Development of the Lungs

Question 1

Which structure is the point of transition from upper to lower respiratory tract?

Answer 1

Larynx

Question 2

What 3 layers comprise the trilaminar embryonic disc?

Answer 2

Ectoderm, mesoderm, endoderm

Question 3

What are the lung stages and what weeks do they occur?

Answer 3

1. Embryonic –> week 4-5 2. Pseudoglandular –> week 5-17 3. Canalicular –> week 16-25 4. Saccular –> week 24-40 5. Alveolar –> late foetal to 8 years

Question 4

When does the lung bud appear?

Answer 4

Day 22

Question 5

Where does lung bud originate from? How does it grow?

Answer 5

Originates as an outgrowth from the ventral wall of the foregut - Grows ventrocaudally, anterior to the gut tube - Eventually divides to form 2 lung buds

Question 6

What are tracheoesophageal ridges? What is there purpose?

Answer 6

• Longitudinal mesodermal folds that form as respiratory diverticulum grows - Separate the respiratory diverticulum from the foregut (separates trachea and oesophagus)

Question 7

What is the respiratory diverticulum? When does it appear?

Answer 7

A ventral outgrowth of foregut endoderm Embryonic period –> day 22

Question 8

What are tracheoesophageal fistualas (TOF) caused by?

Answer 8

Disruption of the formation of the tracheoesophageal ridges leading to abnormal connection between trachea (respiratory portion) and oesophagus

Question 9

How common are TOF?

Answer 9

1 in 3000-4500 live births

Question 10

What is TOF often associated with?

Answer 10

A spectrum of mesodermal defects –> VA(C)TER(L)

Question 11

What are 90% of TOF associated with?

Answer 11

Oesophageal atresia

Question 12

What is oesophageal atresia?

Answer 12

Failure of development of the proximal part

Proximal (upper) oesophagus ends blindly (sac)

Distal (lower) part of the oesophagus communicates with the trachea via a fistula

Question 13

What are prenatal/postnatal complications of TOF?

Answer 13

Prenatally:

1. Too much amniotic fluid as foetus cannot swallow amniotic fluid

Postnatally:

1. Stomach contents can enter lungs (infection)
2. Air can escape into stomach so adomen rapidly distends as stomach fills with air
3. Infant coughs/chokes due to inability to swallow

Question 14

What is an H-type tracheoesophageal fistula?

Answer 14

Fistula between trachea and oesophagus –> rarer (only 4% of cases)

Question 15

What are consequences of H-type Tracheoesophageal fistula?

Answer 15

1. Milk (from oesophagus) may be driven into respiratory system (infection)
2. Stomach contents can enter respiratory system

Question 16

What are the mesodermal defects often associated with TOF?

Answer 16

Vertebral defects (spinal bifida)

Anal atresia (anal canal not formed correctly)

Cardiac defects (most common)

Tracheo-oesophageal fistulas

Esophageal atresia

Renal abnormalities

Limb defects

Question 17

How do lungs form during pseudoglandular stage?

Answer 17

Tubular branching –> during partioning of oesophagus and respiratory diverticulum, right and left lung buds form

Question 18

Describe the order of formation of bronchi during the pseudoglandular stage

Answer 18

Week 5:

1. Trachea divides into 2 1ary bronchi (right and left)
2. 1ary bronchi divide into 2ary bronchi (3 on right, 2 on left)

Week 6:

3. 2ary bronchi branch, resulting in formation of 3ary bronchial buds (bronchial tree)
4. By end of 7th week, the 18 bronchopulmonary segments have been established (10 right, 8 left)
5. Branching continues to form terminal bronchioles by week 16

Question 19

What does developing lung resemble during pseudoglandular stage?

Answer 19

Branched, compound gland of endodermal air-conducting tubules

Question 20

Why do infants born during the Pseudoglanduar Stage not survive?

Answer 20

No alveoli so respiration is not possible

Question 21

What is branching of respiratory tree to form 3ary bronchi caused by?

Answer 21

Signals between endoderm and mesoderm

Question 22

Describe development of bronchi in canalicular period?

Answer 22

Terminal bronchioles start to give rise to respiratory bronchioles with some terminal sacs at the end (around week 24). These give rise to some alveolar ducts.

Question 23

Describe vascularisation during canalicular period

Answer 23

Mesodermal tissues become highly vascularised (develop more capillaries)

Question 24

Describe surfactant production during canalicular period

Answer 24

Surfactant production by type II pneumocytes begins arond week 20-22 but overall is not enough to prevent airways collapsing (atelactasis)

Question 25

What is prognosis of infants born during canalicular period?

Answer 25

Still very poor but is chance of survival

Question 26

What occurs to aid gas exhange during terminal sac period?

Answer 26

Further terminal sacs (primitive alveoli) develop and vascularisation increases dramatically. Epithelium thins and capillaries come into 'contact' with epithelium --\> diffusion is more efficient

Question 27

What is the blood air barrier? When does it form?

