Embryology 2 - CVS/ Circulation/ GI/ Respiratory Flashcards
1- Define congenital heart disease.
2- When do they typically arise?
3- How can CHD be broadly classified according to the presence or absence of what?
1- Abnormalitiesofcardiac structure that are present from birth
2- Third to eighth weekof gestation
3- Cyanosis: blueness of the trunk and mucous membranes
> results from levels of deoxygenated haemoglobin of >3–5 g/dL in the arterial circulation.
Why are cardiovascular congenital anomalies frequently seen with abnormal facial development?
- Neral crest cells contribute to the development of facial bones as well as endocardial cells that line the outflow tracts of heart.
> Neural crest cells are very sensitive to toxic insults and can be damaged by retinoids, alcohol, and many other substances.
One reason for this sensitivity may be that they may lack some of the enzymes that help to scavenge and protect cells from cell-killing free radicals.
How is the heart tube formed?
1- 3 germ layers, mesoderm cells collect at the cranial end of embryo in front of pro-chordal plate. (Heart development starts in head)
2- Heart tube develops from splanchnic layer of lateral plate mesoderm.
3- Endoderm starts secreting growth factors (VEGF) causing the splanchnic layer of lateral plate mesoderm to start differentiating
4- Mesoderm starts specialising creating 2x heart tubes and 2x pericardial cavity
5- Lateral body folding causes heart tubes to fuse and pericardial cavities to fuse. Edges come together.
6- Resulting in 1 heart tube and 1 pericardial cavity.
-Whilst lateral folding occurs heart tube is pulled into pericardial cavity.
- Endoderm folding also makes epithelial lining of GI tract
7- Heart tube is held in place to posterior pericardial cavity wall via Dorsal mesocardium.
Label the images showing Lateral body folding to bring the 2 sides of the cardiac regions to the midline to fuse.
Label the heart tube. At what day is this seen?
What is the caudal/cranial part of heart tube?
What are the 3 divisions of Bulbus cords?
- Day 22
-Caudal pole forms the venous end
-Cranial end is the arterial portion, must sprout vessels to create an open path for blood flow
3 divisions:
1- Truncus arteriosus
2- Conus cordis
3- Trabeculated RV
Describe what happens during cardiac looping.
What day is it complete?
What pathology is it when cardiac looping is reflected?
- Day 28
1- T.A/B.C move to the right and anteriorly
2- P.V moves to the left and downwards posteriorly
3- P.A/S.V move to the left upwards posteriorly.
> Dextrocardia
What are the fates of the different sections of the heart tube?
- Aortic sac
- Truncus arteriosus
- Conus cordis
- Trabeculated portion of RV
- Primitive ventricle
- Primitive atria
- Sinus venosus
- Aortic sac: Aorta
- Truncus arteriosus : Aorta + Pulmonary trunk
- Conus cordis : Ventricular outflow tracts
- Trabeculated portion of RV: Muscular wall of RV
- Primitive ventricle: Left ventricle
- Primitive atria: Right and left atria
- Sinus venosus: Smooth part of right atria, coronary sinus, SA node , AV node, Bundle of his
Label the sinus venosus
At the fourth week, the sinus venosus is responsible for….
- The inflow of blood to the primitive heart, and empties into the primitive atrium.
- It receives venous blood from the right and left sinus horns
What are the Embryonic Veins and where do they receive blood from?
What do they form after birth?
3 major pairs of veins – vitelline, umbilical & cardinal
- Right vitelline vein ( from yolk sac) = SMV, proximal HPV, part of IVC
- Left umbilical vein ( from placenta) = ligamentum teres
- Right cardinal vein (from body) = azygos vein
What is the link between the right atrium and the sinus venosus?
1- Most of the right atrium (the smooth-walled part) is derived by incorporation of the sinus venosus and right sinus horn into the primitive right atrium.
2- Venous flow shifts to the right and the vena cava are formed
3- Right sinus horn expands to accommodate the increased blood flow - opening into the right atrium expands.
4- As R. sinus horn expands, it is incorporated into the right atrium
5- As a result, the opening from the left sinus horn diminishes in size.
