Embryonic Development of the Respiratory System PDF

Embryonic development of the respiratory system Histology-Embryology II Katerina Menelaou, Ph.D. Lecturer, Histology-Embryology [email protected] Lecture outline Overview of the respiratory system Respiratory diverticulum Normal and abnormal development of...

Embryonic development of the respiratory system Histology-Embryology II Katerina Menelaou, Ph.D. Lecturer, Histology-Embryology [email protected] Lecture outline Overview of the respiratory system Respiratory diverticulum Normal and abnormal development of the respiratory tract Nasal cavity Pharynx Larynx Trachea Bronchi Lungs Lecture outline Overview of the respiratory system Respiratory diverticulum Normal and abnormal development of the respiratory tract Nasal cavity Pharynx Larynx Trachea Bronchi Lungs  Overview of the respiratory system Main functions: Respiration Smell Filtration/defense Sound & speech production Eliminate waste (e.g. gases) (Wakim & Grewal, 2022) Lecture outline Overview of the respiratory system Respiratory diverticulum Normal and abnormal development of the respiratory tract Nasal cavity Pharynx Larynx Trachea Bronchi Lungs Development of the respiratory system Begin to form in week 4 of development Laryngotracheal groove: Appears in the floor of the caudal end of the primordial pharynx The primordium of the tracheobronchial tree develops caudal to the fourth pair of pharyngeal pouches Osmosis.org (Moore et al., 2016) Origins of the different organs of the respiratory system Endoderm (of laryngotracheal groove): Pulmonary epithelium Glands Larynx Trachea Bronchi Splanchnic mesoderm (surrounding the foregut): Lungs Connective tissue Cartilage Smooth muscle  Origins of the different organs of the respiratory system End of week 4 of development The laryngotracheal groove has evaginated (protruded) Forms a pouch-like laryngotracheal diverticulum (respiratory diverticulum / lung bud) Diverticulum: an outpouching of a hollow (or a fluid-filled) structure in the body Mesoderm produces retinoic acid Upregulation of transcription factor Tbx4 in the endoderm of gut tube (near respiratory diverticulum) TBX4 induces: Bud formation Lung growth and differentiation (Moore et al., 2016) Development of the respiratory diverticulum The respiratory diverticulum is the primitive form of the respiratory system Outgrowth from the ventral wall of the foregut (Sadler, 2012) Lecture outline Overview of the respiratory system Respiratory diverticulum Normal and abnormal development of the respiratory tract Nasal cavity Pharynx Larynx Trachea Bronchi Lungs Embryonic development of the face Five fascial primordia: Frontonasal prominence Maxillary prominences (x2) From 1st pharyngeal arch Mandibular prominence (x2) From 1st pharyngeal arch Mesenchyme derived from neural crest cells that migrate into the arches during the 4th week (Moore et al., 2016) of development Prominence: an elevation or projection on an anatomical structure Frontonasal Maxillary Mandibular Forehead Upper jaw Upper lip Bridge and tip of the nose Lateral aspects of upper lip Lower lip Plithrum Secondary palate Mandible (jaw bone) Primary palate Maxillary bone Development of the nasal cavities Sections from this level on next slide FNP: frontonasal prominence NP: nasal placode MPX: maxillary prominences (Moore et al., 2016) MDP: mandibular prominences BA: pharyngeal arch Placode: a platelike thickening of embryonic ectoderm from which a definitive structure develops Development of the nasal cavities (Moore et al., 2016) The nasal placodes develop by the end of the 4th week The nasal placodes become depressed and form the nasal pit The surrounding mesenchyme proliferates to form the medial and lateral nasal prominences The nasal pits deepen and form the primordial nasal sacs Development of the nasal cavities (Moore et al., 2016) Each primordial nasal sac grows dorsally, ventral to the developing forebrain The oronasal membrane separates the nasal sacs from the oral cavity Week 6: The oronasal membrane ruptures The oral and nasal cavities start communicating Development of the nasal cavities Vestibule: a space or cavity at the entrance to a canal, channel, tube, or vessel (Moore et al., 2016) The nasal vestibule forms following the development and apoptosis of an epithelial plug The regions of continuity between the nasal and oral cavities are the primordial choanae The primary palate develops into the secondary palate The choanae are now located at the junction between the nasal cavity and pharynx The ectodermal epithelium becomes specialised to form the olfactory epithelium Some