AA Reed Notes.pdf

Development of the respiratory system Upper respiratory tract: nose, nasal cavity and pharynx Lower respiratory tract: larynx, trachea, bronchi and lungs The respiratory tract doesn’t carry out its function until birth. Therefore, its development is not completed until the end of the fetal period. D...

Development of the respiratory system Upper respiratory tract: nose, nasal cavity and pharynx Lower respiratory tract: larynx, trachea, bronchi and lungs The respiratory tract doesn’t carry out its function until birth. Therefore, its development is not completed until the end of the fetal period. DEVELOPMENT OF THE UPPER RESPIRATORY TRACT The upper will be further explained during development of the GI system, in IOS II. In a 4 week embryo, we can find pharyngeal arches at the level of the neck. The caudal arches (IV and V) will give rise to the larynx. The arches are associated with different nerves. Each of the nerves will provide the structures derived from each of the arches. DEVELOPMENT OF THE LOWER RESPIRATORY TRACT In a 4 week embryo, we can identify the appointed structures. The endoderm tube (which arose from the incorporation of the dorsal part of the yolk sac) will give the primitive gut. This gut tube divides into: foregut, midgut and hindgut (from cranial to caudal). At the cranial end, we find the oropharyngeal membrane, and at the end, the cloacal membrane. From the anterior wall of the foregut, a structure known as the respiratory diverticulum arises. The lower respiratory system will develop from this diverticulum which appears during the 4th week. Foldings in the embryo 2 foldings take place at the same time within the embryo, giving it its C shape: Craneo-caudal foldings: cranial and caudal ends grow and fold ventrally. - The most important consequence is the narrowing of the yolk sac, which remains connected only through the vitelline duct. This is also a consequence of the lateral folding, merging the lateral portions of the yolk sac. - Additionally, the mouth becomes anterior to the heart, which folds ventrally. Lateral foldings: the amniotic cavity, found on top of the neural canal, will begin to fold laterally (and cranially) and ends up surrounding the body of the embryo. In the meantime, the mesoderm found along the body of the embryo, at both sides of the notochord, will separate through the formation of what will be the intraembryonic cavity. This gives rise to 2 layers of intraembryonic mesoderm: - Somatic or parietal mesoderm - Visceral or splanchnic mesoderm Result: - As the lateral folds progress, the parietal mesoderm will migrate with the surface ectoderm layer which is going to cover the whole body of the embryo. Therefore, it lines the body of the embryo on its internal surface. - The visceral mesoderm will remain surrounding the gut tube and developing mesoderm around it (ex: cardiogenic area). Therefore, when lateral folds end, the visceral mesoderm will be surrounding the gut tube and the developing viscera. - They divide as the intraembryonic cavity arises in the mesoderm layer. When the lateral and craneo caudal folds end, the cavity will be fully formed and enclosed, surrounding the gut tube. The outer layer is the parietal, the inner one surrounding the gut, the visceral. Difference between B and C: the folds have progressed, so the vitelline duct is much narrower, only remains attached by a very thin duct at the midline.Therefore, some points of cross section won’t show the connection. At this point: the embryo is covered by the amniotic cavity, with the intraembryonic cavity inside and within it, the primitive gut tube. The gut tube will remain attached, suspended from the body wall, by the dorsal mesentery (double layer of mesoderm). Layers of the protruding diverticulum Part of the respiratory viscera will originate from that endoderm layer, while some other viscera will arise from the visceral mesoderm surrounding it: - Endoderm → will give rise to the epithelium (mucosa) of the internal respiratory system - Visceral mesoderm → will give rise to the muscularis externa layer of the respiratory tract: cartilage, connective tissue and smooth muscle of the respiratory system The structure isn’t floating in the cavity, but remains attached to the body through the dorsal mesentery, a double layered structure of mesoderm. Splitting of foregut into