6- All that remains of the left sinus horn is the coronary sinus and oblique vein of the left atrium
What happens to the left atrium?
- Four pulmonary veins are incorporated into the primitive left atrium, forming the smooth inflow portion of the left atrium and the oblique pericardial sinus.
How is Visceral pericardium formed?
- Sinus venosus allows cells to move into the pericardial cavity forming a layer around the heart.
1- What stage does a heartbeat begin? How?
2- What is key about vessels at this stage ?
3- Where do the 1st blood cells arise from?
1- WEEK 4
> Some cells of sinus venosus infiltrate into heart and form primitive conduction system to allow for the heart to start beating.
2- They are paired
3- Yolk sac
How does Atrioventricular valve formation occur?
> Level of PV/PA cross section
1- Neural crest cells migrate and form anterior and posterior endocardial cushions
2- As they grow towards each other they fuse together and we develop 2 canals forming septum intermedium.
3- Endocardial cells start forming valve falls off septum intermedium.
- Annulus rings connect the valves together
4- Off the valves come chord tendinae
Giving us Bicuspid and Tricuspid valves
What day does atrial septa form?
Describe the process.
- Day 30-33
1- Septum primum grows down the middle of both primitive atria towards septum intermedium, leaving a gap as it does not actually reach it. = osteum primum
2- Septum primum continues to grow and reaches septum intermedium closing of osteum primum
3- Another hole develops due to apoptosis of cells towards the top of septum primum = osteum secundum
4- To the right, septum secundum grows down from endocardial cushions to block osteum secundum
5- Still space below septum secundum and osteum secundum which gives foramen ovale (By week 7, the foramen ovale is functional)
*Fossa ovals after birth
When does inter ventricular septation happen?
How does inter ventricular septation occur?
- What part develops from endocardial cushions, what part develops from myocardial cells?
- Week 7 Day 49
1- At apex of heart we develop tissue that moves upwards creating a septum = muscular portion of inter ventricular septum
2- Space remains between B.C/PV so tissue from the septum intermedium grows downwards and fuses with muscular position of inter ventricular septum. This is known as membranous portion of I.V.S
- Membranous made from endocardial cushions
- Muscular made from myocardial cells
How do pulmonary and and aortic outflow tracts develop from truncus arteriosus?
1- Neural crest cells migrate and form endocardial cushions left and right.
- Truncal ridges and bulbar ridges
- Also anterior and posterior ridge forming coming together in the middle at conus cordis
2- Ridges move together spiralling around central axis
3- The ridges fuse and form septums
- This forms Aorticopulmonary septum via specialist movement
4- Blood generally moves up the bulbs cordis and Truncus arteriosus
- Blood flowing from the left ventricle will move from the posterior section of bulbar septum and back of Aorticopulmonary septum then at the middle it will move anterior on top of Aorticopulmonary septum out through the anterior portion of truncal septum.
- Vice versa for blood flowing from the right ventricle.
5- Rotation occurs splitting the structures up neatly.
How do valves form between ventricles and corresponding arteries? (Semilunar valves)
Cross section at Conus cordis and Bulbus cordis junction
1- Neural crest cells form endocardial cushions
- Right, left, anterior and posterior
2- When aorticopulmonary septum forms it rotates in a corkscrew way rotating splitting the right and left cushions in half creating posterior portion and anterior portion.
3- Posterior strucutre becomes left ventricular outflow tract for Aorta.
4- Anterior structure becomes right ventricular outflow tract for Pulmonary trunk.
Link the clinical abnormalities to developmental stage in embyological process.
1- Tetralogy fallot
2- Atrial septal defects
3- Ventricular septal defects
4- Transposition of the great vessels
1- Tetralogy fallot: Problem with septation of the outflow tract 4 issues..
2- Atrial septal defects : Issues with septum formation, too much apoptosis?, not present?
3- Ventricular septal defects: Septums font form due to neural crest cell defect, no membranous septum?
4- Transposition of the great vessels : Aorta and PT swap origns. Neural crest cell problem (responsible for septation of outflow tract)
Migration of neural crest cells occurs when?