epithelial cells differentiate into olfactory receptor cells The axons of these cells constitute the olfactory nerves, which grow into the olfactory bulbs of the brain What can go wrong? Abnormal development of the nasal cavity Abnormal development of the nasal cavity - Congenital arrhinia Less than 1 in a million births Lack of formation of external and internal nasal structures Possible etiologies: Lack of invagination of the nasal placodes Premature fusion of the medial nasal processes Failure of resorption of the nasal epithelial plugs Abnormal migration of neural crest cells Management: Breath through the mouth Tracheostomy tube (Maya & Seguias, 2021) Treatment: Reconstructive surgery at ages 5-6 years old Abnormal development of the nasal cavity – Polyrhinia Complete duplication of the nose resulting in two fully developed noses Treatment: Surgical correction: excision of the medial part of each nose and union of the lateral halves https://pt.slideshare.net/DrHCL/ent-about- development-of-nose/4 Abnormal development of the nasal cavity - Proboscis lateralis Rudimentary nasal structure or appendage that is located off - center from the vertical midline of the face Incomplete formation of one side of the nose Treatment: Heminose reconstruction (Chauhan & Guruprasad, 2010) Lecture outline Overview of the respiratory system Respiratory diverticulum Normal and abnormal development of the respiratory tract Nasal cavity Pharynx Larynx Trachea Bronchi Lungs Development of the pharyngeal apparatus Pharyngeal apparatus: Pharyngeal arches Pharyngeal pouches Pharyngeal grooves / clefts Pharyngeal membranes  Contribute to the formation of the face, nasal cavities, mouth, larynx, pharynx, and neck Osmosis.org https://teachmeanatomy.info/the-basics/embryology/head-neck/pharyngeal-arches/ Development of the pharyngeal apparatus: Pharyngeal arches Week 4: neural crest cells migrate into the future head and neck regions Each pharyngeal arch: Core of mesenchyme (embryonic connective tissue) Covered externally by ectoderm Covered internally by endoderm The arches are separated from each other by the pharyngeal grooves (clefts) Osmosis.org Development of the pharyngeal apparatus: Pharyngeal arches The arches support the lateral walls of the primordial pharynx The stomodeum (primordial mouth) appears as a slight depression of the surface ectoderm Oropharyngeal membrane: Bilaminar membrane Composed of fused ectoderm and endoderm Separates the stomodeum from the cavity of the primordial pharynx Ruptures at 26 days Brings the primordial pharynx and foregut into communication with the amniotic cavity (Moore et al., 2016) Development of the pharyngeal apparatus: Pharyngeal arches Six pharyngeal arches: 1: Chewing (Maxillary and mandibular prominences - jaw formation) 2: Smile (Associated with cranial nerve 7 – facial expression + formation of hyoid bone) 3 + 4: Swallowing (Associated with cranial nerve 9) 5: No major developmental contributions 6: Speaking (Moore et al., 2016) Osmosis.org Development of the pharyngeal apparatus: Pharyngeal arches Each pharyngeal arch contains: Pharyngeal arch artery Pharyngeal arch cartilage Pharyngeal arch muscles Pharyngeal arch nerves https://teachmeanatomy.info/the-basics/embryology/head-neck/pharyngeal-arches/ Development of the pharyngeal apparatus: Pharyngeal arches (Moore et al., 2016) Development of the pharyngeal apparatus: Pharyngeal pouches Endoderm Pharyngeal Derivatives pouch 1st Middle ear cavity Auditory tube 2nd Stroma of palatine tonsil 3rd Inferior parathyroid glands Thymus 4th + 5th Posterior parathyroid glands Ultimobranchial body (Moore et al., 2016) Development of the pharyngeal apparatus: Pharyngeal clefts and membranes The pharyngeal clefts / grooves separate the pharyngeal arches externally (ectoderm) The first pharyngeal cleft becomes the acoustic meatus (ear canal) The pharyngeal membranes form where the epithelia of the grooves and pouches approach each other The first pharyngeal membrane becomes the tympanic membrane (Moore et al., 2016) What can go wrong?  