Development of Lungs and Body cavities

Describe the embryologic development of the larynx, trachea, bronchi, and lungs from the primordial pharynx

Development of lungs and respiratory tree

 The development of lungs and respiratory tree begins with formation of the respiratory diverticulum. The respiratory
diverticulum is an outpouching of the lining of the endodermal foregut (i.e., is the GI) into the surrounding mesenchyme
surrounded by the splanchnic mesoderm.

 The respiratory diverticulum undergoes its first bifurcation and splits

into primary right and left bronchial (lung) buds. These buds are the rudiments
of the two lungs and the right and left primary bronchi.

 Proximal end of the respiratory diverticulum forms the trachea and larynx.
The larynx opens into the pharynx.

 The larynx begin as a slit (laryngotracheal groove) between the fourth

and sixth pharyngeal arches. The laryngeal groove eventually becomes
the laryngotracheal inlet

 The laryngeal inlet undergoes remodeling which includes growth of

laryngeal cartilages, and swellings (arytenoid swellings) which
eventually completely occlude the opening. The inlet opening reopens
later in development, but if does not, it can cause issues like congenital
laryngeal atresia. Here, in this disorder, the re-opening of the laryngeal
inlet does not occur properly. The disorder could lead to CHOAS syndrome
(congenital high airway obstructive syndrome).
o NB = CHAOAS features including stenotic or atretic upper airway, hyperplastic lungs, elevated diaphragm, massive
fetal ascites, and fetal hydrops

 The respiratory diverticulum is initially in open communication with the foregut, but it eventually become separated by
indentations of mesoderm from the later wall, called the tracheoesophageal folds.
 The tracheoesophageal folds fuse in the midline to form the tracheoesophageal septum, which wall off the developing the
trachea (ventrally or anteriorly) and the esophagus (dorsally or posteriorly) except at the level of the laryngeal inlet.

o If this separation does not occur correctly (non-fusion of the tracheoesophageal septum), it may lead to some disorders.
E.g., there may be an open communication between the trachea and esophagus.

o Also, if there is a defect in the tracheoesophageal folds, it may lead to improper connection between the trachea and
esophagus. This improper connection is known as the fistula. In this situation the baby can have a tracheoesophageal
fistula (TEF). In this condition, when the baby ingest food, they will aspirate it.

 There are kinds of TEF, the worst one is called the esophageal atresia. In this disorder, the esophageal forms a
blind sac. A baby with this defect, immediately throws up after been breast fed, and becomes hungry again.

 Remember = the lung is a composite structure of endodermal and mesodermal structures.

o Endoderm gives rise to the mucosal lining of the bronchi and to the epithelial cells of the alveoli. While the remaining
components of the lung: smooth muscle, cartilage supporting the bronchi, and visceral pleura are derived from
splanchnic mesoderm that covered the respiratory diverticulum as it grew out from the mediastinum into the pleural space

 The first round of branching occurs when the primary bronchial buds divides and give rise to 3 secondary bronchial buds on the
right and 2 on the left.
o The secondary bronchial buds give rise to the lung lobes (3 on the right and 2 on the left).
o The pericardioperitoneal canal eventually becomes the pericardial cavity, pleural cavity, and the peritoneal cavities.

 The secondary bronchial divides and give rise to tertiary bronchial buds on both sides, which eventually becomes the
bronchopulmonary segments which are ~ 8 -10 on each lung

 Additional branching occurs which gives rise to the terminal bronchioles. After formation of the terminal bronchioles, a division
will occur to divide them into two or more respiratory bronchioles. These respiratory bronchioles become invested with capillaries
and are called terminal sacs/primitive alveoli.

o Primitive alveoli develop in a cranial to caudal fashion and infants of this stage may die of respiratory insufficiency without
proper intervention. By 36 weeks, the alveoli should be mature
o NB = The lung develop in a cranial to caudal fashion
Compare and contrast the features of the stages of alveolar development and their clinical significance

Pseudoglandular Stage: 6-16 weeks

 The developing lung resembles an exocrine gland.
 The terminal bronchioles have thick walls (simple columnar epithelium) that are surrounded by a dense mesenchyme
 Almost all major lung elements have formed
 The fetus is not compatible with life. That is respiration is not possible and premature infants cannot survive.

