Download EMBRYOLOGY

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Respiratory System
Formation of the Lung Buds
When the embryo is about 4 weeks old, a respiratory diverticulum (lung bud) appears as
an outgrowth from the ventral wall of the foregut. Hence, the epithelium of the internal
lining of the larynx, trachea, bronchi, and lung parenchyma itself, is endodermal. The
cartilagenous, muscular, and connective tissue are derived from splanchnic mesoderm
surrounding the foregut. Initially the lung bud communicates with the esophagus. As the
diverticulum expands caudally, two tracheoesophageal ridges composed of splanchnic
mesenchyme become interposed between the diverticulum and the esophagus. Subsequently,
the ridges fuse to form a tracheoesophageal septum that separates the foregut into a
ventrally placed trachea with lung buds and dorsal to them, the esophagus. Through a
series of interactions with the surrounding mesenchyme, the trachea begins to form its first of
23 sets of bifurcations (lung buds) that continue into post natal life. The developing
respiratory system will maintain its communication with the pharyngeal portion of the
foregut through the laryngeal orifice.
Formation of the Larynx
During the fourth and fifth weeks of gestation, a rapid proliferation of the 4th and 6th
pharyngeal arch mesenchyme converts the slit-like opening, at the site where the lung bud
and esophagus communicate, into a T-shaped glottis. The glottis is bounded by two lateral
arytenoid swellings and cranially, an epiglottis. Mesenchyme surrounding the orifice
differentiates into the thyroid, cricoid, and arytenoid cartilages that form the skeletal
support of the larynx. Like the esophagus, the internal lining of the larynx is endodermal
and also undergoes temporary epithelial occlusion. In the process of recanalization during
the ninth and tenth weeks, a pair of lateral folds and recesses forms the structural basis for the
vocal cords and adjacent laryngeal ventricles. The somitomere derived musculature of the
larynx is innervated by branches of the vagus nerve (X) associated with the 4th arch, namely,
the superior laryngeal nerve: extrinsic laryngeal muscles. Derivatives of the 6th arch are
innervated by the recurrent laryngeal nerve: intrinsic laryngeal muscles.
Trachea, Bronchi, and Lungs
During its separation form the foregut, the lung bud forms the trachea. The two lateral
pockets that expand from the lung bud form the main (primary) left and right bronchi.
The primary bronchi will give rise to secondary bronchi, three on the right and two on the
left, that correspond to the lobes of the right and left lungs. This continues until a maximum
of 23 more divisions have occurred, of which 6 of the divisions occurs postnatally.
The mesoderm surrounding the budding endoderm is what controls the branching of the
respiratory tract. Tissue recombination experiments have shown that the mesoderm
surrounding the trachea inhibits branching, whereas that surrounding the bronchial buds
promotes branching.
With subsequent growth, the lung buds expand into body cavities on both sides of the
foregut known as pericardioperitoneal canals. These canals form the pleural cavities that
are lined by mesoderm. Mesoderm that covers the outside of the lungs is the visceral pleura
and that which covers the inside lining of the body wall becomes the parietal pleura.
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Stages in Lung Development
Embryonic Stage (Weeks 4 – 7)
The embryonic stage includes the initial formation of all bronchopulmonary segments.
During this period the lungs grow to fill the pleural cavities.
Pseudoglandular State (Weeks 8 – 16)
The pseudoglandular stage is the period of formation and growth of the duct system within
the bronchopulmonary segments before their terminal portions form respiratory components.
Histologically, the lungs at this stage appear as glands.
Canalicular State (Weeks 17 – 26)
The canalicular stage is characterized by the formation of respiratory bronchioles at the
terminal buds that were made in the pseudoglandular stage. Additionally, there are intense
ingrowths of blood vessels into the developing lungs in association with the respiratory
bronchioles. Occasionally, a fetus born at the end of this period can survive, but with
intensive care.
Terminal sac Stage (Weeks 26 – Birth)
During the terminal sac stage, the terminal air sacs (alveoli) bud off the respiratory
bronchioles that were formed in the canalicular state. The epithelium lining the alveoli
differentiates into two types of cells: (1) type I alveolar cells (pneumocytes), across which
gas exchange occurs after birth, and (2) type II alveolar cells (secretory epithelium). The
type II alveolar cells secrete surfactant, which spreads over the surface of the alveoli to
reduce surface tension and facilitate expansion of the alveoli during breathing. Research
involving specific markers of the epithelial cells has shown that type II cells form first in the
alveolar lining. After proliferation, some of the type II cells flatten, lose their characteristic
secretory function, and undergo terminal differentiation into type I pneumocytes.
Alveolar period (8 months gestation through childhood)
There is proliferation of alveoli with the majority of alveoli being formed after birth up to
8 years old.
Before birth the fetal lungs are filled with fluid. With increasing amounts of surfactant being
formed, the fetus has a greater chance of survival if born prematurely, especially during the
last two weeks before birth. Fetal breathing movements begin just before birth. These
movements stimulate lung development and condition the respiratory muscles. After birth
and without the fatty surfactant layer, the alveoli would collapse (atelectasis) during
expiration. At 26 to 28 week's gestation there can be survival of the fetus due to some
surfactant production. Surfactant is most adequate two weeks before the 38 weeks' gestation
period is complete.
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Pulmonary problems
Tracheoesophageal Fistulas
The most common family of malformations of the respiratory tract is related to abnormal
separation of the tracheal bud from the esophagus during early development of the
respiratory system. Many common anatomical varieties of tracheoesophageal fistulas exist,
but virtually all involve the stenosis or atresia of a segment of trachea or esophagus and an
abnormal communication between them. These are manifested early after birth by the
newborn's choking or regurgitation of milk when feeding.
Tracheal or Pulmonary Agenesis
These rare malformations are incompatible with life. Tracheal agenesis appears to be due to
defective septation between the esophagus and respiratory diverticulum. Pulmonary
agenesis is a result of a mutation of a gene needed to bring about branching of the respiratory
buds.
Respiratory Distress Syndrome
Respiratory distress syndrome is manifested in infants born prematurely and is characterized
by labored breathing. In infants who die of this condition, the lungs are under inflated and
the alveoli are partially filled with proteinaceous fluid that forms a membrane over the
respiratory surfaces. This is related to insufficiencies in the formation of surfactant by
type II alveolar cells.
Questions
1.
Cartilagenous, muscular, and connective tissue of the respiratory tract are
from _____________.
a. somatic mesoderm
b. septum transversum
c. endoderm
d. splanchnic mesoderm
2.
The trachea directly will develop from the ______ at the ______ wall of the foregut.
a. tracheoesophageal septum / ventral
b. laryngeal orifice / dorsal
c. respiratory diverticulum / ventral
d. respiratory / dorsal
3.
The extrinsic muscles of the larynx are innervated by branches of the _________
laryngeal nerve, which is derived from the ______ pharyngeal arch.
a. superior / 4th
b. recurrent / 4th
c. superior / 6th
d. recurrent / 6th
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4.
The ___________ are the early cavities for the eventual formation of the pleural
cavities.
a. pleuroperitoneal folds
b. pericardioperitoneal canals
c. pleuropericardial folds
d. respiratory diverticulum
5.
The cells that give rise to other alveolar cells and surfactant are _________ alveolar
cells. If these do not make surfactant, ___________ will be the consequence.
a. type II / tracheoesophageal fistula
b. type I / respiratory distress syndrome
c. type II / respiratory distress syndrome
d. type I / tracheoesophageal fistula