Respiratory and Body Cavities Development PDF

Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 1 of 26 DEVELOPMENT OF THE RESPIRATORY SYSTEM AND FORMATION OF THE BODY CAVITIES LECTURE LEARNING OBJECTIVES 1. Describe the form...

Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 1 of 26 DEVELOPMENT OF THE RESPIRATORY SYSTEM AND FORMATION OF THE BODY CAVITIES LECTURE LEARNING OBJECTIVES 1. Describe the formation of the primitive gut. Describe the gut tube through the folding of the embryo. Identify the regions of the 3 subdivisions of the primitive gut tube and the derivatives of the adult digestive tract formed by each subdivision. 2. Describe the development of the respiratory system. Describe the origin and formation of the respiratory diverticulum. Describe the role of retinoic acid induction of the transcription factor TBX4 in the development of the conducting and respiratory development of the lungs. Define the role of the tracheoesophageal ridges and its formation of the tracheoesophageal septum and the laryngotracheal tube. Define the positioning of the laryngeal orifice in relation with the pharyngeal arches. 3. Describe the origin and development of the larynx. Describe the process of recanalization of the larynx and its role in forming the true and false vocal folds. Describe the motor and sensory innervation provided by the 4th and 6th pharyngeal arch in relation to the true vocal fold. 4. Describe the development time-lines of the trachea, bronchial tree of the right and left lungs. Describe the role of the transcription factor sonic hedgehog and its role inducing the neighboring splanchnic mesoderm on lung development. Define the pseudoglandular and canalicular and terminal sac periods of lung development. Describe the role of the type II alveolar cells and their production of surfactant. 5. Describe the transition of the developing lungs into the pleural cavity. Describe the expansion of the lungs into the pericardioperitoneal canals and their investment by visceral pleura. 6. Describe the formation of the pericardial, pleural and peritoneal cavities. Describe the pleuropericardial folds, their contents and the separation of the pericardial cavity from the pericardioperitoneal canals. List the components that form the thoracic diaphragm. Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 2 of 26 7. Describe the formation of the thoracic diaphragm and the compartmentalization of the pleural and peritoneal cavities. Describe the partitioning of the pericardioperitoneal canals into the pleural and peritoneal cavities. Describe the formation of the thoracic diaphragm. 8. Describe the clinical significance of esophageal atresia, tracheoesophageal fistulas, and diaphragmatic hernias. Describe esophageal atresia with or without tracheoesophageal fistulas Describe how esophageal atresia can cause polyhydamnios. Describe postnatal symptoms resulting from a tracheoesophageal fistula. Define and describe diaphragmatic hernias. Lecture Content Outline I. Formation of the gut tube (Primitive gut) A. Folding of the endoderm creates the gut tube and vitelline duct. B. Subdivisions of the gut tube 1. Foregut 2. Midgut 3. Hindgut II. Development of the respiratory system A. Origin from midline 4th-6th pharyngeal arches B. Transcription-induction and formation of the respiratory diverticulum C. Communication of the respiratory diverticulum with foregut D. Formation of the tracheoesophageal ridges, septum and the formation of the laryngotracheal tube. 1. Formation of the lung buds E. Derivatives of the respiratory diverticulum endoderm F. Derivatives of the splanchnic mesoderm G. The laryngeal orifice III. Development of the larynx A. Germ layer sources for the formation of the larynx B. Formation of the laryngeal swellings C. Formation of the thyroid, cricoid and arytenoid cartilages D. The dependence of recanalization in the formation of the paired ventricles of the larynx and true and false vocal folds E. Innervation (motor and sensory) of the larynx 1. Above the true vocal folds 2. Below the true vocal folds Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 3 of 26 IV. Timing and development of the trachea, bronchial tree and the lungs A. Formation of the trachea and bronchial buds 1. Major transcription factors involved 2. Formation of the primary right and left primary bronchi B. Timing and the formation of the right and left secondary bronchial buds C. Timing and transcription factors involved in the formation of the right and left tertiary bronchi (bronchopulmonary segments) D. Classification of the maturation stages of the lungs 1. Pseudoglandular period 2. Canalicular period (terminal bronchioles and respiratory bronchioles) 3. Terminal sac period 4. Alveolar period (Maturation of the lungs) E. Role of breathing movements in lung development F. Role of type II alveolar epithelial cells 1. Activation of alveolar macrophages 2. Macrophage migration and role in the induction of partition. G. Summary of the maturation