Chapter 13 embryology

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What intercostal spaces drain into right supracardinal veins

4th and 11th

Before birth blood returns to fetus via umbilical vein

80% saturation

Ventricular inversion. What is it

AKA L-transposition of the great arteries. Because the pulmonary artery exits the morphologic left ventricle and the aorta exists the morphologically right ventricle

When are the atrioventricular valves formed?

AV valves formed after AV endocardial cushions fuse Each AV orifice surrounded by proliferations of MESENCHYMAL tissue derived from endocardial cushions Bloodstream hollows out and thins tissues on the ventricular surface of these proliferations Mesenchymal tissue becomes fibrous and forms the atrioventricular valves Attached to ventricular wall by muscular cords

Septum formation in the truncus arteriosus and conus cordis Interventricular foramen. Explain what you know

Above the muscular portion of interventricular septum

20% fusion of septum primum and secundum is incomplete

Afterward, narrow oblique cleft remains between atria Probe patency of oval foramen does not allow cardiac shunting of blood

Regarding septum formation in common atrium The passage between the two atrial cavities consists of an obliquely elongated cleft through which blood travels from the right side and flows...

And flows to the left side

Vein anastomosis of cardinal vein

Anterior cardinal vein- left brachiocephalic-blood from left side of head and upper extremity channeled right Terminal portion of left posterior cardinal vein entering the left brachiocephalic vein retained as a small vessel Left superior intercostal vein receives blood from the second and 3rd intercostal spaces Anterior cardinal veins provide primary venous drainage of the head during the 4th week and ultimately from the internal jugular veins.

Cardinal veins- initially form main venous drainage system of embryo Anterior cardinal veins Posterior cardinal veins Cardinal veins form symmetrical system

Anterior-drain cephalic part of embryo Posterior-Drain rest of the embryo

Septum formation in atrioventricular canal Four atrioventricular endocardial cushions. describe them

Appear at the end of the 4th week One on each side of the atrioventricular canal One at the dorsal (superior) border of the atrioventricular canal One at the ventral (inferior) border of the atrioventricular canal

The fifth aortic arch never forms. It forms incompletely or regresses. What are the arch numbers

Arches are numbered I, II, III, IV, and VI During development the arterial pattern becomes modified and some vessels regress completely.

The arteries are the aortic arches which arise from where?

Arise from the aortic sac, which is the most distal part of the truncus arteriosus

Lymphatic system- where does it arise from

Arises from sac like outgrowth of endothelium and veins

Aortic arch system loses symmetrical form with further development. Establishes definitive pattern

Arterial system

With ventriclular inversion, what about arteries

Arteries in normal position, but ventricles are reversed This disorder arises during the establishment of laterality and specification.

Other notable changes

As a result of the caudal shift, the left subclavian shifts its point of origin from the aorta at the level f the 7th intersegmental artery to an increasingly higher point until it comes close to the origin of the left common carotid artery Course of the recurrent laryngeal nerves becomes different on the right and left sides Initially these nerves (branches of the vagus) supply the 6th pharyngeal arches → heart descends and these nerves hook around the 6th aortic arches and ascend to the larynx which accounts for their recurrent course On the right when the distal part of the 6th aortic arch and the 5th aortic arch disappear, the recurrent laryngeal nerve moves up and hooks around the right subclavian artery On the left, the nerve does not move up because the distal part of the 6th aortic arch persist as the ductus arteriosus that later forms the ligamentum arteriosum

What happens to the left common cardinal vein at 10 weeks

At 10 weeks, the left common cardinal vein becomes obliterated and all that remains of the left sinus horn is the oblique vein of the left atrium and coronary sinus.

Where does the heart receive veinous drainage?

At the caudal pole

At the completion of looping what is formed

At the completion of looping the smooth walled heart tube begins to form primitive trabeculae in two sharply defined areas just proximal and distal to the primary interventricular foramen.

Septum formation in common atrium When does the sickle shaped crest grow from the roof of the atrium to the lumen

At the end of the 4th week

How doe the atrial portion shift

Atrial portion shifts dorsocranially and to the left

Where do the atrioventricular cushion cells come from?

