds come to lie between the neural tube and the overlying epidermis. These cells
become the neural crest cells. Both epidermis and neural plate are capable of giving rise toneural
crest cells( This text was adapted from
from Patricia Phelps
Normal development of heart
The heart starts to develop at 3th week and goes until 6th week, during intrauterine life. The heart of
the human beings is about the size of the fist. As the body develops, the heart grows at the same rate as
the fist. On this way, an infant's heart and fist are
about the same size at birth. In human embryos the
heart begins to beat at about 22-23 days, with blood
flow beginning in the 4th week. The heart is therefore
one of the earliest differentiating and functioning
The heart begins very early in mesoderm within the
trilaminar embryonic disc. In the begin the heart looks
like a tube, In the upper part of this tube have two small
tubes named arterial trunks, and in lower part another
two tuber, which are thicker, named Venous channels,
up in the bifurcation is the Atrium. The Cardiac tube
grows rapidly in length and the embryonic ventricle
takes form of a loop for the right of middle sternal line.
According the time is passing by the ventricle follow the middle sternal line and grows and cover the
Atrium and veins. The future left ventricle lies to the left of the intraventricular groove. The right
ventricle communiques with Troncus Arteriosus. The four chambers of the heart is formed from the
convoluted tube, by the development of the tree septa partitioning of the Atria, Ventricles and the
Arteriosus. All this septa develops simultaneously. There is a big groove which separates the Atrium
from Ventricle. At this stage, within the heart still do not posses the septum, that way it looks like a
vagination, but according to time passed, the cell division inside of the heart creates a septa, the
endocardial cushions extend and forms the
Septum, which divides the chambers. From
the intraventricular region occurs the
proliferation of muscular septum that pass
across the Common ventricle toward the
base of the heart, this process also occurs at
the Atrium toward the endocardium
cushions or endocardial cushions refers to a
subset of cells in the primordial heart that
play a vital role in proper heart septation )
and progressively constrict the foramen
between the Atrial chambers, forming the
Foramen Primum. At this moment another
foramen arise, it is named Foramen
Secundum (which provide uninterrupted
blood from right Atrium to the Left) and the Foramen Primum is closed.
In the left Atrium arise a muscular tissue, which extend like a curtain ( which works like a valve) on the
Foramen Segundum, forming the foramen Ovale ( on this way the blood will flow only from the right
Atrium to the left ) .
Originally the right and left ventricle share a common of flow channel, Truncus Arteriosus ( from it arise
the Aortic arches). The bifurcation of the Truncus Arteriosus, represent two of the Aortic arches, the 4th
Aortic archer, which forms the Aorta, and the 6th, which forms the pulmonary artery. From the up tube a
piece of tissue came and twist (at 108 º)
forming single spiral septum which goes toward
the ventricles, is at this moment that the
Atrium-ventricular foramen is obstructed by
mass of endocardium tissue from the
ventricular septum by the Endocardium
cushions and Spiral Aortic septum, now is
completed the heart chambers. The blood from
the left ventricle goes to Aorta, in the right
direction. The blood from the right ventricle
goes to the Pulmonary artery, which pass near
of the aorta turning posteriorly left side of the
The blood from the Superior and Inferior Vena Cava goes to right Atrium and them do the right
Ventricle, which are inject into the pulmonary artery ( flowing in the Ductus Arteriosus ) to the
The resistance to flow through the collapsed lungs is so great that only a small quantity of blood enters
in the Pulmonary arteries. This blood which enters in the Pulmonary arteries back through the
Pulmonary veins into the Left Atrium.
The oxygenate blood from the placenta enters
through a connection in the Inferior Vena Cana, and
goes to the right Atrium through and pass through
Foramen Ovale and enters into the left Atrium,
there they are mixed and then goes from the Left
Ventricle to the Aortic artery.
When the birth occurs the supplement of blood
from the Placenta is interrupt, in order to keep itself
alive the infant must breathe to make the
respiratory exchange in the lungs. When the lungs http://www.youtube.com/watch?v=5DIUk9IXUaI
are filled with oxygen, the resistance of pulmonary
flow is reduced. Oxygenate blood from the lungs goes to Systemic circulation.