esophagus and trachea The diverticulum grows and divides into 2 buds, the lung buds. These buds will have to be completely separated from the digestive tract: this will be achieved through the tracheoesophageal septum, which gradually separates the ventral respiratory diverticulum from the dorsal part of the foregut. The pharynx becomes divided into: a ventral portion, “the respiratory primordium” and a dorsal portion, “the esophagus”. Axial views of the tubes: 2 ridges of tissue, containing endoderm and mesoderm, grow towards the lumen of the tube to form the septum. Separate the trachea, anteriorly, from the esophagus posteriorly. TRACHEO-ESOPHAGEAL FISTULAS Anomalies can arise due to malformations in the tracheoesophageal septum. When the septum doesn’t completely form, a connection is left between the esophagus and trachea. It manifests immediately after birth, as soon as the baby starts breastfeeding. This condition is likely due to defects in the mesoderm layer, which is why it usually manifests along with problems in other mesoderm-derived structures: - VATER (Vertebral anomalies, Anal atresia, Tracheaesophageal fistula, Esophagus atresia, Renal atresia) - VACTERL (VATER + additional Cardiac defects and Limb defects) Occurs in 1/3000 births. - Prenatally, we have an excess of amniotic fluid (as the baby is unable to swallow it), condition known as polyhydramnios - Postnatally, problems manifest immediately after birth: there is regurgitation after feeding, as milk flows into the respiratory tract. Other conditions due to malformations in the septum include: blind tubes at the level of the foregut. Development of the diaphragm. Septum transversum The diaphragm is a thin muscle which separates thoracic and abdominal cavities and participates in respiration. How does it form? It arises from a thick plate of mesoderm, the septum transversum, which appears at the 4th week at the level of the thoracic cavity. This septum will form the central, tendinous portion of the diaphragm. It changes position as the baby grows, going from front to back: - Week 4: it’s at C1 level - Week 8: at the level of T7, at the front, and T12 at the back (as it’s not a flat structure, but dome shaped) Innervation: it’ll be provided by the phrenic nerves, whose origin is the anterior horn of C3-C5. Although found at thoracic level, it’s innervated by nerves coming from cervical level. This is because initially, it’s found at cervical level; the nerves reach it as it’s moving from front to back/down, so it “carries” them with it down the thoracic cavity. Pericardioperitoneal canals As it develops, the diaphragm partially divides thoracic and abdominal cavities. However, this septum doesn’t completely separate these cavities. It grows but at a given point, it stops, leaving 2 canals: the pericardioperitoneal canals. These canals will have to be closed, so other elements will contribute to their closure: Pleuroperitoneal membranes: they grow to cover the cavity, and fuse with the septum transversum Part of the dorsal mesentery: will also be associated with the septum Muscles from the dorsolateral part of the body walls Therefore, we can see that the diaphragm is derived from 4 structures, involved in separating the thoracic from the abdominal cavity: septum transversum (forms the tendinous portion), pleuroperitoneal membrane, dorsal mesentery and muscles from the dorsolateral body wall. CONGENITAL DIAPHRAGMATIC HERNIAS This condition arises when a hole remains in one of the sides of the diaphragm, due to malformations during its development. The pleuroperitoneal membrane doesn’t grow enough. Therefore, they fail to close the pleuroperitoneal canals, leaving a hole. As a consequence, part of the abdominal content can herniate into the thoracic cavity. This will interfere with lung development, as they become compressed; the correct formation of the respiratory system becomes compromised. It will cause problems in breathing, sometimes may even cause death. Occurs in 1/2000 births, usually on the left side (80-90%) rather than the right. When it occurs on the left side, known as the Bochdalek hernia. LUNG DEVELOPMENT INTO THE BODY CAVITY Cross section at the level of the heart and pericardial cavity: Lung buds, which arose from the respiratory diverticulum, grow laterally and craniocaudal. They grow into the intraembryonic cavity in