Embryology of the Respiratory System DA.pdf

Embryology of the Respiratory System  Respiratory System Upper respiratory tract: Nose Nasal cavity & paranasal sinuses Laryngo-pharynx Larynx. Lower respiratory tract: Trachea Bronchi Lungs  Lung Development: 5 Stages Embryonic:...

Embryology of the Respiratory System  Respiratory System Upper respiratory tract: Nose Nasal cavity & paranasal sinuses Laryngo-pharynx Larynx. Lower respiratory tract: Trachea Bronchi Lungs  Lung Development: 5 Stages Embryonic: development of the trachea and primary bronchial buds Pseudoglandular: development of the bronchial tree down to the level of the terminal bronchioles Canalicular: development of the respiratory bronchioles and primitive alveoli Saccular: maturation of the alveoli and production of surfactant Alveolar: increase in number of alveoli capillaries and continued maturation  Embryonic Stage Development of the bronchial tree begins in the embryonic stage, with budding of the embryonic gut tube to form the larynx, trachea and lungs by the end of the stage. The embryonic layers and their associated bronchial tree structures Tissue layer Structures formed in the bronchial tree Endoderm Respiratory epithelium Glands of the respiratory tract Mesoderm Visceral pleura [Splanchnopleuric layer] Connective tissue Bronchial musculature Cartilage Mesoderm Parietal pleura [somatopleuric layer]  Process of development at the embryonic stage The bronchial tree develops off of the foregut of the embryonic gut tube. Occurs 4–7 weeks after conception Embryonic gut tube: Forms from the laterally folded endoderm layer Is surrounded by mesoderm Has 3 sections: Foregut Midgut Hindgut Embryonic gut tube Foregut Midgut hindgut  Lung bud (respiratory diverticulum) Buds off of the ventral side of the foregut around week 4. Simultaneously grows out (ventrally) and down (caudally). Includes both endoderm and surrounding splanchnopleuric mesoderm  Tracheoesophageal Groove (or ridge) As the lung bud grows out and down, the tracheoesophageal groove appears as lateral indentations between the new lung bud and the foregut. The grooves/ridges move in medially, “pinching off” the lung bud, and forming the tracheoesophageal septum. The tracheoesophageal septum creates two separate tubes: Esophagus (posteriorly, from the original foregut) Trachea (anteriorly, from the lung bud) Primary bronchial buds: The trachea bifurcates into the right and left bronchial buds.  Defects at this stage can cause: Tracheoesophageal fistula (TEF): occurs when the tracheoesophageal grooves fail to fully close in the midline Esophageal atresia: portions of the esophagus fail to form; often coexists with TEF Tracheal atresia: partial or complete absence of the trachea below the larynx (lethal): The lower respiratory tract is often connected to the GI tract. Bronchopulmonary sequestration: abnormally formed nonfunctioning accessory lung tissue that is not connected to the rest of the bronchial tree (conducting portion) Development of the Respiratory System  Pseudoglandular Stage Weeks 8-16 The conducting portion of the airways continue to develop, forming bronchioles from the tertiary bronchi formed by the end of week 8. At this point, the mesoderm that will develop into alveoli has not completed development, so there are no formed alveoli. This means that no gas exchange takes place in the lungs. Canalicular Stage (Weeks 16 – 26) Throughout this ten week period the respiratory bronchioles develop by budding off the bronchioles formed during the pseudoglandular stage. The respiratory bronchioles are the first structure in the respiratory portion. Type II pneumocytes: Thicker cuboidal cells (unable to exchange gas) Line most of the respiratory epithelium and alveoli Begin producing surfactant around week 20 Continue to produce amniotic fluid Minimal differentiation into flattened type I pneumocytes that are capable of gas exchange  Terminal Sac Stage (week 26 to Term) The alveoli begin to develop around 26 weeks gestation. Two cell types are present: A. Type I Pneumocytes (Type 1 alveolar cells) – comprising 90% of the alveoli, this cell type is the squamous epithelium that makes up the alveolar walls. B. Type II Pneumocytes (Type 2 alveolar cells) – comprising 10% of the alveoli, this simple columnar cell produces surfactant.  