When the pressure on the left ventricle is biggerthan right the Foramen Ovale is closed.(Robert
Rushmer, congenital malformation of the heart, part 1 )
Pathologies in the Heart Development
The pathologies of heart (cardiac system) during the intrauterine life may be classified according to
defects which follows each embryo development during heart embryogenesis (all the follow disease was
adapted from ‘’Embryology fifth edition – Ronald W. Duded’’).
Pathologies which are linked to Aorticpulmonary Septum:
Persistent Truncus Arteriosus (PTA):It is a rare
genetic disorder and teratogens (virus, metabolic
imbalance, industrial or pharmacological agent ),
which occurs when there is failure of fusion and
descent of the spiral ridges of the truncus and conus
that supposedly divide into aorta and pulmonic
trunck respectively. When the spiral septum fails to
completely descend, the aortic and pulmonic trunks
are left undivided at their outflow. The truncus takes
the place of the both ventricles. The persistent
truncus is always accompanied by a membranous
ventricular septal defect.
The classification of PAT was made in 1949 by Collett and Edwards, according to their classification, it
may be classified by the pattern of the pulmonary arteries:
Type I: truncus -> one pulmonary artery -> two lateral pulmonary arteries
Type II: truncus -> two posterior/posterolateral pulmonary arteries
Type III: truncus -> two lateral pulmonary arteries
Clinic Picture is:
Cyanosis presents at birth (due the mixture of the venous blood- the one which comes from
periphery to the heart- and arterial blood- the one which goes from the heart to periphery )
Heart failure may occur within weeks
Systolic ejection murmur is heard at the left sternal border
Widened pulse pressure ( due the absence of the septum, the diastole are mixed in the both lower
chambers ( ventricle)
Bounding arterial pulses
Loud second heart sound
Increased pulmonary vascularity
Hypocalcemia (if associated with DiGeorge syndrome)
On the X-ray, the heart looks big and the lungs fields look hazy indicating pulmonary over
Treatment and Management:
May be tried surgical repair:
Early surgical correction is preferred. The VSD is closed so that the LV is connected to the
truncus and the pulmonary arteries are detached from the truncus to be attached to the right
ventricle via a conduit.
If early surgical repair can not be done, banding of the pulmonary artery is performed to limit
the blood flow to the lung and control CHF.
Dextro Transposition of the great arteries (d-TGA): Another rare congenital disease, in this case the
infact have the 2 biggest blood vessels exchanged, The Aortic Artery carries blood poor in oxygen to
periphery of the body, and the Pulmonary artery travel though it blood rich in oxygen. Without an
adequate supply of oxygen-rich blood,
the body may not work properly and
the infanct faces serious
complications or death without
The Diagnosis may be during
pregnancy or soon after the baby is
cyanosis (in peripheral areas :
around the mouth and lips,
fingertips, and toes )
Pounding heart ( low
volume of blood arrive in the peripheral arteries )
Ashen or bluish skin color
There are two types of surgery to repair d-TGA:
Arterial Switch Operation: This is the most common procedure and it is usually done in the first
month of life. It restores usual blood flow through the heart and out to the rest of the body.
During this surgery, the arteries are switched to their usual positions—the pulmonary artery
arising from the right ventricle and the aorta from the left ventricle. The coronary arteries (small
arteries that provide blood to the heart muscle) also must be moved and reattached to the
Atrial Switch Operation: This procedure is less commonly performed. During this surgery, the
arteries are left in place, but a tunnel (baffle) is created between the top chambers (atria) of the
heart. This tunnel allows oxygen-poor blood to move from the right atrium to the left ventricle
and out the pulmonary artery to the lungs. Returning oxygen-rich blood moves through the
tunnel from the left atrium to the right ventricle and out the aorta to the body. Although this
repair helps blood to go to the lungs and then out to the body, it also makes extra work for the
right ventricle to pump blood to the entire body. Therefore, this repair can lead to difficulties
later in life.
