Embryology of the Respiratory System Flashcards
Polyhydramnios
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.
Early and Late phases of Lung Development
! Early: positioning of lung primordium
and primary lung bud formation
! Late: mechanism of bronchial branching
and cytodifferentiation
Early phase of lung development
! 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
Development begins in week 4 with formation of
laryngeotracheal (respiratory) diverticulum.
Outgrowth of foregut (future esophagus) into the
surrounding splanchnic mesoderm.
What separates the trachea and esophagus?
Laryngeotracheal diverticulum grows distally.
Separated from esophagus (dorsally) by
tracheoesophageal septum.
Tracheoesophageal Fistula
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
Tracheoesophageal Fistula
& Esophageal Atresia
Most common configuration.
What can cause Tracheoesophageal Fistula
& Esophageal Atresia
Misexpression of Tbx4 causes ectopic endodermal budding and tracheo-esophageal fistula.
How are esophageal atresia &
tracheoesophageal fistula diagnosed and
treated?
! 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.
Tracheal stenosis
Stenosis is a narrowing of something.
The trachea is narrowed and constricted somewhere.
Balloon Dilation and Tracheal stents can be used as treatment.
The bifircation in the trachea is called the
carina of trachea
Splanchnic mesoderm
The splanchnic mesoderm differentiates into the smooth muscle, nerves & blood vessels of the lungs.
Modeling bronchiole development
! Optimized for maximum surface area (gas
exchange)
! Pattern of segmentation also optimized to
minimize resistance to airflow
Stages in Lung Development
! 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)
Embryonic Stage
! Weeks 4-7
! Initial formation of respiratory diverticulum up to formation of all major bronchopulmonary
segments
! Lungs grow into pleural cavities
! Differentiation of pleura
(Pseudo)Glandular Stage (8-16)
! 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
Canalicular Stage
(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.
Terminal Sac
! Alveoli – or terminal sacs – develop from respiratory bronchioles
! Epithelium lining alveoli differentiates into two cell types
Postnatal (Alveolar)
! Up to 90% of alveoli formed after birth
! Primary mechanism is septation of preexisting alveoli
Supernumerary bronchi or lobules
! Abnormal division & lobation
! Supernumerary lobules are relatively common.
! Tracheal bronchus (2%) is usually asymptomatic
Fgf10
Misexpression of Fgf10 causes ectopic endodermal budding, tracheo-esophageal fistula
and ectopic Tbx4 expression
Infant respiratory distress syndrome
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.
Congenital neonatal emphysema
! “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
Pulmonary agenesis
! Complete absence of lungs, bronchi & vasculature
! Bilateral or unilateral
! Bronchial buds do not develop
Pulmonary hypoplasia
! 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.
Potter Syndrome
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.
Polyhydramnios
! High volume of amniotic fluid
! Associated with CNS anomalies & esophageal atresia
(including TEF)
Congenital Diaphragmatic Hernias
! 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
