EMBRIOLOGY OF THE RESPIRATORY SYSTEM

Formation of Embryonic Disk (first three weeks) Gastrulation 15 days

Formation of Embryonic Disk (first three weeks) Implantation of blastocyst Exocoelomic cavity Inner cell mass Formation of amniotic cavity inside inner cell mass Formation of primary yolk sac cavity inside exocoelomic cavity Formation of bilaminar embryonic disc between amniotic cavity & yolk sac Epiblast Layer (amniotic cells - epiblasts) – Future Ectoderm Hypoblast Layer (primary yolk sac cells) – Future Endoderm Gastrulation: Formation of primitive streak & groove on surface of Epiblast Migration of Epiblast cells to Hypoblast & formation of Endoderm Formation of Intraembryonic Mesoderm between Ectoderm & Endoderm from Epiblast cells Formation of the Ectoderm from cells remaining in Epiblast Formation of Trilaminar Enbryonic Disc between amniotic cavity & yolk sac

ESTABLISHMENT of GENERAL BODY FORM (at the beginning of the fourth week) Folding of the flat trilaminar embryonic disk into a cylindrical embryo. Longitudinal Folding in the Median Plane: Cranial and caudal folding Transverse Folding in Horizontal Plane: Right and left lateral to medial folding.

Trilaminar Embryonic Disk (3 weeks)

Trilaminar Embryonic Disk (3 weeks)

Folding in Median & Horizontal Plane (4th week)

Folding in Median & Horizontal Plane (4th week)

Oropharyngeal membrane (ruptures at 24 days)

Cloacal Membrane (ruptures at the end of 7th week)

DEVELOPMENT OF THE FACE (from fourth to eighth weeks) DEVELOPMENT OF THE PRIMITIVE MOUTH – STOMODEUM (beginning of 4th week) Rupture of oropharyngeal; membrane (24th day) DEVELOPMENT OF THE NASAL CAVITY (from the end of 4th week) Rupture of oronasal membrane (6th week) Development of paranasal air sinuses from deverticuli of nasal walls during late fetal life & after birth

DEVELOPMENT OF THE PRIMITIVE MOUTH (STOMODEUM) It develops from five facial primordia: Frontonasal prominence It constitutes cranial boundary Paired maxillary prominences They form lateral boundaries Paired mandibular prominences They constitute caudal boundary

Stomodeum & Nasal Placodes

DEVELOPMENT OF THE NASAL CAVITY Nasal placodes (bilateral right & left oval thickenings of surface ectoderm) develop on each side of inferior part of frontonasal prominence by the end of the fourth week. Horseshoe-shaped elevations at margins of these placodes are formed Medial & lateral sides of each elevation (surrounding one placode) are called as Medial & Lateral Nasal Prominences respectively Nasal placodes now lie in depressions called Nasal Pits Progressive deepening of nasal pits form Nasal Sacs Medial & Lateral Nasal Prominence form a boundary of Naris Nasal sacs are separated from oral cavity by oronasal membrane, which ruptures during the sixth week This forms primitive choanae, which lie posterior to primitive palate After secondary palate develops, choanae lie at junction of nasal cavity and nasopharynx Nasal septum, incisive bone & central part of upper lip develop from merged medial nasal prominences.

Formation of Nasal Placodes

Formation of Nasal Pits & Sacs

Boundaries of Right Nasal Pit

Merging of Medial Nasal Prominences

Formation of Nasal Prominences

Beginning of Merging of Medial Nasal Prominences

Merging of Medial Nasal Prominences is Completed

Derivatives of Merged Medial Nasal Prominences

Development of Nasal Cavity

Components of Inferior Nasal Wall in Adult View from Oral Cavity Interpalatine suture Secondary Palate or Incisive bone (primary palate)

Congenital Anomalies of Middle Face Area: Oblique cleft of the face (persistent nasolacrimal grove) It connect mouth to medial palpebral angle of the orbit Nasolacrimal duct is present as open grove It results from failure of fusion of lateral nasal and maxillary prominences Cleft upper lip, superior alveolar arch and palate It results from failure of fusion of medial nasal and maxillary prominences They could be unilateral or bilateral