Atrioventricular cushion cells derived from overlying endocardial cells that detach from their neighbors and move into the matrix

Because embryo folds cephalocaudally and laterally, how are the caudal regions of the paired cardial primordia arranged.

Because the embryo folds celphalocaudally and laterally, the caudal regions of the paired cardiac primordia are merged except at their caudalmost ends.

Lymphatic system development

Begins development later than cardiovascular system

What is the bending of the cardiac loop due to? When does it end?

Bending due to change in cell shape Creates cardiac loop Completes at day 28

Leaflets of bicuspid valve , where located

Bicuspid valve has two valve leaflets and lies in the left atrioventricular canal

Steps of fetal circulation

Blood fetus umbil vein Approach liver Most blood flow through ductus venosus into inferior vena cava by bypassing liver Small amt enter liver sinusoid mix with portal blood (reg by ductus venosus) INferior vena caval placental blood mix w/ deox blood coming from lower limb

During the formation of cardiac loop, what does the bulbus remain, smooth or rough.

Bulbus remains temporarily smooth walled during formation of cardiac loop

Once primitive ventricle is trabeculated, what is it called

Called the primitive left ventricle

The trabeculated proximal third of the bulbus cordis is called what

Called the primitive right ventricle

When does the cardiac tube bend?

Cardiac tube bends around day 23 as the outflow tract continues to lengthen

Regarding formation and position of the heart tube The central part of horse shoe shaped tube expands to form what.

Central horse shoe shaped tube forms future outflow tract of ventricular regions

How is it the interventricular foramen closed

Closed by outgrowth of tissue from the anterior (inferior) endocardial cushion along the top of the muscular interventricular septum. Tissue fuses with the abutting parts of the conus septum

Closure of the oval foramen caused by increased pressure in the left atrium combined with decreased pressure on the right side

Closure is reversible Crying baby creates a shunt from right to left. This can account for cyanotic periods in the newborn 20% of people poor closure. Probe patent foramen ovale

Circ changes at birth Caused by cessation of placental blood flow at beginning of respiration

Closure of ductus arteriosus by muscular contraction of wall rapidly increase amt blood flowing thru lung vessels Raises presure in l. atrium. Rt atrial pressure decrease as result of interruption of placental blood flow Septum primum apposed to septum secundum and the oval foramen closes

Vascular changes after birth

Closure of umb arteries caused by contraction of smooth muscle walls caused by thermal and mech stimuli and changes in O2 tension Arteries close few min after birth-- obliteration of lumen by fibrous proliferation could take 2-3mo Distal parts of umbilical arteries form medial umbilical ligaments and the proximal parts remian open as the superior vesicular arteries Closure of ductus venosus occurs after closure of umbilical arteries Blood from placenta can enter newborn after birth

Transformation from embryonic to adult arterial system What does 3rd aortic arch turn into

Common carotid artery and first part of internal carotid artery. Remainder of internal carotid is formed by the cranial portion of the dorsal aorta External carotid artery is a sprout of the third aortic arch

Right ventricle is on left side and connects to the left atrium through which valve in ventricular inversion

Connects to the left atrium through the tricuspid valve

Conotruncal cushion cells are derived from where

Conotruncal cushion cells are derived from neural crest cells migrating from the cranial neural folds to the outflow tract region

Septum secundum Describe it.

Crescent shaped fold that appears when the lumen of the right atrium expands as a result of incorporation of the sinus horn

Development of Sinus Venosus What does the crista terminalis do/form into

Crista terminalis forms the dividing line between the original trabeculated part of the right atrium and the smooth walled part (sinus venarum) which originates from the right sinus horn.