of the lungs. V. Transition of the developing lungs into the pleural cavity A. Early development within the splanchnic mesoderm B. Expansion into the pericardioperitoneal canals and acquiring visceral pleura C. Mesothelial lining of the pleura cavity VI. Formation of the pericardial and pleural cavities A. Role of the pleuropericardial folds (membranes) 1. Contents of the folds 2. Closure of the right and left pleuropericardial folds (membranes), forms and separates the pleural and pericardial cavities VII. Formation of the thoracic diaphragm and compartmentalization of the pleural and peritoneal cavities A. Septum transversum B. Pleuroperitoneal folds (membranes) C. Myoblast migration contributing to the muscular part of the diaphragm D. Displacement of the developing thoracic diaphragm from the cervical region to the thoracic region. 1. Motor and sensory innervation of the peripheral rim of the thoracic diaphragm 2 Motor and sensory innervation of the central region of the thoracic diaphragm VIII. Clinical significance A. Esophageal Atresia with or without tracheoesophageal fistulas 1. Defining Atresia 2. Defining Fistula Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 4 of 26 3. Esophageal atresia with tracheoesophageal fistula a. Esophageal atresia b. Tracheoesophageal fistula 4. Full esophageal atresia a. Polyhydramnios B. Diaphragmatic hernias 1. Congenital 2. Parasternal hernia 3. Esophageal hernia Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 5 of 26 FORMATION OF THE PRIMITIVE GUT AND DEVELOPMENT OF THE RESPIRATORY SYSTEM I. FORMATION OF THE GUT TUBE (PRIMITIVE GUT) A. During the third week of development, the gut forms from the folding of the ectoderm, endoderm, and splanchnic mesoderm in a ventral direction. This folding occurs in both a cranial/caudal and lateral direction. As development reaches 28 days, the amniotic cavity almost completely encircles the developing embryo and compresses the yolk sac, such that the upper ~1/3 of it (containing splanchnic mesoderm and underlying endoderm layer) is retained within the forming body cavity to become the gut tube. The portion of the yolk sac that is pinched outside of the amniotic cavity becomes the vitelline duct. The vitelline duct remains continuous with the midgut (Figures 1 below & 2 on next page) and forms a blind-ended duct embedded within the proximal region of the umbilical cord. 17 days 22 days 24 days 28 days Figure 1: Sadler 7.2 Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 6 of 26 B. At 4 weeks the gut tube can be subdivided into three regions. 1. Foregut: gives rise to the pharynx and its derivatives, larynx, trachea, and lungs, esophagus, stomach and proximal duodenum. Development of the stomach and proximal half of the duodenum will be described in a separate presentation. 2. Midgut: gives rise to the small intestine (distal duodenum, jejunum and ilium) and a portion of the large intestine (cecum, ascending colon and ~2/3’s of the transverse colon). To be describe in a later presentation. 3. Hindgut: gives rise to the distal 1/3 of the transverse colon, the descending and sigmoid colon, and rectum up to the pectin line. It is also responsible for the development of the urinary bladder and urethra. To be describe in a later presentation. Figure 2: Sadler 7.2D 28 days Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 7 of 26 II. DEVELOPMENT OF THE RESPIRATORY SYSTEM A. The respiratory system has its origin from the ventral surface of the foregut in a midline region between the 4th-6th pharyngeal arches. B. Respiratory diverticulum period (Week 4-5): At 4 weeks, retinoic acid is released by the underlying mesoderm, which in turn, stimulates the transcription factor TBX4 by the adjacent endoderm of the foregut at the site of the respiratory diverticulum (also called the lung bud or the laryngotracheal diverticulum). TBX4 induces the formation of the respiratory diverticulum (and continued growth of the conducting ducts and respiratory tissues that make up the lungs). C. The respiratory diverticulum is in open communication with the foregut (See Figures 2 on previous page and 3A below). Figure 3: Sadler 14.1 D. When the respiratory diverticulum expands caudally, two parallel longitudinal ridges called the tracheoesophageal ridges initially separate the respiratory diverticulum off of the gut tube (see Figure 4A on the next page) and then will fuse at midline to form the tracheoesophageal septum (See Figure 5 below). This Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 8 of 26 creates the laryngotracheal tube, which then separates the esophagus (dorsally) to the ventrally-positioned developing larynx, trachea and lungs. 