Answer 27

Forms during terminal sac period Exists in gas exchanging region of lungs (alveolar-capillary barrier or membrane) * Prevents air bubbles from forming in blood and from blood entering alveoli * Permeable to O2, CO2, CO etc

Question 28

What are pneumocytes?

Answer 28

The surface epithelial cells of the alveoli

Question 29

What are the 2 types of pneumocytes and what is their function?

Answer 29

Type I --\> Gaseous exchange takes place Type II --\> Secrete surfactant

Question 30

What happens when infant is born during terminal sac period?

Answer 30

Can survive but will likely need ventilation assistance --\> may suffer from respiratory distress sydrome

Question 31

What occurs during alveolar period?

Answer 31

Terminal sacs continue to develop into alveolar ducts with numerous alveoli. 95% of mature alveoli don't develop until after birth

Question 32

What is cartilage, smooth muscle, connective tissue and capillaires formed from?

Answer 32

Visceral mesoderm

Question 33

What is purpose of surfactant?

Answer 33

Forms a film over internal walls of terminal sacs. Reduces surface tension and prevents alveolar from collapsing when there is low pressure.

Question 34

What is respiratory distress syndrome and what is it caused by?

Answer 34

Inadequate surfactant: - Surfactant protein B deficiency - Inadequate production by type II pneumocytes - Type II pnuemocytes haven’t developed enough

Question 35

Where do lungs develop from?

Answer 35

Foregut endoderm

Question 36

How does pleural cavity form?

Answer 36

At about 5 weeks, two longitudianl folds of the **mesoderm** called the **pleuropericardial folds** appear in the lungs and heart. These grow from the **lateral body wall** towards the midline to separate the **pericaridal cavity** (ventrally) and the **pleural cavity** (dorsally)

Question 37

How does pleura form?

Answer 37

Formed from **lateral plate mesoderm** which eventually splits into **visceral** and **parietal** mesoderm layer Visceral mesoderm --\> forms visceral pleura Parietal mesoderm --\> forms parietal pleura

Question 38

What is pulmonary agenesis?

Answer 38

Failure of primitive lung bud to split from bronchial buds leads to absence of lung tissue

Question 39

What are the 2 types of pulmonary agenesis?

Answer 39

Unilater --\> occurs on one side Bilateral --\> incompatible with life

Question 40

What is clinical presentation of unilateral pulmonary agenesis?

Answer 40

- Respiratory distress - Remaining lung is comprimised (lower respiratory tract infection) - 60% have other congential abnormalities - Agenesis of right lung is associated with higher frequency of anomalies - Left agenesis --\> enlarged right lung, deviation of heart and trachea

Question 41

What is difference bewteen pulmonary aplasia and pulmonary agenesis?

Answer 41

* Lung parenchyma absent in both * Short blind-ending bronchus in pulmonary aplasia

Question 42

What is pulmonary hypoplasia? How does it differ from pulmonary aplasia?

Answer 42

Pulmonary aplasia is used to describe the incomplete development of lung parenchyma supplied by a rudimentary bronchus Pulmonary hypoplasia is the incomplete development of the lungs, resulting in an abnormally low number or size of bronchopulmonary segments or alveoli. A congenital malformation, it most often occurs secondary to other fetal abnormalities that interfere with normal development of the lungs. Pulmonary hypoplasia is distinguished by a normal tracheobronchial tree and underdeveloped pulmonary parenchyma.

Question 43

What is congenital diaphragmatic hernia (CDH) and what is it associated with?

Answer 43

May be found in association with pulmonary hypoplasia. * When diaphragm fails to close during prenatal development * Contents from abdomen migrate into chest * Can be fatal during development

Question 44

What is branching morphogenesis? What is consequence of this?

Answer 44

Supernumerary (extra) lobes or segments. Little functional significance as cannot increase gas exchange from extra lobe

Question 45

How can mechanical ventilation during premature birth lead to RDS?

Answer 45

Damage to alveolar lining as fluid and serum proteins leak into alveolus. Continued injury may lead to detachment of alveolar lining. Chronic lung injury in preterm infants may cause bronchopulmonary dysplasia (abnormal formation)

Question 46

What is treatment for RDS?

Answer 46

1. Glucocorticoid (steriod) treatment: * Accelerates foetal lung development and surfactant production * Must be given prior to birth 2. Surfactant therapy * Natural or artificial surfactant * Surfactant A and B proteins more effective

Question 47

What is sufactant protein B deficiency disease?

Answer 47

Genetic - autosomal recessive Fatal disease even with surfactant replacement therapy (only temporary)

Question 48

What is agenesis?

Answer 48

The failure of an organ to develop during embryonic growth and development due to the absence of primordial tissue

Question 49

What is aplasia?

Answer 49

The failure of an organ or tissue to develop or to function normally.