Heart Development - Bolender Flashcards by Timothy Carll

How is the heart tube arranged?

From Superior to Inferior:

Transverse Arteriosum

Bulbis Cordis

Primative Ventricle

Primative Atria

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Which direction does the cardiac tube fold?

To the right

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What disease occurs if the cardiac tube folds in the opposite direction? What is other disorders is this associated with?

Dextrocardia (heart on the right side)

Associated with situs inversus (reversed body) and TGA (transposition of the great arteries)

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What joins with the primative atria? When does this happen?

The sinus venosum (specifically the right and left horn) Day 22

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Which branch of the sinus venosum becomes dominant? What does this mean for circulation of the heart?

The right branch is dominant after the left branch atrophies and connects into the right branch. All deoxygenated blood now empties into the right ventricle.

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After the right branch joins with the left branch, an anastamoses is formed between the right and left side. Which branches are involved?

Anterior Cardinal Vein of the Left Branch

Anterior Cardinal Vein of the Right Branch

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What does the left branch of the sinus venosum form?

It atrophies into the coronary sinus.

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What four branches come off BOTH the left and right sinus venosum?

Anterior Cardinal Vein

Posterior Cardinal Vein

Viteline Vein

Umbilical Vein

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What do the following embryologic structures become: Anastamoses between Cardinal Veins Right Anterior Cardinal Vein Right Vitelline Vein Left Vitelline Vein

Left Brachiocephalic Vein

Superior Vena Cava

Inferior Vena Cava

It atrophies in adults

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Where do the pulmonary veins come from?

They arise from the lungs (?) and fuse with the atria. They DO NOT arise from the sinus venosum.

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How is the definitive left atrium formed? What is the exception?

Absorption of the endothelium of the pulmonary veins

The auricle, which is primative atria.

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Where do the endocardial cushions form? What is their importance?

At the junction of the atria and ventricles

This is the first division of the heart; they will end up becoming the AV valves, septum intermedium, and fibrous valve skeleton.

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What fills the endocardial cushions?

Initially, cardiac jelly, but later, signalling molecules cause an endothelial to mesenchyme transition and migration of mesenchyme into the cushions.

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The primordial atrium is divided during development. What structures contribute to this? (traditional view)

The septum primum, and septum secundum

*Revised view: There is no septum secundum.

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Distinguish between the atrial septum’s foramina primum and secundum.

The foramen primum “forms first”, it is actually the space not filled in by the septum primum. It eventually fills in, while the foramen secundum forms suprior to it and eventually contributes to the foramen ovale.

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How does the foramen ovale only permit R > L shunting?

The flapper valve (the bulk of the interatrial septum) cannot flip beyond the “septum secundum” (actually the superior interatrial fold).

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What congenital disorders could result from abnormal development of the septum primum?

Atrial septal defects

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What tissues contribute to the partitioning of the outflow tract?

Conotruncal/bulbar ridges. Ultimately from cardiac as well as neural crest mesenchymes.

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Which occurs further from the heart apex: Partitioning of the outflow tracts or of the aortic sac?

Aortic sac (downstream of the outflow tracts)

Recall the four cushions that contribute to the formation of the septum which divides the outflow tract.

Right Dorsal Conus Cushion

Left Ventral Conus Cushion

Right Superior Truncus Cushion

Left Inferior Truncus Cushion

*It is questionable how useful this is to know.

The membranous interventricular septum separates the aortic vestibule from the right ventricle. What contributes to it?

Forms from the fusion of the conotruncal septum with the endocardial cushion. These connect to the muscular interventricular septum.

Recall the cell precursors for the following cells:

Purkinje fibers

Cushion cells

Coronary endothelium

Aortic smooth muscle

Purkinje: From cardiogenic mesoderm (ventricular myocytes)

Cushion: From cardiogenic mesoderm (endothelial cells)

Coronary Endothelium: From proepicardium (originally dorsal mesocardium)

Aortic SmoothM: From cardiac neural crest

How many pharyngeal arch arteries are there?

5; 1/2/3/4/6 (5th doesn’t form!)

What is the developmental fate of pharyngeal arch artery 1?

What is the developmental fate of pharyngeal arch artery 2?

What is the developmental fate of pharyngeal arch artery 3?

1: Forms maxillary/ext-carotid aa, otherwise degenerates.
2: Forms hyoid/stapedial aa.
3: Forms common & internal carotid aa.

What is the developmental fate of pharyngeal arch artery 4? What is the developmental fate of pharyngeal arch artery 5? What is the developmental fate of pharyngeal arch artery 6?

4: Forms part of aortic arch (left), and proximal right subclavian (right). Never formed! 6: (left) left pulmonary artery and ductus arteriosus. (right) right pulmonary artery.

Distinguish between the pulmonary circulations during fetal growth and after birth.

In utero: High resistance because collapsed. After first breath, resistance drops and flow increases. The ductus arteriosus and foramen ovale shut.