1. As the respiratory diverticulum elongates caudally, it will give rise to a pair of lung buds that will form the right and left primary bronchi and lungs (See Figures 4 & 5). Figure 4: Sadler 14.2 Figure 5: Moore 10-2 Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 9 of 26 E. The endoderm of the respiratory diverticulum forms the epithelium and glands of the larynx, trachea, bronchi and lungs. F. The underlying splanchnic mesoderm gives rise to smooth muscle, connective tissues and cartilages associated with the trachea & bronchi & bronchioles. G. The laryngeal orifice (inlet) remains as a midline communication between the pharynx and the developing larynx (See Figure 4 on previous page). III. DEVELOPMENT OF THE LARYNX A. The larynx develops from endoderm (gives rise to the internal lining of the larynx) and from the underlying mesenchyme (forms the laryngeal cartilages, and muscles of the larynx) in the region immediately rostral to the laryngotracheal tube (between the 4th and 6th pharyngeal arches). See Figure 6 on the next page. B. Rapid proliferation of the mesenchyme produces 2 lateral laryngeal swellings that continue to expand the growth of the larynx laterally and anteriorly. This growth causes the transverse slit of the laryngeal office (formed at week 4) to form the “T- shaped” laryngeal opening at 6 weeks. See Figure 6A on the next page. C. Continued growth of the thyroid, cricoid and arytenoids cartilages (derived from mesenchyme for the 4th-6th pharyngeal arches), along with the formation of the epiglottis (between the 3rd and 4th pharyngeal arch, is completed by 12 weeks (See Figure 4 on previous page and Figure 6 on the next page). Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 10 of 26 Figure 6: Sadler 14.4 D. During this same period (4-9 weeks) of growth, the epithelium lining the cavity of the larynx is temporarily occluded. Beginning at week 9, there is reopening of the cavity of the larynx (process is called recanalization; see Figure 7), which gives rise to the formation of the paired ventricles, which form the false and the true vocal folds. E. Sensory and motor innervation of the larynx 1. Sensory and motor innervation of the larynx above the vocal folds: Figure 7: Sadler 15.18 Innervation of the mucosa and muscles superior to the true vocal folds are derived from the 4th pharyngeal arch are provided by the superior laryngeal nerves (from CN X). 2. Sensory and motor innervation of the larynx below the vocal folds: Innervation of the muscles and mucosa inferior to the true vocal folds are derived from the 6th pharyngeal arch, and provided by the right and left recurrent laryngeal nerves (from CN X). Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 11 of 26 IV. DEVELOPMENT OF THE TRACHEA, BRONCHIAL TREE AND THE LUNGS A. At the beginning of the 5th week, the respiratory diverticulum (Lung bud) and associated splanchnic mesoderm give rise to the formation of trachea (midline) and a pair of laterally orientated sacs called the bronchial buds (See Figure 5 on page 8 of my notes). 1. Release of the transcription factor sonic hedgehog by the epithelial cells stimulates the surrounding splanchnic mesoderm to release a series of fibroblast growth factors. 2. The release of these growth factors causes the bronchial buds to lengthen and enlarge to form the right and left primary (main) bronchi. B. At the end of the 5th week the right bronchial bud then gives rise to three secondary bronchial buds (corresponding to the three lobar branches in the right lung in the adult). The left bronchial bud forms two secondary bronchial buds, which corresponds to the two lobar branches of the left lung in the adult (See Sadler Figure 8 below, and Figures 9 &10 on the next page). Figure 8: Sadler 14.5 Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 12 of 26 Figure 9: Sadler 14.6 C. At the beginning of the 6th week, continued release of sonic hedgehog, promotes the epithelium of the developing lungs to initiate the outgrowth of 10 tertiary (segmental) bronchi in the right lung, and 8 tertiary bronchi in the left lung. These will form the bronchopulmonary segments of the adult right and left lungs (see Figure 10). D. Classification of the maturation stages of the lungs: Embryologist describe 4 distinct stages of the dividing duct system in the developing lung. Figure 10: Sadler 14.7 Listed in order of their development, they are described as: Pseudoglandular, Canalicular, Terminal sac, and Alveolar periods. Note: It is important to point out here that there are timing overlaps between the development stages listed above. This is because the proximal segments of the bronchial tree mature at a faster rate than the distal branches. 1. Pseudoglandular period (weeks 5-16): The conducting system of the bronchial tree forms during this period. Note that, the development of respiratory bronchioles and Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 13 of 26 alveoli, has yet to occur. Thus, survival resulting from a premature birth at this stage is not possible. 