15 - Lung development

Question 1

What are the phases in the timeline of lung development? At how many weeks does each stage occur?

Answer 1

• embryonic phase: 0-7 weeks
• pseudoglandular phase: 5-16 weeks
• cannalicular phase: 16-27 weeks
• saccular/alveolar: 28-40 weeks
• postnatal/adolescence

Question 2

What happens in the embryonic phase of lung development?

Answer 2

the lungs bud into the mesenchymal tissue

the trachea branches into the the main bronchi

Question 3

What happens in the pseudoglandular phase of lung development?

Answer 3

• development of the conducting airways
• development of the bronchi and bronchioles
• branching morphogenesis of airways into mesenchyme
• pre-acinar airways all present by 17 weeks
• development of cartilage, gland and smooth muscle tissue – continues into canalicular phase

Question 4

What happens in the canalicular phase of lung development?

Answer 4

• development of the conducting airways
• development of blood-gas barrier
• peripheral airspaces enlarge
• thinning of epithelium by underlying capillaries (allows age exchange)
• epithelial differentiation into Type 1 and Type 2 cells
• surfactant first detectable at 24-25 wks

Question 5

What happens in the alveolar phase of lung development?

Answer 5

the alveoli appear

Question 6

What changes in lung development occur during adolescence?

Answer 6

the alveoli multiply and enlarge in size with chest cavity

Question 7

Describe the blood vessel development alongside the development of the lungs

Answer 7

the pulmonary vessels develop alongside the airways

• there is addition of newly formed endothelial tubes at the lung periphery as each airway division occurs
• as the capillaries add on at the periphery the arteries and veins get longer
• vasculogenesis and branching morphogenesis occur in the early stages of lung development
• the blood-brain barrier forms in the later stages
• alveo and angiogenesis take place very late on

Question 8

What are the pre-acinar airways and when are they fully formed by?

Answer 8

the conducting airways that are not involved in gas exchange

present by 17 weeks

Question 9

What factors drive branching morphogenesis?

Answer 9

• epithelial cells at tips of buds are highly proliferative multipotent progenitor cells
• the 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 10

What are the control mechanisms for development?

Answer 10

• epithelial-mesenchymal interaction - for branching morphogenesis
• Genetic and Transcription factors [TTF-1] involved in early bud formation
• Branching development in humans follows a bifurcation pattern
• later, a variety of growth factors are important

Question 11

What are the growth factors involved in lung development? (inductive and inhibitory)

Answer 11

inductive - FGF and EGF

inhibitory - TGFβ and retinoid acid

Question 12

What is the process of endothelial differentiation?

Answer 12

• they differentiate in the mesenchyme around the lung bud
• vasculogenesis (they coalesce to form capillaries)
• the airwayss act as structural template
• VEGF produced by epithelial cells stimulates endothelial differentiation

Question 13

End of the pseudoglandular and beginning of the canalicular phase

Answer 13

• all airways and blood vessels to the level of the terminal bronchiolus are present
• the appearance of the lung changes as the lung enters the canalicular stage

Question 14

Give the mechanism of formation of the alveolar walls

Answer 14

The saccular wall has an epithelium on both sides with double capillary network. There are myofibroblasts and elastin fibres at intervals along the wall.

Secondary septa (the folds of of the alveolar sacs) develop from wall led by elastin (produced by myofibroblast). Capillary lines both sides with matrix between.

Capillaries coalesce to form one sheet alveolar wall, thinner and longer with less matrix. Muscle and elastin are still at tip

Question 15

Describe the lungs at birth

Answer 15

Volume small and related to body weight
All airways present and differentiated (cartilage, glands, muscle, nerves) 
33-50% alveoli allow normal gas exchange
Blood-gas barrier is fully developed
Most arteries and veins present

Question 16

What happens to the blood vessels at birth?

Answer 16

• Decrease in pulmonary vascular resistance
• 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 (high volume), LOW RESISTANCE PULMONARY VASCULAR SYSTEM

Question 17

What are the possible mechanisms to increase flow after birth?

Answer 17

• expansion of alveoli dilates arteries (direct physical effect)
• expansion stimulates release of vasodilator agents (NO, PGI2)
• inhibition of vasoconstrictors present during foetal life
• direct effect of oxygen on smooth muscle cells

Question 18

Describe the airway growth during childhood and adolescence

Answer 18

• lung volume increases x30
• airways increase in length and width x 2-3
• during the early period, there is dysanaptic growth - alveoli grow more than airways (airways relatively large in infants)

Question 19

Describe the growth of alveoli during childhood and adolescence

Answer 19

• increase in number up to 2-3 years
• increase in size and complexity —–> increase SA
• increase in arteries, veins and capillaries alongside the alveoli

Question 20

Describe the process of multiciliation in airway cells

Answer 20

• dividing progenitor cells exit the cell cycle
• centrioles are amplified
• apical docking of centrioles
• cilium maturation

Question 21

Describe the bronchial cartilage

Answer 21

• Incomplete rings posteriorly
• Irregular plates
• Calcify with age
• Can be malacic (abnormal softening of the tissue):

Question 22

What is primary ciliary dyskinesia?

Answer 22

absence/disfunction of inner dynein arm on cilia - leads to abnormal cilia beating movement

Question 23

What is malacia?

Answer 23

softening of the bronchial cartilage

Question 24

Give some abnormalities of lung growth

Answer 24

• agenesis - a complete absence of lung and vessels - causes distortion of mediastinum and diaphragm
• aplasia - blind-ended bronchus - no lungs or vessels
• hypoplasia (under development) - bronchus and rudimentary lung are present, but all elements are reduced in size and number
  (usually secondary and sue to lack of space or growth)

Question 25

What is Cystic Pulmonary Airway Malformation (CPAM)?

Answer 25

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

Question 26

What is pulmonary sequestration?

Answer 26

where a piece of lung tissue is not attached to the pulmonary arterial blood supply (as is the case in normally developing lung) This sequestered tissue is not connected to the normal bronchial airway architecture, so fails to contribute to respiration of the organism.

Question 27

What is an intralobar sequestration?

Answer 27

characterised by the presence of nonfunctional parenchymal lung tissue, receiving systemic arterial blood supply. It lacks normal communication with tracheobronchial tree. (75% of pulmonary sequestrations) Abnormal segment share visceral pleural covering of normal lung Lower lobe predominance - preferentially affects the lower lobes. 60% affect the left lower lobe, 40% the right lower lob Due to chronic bronchial obstruction and chronic postobstructive pneumonia

Question 28

Scimitar syndrome

Answer 28

associated right lung and right pulmonary artery hypoplasia | - can cause dextrocardia