Organogenesis 2: Respiratory and Gut
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Briefly comment on the susceptibility to malformations of a developing foetus
- The greatest period of sensitivity to teratogens seems to be 3-8 weeks development
- - After this period, we get period of decreasing sensitivity while organ function matures
- 2-3% of all live born babies have a congenital defect. Main causes are;
- - Gene defects 15-20%
- - unknown/multifactorial 65-70%
Describe how the foregut differentiates to give the primitive "lung buds"
- When the embryo is approximately 4 weeks old, the respiratory diverticulum (lung bud) appears as an outgrowth from the ventral wall of the foregut
- - epithelium of the internal lining of the larynx, trachea, and bronchi, as well as that of the lungs, is entirely of endodermal origin.
- - cartilaginous, muscular, and connective tissue components of the trachea and lungs are derived from mesoderm surrounding the foregut
- - two longitudinal ridges, the tracheoesophageal ridges, separate the lung buds from the foregut. When these ridges fuse the foregut is divided into;
- - a dorsal portion, the esophagus,
- - a ventral portion, the trachea and lung buds
What events complete the embryonic development of the lungs (4-5 weeks)
- At the beginning of the fifth week, each of these lung buds enlarges to form right and left main bronchi.
- - right forms three secondary bronchi, and the left, two
- - thus foreshadowing the lung lobes
- Repetitive branching = called branching morphogenesis occurs until bronchioles begin to form
Outline the 5 phases of lung development
- Embryonic: 4-5wk Lung buds, bronchopulmonary segments
- Pseudoglandular: 5-16 wk branching, terminal bronchioles
- Canalicular: 16-26 wk formation of the terminal sacs, beginning of vascularisation
- Terminal sac: 26-40 wk expansion of number of terminal sacs, type I &II
- Alveolar: 32wk-childhood alveoli mature
Comment on the importance of alveolar development with respect to the survival of a premature infant
- Alveolar development happens very late in foetal development; epithelial cells remain thick and lack type II pneumonocytes
- Surfactant is particularly important for survival of the premature infant. When surfactant is insufficient, the air-water (blood) surface membrane tension becomes high, bringing great risk that alveoli will collapse during expiration.
- - As a result, respiratory distress syndrome (RDS) develops; a common cause of death in the premature infants.
- - Recent development of artificial surfactant and treatment of premature babies with glucocorticoids to stimulate surfactant production have reduced the mortality associated with RDS and allowed survival of some babies as young as 5.5 months of gestation.
Describe the formation of the diaphragm
- The septum transversum is a thick plate of mesodermal tissue occupying the space between the thoracic cavity and the stalk of the yolk sac
- - it does not completely separate the cavities but leaves large openings, the pericardioperitoneal canals, on each side of the foregut
- Although the pleural cavities are separate from the pericardial cavity, they remain in open communication with the abdominal (peritoneal) cavity by way of the pericardioperitoneal canals.
- There are 4 embryonic structures which compose the diaphragm (coloured below)
- During further development, the opening between the prospective pleural and peritoneal cavities is closed by crescent-shaped folds, the pleuroperitoneal folds.
- - Gradually, the folds extend to fuse with the mesentery of the esophagus and with the septum transversum
- The connection between the pleural and peritoneal portions of the body cavity is closed by the pleuroperitoneal membranes.
- Further expansion of the pleural cavities relative to mesenchyme of the body wall adds a peripheral rim to the pleuroperitoneal membranes. Once this rim is established, myoblasts migrate to form the muscular part of the diaphragm.
What structures do the embryonic components of the diaphragm come to be?
- These 4 embryonic structures come to be;
- - Pleuroperitoneal membranes: dorsal part of the diaphragm
- - Mesentery of the esophagus: L and R Crura
- - Septum transversum : central tendon
- - Mesoderm of the body wall: Muscular part of the diaphragm
What are the consequences of malformation of the diaphragm?
- Congenital diaphragmatic hernia: one of the more common malformations in the newborn (1 per 2,000)
- - due to failure of one or both of the pleuroperitoneal membranes to close the pericardioperitoneal canals. In that case, the peritoneal and pleural cavities are continuous with one another along the posterior body wall.
- This hernia allows abdominal viscera to enter the pleural cavity. In 85% to 90% of cases, the hernia is on the left side, and intestinal loops, stomach, spleen, and part of the liver may enter the thoracic cavity.
- - The abdominal viscera in the chest push the heart anteriorly and compress the lungs, which are commonly hypoplastic.
- A large defect is associated with a high rate of mortality (75%) from pulmonary hypoplasia and dysfunction.
Give a general outline of the developmental events in the gastro-intestinal tract
- Week 3: Tubular gut forms
- Week 4: Primordia of liver, pancreas and trachea are visible
- Week 5: Expansion and rotation of the stomach, and intestinal loop form
- Week 6: Urorectal septum begins to subdivide cloaca into rectum and urogenital sinus
- Week 7: Herniation of the intestinal loop, rapid growth of the liver
- Week 8: Counterclockwise rotation of herniated loop, neural crest precursors start to enter gut
- Week 9-10: Return of the herniated gut into the body cavity, and differentiation
Describe the division of the gastro-intestinal tract into foregut, midgut and hindgut.