2. The Canalicular period (encompassing weeks 16-24) involves the formation of the duct system that is responsible for providing gas exchange. a. At 16 weeks terminal bronchioles (the last division of the conducting passage way) divide to give rise to several respiratory bronchioles (See Figure 11A on the next page). These ducts are characterized by cuboidal epithelium surrounded by smooth muscle, the absence of cartilage, and rapidly forming capillary beds within the surrounding mesenchyme. b. Optimal blood gas exchange and the absence of surfactant release (see next section) has yet to be established during this phase, and thus makes premature birth survival at this stage an extreme challenge. 3. The Terminal sac stage: (weeks 24-birth): By the end of the 6th month 4-6 primitive terminal sacs (also called primordial alveolar sacs) form off of a respiratory bronchiole. a. These sacs are characterized by a single layer of flattened epithelial cells that are in close proximity to capillaries within the underlying mesoderm (See Figure 11B on the next page). b. Note, limited gas/blood exchange is possible during the terminal sac stage, as the developing capillary/endothelial associations of the primitive Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 14 of 26 alveolar sacs are capable of facilitating blood/gas exchange at this time (week 26 and beyond). c. In addition, by week 26, the type II respiratory epithelial cells are releasing surfactant (a phospholipid-rich fluid which lowers the tension at the air-alveolar interface) into the lumen of the duct system, at levels sufficient to support premature birth at this time. d. By 26 weeks, the number of alveolar sacs is sufficient to provide adequate blood-gas exchange to support survival of a premature birth. Figure 11: Sadler 14.8 16-24 weeks: Canalicular 24 weeks-birth: (Terminal sac stage) respiratory period (no gas exchange is epithelium (Type 1), form primordial terminal sacs and possible at this stage). begin to associate with thin capillary epithelium, to form primitive alveoli. At week 26, functional Survival following premature blood/gas exchange can occur in the event of birth at 16 weeks is not premature birth. Key to this, is at this time, surfactant possible. levels released by the Type II respiratory epithelium reaches optimal levels in the lumen to promote adequate CO2-O2 gas exchange. Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 15 of 26 e. By the sixth month of development, the respiratory tree has undergone 17 generations of subdivisions. f. Note that, an additional 6 subdivisions of the alveoli tree will occur during post-natal life. 4. Alveolar stage (Maturation of the lungs): (Late gestation-into early childhood). a. Beginning late in gestation (~8 months), the type I alveolar cells (squamous epithelium) and the endothelial layer of the capillaries associated with the newly forming alveolar sacs expand and become thinner to increase the surface area between the two regions (see Figure 12)). This significantly improves the efficiency of the blood gas exchange rates, and these structures are now classified as “mature alveoli”. b. Maturation of alveoli and addition of new alveoli continue after birth. New alveoli are added until the child is approximately 8 years of age. Figure 12: Sadler 14.9 Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 16 of 26 E. Breathing movements begin before birth and are important for further lung development and the strengthening of the respiratory muscles (thoracic diaphragm and intercostal muscles). 1. Amniotic fluid fills the lungs during this period. At birth, the aspiration of amniotic fluid precedes the first natural breath. F. The type II alveolar epithelial cells produce and release surfactant, which is responsible for reducing the surface tension of the air-alveolar interface, which in turn, prevents the collapsing of the alveoli in the post-natal lung. 1. Surfactant release by type 2 cells begin around weeks 20- 22, however surfactant release does not reach levels sufficient to sustain life until around weeks 26-28. 2. Prenatal role of surfactant release: By week 34, elevated levels of surfactant secretions by the Type II cells continue to be released into alveolar duct, and mix with the amniotic fluid (which fills the entire conducting and respiratory duct system of the developing lungs). a. This increase of surfactant within the developing duct system of the lungs activates indigenous alveolar macrophages to produce and release immune-system proteins, including interleukin-1β. b. Released alveolar macrophages are responsible for the induction of partition: Through the breathing process of the fetus, the activated macrophages exit the lung tissue into the anionic fluid-filled duct system, and are expelled into the Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 17 of 26 amniotic cavity. There they will cross the chorion and make their way into the maternal uterus. Upon entering the maternal uterus, they release interleukin-1β, which results in an increase production and release of prostaglandins by the uterus. This in turn, increases and strengthens uterine contractions that leads to parturition. G. Summary of the maturation of the lungs Pseudoglandular period: 1. Development period: Weeks 5-16 2. Branching of the bronchial tree all the way down to the terminal bronchiole. 