LUNG DEVELOPMENT

OLEKSANDR KUDIN
STAGES OF DEVELOPMENT

¡  Embrionic period
¡  Pseudoglandular stage
¡  Canalicular stage
¡  Sacular and Alveolar stages
EMBRYONIC PERIOD

¡  2-7 weeks
¡  Appears as ventral bud to esophagus ~26 days
¡  Branches into two lungs at 33 days
¡  Lobar airways formed at 37 days
¡  Segmental airways at 42 days and subsegmental bronchi by 48 days

¡  Factors: Thyroid transcription factor-1, FGF-7, FGF-10, EGF. Fibronectin, Laminin, Collagen IV, PDGF.
PSEUDOGLANDULAR STAGE

¡  5-18 weeks
¡  15-20 generation of airway branching
¡  Epithelial development
¡  Growth of pulmonary vasculature
CANALICULAR STAGE

¡  16-25 weeks
¡  Previable lung Potentially viable lung
¡  Formation of acinus, Development of potential air-blood barrier, beginning of surfactant synthesis
SACCULAR AND ALVEOLAR STAGES

¡  24 weeks – term
¡  Further development of terminal sac
¡  Alveolarization ~32 weeks (at term 50-150 mln, continue to form well into adulthood)
MODULATORS OF ALVEOLARIZATION

¡  Negative effect
¡  Mechanical ventilation
¡  Ante- and postnatal corticosteroids
¡  Pro-inflammatory mediators
¡  Chorioamnionitis
¡  Hyperoxia or hypoxia
¡  Poor nutrition
¡  Positive
¡  Retinoids
¡  Thyroxin
FETAL LUNG FLUID

¡  Volume at term ~ 40 ml/kg

¡  Contains little protein
¡  Formation – active transport of Cl from interstitium into lumen
¡  Production rate 4-5 ml/kg/hr ~400 ml/day at term
¡  Some outflow into esophagus and some into amniotic fluid
¡  Both production and clearance important for lung development
PROTEINS OF SURFACTANT

¡  SP-A:
¡  Forms multimeric protein
¡  Serves as innate host defense protein and regulates inflammation
¡  Binds to pathogens, facilitates phagocytosis
SP-B:
§  Contained in lamellar bodies
§  Facilitates absorption of surface lipids and development of low surface tension

SP-C:
§  Associated with lipids in lamellar bodies
§  Deficiency Interstitial lung disease

SP-D:
§  Host defense molecule
§  Binds pathogens and facilitates their elimination
PRODUCTION OF SURFACTANT

¡  Type II cells
¡  Glucose, Ph, fatty acids – substrates for synthesis
¡  Lipoprotein complex condensed in lamellar bodies
¡  Stimulators of secretion:
¡  β-agonists
¡  ATP
¡  Mechanical stretch
SURFACTANT POOLS

¡  Term infant – 100 mg/kg. Preterm infants 5-10 mg/kg

¡  Infants with RDS normalize their surfactant pool by 4-5 days of life
¡  Secretion of surfactant takes longer than synthesis
¡  Half life of surfactant – few days
¡  90% of phospholipids are recycled in neonates (Adults ~50%)
SURFACTANT POOLS AFTER EXOGENOUS ADMINISTRATION

¡  Increases both alveolar and tissue pools

¡  Function of administered surfactant improves within hours (transformation by lung)
¡  No feedback inhibition of native surfactant production
¡  Slow catabolic rate
SURFACTANT IN ALVEOLI

¡  Lamellar bodies Tubular myelin(reserve pool)

¡  New surfactant is squeezed out of this structure
¡  Old surfactant forms small vesicles that are cleared from airways
¡