Embryology LC12: Embryonic Development of the Respiratory System PDF

R OUTLINE I. THE GUT TUBE AND THE BODY CAVITY A. Formulation of Body Cavity B. Serous Membranes C. Abdominal Cavity D. Diaphragm and Thoracic Cavity E. Formation of Dia...

R OUTLINE I. THE GUT TUBE AND THE BODY CAVITY A. Formulation of Body Cavity B. Serous Membranes C. Abdominal Cavity D. Diaphragm and Thoracic Cavity E. Formation of Diaphragm II. RESPIRATORY SYSTEM A. The lung bud form during the 4th week B. Splitting of the foregut into esophagus and trachea C. Tracheo-Esophageal fistulas D. Clinical correlation E. Successive stages in the development of larynx F. Clinical correlation III. GROWTH OF LUNGS INTO THE BODY CAVITY A. Differentiation of Pleural Membranes B. Pleuropericardial Folds Separate Pleural and Pericardial Cavities C. Extension of the Septum Transversum, Partially Divides Abdominal and Thoracic Cavities D. Congenital Diaphragmatic Hernia E. Initial Patterning of the Lungs Figure 1. Mesodermal Layers IV. DEVELOPMENT OF HUMAN LUNG A. Endoderma/Mesenchymal Interactions Together, the visceral (splanchnic) layer of lateral plate mesoderm B. Signaling Molecules and underlying endoderm are called the splanchnopleure. C. Stages of Maturation of the Lungs The space created between the two layers of lateral plate D. Development of Lung Tissue (Air Exchange) mesoderm constitutes the primitive body cavity. E. Surfactant Proteins Augment Function of Phospholipid On the central axis, we have the neural tube and the derivatives Surfactants of the mesoderm (Paraxial, Intermediate and Lateral Plate F. Clinical Correlation Mesoderm). The Lateral Plate Mesoderm will split into two forming the primitive body cavity formation. The one that will be continuous with the ectoderm is the somatic I. THE GUT TUBE AND THE BODY CAVITY while the splanchnic will be near the endoderm. During the 4th week, the sides of the embryo begin to grow ventrally forming two lateral body wall folds. FORMATION OF THE BODY CAVITY At the end of the 3rd week, the intra-embryonic mesoderm ○ Lateral body wall folds differentiates into paraxial mesoderm, which forms somitomeres and consist of the parietal layer of the lateral somites that play a major role in forming the skull and vertebrae. plate mesoderm, overlying ectoderm, and ○ Intermediate mesoderm the cell from the adjacent somites that Contributes to the urogenital system migrate into the mesoderm layer across ○ Lateral plate mesoderm the lateral somitic frontier. Involved in forming the body cavity As these folds progress, the endoderm layer also folds ventrally and closes to form the gut tube. The lateral plate mesoderm split into two layers: By the end of the 4th week, the lateral body wall folds meet in ○ Parietal (somatic) Layer the midline and fuse to close the ventral body walls. Adjacent to the surface ectoderm (outer part) This closure is aided by growth of the head and tail regions (folds) and continuous with the extraembryonic that cause the embryo to curve into the fetal position. parietal mesoderm layer over the amnion. Closure of the ventral body wall is complete except in the region ○ Visceral (splanchnic) Layer of the connecting stalk (future umbilical cord). Adjacent to the endoderm forming the gut Similarly, closure of the gut tube is complete except for a tube and continuous with the visceral layer of connection from the midgut region to the yolk sac that forms the the extraembryonic mesoderm covering the vitelline duct (yolk sac). yolk sac. ○ This duct is incorporated into the umbilical cord, becomes very narrow, and degenerates between the second and third months of gestation. *Note that throughout the process of body cavity and gut tube development, the parietal and visceral layers of the lateral plate mesoderm are continuous with each other at the junction of the gut tube with the posterior body wall. Page 1 of 10 [EMBRYOLOGY] 1.12 Embryonic Development of the Respiratory System – Dr. Gail Domecq T. Tanawit position between the primitive thoracic and