3. No respiratory bronchioles or alveoli are present. 4. Incompatible with sustaining life. Canalicular period: 1. Development period: Weeks 16-24 2. Branching of the terminal bronchioles gives rise to two or more respiratory bronchioles. 3. The blood/gas exchange between capillaries and respiratory bronchioles is incomplete. 4. Low levels of surfactant secretion begins late in this phase 5. Premature survival, up to 24 weeks, is not favorable. Terminal sac period: 1 Development period: Weeks 24-Birth 2. Terminal sacs (primitive alveoli branch and associate with capillaries to establish a functioning blood/gas exchange barrier). 3. Surfactant levels increase late in this phase 4. Premature survival is favorable at 26 weeks. Alveolar period: 1. Development period: Late gestation-early childhood 2. Terminal sacs (primitive alveoli) become mature alveoli. Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 18 of 26 V. TRANSITION OF THE DEVELOPING LUNGS INTO THE PLEURAL CAVITY A. Early development of the lungs occurs within the splanchnic mesodermal layer. B. Visceral mesothelial covering of the lungs: As growth of the lungs proceeds, they expand into the pericardioperitoneal canals (precursor to the pericardial and the pleural cavities) and are invested by a serous mesothelium (derived from the splanchnic mesoderm) called the visceral pleura that completely invests the surfaces of the right and left lungs. C. Mesothelial lining of the pleural cavity: Note, that as the pleural cavity develops, the walls of the pleural cavity (mediastinum, thoracic wall and diaphragm) are covered by a serous mesothelium (derived from the somatic mesoderm) called the parietal pleura. See Figures 9 & 10 on page 12 of my notes. VI. FORMATION OF THE PERICARDIAL AND PLEURAL CAVITIES IN THE THORAX A. Pleuropericardial folds (membranes): By end of the 6th week, two lateral folds (pleuropericardial folds) appear. They are positioned off of the lateral body wall and grow medially (Figure 13 on the next page). 1. Contents of the pleuropericardial folds: Each fold contains a corresponding Phrenic N. and Cardinal vein (See Figure 13 on the next page). 2. By the 7th week, the pleuropericardial folds fuse with each other to separate the pericardial cavity from the pleural cavity (See Figures 13 and 14 on the next page). Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 19 of 26 A B ~week 7 Figure 13: Sadler 7.5 Aorta Figure 14: Sadler 7.6 Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 20 of 26 VII. FORMATION OF THE THORACIC DIAPHRAGM AND COMPARTMENTILIZATION OF THE PLEURAL AND PERITONEAL CAVITIES A. During the 5th week the septum transversum (a ventral midline thickened plate of mesodermal tissue, derived from splanchnic mesoderm) occupies the space between the primitive thoracic and abdominal cavities (See Figure 15 on next page). Septum transversum does not completely separate the primitive thorax and abdominal cavities, and leaves bilateral openings on the right and left sides (lateral to the foregut) called pericardioperitoneal canals (See Figure 13 on the previous page). B. At approximately week 7, a pair of crescent-shaped folds, called pleuroperitoneal folds (membranes), close off the openings of the pericardioperitoneal canals by extending medially and ventrally. The pleuroperitoneal folds fuse with the mesentery of the esophagus and the septum transversum (See Figure 15 on next page). It is at this moment that all three cavities (pericardial, pleural and peritoneal) are fully compartmentalized from each other. Note that on the inferior right side of the diaphragm the majority of the liver (e.g. rt lobe, caudate and quadrate lobes) occupy its inferior surface. In contrast, on the left side, the smaller left lobe of the liver only occupies a portion of the left diaphragm leaving this side of the thoracic diaphragm vulnerable to incomplete closure of the left pleuroperitoneal fold and is clinically defined as being a “congenital diaphragmic hernia”. Failure to close will result in a left hypoplastic lung (collapsed lung), due to the pleural cavity being in full communication with the peritoneal cavity. Note, with the right plural cavity being open to the peritoneal cavity will increases the volume to the exposed left lung and resulting from this, and significantly decreases the negative pressure needed to maintain and inflate the left lung tissue upon inspiration. In addition, failure of closure on the left side presents the likelihood of the stomach and/or small intestines gaining Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 21 of 26 entrance (e.g., herniate) into the left pleural cavity (See Figure 18 on the last page of these notes). Figure 15: Sadler 7.7 C. At approximately 12 weeks, myoblasts from cervical somites 3, 4 and 5, infiltrate both the pleuroperitoneal membranes and the septum transversum along the rim of the forming diaphragm. This will give rise to the muscular part of the diaphragm. 