Levo- transposition of the great artery( L-TGA ) :Is a acyanotic congenital heart defect, which
correspond the flow of blood whiting the heart. It forms due an abnormal leftward looping of the
primitive heart, which results in the morphologic
Left ventricle that will be positioned to the right
of the morphologic Right ventricle and to both
atrioventricular and ventriculoarterial
discordance . In a normal heart, theoxygenated
blood is pumped from the Right Atrium into the
Right Ventricle, then through the pulmonary
artery to the lungs where it is oxygenated. The
oxygen-rich blood then returns, via
the Pulmonary Veins, to the left atrium from
which it is pumped into the left ventricle, then
through the aorta to the rest of the body,
including the heart muscle itself.
The clinical picture may be divided into two groups, according to the infant conditions
Simple l-TGA does not immediately produce any visually identifiable symptoms, but since each
ventricle is intended to handle different blood pressures, the right ventricle may eventually
hypertrophy due to increased pressure and produce symptoms such as dyspnea or fatigue.
Complex l-TGA may produce immediate or more quickly-developed symptoms, depending on the
nature, degree and number of accompanying defect(s). If a right-to-left or bi-directional shunt is
present, the list of symptoms may include mild cyanosis.
The Diagnosis may be performed when the infant still is in theuterowith an ultrasound after 18 weeks
gestation. However, many cases of simple l-TGA are "accidentally" diagnosed in adulthood, during
diagnosis or treatment of other conditions.
In the Simple l-TGA has a very good prognosis, with many individuals being asymptomatic and not
requiring surgical correction
In a number of cases, the (technically challenging) "double switch operation" has been successfully
performed to restore the normal blood flow through the ventricles.
Teatralogy of fallot :Is a congenital heart defect which involve 3-4 anatomical abnormalities of the
heart, that is way it got this name ( teatra is from Greek language, that means ‘’four’’).The heart
1. Pulmonary Infundibular Stenosis: A
narrowing of the Right Ventricular
outflow tract. May occurs in the
pulmonic stenosis ) ou Pulmonary
valve ( Valvular stenosis ).
2. Right Ventricular Hypertrophy:
Occurs a change in the ventricle wall,
it becomes thicker then usual,
causing bloot-shaped appearance
when takes X-ray picture from the
3. Ventricular septal Defect: Arise a hole between the two Ventricles. Is more accentuated at the
upper part of the Septum. In some case is possible the margin of the Septum get a narrowing.
4. Overriding Aorta: In this case arise a bifurcation oih the Aortic valve, which is located at the
upper part of the ventricular Septal and is connected with the both Ventricle.
The clinical features of tetralogy of Fallot are directly related to the severity of the anatomic defects.
Infants often display the following:
Difficulty with feeding
Failure to thrive
Episodes of bluish pale skin during crying or feeding (ie, "Tet" spells)
Exertional dyspnea, usually worsening with age
RV predominance on palpation
A bulging left hemithorax
Aortic ejection click
Squatting position (compensatory mechanism)
The Diagnosis is possible through: Hemoglobin and hematocrit values are usually elevated in
proportion to the degree of cyanosis. Patients with significant cyanosis have the following, in
association with a tendency to bleed: Decreased clotting factors, Low platelet count, Diminished
coagulation factors, Diminished total fibrinogen, Prolonged prothrombin and coagulation times.
Imaging studies include the following: Echocardiography, Chest radiographs,Magnetic resonance
Surgery is the only effective treatment for tetralogy of Fallot. There are two types of surgery that may be
performed, including intracardiac repair or a temporary procedure that uses a shunt. Most babies and
children will have intracardiac repair.
Tetralogy of Fallot treatment for most infarct involves a type of open-heart surgery called
intracardiac repair. This surgery is typically performed during the first year of life. During this
procedure, the surgeon places a patch over the ventricular septal defect to close the hole between
Occasionally babies need to undergo a temporary surgery before having intracardiac repair. If the
infant was born prematurely ( during or before 37 week )) doctors will create a bypass between the
aorta and pulmonary artery which increases blood flow to the lungs.
