Download Development of the Respiratory System

UNIVERSITY OF GUYANA
MEDICAL REHABILITATION
EMBRYOLOGY
EMBRYOLOGICAL DEVELOPMENT OF:
THE CARDIOVASCULAR SYSTEM
&
THE RESPIRATORY SYSTEM
Group 1
Jennifer Haynes
Anita Narine
Neil Barry
Zoe Daniels
Origin/Derivative of Cardiovascular System
Tissue of the cardiovascular system—heart, blood vessels, and blood
Cells —originates from the mesodermal germ layer of the embryo. Although
initially paired, by the 22nd day of development the two tubes form a single,
slightly bent heart tube consisting of an inner endocardial tube and a surrounding
myocardial mantle. During the 4th to 7th weeks the heart divides into a typical
four-chambered structure.
Development
During the third week of gestation (days 15–21), the following stages occur:
development of the primitive streak—gastrulation (day 15); formation of intraembryonic mesoderm (day 16); mesoblast differentiation—somatopleura and
splanchnopleura (day 17); development of blood islets, the cardiogenic region,
and primitive heart tubes (day 19); and formation of the primitive endocardial
tube (day 21).
During this time the bilaminar germ disc grows, especially in the cephalo-caudal
axis. At the beginning of the third week, a midline structure called the primitive
streakappears in the epiblast, near the caudal end of the disc. Epiblast cells
detach along the primitive streak and migrate into the space between the epiblast
and hypoblast layers as part of gastrulation.
The migration forms a third layer called the intra-embryonic mesoderm (in red)
(as seen in panel A) which goes to the cephalic end of the embryo. In this third
layer, cellular groups, called blood islets, can be distinguished that form the shape
of a horse shoe (panel B) . At the cranial end of the embryo, the blood islets form
the cardiogenic region. Laterally, the angioblastic cords coalesce. On day 17, the
lateral layer divides into two layers (panel C): the ventral layer will produce a pair
of endocardial tubes and the dorsal layer will produce the two aortae (panel D).
Embryonic folding brings the endocardial tubes into the ventral thorax where they
fuse to form a single primitive heart tube(panel E). At this stage of development,
the embryo is 2–3 mm long.
Panel F shows the primitive heart tube. Starting at the inflow tract, we see
the sinus venosus receiving the venous blood of the embryo, followed by
the primitive atrium, the primitive ventricle, the bulbus cordis, and finally
the truncus arteriosus which divides into paired dorsal aortae forming the
outflow tract of the primitive heart tube.
DEVELOPMENT OF SEPTUM
The septum is the dividing wall between the right and left sides of the heart. That
portion of the septum that separates the right and left atria of the heart is termed
the atrial, or interatrial, septum, whereas the portion of the septum that lies
between the right and left ventricles of the heart is called the ventricular, or
interventricular, septum.
Septum formation in the heart in part arises from development of endocardial
cushion tissue in the atrioventricular canal (atrioventricular cushions)
and in the conotruncal region (conotruncal swellings). Because of the key
location of cushion tissue, many cardiac malformations are related to abnormal
cushion morphogenesis.
Septum Formation in the Atrium
The septum primum, a sickle-shaped crest descending from the roof of the
atrium, begins to divide the atrium in 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 that creates an opening in
the septum primum. Finally, a septum secundum forms, but an interatrial
opening, the oval foramen, persists. Only at birth, when pressure in the left
atrium increases, do the two septa press against each other and close the
communication between the two.
Abnormalities in the atrial septum may vary from total absence to a small opening
known as probe patency of the oval foramen.
Septum Formation in the Atrioventricular Canal
Four endocardial cushions surround the atrioventricular canal. Fusion of the
opposing 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. Persistence of the common
atrioventricular canal and abnormal division of the canal are well-known defects.
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. Although this abnormality may be
isolated, it is commonly combined with other compensatory defects.
Septum Formation in the Bulbus. The bulbus is divided into (a) the truncus
(aorta and pulmonary trunk), (b) the conus (outflow tract of the aorta and
pulmonary trunk), and (c) the trabeculated portion of the right ventricle. The
truncus region is divided by the spiral aorticopulmonary septum into the two
main arteries. The conus swellings divide the outflow tracts of the aortic and
pulmonary channels and with tissue from the inferior endocardial cushion close
the interventricular foramen. Many vascular abnormalities, such as transposition
of the great vessels and pulmonary valvular atresia, result from abnormal
division of the conotruncal region; they may involve neural crest cells that
contribute to septum formation in the conotruncal region.
The aortic arches lie in each of the five pharyngeal arches. Four important
derivatives of the original aortic arch system are (a) the carotid arteries (third
arches); (b) the arch of the aorta (left fourth aortic arch); (c) the pulmonary artery
(sixth aortic arch), which during fetal life is connected to the aorta through the
ductus arteriosus; and (d) the right subclavian artery formed by the right fourth
aortic arch, distal portion of the right dorsal aorta, and the seventh
intersegmental artery. The most common vascular aortic arch abnormalities
include (a) open ductus arteriosus and coarctation of the aorta and (b) persistent
right aortic arch and abnormal right subclavian artery, both causing respiratory
and swallowing complaints.