1. Septum transversum forms the central tendon of the diaphragm. 2. The right and left diaphragmatic crura develop from the mesentery associated with the esophagus. 3. Central innervation (motor and sensory) of the thoracic diaphragm is provided by ventral rami from C3-C5 dermatomes which form the right and left phrenic nerves. D. Beginning at the 3rd month of development, the accelerated growth and elongation of the embryo and the expansive growth of the lungs, displaces the positioning of the diaphragm inferiorly, from its cervical starting position, to the lower thoracic/upper Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 22 of 26 lumbar level. This repositioning of the diaphragm, and the ingrowth of the muscular wall from the thoracic region (See Figure 15C), brings with it mixed sensory innervation, whereby: 1. Sensory & motor innervation of the peripheral diaphragm: The peripheral rim of the diaphragm is innervated by lower intercostal nerves. 2. Sensory & motor innervation of the central diaphragm: The central portion of the diaphragm receives motor and sensory innervation from the right and left phrenic nerves (provided by spinal roots C3-5). VIII. CLINICAL SIGNIFICANCE A. Esophageal Atresia w/ or w/out tracheoesophageal fistulas: Occurrence is 1:3000 births, and is the result of the abnormal partitioning by the tracheoesophageal septum of the esophagus and the trachea. This usually results in esophageal atresia (an abrupt closure of the esophagus) with or without trachea- esphageal fistulas. See Figure 17 on the next page. 1. Atresia is defined as a blunt (blind) ended closure of a normal opening or passage. 2. Fistula is defined as pathological sinus or abnormal passage leading from one organ/structure to another. 3. Esophageal atresia with tracheoesophageal fistula is the most common (accounts for ~90%) of the observed defects in the partitioning of the respiratory and digestive tubes by the tracheoesophageal septum (See Figure 16A on the next page and in Figure 17 on the next page). Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 23 of 26 a. Esophageal atresia results in the proximal part of the esophagus ending as a blind pouch (See Figure 16 A&B and Figure 17 on the next page). b. Tracheoesophageal fistula is defined by an abnormal connection between the esophagus and the trachea. i. Five possible variations of a tracheoesophageal fistula are shown in Figure 16 A,C, D, and E, with 16A being the most common (90%). Also see in Figure 17A & B on the next page. Figure 16: Sadler 15.7 Sadler Fig. 15.7 Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 24 of 26 ii. Diagnosis for esophageal atresia with tracheoesophageal fistula: At birth, feeding results in violent coughing and choking as food intake can only pass though the trachea due to the proximal end of the esophagus being blocked (atresia). These babies will have difficulty in breathing due to all ingested fluids being diverted into the trachea (Figure 16A). Fluid accumulation in the lungs can lead to pneumonia if not surgically corrected. Figure 17: Moore 10-7 4. Full esophageal atresia in the neonate (Shown in Figure 16B and 16D on the previous page) completely prevents passage of amniotic fluid from the pharynx/proximal esophagus into the stomach/intestinal tract. a. Polyhydramnios: Esophageal atresia prevents the neonate from swallowing and passing amniotic fluid Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 25 of 26 into the gastro-intestinal tract (where it would normally be absorbed into the neonate’s blood- stream and then transported across the neonate/maternal placenta barrier to be excreted). This results in an increase accumulation of excess amniotic fluid within the amniotic sac (a process called polyhydramnios). B. DIAPHRAGMATIC HERNIAS: 1. Congenital: a. A common malformation in newborn (1:2000 births) most frequently caused by the failure of one or both pleuroperitoneal membranes to close the pericardioperitoneal canal(s). See Figure 18 on next page. b. In 90% of the cases, the abdominal viscera (stomach, large and/or small intestine) can be found in the pleural cavity. See Figure 18 on next page. 2. Parasternal hernia: Failure of the muscle fibers to form near the sternal attachment of the diaphragm can result in a small peritoneal sac containing small intestine entering the mediastinum region of the chest. 3. Esophageal hernia: This defect can result from the under- development of the esophagus (e.g. shortening) or the failure of the pericardioperitoneal canal to close, whereby the upper portions of the stomach (cardiac, fundus and in extreme cases, a portion of the body of the stomach) herniate into the thorax. See Figure 18 on the next page. Respiratory and Body Cavities Development Dennis J. Goebel, Ph.D. Page 26 of 26 X-ray to the right shows intestines within the pleural cavity on the right side, due to incomplete closure of the pericardioperitoneal canal. Figure 18: Sadler 7.8