lung-embryology-review by xiuliliaofz

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									You’re Only An
Embryo Once
Review of Development of the
     Respiratory System
                  Embryonic Stage
                  22 days to 6 weeks
   Day 22: Formation of a ventral outpouching from the
    endodermal foregut—respiratory diverticulum
       Grows ventrocaudally through mesenchyme around the
   Days 26-28: First bifurcation—primary bronchial
    buds which give rise to the right and left lungs
       Proximal end of diverticulum forms the trachea and larynx
       Glottis forms at the original point of the diverticulum
               Embryonic Stage
               22 days to 6 weeks
   5th week: First round of branching
     Highly stereotypical: 3 secondary bronchial buds
      on right, 2 on left
     Secondary bronchial buds give rise to the lung lobes
             Pseudoglandular Stage
                 6 to 16 weeks
   During 6th week: more variable round of
    branching leading to 10 tertiary bronchi
       Tertiary bronchi become the bronchopulmonary
   By week 16: 14 successive branchings have
    occurred producing the terminal bronchioles
                 Canalicular Stage
                  16 to 28 weeks
   Each terminal bronchiole divides into 2 or more
    respiratory bronchioles
   These branches progress in a craniocaudal direction
   Mesodermal tissue surrounding these structures
    become highly vascularized, presumably via angiogenesis
   Blood vessels begin to come closely apposed to lung
   Lung epithelium begins to differentiate into
    specialized cell types
                  Saccular Stage
                  28 to 36 weeks
   By week 36, the first formed terminal branches
    are invested in a rich capillary network forming
    terminal sacs or primitive alveoli
     Only about 5% to 20% of all terminal sacs are
      formed before birth
     Terminal sacs continue to be formed well into
     Form and differentiate in craniocaudal progression

     Process mostly complete by age 2 years
             Alveolar Stage
     36 weeks to Term (and beyond)
   Continued maturation of terminal sacs into
    mature alveoli
     Septation is the process in which alveoli are further
      subdivided occurs after birth
     About 20 to 70 million terminal sacs in each lung
      before birth, 300 to 400 million alveoli in each
      mature lung
     Each septum contains smooth muscle and capillaries
         Additional Considerations
   Lung a composite of endodermal and
    mesodermal tissues
       Implications for inflammation, repair, and neoplasia
          Clinical Correlation
      Developmental Abnormalities
   Pulmonary hypoplasia or agenesis
   Tracheoesophageal fistula and esophageal atresia
   Foregut cysts
   Pulmonary sequestrations
             Clinical Correlation
Neonatal Respiratory Distress Syndrome
   Immaturity of the lungs
   Deficiency of pulmonary surfactant
                    Research Issues
Approaches for Studying Lung Development
   Organ Culture
   Transgenic and Gene-Targeting Techniques
       Engineered loss-of-function mutations (knock-outs) and
        gain-of-function transgene mutations
       Identification of important transcription factors
       Models of human pulmonary disease
   Molecular and Cellular Models
       Demonstrate that branching morphogenesis is regulated by
        reciprocal interaction between the endoderm and mesoderm
       Components of ECM and growth factors and their receptors
       Expression in cell-specific and time-specific contexts
       Genes regulating differentiation of specialized cell types

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