Organogenesis 1: Heart
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What happens to the Epiblast at 2 weeks?
- Surface epiblast cells move through the primitive streak and migrate between the hypoblast and epiblast
- The first cells to move inward displace the hypoblast to create the definitive endoderm.
- Once definitive endoderm is established, inwardly moving epiblast forms mesoderm.
- What is left over becomes the ectoderm
Describe an embryo at the 3 week stage of development. What is the major process that occurs at this stage?
Name the germ layers and describe what types of tissue/organs they form in the developing embryo.
- The most characteristic event occurring during the third week of gestation is gastrulation, the process that establishes all three germ layers (ectoderm, mesoderm, and endoderm) in the embryo
- 1. Endoderm: Lining of internal organs gastrointestinal (trachea, pancreas, liver), respiratory, and endocrine systems
- 2. Mesoderm: Muscles (including myocytes/heart muscle), gonads, kidneys, connective tissue, and the notochord
- 3. Ectoderm: CNS (brain and spinal cord), skin
General Overview: Describe the 5 events in the formation of the heart from a simple tube and when they happen
- 1. Formation and folding of tube that will become the heart.
- 2. Separation into atria & ventricles
- 3. Division of common atria to form R & L atria.
- 4. Division of common ventricle into R & L ventricles
- 5. Formation of aorta and pulmonary trunk
Describe the separation into atria & ventricles
- Separation into atria and ventricles: Formation of the atrioventricular canals
- - At the end of the fourth week, two mesenchymal cushions, the atrioventricular endocardial cushions, appear at the anterior and posterior borders of the atrioventricular canal
- - form initial division of atria and ventricles
- - grow into canal - meet and fuse to separate atrioventricular canal into right and left channels
- Notice how initially a single tube, cushions caving in laterally, and inferior/superiorly divide the atria and ventricles
- - simultaneously the common atria and ventricles will be subdivided into L and R (later)
Describe the septation of the common atrium into a right and left atria.
- At the end of the fourth week, the septum primum grows down from the roof of the primitive atrium toward the endocardial cushions (essentially sealing off the left and right atrium).
- But before it is sealed off, apoptosis occurs to the superior proportion of the septum primum. This is what forms the valve for the foramen ovale (later the fossa ovalis)
- A thicker septum secundum forms through a downgrowth parallel to the septum primum. However growth stops before the endocardial cushions and a gap is left. This gap is the foraman ovale.
- - Upon birth, the shunt easily closes with a backlog of pressure from left to right
Why is there a shunt from right to left atrium?
- Poorly oxygenated blood enters from the foetus at the superior vena cava
- Well-oxygenated (from placenta) blood enters at the inferior vena cava and is able to push through the valve of the foramen ovale
- This means that the left side of the heart receives better-oxygenated blood than the right side (for the heart and brain)
- Furthermore, the lungs are still developing and would be water-logged and a bypass is required
Discuss how an atrial septal defect (3) could arise during heart development (using diagrams if you wish)
- A. Normal atrial septum formation.
- B,C. endocardial cushion defect caused by excessive resorption of the septum primum.
- D,E. Similar defect caused by failure of development of the septum secundum.
- F. Common atrium, or cor triloculare biventriculare, resulting from complete failure of the septum primum and septum secundum to form.
Describe the formation of R and L ventricles
- what happens if the process does not complete?
- By the end of the fourth week, the two primitive ventricles begin to expand.
- - however the medial walls of the expanding ventricles become apposed (stay put) and gradually merge, forming the muscular interventricular septum.
- Sometimes, the two walls do not merge completely, and a cleft between the two ventricles appears.
- - In the foetal heart, this allows communication between the two ventricles.
- The interventricular foramen, (i.e. above the muscular portion of the interventricular septum) is eventually closed by outgrowth of tissue from the inferior endocardial cushion along the top of the muscular interventricular septum.
- - This tissue fuses with the abutting parts of the conus septum. (see in later slide)
- - Complete closure of the interventricular foramen forms the membranous part of the interventricular septum.
Discuss how a ventricular septal defect could arise during heart development (using diagrams if you wish).