What is the function of the ductus venosus? What does it form in an adult?

Shunts fresh blood from the placenta around the liver to the IVC. (not sure why the liver doesn't deserve fresh blood) Forms the ligamentum teres.

How does the brain end up with more oxygenated blood than the rest of systemic circulation in utero?

Aortic arches contribute to head/neck circulation upstream of the site of mixture from ductus arteriosus.

What facilitates the flow of oxygen from maternal to fetal blood?

At the placenta, fetal venous blood has a lower Po₂, and fetal hemoglobin has a higher affinity for oxygen than adult Hb.

What comprises the Pentalogy of Cantrell? Where is it seen?

Ectopia Cordis, VSD, Sternal cleft, Diaphragmatic hernia and Omphalocele. Results from failure of closing of the ventral/anterior body wall.

In very early development, what veins flow into the primitive sinus venosus?

An umbilical vein, vitelline vein, and a common cardinal vein (union of two cardinals per side)

Why is dextrocardia associated with Kartagener's syndrome?

Kartagener's syndrome involves mutation of ciliary protein, which is necessary for the left-side folding of the heart.

What is the name of the structure that divides the primitive AV canal? From what does it form? What is the name of the structure that divides the primitive outflow tract? From what does it form?

The septum intermedium, formed from the union of the superior and inferior endocardial cushions. The aorticopulmonary septum, formed from the conotruncal ridges and neural crest mesenchyme.

1) Where are cardiac precursor cells initially located in the developing embryo? 2) What area in the embryo influences the specification and migration of these precursors?

1) Splanchnic Mesoderm 2) Anterior Endoderm

1) What is the primary heart field shaped like? 2) What gene do the precursor cells in this field express? 3) What happens in the (functional) absence of this gene?

1) A crescent / inverted U (Cardiogenic crescent) 2) **Nkx2.5 **- t**he "Tin Man" gene** 3) Absence of Nkx2.5 results in **acardia** (obviously lethal)

1) How does embryonic folding in the *cranial-caudal (sagittal)* plane move the primary heart field? 2) How does embryonic folding in the *transverse* plane change the primary heart field?

1) This first folding relocates the heart field from a **superior** position ("above" the brain) to a **ventral** one. 2) This second folding **unites the heart primordia in the midline**.

What is the dorsal mesocardium?

Following folding in the transverse plane, the now united and midline-centered heart tube is connected to the dorsal part of the embryo by a temporary **stalk**, called the dorsal mesocardium.

What structural pathology of the heart can result when the anterior thoracic wall fails to close properly? What combination of pathologies is this often seen as a part of? Can you name the other pathologies?

Ectopia Cordis (External Heart) **Pentalogy of Cantrell** 1) Ectopia Cordis 2) Ventricular Septal Defect 3) Sternal Cleft 4) Diaphragmatic Hernia 5) Omphalocele (superior abdominal wall defect)

1) The primitive heart tube consists of what primitive heart chambers? 2) Where are additional heart segments added from? What segments are added?

1) Left Ventricle (only!) 2) Cells are contributed by the **secondary heart field**, including the **outflow region, primitive RV, primordial atrium, AV canal, and sinus venosus**

True or false: the mature heart is the sum of the primitive heart segments.

**False**. More **maturation**, **partitioning**, etc. are required. The segments of the primitive heart DO NOT equal the chambers of the mature heart!

1) Where is the secondary heart field located? 2) What embryonic tissue is it believed to derive from? 3) What is the master gene for this heart field?

1) **Medial and Dorsal** to the primary heart field 2) Splanchnic mesoderm? (not known for sure) 3) **I****sl-2** is the master gene (I believe the letters are i-s-L, but am not sure)

1) What layer lies between the endocardium and myocardium of the primitive heart tube? 2) What fourth layer is added externally to the tube? 3) Where does this fourth layer derive from?

1) Cardiac Jelly 2) Epicardium - formed by cells that migrate over the other primordial heart structures 3) From the **proepicardial organ**, a derivative of the coelomic epithelium that overlies the inflow region (aka the **dorsal mesocardium** stalk!)

What cells do Purkinje fiber cells originate from?

Ventricular Myocytes

How does the proepidcardium contribute to the formation of the coronary vessels?

The proepicardial cells differentiate into coronary SMCs, endothelial cells, and fibroblasts that make up coronary vessels.

What veins carry blood to the sinus venosus of the simple tubular heart from: 1) The placenta? 2) The embronic gut? 3) The embryonic head & trunk? What is the O₂ content of the blood in these veins? 4) Where does the blood go from the heart?

1) Umbilical veins (O₂ rich) 2) Vitelline veins (O₂ poor) 3) Common Cardinal veins (O₂ poor) 4) Primitive RV → Aortic sac → pharyngeal arch arteries

What is the first step in chamber formation and partitioning of the simple tubular heart?

Cardiac Looping