Molecular regulation of cardiac development cardiac looping is dependent on several factors. what are they

Dependent on laterality pathway Expression of transcription factor PITX2

Secondary heart field (SHF)

Derivatives are the remainder of the right ventricle and the outflow tract (conus cordis and truncus arteriosus) Contributes cells to formation of atria and caudal end of the heart Resides in splanchnic mesoderm ventral to pharynx

Where is the dorsal mesocardium derived from

Derived from the SHF

Regarding formation and position of the heart tube The developing heart tube bulges while forming into what cavity

Developing heart bulges into pericardial cavity. Remains attached to dorsal side of the pericardial cavity by a fold of mesodermal tissue (dorsal mesocardium)

The intraembryonic (primitive body)cavity over it develops into what cavity

Develops into pericardial cavity

Development of Sinus Venosus The inferior portion of the right venous valve develops into what two parts

Develops into valve of the inferior vena cava Valve of the coronary sinus

Arterial system aortic arches Aorticopulmonary septum divides what

Divides the truncus arteriosus and in turn divides the outflow channel of the heart into the ventral aorta and pulmonary trunk

Other notable changes regarding aortic arch formation

Dorsal aorta between the entrance of the 3rd and 4th arches known as the carotid duct is obliterated Right dorsal aorta disappears between the origin of the 7th intersegmental artery and the junction with the left dorsal aorta Cephalic folding, growth of the forebrain and elongation of the neck push heart into the thoracic cavity

What is tetralogy of fallot due to?

Due to the unequal division of the conus resulting from anterior displacement of the conotruncal septum.

Septum formation in the truncus arteriosus and conus cordis

During 5th week pairs of opposing ridges appear in the truncus Truncus swellings or cushion

Aortic arches. What are they embedded in and where do they terminate

Embedded in the mesenchyme of the pharyngeal arches and terminate in the right and left dorsal aortae

Septum formation in the truncus arteriosus and conus cordis When do the primitive ventricles start to expand

End of the 4th week

Name the three heart tube layers

Endocardium- Internal endothelial lining of the heart Myocardium- muscular wall of the heart epicardium (or visceral pericardium)- covers outside of the tube

What happens after enter lower limbs

Enter rt atrium. go to oval foramen Most blood pass to left atrium Some doesn't because septum secundum Mix with desaturated blood returning from head and arms in left atrium. Go to left ventricle and ascending aorta

The communication between the two sinuses is initially wide. This changes, and ...

Entrance to sinus shifts to the right Shift is caused by left to right shunts of blood, which occur in the venous system during weeks four and five of development

Where are coronary arteries derived from

Epicardium

The secondary heart field exhibits ______

Exhibits laterality, that ensures that the vessels are leaving and entering the appropriate region of the heart

Molecular regulation of cardiac development PITX2 importance

Expressed in lateral plate mesoderm on the left side May play a role in deposition and function of extracellular matrix molecules that assist in looping

Molecular regulation of cardiac development HAND1 and HAND2

Expression upregulated by NKX2.5 Transcription factors that are expressed in primitive heart tube and that later become restricted to the future left and right ventricles respectively. Contribute to expansion and differentiation of ventricles

Junction between the ventricle and bulbus cordis is externally indicated by what.

Externally indicated by bulboventricular sulcus. It remains narrow and is called the primary interventricular foramen

Umbilical artery o2 sat is 58%

Fetal life, high resist pulmonary vessels, most blood passes through ductus arteriosus to descending aorta. mix with blood from proximal aorta. Blood flows towards placenta by way of umbilical arteries

29 day embryo. What happens here

First and second aortic arches have disappeared Third and fourth and sixth arches are large Conotruncal regions have divided so that the 6th arches are now continuous with the pulmonary trunk

Semi lunar valves

First visible as small tubercles found on main trunkus swelling

Development of Sinus Venosus The sinoatrial orifice is flanked on each side by what

Flanked on each side by a valvular fold (right and left venous valves)

Distal parts of the bulbus (truncus arteriosus) form what

For the roots of the proximal portion of the aorta and pulmonary artery.

Second aortic arch disappears and the remnant of arch from what

Form hyoid and stapedal arteries

What is the cardiac jelly

Formed as myocardium thickens and secretes a layer of extracellular matrix that is rich in hyaluronic acid

What does the aortic sac form

Forms right and left horns, which give rise to brachiocephalic artery and the proximal segment of the aortic arch respectively

Formation of cardiac loop Atrioventricular junction remains narrow. What does it form?

