1. Development of the Respiratory System Dr. Pat McLaughlin Professor, Department of Neural & Behavioral Sciences X6414, C3727 pxm9@psu.edu

2. Learning Objectives To understand the concepts associated with development of the respiratory system To understand the structural development of the major components: lungs, trachea, bronchi, larynx To understand how and why abnormalities resolve when development is incomplete and/or incorrect

3. Upper respiratory system: nose, nasopharnyx, and oropharynx Lower respiratory system: larynx, trachea, bronchi, lungs Formation begins in 4 th week Outgrowth of ventral wall of primitive foregut Endodermal origin Mesodermal derivation - Parts of trachea and lungs are derived from splanchnic mesoderm

4. Key structures Laryngotracheal groove Respiratory diverticulum Lung bud Tracheoesophageal folds Laryngotracheal tube Dorsal esophagus

5. Larynx Laryngotracheal diverticulum T-shaped glottis Thyroid, cricoid, arytenoid cartilages Vocal cords – Folds and recesses

6. Trachea Respiratory diverticulum C-shaped cartilage – open posteriorly (dorsal) Derived from endoderm and splanchnic mesoderm (smooth muscle, CT, cartilage rings)

7. Bronchi Lung divides into 2 bronchial buds Form primary bronchi Right 1 o bronchus is larger, more vertical than Left 1 o bronchus Right bronchus has 3 secondary bronchi - Superior, middle, inferior Left bronchus has 2 secondary bronchi – Superior, inferior

8. Lungs 4 periods of lung development Embryonic stage (weeks 4-6) Formation of the respiratory diverticulum and formation of major bronchopulmonary segments. Lungs begin to grow and fill pleural cavities in a bilateral fashion. Pseudoglandular (5-16 weeks) Involves major growth phase of the duct system. Lung branches into endodermal tubules with comprise the air conducting system - NO gas exchange - NO respiration - NO survival if birth occurs Canalicular (16-26 weeks) Formation of respiratory bronchioles, resulting from budding of the terminal parts. Also growth of blood vessels into the lungs. Respiratory bronchioles and terminal sacs (primitive alveoli) develop. Birth before 20 weeks - rarely survive Terminal sac period (26 weeks - birth) Alveoli develop as terminal sacs – and bud off from Increase in number of terminal sacs and vascularization

9. Lung Development Type I cells, predominant, blood-lymph capillary interaction Type II cells, secrete surfactant Growth of lungs is due to increase in number of respiratory bronchioles and alveoli, not increase in size Growth continues for up to 10 yr postnatally

10. Membranes Lungs are resting in the pericardioperitoneal canals which narrow as the lungs grow. Pleuroperitoneal folds and pleuropericardial folds separate the pericardioperitoneal canals from the peritoneal and pericardial cavities, respectively. Remaining space forms the primitive pleural cavities. Membrane that covers the outside of lung is visceral pleura. Somatic mesoderm that covers the body wall from the inside is the parietal pleura and the space in between is the pleural cavity. Diaphragm is formed from the following components: Septum transversum (grows dorsally from body wall to separate liver + heart) Pleuroperitoneal membranes Dorsal mesentery of esophagus (middle portion) Lateral body walls

11. Clinical Defects Esophageal atresia Tracheoesophageal fistulas Respiratory distress syndrome Hyaline membrane disease Oligohydramnios