The vitelline arteries initially supply the yolk sac but later form the celiac,
superior mesenteric, and inferior mesenteric arteries, which supply the foregut,
midgut, and hindgut regions, respectively.
The paired umbilical arteries arise from the common iliac arteries. After birth the
distal portions of these arteries are obliterated to form the medial umbilical
ligaments, whereas the proximal portions persist as the internal iliac and
vesicular arteries.
Venous System
Three systems can be recognized: (a) the vitelline system,
which develops into the portal system; (b) the cardinal system, which forms
the caval system; and (c) the umbilical system, which disappears after birth.
The complicated caval system is characterized by many abnormalities, such as
double inferior and superior vena cava and left superior vena cava.
Lymphatic System
The lymphatic system begins its development later than the cardiovascular
system, not appearing until the fifth week of gestation. The lymphatic vessels
originate from mesenchyme or may arise as saclike outgrowths from the
endothelium of veins.
Six primary lymph sacs are formed: two jugular, at the junction of the subclavian
and anterior cardinal veins; two iliac, at the junction of the iliac and posterior
cardinal veins; one retroperitoneal, near the root of the mesentery; and one
cisterna chyli, dorsal to the retroperitoneal sac.
Numerous channels connect the sacs with each other and drain lymph from the
limbs, bodywall, head, and neck. Two main channels, the right and left thoracic
ducts, join the jugular sacs with the cisterna chyli, and soon an anastomosis forms
between these ducts.
The thoracic duct then develops from the distal portion of the right thoracic duct,
the anastomosis, and the cranial portion of the left thoracic duct.
The right lymphatic duct is derived from the cranial portion of the right thoracic
duct. Both ducts maintain their original connections with the venous system and
empty into the junction of the internal jugular and subclavian veins. Numerous
anastomoses produce many variations in the final form of the thoracic duct.
PART II –
RESPIRATORY
SYSTEM
When development does occur and description of the Respiratory System
The respiratory system develops after the fourth week of gestation. The
development of the respiratory system has many constituent components.
Gaseous exchange occurs in the alveoli. The development of the respiratory
system involves the endoderm and the mesoderm that surrounds it. The location
of the bud along the gut tube is determined by signals from the surrounding
mesenchyme, including fibroblast growth factors (FGFs) that “instruct” the
endoderm. Hence epithelium of the internal lining of the larynx, trachea, and
bronchi, as well as that of the lungs, is entirely of endodermal
origin. The cartilaginous, muscular, and connective tissue components of the
trachea and lungs are derived from splanchnic mesoderm surrounding the
foregut
Early Development
The early development of the lungs lags behind the development of the heart and
great vessels. However, as development proceeds the lungs will eventually occupy
more of the thoracic cavity than the heart. This will be discussed further in the
partitioning of the body cavities.
Development of the Respiratory System
We will begin with the development of the larynx and continue caudally.
 Larynx: The larynx is first seen as an outgrowth from the foregut. The
outgrowth of tissue is called the respiratory diverticulum or the lung bud.
The formation of the lung bud occurs when two lateral folds of splanchnic
mesoderm and endoderm meet in the midline and separate the larynx and
trachea from the esophagus. The lung bud is a ventral diverticulum of
endoderm that arises from the floor of the foregut caudal to the pharynx.
The diverticulum forms a groove in the floor of the pharynx called the
laryngotracheal groove. Cephalic to the laryngotracheal groove is the
epiglottal swelling. On either side of this groove are the developing
arytenoid swellings.
 The epithelium of the larynx develops from the endoderm of the foregut.
However, the muscles and cartilage arise from the 4th and the 6th arches.
The development of these structures will be discussed in a later.
 Trachea: The trachea develops caudal to the larynx. The epithelium
develops from the endoderm and the tracheal cartilage and muscles
develop from splanchnic mesoderm. Early in development the trachea
bifurcates into the left and right bronchi.
 Bronchi and Bronchioles: As the bronchi develop they continue to branch.
The right bronchus gives off three diverticula and the left bronchus gives
off two diverticula. These diverticula become the lobar bronchi and
indicate that the right lung will have three lobes and the left lung will have
two lobes. Each of the bronchi at this stage will divide into smaller bronchi.
The branching of the bronchi continues until the bronchioles begin to
form. In all there are 17 divisions of the bronchi until the sixth fetal month
is reached. However, by early childhood there will be a total of 24
generations of branching that occurs.
Maturation of the Lungs
As the lungs develop and divide into smaller divisions there are changes in the
vascular supply of the lungs as well. The lungs can be described as undergoing 4
phases of development.
 During the first phase of development, the pseudoglandular period, the
bronchi are dividing into smaller and smaller units, the bronchioles. This
period occurs from the 2nd month through the end of the 4th month.
During the next 2 and 1/2 months the respiratory bronchioles are formed.
They will give rise to alveolar ducts. This is called the canalicular period.
