Development of Trachea, tracheobrachial and lungs

Question 1

respiratory primordium

Answer 1

develops as the laryngotracheal groove

the lung bud appears by the end of the 4th week as the laryngotracheal groove protrudes to form a laryngotracheal diverticulum

this diverticulum elongates and its distal end enlarges to form a globular respiratory bud (origin of respiratory tree).

Question 2

Respiratory primordium

Answer 2

the tracheoesophageal

folds develop; fuse to form the

tracheoesophageal septum;

opening of the laryngotracheal tube into the pharynx - primordial laryngeal inlet.

Question 3

Development of larynx

Answer 3

epithelial lining develops from the endoderm of the cranial end of the laryngotracheal tube

epiglottis develops from the caudal part of the hypopharyngeal eminence (ventral ends of the 3rd and 4th pharyngeal arches);

at the cranial end of the laryngotracheal tube paired arytenoid swellings are formed

arytenoid swellings convert the primordial glottis into a T- shaped laryngeal inlet

Question 4

Laryngeal atresia

Answer 4

results from failure of recanalization of the larynx;

• produces obstruction of the upper fetal airway – congenital high airway obstruction syndrome;
• distal to the region of atresia or stenosis, the airways become dilated, the lungs are enlarged and filled with fluid;
• the diaphragm is either flattened or inverted;
• fetal ascites and/or hydrops is present.

Question 5

Laryngeal web (incomplete atresia)

Answer 5

results from incomplete
recanalization of the larynx during the 10th week;
- a membranous web forms at the level of the vocal folds;
- partially obstructing the airways;
- treatment is by endoscopic dilation

Question 6

Development of the trachea

Answer 6

the laryngotracheal diverticulum forms the trachea and two lateral outpouchings, the primary bronchial buds;

• the endodermal lining differentiates into the epithelium and glands of the trachea;
• the cartilage, connective tissue, and muscles of the trachea are derived from the splanchnic mesenchyme surrounding the laryngotracheal tube.

Question 7

Tracheoesophageal fistula (TIF)

Answer 7

results from incomplete division of the cranial part of the foregut into respiratory and esophageal parts during the 4th week (incomplete fusion of the tracheoesophageal folds

The usual anomaly: superior esophageal atresia with distal TEF.
Symptoms:
Infants cannot swallow;
frequently drool saliva at rest;
immediately regurgitate milk when fed.
Risks:
pneumonia and respiratory compromise due to gastric and intestinal contents reflux from the stomach through the fistula into the trachea and lungs

Question 8

Laryngotracheoesophageal cleft

Answer 8

persistent connection of variable lengths between the larynx, trachea and esophagus;
- symptoms are similar to those of
tracheoesophageal fistula;
- aphonia is a distinguishing feature

Question 9

Tracheal stenosis and atresia

Answer 9

probably result from unequal partitioning of the foregut into the esophagus and trachea;

• sometimes there is a web of tissue obstructing airflow (incomplete tracheal atresia

Type I: long-segment stenosis involving almost the entire trachea.
Type II: funnel shaped trachea of various locations and variable lengths.
Type III: short-segment stenosis with or without anomalous right upper lobe bronchus.
Type IV: bridge bronchus

Question 10

Tracheal diverticulum

Answer 10

consists of a blind, bronchus-like projection from the trachea;

• the outgrowth may terminate in normal- appearing lung tissue, forming a tracheal lobe of the lung;
• may cause recurrent infection and respiratory distress in infants

Question 11

Development of bronchi and lungs

Answer 11

at the caudal end of the laryngotracheal diverticulum forms the respiratory bud (week 4);

• divides into 2 primary bronchial buds;
• these grow laterally into the pericardioperitoneal canals;
• differentiate into the bronchi and their ramifications in the lungs;
• the connection of each bronchial bud with the trachea enlarges to form the primordia of the main bronchi (week 5

Question 12

Development of bronchi and lungs: the main bronchi subdivide into

Answer 12

secondary bronchi that form lobar branches;

• each lobar bronchus undergoes progressive branching;
• the segmental bronchi begin to form by the 7th week;
• with the surrounding mesenchyme they form the primordia of the bronchopulmonary segments;
• by 24th week ≈ 17 orders of branches have formed and respiratory bronchioles have developed;
• an additional 7 orders of airways develop after birth.

Question 13

Development of bronchi and lungs: bronchial cartilaginous plates, smooth muscle and connective tissue, the pulmonary connective tissue and capillaries develop from

Answer 13

the surrounding splanchnic mesenchyme;

• a layer of visceral pleura is formed from the splanchnic mesoderm;
• the thoracic body wall becomes lined by a layer of parietal pleura, derived from the somatic mesoderm.

Question 14

Maturation of the lungs

Answer 14

This process is divided into 4 stages: pseudoglandular,
canalicular,
terminal sac,
and alveolar.