Forms the atrioventricular canal that connects the common atrium and the early embryonic ventricle

Regarding blood islands, they unite and form horseshoe shaped endothelial lined tube surrounded by myoblasts. What does this form?

Forms the cariogenic region

Right hepatocardiac channel forms the hepatocardiac portion of what

Forms the hepatocardiac portion of the inferior vena cava

Complete closure of interventricular foramen forms what part of the interventricular septum

Forms the membranous part

What does the midportion of the conus cordis form during cardiac loop formation

Forms the outflow tracts of both ventricles.

Where do the progenitor heart cells reside?

Found in the epiblast adjacent to the cranial end of the primitive streak. They migrate through streak to splanchnic layer of lateral plate mesoderm and form horseshoe shaped cluster of cells Horseshoe cluster of cells called PRIMARY HEART FIELD (PHF) -is cranial to the neural folds

Cardiac tube organized via regions along craniocaudal axis from where?

From the conotruncus of the right ventricle to the left ventricle of the apical region

Atrioventricular canal enlarges to the right and blood passing through the atrioventricular orifice has direct access to which ventricle

Has direct access to primitive left and right ventricles

Formation of the cardiac loop Lengthening is essential for the formation of the right ventricle, the outflow tract region and the looping process. If you inhibit lengthening, what happens

If you inhibit lengthening, you get outflow defects.

During molecular regulation of cardiac development, signals from the anterior (cranial) endoderm induce what

Induce a heart forming region in overlying splanchnic mesoderm by inducing NKX2.5 Note: these signals require secretion of BMPs 2 and 4 -----They are secreted by LATERAL PLATE MESODERM

cells that establish PHF are induced by what...

Induced by underlying PHARYNGEAL ENDODERM to form cardiac myoblasts and blood islands that form blood cells and vessels via vasculogenesis

Holt oram syndrome facts

Inherited autosomal dominant Caused by mutation in TBX5 gene Preaxial limb abnormalities Atrial septal defect Muscular defects in interventricular septum.

Pacemaker initially lies where

Initially lies at the caudal part of the left cardiac tube

Umbilical Arteries

Initially paired ventral branches of the dorsal aorta that course to the placenta in close association with the allantois. Each artery acquires a secondary connection with the dorsal branch of the aorta during the 4th week → common iliac After birth proximal portions persist as internal iliac and superior vesical arteries Distal parts are obliterated to form the medial umbilical ligaments

Regarding formation and position of the heart tube What does the heart tube consist of (layers)

Inner endothelial lining and outer myocardial layer

Outflow tract defects during septum formation can result from

Insults to SHF or cardiac neural crest cells These insults disrupt formation of conotruncal septum Get things such as tetralogy of fallot, pulmonary stenosis, persistent truncus arteriosus, and transposition of great vessels

Ventral septal defect (VSD)

Involves membranous or muscular section of the septum Most common congenital cardiac malformation Membranes re usually more serous

Regarding septum secundum, when upper portion of septum primum disappears, the remaining part becomes what

It becomes the valve of the oval foramen

Regarding molecular regulation of cardiac development What does BMP activity and WNT inhibition cause?

It causes expression of NKX 2.5

What happens to muscular cords during development of AV valves

It degenerates and is replaced by a dense connective tissue Valves consist of connective tissue covered by endocardium Connected to thick muscular trabeculae in the wall of the ventricle (papillary muscles) by the chordae tendinae

Regarding formation and position of the heart tube What eventually happens to the middle section of the dorsal mesocardium

It disappears, creating the transverse pericardal sinus that connects both sides of the pericardial cavity.

FGF8 signaling in arch ectoderm. What is it needed for

It is important for 4th arch development

What does the cardiac jelly do during heart formation

It separates the myocardium from the endothelium

What are the masses of tissue that form the septum known as?

Known as endocardial cushions and their formation depends on the synthesis and deposition of extracellular matricies and cell migration and proliferation.

Where does the later atrioventricular cushion appear?