abdominal cavities when the cranial end of the embryo grows and curves into the fetal position. This septum does not separate the thoracic and abdominal cavities completely but leaves large openings, the pericardioperitoneal canals, on each side of the foregut. Parietal (somatic) mesoderm lines embryonic body cavity (coelom) Visceral (Splanchnic) mesoderm covers endodermal gut tube Gut tube suspended from body wall by dorsal mesentery. When lung buds begin to grow, they expand caudolaterally within the pericardioperitoneal canals. As a result of the rapid growth of the lungs, the pericardioperitoneal canals become too small, and the lungs Figure 2. Lateral folding of the embryo. begin to expand into the mesenchyme of the body wall dorsally, laterally, and ventrally. Ventral and lateral expansion is posterior to the pleuropericardial folds. At first, these folds appear as small ridges projecting into the primitive undivided thoracic cavity. With expansión of the lungs, mesoderm of the body wall forms two components: the definitive wall of the thorax and the pleuropericardial membranes, which are extensions of the pleuropericardial folds that contain the common cardinal veins and phrenic nerves. Subsequently, descent of the heart and positional changes of the sinus venosus shift the common cardinal veins toward the midline, and the pleuropericardial membranes are drawn out in mesentery-like fashion. Finally, they fuse with each other and with the root of the lungs, and the thoracic cavity is divided into the definitive pericardial cavity and two pleural cavities. In the adult, the pleuropericardial membranes form the fibrous pericardium. Figure 3. Cranio-Caudal Folding FORMATION OF DIAPHRAGM Although the pleural cavities are separate from the pericardial SEROUS MEMBRANES cavity, they remain in open communication with the abdominal Some cells of the parietal layer of the lateral plate mesoderm lining (peritoneal) cavity by way of the pericardioperitoneal canals. the intraembryonic cavity become mesothelial and form the parietal During further development, the opening between the layer of the serous membranes lining the outside of the peritoneal, prospective pleural and peritoneal cavities is closed by crescent- pleural, and pericardial cavities. shaped folds, the pleuroperitoneal folds, which project into the The parietal layer is in the outermost part of the serous membranes. caudal end of the pericardioperitoneal canals. In a similar manner, cells of the visceral layers of the lateral plate Gradually, the folds extend medially and ventrally, so that by the mesoderm form the visceral layer of the serous membranes covering seventh week, they fuse with the mesentery of the esophagus the abdominal organs, lungs, and heart. and with the septum transversum. Abdominal (Peritoneal Serous Membrane), Lungs (Pleural Serous The connection between the pleural and peritoneal portions of Membrane), and the Heart (Pericardial Serous Membrane). the body cavity is closed by the pleuroperitoneal membranes. Serous membranes are made up of simple cuboidal epithelium. Further expansion of the pleural cavities relative to mesenchyme of the body wall adds a peripheral rim to the pleuroperitoneal ABDOMINAL CAVITY membranes. Visceral and parietal layers of serous membrane are continuous with Once this rim is established, myoblasts originating from somites each other as the dorsal mesentery (like an anchor), which suspends at cervical segments three to five (C3-5) penetrate the the gut tube from the posterior body wall into the peritoneal cavity. membranes to form the muscular part of the diaphragm. Dorsal mesentery extends continuously from the caudal limit of the Thus, the diaphragm is derived from the following structures: foregut to the end of the hindgut. Ventral mesentery exists only from the caudal foregut to the upper ○ The septum transversum, which forms the central portion of the duodenum and results from thinning of the mesoderm tendon of the diaphragm of the septum transversum. ○ The two