- As a result of cephalocaudal (i.e. head to tail) and lateral folding of the embryo, a portion of the endoderm-lined yolk sac cavity is incorporated into the embryo to form the primitive gut.
- - Two other portions of the endoderm-lined cavity, the yolk sac and the allantois, remain outside the embryo
- The primitive gut forms a tube, forming the foregut (towards the head) and hindgut (at the tail).
- The middle part, the midgut, remains temporally connected to the yolk sac by means of the vitelline duct, or yolk stalk.
Describe the derivatives of the foregut, midgut and hindgut. And the main arterial supply
- Now divided into the 3 gut sections, the tissue undergoes organ specification
Describe the formation of the esophagus and stomach
- Re. oesophagus, see earlier notes about lung buds and the Tracheoesophageal septum
- Stomach: appears as a growth of the foregut tube in the fourth week of development.
- During the following weeks, its appearance and position change greatly as a result of the different rates of growth;
- - dorsal wall grows faster than ventral wall
- - it also rotates; ventral surface rotates right and dorsal moves left (hence why greater curvature is lateral)
* What is the midgut?
- In the adult, the midgut begins immediately distal to the entrance of the bile duct into the duodenum and terminates at the junction of the proximal two thirds of the transverse colon with the distal third.
- Over its entire length, the midgut is supplied by the superior mesenteric artery
Describe the development of the primary intestinal loop and the process of physiological herniation
- In the 5-week embryo, the midgut is suspended from the dorsal abdominal wall by a short mesentery and communicates with the yolk sac by way of the vitelline duct or yolk stalk.
- Development of the midgut is characterized by its very rapid growth. The rapid elongation of the gut and its mesentery happens faster than the body of the embryo, resulting in formation of the primary intestinal loop.
- The primary loop is spatially forced into the umbilicus. This process is called "physiological herniation", and happens because the abdominal cavity temporarily becomes too small to contain all the rapidly growing intestinal loops (sixth week of development)
- - At the loop's apex, it remains in open connection with the yolk sac by way of the narrow vitelline duct/yolk stalk.
- - The cephalic limb of the loop develops into the distal part of the duodenum, the jejunum, and part of the ileum.
- - The caudal limb becomes the lower portion of the ileum, the cecum, the appendix, the ascending colon, and the proximal two thirds of the transverse colon.
Describe the rotation of the midgut in it's development. What are the consequences of this process on the permanent positioning of components of the G-I tract?
- Rotation of the Midgut: as it grows, the primary intestinal loop rotates around an axis formed by the superior mesenteric artery.
- When viewed from the front, this rotation is counterclockwise, and it amounts to approximately 270° when it is complete.
- Even during rotation, elongation of the small intestinal loop continues, and the jejunum and ileum form a number of coiled loops.
- The large intestine likewise lengthens considerably but does not participate in the coiling phenomenon. Rotation occurs during herniation (about 90°), as well as during return of the intestinal loops into the abdominal cavity (remaining 180°).
What are some examples of mishaps in the herniation/rotation process of gut development?
- Omphalocoele: a body wall defects involving herniation of abdominal viscera. The viscera, which may include liver, small and large intestines, stomach, spleen, or gallbladder, are covered by amnion.
- - The origin of the defect is a failure of the bowel to return to the body cavity from its physiological herniation during the 6th to 10th weeks.
- Malrotation of gut: Abnormal rotation of the intestinal loop may result in twisting of the intestine (volvulus) and a compromise of the blood supply. Normally, the primary intestinal loop rotates 270° counterclockwise. Occasionally, however, rotation amounts to 90° only. When this occurs, the colon and cecum are the first portions of the gut to return from the umbilical cord, and they settle on the left side of the abdominal cavity (left picture). The later returning loops then move more and more to the right, resulting in a left-sided colon.
- - Reversed rotation of the intestinal loop occurs when the primary loop rotates 90° clockwise. In this abnormality, the transverse colon passes behind the duodenum (right picture above) and lies behind the superior mesenteric artery.
- Meckel’s diverticulum: Failure of the vitelline duct (a.k.a yolk sac) to close
Describe the formation of the enteric nervous system from neural crest precursors
- Neural crest cells migrate from the neural folds to the wall of the bowel to form parasympathetic ganglia; which provide gut motility
- Congenital megacolon: is due to an absence of parasympathetic ganglia in the bowel wall (aganglionic megacolon or Hirschsprung disease)
- - Mutations in genes involved in crest cell migration, can result in congenital megacolon
- - usually only part of the colon is involved; 10% to 20% are the transverse and right-side colonic segments involved, and in 3%, the entire colon is affected.
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