3. Stages of lung development
First 7 weeks
Embryonic stage
7 to 16 weeks
Pseudo glandular stage
16 to 25 weeks
Canalicular stage
25 to 36 weeks
Saccular stage
36 weeks to early childhood
Alveolar stage
4. EMBRYONIC STAGE
• First 7 weeks of gestation
• WEEK 4: Lung 1st appears as ventral outgrowth of the foregut endoderm
known as “respiratory diverticulum”[Lung bud]
• WEEK 5: Lung bud grow into surrounding mesenchyme and branches
into right and left mainstem bronchi
6. Cont…..
NOTE:
➢Epithelium of trachea, bronchi, bronchioles, alveoli develop from
endoderm of foregut
➢Cartilage , muscles, connective tissue, pleura develops from
surrounding splanchnic mesoderm
• Vasculogenesis occurs simultaneously; with the development of the
two pulmonary arteries from the 6th aortic arches
7. Cont………
• This plexus initially connects to the systemic veins draining blood from proximal
gut and developing trachea.
• Later they also establish connection with the pulmonary vein (appears as a
small tubule growing out from the left atrial portion of the heart) .
• By 7 weeks of gestation, the adult pattern of central vascular and airway
structures consisting of lobar and segmental branches is present.
10. PSEUDO GLANDULAR STAGE
• From 7 to 16 weeks of gestation
• At the end of 7 weeks each lung resembles a small tubulo-acinar gland and is
described as the beginning of the 'pseudoglandular' stage
• During this stage there is repetitive sprouting and bifurcations of the lung buds
resulting in the formation of preacinar airways by the process of 'branching
morphogenesis' (BM).
12. Cont……
• Developing airway lined by cuboidal epithelium filled with glycogen
surrounded by simple mesenchyme
• Week 10: Cartilage and smooth muscle starts to develop
• Week 13: Proximal airways starts differentiating in to ciliated columnar
epithelium, goblet cells and basal cells.
• Differentiation progresses distally
13. Cont…
• Week 14: Airway branching reaches till 20 generations
that terminate in primitive terminal bronchioles
• By the end of this stage type 2 pneumocytes and
primitive pulmonary vasculature starts to develop
• By 20 weeks of gestation, the full numbers of
pre acinar pulmonary vessels are present in each
segment.
14. CANALICULAR STAGE
• From 16 to 25 weeks of gestation
• Canaliculi branch out of terminal bronchioles to form acinus composed of
1) Respiratory bronchioles
2) Alveolar ducts
3) Alveolar sacs
• The main features of this stage are the onset of formation of a thin air-blood
barrier and surfactant secretion
15. Cont....
• Vascular differentiation: Vascular and epithelial basement membranes
begin to fuse to form air blood barrier for gas exchange
• Epithelial differentiation:
➢ Type 2 pneumocytes begins to differentiatein to type1 pneumocytes
➢Lamellar bodies form in type 2 cells, surfactant synthesis begins(20weeks)
NOTE: Lungs become potentially viable by the end of this stage
17. SACCULAR STAGE
• From 25 to 36 weeks of gestation
• In this stage terminal saccules which are alveolar ducts that are
continuing to elongate, branch and widen continue to develop
• In saccular stage, each acinus composed of terminal bronchiole with
three to four respiratory bronchioles that end in a transitional duct
from which saccules arise
18. Cont…..
• By week 36: All generations of conducting and respiratory bronchioles
are formed
• Blood air barrier is reduced to 3 layers 1)Type 1 pneumocytes
2)Fused basement membrane
3)Capillary endothelium
• At birth 20 × 10 6 saccules are present
19. ALVEOLAR STAGE
• From 36 weeks to early childhood
• Saccular epithelium begins to fold over elastin and collagen fibers to
from alveolar septa
• Initially primary septum separates alveolar saccules with double layer
of capillaries
20. Cont…………..
• ALVEOLARIZATION: After birth, terminal saccules continue to fold and divide in
to smaller units, the alveoli.
• Secondary septa containing pulmonary vessels, elastin and collagen separate
alveolar sacs
• 50 – 150 million alveoli are present at birth and 500 million in adult
• The increase in alveoli parallels the increase in alveolar surface are
1)2.8 m2 at birth
2)32 m2 at at 8 years of age
3)75 m2 by adulthood
26. Factors controlling lung development
• Normal airway branching requires both epithelial and mesenchymal
elements, controlled by molecular and mechanistic factors.
• Lung specification begins with the expression of the transcription
factor Nkx2.1 in the endodermal cells on the anterior aspect of the
ventral foregut
• Wnt signalling plays a crucial role in specifying Nkx2.1 15
• Retinoic acid signalling is also essential for lung bud initiation.