pleuroperitoneal membranes These mesenteries are double layers (outer parietal and inner ○ Muscular components from somites at cervical visceral layer) of the peritoneum that provide a pathway for blood segments three to five vessels, nerves, and lymphatics to the organs. ○ The mesentery of the esophagus, in which the crura of the diaphragm develops. DIAPHRAGM AND THORACIC CAVITY During the fourth week, the septum transversum lies opposite The septum transversum is a thick plate of mesodermal tissue cervical somites, and nerve components of the third, fourth, and occupying the space between the thoracic cavity and the stalk of fifth cervical segments of the spinal cord grow into the septum. the yolk sac. At first, the nerves, known as phrenic nerves, pass into the ○ The septum is derived from visceral (splanchnic) septum through the pleuropericardial folds. (It is not completely mesoderm surrounding the heart and assumes its separate from the thoracic to the abdominal curve) Page 2 of 10 [EMBRYOLOGY] 1.12 Embryonic Development of the Respiratory System – Dr. Gail Domecq T. Tanawit This explains why further expansion of the lungs and descent of Mesoderm increases production of Retinoid Acid. the septum shift the phrenic nerves that innervate the diaphragm ○ Upregulates TF TBX4 into the fibrous pericardium. The appearance and location of the lung bud are dependent upon an Although the septum transversum lies opposite cervical segments increase in retinoic acid (RA) produced by adjacent mesoderm. This during the fourth week, by the sixth week, the developing increase in RA causes upregulation of the transcription factor TBX4 diaphragm is at the level of thoracic somites. expressed in the endoderm of the gut tube at the site of the The repositioning of the diaphragm is caused by rapid growth of respiratory diverticulum. the dorsal part of the embryo (vertebral column), compared with TBX4 induces formation of the bud and the continued growth and that of the ventral part. differentiation of the lungs. By the beginning of the third month, some of the dorsal bands of Lung bud initially has open communication with the foregut. the diaphragm originate at the level of the first lumbar vertebra. Caudal expansion The phrenic nerves supply the diaphragm with its motor and When the diverticulum expands caudally, however, two longitudinal sensory innervation. ridges, the tracheoesophageal ridges, separate it from the foregut. Because the most peripheral part of the diaphragm is derived When tracheoesophageal ridges fuse to form tracheoesophageal from mesenchyme of the thoracic wall, it is generally accepted septum, foregut is divided into: that some of the lower intercostal (thoracic) nerves contribute ○ Dorsal portion – esophagus sensory fibers to the peripheral part of the diaphragm. ○ Ventral portion – Trachea and Lung buds There are times where there is a problem in the closing of the Respiratory primordium maintains laryngeal communication (with pleuroperitoneal membrane causing hernia sa singit the pharynx) through the laryngeal orifice. (Diaphragmatic Hernia) which is a congenital diaphragmatic The respiratory tract is derived from foregut endoderm and hernia; 1/2000 gets it; causation is failure to close of 1 or 2 associated mesoderm. pleuro-peritoneal cavity. Figure 5. Embryo of approximately 25 days of gestation showing the relation of the respiratory diverticulum to the heart, stomach, and liver. Figure 6. Sagittal section through the cephalic end of a 5-week embryo showing Figure 4. Embryology of the diaphragm. The respiratory tract is derived from the openings of the pharyngeal pouches and the laryngotracheal orifice. the foregut endoderm and associated mesoderm THE LUNG BUD FORM DURING THE 4TH WEEK II. RESPIRATORY SYSTEM Initially appear as the respiratory diverticulum, which is a ventral outgrowth of foregut endoderm. Mesoderm dependent process. 