Abnormal development of the pharynx – Micrognathia Also known as mandibular hypoplasia Abnormal development of the first pharyngeal pouch Undersized lower jaw Etiology: Pierre Robin syndrome Trisomy 13 (Patau syndrome) Fetal alcohol syndrome Symptoms: Feeding or breathing problems Teeth malocclusion (abnormal alignment) Treatment: Corrective surgery Orthodontic braces to alleviate symptoms  Abnormal development of the pharynx – DiGeorge syndrome Microdeletion of chromosome 22 at a location known as 22q11.2 Developmental anomalies of the third and fourth pharyngeal pouches (swallowing) Diagnosis Genetic testing X-ray or CT scans (look for heart defects) Physical examination Symptoms (CATCH) Cardiac anomalies Abnormal facies Thymic hypoplasia or aplasia Cleft palate Hypocalcemia (McDonald-McGinn et al., 2015)  Abnormal development of the pharynx – DiGeorge syndrome Complications Autoimmune disorders Impaired hearing and vision Learning disabilities due to hearing and vision problems Feeding problems due to cleft lip or palate Treatment Antibiotic medications Calcium supplementation Ear tubes or hearing aids Occupational therapy to improve developmental and behavioral issues Physical therapy to improve mobility and movement https://www.mayoclinic.org/ Replacement of missing hormones such as parathyroid hormone, growth hormone or thyroid hormone Surgery to repair a heart defect or cleft palate Lecture outline Overview of the respiratory system Respiratory diverticulum Normal and abnormal development of the respiratory tract Nasal cavity Pharynx Larynx Trachea Bronchi Lungs Development of the larynx Main functions: Breathing Creating vocal sounds Preventing food and other particles from getting into your trachea, lungs and the rest of your respiratory system => initiation of coughing The epithelium lining the larynx is of endodermal origin The cartilages and muscles of the larynx arise from the mesenchyme in the 4th and 6th pairs of pharyngeal arches Osmosis.org Development of the larynx The respiratory primordium communicates with the pharynx through the laryngeal orifice Orifice: The entrance or outlet of any body cavity (Sadler, 2012) Development of the larynx Rapid proliferation of the mesenchyme (pharyngeal arch): Produces two arytenoid swellings The arytenoid swellings grow toward the tongue Changes the appearance of the laryngeal orifice from a sagittal slit to a T-shaped opening (Sadler, 2012) Rapid proliferation of the epithelium (pharyngeal pouch): Temporary occlusion of the laryngeal lumen Week 10: Recanalisation of the larynx Formation of the laryngeal ventricles Bound by folds of mucous membrane that evolve into the vocal folds (cords) and the vestibular folds  Development of the larynx (Sadler, 2012) The mesenchyme of the 4th and 6th pharyngeal arches transforms into cartilage: Thyroid cartilage: protects and supports the vocal cords Cricoid cartilage: fully encircles the trachea Arytenoid cartilage: essential to produce vocal sounds The epiglottis develops from the 3rd and 4th pharyngeal arches The laryngeal muscles develop from myoblasts in the 4th and 6th pharyngeal arches What can go wrong? Abnormal development of the larynx – Laryngeal atresia Rare birth defect Etiology: The larynx fails to open during intrauterine development No recanalisation in week 10 The larynx remains blocked by cartilage when the infant is born Children’s hospital of Philadelphia Atresia: The absence or closure of a normal body orifice or tubular passage  Abnormal development of the larynx – Laryngeal atresia Congenital high airway obstruction syndrome (CHAOS) Complications: Dilated airways Hyperplastic lungs => compression of the heart and great vessels Flattened diaphragm Diagnosis: Prenatal ultrasonography Treatment: Immediate tracheostomy at birth  Abnormal development of the larynx – Laryngomalacia Normal Congenital laryngeal stridor M:F ratio is 2:1 Omega shaped larynx Possible etiologies: Congenital malformation of the larynx associated with abnormal flaccidity of laryngeal cartilage Laryngomalacia Delayed development of neuromuscular control resulting in laryngeal hypotonia Anatomical abnormality Mount Nittany Health Abnormal development of the larynx – Laryngomalacia Symptoms: Inspiratory stridor (high-pitched, wheezing sound caused by disrupted airflow) Prolonged feeding time Normal Laryngomalacia Emesis Choking Coughing Weight loss Treatment: Acid reflux suppression After supraglottosplasty Feeding modulation Posture – upright Supraglottoplasty Tracheostomy Children’s ear nose, and throat center Lecture outline Overview of the respiratory system Respiratory diverticulum Normal and abnormal development of the respiratory tract Nasal cavity Pharynx Larynx Trachea Bronchi Lungs Development of the trachea Initially, the respiratory diverticulum is in open communication with the foregut Diverticulum expands caudally Development of the tracheoesophageal ridges that separate the diverticulum from the foregut The ridges fuse to form the tracheoesophageal septum: Foregut dorsal portion: esophagus Foregut ventral portion: (Sadler, 2012) trachea and lung buds (Moore et al., 2016) Development of the trachea Main function: Is ciliated