Embryology of the Respiratory System

Question 1

Polyhydramnios

Answer 1

Polyhydramnios (polyhydramnion, hydramnios, polyhydramnios) is a medical condition describing an excess of amniotic fluid in the amniotic sac. It is seen in about 1% of pregnancies.

Question 2

Early and Late phases of Lung Development

Answer 2

! Early: positioning of lung primordium
and primary lung bud formation

! Late: mechanism of bronchial branching
and cytodifferentiation

Question 3

Early phase of lung development

Answer 3

! Location determined by TBX4 from T-box transcription factor gene family

! Linked to increase in retionic acid (RA) produced by adjacent mesoderm

! Expressed in endoderm surrounding the foregut

! Induces formation, growth & continued differentiation

Question 4

Development begins in week 4 with formation of

Answer 4

laryngeotracheal (respiratory) diverticulum.

Outgrowth of foregut (future esophagus) into the
surrounding splanchnic mesoderm.

Question 5

What separates the trachea and esophagus?

Answer 5

Laryngeotracheal diverticulum grows distally.
Separated from esophagus (dorsally) by
tracheoesophageal septum.

Question 6

Tracheoesophageal Fistula

Answer 6

When a tube should be opened but it is closed that is
called atresia.

! Most common malformation

! Abnormal communication between trachea & esophagus

! Caused by improper formation of tracheoesophageal
septum

Question 7

Tracheoesophageal Fistula
& Esophageal Atresia

Answer 7

Most common configuration.

Question 8

What can cause Tracheoesophageal Fistula
& Esophageal Atresia

Answer 8

Misexpression of Tbx4 causes ectopic endodermal budding and tracheo-esophageal fistula.

Question 9

How are esophageal atresia &
tracheoesophageal fistula diagnosed and
treated?

Answer 9

! The presence of EA is suspected in an infant with excessive salivation (drooling) that is frequently accompanied by choking, coughing and sneezing.

! When fed, these infants swallow normally but begin to cough and struggle as the fluid returns through the nose and mouth.

! The infant may become cyanotic (a result of laryngospasm) & may stop breathing as the overflow of fluid from the blind pouch is aspirated the trachea & lungs.

Question 10

Tracheal stenosis

Answer 10

Stenosis is a narrowing of something.

The trachea is narrowed and constricted somewhere.

Balloon Dilation and Tracheal stents can be used as treatment.

Question 11

The bifircation in the trachea is called the

Answer 11

carina of trachea

Question 12

Splanchnic mesoderm

Answer 12

The splanchnic mesoderm differentiates into the smooth muscle, nerves & blood vessels of the lungs.

Question 13

Modeling bronchiole development

Answer 13

! Optimized for maximum surface area (gas
exchange)

! Pattern of segmentation also optimized to
minimize resistance to airflow

Question 14

Stages in Lung Development

Answer 14

! Embryonic – weeks 4-7
! (Pseudo)Glandular – weeks 8-16
! Canalicular – weeks 17-26 (Important since viability occurs here!)! Terminal sac – weeks 26 to birth
! Postnatal (Alveolar)

Question 15

Embryonic Stage

Answer 15

! Weeks 4-7

! Initial formation of respiratory diverticulum up to formation of all major bronchopulmonary
segments

! Lungs grow into pleural cavities

! Differentiation of pleura

Question 16

(Pseudo)Glandular Stage (8-16)

Answer 16

! Major formation & growth of duct systems within bronchopulmonary segments

! No respiratory components, no gas exchange

! Histological structure resembles a gland

! Induction of vasculogenesis of pulmonary veins is thought to be mediated by
vascular endothelial growth factor (VEGF), which is expressed in the epithelium of terminal buds in the human fetal lung during the late pseudoglandular phase

Question 17

Canalicular Stage

Answer 17

(Weeks 17-26)

! Formation of respiratory bronchioles & terminal sacs (primitive alveoli)

! Vascularization increases
! Capillaries found in walls

Big problem with babies born around
22-26 weeks is that their lungs aren’t
developed enough to get oxygen to their
tissues.

Question 18

Terminal Sac

Answer 18

! Alveoli – or terminal sacs – develop from respiratory bronchioles

! Epithelium lining alveoli differentiates into two cell types

Question 19

Postnatal (Alveolar)

Answer 19

! Up to 90% of alveoli formed after birth

! Primary mechanism is septation of preexisting alveoli

Question 20

Supernumerary bronchi or lobules

Answer 20

! Abnormal division & lobation

! Supernumerary lobules are relatively common.

! Tracheal bronchus (2%) is usually asymptomatic

Question 21

Fgf10

Answer 21

Misexpression of Fgf10 causes ectopic endodermal budding, tracheo-esophageal fistula
and ectopic Tbx4 expression

Question 22

Infant respiratory distress syndrome

Answer 22

Not enough surfactant present.

! IRDS occurs primarily in the immature lung.

! (1) 60 % of cases occur in infants born at less than 28 weeks’ gestation

! (2) 5 % of cases occur in infants born at less than 37 weeks’ gestation.

! Labored breathing

! Deficiency/absence of surfactant

! Coats alveoli & maintains alveolar patency

! Atelectasis is the incomplete expansion or collapse of parts of or a whole lung.

Question 23

Congenital neonatal emphysema

Answer 23

! “Emphysema’ is a misnomer - no destruction of alveolar walls

! Over-distention with air of one or more lobes of the lung

! Caused by collapsed bronchi

! Bronchial cartilage does not develop

Question 24

Pulmonary agenesis

Answer 24

! Complete absence of lungs, bronchi & vasculature

! Bilateral or unilateral

! Bronchial buds do not develop

Question 25

Pulmonary hypoplasia

Answer 25

! Poorly developed bronchial tree

! Partial (small segment) or Total (entire lung)

! Bilateral renal agenesis

! Insufficient amniotic fluid (oligohydraminos) & increased pressure on fetal thorax

Can’t practice breathing so lungs don’t grow properly.

Question 26

Potter Syndrome

Answer 26

Pulmonary hypoplasia – for normal development amniotic fluid must be brought into the lung by fetal breathing movements, leading to distension of the developing lung.

Problem is renal agenesis usually.

Question 27

Polyhydramnios

Answer 27

! High volume of amniotic fluid

! Associated with CNS anomalies & esophageal atresia
(including TEF)

Question 28

Congenital Diaphragmatic Hernias

Answer 28

! Herniation of abdominal contents into pleural cavity

! Caused by failure of pleuroperitoneal membranes to fuse with other components

! Most common on left posterolateral side

! Clinical signs: unusually flat abdomen, breathlessness & cyanosis