4th week Retinoic Acid produced by adjacent mesoderm induces expression of Endodermal derivative (origin) TBX4 in foregut endoderm. TBX4 induces growth and differentiation ○ Epithelium of the internal lining of Larynx, trachea, of the trachea and lungs. bronchi, Lungs Splanchnic Mesoderm SPLITTING of the FOREGUT INTO ESOPHAGUS and TRACHEA ○ Cartilage, muscle and connective tissue components of Trachea-esophageal ridges: longitudinal ridges that eventually fuse to the trachea and lungs separate trachea from the esophagus. Respiratory diverticulum (lung bud) formation from the ventral wall of foregut Page 3 of 10 [EMBRYOLOGY] 1.12 Embryonic Development of the Respiratory System – Dr. Gail Domecq T. Tanawit CLINICAL CORRELATIONS Tracheoesophageal Fistula Figure 7. Successive stages in development of the respiratory diverticulum showing the ridges and formation of the septum, splitting the foregut into esophagus and trachea with lung buds. Figure 9. Tracheoesophageal Fistula in male fetus. The upper esophageal segment ends blindly (pointer). TRACHEO-ESOPHAGEAL FISTULAS Tracheal Agenesis ○ Lungs bud off esophagus Figure 8. Various types of esophageal atresia and/or TEFs. A. The most frequent abnormality [90% of cases) occurs with the upper esophagus ending in a blind Figure 10. Tracheal Agenesis pouch and the lower segment forming a fístula with the trachea. B. Isolated esophageal atresia (4% of cases]. C. H-type TEF [4% of cases). D,E. Other SUCCESSIVE STAGES in the DEVELOPMENT of LARYNX variations [each 1% of cases] The epithelial lining of the larynx is of endodermal origin, which proliferates and temporarily OCCLUDES the lumen of the larynx. A Incomplete separation and or atresia of trachea and esophagus (B on combination of apoptosis and growth of the wall of the larynx allows the right shows esophageal atresia) recanalization by about 10 weeks. Defect likely in mesoderm and usually associated with other defects The cartilages and muscles of the larynx arise from mesenchyme involving mesoderm (cardiovascular malformations, VATER/VACTERL, from the 4th and 6th pharyngeal arches are innervated by branches etc.) of the vagus nerves (4th arch by the superior laryngeal branch, 6th VATER= Vertebral anomalies, Anal atresia, Tracheoesophageal fistula, arch by the recurrent laryngeal branch.) Esophageal atresia, Renal atresia. As a result of rapid proliferation of this mesenchyme, the laryngeal VACTERL= VATER + Cardiac Defects and Limb Defects. orifice changes in appearance from a sagittal slit to T-shaped opening Occurs in approx. 1/3000 births, most (90%) are that shown (A) above. Complications: ○ PRENATAL: Polyhydramnios: due to inability to swallow amniotic fluid in uterus ○ POSTNATAL: Gastrointestinal: Infants cough and choke when swallowing because of accumulation of excessive saliva in mouth and upper respiratory tract. Milk is REGURGITATED IMMEDIATELY after feeding. Respiratory: Gastric contents may also reflux into the trachea and lungs, causing choking and often leading to PNEUMONITIS. Figure 11. Laryngeal orifice and surrounding swellings at successive stages of development. A. 6 weeks.B. 5 weeks c. 6 weeks D. 10 weeks. *SURGICAL REPAIR (NEONATAL OR UTERO) NOW RESULT IN 85% SURVIVAL RATES. Vacuolization and recanalization produce a pair of lateral recesses, the laryngeal ventricles. These recesses are bounded by folds of tissue that differentiate into the false and true vocal cords. Page 4 of 10 [EMBRYOLOGY] 1.12 Embryonic Development of the Respiratory System – Dr. Gail Domecq T. Tanawit All laryngeal muscles are innervated by branches of the 10th cranial (peritoneal) cavity by way of the pericardioperitoneal nerve; the vagus nerve. The superior laryngeal nerve innervates canals derivatives of the fourth pharyngeal arch, and the recurrent o Further expansion of the pleural cavities relative to laryngeal nerve innervates derivatives of the sixth pharyngeal arch. mesenchyme of the body wall adds a peripheral rim to When the mesenchyme of the two arches transforms into the the pleuroperitoneal membranes thyroid, cricoid, and arytenoid cartilages, the characteristic adult shape of the laryngeal orifice can be