- Ventricular septal defects (VSDs) involving the membranous or muscular portion of the septum are the most common congenital cardiac malformation
- *Additional information you probs don't need to know*
- - VSDs occur as an isolated condition in 12/10,000 births.
- - Most (80%) occur in the muscular region of the septum and resolve as the child grows.
- Membranous ventricular septal defects (VSDs) usually represent a more serious defect and are often associated with abnormalities in partitioning of the conotruncal region.
- - Depending on the size of the opening, blood carried by the pulmonary artery may be 1.2 to 1.7 times as abundant as that carried by the aorta.
What is the Tetralogy of Falot?
- Tetralogy of Fallot: the most frequently occurring abnormality of the conotruncal region
- - due to an unequal division of the conus resulting from anterior displacement of the conotruncal septum (in other words, the aorta got way more tubing than the P. trunk).
- Displacement of the septum produces four cardiovascular alterations;
- (a) a narrow right ventricular outflow region, pulmonary infundibular stenosis;
- (b) a large defect of the interventricular septum;
- (c) an overriding aorta that arises directly above the septal defect; and
- (d) hypertrophy of the right ventricular wall because of higher pressure on the right side.
- Tetralogy of Fallot, which is not fatal, occurs in 9.6/10,000 births
Describe common congenital abnormalities with the great vessels
- (A) Transposition of the great vessels: when the conotruncal septum fails to follow its normal spiral course and runs straight down.
- - As a consequence, the aorta originates from the right ventricle (carrying deoxygenated blood), and the pulmonary artery originates from the left ventricle. It is usually accompanied by an open ductus arteriosus.
- (B) Pulmonary valvular atresia: Valvular stenosis of the pulmonary artery or aorta occurs when the semilunar valves are fused for a variable distance. In the case of a valvular stenosis of the pulmonary artery, the trunk of the pulmonary artery is narrow or even atretic.
- - The patent oval foramen then forms the only outlet for blood from the right side of the heart.
- - The ductus arteriosus, always patent, is the only access route to the pulmonary circulation.
Considering this diagram, what is the physiological purpose of the ductus arterious?
- The foetal lung capillaries is high resistance and water logged until the baby takes its first breaths
- - in other words the pulmonary circuit has no real business receiving too much blood flow when the placenta is the main source of oxygen
- - so blood leaving the right ventricle (destined for the pulmonary arteries and into the pulmonary circuit in adults) needs somewhere else to go. It instead enters the aorta through the ductus arteriosus; destined to be re-oxygenated at the placenta
What are the changes to the foetal heart at birth?
- Infant takes first breath; lungs inflate with air, pulmonary capillaries expand, resistance to blood flow through the lungs decreases.
- Blood leaving the right ventricle now has the option of a low-resistance pathway into the lungs, or a high-resistance pathway through the ductus arteriosus into the systemic circuit. It prefers the low-resistance pathway into the lungs.
- For the first time, a large volume of blood returns to the left atrium via the pulmonary veins. Left atrial pressure increases.
- The umbilical vein constricts and/or is clamped. Venous return from the placenta drops to zero. Inflow to the right atrium decreases, right atrial pressure falls.
- LA pressure now exceeds RA pressure; blood begins to flow from left atrium to right; the flap valve of the foramen ovale closes, thus separating the two atria.
- Smooth muscle in the wall of the ductus arteriosus contracts in response to increased oxygen tension in the blood. After 10-15 hours the ductus is closed. The systemic and pulmonary circuits are now physiologically separate.
- Septum secundum
- Foramen ovale
- Septum primum
- Membranous septum: RV to LV shunt and pathological weakpoint
Recap: What are the purposes of the shunts (i.e. the foramen ovale, Ductus arteriosus and ductus venosus)
- Oval foramen: Blood from R to L atrium
- - it allows for maximal O2 and blood to the developing foetal brain
- Ductus arteriosus: directs blood (destined for the pulmonary circuit) into descending aorta
- - allowing for it to travel to the placenta for reoxygenation
- Ductus venosus: This second shunt bypasses the liver, which is largely non-functional at this stage in foetal development.
- - ductus venosus allows blood from the umbilical vein, approximately 50% of CCO, to enter the inferior vena cava directly, without ever entering the liver.
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