1- What are NCC involved in?
2- What do cells that participate in the heart septation make? What does this explain?
3- What are NCC sensitive to? What explains this sensitivity?
1- Septation of the outflow tract and perhaps other regions as well - to forming the septa.
2- Make all of the bones of the face and some of the skull. > explains why many children with craniofacial defects (e.g., cleft lip or palate, etc.) also have cardiac defects
3- Toxic insults which are damaging such as retinoids, alcohol, and many other substances > lack some of the enzymes that help to scavenge and protect cells from cell-killing free radicals
Describe foetal circulation.
What are the 3 shunts.
1- Blood flows through umbilical vein (left 1 persists) through Ductus Venosus into IVC carrying oxygenated blood.
2- Blood moves up IVC and empties into R.A
- Pressure in R.A > L.A so blood bypasses R.V and moves via Foramen Ovale into L.A.
3- L.A pumps blood to L.V
4- L.V pumps blood through Aorta to descending aorta
5- Some blood moves from R.A to R.V
- This blood moves up Pulmonary trunk it can go into pulmonary arteries BUT it mainly goes through Ductus arteriosus as pressure in pulmonary circulation < pressure in Aorta.
6- Decending aorta > Common iliac artery > Internal iliac artery > 2 Umbilical arteries taking blood back to placenta carrying deoxygenated blood.
What happens during post-natal circulation?
- Right side pressure drops less than left side
- Left side pressure greater than right side
= Foramen oval closes completely > Fossa ovalis
What are the human remnants:
1- Ductus arteriosus
2- Ductus venosus
3- Foramen vale
- Umbilical artery
- Umbilical vein
- Allantois
What do the first 3 Bypass?
- Ductus arteriosus: Ligamentum arteriosus
- Ductus venosus: Ligamentum venosum
- Foramen vale: Fossa ovalis
- Umbilical artery: Medial umbilical ligament > Superior vesical artery
- Umbilical vein: Ligamentum teres hepatice
- Allantois: Median umbilical ligament
1- Ductus arteriosus - P.T > Arch of Aorta
2- Ductus venosus - Umbilical vein > IVC
3- Foramen vale - R.A > L.V
What forms the gut tube? What is the gut tube suspended by?
- Lateral body walls fold to close ventral body, forming the gut tube
> Suspended by dorsal mesentery from the dorsal wall, and runs from the bottom of the oesophagus to the rectum
1- How is peritoneum formed?
2- What type of peritoneum does the dorsal mesentery consist of?
1- Submesoderm lining of intra-embryonic body cavity forms peritoneum.
- Visceral surrounds gut tube
- Parietal surrounds intra-embryonic cavity
2- Visceral peritoneum that reflects off the gut onto the posterior wall, and is continuous with the parietal layer
How does the foregut develop? Why is the pancreas referred to as secondarily retroperitoneal?
- As the liver enlarges, the entire gut tube twists, to put the liver to the right of the stomach and the spleen to the left.
> Because of the dorsal position of the pancreas, as the spleen moves to the left, the pancreas becomes pressed against the dorsal wall of the abdomen, and fuses to it. Because it has been intraperitoneal during its development, it is therefore referred to as secondarily retroperitoneal. Compare this to the kidneys, which develop retroperitoneally, and so can be termed primarily retroperitoneal.
What adult structures do the respective layers become…
Intraembryonic cavity
Serous membrane
Parietal mesoderm
Visceral mesoderm
Intraembryonic cavity > Peritoneal cavity
Serous membrane > Peritoneum
Parietal mesoderm > Abdominal wall muscles
Visceral mesoderm > Muscles of the gut wall
*gut is lined with endoderm, and note the developing spinal cord, dorsal to the gut
1- What is the vitelline duct?
2- How is the vitelline duct formed?
3- How long does the vitelline duct remain for?
4- Through which region does the vitelline duct run from?
1- Narrow connection to the mid gut from the yolk sac
2- The yolk sac is pinched down by body folding to form the narrow connection
3- 12th-14th weeks of gestation
What are the 4 gut regions, and where do they run from?