recognized. CLINICAL CORRELATIONS Laryngeal Atresia ○ Failure of recanalization results in obstruction of the upper airway – congenital high airway obstruction syndrome (CHAOS). The atresia or stenosis causes lower airways to become dilated, lungs to enlarge and become ○ Echogenic and the diaphragm becomes flattened or inverted. Can be detected by ultrasound. Laryngeal Web ○ Results from partial recanalization of the larynx during the 10th week. A membranous web forms at the level of the vocal cords, partially obstructing the airway. ○ Progressive changes in the development of the Figure 13. Endoderm of the lower part of L-T Tube. laryngotracheal tube. ○ Endodermal lining distal to the larynx differentiates into the epithelium and glands of the trachea and pulmonary epithelium. The cartilage, connective tissue and muscles of the trachea derived from splanchnic mesenchyme. III. GROWTH OF LUNGS INTO THE BODY CAVITY Foregut endoderm surrounded by visceral (splanchnopleuric) mesoderm and suspended in the body wall by dorsal mesentery. As lungs grow, they expand into the body cavity. Figure 14. A. Ventral view of the bronchial buds covered by visceral pleura. B. Once the pericardioperitoneal canals separate from the pericardial and peritoneal cavities, respectively, the lungs expand in the pleural cavities. Note the visceral and parietal pleural cavity. The visceral pleura extends between the lobes of the lungs. PLEUROPERICARDIAL FOLDS SEPARATE PLEURAL and PERICARDIAL CAVITIES Separating the abdominal and thoracic cavities —> development of the septum transversum and diaphragm. As the embryo folds, a connective tissue structure, the septum transversum, forms between the heart and body stalk (refer to figure 16). Ventral and Lateral expansion is posterior to pleuropericardial folds; these folds appear as small ridges projecting into the primitive undivided thoracic cavity. As the lungs expand, mesoderm of the body wall splits into two components; (1) the definitive wall of the thorax and (2) the pleuropericardial membranes - extensions of pleuropericardial folds that contain the common cardinal veins and phrenic nerves. Figure 12. Formation of the dorsal mesentery. A. The primitive gut tube initially Subsequently, descent of the heart and positional changes of the hangs from the posterior body wall by a broad bar of mesenchyme but, B, in sinus venosus shift the common cardinal veins toward the midline, regions inferior to the septum transversum this connection thins out to form a and the pleuropericardial membranes are drawn out in membranous dorsal mesentery composed of reflected peritoneum. mesentery-like fashion. Finally, they fuse with each other and with the root of the lungs, and DIFFERENTIATION of PLEURAL MEMBRANES the thoracic cavity is divided into the definitive pericardial cavity and The lung buds “punch” into the visceral mesoderm. The mesoderm, two pleural cavities. which covers the outside of the lung, develops into the visceral In the adult, the pleuropericardial membranes form the fibrous pleura. pericardium. The somatic covering the body wall from the inside becomes the parietal pleura. The space between is the pleural cavity. o Pleural cavities are separated from the pericardial cavity, they remain in open communication with the abdominal Page 5 of 10 [EMBRYOLOGY] 1.12 Embryonic Development of the Respiratory System – Dr. Gail Domecq T. Tanawit Figure 17. Septum Transversum formation. Figure 15. Development of the heart 5th to 8th week. Figure 16. Development of the septum transversum. EXTENSION of the SEPTUM TRANSVERSUM PARTIALLY DIVIDES ABDOMINAL Figure 18. Extension of the septum transversum partially divides and THORACIC CAVITIES abdominal and thoracic cavities. Grows in a roughly transverse plane from front to back Is initially at the level of C1 but is displaced caudally by differential growth of the embryo. CONGENITAL DIAPHRAGMATIC HERNIA At week 5-6, myoblasts migrate into septum, carrying innervation relatively common (1/2000 births) with them (ventral rami