Lung Development Flashcards
Timeline of lung development
Majority of the network (airways AND circulation) develops during?
Alveoli development?
- Embryonic Phase (0→7 weeks).
a. Vasculogenesis and branching morphogenesis begins here. - Pseudoglandular Phase (5→17 weeks).
a. Vasculogenesis and branching morphogenesis continues. - Canalicular Phase (16→27 weeks).
a. Respiratory tissue begins to grow here.
b. Blood gas barrier supply forms. - Saccular/Alveolar Phase (28→40 weeks).
a. Alveolar and angiogenesis occurs. - Postnatal (adolescence
Majority of the network (airways AND circulation) develops during early foetal life.
Alveoli appear before birth and continue to grow in early childhood.
Vasculogenesis (process of blood vessel formation in the embryo) closely matches the airway generation throughout development.
Scimitar Syndrome
Characterised by?
▪ Anomalous pulmonary venous drainage of the right lung to the IVC, usually close
to the junction of the right atrium.
▪ There is associated right lung and right pulmonary artery hypoplasia.
o Essentially a small right lung with hypoventilation.
▪ Characterised by Dextrocardia (heart is pulled to the right instead of left).
▪ Anomalous systemic arterial supply.
▪ To the right of the IVC, you can see a scimitar shaped vessel → hence name.
Embryonic Phase – Branching Morphogenesis and Vasculogenesis – 0 → 7 Weeks.
Shows the general development of the lungs in increments of 7 days, 7 days and 14 days.
▪ Left lung develops 2 lobes.
▪ Right lung develops 3 lobes.
▪ Individual lobes can be affected and shown up on x-rays so for example, a single lobe may display oedema.
Pseudoglandular Phase – 5 → 17 Weeks.
▪ Characterised by branching morphogenesis of airways into mesenchyme.
▪ Pre-acinar airways are then all present by 17 weeks.
▪ Middle lobe of right lung is most often affected by aspirations as objects naturally fall into it.
▪ Development of cartilage, gland and smooth muscle tissue begins and continues into Canalicular phase.
o Bronchial cartilage displays incomplete rings posteriorly (complete is very bad), irregularity, calcify with age and can malacic.
o Malacic – abnormal softening of organs or tissues.
▪ General malcia – laryngotracheomalcia.
• E.g. Laryngomalacia – abnormal softening of the
larynx which can lead to airway collapse.
▪ Localised malcia – malacic segment.
Factors Driving Branching Morphogenesis
▪ Lung buds – consistent appearance during airway formation (5→17 weeks in man).
o Epithelial cells at the tips of each bud are highly proliferative and can differentiate as needed.
o Genetic and transcription factors (TFF-1) are involved in early bud development.
▪ Epithelial-mesenchymal interaction essential for branching morphogenesis.
▪ Branching in humans follows a bifurcation pattern.
Growth Factors for Lung Development – Inductive
▪ FGF – for branching morphogenesis.
▪ EGF – epithelial proliferation and differentiation.
Growth Factors for Lung Development – Inhibitory
▪ TGF-beta – matrix synthesis, surfactant production,
inhibits proliferation of epithelium and angiogenesis.
▪ Retinoic Acid – inhibits branching.
Primary Ciliary Dyskinesia
▪ A movement disorder due to a loss of ciliary proteins in the axon.
▪ The dynein arms required to lose cilia are lost
A circulation is present by
5 weeks’ gestation (since conception)
Congenital Thoracic Malformations
CPAM/CCAM – Cystic Pulmonary Airway Malformation
Congenital Lobar Emphysema/Congenital Large Hyperlucent Lobe (CLHL)
Intra-lobar Sequestration
Lung Growth Abnormalities
CPAM/CCAM – Cystic Pulmonary Airway Malformation
▪ Characterised by a defect in pulmonary mesenchyma with abnormal differentiation in the 5th→7th week.
▪ A normal blood supply is present but it can be associated with sequestration.
▪ Type 2 CPAM/CCAM is characterised by multiple small cysts which pool in the lung tissue and is caused by
hyperplasia of epithelium separated by underdeveloped alveolar tissue.
o Can be associated with renal agenesis, CVD defects and diaphragmatic hernias.
Congenital Lobar Emphysema/Congenital Large Hyperlucent Lobe (CLHL)
▪ Progressive lobar overexpansion:
o Due to weak cartilage, extrinsic compression, one-way valve effect or alveoli expansion.
▪ Affects more males than females.
▪ CHD association.
Intra-lobar Sequestration
Makes up 75% of pulmonary sequestrations.
▪ Sequestration – loss of blood or its fluid content into spaces within the body.
▪ Characterised by abnormal segment share of visceral pleura covering of the normal lung – the loss of
connection of the lobes with the bronchial tree and pulmonary veins.
▪ Due to chronic bronchial obstruction and chronic post-obstructive pneumonia.
Lung Growth Abnormalities
▪ Agenesis – complete absence of lungs and vessels.
o VERY RARE and commonly associated with other pathology.
o Normally an associated mediastinal shift towards an opaque hemithorax.
▪ Aplasia – blind ending bronchus with no lung or vessels.
▪ Hypolasia – bronchus and rudimentary lung are all present but reduced in size and number. o Common (relatively) and usually secondary. o Due to a lack of space (intrathoracic/extrathoracic) or lack of growth.
Early Blood Vessel Development
What is present on endothelial cells
Important control of early blood vessels is achieved by?
▪ CD31 is present on endothelial cells and these differentiate into the mesenchyme surrounding the lung buds.
▪ The endothelial cells coalesce to form capillaries in a process known as Vasculogenesis.
▪ VEGF (vascular endothelial growth factor) produced by the epithelial cells stimulates the endothelial
differentiation.
▪ Important control of early blood vessels is achieved by:
o VEGF, Flk-1 (VEGF receptors), IGF/IGFR (aids capillary development), eNOS (stimulates proliferation and
tube formation), Angiopoietin ((with the Tie receptor) and is important in wall differentiation).
▪ By the end of Pseudoglandular phase, all airways and blood vessels to the level of the terminal bronchioles are
present.
