Resp 15 - Lung development

Question 1

When does the tracheal bud develop from the foregut?

Answer 1

4-5 weeks

Question 2

By what point is bronchial branching complete?

Answer 2

16 weeks

Question 3

Describe the steps in the timeline of development of lungs.

Answer 3

Embryonic phase - 0-7 weeks; lung buds, main bronchi

Pseudoglandular - 5-17 weeks; conducting airways, bronchi & btonchioli

Canalicular - 16-27 weeks; respiratory airways, blood gas barrier

Saccular/Alveolar - 28-40 weeks; alveoli appear

Question 4

How does branching morphogenesis happen?

Answer 4

Happens in mesenchymal tissue. Lung bud pushes into mesenchyme to form airways which divide.

Question 5

When is pseudoglandular phase? What happens?

Answer 5

5-17 weeks
Branching morphogenesis of airways into mesenchyme.
Pre-acinar airways all present by 17 weeks.
Development of cartilage, gland and smooth muscle

Question 6

Which factors drive branching morphogenesis?

Answer 6

There are inductive (ex FGF, EGF) and inhibitory (TGFbeta, retinoic acid) growth factors.

Complex signaling between GF, cytokines, receptors to control growth.

Epithelial cells at tip of bud are highly proliferative multipotent progenitor cells

Question 7

How are capillaries formed during lung development?

Answer 7

Endothelial cells differentiate in the mesenchyme surrounding the lung bud. They collapse to form capillaries - process called vasculogenesis.
VEGF produced by epithelial cells stimulates endothelial differentiation.

Question 8

Which phase happens during 16-27 weeks? What happens?

Answer 8

Canalicular stage
Start to see structure of airways at the periphery.
Thinning of epithelium by underlying capillaries allowing gas exchange - blood-gas barrier, epithelial differentiation into types I and II.
Surfactant 24-25 weeks (baby viable 24 weeks)

Question 9

Describe the mechanism of formation of alveolar walls.

Answer 9

1. saccule wall, epithelium on both sides with double capillary
2. Secondary septa develop from wall led by elastin produced by myofibroblasts. Capillary lines both sides with matrix between.
3. Alveolar wall formation - one sheet, capillaries coalesced.

Question 10

What happens after Cannalicular stage?

Answer 10

Saccular/Alveolar stage- 28-40 weeks.
Alveoli appear.
1/3 to 1/2 of adult number at term.

Question 11

How does an infant go from placental circulation to normal lung circulation?

Answer 11

• Expansion of alveoli dilates arteries; direct physical effect.
• Expansion releases vasodilators (NO, PGI2)
• Inhibition of vasoconstriction present during foetal life (ET)
• Direct effect of oxygen on SMC.
• -> decrease in pulmonary vascular resistance
• > low pressure, low resistance

Question 12

What type of epithelium lines the airways?

Answer 12

Single layer of columnar epithelium

Question 13

What is another name for primary ciliary dyskinesia?

Answer 13

Kartagener’s syndrome

Question 14

What happens in primary ciliary dyskinesia?

Answer 14

Mutation of cilia. Causes inadequate mucus clearance because no hooks to hold onto mucus.

Question 15

What is the only complete cartilage ring around the trachea?

Answer 15

Circoid cartilage

Question 16

What are the types of lung growth abnormalities?

Answer 16

Agenesis (complete absence)
Aplasia - blind ending bronhcus, no vessel
Hypoplasia - all present but reduced in size

Question 17

By what is caused hypoplasia? Give examples

Answer 17

• Lack of space; intrathoracic or extrathoracic. Eg. hernia, chest wall pathology, lymphatic/cardiac mass.
• Lack of growth
  Eg. Congenital Thoracic Malformation CTM

Question 18

What causes agenesis?

Answer 18

Abnormal flow in 4th week. Commonly associated with other pathology. Rare.

Question 19

What is Cystic Pulmonary Airway Malformation CPAM (aka CCAM)?

Answer 19

Defect in pulmonary mesenchyma, abnormal differentiation 5-7th week.
Normal blood supply.

Type 2 CCAM - multiple small cysts
Associated with renal agenesis, CV defects, diaphragm hernia. Overgrowth of bronchiolar epithelium.

Question 20

What is Congenital Lobar Emphysema aka Congenital Hyperlucent Lobe (CLHL)?

Answer 20

Progressive lobar expansion
Underlying cause: weak cartilage, compression, alveoli expand..
On scan looks like emphysema in smokers - lots of air because bronchi blocked.

Question 21

Describe intralobar sequestration.

Answer 21

Growth of a part of lung that is not connected to the rest, ie. bronchi.
Abnormal blood supply which can be quite significant – need to block vessel by cardiologist, otherwise shunting can cause heart failure.