Lung development Flashcards
Macroanatomy of the respiratory system
- Trachea
- Primary/main bronchi
- Secondary/lobar bronchi
- Tertiary/segmental bronchi
- Bronchioles
- Terminal bronchioles
- Respiratory bronchioles
- Alveoli
airway epithelium
- Bronchi: pseudostratified ciliated columnar cells
Goblet cells (mucus)
Ciliated cells
Basal cells - Terminal bronchioles: simple ciliated columnar epithelium
No more goblet cells
More clara/club cells - Respiratory bronchioles: simple ciliated cuboidal epithelium
- Alveoli: simple squamous (type 1) and cuboidal (type 2)
Type 1 and type 2 cells (pneumocytes)
Macrophages
stem cell niches
- Trachea and bronchi: basal cells –> basal, ciliated, goblet,
club cells - Ducts of submucosal glands: undifined SMG duct cells –>
serous, ciliated, mucous tubule, colelcting duct and
myoepithelial cells - Bronchioles: variant club cells –> club, ciliated and goblet
- Brochoalveolar junction: bronchoalveolar stem cells –> club, ciliated, goblet, AEC1&2
- Alveoli: AEC2 –> AEC1&2
surfactant: definition and production
Pulmonary surfactant is a surface-active complex of phospholipids 90% (DPPC) and proteins 10% formed by type II alveolar cells.
surfactant functions
phospholipids –> DPPC: lower surface tension to prevent fluid accumulation and atelectasis and to increase pulmonary compliance
proteins –> SP-A and SP-D (hydrophilic): collectins, collagen-like proteins that have a C-type lectin domain to opsonize, neutralise and lyse pathogens or to activate leukocytes (they need to trimerize and form octa and dodecmers)
SP-B and SP-C: hydrophobic, prevent atelectasis
lung tissue origins
• Endoderm –> foregut –> epithelial cells
• Mesoderm –> connective tissue (cartilage, pleura),
smooth muscle cells and blood vessels)
• Ectoderm –> nerves
stages of lung development
- embryonic stage: week 4-7
- pseudoglandular stage: week 8-16
- canalicular stage: week 17-26
- terminal sac stage: week 26-birth
- postnatal alveolar stage: late fetal - early childhood
embryonic stage
- Week 4 –> diverticulum of the ventral wall of the
foregut endoderm sprouts
• All of these cells are NKX2.1 (TTF1 transcription
factor) positive
• This initial lung bud creates the trachea and the
larynx
• Later the lung bud sprouts 2 bronchial buds:
primary bronchi - Week 5 –> the bronchial buds bifurcate into 3
secondary bronchi on the right and 2 on the left - Week 6-7 –> 10 generations of bronchi and
bronchioles form
pseudoglandular stage
- Further branching leads to terminal bronchiole
formation –> conduction zones are formed - The lung has a gland like histology hence the name
- Vessel invaginate the mesenchyme and elongate
parallel to the airway ducts
canalicular stage
- Formation of respiratory bronchioles at the tips of
terminal bronchioles by budding and branching
(multiple respiratory per terminal) - Ingrowth of vessels/capillaries continues
terminal sac stage
- Formation of alveolar sacs by budding and branching
off from respiratory bronchioles - Expansion of capillary network
postnatal alveolar stage
- Expansion of alveoli by septation
• This secondary septation is driven by connective
tissue that divides alveolus –> elastin
• Alveolar cells then invade the tissue to cover the
septum and capillaries grow into the septum - Expansion of capillary network –> 90% form after birth
preterm delivery and lungs
Delivery before week 34 –> immature lungs and not enough surfactant to breathe
In this case ventilation is needed –> can cause bronchopulmonary displasia
BPD can be prevented by:
- giving surfactant after birth
- giving steroids (pre and postnatal) to mature the lungs
faster and to stimulate surfactant production
- giving retinoic acid and increased nutrition to stimulate
lung developpment