Embryology of LIVER PANCREAS SPLEEN and THE RESPIRATORY

Embryology of LIVER, PANCREAS, SPLEEN and THE RESPIRATORY SYSTEM

Laryngotracheal orifice

6 weeks

12 weeks.

5 weeks 6 weeks

8 weeks

Expansion of the lung buds into the pericardioperitoneal canals. At this stage the canals are in communication with the peritoneal and pericardial cavities. Ventral view of lung buds

Once the pericardioperitoneal canals separate from the pericardial and peritoneal cavities, respectively, the lungs expand in the pleural cavities. Note the visceral and parietal pleura and definitive pleural cavity. The visceral pleura extends between the lobes of the lungs

Histological and functional development of the lung. . The canalicular period lasts from the 16 th to the 26 th week. Note the cuboidal cells lining the respiratory bronchioli.

The terminal sac period begins at the end of the sixth and beginning of the seventh prenatal month. Cuboidal cells become very thin and intimately associated with the endothelium of blood and lymph capillaries or form terminal sacs (primitive alveoli).

Lung tissue in a newborn. Note thin squamous epithelial cells (also known as alveolar epithelial cells, type I) and surrounding capillaries protruding into mature alveoli.

TOPICS HIGHTLIGHTS. LIVER AND GALL BLADDER. PANCREAS. SPLEEN. ANOMALIES OF LIVER/ G. BLADDER/ PANCREAS AND SPLEEN. • THE RESPIRATORY SYSTEM, LARYNX, TRACHEA, BRONCHI, LUNGS. • • • ANOMALIES OF LARYNX, TRACHEA, BRONCHI, LUNGS. • BODY CAVITIES, PLEURAL AND PERITONEAL CAVITY. • DIAPHRAGM, DEVELOPMENT AND ANOMALIES.

HIGHLIGHTS 1/4 • Liver and biliary passages (endoderm) are derived from the hepatic bud. • Hepatic bud arises from the gut at the junction of foregut and midgut. • Pancreas (endoderm) develops from two buds, • Dorsal and ventral. • Most of pancreas is formed from the dorsal bud. • Spleen (mesoderm) develops in the dorsal mesogastrium.

HIGHLIGHTS 2/4 • The respiratory system develop from a median diverticulum of the foregut (endoderm). • The diverticulum divides into right and left lung buds. • The larynx and trachea develop from the diverticulum, cranial to its division. • The lung buds undergo repeated division to establish the bronchial tree and alveoli of the lung.

HIGHLIGHTS 3/4 • The peritoneal, pericardial and pleural cavities develop from the intra-embryonic coelom. • Intra-embryonic coelom consist of right and left halves. • These two halves are connected across the middle line, (cranial to the prochordal plate). • The pericardial cavity is derived from the median midline part of the intra-embryonic coelom.

HIGHLIGHTS 4/4 • The peritoneal cavity is derived from the right and left limbs of the intra-embryonic coelom. • The pleural cavities are formed from right and left pericardio-peritoneal canals that connect the pericardial and peritoneal cavities. • The diaphragm develops in relation to the septum transversum. • The diaphragm receives contributions from; – The pleuro-peritoneal membranes, – The body wall, – The mesenteries of the oesophagus.

LIVER 1/3 • At the point of junction between foregut and midgut. • Liver develops from the endodermal bud that arises from the ventral aspect of the gut, • This bud grows into ventral mesogastrium and passes through it into the septum transversum. • The bud enlarges, and divides into a larger cranial part called pars hepatica, and smaller caudal portion called the pars cystica. • The pars hepatica divides into right and left parts, (right and left lobes).

LIVER 2/3 • Hepatic trabeculae; • The cells of these divisions are broken up into interlacing columns called hepatic trabeculae. • Sinusoids of the liver; • The umbilical and vitelline veins are broken up to form the sinusoids of the liver. • Sinusoids of the liver are also formed from the mesenchyme of the septum transversum. • Liver parenchyma + bile capillaries • Endodermal cells of the hepatic bud give rise to the parenchyma of the liver and to the bile capillaries. • Capsule + fibrous tissue • The mesoderm of the septum transversum forms the capsule and fibrous tissue basis of the liver.