Fetal Breathing Fetal breathing involve muscle contractions causing inhalation and exhalation of amniotic fluid – from 20-21 weeks. Prior to birth, the lungs are filled with amniotic fluid, mucus, and surfactant. During parturition the fetal thoracic cavity is compressed, expelling much of this fluid. Some fluid remains, however, but is rapidly absorbed by the body shortly after birth.  Respiratory Distress Syndrome Surfactant is clinically relevant in the pathophysiology of newborn respiratory distress syndrome. This occurs when a baby is born before the full development of type II pneumocytes, meaning their lungs do not produce sufficient surfactant. Without the surfactant, the alveoli need higher pressures to expand which the baby cannot easily generate, resulting in difficulty breathing and signs of respiratory distress. If premature birth is unavoidable, the mother should be given glucocorticoids (steroids), which stimulate the production of surfactant in the fetus and improve their ability to breathe after birth. Gastrointestinal Embryology  Formation of the Primitive Gut Cephalocaudal and lateral folding of embryo formation of blind end tube from cephalic until caudal portion of embryo Primitive Gut 4 sections of primitive gut: 1. Pharyngeal gut 2. Foregut 3. Midgut 4. Hindgut The foregut and hindgut develop from the head and tail blind pouches, and the midgut develops from the portion that is continuous with the yolk sac (the Vitelline duct) Diagram - The gut tube in the By the fifth week, the abdominal portion developing embryo. The blind of the foregut is visibly divided into pouches that form the foregut and the the esophagus, stomach, and proximal hindgut are prevented from being duodenum. open by the buccopharyngeal and the cloacal membranes  Peritoneum Intraembryonic coelom derived from mesoderm, 3rd week, with the aid of the diaphragm forms the thoracic and abdominal cavities. A membrane (peritoneum) lines the Intraembryonic coelom. Differentiates into pleural and peritoneal membranes. The are connected to key organs developing in the coelom.  Mesenteries A mesentery is a double fold of the peritoneal membrane that suspends the gut tube within the Intraembryonic coelom away from the abdominal wall. Allows for gut tube motility, provides path for blood and nerve supply from abdominal wall to the gut tube. 2 mesenteries attached to the gut tube: The dorsal mesentery attaches the ‘back’ of the gut tube to the posterior abdominal wall. It runs the whole length of the gut tube (dorsal mesogastrum) The ventral mesentery attaches the ‘front’ of the gut tube to the anterior abdominal wall. It only attaches the foregut, and it ends with the end of the foregut leaving a free edge (ventral mesogastrum). Primitive Mesentery  Intraperitoneal and Retroperitoneal organs Organs that are fully covered by mesentery are intraperitoneal organs Organs that are directly attached in posterior body wall and covered by mesentery only on their anterior part are retroperitoneal organs. Primarily Retroperitoneal – these organs were never covered peritoneum or had a mesentery. These organs developed outside of the abdominal cavity, like the kidneys. Secondarily Retroperitoneal – these organs did have a mesentery, but as the organs grew, this mesentery fused with the posterior abdominal wall, e.g. ascending and descending colons.  Omenta Omenta are sheets of visceral peritoneum (peritoneum contained within the abdominal cavity covering intraperitoneal organs). Extending from the stomach and duodenum to other organs. They form the boundary of the lesser and greater sacs. Greater omentum, four layers of visceral peritoneum, attaches to the greater curvature of the stomach and to the transverse colon. ‘policeman of the abdomen’. The lesser omentum is made up of only two layers of visceral peritoneum, and attaches to the lesser curvature of the stomach and to the liver.  