Embryology & Congenital abnormalities Flashcards
The body cavities (coela) are formed very early during embryogenesis from witch layer?
from endoderm and mesoderm
- body cavities (pleura, etc.) = mesoderm
- lining of respiratory system = endoderm
What are the 3 cavities formed by the intra-embryonic mesenchyme? How does it happens ?
3 cavities :
- Pericardial
- Pleural (in the thorax)
- Peritoneal (in the abdomino-pelvic region)
Once your mesenchyme is form, continuous coelum will be formed, by mesenchymal-epitheial transition (MET) initially called the coelomic epithelium. Later this epithelium will appears as a simple epithelium called mesothelium (full of mesenchymal stem cells). This horseshoe-shaped body cavity will form the 3 separate body cavities after folding of the embryo.
What are the 3 parts of the gut formed during embryogenesis? Which one forms the respiratory system ? To which one the yolk sac is attached ?
- Foregut
- Pharynx
- Eosophage
- Respiratory system
- Midgut
- attached to the yolk sac
- Hindgut
The gut originated from which type of layer?
The definitive endoderm (the part that’s forming the yolk sac)
What are the 5 stages of lung morphogenesis?
- Embryonic phase
- Pseudoglandular phase
- Canacular phase
- Terminal sac phase
- Postnatal aleveolation : alveolar formation isn’t complete until 8 y.o kid
In the embryonic phase, from which part is formed the respiratory system? What fills this growth ?
- The lower respiratory system begins to develop around mid fourth week from a groove (laryngo-tracheal groove in the foregut) that mark the primordium of the trachea and future laryngeal region in the proximal region connected to the pharynx
- The future oesophagus is filled with cells (overgrowth)
In which phase of lung morphogenesis are the primary bronchis formed?
Embryonic phase
In witch phase of lung morphogenesis are the tertiary bronchis formed?
Pseudoglandular phase
Which phase of lung morphogenesis is called the vascular/angiogenesis phase?
Canalicular phase (occurs with VEGF secretion form growing tips).
- You have creation of primary alveoli (terminal saccules) that makes gas exchange possible
What is the Sonic Hedgehog gene affects on lung embryogenesis?
- Endodermal-mesenchymal interaction during separation of the trachea and oesophagus
- Branching morphogenesis
- If not working, might cause fistulae between the oesophagus and trachea
What is the consequence of failure in recanalization of the gut & trachea (Atresia)?
Defective Apoptosis:
- Associated with Down’s and other genetic causes
- Associated with vascular insufficiency in embryogenesis
What are the basic mechanism underlying anomaies seen in the respiratory and gut system
-
genetic causes :bad MET interaction, problem with oesophagus/trachea branching
- defective sonic-hedgehog : affect normal tracheo-oesophageal septum and branching morphogenesis (Shh)
-
normal recanalization of the trachea and gut
-
Atresia : failure in normal recanalization of the gut and trachea involving defective apoptosis (cells stay and block the trachea and oesophagus)
- vascular insufficiency during embryogenesis = abnormal gut wall formation
- abnormal amniotic fluid turnover as a consequence gut atresia affecting normal branching morphogenesis of the lung (the amniotic fluid goes right to the buds and you expect a normal turnover of amniotic fluid aka it circulates and gets reabsorbed by the gut)
-
Atresia : failure in normal recanalization of the gut and trachea involving defective apoptosis (cells stay and block the trachea and oesophagus)
What are the 3 major and subtle causes of hypoplasia of the lung?
- Renal agenesis abnormalities –> Olifohydramios –> lung hypoplasia
- Premature ruptured foetal membranes –> lung hypoplasia
- Inadequate thoracic space / diaphragmatic hernia –> lung hypoplasia
What are the 3 things in the respiratory system formed by the Endoderm?
- Airway epithelium
- Airway glands
- Pulmonary epithelium
What are the 3 things of the respiratory system formed by the mesoderm?
- Connective Tissue
- Cartilage
- Smooth Muscle
Symptoms
- Excessive salivation
- Respiratory distress
- Choking on feeds
- Maternal Polyhydramnios (an excess of amniotic fluid in the amniotic sac)
What’s the dx ?
ABNORMALITIES OF TRACHEAL BUDDING : Esophageal Atresia & Tracheo-Esophageal Fistula
- In 8% of cases, you have atresia : no connection between the esophagus and the trachea at all
- In 85% of cases, you have a fistula: an abnormal connection between the trachea and the esophagus
Asymptomatic or acute or chronic aero-digestive tract symptoms
What’s the dx?
Bronchopulmonary Foregut Cyst
- Cystic remnant of the budding process, found in the mediastinum
- had origin in the respiratory tract and in the gastrointestinal tract so you can find both epithelium (GI muscle pattern and cilliated columnar epithelium)
- Prone to infection
- We see a massive lung expansion
What’s the dx ?
Congenital Lobar Emphysema
- Failure of bronchial mesenchyme
- Dysplastic bronchial cartilage collapses during expiration
- Severe air trapping and hyperinflation of affected lobe
- We see a massive lung expansion
- Symptoms are due to presence of a large non-functional mass or delayed infections
- Most cases are detected in-utero and most neonates are asymptomatic
What’s the dx?
Congenital Cystic Adenomatoid Malformation (CCAM)
- Segment of lung arrests development in the pseudoglandular period
- Overgrowth of terminal bronchioles coupled with deficiency of alveoli
- The affected segment is cystic and glandular (adenomatoid)
What is Pulmonary Sequestration?
- Aberrant non-functional masses of normal lung tissue that do not communicate with the normal tracheobronchial tree and have a systemic vascular supply.