Later atrioventricular cushion appears on the right and left borders of the canal

What happens to the left sinus horn around week 5

Left sinus horn loses its imporance around the 5th week when obliteration of right umbilical and left vitelline veins occurs

W/ ventricular inversion

Left ventricle is on the right side and connects to the right atrium through mitral valve

Where do truncus swellings or cushions lie.

Lie on right superior wall. These grow distally and to the left Others lie on the left inferior wall (left inferior truncus swelling). These grow distally and to the right. The swellings grow towards the aortic sac and twist around each other, foreshadowing the spiral course of the future septum

Tricuspid has three valve leaflets and lies on which side

Lies on the right side.

Additional vascular changes after birth Ductus venosus obliterated What does it form

Ligamentum venosus

Mixing may occur at following places

Liver- mix with sm amt of blood from portal sys Inf vena cava carries deox blood from lower ext. pelvis kidney Rt atrium via mix w/ blood from head and upper limbs L atrium by mix with blood from lungs Entrance of ductus arterosus into descending aorta

Aortic arch system loses what.

Loses symmetrical form with further development and establishes a definitive pattern

We have a lower concentration of RA where

Lower concentration of RA at the more anterior cardiac regions (this is the ventricles and outflow tract). Note this contributes to the specification of these structures NOTE: RA can produce a variety of cardiac defects due to role in cardiac signalling

Describe what happens after birth

Lung circulation begins and pressure of left atrium increases- valve of oval foramen is pressed against the septum secundum, which obliterates the oval foramen. This separates the left and right atria

What transcription factor regulates lymphatic lineage

Lymphatic lineage regulated by PROX1

Formation of the cardiac septa When are the major septa of the heart formed?

Major septa of the heart formed between days 27 and 37 of development

At the end of the 4th week, what takes place

Medial walls of ventricles merge and form muscular interventricular septum Note: sometimes do not merge completely and get a deep apical cleft between the two ventricles.

Additional vascular changes after birth Ductus arteriosus closes by contraction of muscular wall immediately after birth. What is it mediated by

Mediated by bradykinin- it's released by lungs on initial inflation

Mesenchymal cells contribute to __ Smooth muscle cells contribute to ___

Mesenchymal endothelial Smooth muscle Coronary arteries

Formation of the left atrium and pulmonary vein Describe the process

Mesenchyme at the caudal end of the dorsal mesocardium proliferates Septum primum grows downward from roof of common atrium and the proliferating mesenchyme forms the dorsal mesenchymal protrusion (DMP) This grows with the septum primum towards the atrioventricular canal

Tetralogy of fallot is the most frequent abnormality of which region

Most frequent abnormality of the conotruncal region

When is most of the aortic arch gone.

Most of aortic arch gone by day 27. Small portion persists to form maxillary artery

Hypertrophic cardiomyopathy symptoms and facts

Mutation in genes regulating production of sarcomere proteins May result in sudden death, especially in athletes Autosomal dominant Most mutations target beta myosin heavy chain gene Disruption of cardiac muscle cells (myocardial disarray) May adversely effect cardiac output and or conduction.

Atrioventricular node and bundle of his are derived from two soures

Myocardial cells in the left wall of teh sinus venosus Myocardial cells from the atrioventricular canal Final position of cells is at base of interatrial septum

What is the master gene for heart development

NKX2.5

Regarding formation and position of the heart tube Is there ventral mesocardium?

NO

The bulbis cordis is narrow, except for what portion? What does it form?

Narrow except for proximal third Forms the trabeculated part of the right ventricle.

What are the four alterations of tetraology of fallot

Narrow right ventricular outflow region Large defect in interventricular septum Overriding aorta that lies directly above the septal defect Hypertrophy of the right ventricular wall because of higher pressure on the right side

Septum formation methods

Narrow strip of tissue in wall fails to grow and areas on each side expand rapidly Narrow ridge forms between expanding portions. The two expanding portions continue to grow and merge forming a septum This type of septum never fully divides the canal because a narrow communicating canal exists between the two expanded sections. This narrow canal may be closed by the proliferation of neighboring tissues.