27. Pathology of lung development
• The timing and the severity of the embryological insult predict the
morphology of the final lesion
• Agenesis: A complete arrest in the development of a bronchus and its
blood supply
• Bronchogenic cyst: A minor localized insult followed by normal
development of the distal tracheobronchial tree, lung parenchyma and
pulmonary vessels
28. Cont……..
• Sequestration: Arrested pulmonary artery growth with continued
development of the bronchial tree supported by its normally regressing
capillary network from the systemic vessels
• Congenital pulmonary adenomatoid malformations/CPAM: Disrupted
tracheobronchial connection, continuation of the pulmonary artery supplying
the abnormal lung segment
• Peripheral lesions of the terminal and respiratory branches and alveoli, such as
congenital lobar emphysema suggest a defect occuring late in development.
34. Diagnosis
• Antenatal diagnosis: Prenatal ultrasound
➢Macrocystic: Multiple/single cyst >5mm in diameter
Microcystic: Solid echogenic mass(should be differentiated from other)
• Postnatal diagnosis: CXR/CT – Usually appears as multiple cysts mostly
involving lower lobe. Type 3 lesions appear as solid mass
• Prognosis depends on size of the lesion rather than type of lesion
36. Management
• Rule out other malformations(CHD,CDH,RA,ELS)
• Regular antenatal ultrasound to look for development of hydrops
• CVR(cpam volume ratio)
₌0.52 x Lenght x Height x Width in cms /Head circumference in cms
➢CVR > 1.6 is predictive of increased risk of hydrops(80%) on followup
• Postnatally all patients with CPAM need lobectomy
40. Pulmonary sequestration(PS)
• Defined as mass of non functioning lung parenchyma without
communication with the tracheobronchial tree and with an
anomalous systemic blood supply
• TYPES
Intralobar sequestrations(ILS)
• Constitute 75% of all PS
• Contained within the pleura along with
normal lung
• Usually basilar segment of lowerlobe
involved
• Left >Right
• Venous drainage to pulmonary veins
Extralobar
sequestration(ELS)
• Constitute 25%of all PS
• Outside the pleura of normal lung
• Intrathoracic – BlW lower lobe and
diaphragm
• Systemic venous drainage
• Associatedwith other defects
42. Management
• In 2/3rd cases size decreases on followup
• May develop hydrops due to massive effusion
• <32 weeks- Thoracoamniotic shunt
• >32weeks- Early delivery followed by surgery
•
ANTENATAL
• Lobectomy for ILS and mass resection for ELS
• INDICATIONS-1) All cystic sequestrations
2) Symptomatic
3) All ILS
POSTNATAL
46. Cont…..
• Clinical features: Asymptomatic/neonatal respiratory distress/
recurrent infections
• Diagnosis:
• Antenatal – Solid echogenic thoracic mass without abnormal blood
supply
• Postnatal- CXR: Opacity(initial few days), hyperlucent lobe with
surrounding atelectasis
CECT: Above + bronchial anatomy
V-P scan: Delayed uptake and washout of isotope,
decreased blood supply
Bronchoscopy: If foreign body aspiration suspected
47. Management
• Emergency thoracotomy ( Severe NRD)
• Lobectomy
• High frequency ventilation and selective bronchial intubation
• Management of asymptomatic and mildly symptomatic cases is
controversial.
49. Bronchogenic cyst
• Solitary unilocular cystic structure filled with fluid or mucus
• Lined by respiratory epithelium and contains hyaline cartilage in cyst wall
• LOCATION: Lung parenchyma/hilum/mediastinum/extra thoracic
• PATHOLOGY: Aberrant outpouching from foregut, do not communicate with
foregut/airway
• Clinical features: Abscess formation/ bronchial compression
/malignancy(pleuropulmonary blastoma)
50. Cont….
• Diagnosis:
CXR- Thin walled water density mass lesions without air-fluid levels
CECT- Wall enhancement if infected
• MANAGEMENT: Lobectomy/segmentectomy(intraparenchymal)
Excision(mediastinal)
56. Applied anatomy
➢Collateral circulation:
• Canals of lambert(120 ⴑm) are accessory connections in the lungs between
bronchioles and adjacent alveoli
• Pores of kohn(3-13ⴑm) connect alveoli to adjacent alveoli
• Martins channels(30 ⴑm) are interbronchiolar connections
• Modulate ventilation perfusion mismatch in diseased states
• Absent in newborn, starts developing from 4 yrs of age. More significance in
adult
57. Cont…..
• These connections have role in spreading of infection in “lobar
pneumonia”
• In children these connections are poorly developed which limits
infection and contribute to “round pneumonia”
• These connections play an important role in prevention of collapse
