Respiratory Systems 14 - Lung Development in Childhood

Question 1

Briefly summarise the timeline of lung development

Answer 1

• Embryonic phase (0-7 weeks) lung buds/main bronchi
• Pseudoglandular (5-17 weeks) conducting airways, bronchi & bronchioli
• Canalicular (16-27 weeks) respiratory airways and blood gas barrier
• Saccular/alveolar (28-40 weeks) alveoli appear
• Postnatal/ adolescence - alveoli multiply and enlarge in size with chest cavity

Question 2

How does interaction between airways and pulmonary vessels occur throughout development?

Answer 2

• Vasculogenesis occurs as branching morphogenesis occurs

- Alveo and angiogenesis occur

Question 3

When do alveoli appear?

Answer 3

• Before birth, though they continue to grow in early childhood
• 1/3 to 1/2 the adult number by term

Question 4

Describe what occurs in lung development during the pseudoglandular phase.

Answer 4

• Braching morphogenesis of airways into mesenchyme
• Pre-acinar airways all present by 17 weeks
• Development of cartilage, gland and smooth muscle tissue begins

Question 5

List the factors driving branching morphogenesis

Answer 5

• Lung buds (consistent appearance during airway formation)
• Epithelial cells at the tips of lung buds are highly proliferative multipotent progenitor cells
• Cells behind the tip divide and differentiate into the various cell types
• Communication between epithelial cells in distal branching lung buds and surrounding mesenchyme

Question 6

List the inductive growth factors in lung development

Answer 6

• FGF (branching morphogenesis, subtypes found in epithelium and mesenchyme)
• EGF (epithelial proliferation and differentiation)

Question 7

List the inhibitory growth factors in lung development

Answer 7

• TGF beta (matrix synthesis surfactant production, inhibits proliferation of epithelium and blood vessels)
• Retinoic acid (inhibits branching)

Question 8

Describe the process of endothelial differentiation

Answer 8

• Endothelial cells differentiate in the mesenchyme around the lung bud
• They coalesce to form capillaries in vasculogenesis
• Airways act as structural template
• VEGF produced by epithelial cells stimulates endothelial differentiation

Question 9

Describe what happens in lung development in the canalicular stage

Answer 9

• Airspaces at the periphery emerge
• Thinning of epithelium by underlying capillaries allows gas exchange
• Blood gas barrier required in post-natal life
• Epithelial differentiation into type I and II cells
• Surfactant first detectable at 24-25 weeks
• Babies become viable at 24 weeks

Question 10

Describe the mechanism of formation of alveolar walls

Answer 10

• Saccule wall is where there is epithelium on both sides with a double capillary network
• Secondary septa develop from the wall led by elastin produced by myofibroblasts. Capillaries line each side with matrix inbetween
• Capillaries coalesce to form one sheet alveolar wall, thinner and longer. Muscle and elastin are at the tip

Question 11

Describe the appearance of the lung at birth in man

Answer 11

• Volume is small and related to body weight
• All airways are present and differentiated
• Blood gas barrier present
• 22-50% alveoli (normal gas exchange)
• Most arteries and veins present

Question 12

List the possible mechanisms to increase flow after birth

Answer 12

• Expansion of aleoli dilates arteries
• Expansion stimulates release of vasodilator agents
• Inhibition of vasoconstrictors present during fetal life
• Direct effect of oxygen on smooth muscle cells

Question 13

Describe the changes at birth in blood vessels

Answer 13

• Decrease in pulmonary vascular resistance
• 10 fold rise in pulmonary blood flow
• Arterial lumen increases and wall thins rapidly
• Change in cell shape and cytoskeletal organisation (not loss of cells)
• Once thinning has occurred, arteries grow and maintain a relatively thin wall
• Low pressure, low resistance pulmonary vascular system

Question 14

What is primary ciliary dyskinesia?

Answer 14

• A rare genetic condition where there are no dyenin arms

- This means that cilia are immobile, and there is a build up of mucous

Question 15

List the issues that may be seen in congenital bronchial cartilage defects

Answer 15

• Incomplete rings posteriorly
• Irregular plates
• Calcify with age
• Generalised (laryngotracheomalacia)
• Localised (malacic segment which may occur due to external compression)

Question 16

List the types of lung growth anomalies

Answer 16

• Agenesis (complete absence of lung/vessel - rare)
• Aplasia (blind ending bronchus, no lung or vessel)
• Hypoplasia (bronchus and rudimentary lung are present, but all elements are reduced in size and number - common)

Question 17

What causes hypoplasia of the lung?

Answer 17

• Usually secondary
• Due to lack of space (hernia, ogliohydramnios, lymphatic or cardiac mass)
• Lack of growth (congenital)

Question 18

What is cystic pulmonary airway malformation?

Answer 18

• Defect in pulmonary mesenchyma, abnormal differentiation 5-7th week
• Normal blood supply
• Type 2 involves multiple small cysts

Question 19

What is congenital lobar emphysema?

Answer 19

• Progressive lobar overexpansion
• Caused by weak cartilage, extrinsic compression, one way valve effect.
• Alveoli can expand
• Associated with CHD

Question 20

Discuss the prevalence of congenital lobar emphysema.

Answer 20

• More common in the Left upper lobe, then right middle and then right upper lobe
• Affects males more than females

Question 21

What is intralobar sequestration?

Answer 21

• Abnormal segment share
• No communication to tracheobronchial tree
• Lower lobe predominance
• Due to chronic bronchial obstruction