Omenta The epiploic foramen (foramen of Winslow) is the connection between the lesser and greater sacs. Diagram - The greater (in red) and lesser (in blue) sacs in the transverse plane. It shows the epiploic foramen very clearly Omenta The greater and lesser omenta are formed from the dorsal and ventral mesogastrium (of mesodermal origin). As they rotate with the stomach they create the greater and lesser sacs. Diagram - The greater sac (in pink) and the lesser sac (in blue) in the sagittal plane. Remember the lesser omentum runs between the liver and the stomach, with the epiploic foramen connecting the greater and lesser sacs. The greater omentum (labelled) is the ‘flap’ with four layers of visceral peritoneum  Embryonic Origins The foregut, midgut and hindgut (primitive GIT) all have singular blood supply, these arteries supplies all of the structures that eventually develop form these segments. Each structure also has a specific pattern of visceral nervous innervation which has implications for localization of visceral pain. Structures that develop from border regions eg duodenum have dlood supply from both.  Foregut Development The foregut is supplied by the coeliac trunk and the greater splanchnic nerve (T5-9 nerve roots). Pain in these organs will localize to the epigastric region (T5-9 dermatomes). Organs that develop from the foregut are: Oesophagus Stomach Pancreas Liver Gallbladder Portion of the duodenum that is proximal to the entrance of the bile duct  Development of the Stomach Development begins around the 4th week. Fusiform dilation of the foregut: site of primordial stomach The lengthening oesophagus places the stomach below the diaphragm Posterior wall grows more quickly than anterior wall → develops a C shape Posterior wall → greater curvature Anterior wall → lesser curvature  Rotation of the Stomach 90-degree rotation clockwise around longitudinal axis: Greater curvature (dorsal): Rotates anteriorly and to the left Left vagus nerve innervates anterior wall Lesser curvature (ventral): Rotates posteriorly and to the right Right vagus nerve innervates posterior wall Smaller rotation clockwise around the anteroposterior axis: Cardiac portion of the stomach moves down and to the left Pyloric portion moves up and to the right Mesogastrium change in position durung stomach rotation  Development of the Duodenum Development begins in the 4th week Above the ampulla of Vater: derived from caudal part of the foregut → supplied by the celiac artery Below the ampulla of Vater: derived from cranial part of the midgut → supplied by SMA Elongates and forms C-shaped loop Joins together with the developing pancreas attached to the posterior body wall  Duodenal Obliteration and Recanalization Week 5: rapid cell proliferation in its walls leads to complete obstruction of the duodenal lumen By the end of week 8: Vacuoles form within the duodenum Vacuoles grow and merge → lumen recanalization Clinical relevance: failure of the lumen to fully recanalize results in either: Duodenal stenosis: narrowing of the duodenum Duodenal atresia: a complete obstruction persists; presents with bilious emesis and a double-bubble sign on radiography  Liver and Biliary ducts Development begins in the 3rd‒4th week Appears from the caudal portion of the foregut as the hepatic diverticulum, which goes on to form the: Liver (endoderm differentiates into hepatocytes) Intrahepatic ducts Extrahepatic portions of the hepatic ducts As the hepatic diverticulum enlarges, the connection to the duodenum narrows → common bile duct  Liver and Biliary ducts A smaller bud grows off the caudal side of the hepatic diverticulum: Forms the gallbladder Connection between the caudal bud and the gallbladder → cystic duct The hepatic diverticulum grows into the ventral mesogastrium. Within weeks 5-9: hematopoietic stem cells invade the liver and induces hematopoiesis – uptill the 28th week. Synthesis of bile acid Week 12: beginnining of bile secretion by hepatocyte Pancreatic Embryology  Pancreas Begins approx. week 5, as outpouching of the endodermal lining of the duodenum (ventral and dorsal pancreas). Growth of dorsal pancreas  ventral pancrease. Ventral pancreas and common bile duct rotates towards dorsal pancreas. Finally, the ventral and dorsal pancreas join. In adult, head of pancreas = ventral and dorsal pancreas, ventral process = uncinated process, body and tail of the pancreas = dorsal pancreas  The Midgut Supplied by the superior mesenteric artery (SMA) and lesser splanchnic nerve (T10-11). Pain in these