and produces mucus to help trap particles in inspired air The endoderm of the tube gives rise to the epithelium and the glands of the trachea The mesenchyme surrounding the tube forms the connective tissue, muscle, and cartilage (Moore et al., 2016) What can go wrong? Abnormal development of the trachea: Tracheoesophageal fistula Abnormal passage between the trachea and esophagus Most common anomaly of the lower respiratory tract 1:3000 – 1:4500 live births Mainly affects males Can be associated with esophageal atresia Causation: Incomplete division of the cranial part of the foregut into esophageal and respiratory parts Incomplete fusion of the esophageal folds Defective tracheoesophageal septum Fistula: an abnormal connection or https://www.msdmanuals.com/ passageway that connects two organs or vessels that do not usually connect Abnormal development of the trachea: Tracheoesophageal fistula Most common variety: Blind ending of the superior part of the esophagus (esophageal atresia) and a joining of the inferior part to the trachea near its bifurcation Accumulation of excessive amounts of liquid in the mouth and upper respiratory tract Cough and choke when swallowing Regurgitation (Moore et al., 2016) Gastric contents may also reflux from the stomach through the fistula into the trachea and lungs, which may result in Bifurcation: The point or area at which something divides into two pneumonia or pneumonitis branches or parts Abnormal development of the trachea: Tracheoesophageal fistula Treatment: Corrective surgery Children’s Minnesota, 2022 Abnormal development of the trachea: Tracheal stenosis and atresia Normal Tracheal stenosis Narrowing (stenosis) and obstruction (atresia) of the trachea Rare birth defect Associated with TEF Causation: Unequal partitioning of the foregut into the esophagus and trachea Treatment: Resection and anastomosis (removing the narrowed portion and re-connecting Oe: oesophagus; Hy: hyoid; Th: thyroid cartilage; the normal wider portions) Cr: cricoid cartilage; Al: annular ligaments; Ca: carina; Br: Bronchus; St: stomach; (Sher & Liu, 2016) Lecture outline Overview of the respiratory system Respiratory diverticulum Normal and abnormal development of the respiratory tract Nasal cavity Pharynx Larynx Trachea Bronchi Lungs Development of the bronchi (Sadler, 2012) The buds divide into two lateral outpocketings: primary bronchial buds At the beginning of 5th week, the primary bronchial buds enlarge to form the left and right main bronchi The right bronchus forms three secondary bronchi The left bronchus forms two secondary bronchi Tertiary bronchial buds (segmental bronchi ) are then formed (future bronchopulmonary segments): 10 in the right lung, 8 in the left lung The lung buds expand into the pericardioperitoneal canals Development of the bronchi Visceral pleura: Mesoderm that covers the outside of lung Parietal pleura: Mesoderm that covers the body wall from the inside Pleural cavity: The space between the visceral pleura and the parietal pleura (Sadler, 2012) What can go wrong?  Abnormal development of the bronchi: Bronchial atresia Two types: Proximal: Focal interruption of a lobar bronchus Peripheral: Focal interruption of a segmental or subsegmental bronchus Secondary bronchi = Lobar bronchi Tertiary bronchi = Segmental bronchi Possible etiology: Intrauterine ischemia after the 16th week of gestation Symptoms: Most asymptomatic Recurrent infections Dyspnea Coughing Wheezing Abnormal development of the bronchi: Bronchial atresia Complications: Peripheral mucus impaction (bronchocele or mucocele) Hyperinflation of the obstructed lung segment Diagnosis: Computed tomography scan (Sago et al., 2020) Bronchofibroscopy Treatment: Thoracoscopic surgery Local resection Lobectomy / Segmentectomy (Cleaveland clinic, 2021) Lecture outline Overview of the respiratory system Respiratory diverticulum Normal and abnormal development of the respiratory tract Nasal cavity Pharynx Larynx Trachea Bronchi Lungs Development of the lungs The stages overlap because cranial segments mature faster than caudal segments (Schittny, 2017) Development of the lungs – Embryonic stage Weeks 4-7 of development Lung buds Primary bronchial buds Main bronchi Secondary bronchi Tertiary bronchi (Sadler, 2012) Development of the lungs – Pseudoglandular stage Weeks 5-17 of development Generation of the bronchial tree Tertiary bronchi divide into many primary bronchioles Primary bronchioles divide (branch) into terminal bronchioles The terminal section of the non-respiratory conducting airway No respiratory bronchioles or alveoli are present => No gas exchange