PHo

Notes | Embryology 07 Body Cavity & Respiratory System Objectives Know the key stages in body cavity and respiratory system development Know the key time points of body cavity formation and respiratory system development Know some of the key transcription factors involved with body cavity development and respiratory system development Know some of the problems and developmental disorders that occur during body cavity formation and respiratory system development. 1. A Tube on Top of a Tube a. Neural Tube and Gut Tube is formed around 3rd or 4th week of development (from ectoderm & endoderm respectively) b. Mesoderm holds the two tubes together c. Lateral plate mesoderm folds in on itself, splitting into the visceral (splanchnic) and parietal (somatic) layers d. Space between visceral and parietal layers is the primitive body cavity 2. Membrane/Body Cavity Formation a. Parietal layer and overlying ectoderm are called somatopleure b. Visceral layer and underlying endoderm are called splanchnopleure c. In 4th week, lateral body wall folds in on itself (Look at first picture) i. Folds consist of parietal mesoderm, ectoderm, and cells from adjacent somites ii. Will meet in midline and fuse to form ventral/anterior body wall d. As the lateral body wall folds, the endoderm layer also folds ventrally and closes to form the gut tube i. Connection of midgut region to yolk sac still exists this connection is called the Vitelline duct e. Serous Membranes i. Cells of both the parietal and visceral layer mesoderm become mesothelial cells that form the parietal and visceral layer of serous membrane 1. Visceral Layer surrounds the gut tube/organs 2. Parietal Layer Everything else ii. Visceral and parietal layers are continuous with each other as the dorsal mesentery, which suspends the gut tube from the posterior body wall into the peritoneal cavity 1. Extends continuously from the caudal limit of foregut to end of hindgut. iii. Ventral mesentery exists from the caudal foregut to the upper portion of the duodenum and results from thinning of mesoderm of the septum transversum 1. Septum transversum - a block of mesoderm that forms connective tissue in the liver and the central tendon of the diaphragm 3. Diaphragm and Thoracic Cavity a. Septum transversum - thick mesodermal tissue plate occupying the space between the thoracic cavity and stalk of the yolk sac b. Septum transversum starts separating Thorax from Abdomen i. It is derived from visceral mesoderm surrounding the heart ii. Is between the primitive thoracic and abdominal cavities iii. Has large openings, the pericardioperitoneal canals, on each side of foregut for communication c. Lungs grow caudolaterally within the pericardioperitoneal canals i. These lungs are growing from the lung buds ii. Lung grows quickly and canals become too small

PHo Notes | Embryology 07 Body Cavity & Respiratory System 1. Lung buds will grow into body wall dorsally, ventrally, and laterally a. Its ventral and lateral expansion is occurring behind (posterior) to the Pleuropericardial folds b. Pleuropericardial folds the initial small ridges projecting into primitive thoracic cavity (that will later form the Pleuropericardial membrane) 2. Expansion of lungs splits mesoderm of body wall into 2 compartments (?): a. Definitive wall of thorax b. Pleural Pericardial Membranes i. These membranes are extensions of Pleuropericardial folds ii. They contain Veins and Phrenic Nerves iii. Pericardioperitoneal canals transforms into the pleural cavities by Pleuropericardial membranes/folds d. Growth of heart and changes in sinus venous spreads the Pleuropericardial membranes out e. Pleuropericardial membranes folds/fuses, and with the root of the lungs, the thoracic cavity is divided into the pericardial cavity and 2 pleural cavities i. Membranes become the fibrous pericardium in adults ii. Summary of this: Fusion of Pleuropericardial membrane Pericardial Cavities

4. Formation of the Diaphragm a. Pleural cavities and pericardial cavity are still in contact with the abdominal (peritoneal) wall by pericardioperitoneal canals b. These Pericardioperitoneal canals will be closed by Pleuroperitoneal folds c. Pleuroperitoneal folds extend medially ventrally towards the esophageal mesentery and the septum transversum and then fuses with them i. Fusion separates the thoracic cavity from the abdominal cavity d. All openings between the pleural and peritoneal cavities are closed by the Pleuroperitoneal folds e. Further expansion of pleural cavities relative to mesenchyme of the body wall adds a Peripheral rim to the Pleuroperitoneal membranes i. In other words, pleural cavities expand inferiorly and forms the peripheral rim ii. Peripheral rim triggers myoblasts from somites at C3-5 to penetrate the membranes to form the muscular diaphragm