which the heart is embedded. As they expand, the pleuropericardial membranes/folds will arise, to separate pericardial from pleural cavities. This membrane will delimit the space into which the lungs expand. The lungs grow into their corresponding pleural cavities and as they expand, the cavity itself becomes reduced. Keep in mind: at the beginning there is a common cavity, the intraembryonic cavity ,for the 3 regions (peritoneal, pericardial and pleural cavities). They’ll become separated by the - Diaphragm and pleuroperitoneal membranes - Pleuropericardial membrane Pleural cavities Initially, the pleural cavities are large, but become reduced as the lungs grow into them. Therefore, both membranes (visceral and parietal, from the corresponding intraembryonic cavity) come very close to one another. The visceral mesoderm which surrounds and expands with the lungs, will become very close to the parietal mesoderm recovering the walls of the pleural cavity. - Splanchnic/visceral pleura - Somatic/parietal pleura Finally, what we have is that the lungs are SURROUNDED by the pleural cavities, NOT CONTAINED within them (same as what happened with the heart and pericardium). Branching of the lung buds From the bronchial buds, the primary bronchi arise - Left primary bronchus: it’s divided into only 2 secondary bronchi (superior and inferior), which will penetrate the 2 lobes that the left lung will have. - Right primary bronchus: it will branch into 3 secondary bronchi (superior, middle and inferior), for the 3 right lung lobes Secondary/lobar bronchi will continue to divide and give off tertiary/segmental bronchi: - 8 tertiary bronchi on the left side - 10 tertiary bronchi on the right side For each of the segments within the lobes of both lungs. Branching regulation Members of the fibroblast growth factor family regulate this branching: FGF-2 and FGF-10, mainly. Stages of lung maturation As a review: 1ary bronchi → 2ary bronchi → 3ary bronchi → terminal bronchioles → respiratory bronchioles → alveolar ducts → alveolar sacs 4 IMPORTANT PERIODS in the histological development of the respiratory system: 1. Pseudoglandular period (5th-16th week): Branching has continued to form terminal bronchioles. Tertiary bronchi give off 23 terminal bronchioles. There are no respiratory bronchioles or alveoli present yet. If the baby is born during this period, it will not survive (no effective gas exchange) 2. Canalicular period (16th-26th week): each terminal bronchiole divides into 2 or 3 respiratory bronchioles, which in turn divide into 3-6 alveolar ducts. At this period, the baby could survive under intense care. 3. Terminal sac period (26th week till birth): the terminal sacs/primitive alveoli form, and the capillaries establish close contact with them at this point. The baby could survive if born during this period, but would probably need surfactant and oxygen to aid the baby in respiration. 4. Alveolar period (8 months to childhood): primitive alveoli mature. They will have a very very thin layer in contact with the capillaries (epithelial-endothelial contact), so gas exchange will be very effective and can occur to a great extent. Initially, epithelium is thicker, but ends up being a very thin squamous epithelium in close contact with the capillaries. At the terminal sac stage (around the end of the 6th month), type II pneumocytes start to secrete surfactant, a fatty substance which decreases surface tension in fluids and aids in respiration. If there’s not enough of this substance = problems in breathing. In cases of early labor (premature babies), one of the premature drugs administered to the mother are corticosteroids, which help and stimulate the lungs to mature and secrete surfactant, giving more chances for the premature baby to breathe correctly. KEY POINTS - Development of respiratory system: starts at week 4 Larynx: arises from caudal pharyngeal arches (IV-V) Trachea and lungs buds: form from the respiratory diverticulum and separate through the formation of the tracheoesophageal septum Type II pneumocytes will secrete surfactant, essential for respiration There are 4 stages of alveolar development: ○ Pseudoglandular stage: terminal bronchioles arise ○ Canalicular phase: respiratory bronchioles + alveolar ducts arise ○ Terminal phase: terminal sacs/alveolar sacs arise ○ Alveolar stage: primitive alveoli mature