(This text was adapted from http://www.levinechildrenshospital.org/body.cfm?id=390)
Pathologies which are linked to Atrial Septum
Probe patency of the foramen ovale( PFO ) : This pathology arise in the Foramen Ovale, which
normally is closed after the birth by the pressure which the lungs
makes at that part. Normally, the left atrial pressure keeps the
foramen closed, but if right atrial pressures rise with
pulmonary hypertension ,the foramen may open.
History of stroke or transient ischemic event of undefined
Migraine or migrainlike symptoms - Whether symptoms are due
to transient ischemic attacks or paradoxical embolism is not
Neurologic decompression sickness - Seen with PFO in a small percent of scuba divers
Systemic embolism, such as renal infarction
Paradoxical embolism caused by right atrial tumors that increase right atrial pressure
Left-sided valve disease in carcinoid syndrome
The usual care for a patient who has had a stroke is using of blood-thinning medications, such as aspirin
or the prescription drugs warfarin (Coumadin) or clopidrogrel (Plavix). These drugs keep the blood cells
from sticking together, reducing the risk of blood clot development that could lead to new TIAs or
However, there are risks and inconveniences associated with the long-term use of blood-thinning
Development of ulcers
Bleeding in the brain
Blood in the urine
Bleeding in the rectal tissue
The need to avoid activities that could result in injury, which could trigger internal or external bleeding
(This text was adapted from http://library.med.utah.edu/WebPath/CVHTML/CV103.html and
Premature Closure of the Foramen Oval: Premature closure of the foramen ovale is a rare and
deleterious condition that can occur as an isolated defect or in association with other congenital
Although a number of cases have been reported, early case reports often confused probe patency and
premature closure. Several previous reports described edematous infants dying in cardiac failure and
ascribed these findings in cardiac failure and Septum secundum,which had covered but nor sealed the
foramen ovale. Infants with premature closure of the foramen ovale usually are cyanotic or shortly after
birth, develop signs of congestive failure, and die in the first few days of life. Only five from 20 lived
more than one day. Little attention has been paid in previous reports to an abnormality is observed in
the muscle of the left side of the heart associated with this lesion.
Common atrium ( cortrilocularebiventriculare ) : It forms a congenital heart defect that enables
blood flow between two compartments of the heart called the left and rightatria. Normally,
the right and left atria are separated by a septum called the interatrial septum. If this septum is
defective or absent, then oxygen-rich blood can flow directly from the left side of the heart to mix with
the oxygen-poor blood in the right side of the heart, or vice versa.
The symptoms depend on the level of development of the septum. A person with no other heart defect,
or a small defect (less than 5 millimeters) may not have symptoms, or the symptoms may not occur until
middle age or later.
Symptoms that do occur may begin at any time after birth through childhood, and can include:
Frequent respiratory infections in children
Sensation of feeling the heart beat (palpitations) in adults
The diagnosis may be as a result of echocardiography.
ASD may not need treatment if there are few or no symptoms, or if the defect is small. Surgery to close
the defect is recommended if the defect causes a large amount of shunting, the heart is swollen, or
A procedure has been developed to close the defect without surgery.
The procedure involves placing an ASD closure device into the heart through tubes called
The health care provider makes a tiny surgical cut in the groin, then inserts the catheters into a
blood vessel and up into the heart.
The closure device is then placed across the ASD and the defect is closed.
Not all patients with atrial septal defects can have this procedure.
Pathologies which are linked to Atrium-Ventricular Septum
Tricuspid atresia: is the third most common form of cyanotic congenital heart disease it is a heart
defect present at birth in which one of the valves
(tricuspid valve) between two of the heart's
chambers isn't formed. Instead, there is solid tissue
between the chambers. It is caused by a insufficient
amount of AV cushions cells, which results in a
condition in which there is complete agenesis
(refers to the failure of an organ to develop
during embryonic growth and development due to
the absence of primordial tissue) of the tricuspid
valve, that is way there is no communication
between the right atrium and right ventricle. If the
infant is born with tricuspid atresia, blood can't flow
through the heart and into the lungs to pick up
oxygen as it normally would. The result is the lungs
can't supply the rest of the infant body with the
oxygen it needs.
