Lung Development

Question 1

What are the 4 main phases of lung development

Answer 1

Embryonic phase
Pseudoglandular phase
Canalicular phase
Saccular/alveolar phase

Question 2

When can gas exchange take place in lung development

Answer 2

From the canicular phase onwards

Question 3

Describe the embryonic phase

Answer 3

0-7 weeks
Lungs buds
Formation of the main bronchi
Branching morphogenesis

Question 4

Describe the pseudo glandular phase

Answer 4

5-17 weeks
Conducting airways formation
Bronchi and bronchioli
Pre-acinar airways (17 weeks)
Cartilage, glands and smooth muscle tissue development
Branching morphogenesis of airways -> mesenchyme

Question 5

Describe the canalicular phase

Answer 5

15-27 weeks
Respiratory airways
Blood gas barrier development - thinning of the epithelium around capillaries
Differentiation into type I and II pneumocytes
Surfactant production (24 weeks)

Question 6

Describe the saccular/alveolar phase

Answer 6

28-40 weeks

Alveogenesis and angiogenesis

Question 7

What are the landmarks in lung development at the following times: 6 weeks, 16 weeks, 30 weeks, newborn, 3 year old

Answer 7

6 weeks - lobar airways
16 weeks - pre-acinar airways
30 weeks - respiratory airways present. alveoli seen
newborn - 1/3-1/2 alveolar number present
3 year old - most alveoli present

Question 8

Describe vasculogenesis

Answer 8

Asymmetric

Occurs in the embryonic and pseudo glandular phase

Question 9

What drives branching morphogenesis

Answer 9

Lung buds
Epithelial cells at the tips of the buds are highly proliferative
Cells behind the tip divide and differentiate
Communication between epithelial cells in distal branching lung buds and mesenchyme

Question 10

What are the inductive growth factors

Answer 10

FGF - branching morphogenesis. subtypes found in the epithelium and mesenchyme
EGF - epithelial proliferation and differentiation

Question 11

What are the inhibitory growth factors

Answer 11

TGFbeta - matrix synthesis, surfactant production, epithelium and blood vessel proliferation inhibition
retinoic aid - inhibits branching

Question 12

Explain the process of vasculogenesis

Answer 12

Lung buds produce VEGF at the tip
Mesenchyme forms a matrix around the developing airway
They coalesce to form capillaries

Question 13

Explain the process of alveolar wall formation

Answer 13

1. Saccule wall formation. The epithelium on both sides with a double capillary network. Myofibroblast and elastin fibres at intervals along the wall
2. Secondary septa. Elastin produced by myofibroblast leads development as the capillary lines both sides with matrix between
3. Capillaries coalesce to form one sheet of alveolar wall, thinner and longer with less matrix. Muscle and elastin remain at the tip

Question 14

What factor determines how prematurely a baby cam be born

Answer 14

Surfactant production

Question 15

Describe the lungs at birth

Answer 15

Volume is small (Related to body weight)
All airways are present and differentiated 
Less developed blood gas barrier
less alveoli 
Most arteries and veins

Question 16

What are the changes in the blood vessels at birth

Answer 16

Decrease in pulmonary vascular resistance -> increases blood flow 10x
Arterial lumen increases, wall thins -> growth
No loss of cells
Low pressure, Low resistance

Question 17

What are the changes to the lungs in childhood and adolescence

Answer 17

Airways increase in length 
Alveoli increase in number
(adults 300-600million)
Alveoli become more complex
Arteries and veins also increase

Question 18

Describe primary ciliary dyskinesia

Answer 18

Autosomal recessive
Cilia are completely stationary 
Dynein arms are absent (ATPase that helps motility move relative)
Impedes on lung development
No primary immune response
Lower levels of nasal NO

Question 19

Describe cartilage defects

Answer 19

Normally incomplete cartilage with irregular plates
They calcify with age
Can be malalic (floppy)

Question 20

Describe malalic cartilage

Answer 20

Generalised - slowly with age e.g. laryngotracheomalcia
Localised - often occur due to other issues such as problems with the heart, Malacic segment which may occur due to external compression

Question 21

What is laryngomalacia

Answer 21

epiglottis are omega shaped and the folds collapse into the airway and block it

Question 22

What is agenesis

Answer 22

Complete absence of lung and vessel
Rare
Abnormal flow in the 4th week
Commonly associated with other pathology
Mediastinal shift towards an opaque hemithorax

Question 23

What is aplasia

Answer 23

Blind ending bronchus, no lung or vessel

Question 24

Describe hypoplasia

Answer 24

Everything is present, all elements are reduced in size and number
Common and usually secondary
Lack of space (intra/extrathoracic)
Lack of growth (congenital thoracic malformation)
Small lung volumes in post natal children - oligohydramnios (lack of fluid)

Question 25

Describe congenital pulmonary airway malformation

Answer 25

Mostly antenatal
Defect in the mesenchyme
Abnormal differentiation
Normal blood supply

Question 26

Describe type 2 congenital pulmonary airway malformation

Answer 26

Multiple small cysts

May be associated with renal agenesis, cardio defects, diaphragmatic hernia and syrgomyelia

Question 27

What is congenital lobar emphysema

Answer 27

progressive lobar over expansion
Caused by weak cartilage, extrinsic compression, one way valve effect and alveolar expansion
males>females

Question 28

What is intralobar sequestration

Answer 28

Abnormal segments share visceral pleura
No communication to the tracheobronchial tree
Due to chronic bronchial obstruction and chronic post obstructive pneumonia

Question 29

What is scimitar syndrome

Answer 29

Dextrocardia - heart switches to the opposite direction
Anomalous pulmonary venous drainage of the right lung to the IVC
associated with hypoplasia of the right vein and lung