Respiration is not possible => fetuses (Moore et al., 2016) born during this period are unable to survive Development of the lungs – Canalicular stage Weeks 16-26 of development Each terminal bronchiole divides into two or more respiratory bronchioles Respiratory bronchioles divide into three to six alveolar ducts The surrounding mesenchyme becomes highly vascular Respiration is possible => fetuses born at 24-26 weeks may survive if given intensive care (Moore et al., 2016) Development of the lungs – Saccular stage 24 weeks to birth Terminal sacs (primitive alveoli) form Capillaries establish close contact The blood-air barrier is established, which permits adequate gas exchange for survival (Moore et al., 2016) Development of the lungs – Saccular stage By 26 weeks: Type I pneumocytes Squamous epithelial cells of endodermal origin Gas exchange Type II pneumocytes Rounded secretory epithelial cells Secrete pulmonary surfactant (phospholipoprotein) Production begins at 20-22 weeks Expansion of terminal sacs Present in small amounts in premature infants Development of the lungs – Alveolar stage 8 months to childhood Terminal sacs begin to differentiate into mature alveoli Mature alveoli have well- developed epithelial endothelial (capillary) contacts Alveoli continue to form through early adulthood (Moore et al., 2016) Development of the lungs – Alveolar stage Gas exchange through placenta Production of surfactant in the alveolar sacs Transformation of the lungs into gas-exchanging organs Establishment of parallel pulmonary and systemic circulations Autonomous gas exchange after birth Sox17, Wnt signalling Morphogenesis and formation of blood vessels in the lungs Development of the lungs – Alveolar stage Factors essential for normal lung development: Adequate thoracic space for lung growth Adequate amniotic fluid volume Aspiration of amniotic Fetal breathing movements Exert force fluid into the lungs Birth: Lungs are half-filled with fluid Aeration: intra-alveolar fluid is replaced by air The fluid in the lungs is cleared at birth by three routes: Through the mouth and nose by pressure on the thorax during vaginal delivery Into the pulmonary capillaries and pulmonary arteries and veins Into the lymphatic vessels Development of the lungs Pseudoglandular Tertiary bronchi stage Primary bronchioles Terminal bronchioles Canalicular stage Respiratory bronchioles Alveolar ducts Alveolar Saccular stage Terminal sacs stage Alveoli The Ohio State University What can go wrong? Abnormal development of the lungs: agenesis, aplasia, hypoplasia Pulmonary agenesis: Complete absence of lung tissue (90% of cases is unilateral) Etiology: Vascular in origin Disruption of the dorsal aortic arch blood flow during the fourth week of gestation https://www.ankitparakh.com/conditions- treated/congenital-lung-diseases/ Abnormal development of the lungs: agenesis, aplasia, hypoplasia Pulmonary aplasia: Complete developmental arrest of the primitive lung bud Pulmonary hypoplasia: Small, underdeveloped lungs (Unilateral / bilateral) Etiology: Associated with congenital diaphragmatic hernia Changes in growth factors Primary (idiopathic) or secondary (environmental factors / congenital anomalies) https://www.ankitparakh.com/conditions- treated/congenital-lung-diseases/ Abnormal development of the lungs: agenesis, aplasia, hypoplasia Symptoms: Dyspnea Respiratory distress Recurrent pulmonary infections Limited exercise tolerance Complications: Death Treatment: Surgical resection Pulmonary hypoplasia: Antenatal corticosteroids enhance fetal lung maturation in pregnancies less than 34 weeks of gestation Abnormal maturation of the lungs: Neonatal respiratory distress syndrome Also known as: Hyaline membrane disease Surfactant deficiency lung disease 2% of live newborns Etiology: Premature birth Prolonged intrauterine asphyxia => irreversible changes to type II alveolar cells => surfactant insufficiency => underinflated lungs Surfactant: Keeps the lungs fully expanded so that newborns can breathe in air once they are born Abnormal maturation of the lungs: Neonatal respiratory distress syndrome Symptoms / complications: Fast breathing very soon after birth Grunting “ugh” sound with each breath Changes in color of lips, fingers and toes Widening of the nostrils with each breath Chest retractions Babies with mild symptoms improve after 3-4 days Death at around 2-7 days after birth (if the condition doesn’t improve) Prevention / Treatment (more than 90% will survive): Prevent a premature birth Corticosteroids before delivery (for fetal lung maturation) Supplementary oxygen Artificial surfactant Thank you!