Bilateral Oblique Cleft of the Face

Unilateral Cleft Upper Lip, Superior Alveolar Arch & Palate Right

Bilateral Cleft Upper Lip, Superior Alveolar Arch & Palate After Orthopedic Correction

Remaining Bilateral Cleft Palate in Adult

DEVELOPMENT OF THE BRANCHIAL APPARATUS (arches, pouches, grooves, membranes) Branchial arches (from 1 to 6) develop early in week 4 as neural crest cells migrate through the mesenchyme to the future head and neck region, forming elevations of mesoderm on each side of the primitive pharynx.

BRANCHIAL APPARATUS INCLUDES: Branchial arches Branchial membranes Branchial grooves Branchial pouches

A Typical Branchial Arch Contains: An aortic arch Derivatives of branchial arch arteries A cartilaginous road Derivatives of branchial arch cartilages A nerve Derivatives of branchial arch nerves A muscular component Derivatives of branchial arch muscles

Development of Branchial Apparatus

FURTHER DEVELOPMENT OF THE BRANCHIAL APPARATUS AND ITS DERIVATIVES DEVELOPMENT OF THE LARYNX, TRACHEA, BRONCHIAL TREE, LUNGS AND PLEURA

Development of Lower Airway & Lungs The lower airway and lungs develop as an outgrowth from the primitive gut. A laryngotracheal diverticulum buds out from the primitive pharynx about the fourth week. Its blind end forms the lung bud. The tracheoesophageal septum separates the growing lung bud from the esophagus. The lung bud continues to elongate and branch into bronchial buds, secondary bronchi etc. About 24 orders of branches are eventually formed, with the last few being formed after birth. The endoderm of the lung bud gives rise only to the epithelium and glands of the lower airway. The mesenchyme, that surrounds the bud, gives rise to all other structures: connective tissue, cartilage, muscle, vessels & pleurae.

Scheme of Development of Lower Airway & Lungs

Scheme of Development of Lower Airway & Lungs Bud Bronchial

View of Developing Lower Airway & Lung Bud

Development of Laryngeal Inlet

Development of Trachea & Lung Buds

Separation of Trachea from Esophagus

CONGENITAL ABNORMALITIES OF TRACHEA: Tracheoesophageal Fistula (Common): Communication connecting trachea & esophagus that occurs in every 2500 births It has four main varieties: 1. Superior portion of esophagus ends blindly (esophageal atresia), inferior portion joins trachea near its bifurcation (most common – 90%) 2. Esophagus has communication with trachea near its bifurcation 3. Upper end of esophagus has communication with trachea near its bifurcation, whereas the lower portion ends blindly 4. Upper end of esophagus has communication with trachea, whereas the lower portion of esophagus also has communication with trachea near its bifurcation Tracheal Stenosis (narrowing) and Atresia (closure) Tracheal diverticulum

Tracheoesophageal Fistula - 1

Tracheoesophageal Fistula - 2

Tracheoesophageal Fistula - 3

Tracheoesophageal Fistula - 4

Development of Lungs

Development of Lungs

Development of Lungs

Development of Lungs

Development of Lung Buds: 41-45 days

Development of Lungs: 13 weeks Posterior View

Adult Lungs – Front View Not Smoker Smoker

Periods of Lung Development Pseudoglandular period (5 – 17 weeks) Canalicular period (16 – 25 weeks) Terminal sac period (24 weeks to birth) Alveolar period (late fetal period to 8 years after birth)

Periods of Lung Development From 5-17 weeks the branching forms the bronchi and terminal bronchioles. From 17-24 weeks the diameter of the tube increases and respiratory bronchioles and alveolar ducts develop. At 25 weeks the alveolar ducts give rise to primitive alveoli with cuboidal epithelium. By 26 weeks the alveoli have become vascularized. By this stage the production of surfactant has begun and the fetus might survive if born prematurely.