LIVER 3/3 • The fetal liver is an important centre of blood formation (haemopoiesis). • Large aggregations of blood-forming cells are present between hepatic cells and blood vessels. • Bile formation begins when the fetus is about three months old. • The bile is responsible for the black colour of the first stool (meconium) passed b the newborn.

GALL BLADDER AND BILIARY PASSAGES Gall bladder and cystic duct, Arise from the pars cystica of the hepatic bud. Bile duct, Arise from the hepatic bud proximal to the pars cystica. The bile duct at first opens on to the ventral aspect of the developing duodenum. • Then it comes to open on the dorsomedial aspect of the duodenum along with the ventral pancreatic duct. • Why ? ? ? ? ? • • • – Differential growth of the duodenal wall, – Rotation of the duodenal loop.

PANCREAS 1/3 • Develops from two endodermal buds, dorsal and ventral. • The ventral bud arises in close relation to the hepatic duct, (between the hepatic duct and the duodenum). • The dorsal bud arises from the dorsal aspect of the gut. • The dorsal bud grows into the mesoduodenum and the dorsal mesogastrium. • When the duodenal loop falls to the right, the ventral bud comes to point to the right and the dorsal bud to the left. • As a result of differential growth of the wall of the gut, the attachment of the ventral bud (along with the bile duct) also shift to the left side.

PANCREAS 2/3 • These two buds fuses to form one mass. • The ventral bud forms the lower part of the head and the uncinate process of the pancreas. • The dorsal bud forms the upper part of the head, the body and the tail of the pancreas. • Duct system is established as follows; – The ducts of the dorsal and ventral buds anastomose with each other. – The duct of the dorsal bud forms the accessory pancreatic duct. – The main pancreatic duct is formed from the dorsal and ventral buds. • Distal part is formed from the dorsal bud, • Proximal part is formed from the ventral bud.

PANCREAS 3/3 • The main pancreatic duct opens into the duodenal papilla, along with the bile duct. • The secretory elements of the pancreas are formed by the proliferation of the primitive ducts. • The islets of Langerhans are also derived from the primitive duct system.

SPLEEN 1/1 • Develops as a collection of mesenchymal cells in the dorsal mesogastrium. • Some of these cells are contributed by the coelomic epithelium lining the mesogastrium. • The mesenchymal cells differentiate into lymphoblasts and other blood forming cells. • The mesenchymal cells proliferate, they form a mass, • The mass projects to the left and is covered by peritoneum. • The gastrosplenic ligament and the lienorenal ligament are derived from the dorsal mesogastrium.

ANOMALIES • Liver anomalies; 1. 2. 3. 4. Rudimentary left lobe. Anomalous lobation. Reidel’s lobe. Absence of quadrate lobe with the absence of gall bladder. 5. Accessory liver in the falciform ligament.

ANOMALIES OF THE GALL BLADDER 1. 2. 3. 4. Anomalies of the shape. Anomalies of position. Duplication. Other anomalies.

Gall bladder/ Anomalies of the shape 1) Phryngian cap (folded fundus). 2) Hartmann’s pouch (infundibulum projection).

Anomalies of position. I. Lie Transversely under the right lobe, or lie under the left lobe of the liver. II. Floating gall bladder. III. Embedded in the substance of the liver.

Duplication A. The lumen may be partially or completely subdivided by a septum, (septum may extend to the cystic duct). B. The gall bladder may be partially or completely duplicated.

Other anomalies i. Sessile bladder, (no cystic duct ? ? ? ). ii. Absent gall bladder. iii. Diverticula, (may arise any from part of t e organ)

Anomalies of the extrahepatic duct system 1. Abnormal length (abnormal short/ long). 2. Abnormal mode of termination; a) The cystic duct join the left side of the CHD. b) The cystic duct may end in the Rt. Hepatic Duct. c) The cystic duct may be anterior to the duodenum before joining the CBD. d) The CBD may open into the pyloric or cardiac end of the stomach. 3. Atresia. 4. Duplication (accessory cholecystohepatic duct/ between the right lobe and the gall bladder, cystic duct or CBD).