from C3, 4, 5) Hiatal hernias are most frequent, but effects are rather minor due to - Hence, the course of the phrenic nerve small size of defect By week 8, it is angled downward such that the front of the septum is Hernias due to failure of one or both pleuroperitoneal membranes to at about T7, back edge is at about T12 (similar to adult). close off pericardioperitoneal canals have much more significant The septum transversum stops at the gut tube, leaving two open clinical impact because herniated abdominal contents interfere with passageways on the left and right sides, aka the lung development. “pericardioperitoneal canals” (aka pleural canals, shown in Figure 80-90% of hernias with clinical impact are on the left side. Large 17) defects have mortality due to extent of lung hypoplasia and Closing off these canals requires growth from the dorsolateral body dysfunction wall, aka the “pleuroperitoneal membranes” (Refer to Figure 17 A A large defect is associated with the high rate of mortality (75%) from and B) pulmonary hypoplasia and dysfunction Defects in this process cause congenital diaphragmatic hernias Types of diaphragmatic hernia; (1)parasternal hernia (2)esophageal (CDH): abdominal contents herniate into pleural cavities and hernia interfere with lung development. Parasternal hernia This septum does not separate the thoracic and abdominal cavities o defect is frequently seen in the anterior portion of the completely but leaves a large opening in the pericardioperitoneal diaphragm canal. Esophageal hernia o congenital shortness of esophagus. Upper portions of the stomach are retained in the thorax and the stomach is constricted at the level of diaphragm. Page 6 of 10 [EMBRYOLOGY] 1.12 Embryonic Development of the Respiratory System – Dr. Gail Domecq T. Tanawit III. DEVELOPMENT OF HUMAN LUNG (Note : panel 1 is as viewed from the front; panels 2& 3 are as viewed from the back) 9=L inferior lobe primordium (see Figure 21) Figure 19. Congenital Diaphragmatic Hernia. INITIAL PATTERING of the LUNGS First three branching events are stereotyped : o Trachea into two primary bronchi (left and right) o Left primary bronchus into two secondary bronchus (corresponding to the two lobes of the left lung) All of these will be coming from the endoderm from the pharyngeal pouches 1, 2, and 3. o 28th day: development of the trachea o 32nd day: formation of the primary bronchial bud Figure 21. Human Lung Development o 33rd day: formation of the primary bronchi o 35th day: formation of the lobes (right upper lobe, middle lobe, and right lower lobe) ENDODERMAL/MESENCHYMAL INTERACTIONS IMPORTANT FOR BRANCHING o the development is almost complete on the 7th week MORPHOGENESIS Three secondary buds form on the right (corresponding to the 3 Right side cultured unperturbed after dissection (ie. covered by lung lobes on the right) and ten tertiary(segmental) bronchi form in the mesenchyme) right lung. Eight bronchi form in the left lung establishing the 18 Left bronchial tip covered with tracheal mesenchyme. bronchopulmonary segments of the adult human lung. Note: no branching occurs at left bronchial tip due to tracheal mesenchyme inhibition Figure 22. Dissected embryonic mouse. Figure 20. Development of the major branching patterns of the lungs. Page 7 of 10 [EMBRYOLOGY] 1.12 Embryonic Development of the Respiratory System – Dr. Gail Domecq T. Tanawit SIGNALING MOLECULES KNOWN TO BE IMPORTANT FOR LUNG BUDDING and Many more terminal sacs develop, with very thin BRANCHING MORPHOGENESIS epithelium and capillaries bulging into the developing alveoli. Blood-air barrier becomes well developed. Tbx/RA signaling induces mesenchyme to secret FGF10, which Surfactant production is sufficient to prevent atelectasis. induces epithelial growth. Surfactant production begins at 20 to 22 weeks Branching initiated by BMP4 secretion of apical cells (arrests their Terminal sacs (primitive alveoli) form, and capillaries proliferation). Epithelium also secrets SHH, which inhibits establish close contact. mesenchyme