Periods of Lung Development

Pseudoglandular (5-17 w) & Canalicular (16–25 w) Periods

Canalicular (16–25 w) & Terminal Sac (24w to birth) Periods

Periods of Lung Development Barriers to survival born by 26 week are the small surface area available for gas exchange, lack of adequate development of the pulmonary vasculature and insufficient surfactant production. The lung must develop further however before it is mature. This process of maturation continues for about eight years, as the number of alveoli increase.

Developed Respiratory System

CONGENITAL ABNORMALITIES: INFANT RESPIRATORY DISTRESS SYNDROME (IRDS): Also called Hyaline Membrane Disease Congenital Lung Cysts Agenesis of Lungs or one Lung Lung Hypoplasia Accessory Lung Lobe of Azygos Vein

Features of Respiratory Distress Syndrome Infants born premature with weights of up to 1.5 kg show RDS Their surfactant producing cells (type II pneumocytes & Clara cells) are not properly developed Deficiency of pulmonary surfactant In absence of surfactant alveoli tend to collapse during exhalation Lungs are under inflated, alveoli contain a fluid of high protein content that resembles a hyaline (glassy) membrane Prolonged intrauterine asphyxia may also produce irreversible changes in type II alveolar cells (responsible for surfactant production) Infants develop rapid, labored breathing Infants must inhale each time with extra force to reopen alveoli on next breath and they rapidly becomes exhausted

DEVELOPMENT OF THE PLEURA AND PLEURAL CAVITIES Pleural cavities develop from the Intraembryonic Coelom Right pleural cavity forms from Right Pericardio-Peritoneal Canal Left pleural cavity forms from Left Pericardio-Peritoneal Canal Pleurae develop from the Lateral Mesoderm of Three Laminar Embryonic Disc Parietal Pleura – from Somatopleure Visceral Pleura – from Splanchnopleure

3 Somite Embryo of 21 Days

Position of Intraembryonic Coelom

Development of Pleural Cavities

Development of Pleural Cavities

Development of Diaphragm Diaphragm develops from 4 sources: 1) Septum Transversum 2) Pleuroperitoneal Membranes 3) Dorsal Mesentery of Esophagus 4) Body Wall

Diaphragmatic Hernias

FETAL CIRCULATION: Oxygenated Blood Oxygenated Blood from Placenta  Umbilical vein  Branch of Hepatic Portal Vein  Ductus venosus  Inferior Vena Cava (Mixture with Venous blood)  Right atrium  Foramen Ovale  Left atrium  Left ventricle  Aorta  Mixture with Venous blood from Pulmonary trunk Systemic circulation  Umbilical artery  Placenta 

FETAL CIRCULATION: Deoxygenated Blood Venous blood from Superior Vena Cava  Right atrium  Right ventricle  Pulmonary trunk  Left pulmonary artery  Ductus arteriosus  Left end of aortic arch  Descending aorta: Mixture with Arterial blood  Umbilical artery  Placenta 

Prenatal circulation

Aeration of Lung at Birth Lungs at birth are half filled with amniotic fluid because breathing movements occur before birth to cause aspiration of amniotic fluid into the lungs Fluid in lungs is cleared by three routes: Through mouth and nose by pressure on thorax during delivery Into pulmonary capillaries and blood vessels Into lymphatic capillaries and vessels

CHANGES THAT OCCUR AFTER BIRTH After birth, the circulation of fetal blood through the placenta ceases: Delivery of oxygenated blood to fetus via umbilical vein ceases The sphincter of ductus venosus constricts so all blood entering the liver passes through the hepatic sinusoids Fall of blood pressure in the IVC and right atrium occur Hypoxia of all tissues is increasing Respiratory centers of the brain stem are stimulated by carbon dioxide Inspiratory muscles contract, thoracic cage is expanded Expansion of the lungs and First Breath takes place Inspired air enters respiratory passageways, pushes the contained fluids out of the way and inflates the bronchial and respiratory trees Infant’s lungs begin to function and newborn infant utters a loud cry

CHANGES THAT OCCUR AFTER BIRTH Fall in pulmonary vascular resistance Ductus arteriosus constricts Increase in pulmonary blood flow Left atrium pressure becomes higher than in right atrium Valve of oval foramen is pressed against septum secondum Foramen ovale closes

Postnatal circulation

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