- Can be intralobar or extralobar
- Embryologic origin unclear, but felt to represent another bronchopulmonary foregut malformation
What are the 2 pleural cavities congenital abnormalities?
- Empyema (filled with pus)
- Pneumothorax (bullae)
What is Congenital Diaphragmatic Hernia?
- Incidence 1:2000 live births
- Failure of development of the posterolateral segment of either hemidiaphragm
- Herniation of abdominal organs into the chest early in gestation
- Associated with severe lung hypoplasia secondary to inadequate thoracic space (both lungs are underdevelop)
- the majority are of the left lungs (80-90%)
- LEAD TO RESPIRATORY FAILURE
What is Eventration of the Diaphragm?
- Congenital: defective development or innervation
- Acquired: Injuries to the phrenic nerve, traction injury during birth or iatrogenic surgical injury
Both types may be asymptomatic or cause respiratory distress due to paradoxical diaphragmatic motion.
What are the clinical implications of surfactant deficiency?
- Lecithin:Sphingomyelin (L:S) ratio < 2 in amniotic fluid implies fetal surfactant deficiency and lung immaturity
- Antenatal steriod therapy promotes Type II pneumocyte development and lung maturation.
- This helps obstetricians and pediatric surgeons time the delivery to minimize the risk of respiratory distress syndrome (RDS) and hyaline membrane disease (HMD)
- There is also surfactant therapy
- surfactant is given by the trachea route to premature kids, infants with congenital lung anomalies, etc.
What is the main difference between a fetal and a newborn circulation?
In the fetal heart, there is a right to left shunt because the lungs don’t need no oxygenate the blood (gets it from placenta). The neonatal circulation however is in series, there is no mixed oxygen blood; it’s either oxygenated or not. Therefore, it is not normal for a neonate to have a shunt.
How does the folding of the embryo happen ? What does it lead to (main events) ?
- Once you have a cylindrical embryo, a primitive gut is formed from the definitive endoderm of the trilaminar embryo (the yolk sac is gonna become the gut)
- body cavities will be repositioned
- amniotic cavity will surround the embryo by expending and reducing the extra-embryonic cavity
How does the 3 part of the gut form ? What will the yolksac connected to ? What about the umbilical cord ?
- As the amniotic fluid grows and surround the embryo, the yolk salk is getting smaller and this gut is begining to push to form a fore, mid and hid gut.
- the yolk sac will always be connected to the midgut
- as the amnion is comming arouond the 3D embryo, it’s going to clamp around where the yolk sac was and it’s going to form the umbilical cord.
What’s the 3 most essential embryonic events affecting the lung development ? Why ?
- diaphragm formation : essential for the normal development of the lungs (ça lui donne de l’espace !!!)
- amniotic fluid circulation and adequate volume: help de growth of the respiratory buds (growth of the alveoli)
- Fetal breathing movements
What is recanalization and circulation of amniotic fluid ?
Apoptosis (that begins at week 4 and end at week 7) to open up the cloacal membrane and allow amniotic fluid to circulate through the canalized gut into tne amniotic cavity
Main structures of diaphragm formation ? Where do the innervation come from ?
- septum transversum : mesenchyme below the heart, will separate the pleural and peritoneal cavity
- left pleuro-peritoneal cavity : area between the pleural and peritoneal cavity
- mes-oesophagus : going around the oesophagus
** you’ll also need muscle formation from the cervical myotomes later
Phrenic nerve passage through the pericardio-pleural mesenchyme to diaphragm
what is the tracho-oesophageal mesenchyme role ?
to form a septum between the forming trachea and oesophagus (trachea-oesophagus septum) that separates the caudally extending trachea from the defined oesophagus
How is the lung formed (and pleurae)
- The foregut is surrounded by mesenchyme and the 2 pleural cavities (left and right).
- Once the trachea forms, the lungs buds (most caudal endodermal portion of the trachea) will grow towards each of the pleural cavities
why is the Shh gene important in lung development ?
Right at the tip of the respiratory buds, you have Shh that interacts with the mesenchyme and causes the proliferation right at the tip (dichotomous branching). Anything that’ll affect this gene will affect dichotomous branching and proliferation of distal tips.
what is an azygos lobe ?
If the azygos vein normally going over the top of the right bronchus doesn’t go there but through the substance of the lungs to reach the heart instead, it’s going to make an excess lobe
what happens during the terminal sac phase ?
alveolar endodermal epithelium differentiates into 2 types of functionnal cells (type 1 pneumocytes and type II that are surfactant secretor cells)
What are the different mechanism involved in gut anomalies ?
- hypoplasia of gut wall atresia of gut : a segment of the gut isn’t getting blood supply
- duplication of gut wall : incomplete due to apoptosis
- stenosis : due to smooth muscle hypertrophy
What are the different anomalies of the trachea and oesophagus ?
- failure of T-O septum
- atresia of oesophagus
- atresia of trachea
- T-O fistula
- regurgitation of oesophagus and air in stomach
What is Potters syndrome ? What’s the contrary
BOTH ARE AMNIOTIC FLUID TURNOVER
-
Potter syndrome : When the kidneys aren’t working properly (agenesis of kidneys), this will result in too little amniotic fluid (oligohydramnios) and associated severe hypoplasia of the lungs
- you have undeproduction of amniotic fluid
- The contrary, polyhydramnios is when the gut is obstructed and can’t accumulate amniotic fluid properly = problem too
In what stage of respiratory development does the type II cells increase and secrete surfactant ?
Terminal Saccular Period