proliferation and FGF0 secretion. Mesenchymal cells secrete TGF10 secretion. Mesenchymal cells secrete TGF B which D. Alveolar Period (late fetal period to age 8): promotes deposition of ECM. Alveoli-like structures are present during the 32nd week. FGF10 signaling NOT inhibited at lateral aspects of both, promoting Epithelial lining sacs attenuate lining of extremely thin growth on either side squamous epithelia, capable of gas exchange. By the end of the 6th month, 17 generations of subdivisions had 95% of characteristic mature alveoli develop after birth. formed. Six more divisions occur during postnatal life for 23 At 38 weeks, the lungs are capable of respiration because branching events in the adult human lung the alveolocapillary membrane (pulmonary diffusion Branching continues to be regulated by epithelial mesenchymal barrier or respiratory membrane) is sufficiently thin to interactions (deriving from endodermal epithelial lung buds and allow gas exchange. splanchnic mesoderm surrounding them). At birth, mammalian lungs are far from mature. Main point Respiratory movements after birth bring air into the ○ Branching morphogenesis in the lungs is mesoderm and lungs, which expand and fill the pleural cavity. Although retinoid-dependent (among other factors). Late disruption the alveoli increase somewhat in size, growth of the lungs may have minor effects whereas early disruption may after birth is due primarily to an increase in the number of result in hypoplasia or even agenesis. respiratory bronchioles and alveoli. It is estimated that only one-sixth of the adult number of alveoli are present at birth. The remaining alveoli are formed during the first 10 years of postnatal life through the continuous formation of new primitive alveoli. Major mechanism for increase is the formation of secondary connective tissue septa that divide existing alveolar sacs. Initially, the secondary septa is relatively thick. In time, they transform into thinner mature septa capable of full respiratory exchange function. Figure 23. Signaling molecules known to be important for lung budding and branching morphogenesis. A, The tip of an elongating respiratory duct. Fibroblast growth factor-10 (FGF-10) secretion in the mesenchyme stimulates the growth of the tip of the epithelial duct toward it. B, The prelude to branching. Inhibition of FGF-10 signaling at the tip of the duct leads to stabilization of that area. C, Cleft formation. STAGES OF MATURATION OF THE LUNGS A. Pseudoglandular Period (5-17 weeks) By 17 weeks, all major elements have formed except those involved with gas exchange (fetuses unable to survive if born at this stage). Branching has continued to form terminal bronchioles. No respiratory bronchioles or alveoli are present. B. Canalicular Period (16-26 weeks): Bronchi and terminal bronchioles become larger; lung tissue becomes high vascular. Surfactant production begins around week 22, but not enough to prevent airway collapse (atelectasis). Alveolar ​ Figure 24. Evaluation of fetal thorax under the microscope. A and B, ducts with terminal sacs form by week 24, so limited early stages of lung development. C and D alveolocapillary respiration is possible. membrane is thin and some capillaries bulge into the terminal sacs Respiration is possible at the end (26 weeks): some and alveoli. thin-walled terminal sacs (primordial alveoli) have developed; lung tissue is well vascularized Each terminal bronchiole divides into two or more respiratory bronchioles, which in turn divide into three to six alveolar ducts. C. Terminal Sac Period (26 weeks to birth): Page 8 of 10 [EMBRYOLOGY] 1.12 Embryonic Development of the Respiratory System – Dr. Gail Domecq T. Tanawit DEVELOPMENT of LUNG TISSUE TEST YOUR KNOWLEDGE 1. Within hours after birth, a baby, whose mother is diabetic, had a rising respiratory rate and labored breathing. The baby became cyanotic and died. Postmortem histologic examination revealed collapsed alveoli lined with eosinophilic material. What is the diagnosis? a. Congenital