Question 15

Pseudoglandular stage (6-16 weeks)

Answer 15

lungs histologically resemble exocrine glands;

• by 16 weeks, all major elements of the lung have formed, except those involved with gas exchange

fetuses born during this period are unable to survive

Question 16

Canalicular stage (16-26 weeks)

Answer 16

the lumina of the bronchi and terminal bronchioles become larger;

• the lung tissue becomes highly vascular;
• by 24th week, each terminal bronchiole has given rise to 2 or more respiratory bronchioles;
• each respiratory bronchiole divides into 3-6 passages - primordial alveolar ducts;
• respiration is possible at the end of the canalicular stage;
• a fetus born toward the end of this period may survive if given intensive care

Question 17

Terminal sac stage (26-32 weeks)

Answer 17

more terminal sacs develop (lined mainly by type I pneumocytes),

• capillaries proliferate rapidly, begin to bulge into developing alveoli;
• lymphatic capillaries develop actively;
• establishment of the blood - air barrier (permits adequate gas exchange for survival of the fetus if it is born prematurely);
• type II pneumocytes begin surfactant production at 20 to 22 weeks;
• by 26-28 weeks sufficient alveolar sacs and surfactant are present to permit survival of a prematurely born infant;
• the production of surfactant increases during the last 2 weeks of pregnancy

Question 18

Alveolar stage (32 weeks – 8 years)

Answer 18

sacs analogous to alveoli are present at 32 weeks;

• ≈ 95% of mature alveoli develop postnatally;
• immature alveoli have the potential for forming additional primordial alveoli;
• as these alveoli increase in size, they become mature alveoli;
• first few months after birth are characterized by the multiplication of alveoli and capillaries;
• ≈ 150 million primordial alveoli, one half of the adult number, are present in the lungs of a full-term neonate;
• on chest radiographs, the lungs of neonates are denser than adult lungs.

Question 19

Molecular control of the lungs development

Answer 19

Wnt/Bcatenin signaling required for the induction of the respiratory tree.

The differentiation of respiratory-type epithelial cells:
expression of TTF1 (NKX2.1), HNF 3β, and GATA6, as well as RA receptors, and Hox domain-containing genes.

Hox genes specify the anteroposterior axis in the embryo.

FGF10 – induction of the outgrowth of the respiratory bud.

Wnt7b - mesenchymal proliferation and blood vessel formation in the lung.

The Shh-Gli modulates the expression of FGF10, which controls the branching of the bronchial buds.

RA regulates Hox a5, b5, and c4.

Question 20

Fetal breathing movements (FBMs

Answer 20

occur before birth;

• exerting sufficient force to cause aspiration of some amniotic fluid into the lungs;
• stimulate lung development
• the pattern of FBMs is widely used in the monitoring of labor and as a predictor of fetal outcome in a preterm delivery.

Question 21

Aeration of the lungs at birth

Answer 21

At birth, the lungs are approximately half-filled with fluid derived from the amniotic cavity, lungs, and tracheal glands.

The fluid in the lungs is cleared at birth by 3 routes:

• through the mouth and nose by pressure on the fetal thorax during vaginal delivery;
• into the pulmonary arteries, veins, and capillaries;
• into the lymphatics.

Question 22

Respiratory distress syndrome

Answer 22

also known as hyaline membrane
disease (HMD);

• caused by surfactant deficiency;
• the lungs are underinflated;
• the alveoli contain a fluid with a high protein content (resembles a glassy or hyaline membrane);
• ground glass on X-ray;
• administration of exogenous surfactant (surfactant replacement therapy) reduces the severity of RDS and neonatal mortality.
• the corticosteroids (betamethasone) are routinely used for prevention of RDS in preterm labor

Question 23

Oligohydramnios and lung development

Answer 23

severe and chronic oligohydramnios because of leads to retardation of lung development;

• severe pulmonary hypoplasia results from restriction of the fetal thorax

Question 24

Lobe of azygos vein

Answer 24

develops when the apical bronchus grows superiorly, medial
to the arch of the azygos vein;

• the vein lies at the bottom of a fissure in the superior lobe;
• this produces a linear marking on a radiograph of the lungs

Question 25

Congenital lungs cyst

Answer 25

Cysts are formed by the dilation of the terminal bronchi.
Several cysts make a honeycomb appearance on radiographs.

Congenital cysts are usually located at the periphery of the lungs.

Question 26

Agenesis of lungs

Answer 26

failure of the respiratory bud to develop;

• unilateral agenesis is more common than bilateral and is compatible with life;
• the heart and other mediastinal structure are shifted to the side of agenesis;
• the only present lung is hyperexpanded.

Question 27

Lung hypoplasia

Answer 27

usually caused by congenital diaphragmatic hernia

• characterized by a markedly reduced lung volume and hypertrophy of the smooth muscle in the pulmonary arteries;
• the pulmonary hypertension leads to decreased blood flow through the lungs as more of it gets shunted to the aorta through the Botalli duct.

Question 28

Accessory lung (pulmonary sequestration)

Answer 28

Mostly located at the base of the left lung (60%) and nonfunctional.

It doesn’t communicate with the tracheobronchial tree.

It’s blood supply is usually systemic.