organs will localize to the periumbilical region (T10-11 dermatomes). Organs that develop from the midgut are: Portion of the duodenum that is distal to the entrance of the bile duct (ampulla of Vater) Jejunum Ileum Caecum and appendix Ascending colon Proximal 2/3 of the transverse colon  Rotation and physiological herniation of the midgut By the early 6th week, the continuing elongation of the midgut, combined with the pressure resulting from the dramatic growth of other abdominal organs (particularly the liver),forces the primary intestinal loop to herniate into the umbilicus. Rotation and physiological herniation of the midgut During the 10th week, the midgut retracts into the abdomen. as the intestinal loop reenters the abdomen, it rotates counterclockwise through an additional 180 degrees, so that now the retracting colon has traveled a 270- degree circuit relative to the posterior wall of the abdominal cavity The cecum consequently rotates to a position just inferior to the liver in the region of the right iliac crest. The intestines have completely returned to the abdominal cavity by the 11th week. Formation of gut lumen and villi Formation of gut lumen and villi Between the 6th and 8th weeks, the lumen of the gut tube becomes solidly filled by epithelium, and then is gradually recanalized. During recanalization, mesodermal extensions project into the lumen and together with the overlying epithelium form the villi of the intestines. Omphalocele: failure of the loops to return Gastroschisis: herniation through the body wall Duplications and diverticula Abnormal rotation Volvulus: the gut twist around themselves  Hindgut The hindgut is supplied by the inferior mesenteric artery (IMA) and least splanchnic nerve (T12 nerve root). Pain in these organs will localise to the suprapubic region (T12 dermatome). Organs that develop from the hindgut are: Distal 1/3 of the transverse colon Descending colon Sigmoid colon Rectum Structures of cloacal origin: Upper 2/3rds of the anal canal (superior to the pectinate line) Bladder Urethra  Hindgut The hindgut during development is covered by the cloacal membrane and communicates with the developing genitourinary tract as a structure known as the cloaca. In this area ectoderm meets endoderm without any dividing mesoderm - the pectinate line. Within the 4th – 6th week, the urorectal septum partitions the cloaca into the urogenital sinus and a dorsal anorectal canal  Hindgut/urorectal septum The distal one third of the anorectal canal forms from an ectodermal invagination called the anal pit. Hindgut/endoderm-derived: proximal ⅔ of the anal canal, lined by columnar epithelial cells Ectoderm-derived: distal ⅓ of the anal canal, lined by stratified squamous epithelial cells  The Anal Canal The anal canal is divided into histologically distinct sections by the pectinate line. Above the pectinate line, the anal canal is developed from the endoderm. As a result, it is supplied by inferior mesenteric artery and the least splanchnic nerve. The sphincters also have parasympathetic innervation by nerves of roots S2, S3 and S4 only stretch can be sensed in this region Below the pectinate line, the anal canal is developed from the ectoderm. The canal at this point it supplied by the pudendal artery and the pudendal nerve (spinal nerve root S2, S3 and S4). somatic sensations of temperature, touch and pain can be detected  Hindgut Abnormalities If there are issues in septation of the cloaca or rupture of the membrane this can cause abnormalities in the adult anatomy. Imperforate Anus – the cloacal membrane does not rupture and so persists meaning there is no outlet from the gastrointestinal tract and therefore no anus. This will need surgical fixation. Fistulae – if there are holes in the septum there can be abnormal connections between the anus and the bladder as they are not properly separated in development. Anorectal Agenesis – a severe defect where there is no development of the anus or rectum rather than simply no outlet. HD is due to an absence of parasympathetic ganglia in the bowel wall (aganglionic megacolon or Hirschsprung disease)  Mutations in the RET gene, a tyrosine kinase receptor involved in crest cellmigration GIT Development and Vascularization Thanks