Anomalies of the pancreas 1. Annular pancreas. 2. Divided pancreas. 3. Accessory pancreatic tissue (may be found in the stomach, duodenum, jejunum, Meckel’s diverticulum, gall bladder and spleen). 4. Inversion of pancreatic duct (persistence of the embryonic arrangement of the ducts/ the greater part of the pancreas is drained through the minor duodenal papilla.

Anomalies of the spleen 1. Lobulated spleen. 2. Absent (rare). 3. Accessory spleen; a. At the hilum of the spleen. b. In the gastrosplenic ligament. c. In the lienorenal ligament.

The Respiratory System 1/2 • The respiratory system develops from a median diverticulum of the foregut. • The connective tissue, cartilage and muscle, in relation to the organs of respiration are derived from the splanchnopleuric mesoderm. • The median diverticulum is first seen as a midline groove (tracheobronchial groove), in the floor of the developing pharynx. • Tracheobronchial groove is just caudal to the hypobranchial eminence.

The Respiratory System 2/2 This groove is flanked by the six pharyngeal arches. The distal part of the groove is separated from the oesophagus. The proximal end continues to communicate with the pharynx. The free end of the diverticulum become bifid. Each subdivision is called the lung bud. The part of the diverticulum cranial to the bifurcation forms the larynx and trachea. • The lung buds form the bronchi and lung parenchyma. • • •

LARYNX • Develops from the cranial most-part of the respiratory diverticulum. • The communication between the diverticulum and the pharynx persists as the inlet of the larynx. • Epiglottis is formed from the caudal part of the hypobranchial eminence. • The thyroid, cricoid, and arytenoid cartilages are derivative of the 4 th , 5 th and 6 th pharyngeal arches.

TRACHEA AND BRONCHI • Trachea develops from the part of the respiratory diverticulum, that lies between the point of its bifurcation and the larynx. • The two primary divisions of the respiratory diverticulum form the right and the left principal bronchi. • The right division divides into three lobar bronchi. • The left bronchus divides into two lobar bronchi. • The left bronchus lies more transversely than the right bronchus. • The right main bronchus is wider, shorter, and more vertical than the left main bronchus. The right main bronchus subdivides into three lobar bronchi while the left main bronchus divides into two. The lobar bronchi divide into tertiary bronchi, also known as segmental bronchi, each of which supplies a bronchopulmonary segment There are ten segments per lung, but due to anatomic development, several segmental bronchi in the left lung fuse, giving rise to eight

LUNGS 1/3 • The substance of the lungs is derived formed by further subdivisions of the lobar bronchi. • The total number of subdivisions of each main bronchus are about 17 before birth. • 6 more subdivisions after birth. • Alveoli !!!!!!/////? ? ? ? ? • After the establishment of the bronchial tree, ALVEOLI are formed by expansion of the terminal parts of the tree. • Mesoderm separates the lung parenchyma, developing from the lobar bronchi. • This mesoderm forms the connective tissue basis of the lung. • Mesoderm also gives rise to the pleura.

LUNGS 2/3 • The pleura lines the surface of each lobe separately. • The lobes come to be separated by fissures. • During the fetal life, the lining epithelium is a cubical epithelium. (the canalicular phase of lung development). • After birth, /with the onset of respiration/ the alveoli become dilated and their lining epithelium become thin. • In the postnatal period there is a considerable increase in the number of alveoli. • The pulmonary circulation is established early in fetal life. • At first most of the blood is short-circuiting through • The foramen ovale and the ductus arteriosus.

LUNGS 3/3 • The amount of blood circulating through the lungs progressively increases, • By the seventh month of intrauterine life the circulation is rich enough to provide adequate oxygen for sustaining life. • Within the respiratory passages, some cells become specialized for production of surfactant. • Surfactant forms a thin layer over the alveoli and reduce the surface tension. • Before birth the respiratory passages are full of fluid, • The fluid also contains surfactant. • When the new born begins to breath, the fluid is absorbed and partly expelled. • The surfactant remains as a thin layer lining the alveoli. • Surfactant prevents collapse of alveoli during expiration. • In premature ? ? ? ? ? ? /////

ANOMALIES • Anomalies of the larynx 1. 2. 3. 4. 5. Laryngocoele. Congenital stenosis or atresia. Duplication (entire larynx, or part of it). Laryngoptosis (low lying in the neck). Laryngeal cartilage absence (one or more). • Anomalies of the trachea a. b. c. Tracheo-oesophageal fistula. Diverticulum. Accessory bronchi. Such bronchus may be; i. Blind. ii. Supply accessory lobe. iii. Replace a normal bronchus in one of the lungs d. Absent trachea (very rarely). (bronchi arise from blind bifurcation or from oesophagus).