emphysema b. Respiratory distress syndrome c. Cystic fibrosis d. Tracheoesophageal fistula e. Pulmonary carcinoma 2. The trachea is lined with pseudostratified ciliated columnar epithelium with goblet cells. This epithelium is derived from a. Neuroectoderm b. Endoderm c. Ectoderm d. visceral mesoderm e. mesoderm of fourth and sixth pharyngeal arches 3. Smooth muscle, connective tissue, and cartilage of primary bronchi are derived from which one of the following sources? a. Neuroectoderm b. Endoderm c. Ectoderm d. Visceral mesoderm e. Mesoderm of pharyngeal arches 4 and 6 4. Components of the blood–air barrier in the lung are derived from which of the following sources? a. Ectoderm only b. Visceral mesoderm only c. Visceral mesoderm and ectoderm d. Endoderm and ectoderm Figure 25. Histological development of the lung: Terminal Sac Period of e. Visceral mesoderm and endoderm Newborn. A. Canalicular Period (16-26th week) cuboidal cells lining the 5. eIn which stage of lung maturation is the blood–air barrier respiratory bronchiole, B. Terminal Sac Period (end of the 6th and beginning of established? the 7th prenatal month) Cuboidal cells become very thin and intimately a. Embryonic period associated with the endothelium of blood and lymph capillaries or form terminal b. Pseudoglandular period sacs [primitive alveoli), C. Alveolar Period (late fetal to childhood) thin squamous c. Canalicular period epithelial cells [alveolar epithelial cells, type I] and surrounding capillaries d. Terminal sac period protruding into mature alveoli. e. Alveolar period 6. Collapse of bronchi caused by failure of bronchial cartilage SURFACTANT PROTEINS AUGMENT FUNCTION of PHOSPHOLIPIDS development is indicative of which one of the following congenital SURFACTANTS malformations? a. Congenital bronchial cysts ​ Surfactant A: activates macrophage to elicit contractions, also b. Congenital neonatal emphysema important in host defense c. Tracheoesophageal fistula ​ Surfactant B: organizes into tubular structure that are much more d. Hyaline membrane disease efficient at reducing surface tension (specific deficiency in Surfactant e. Pulmonary hypoplasia B can lead to respiratory distress) 7. Development of which of the following is the first sign of respiratory ​ Surfactant C: enhances function of surfactant phospholipids system development? ​ Surfactant D: important in host defense. a. Tracheoesophageal septum ​ b. Hypobranchial eminence c. Primitive foregut d. Tracheoesophageal fistula e. Respiratory diverticulum 8. A young mother brings her recently born infant into your office and complains that the infant gags and chokes after swallowing milk. A physical examination indicates excessive saliva and mucus around the mouth and nose, abdominal distention, pneumonitis, and radiographs indicate air in the infant’s stomach. What is the most likely cause? a. Hypertrophic pyloric stenosis a. Tracheoesophageal fistula b. Congenital lobar emphysema c. Respiratory distress syndrome d. Pulmonary hypoplasia Figure 26. The four major surfactant proteins; A, B, C, and D. Page 9 of 10 [EMBRYOLOGY] 1.12 Embryonic Development of the Respiratory System – Dr. Gail Domecq T. Tanawit 9. Which of the following components of the respiratory tract would be directly affected by a developmental failure of normal differentiation of the foregut endoderm? a. Nasal epithelium b. Intrinsic laryngeal muscles c. Bronchial cartilages d. Trachealis muscle e. Alveoli 10. A 25-year-old man is brought to the emergency room after suffering a deep stab wound directly through the right 5th intercostal space in the midclavicular line. Which of the following structures is most likely pierced? a. Superior lobe of the lung b. Lingula of the lung c. Inferior lobe of the lung d. Apex of the lung e. Middle lobe of the lung 1. B, 2. B, 3. D, 4. E, 5. D, 6. B, 7. E, 8. B, 9. E, 10. E REFERENCES Sadler, T. W., et.al. (2019). Langman's medical embryology (14th ed.). Lippincott Williams & Wilkins. Sirmata Trans Tanawit, G., PPT Lecture Page 10 of 10