1) Review of Mature Anatomy - Lungs!- Right lung: 3 lobes- superior, middle, lower!- Left lung: 2 lobes- upper and lower, L lung has to make room for heart, lingula (tongue) of the L upper lobe in the analogue of R middle lobe!- Ventilation: movement of air thru conducting system!- Respiration: exchange of gas across membrane!- Components of respiratory system!- conducting zone: larynx, trachea, bronci, bronchioles, terminal bronchioles!- respiratory zone: respiratory bronchioles, alveolar ducts and sacs, alveoil!- bronchoiles don't have cartilage, smooth m. absent at levels of alveoli (becomes progressively thinner)!- dense network of capillaries and alveoli!- clinicians: alveolus= terminal respiratory unit of the scientist!- alveolar ducts and 2,000 alveoli, approx. 5 mm in diameter !- Respiratory membrane (lining of alveoli)!- Type I cells (pneumocytes): 90% of alveolar surface, fused basement membrane w/capillaries, thin walled!- Type II cells (pneumocytes): secrete surfactant (a complex phospholipid) that decreases surface tension preventing the collapse of the alveolus, reduces effort of ventilation, less air needed to maintain voume 2) Development of the lung--Stages of lung development - dev. of the resp. systems begins on Day 22, ends in childhood (about age 8) , dev. lof trachea and lungs!- no clear dividing line between eacch stage!- story of branching and re-branching over 23 generations!- part of the organogenetic period in weeks 4-8: folding and growth of the embryo also occurs a. Embryonic stage: Day 26- Wk. 6!- Primordia of both lungs and lobes!- 3 branchings (first bifurcation Day 26)!- Day 22:!- lung bud forms, arises from endoderm of foregut!- respiratory diverticulum= lung bud!- grows into surrounding mesochyme!- Tracheoesophageal fold begins partitioning (pinching in) of foregut into esophagus and laryngotracheal tube!- Day 22-26: Respiratory diverticulum grows ventrocaudally, surrounded by mesochyme !- Week 4: !- pharyngeal appparatus and respiratory system!- primordial pharynx and laryngotracheal groove!- larynx develops below 4th pharyngeal arch: sulcus epithelium from endoderm, muscles from mesoderm of arches 4 and 6--> innervated by vagus nerve, laryngeal cartilages derived from mesoderm of 4 and 6!- Day 26:!- First bifurcation!- Stem begins to separate from pharynx (esophagus)!- proximal stem forms the trachea and larynx!- formation of trachea may be indep. of formation of proximal bronchia buds!- Week 5:!- primary bronchi branch early !- right 3 secondary bronchial buds: upper, middle, and inferior!- left 2 secondary bronchial buds: superior and inferior!- Week 6:!- further branching:!- 10 tertiary bronchi per side!- bronchopulmonary segments --> will become !segments of the mature lung! b. Pseudoglandular stage: Weeks 6-16 - Lung looks like a gland on histology!- 14 branchings to terminal bronchioles (dev. of lower !conducting airways to terminal bronchioles)!- Lower conduction system!- Airways differentiate!- Mucous glands develop!- Smooth muscle!- Connective tissue!- Epithelial-mesenchymal induction occurs: complex, large # of factors involved incl. various growth factors, txn factors!- cartilage begins to develop in mesenchyme (middle ring), outer ring is embryonic CT!- Week 12:!- laryngotracheal tube: further differentiation--> epithelium and glands, CT, muscle, cartilage !- Lungs expand into splanchnic mesenchyme adjacent to walls of primordial pleural cavities!- Pleural/pericardioperitoneal channels: lungs grow here, the channels enlarge as the lungs enlarge !! c. Canalicular stage (canals): Weeks 16-26 - 3 divisions!- Respiratory vasculature!- Respiratory bronchioles developing!- Beginning of relationship between capillaries and terminal respiratory units!- Last few generations of airways added!- Angiogenesis:!- Proliferation of microvasculature -- pericanicular network!- Cells sep. by only 1 basement membrane (formation of blood-air barrier, governing not understood)!- Heart developing during this time!- Pulmonary arches branch off from 6th aortic arteries and descend to newly formed lung buds.!- R 6th arch --> right pulmonary artery!- L 6th arch --> pulmonary trunk!- pulmonary veins develop as an evangination in sinoatrial part of heart!- Cell specialization!- Ciliated!- Secretory !- Alveolar precursor cells!- Type 1: alveolar wall!- Type 2: Surfactant production!! d. Saccular/Terminal sac stage: 26 weeks -> birth!- Last divisions!- Alveolar ducts!- Terminal sacs (primitive alveoli)!- some gas exchange possible!- 20-70 million sacs ante-partum!- process continues post-partum!- at birth, you have 1/6th of your adult alveoli!- Lung gets aerated appearance!- But at birth, lungs are still filled w/fluid (a newborn's lungs will sink if placed in water)!- Distal airways expand!- Interstitial space decreases!- Dense capillary network forms!- Surfactant production!- Type 2 cells begin making surfactant--prior to this infant won't be able to survive!- increases chance of survival if born prematurely!- Elastin deposition!- imp. for alveolar formation! e. Alveolar stage: Begins Week 28-32/8 months (in utero)--> childhood - Continues after birth, not a clear transition from saccular to alveolar!- Epithelium thins!- Septation!- Capillary nets fuse!- Doubling of the capillary net!- 300-400 M alveoli!- Distal airways expand 3) Development of the diaphragm - Diaphragm is composed of 4 things:!1) Septum transversum!2) Plueroperitoneal membranes!3) Body wall mesoderm!4) Esophageal mesenchyme!- Folding produces intraembryonic coelom!- dorsal mesentery and ventral mesentary!- most of ventral mesentary disappears!- dorsal mesocardium and ventral mesocardium!- Septum transversum- gets lower and lower as the embryo grows up and forward!- develops from ventral body wall as semicircular shelf!- partially separates primitive pericardial and peritoneal portions of coelom!- Pleural or pericardioperitoneal channels/cannals!- lungs grow here!- enlarge as the lungs enlarge!- close to complete the diaphragm!- Pleuroperitoneal folds are closing at the caudal end --> gives us 2 cavities!- become prominent as expanding lungs push into mesoderm of the body!- wall fuses w/spetum transversum and mesentary of the esophagus!- 2 cavities: pericardial and pleural cavities!- Week 5: - arrows indicate communications between pericardioperitoneal canals and pericardial cavity!- Week 6: - arrows indicate development of the pleural cavities as they expand into the body wall!-
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