ANOMALIES OF THE LUNGS AND BRONCHI 1. 2. 3. 4. Agenesis or hypoplasia. Lung hernia through the inlet of the thorax/ defect in the thoracic wall/ into mediastinum or into opposite pleural cavity. Displaced bronchi. May arise from the trachea above the bifurcation or from the oesophagus, they may supply a normal segment, an accessory lobe or may be blind. Abnormalities of lobes. 1) Absence of fissures that normally present. – reduction in lobe number. 2) Presence of abnormal fissure; i. ii. iii. iv. Transverse fissure in the left lobe. Cardiac lobe ( medial basal segment separated by a fissure). Superior segment of the lower lobe may be separated (like above). Azygos lobe – part of the upper lobe of right lung may come medial to the azygos vein. --- mesoazygos (parietal pleura suspends the vein). 3) Accessory lobes. Depending from where it arises, 4) Sequestration of lung tissue. Frequently seen in the lower lobe of the left lung; a. b. Upper accessory lobe. Lower accessory lobe. i. ii. Lobar sequestration. Intralobar sequestration.

BODY CAVITIES 1/2 • The pericardial, pleural, and peritoneal cavities are derivatives of the intra-embryonic coelom. • By the formation of this cavity the lateral plate mesoderm is split into Parietal (somatopleuric) and visceral (splanchnopleuric) layer. • The parietal and visceral layers of the pericardium, pleura and peritoneum are formed from these layers of mesoderm. • The mesodermal cells lining the cavities is called Mesothelium. • The mesothelium gives the peritoneum, pleura and pericardium their smooth surfaces.

Growth of the lung buds into the pericardioperitoneal canals. Note the pleuropericardial folds.

B Transformation of the pericardioperitoneal canals into the pleural cavities and formation of the pleuropericardial membranes. Note the pleuropericardial folds containing the common cardinal vein and phrenic nerve. Mesenchyme of the body wall splits into the pleuropericardial membranes and definitive body wall. B. The thorax after fusion of the pleuropericardial folds with each other and with the root of the lungs. Note the position of the phrenic nerve, now in the fibrous pericardium. The right common cardinal vein has developed into the superior vena cava.

BODY CAVITIES 2/2 • The intra-embryonic coelom is a horseshoe-shaped cavity, • Having a narrow midline portion and two lateral parts. • The midline part lies near the cranial end of the embryonic disc. • The pericardial cavity is formed from this midline part. • The two lateral limbs (parts) of the coelom form the peritoneal cavity. • Pericardio-peritoneal canals are pair of narrow canals, connect the two cavities for some time. • These two canals enlarge greatly to form the pleural cavities.

PLEURAL CAVITY • After formation of the head fold, the pericardium comes to lie on the ventral aspect of the embryo, • The pericardio-peritoneal canals wind backwards on either side of the foregut. • The lung buds invaginate these canals. • As the buds enlarge to form the lungs, the canals balloon out to form the pleural cavities. • Pericardio-pleural opening connect the pericardial and the pleural cavities. • Pleuro-peritoneal opening connect the peritoneal and the pleural cavities. • Pericardio-pleural and pleuro-peritoneal openings are closed by the pericardio-pleural and pleuro-peritoneal membranes. • Pericardio-pleural membrane forms the fibrous pericardium. (why phrenic nerve courses over the pericardium).

PERITONEAL CAVITY • The peritoneal cavity is formed from the two limbs of the horsesheshped intra-embryonic coelom. • The two part are at first separate, • BUT • Fuse to form one cavity. • The two halves of the peritoneal cavity remain separate in the cranial part of the abdomen. • The attachment of the mesentery of the primitive gut on the posterior abdominal wall is at first in the midline. • Then the line of attachment of the mesentery becomes complicated. • The peritoneal cavity is subdivided into a number of pockets that are partially separated by folds of peritonium.