1- Pharyngeal gut: from the oropharyngeal membrane to the respiratory diverticulum.
2- Foregut: from the lung bud diverticulum to the bile duct.
3- Midgut: from the bile duct to the first two-thirds of the transverse colon.
4- Hindgu:t from the last third of the transverse colon to the cloacal membrane.
What are the arteries of the gut? What are they derived from?
Celiac artery supplies the foregut
Superior mesenteric artery supplies the midgut
Inferior mesenteric artery supplies the hindgut
> Vitelline vessels
Gut Buds:
1- What do buds at the pharynx form?
2- What proliferates to form buds for lungs, liver, gallbladder and pancreas?
3- How do lungs grow?
4- How does the liver grow?
1- Buds form glands in the neck and thorax
2- Endoderm of the foregut
3- Proliferation of endoderm at the caudal end of the pharynx that forms the respiratory diverticulum (lung bud)
4- Proliferation of gut endoderm forms liver buds into the septum transversum
How are hepatic sinusoids formed?
- As liver cells proliferate, vitelline veins in the region, together with some parts of the proximal segments of the umbilical veins, form the hepatic sinusoids
Respiratory and GI system cleavage :
1- Where does the respiratory system bud out from? How?
2- How are alveolar cells formed?
2B- How are Smooth muscles and cartilage formed?
2C- How is pleura formed?
2D- How are the muscles and bones formed of the thoracic wall?
3- How many alveolar cells are present at birth?
4- What is respiratory distress syndrome?
1- Buds anteriorly from the GI tract
- Respiratory diverticulum emerges anteriorly from the gut tube Day 25
- It then forms the trachea which splits into two lung buds.
- Outpouching elongates ventrally and caudally before bifurcating into two primary bronchial buds by 5 weeks.
- By the 6th week of development, the lobar buds have started to develop
- 8 weeks the adult lobes and fissures of the lungs are visible. The lungs however, are not fully mature until shortly before birth and remain fluid filled until the first breath
2- By differentiation from gut endoderm of lung buds
2B- Visceral mesoderm,
2C- Serous membrane lining the intraembryonic cavity.
2D- Parietal mesoderm will lead to the muscles and bones of the thoracic wall and the ectoderm will be the skin covering it.
3- 16% → remainder develop for 10 years
4- Condition in premature infants (<7 months) that results in an insufficient amount of surfactant produced due to insufficient amount of type II alveolar cells produced
→ increased surface tension → collapse of alveoli 8 out of 10
babies born at 26 weeks survive
How is the pancreas formed?
> How does an annular pancreas form?
- Ventral and dorsal buds form off of the gut tube
- Ventral bud then move to lie underneath dorsal one, so that they are now in contact
> ventral pancreas doesn’t come round properly during rotation, so it completely encapsulates (forms a ring) around the duodenum
How does stomach form?
- As stomach lengthens, posterior part will begin to increase in size → greater curvature (A,B,C)
- Posterior part swings down to left, and anterior part swings to the right. (D)
- Stomach dilates further increases in size, and undergoes some rotation so fundus tips over so that it can find a space for itself to sit in (E)
How is the primary intestinal loop formed?
What serves as the axis for this rotation?
How is the loop connected to the yolk sac?
What happens to the loop in the 6th week?
What happens to the loop in the 10th week?
*What causes herniation of gut?
1- 8 weeks Midgut also undergoes rotation. Initially, this rotation is 90 degrees counterclockwise and forms the primary intestinal loop.
2- The axis for the rotation is the superior mesenteric artery that supplies the midgut.
3- Note that the point of the loop is connected to the yolk sac by the vitelline duct.
4- As this loop forms in the sixth week, it herniates into the umbilical cord, a process called “physiological umbilical herniation.”
5- Loops of bowel will return to the abdominal cavity in the 10th week.
- As the loops are retracted a few weeks later, they continue to grow and rotate an additional 180 degrees.
(undergoes 270˚ rotation in total)
*The gut loops herniate into the umbilical cord owing to rapid liver growth. By the 12th week, the herniated loops can return because hepatic growth slows and expansion of the abdominal cavity creates space within the developing embryo/fetus.