During this time period the epithelium remains as a cuboidal epithelium
and the capillaries while proliferating do not approach the respiratory
epithelium.
 The next phase of development occurs from the 7th month until birth.
During this period, the terminal sac phase / saccular phase, the number of
capillaries increases and the capillaries approach the respiratory
epithelium. At the same time the terminal sacs form. These result in the
formation of a squamous epithelium, made up of type I alveolar epithelial
cells, which will permit gaseous exchange. Hence, from the 7th month on
the fetus is capable of survival. It is also starting with the 7th month that
type II alveolar epithelial cells develop. These type II cells produce
surfactant, the fluid that reduces the surface tension at the alveolar cell
surface.
Finally, from the 8th month on, the mature alveoli continue to be formed with an
increase in the amount of surface area where capillaries and alveolar cells are in
contact. This period of lung development is the alveolar period and actually can
last through age ten. The growth of the lungs after birth is mainly the result of
increases in the number of alveoli during this time.
Table showing the Summary of Human Lung Stages/ Maturation of the Lungs
Stage
Embryonic
Human
Features
week 4 to lung buds originate as an outgrowth from the ventral wall of
5
the foregut where lobar division occurs
Pseudoglandu week 5 to conducting epithelial tubes surrounded by thick mesenchyme
lar
Canalicular
Saccular
Alveolar
17
week 16 to
25
week 24 to
40
are formed, extensive airway branching
bronchioles are produced, increasing number of capillaries in
close contact with cuboidal epithelium and the beginning of
alveolar epithelium development
alveolar ducts and air sacs are developed
late fetal secondary septation occurs, marked increase of the number
to 8 years and size of capillaries and alveoli
Clinical Implications
The absent or insufficient surfactant in the premature baby causes respiratory
distress syndrome (RDS) because of collapse of the primitive alveoli (hyaline
membrane disease).
Congenital cysts of the lung; which are formed by dilation of terminal or larger
bronchi. These cysts may be small and multiple, giving the lung a honeycomb
appearance on radiograph, or they may be restricted to one or more larger ones.
Cystic structures of the lung usually drain poorly and frequently cause chronic
infections.
The mesoderm surrounding the trachea inhibits branching whereas the mesoderm
surrounding the bronchi stimulates branching.
Formation of the respiratory system is regulated by a flow of molecules:
 Fibroblast growth factor 10 (FGF10)
 The Hox genes:
 Sonic hedgehog
Other molecules in the mesoderm regulate branching and differentiation of epithelia of lung
buds. The main regulatory molecules are:
 . N-Myc – stimulates branching
 Fibronectin and Collagen types I and III - stabilize branching sites
 Syndecan and Tenascin - stabilize the epithelia
 Epimorphin organizes the epithelium, including the polarity of the cells and their
arrangement in the epithelium.
Diagram showing asymmetric branching in week 5 forms the lobes of the lungs
3 secondary buds on the right bronchi; upper middle and lower lobe
2 secondary buds on the left bronchi; upper and lower lobe
th
In week 6 the 4 set of branching forms tertiary bronchi and the broncho-pulmonary
segments;
Ten on the right side and eight on the left side
Right side
Upper lobe – apical, anterior, posterior
Middle lobe – medial, lateral
Lower lobe – apical lateral basal , anterior basal , posterior basal
Left side
Upper lobe – apical, anterior, posterior
Lower lobe – apical lateral basal , anterior basal , posterior basal
During weeks 7 to 16 branching occur about 14 times to the level of terminal bronchioles. At
this stage there are no alveoli. The fetal lung during this period is described as the glandular
stage because the terminal bronchioles resemble glandular acini. The bronchi, containing
cartilage in their walls, identify the sections as fetal lung.
Development of the lung goes through 4 stages:
 The glandular stage – weeks 7 to 16
 The canalicular stage – weeks 16 to 28
 The saccular stage – weeks 28 to 36
 The alveolar stage – weeks 36 to 40
Clinical Implications
Babies born before 28 weeks have very small chances of survival because they
lack pulmonary alveoli. A few manage to survive following intensive respiratory
assistance. Babies born between 32 and 36 weeks usually suffer from the
respiratory distress syndrome due to lack of surfactant secreted by pneumocytes
type II. The respiratory distress syndrome is treated by:
 Intensive respiratory assistance .
 Surfactant therapy including surfactant lipoprotein and surfactant associated
proteins A,B and C.
REFERENCES
o Langman's Medical Embryology 11th ed., Sadler, T W, (Thomas W.);
Langman, Jan. Philadelphia : Wolters Kluwer Lippincott Williams &
Wilkins
o Developmental Biology, 6th ed., Gilbert, Scott F; Sunderland (MA):
Sinauer Associates; 2000
o Larsen's human embryology 4th ed. Schoenwolf, Gary C; Larsen,
William J, (William James). Philadelphia, PA : Elsevier/Churchill
Livingstone
 http://search.medicinenet.com/search/search_results/default.aspx?Search
what=1&query=mesoderm&I1=Search
 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1767109/