Canalicular Stage: 16-28 weeks

 This stage overlaps the pseudoglandular stage.
 The lumina of the bronchi and terminal bronchioles enlarge.
 The lung tissues becomes highly vascularized
 Terminal bronchioles give rise to 2 or more respiratory bronchioles
o These respiratory bronchioles will end in primordial alveolar ducts and terminal sacs
 By the end of this stage, respiration is possible by the end of this stage.
o Although this stage is compatible with life, most fetuses die. While respiration can occur, it is not efficient and still requires
more maturation to do its job well and sustain life.

Terminal Sac Stage: 28-36 weeks

 Numerous terminal sacs (saccules) develop, and their epithelium becomes very thin
 Capillaries from the surrounding mesoderm bulges into terminal sacs and thereby establishes a blood-air barrier.
o The blood-air barrier permits adequate gas exchange for survival of the fetus if it is born prematurely
 The terminal sacs are lined mainly by type I pneumocytes—that form the surface for gas exchange
o The type I pneumocytes are squamous epithelial cells of endodermal origin.
o NB = the pneumocytes started differentiating in the canalicular stage, however, more, and higher number of
differentiations occurs here in this stage
 The type II pneumocytes produce pulmonary surfactant and can replace damaged type I cells.
  Respiration is possible and fetuses can survive

Alveolar: 36 weeks - term/into postnatal life

 By week 32, sacs analogous to alveoli are present.
 Internally, the lungs are functional but utilized birth
 The alveoli matures after birth through enlargement and subdivisions
o There about 20-70 million alveoli present at birth. About 300-400 million alveoli are present by 8 years of age. The major
mechanism for the increase in the number of alveoli is the formation of secondary septae that partition existing alveoli.

Describe extrinsic factors necessary for normal lung development

Maturation of the lungs

 There are three critical factors that influence the maturation of the lungs.
1. Fetal breathing movements (FBMs)
2. Adequate thoracic space,
3. Adequate amniotic fluid volume
FBM
 Fetal breathing movements occur in utero and cause the aspiration of amniotic fluid into the lungs.
 Breathing against this resistance conditions the respiratory muscles and stimulates lung development.
 They are also used to diagnose labor and predict fetal outcomes.
 The lungs are about half filled with fluid at birth, which is either expelled by the pressure of vaginal delivery or absorbed by
the vasculature.

Apply your knowledge of lung development to explain the embryologic basis for common congenital anomalies of the
respiratory system.

Congenital high airway obstructive syndrome (CHAOS)

 It is a rare but fatal disease with predictably characteristic features including stenotic or atretic upper airway, hyperplastic lungs,
elevated diaphragm, massive fetal ascites, and fetal hydrops.

Congenital laryngeal atresia

  In this disorder, there is a complete upper airway obstruction when the larynx fails to open during a baby’s development in utero -
reopening of the laryngeal inlet does not occur properly. Congenital laryngeal stenosis is similar, but not a complete block of the
larynx.

Tracheoesophageal fistula (TEF)

 Here, there is an abnormal communication between the trachea and esophagus that results from improper division of the foregut
by the tracheoesophageal septum.

Esophageal atresia
 This is a type of TEF. Here, the esophagus forms a blind sac. The cause of EA is thought to be failure of the esophageal
endoderm to proliferate rapidly enough during the fifth week to keep up with the elongation of the embryo.
o Both TEF and EA are dangerous to the newborn because they allow milk and other fluids to be aspirated into the lungs.
 Esophageal atresia has an adverse effect on the intrauterine environment before birth: the blind-ending
esophagus prevents the fetus from swallowing amniotic fluid and returning it to the mother via placental
circulation. This leads to polyhydramnios and consequent distention of the uterus.

Respiratory distress syndrome

 This is caused by a deficiency or absence of surfactant that is produced by type II pneumocytes. When there is not enough
surfactants, the alveoli collapses.

Pulmonary agenesis
 This results when the respiratory diverticulum fails to split into right and left bronchial buds and to continue growing.

Pulmonary hypoplasia
 Here, there is a reduced number of pulmonary segments or terminal air sacs. It often represents a response to some condition
that reduces the volume of the pleural cavity, thus restricting the growth of the lungs.