The infant with tricuspid atresia tire easily, are often short of breath andhave blue-tinged skin.
Generally it is accompanied by: Patent foramen ovale, Intravetricular septum defect, overdeveloped left
ventricle, and underdeveloped right ventricle. (this text was removed from Embryology fifth edition –
Ronald W. Duded ).
Persistent Common AV Canal:is caused by failure of fusion of the dorsal and ventral AV cushions. It
results in a condition in which the common AV canal is never partitioned into the right and left
AV canals, so that a large hole can be found in the center of the heart. Consequently, the tricuspid and
bicuspid valves are represented by one valve common to both sides of the heart. Two common
hemodynamic abnormalities are found:
1. .Left-right shunting of the blood from the left atrium to the right atrium, causing an enlarged right
atrium and right ventricle.
2. Mitral valve regurgitation, causing an enlarged left atrium and left ventricle.
The Clinical Picture:
Ventricular septal defectmurmur
The diagnosis may be done by Heart Rate
Monitors, Irregular Heartbeat Detection, Heart
Electrocardiogram (ECG), Testing, Home
Normally may be done a surgurywhich involves closure of the atrial and ventricular septal defects and
restoration of a competent left AV valve as far as is possible. Open surgical procedures require a heartlung machineand are done with a median sternotomy. Surgical mortality for uncomplicated
ostiumprimum defects in experienced centers is 2%; for uncomplicated cases of complete
atrioventricularcanal, 4% or less. Certain complications such as tetralogy of Fallot or highly unbalanced
flow across the common AV valve can increase risk significantly.
Elbstein’s anomaly:is caused by the failure of the posterior and septal leaflets of the tricuspid valve to
attach normally to the annumlusfibrosus;
instead they are displaced inferiorly into the
right ventricle. It is divided into a larger,
upper, ‘’atrialized’’ protion and a small,
lower, functional portion. Due to the small,
funcutionalprotion of the right ventricle,
there is reduced amount of blood available
to the pulmonary trunk. It is usually
associated with an ASD and Maternal
Symptoms range from mild to very severe. Often, symptoms develop soon after birth and include bluishcolored lips and nails due to low blood oxygen levels. In severe cases, the baby appears very sick and has
trouble breathing. They are:
Failure to grow
Shortness of breath
Very fast heartbeat
The diagnosis is made by: Chest x-ray, Magnetic resonance imaging (MRI) of the heart, Measurement of
the electrical activity of the heart (EKG), Ultrasound of the heart (echocardiogram).
Treatment depends on the severity of the defect and the specific symptoms. Medical care may include:
Medications to help with heart failure
Surgery to correct the valve may be needed for children who continue to worsen or who have
more serious complications
Embryology fifth edition – Ronald W. Duded ( BRS - Board review series ) – chapter 5; from page 37-47
USMLE : Falcon Online (Anatomy) – From this collection of videos was adapted to get the materials to
formulate the ‘’Initial concepts’’ and another part of the scientific project.
Histology lectures from KSMU(General ideas about organization of the scientific project)
http://biology.kenyon.edu/courses/biol114/Chap14/Chapter_14.html(was adapted Gastrulation and
http://www.youtube.com/watch?v=5DIUk9IXUaI(Robert Rushmer, congenital malformation of the heart,
part 1 )
http://php.med.unsw.edu.au/embryology/index.php?title=Cardiovascular_System__Heart_Development(General ideas about the heart pathology)
http://php.med.unsw.edu.au/embryology/index.php?title=Cardiovascular_System__Heart_Development(General ideas about the scientific project)
http://library.med.utah.edu/WebPath/CVHTML/CV103.html(General ideas about the scientific
projectProbe patency of the foramen ovale -PFO)
http://www.levinechildrenshospital.org/body.cfm?id=390(General ideas about the scientific projectand
Tetralogy of Fallot)
http://archpedi.jamanetwork.com/article.aspx?articleid=500686(General ideas about the scientific
projectand Tetralogy of Fallot Atrial septal defect -ASD).