It is thought that what cells contributes the formation of semi lunar valves

Neural crest

Arterial system aortic arches What do neural crest cells do regarding arch development

Neural crest cells in each pharyngeal arch contribute to the coverings of the arch vessels and also regulate patterning of the vessels Signals from endoderm and ectoderm lining the arches provide interactive signals to crest cells to regulate the patterning process

Septum secundum never forms a ______ partition in the atrial cavity

Never forms a compltete partition

Transformation from embryonic to adult arterial system 5th aortic arch

Never forms or forms incompletely then regresses.

When does lymphatic development occur

Occurs at week 5 of gestation

Where does formation of the proepicardial organ occur during development

Occurs in the mesenchymal cells located at the caudal border of the dorsal mesocardium.

Molecular regulation of cardiac development NOTCH signalling Ligand that occurs through and what it does

Occurs through ligand JAG1 Responsible for upregulation of FGFs in the SHF that regulate migration an differentiation of neural crest cells essential for outflow tract separation and for development and patterning of aortic arches.

Atrial septal defect (ASD)

Ostium secundum defect is the most common type May be caused by excessive cell death and resorption of the septum primum or inadequate development of septum secundum

Where is PITX expressed. What is it known as

PITX is known as the master gene for sidedness Expressed in the aortic sac, SHF and arch mesoderm, it regulates laterality during restructuring of the original aortic arch pattern

Molecular regulation of cardiac development Sonic Hedgehog SHH

Partially regulates lengthening of the outflow tract of SHF Expressed by pharyngeal arch endoderm. Acts through its receptor PTC

Umbilical veins

Pass on each side of the liver, but some connect with the hepatic sinusoids Proximal part of umbilical veins and remainder of right umbilical vein disappear Left umbilical vein is left to carry blood from the placenta to the liver Ductus venosus bypasses the sinusoidal plexus of the liver. Birth → left umbilical vein and ductus venosus are obliterated to form → ligamentum teres hepatus and ligamentous venosum, respectively

Transformation from embryonic to adult arterial system 4th aortic arch

Persists on both sides with a different fate on each side Left- part of aortic arch between left common carotid and left subclavian Right- most proximal segment of right subclavian artery is formed by a portion of the right dorsal aorta and the 7th intersegmental artery

Formation of the cardiac septa The cushions are populated with cells doing what

Populated with cells migrating and proliferating into the matrix

Third aortic arch is large

Primitive pulmonary artery is present as a major branch of the 6th arch before formation complete

how is the epicardial layer of the heart formed during development

Proepicardial organ cells proliferate and migrate over the surface of the myocardium and form the epicardial layer of the heart.

Where does the heart begin to pump blood out

Pumps blood out of the first aortic arch into the dorsal aorta at its cranial pole

Where is retinoic acid produced?

RA produced by mesoderm adjacent to the presumptive sinus venosus and atria

Development of Sinus Venosus At the middle of the 4th week the sinus venosus receives venous blood from which regions

Receives venous blood from the right and left sinus horns

Formation of the cardiac septa Regions where cushions form have an increased synthesis of what

Regions where cushions form have an increased synthesis of extracellular matrix that produces endocardial cell covered protrusions into lumen. These protrusions develop into the atrioventricular and conotruncal regions

Numerous channels connect sacs to each other and drain lymph from the limbs, body wall, head and neck.

Right and left thoracic ducts- join jugular sacs with cisterna chyli- anastomoses eventually form between these ducts Thoracic duct develops from distal part of right thoracic duct and the cranial portion of the left thoracic duct Right lymphatic duct- derived from cranial portion of the right thoracic duct.

In the fully developed heart, Embryonic right atrium contains...

Right atrial appendage containing the pectinate muscles Smooth walled sinus venarum originates from the right horn of the sinus venosus

Development of Sinus Venosus Right sinus horn and veins enlarges as a result of left to right shunts of blood

Right horn now forms the only communication between original sinus venosus and atrium It is then incorporated into the right atrium to form the smooth walled part of the right atrium.