Detail the process by which the horseshoe shaped intraembryonic coelom is transformed into various serous cavities of the
body.

 The intraembryonic coelom a horse-shoe shaped cavity (space between 2 layers of the lateral plate) that runs through the
trilaminar disc. In other it is just a space.
 The intraembryonic coelom creates a cavity within the embryo into which organs grow
o The heart grow into the pericardial cavity; the lung grow into the pleural cavities and the intestine grow into the peritoneal
cavity
o The intraembryonic coelom area around the mobile organs to help with their movement during life. The intraembryonic
coelom cavity is lined with cells that secrete fluids (pericardial, pleural, and peritoneal fluid) that help lubricate the
structures/organs and to allow them to move freely within that sac in which they grow in.
o NB = There is one pericardial cavity, 2 pleural cavities and one peritoneal cavity

 As alluded before, the intraembryonic coelom (IC) is initially one continuous space. To from the definitive adult pericardial,
pleural, and peritoneal cavities, partitions must form.

 The first partition to develop is the septum transversum. The septum transversum is a block-like wedge of mesoderm that
forms a ventral structure that partially divides the coelom into a thoracic primitive pericardial cavity and an abdominal
peritoneal cavity.

 Cranial body folding and differential growth of the head and neck regions translocate the septum transversum to the position of
the future diaphragm.

 Pleuropericardial folds forms on the lateral body wall of the primitive pericardial cavity in a coronal plane and grow medially to
fuse with each other and with the ventral surface of the foregut mesoderm, thus subdividing the primitive pericardial cavity into 3
compartments: a definitive pericardial cavity (ventrally) and two pleural cavities (dorsa laterally).
o NB = The pleuropericardial folds are three-layered, consisting of mesenchyme sandwiched between two epithelial layers;
all three layers are derived from the body wall.

 Pleural cavities can initially communicate with the peritoneal cavity through a pair of pericardioperitoneal canals passing dorsal
to the septum transversum. However, a pair of transverse pleuroperitoneal membrane (mesodermal derived) grows ventrally
from the dorsal body wall over the transverse septum and fuse (when fused form a portion of diaphragm), thus closing off the
pericardioperitoneal canals.
o NB = Th left pericardioperitoneal canal is larger than the right and closes later
o NB = The pleuroperitoneal membrane are called so because they do not contact the septum transversum until after the
pericardial sac is formed; thus, after they fuse with the septum transversum, they separate the definitive pleural cavities
from the peritoneal cavity.
Describe the development of the diaphragm from its various embryologic components.

 The diaphragm separates the pleural cavities from the peritoneal cavity. It is formed through the fusion of tissue from four
different embryonic sources.
1. The septum transversum. Most of the septum transversum then gives rise to the non-muscular central tendon of the
diaphragm
2. The paired pleuroperitoneal membranes. These are sheets of somatic mesoderm that develop from the dorsal and
dorsolateral body wall. Remember they seal off the pericardioperitoneal canals. The phrenic nerves pass through these
membranes and innervate them.
3. The mesoderm of the body wall. This contributes to the muscle to the peripheral portion of the definitive diaphragm.
4. The esophageal mesoderm. The esophageal mesoderm is invaded by myoblasts and forms the crura of the diaphragm in
the adult and part of the central tendon

Apply your knowledge of the diaphragm to explain the common anomalies associated with its development and their effects
on the rest of the developing fetus

Congenital diaphragmatic hernia

 It is a herniation of abdominal contents into the pleural cavity caused by a failure of the pleuroperitoneal membrane to develop or
fuse with the other components of the diaphragm.

 Most commonly found on the left posterolateral side and is usually life threatening because lung development is delayed and
abdominal contents compress the lung buds, causing pulmonary hypoplasia. It is associated with polyhydramnios

Eventration of diaphragm
 Here, the pleuroperitoneal membrane does fuse/close, however, it is too thin. It did not to receive the necessary collagen
required to make it tendinous.

 So as a consequence, the defective musculature allows the abdominal contents to balloon or eventrate into the pulmonary
cavity, while still covered by the diaphragm.

 This condition can also result in pulmonary hypoplasia or hypertension, which may be fatal.