DEVELOPMENT OF THE LESSER SAC ½ skip • There are three processes involved in the formation of the lesser sac; 1. Right and left pneumato-enteric recesses are formed in the dorsal mesogastrium, the left disappears, the right recess enlarges considerably and extends to the left to form part of the lesser sac that lies behind the stomach. It extends cranially, on the right side of the oesophagus and behind the liver. At the establishment of the diaphragm the upper part forms the infracardiac bursa, the lower part forms the superior recess of the lesser sac. 2. The right recess extends to the left, the stomach changes its orientation, so the posterior border (to which the dorsal mesogastrium was attached faces to the left). This border forms the greater curvature.

DEVELOPMENT OF THE LESSER SAC 2/2 • The ventral border (to which the dorsal mesogastrium was attached) comes to face to the right and forms the lesser curvature. The ventral mesogastrium may now called the lesser omentum. A part of peritoneal cavity comes to lie behind the lesser omentum. This part of the peritoneal cavity now forms part of the lesser sac. 3. With the altered orientation of the stomach, the dorsal mesogastrium may be subdivided into two parts; Part A and Part B Part a gives rise to ; The gastrosplenic ligament. The lienorenal ligament. Part B forms the greater omentum that projects below the level of the stomach and becomes folded on itself. The space within this fold forms the lower part of the lesser sac.

DIAPHRAGM • The diaphragm is a partition that separates the thoracic and abdominal cavities. • The pericardial and pleural cavities are above (cranial to) it, • The peritoneal cavity is caudal to it. • The development of the diaphragm is intimately related to the development of these cavity. • The septum transversum forms a mesodermal mass lying caudal to the pericardial cavity. • Posterior to the septum transversum the pleural and the peritoneal cavities communicate through the pleuro-peritoneal canals (that lie on either side of the oesophagus). • The partition between the thorax and the abdomen is completed when the pleuro-peritoneal canals are closed by the formation of the pleuro-peritoneal membrane.

DEVLOPMENT OF THE DIAPHRAGM • The diaphragm enlarges at the expense of the body wall. • The diaphragm is formed from the following components; 1. Septum transversum. 2. Pleuro-peritoneal membranes. 3. Ventral and dorsal mesenteries of the oesophagus. 4. Mesoderm of the body wall, including the mesoderm around the dorsal aorta.

Anomalies of the Diaphragm 1. 2. 3. Very rarely, an accessory diaphragm may be present in the thoracic cavity. (when it is present it partially subdivides the lung into two parts. Congenital eventation of the diaphragm. (the muscle may be thin and aponeurotic and may bulge upwards into the thorax, the bulging may be unilateral or may be confined to a small area. Parts of the diaphragm may fail to develop resulting in gaps in the muscle. Abdominal contents may pass through these gaps to produce diaphragmatic hernias. i. iii. iv. Diaphragmatic hernia may be; Posterolateral: (due to failure of a pleuro-peritoneal canal to close). Posterior: (due to the failure of the development of the crura). Retrosternal: (due to abnormally large gap between the sternal and costal parts of the muscle. Central: (through the dome of the diaphragm) occasionally one entire half (usually the left) of the diaphragm may be absent.

Development of the diaphragm. Pleuroperitoneal folds appear at the beginning of the fifth week

Pleuroperitone al folds fuse with the septum transversum and mesentery of the esophagus in the seventh week, separating the thoracic cavity from the abdominal cavity Transverse section at the fourth month of development. An additional rim derived from the body wall forms the most peripheral part of the diaphragm.

Timetable of some events Described in this lecture Age Developmental event 3 weeks The hepatic bud appears. The pancreatic bud appears thereafter. 4 weeks The septum transversum is established. The tracheobronchial diverticulum is formed. 6 weeks The diaphragm descends to the thoracic level. 7 weeks Fusion of dorsal and ventral pancreas. 3 months Bile formation begins. Pancreatic islets are formed. 5 months Insulin secretion begins