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  1. LUNG DEVELOPMENT Dr Anjana A Junior Resident Dept of Pulmonary Medicine
  2. Introduction • Development of the lung can be divided into two phases, lung growth (structural development)and lung maturation (functional development) • As gestation progresses, progressive branching of the airways and finally development of alveolar spaces capable of gas exchange in the last trimester • The surfactant system, composed of phospholipids that decrease surfacetension within the alveoli and prevent alveolar collapse during exhalation, develops in the last trimester,and reaches maturity by approximately 36 weeks • Lung development continuous even after birth. • The alveoli develop in increasing numbers until the age of 8 years and increase in size until growth of the chest wall is finished.
  3. • The full-term infant, with an estimated 50 million alveoli, has the potential to add another 250 million alveoli and increase its total alveolar surface area from approximately 3 to 70 m2 at maturity. • Lung buds are lined by endodermally derived epithelium which differentiates into respiratory epithelium that lines the airways and specialized epithelium that lines the alveoli. • The innervation of the lungs is derived from ectoderm, while the mesoderm is the origin of pulmonary blood vessels, smooth muscle, cartilage and other connective tissue.
  4. PHASES OF LUNG DEVELOPMENT • Embryonal Phase • Pseudoglandular Phase • Canalicular Phase • Saccular Phase • Alveolar Phase
  5. EMBRYONAL PHASE(3-6 weeks) • It starts by formation of a groove in the ventral lower phaynx- Sulcus laryngotrachealis (28 days) • The lung begins to emerge as a bud from this goove called the true lung primordium (30 days)which elongates and forms trachea and subdivides into two bronchial buds (33days) , which then separates from the esophagus forming a tracheoesophageal septum. • The right lung bud is directed caudally and left lung bud more laterally. • Further division leads to formation of 3 buds on right and 2 on left. They correspond to pulmonary lobes. • By the end of embryonic phase, segments arise. • Development progresses in the 8 week old embryo as the lobar buds
  6. • The left and right pulmonary artery and vein develops at about 5 weeks of gestation • The respiratory epithelium is developed from endoderm referred as foregut bud. • The diaphragm also develop during the embryonal stage of lung development. Complete development of diaphragm occurs by approx. week 7 of gestation.
  7. Pseudoglandular Phase(5-16 weeks) • Named after the distinct glandular appearance of the developing lung, extends to week 16 of gestation. • Air conducting bronchial tree till the terminal bronchiole is set down(16 gen) • Distal strutures are the terminal bronchioles, which later differentiate into respiratory bronchioles and alveolar ducts. • Once pattern is laid, the subsequent growth of airways is in size only. • Differenciation of lung epithelium begins. • Transition from formation of bronchial epithelial cells (ciliated columnar and goblet cells) to alveolar type II cells.
  8. STRUCTURE DEVELOPMENT GESTATIONAL AGE Cilia appears on surface of epithelium of the trachea and the mainstem bronchi 13 weeks Goblet cells appears 13 -14weeks Submucosal glands arises as solid buds from basal layer of epithelium 15-16 weeks The development of cartilage 10-24 weeks Lymphatics appear 8-10weeks
  9. Canalicular phase( 15-25 weeks) • The canalization of the mesenchyme by respiratory airways and capillaries. • Gas exchanging portion of the lung is formed and vascularised. • Each terminal bronchiole divides into 2 or more respiratory bronchioles- divide into 3-6 alveolar ducts. • Remarkable changes in airway epithelium and surounding mesenchyme. • By 20 weeks, differentiation of the cubic type II pneumocyte into flattened type I pneumocytes occur. • Along the acinus in close proximity- invasion of capillaries into mesenchyme- future gas exchange. • Appearance of lamellar bodies in type II pneumocytes-surfactant storage.
  10. Saccular phase(24 weeks to term) • Lung epithelium produces maximum amniotic fluid. • Type II pneumocytes start to secrete surfactant. • Clusters of sacs form on the terminal bronchioli. Last generation of airspaces appear. • At birth, these airspaces are called primitive saccule. • Smooth walled sacculi form at the end of airway lined by type I and II pneumocytes. • Primary septa between the sacculi are thick and contain two network of capillaries. • Substantial thinning of the interstitium occurs( apoptosis and ongoing differentiation of mesenchymal cells)
  11. • the interstitial fibroblasts begin the production of ECM in the interductal and intersaccular space. • At the end of saccular stage, the lung parenchyma possesses thick, immature septa that contain a double-layered capillary network.
  12. Alveolar phase(late fetal period to childhood) • Begin in the last few weeks of pregnancy. • The saccules continue to mature following birth. • The first alveoli are formed from new sacculi. • Saccules doenot acieve adult configuration until 5 weeks after birth. • Functioning alveoli- connected to alveolar duct , lined by type I cells, intimately in contact with pulmonary capillaries.,contain surfactant, have pores of Kuhn connecting to adjacent alveoli • Almost 1/3 of the roughly 300 million alveoli are completely developed at birth. • By the age of 8, complete dvelopment of 300 million alveoli occurs.
  13. • Lymphatic network is well developed . • Before birth the alveolar sacculi become increasingly complex structurally. A large number of small protrusions form along the primary septa. • These become larger and subdivide the sacculi into smaller subunits, the alveoli, which are delimited by secondary septa. • Formation of new septa within terminal sacs is the mainstep for differentiation of the terminal saccule into alveoli( Alveolarization)
  14. Lung Stage Weeks Features Vascular Embryonic week 4 to 5 lung buds originate as an outgrowth from the ventral wall of the foregut where lobar division occurs extra pulmonary artery then lobular artery Pseudoglandular week 5 to 17 Branching has continue form terminal bronchioles. No respiratory bronchioles oralveoli are present. Pre-acinar arteries Canalicular week 16 to 25 Each terminal bronchiole divides into2 or more repiratory bronchioles, which in turn divideinti 3-6 alveolar ducts. Intra-acinar arteries Saccular week 24 to 40 Terminal sacs (primitive alveoli) form,and capillaries etablish close contact alveolar duct arteries Alveolar late fetal to 8 years secondary septation occurs, alveoli increase in size and number. mature alveoli have well developed capillary contacts. alveolar capillaries
  15. VASCULAR SYSTEM • At about 32 days pulmonary trunk appears from truncus arteriosus. • Pulmonary arteries -6th left aortic arch.This joins the vascular system that has already formed in the lung bud. Its branches divide in correspondence with those of the bronchial tree. • Supernumerary arteries occur with increasing frequency towards the periphery and supply structures adjacent to the main bronchi and neighbouring acini.
  16. • Majority of periacinar branches are formed by 16 th week • 12 wks –conventional and supernumerary branches in the same proportion • Post natally-upto 18 months, conventional branches increase • Then supernumerary branches increase till 8 yrs
  17. Pulmonary vein • in the embryonic period pulmonary venous blood drains via the splanchnic plexus in to the primordia of the systemic venous system(cardinal and umbilico vitelline veins) • Pulmonary vein develops from the cranial out pouching of the sinoatrial region of heart

Notas do Editor

  1. Decrease in interstitial tissue and thinning of airspace walls. hosphatidylinositol (v phosphatidyl choline and phosphatidyl glycerol in late gestation)