Development of the Respiratory System PDF

Development of the respiratory system MD3001 September 2023 Dr. Alex Gardner [email protected] Learning outcomes By the end of this lecture, time spent in the dissecting room, and further private study you should be able to: • • • • Describe the embryonic development of the trachea and bron...

Development of the respiratory system MD3001 September 2023 Dr. Alex Gardner [email protected] Learning outcomes By the end of this lecture, time spent in the dissecting room, and further private study you should be able to: • • • • Describe the embryonic development of the trachea and bronchi Describe the embryonic development of the lungs and pleura Describe the embryonic development of the diaphragm Be able to discuss the congenital abnormalities that may affect the respiratory system and diaphragm MD3001 2023 2 Sources/recommended reading Chapters 7 and 14 https://meded.lwwhealthlibrary.com/multimediaplayer.aspx?MultimediaID=19450544 MD3001 2023 3 Revision – fertilisation to implantation • All humans start as two cells, that form a zygote • This undergoes divisions and implants into the mothers uterus Zygote Morula (Day 3) Blastocyst MD3001 2023 4 Revision – fertilisation to implantation • Implantation occurs by days 7-9 • Two layers of cells form from the inner cell mass – epiblast and hypoblast Inner cell mass Amniotic cavity Blastocoele Day 6 MD3001 2023 Epiblast Day 9 Hypoblast 5 Germ layers - gastrulation • A three-layer (trilaminar) disc forms • All three layers derive from the epiblast via a process termed gastrulation (day 17) • The three layers are ectoderm, mesoderm and endoderm • These three “germ layers” subsequently develop into all tissues of the body MD3001 2023 6 Germ layer derivatives • Young & Black 2004 Somites! MD3001 2023 7 Development of body cavities • The mesoderm develops into distinct parts, termed paraxial, intermediate and lateral plate mesoderm • Lateral plate mesoderm is divided into parietal and visceral layer by the development of intra embryonic coelom • Parietal layer forms the body walls • Visceral layer forms connective tissue of respiratory systems MD3001 2023 8 Development of body cavities • The mesoderm develops into distinct parts, termed paraxial, intermediate and lateral plate mesoderm • Lateral plate mesoderm is divided into parietal (somatic) and visceral(splanchnic) layers by the development of intra embryonic coelom MD3001 2023 9 Development of body cavities • The mesoderm develops into distinct parts, termed paraxial, intermediate and lateral plate mesoderm • Lateral plate mesoderm is divided into parietal (somatic) and visceral(splanchnic) layers by the development of intra embryonic coelom • Intra embryonic coelom forms a “horseshoe” shape around the developing head MD3001 2023 10 Development of body cavities • The embryonic “disc” folds in two planes – cranio-caudally and laterally • Lateral folding causes closing of the body walls and “entrapment” of intraembryonic coelom into a closed body cavity • Cavity lined by somatic LP mesoderm, gut tube/mesentery by visceral LP mesoderm MD3001 2023 11 Development of body cavities • The embryonic “disc” folds in two planes – cranio-caudally and laterally • Lateral folding causes closing of the body walls and “entrapment” of intraembryonic coelom into a closed body cavity • Cavity lined by somatic LP mesoderm, gut tube/mesentery by visceral LP mesoderm MD3001 2023 12 Development of body cavities • The embryonic “disc” folds in two planes – cranio-caudally and laterally • causes the developing heart, septum transversum and associated intra-embryonic coelom to move caudally • N.B. folding in both dimensions occurs concurrently Day 21 Day 25 MD3001 2023 13 Development of body cavities • The continuous primitive body cavities must then undergo partitioning • Lungs buds invaginate into pericardioperitoneal canals forming pleural cavities and pleuropericardial folds (a ridge of mesenchyme = embryonic connective tissue) separate the pericardial and pleural cavities • pleuropericardial folds form fibrous pericardium Day 28 MD3001 2023 ~5 weeks 14 Development of body cavities - diaphragm • The diaphragm forms to separate thoracic and abdominopelvic cavities • Pleuroperitoneal membranes grow medially • Fuse with mesentery of oesophagus (forms crura of diaphragm) • Continue growth, over septum transversum MD3001 2023 15 Development of body cavities - diaphragm • Fused area = central tendon of diaphragm • Peripherally, a CT scaffold with migrating myoblasts (C3,4,5 somites) • Phrenic nerve accompanies • Composed of septum transversum, pleuroperitoneal membranes, mesentery of oesophagus and the body wall (myoblasts) MD3001 2023 16 Development of lungs • Day 28 – respiratory diverticulum (lung bud) develops • It is an outpouching of the foregut – thus endoderm and visceral LP mesoderm origin MD3001 2023 17 Development of lungs • Day 28 – respiratory diverticulum (lung bud) develops • It is an outpouching of the foregut – thus endoderm and visceral LP mesoderm origin • Tracheoesophageal ridges fuse to form tracheoesophageal septum • Formation of trachea and primary bronchial buds MD3001 2023 18 Development of lungs • Day 28 – respiratory diverticulum (lung bud) develops • It is an outpouching of the foregut – thus endoderm and visceral LP mesoderm origin • Tracheoesophageal ridges fuse to form tracheoesophageal septum • Separating the trachea and oesophagus – maintains communication via laryngeal orifice MD3001 2023 19 Development of larynx • Pharyngeal arches 4 and 6 contribute to larynx • Each arch has a mesenchymal core with neural crest cells (giving rise to a cartilage), ectoderm outer layer and endoderm inner layer • Each arch is associated with a cranial nerve Arch CN 1 5 2 7 3 9 4 10 6 10 MD3001 2023 20 Development of larynx • Internal epithelium of larynx is from endoderm • Laryngeal muscles and cartilages come from fusing of mesenchyme from arches 4 and 6 MD3001 2023 21 Lung development 5 weeks 6 weeks 8 weeks • Primary bronchial buds undergo divisions – lobar, and bronchopulmonary segments • Rapidly filling pericardioperitoneal canals MD3001 2023 22 Lung development • Generational divisions to create bronchial tree • Four phases of lung development • ~week 24 is the earliest a baby can be born prematurely and survive – lung development is a major factor in survival • Development continues after birth (6 more generations, tripling number of alveoli) MD3001 2023 Pseudoglandular period 5–16 weeks Canalicular period 16–26 weeks Saccular period 26 week to birth Alveolar period 8 months to childhood (8 years) 23 Lung development • Phase 1 – Pseudoglandular • Weeks 5-16 • Branching up to terminal bronchioles (no respiratory bronchioles or alveoli) MD3001 2023 24 Lung development • Phase 2 – canalicular, week 1626 – form primitive alveoli with cuboidal epithelium, capillaries also developing • Phase 3 – saccular stage, week 26 – birth, increased alveoli and respiratory bronchioles and capillaries, epithelial changes, formation of type 1 and 2 pneumocytes, surfactant production MD3001 2023 25 Lung development • Phase 4 – alveolar phase – birth to 8 years – increased numbers of alveoli, divisions/partitions within alveoli increasing surface area MD3001 2023 26 Congenital abnormalities Congenital diaphragmatic hernia • 1 in 2000 births • Postero-lateral (Bochdalek) ~95% of cases • Parasternal (Morgagni) 2% of cases • Abdominal organs can enter thoracic cavity, preventing lungs from developing fully • Intervention possible, fetoscopic endoluminal tracheal occlusion https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940711/ MD3001 2023 27 Congenital abnormalities Congenital diaphragmatic hernia • 1 in 2000 births • Postero-lateral (Bochdalek) ~95% of cases • Parasternal (Morgagni) 2% of cases • Abdominal organs can enter thoracic cavity, preventing lungs from developing fully • Intervention possible, fetoscopic endoluminal tracheal occlusion https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940711/ MD3001 2023 28 Congenital abnormalities Oesophageal atresia and tracheoesophageal fistula • 1 in 3000 births, defect in partitioning of tracheoesophageal septum • May be diagnosed in utero (excess amniotic fluid) • Surgical correction after birth • May accompany other defects: – VACTERL association (Vertebral anomalies, Anal atresia, Cardiac defects, Tracheoesophageal fistula, Esophageal atresia, Renal anomalies, and Limb defects MD3001 2023 4% 4% 90% 1% 1% 29 Congenital abnormalities Respiratory distress syndrome • Premature birth, insufficient surfactant • Alveoli are therefore in a collapsed state • 20% of newborn mortality • Managed by artificial surfactant or giving mother glucocorticoids to stimulate surfactant Congenital pulmonary airway malformation • 1 in 30,000 births • A lobe is replaced by non functional cystic tissue • Often asymptomatic (75%), surgical excision after birth Supernumerary lobules Ectopic lobules MD3001 2023 30 SBA style q • Development of the lower respiratory tract in several stages. What is the first stage of this process? • Canalicular • Pseudoglandular • Alveolar • Saccular • Glandular 31 SBA style q • The final stage of lung development involves Divisions of the alveoli, which continues after birth. Until what age does this process occur? • 6 months • 1 year • 16 years • 8 years • 40 years 32