1. Respiratory System Foregut- 3 parts First part- primitive pharynx Second part- lung bud & esophagus Third part- Stomach.

3. Development of respiratory System Begins in the 4 th Wk of Intrauterine Period. The Endoderm give rise to Epithelium and Glands Along the respiratory Tract. The Mesoderm (Splanchic) give rise to Cartilages, Connective Tissue and Smooth muscle. Steps: 1.Appearance of Laryngotracheal Diverticulum (Lung Bud) appears Anterior to Foregut. This is Common to both developing Trachea and Pharynx. 2. Enlargement of Laryngotracheal Diverticulum to form Respiratory Bud. 3.Appearance of Laryngotracheal Septum to Separate the Diverticulum to Anterior Laryngotracheal Tube and a Posterior Primordium of Oropharynx.

4. Formation of the Lung bud

5. Trachea & Bronchi Tracheoesophageal Septum Separates from the esophagus Lung bud –forms trachea & right & left bronchial buds week5 Each bronchial bud expands & form right & left main bronchi Secondary bronchi- Asymmetric branching forms the lobes of the lung Week 4 Week 5

6. 4.Formation of Primary Bronchial Buds: by division of Laryngotracheal Diverticulum by 5 th WK. 5. Formation of Secondary Bronchial Buds. They divide as Left into Two lobes and Right into three corresponding to number of lobes in each lung. 6. Appearance of Segmental Bronchi; 10 in right and 8 in Left Lungs. The Segmental Bronchi give rise to Bronchopulmonary Segments. This give rise to respiratory bronchioles. By 24 th WK; 17 order of division occur and Additional 7 order of division occur after birth. Formation of the Lung bud

7. Main division of bronchial tree (week 7) - Each Secondary Bronchus Undergoes Progressive Branching & form Tertiary Bronchi & The Broncho-pulmonary Segments, 10 in the Right & 8 in the Left lung -By The End Of 6 th Month- Respiratory Bronchioles have developed -An Additional 7-Order Division of Respiratory Bronchioles form after birth. 1. Right upper lobe 2. Left upper lobe 3. Right lower lobe 4. Left lower lobe 5. Right middle lobe 6. Splanchnic mesoderm 7. Bronchial buds 8. Visceral pleura

8. Formation of pleural cavity 1. Lung bud 2. Heart 3. Common cardinal vein 4. Aorta 5. Pleuropericardial membran 6. Pericardial cavity

9. Serous membrane of the lungs The lungs acquire a layer of Visceral Pleura from the Splanchnic Mesenchyme. The thoracic body wall becomes lined by a layer of Parietal Pleura derived from the Somatic Mesoderm. Pleural cavity: space between Visceral And Parietal Pleura

10. Development of the lungs (4 stages) Pseudo-glandular Stage (5-16 wk): Looks like Glandular Tissue. Repeated branching (14 times) to the level of terminal bronchioles Canalicular Stage (16-26 wk): respiratory bronchioles develop. Saccular stage (26wk-birth): terminal sacs (primary alveoli) form Alveolar stage (8 month): alveoli mature a) type I & II pneumocytes differentiate b) production of Surfactant

11. Pseudo-glandular Stage (5-16 wk): The Developing Lungs resemble an Exocrine Gland in structure (tubulo- acinous gland). All Elementary parts start to appear. Bronchial tree has undergone 16-20 order of division 1.Mesenchme Tissue 2.Alveolar Type II Cell begin to appear. 3.Capillary Appear. The developing broncho-pulmonary epithelium begins to produce amniotic fluid, which is also found in the lungs up to the time of birth.

12. Canalicular Stage (16-26 wk): In this phase the canaliculi branch out of the terminal bronchioli. All of the air spaces that derive from a terminal bronchiolus form an acinus. Each Acinus comprises respiratory bronchiole and the alveolar ducts and later the alveolar sacculi. The chief characteristic of this canalicular phase is the Alteratin Of The Epithelium and the surrounding Mesenchyma. Along the acinus, which develops from the terminal bronchiolus, an Invasion Of Capillaries into the mesenchyma occurs. The capillaries surround the acini and thus form the foundation for the later exchange of gases. The lumen of the tubules becomes wider and a part of the epithelial cells get to be flatter.The Type I Pneumocytes Differentiate Out Of The Type II Pneumocytes.

13. Canalicular Stage (16-26 wk):

14. Saccular stage (26wk-birth): Sacs form on the Terminal Bronchioli Terminal sacs (primary alveoli) form. Lining epithelium becomes Flat (Squamous) and Capillaries Appear and get Closer to Alveoli. Mainly Alveolar Type 1 Cells, Less Alveolar type 2 cells

15. Saccular Phase 1.Type I Alveolar Cell 2.Saccular Space. 3.Type II Alveolar Cell. 4.Basal Membrane of Air Passage. 5.Basal Membrane of Capillary

16. Saccular Stage (26 wk- birth)

17. Alveolar stage (8 month) Alveoli mature. More Type I & II Pneumocytes Differentiate. Production of Surfactant Begins. Alveolar Ducts Appear. Transformation of Lungs from Secretory structure into Gases Exchange Structure. Establishment of Parallel Pulmonary and Systemic Circulations.

18. Final Stage 95% of mature Alveoli complete Development Postnatally. Mainly Completed by 3-years and terminal by age 8 years. Water drinking (Amniotic Fluid) Occur during Final stages (Alveolar) Training Purposes. Hence Oligohydamnios can cause retarded lung development. Alveolar Type 2 Cells develop during Last Few WKS And Continue After Birth. Hence Premature Babies may Suffer from Respiratory Distress Syndrome

19. Lung Development

20. Developmental Overview Week 4 - laryngotracheal groove forms on the ventral aspect of the foregut. Week 5 - left and right lung buds push into the pericardioperitoneal canals (primordia of pleural cavity) Week 6 - descent of heart and lungs into thorax. Pleuroperitoneal foramen closes. Week 7 - enlargement of liver stops descent of heart and lungs. Month 3-6 - lungs appear glandular, end month 6 alveolar cells type 2 appear and begin to secrete surfactant. Month 7 - respiratory bronchioles proliferate and end in alveolar ducts and sacs.

21. Clinical Implications Tracheoesophageal fistula (TEF) A fistula may exist connecting trachea and esophagus and resulting in abnormal communication between the 2. The fistula is usually associated with superior Esophageal Atresia. In a newborn infant, this is associated with Coughing And Choking Upon Swallowing. Gastric contents may reflux into the trachea and lungs resulting in pneumonia or pneumonitis (inflammation of the lungs). Respiratory Distress Syndrome (RDS): Surfactant Deficiency

22. Tracheo-esophageal Fistula/ Esophageal Atresia