PHo Notes | Embryology 07 Body Cavity & Respiratory System f. Diaphragm is composed of: i. The septum transversum (central tendon) ii. 2 Pleuroperitoneal membranes iii. Muscular components from C3-C5 somites iv. Mesentery of esophagus (Crura of diaphragm) g. Phrenic nerves are shifted into the fibrous pericardium due to lung expansion i. Phrenic nerve initially pass into septum through the Pleuropericardial folds ii. Since the folds move because of lung expansion and the septum descends, the phrenic nerve is shifted h. Rapid growth of dorsal aspect of embryo shift position of diaphragm i. Diaphragm transposes more inferior! ii. Initially at cervical region, thoracic region in 6 weeks, far enough for L1 bands at 3rd month 5. Problems a. Abnormal body wall closure i. Ectopia Cordis failure of lateral body wall to fuse; heart ends up outside ii. Gastroschisis failure of abdominal wall to fuse; intestinal loops are exposed to amniotic fluid (which is toxic to the organ); subjected to twisting = necrosis!!! iii. Bladder Exstrophy Herniation of bladder iv. Cloacal Exstrophy Cloaca has not been divided to form the urogenital and urological system; pretty severe since rectum and bladder are outside (more in Urinary Lecture) v. Omphalocele not a condition in which the body wall fails to close! 1. Portions of gut tube are normally herniated into umbilical cord during development 2. Omphalocele is when they fail to return into abdominal cavity 3. Can be a sign of other problems (show also as increase in alpha-fetoprotein) b. Diaphragmatic Hernias i. Caused by failure of Pleuroperitoneal fold to close pericardioperitoneal canals

Respiratory System
1. Development (4 weeks) a. Lung bud is an outgrowth of ventral wall of respiratory diverticulum i. The respiratory diverticulum is developed off from the gut tube (endoderm) b. Lung buds are under the control of TBX4 and Retinoic Acid i. Retinoic acid is produced by adjacent tissues 1. RA triggers upregulation of TBX4 during lung bud development ii. TBX4 induces formation of lung bud and continued growth c. Epithelium of Respiratory System is Endodermal Derived d. Cartilaginous, muscular, and connective derived from splanchnic mesoderm e. The superior gut tube develops into Pharyngeal Arches i. Larynx cartilage and musculature develop from the 4th and 6th arches 2. Development of Larynx a. At pharyngeal arches 4, a slit appears called the laryngeal orifice i. Above it, the 3rd Pharyngeal arch becomes the epiglottal swelling ii. Below it, the arches become laryngeal swellings b. The laryngeal orifice slit becomes T-shaped i. The 5th and 6th arch develop arytenoid swellings on the sides c. Arytenoid swellings and epiglottal swellings surround the laryngeal orifice i. Tissue that bound laryngeal ventricles on sides become true and false vocal cords d. Laryngeal muscles are innervated by the Vagus nerve

PHo Notes | Embryology 07 Body Cavity & Respiratory System 3. Development of Respiratory Tree a. The respiratory diverticulum is an outgrowth of the foregut tube and is connected to it by tracheoesophageal ridges. b. Ventral dorsal arrangement happens, and the respiratory diverticulum will position ventrally to the gut tube c. Tracheoesophageal ridges fuse to form tracheoesophageal septum; separates the respiratory diverticulum from gut d. Growth of lung buds: i. 3 buds form to the right and 2 to the left at the 5th week ii. They grow in the pericardioperitoneal canals iii. Branching of the buds involves FGF (Fibroblast growth factor) 1. Moves caudally, and at birth, the bifurcation of trachea is at T4 iv. At the end of growth, they are encapsulated 1. Visceral pleura, pleural space, parietal pleura v. Alveoli will grow rapidly at the 7th month 4. Lung Maturation a. Type 1 cells i. Thin squamal cells; Surrounds capillaries and gas exchange surfaces b. Type 2 Cells i. Cuboidal; Synthesize and secrete surfactant c. Surfactant i. Lowers surface tension in alveoli membranous surface contact ii. Concentration in utero increases rapidly during final 2 weeks of (indication of birth) d. Alveoli maturation doesnt happen until birth i. Surfactant reacts with macrophages in amniotic cavity ii. Macrophages enter uterus and produce interleukin-1, IL-1 1. IL-1 increases prostaglandin production/concentration and triggers contractions e. Upon initial breath, aspiration of the amniotic fluid conditions the lungs i. Coats alveoli with layer of surfactant, which prevents lung collapse 5. Abnormalities a. Esophageal Atresia i. With/Without Tracheoesophageal Fistula (TEF) 1. Fistula inappropriate connection ii. 90% - upper portion of esophagus end in blind pouch with lower forming fistula with trachea iii. Isolated esophageal atresia (H Type TEF) - ~4%

b. Failure of Trachea and Esophagus Partitioning i. 33% also have other defects 1. VACTERL Anal Atresia, Cardiac Defects, TEF, esophageal atresia, renal anomalies, limb defects ii. Complications include: 1. Polyhydraminos excess amniotic fluid in amniotic cavity 2. Passage of gastric contents and/or amniotic fluid into lungs a. Results in Pneumonia and Pneumonitis (Inflammation of Lungs) 3. Respiratory Distress Syndrome (RDS) not enough surfactant; alveoli collapse on initial breath (Accounts for 20% of premature baby deaths)