Regarding SHF, cells on the right side contribute to the ______ side outflow tract Cells on the left side contribute to the ______ side outflow tract

Right side left side of outflow tract Left side right side outflow tract

What makes up azygos veins

Right supracardinal vein and part of posterior cardinal vein

5th aortic arch (AKA pulmonary arch) Gives off an important branch that grows towards the developing lung bud

Right- proximal part become proximal segment of right pulmonary artery Distal part of the arch loses connection with the dorsal aorta and disappears Left- distal part persists during intrauterine life as the ductus arteriosus

Formation of cardiac loop Heart and tube continue to elongate as cells added from the SHF end to ______

SHF end to the cranial end

What regulates migration and proliferation of cardiac neural crest cells.

SHF through the NOTCH signaling pathway regulates the migration and proliferation of cardiac neural crest cells.

Defects in the outflow tract, aortic arch and other cardiac defects can be traced back to which genes (name 3)

SHH, NOTCH, and JAG1

Formation of the left atrium and pulmonary vein Main stem of pulmonary vein opens into the left atrium and sends branches where

Sends branches to left lung The expansion of left atrium continues and main stem is incorporating into the posterior wall until branching of vessel occurs resulting in 4 separate openings for pulmonary veins into the atrial chamber

Conotruncal portion of the heart tube initially on the right side of the pericardial cavity. Where does it shift to? What is the change a result of

Shifts gradually to a more medial position change a result of formation of two transverse dilations of the atrium, bulging on each side of bulbis cordis.

During formation of the conducting system of the heart What assumes pacemaker function

Sinus venosus assumes pacemaker function As sinus incorporated into the rt atrium, pacemaker tissue lies near the opening of the superior vena cava. Results in the SA node being formed

Formation of the left atrium and pulmonary vein Each atrium develops by expansion and incorporation of vascular structures Sinus leads to.... Stem of pulmonary leads to...

Sinus=right atrium Stem of pulmonary vein=left atrium

Regarding formation and position of the heart tube where does the central portion of the cardiogenic area start off?

Starts off anterior to oropharyngeal membrane and the neural plate

Formation of cardiac loop Atrial portion starts off as what

Starts off as a paired structure outside the pericardial cavity, but then forms a common atrium and is incorporated into pericardial cavity

What does the mesoderm at this region produce (at the presumptive venous sinus and atria)

Structures express the gene retinaldehyde dehydrogenase when exposed to RA This in turn allows them to make their own RA and commits them to becoming CAUDAL cardiac structures.

Vein anastomosis Subcardinal veins

Subcardinal veins lead to left common iliac Right sarcocardinal vein becomes the sarcocardinal segment of the inferior vena cava When renal segment of inferior vena cava connects with hepatic segment the inferior vena cava complete with hepatic, renal and sacrocardinal segments

At 5th and 7th week, other veins are formed

Subcardinal veins- drain kidneys Sacrocardinal veins- drain lower extremities Supracardinal veins- drain body wall by way of the intercostal veins taking over the function of the posterior cardinal veins

cardinal veins Major portion of posterior cardinal veins are obliterated. What happens then

Supracardinal veins assume greater role in draining body wall

How is the heart suspended eventually

Suspended in the cavity by blood vessels at the cranial and caudal poles

Septum formation in the truncus arteriosus and conus cordis After complete fusion, the ridges form the aorticopulmonary septum that divides the truncus into an aortic and pulmonary channel.

Swellings develop along the dorsal and LEFT VENTRAL walls of the conus cordis. These grow towards each other and unite distally with the truncus septum. The two conus swellings fuse, septum divides the conus into the anteriolateral portion (outflow tract of right ventricle) and a posteriomedial portion (outflow tract of the left ventricle.

Septum formation in atrioventricular canal At the end of the 5th week the posterior extremity of the flange terminates where

Terminates midway along the base of the dorsal endocardial cushion and is much less prominent than before

Regarding formation and position of the heart tube When neural tube closes and brain vesicles form. What occurs

The CNS grows rapidly Grows cranially, extends over central cardiogenic region and the future pericardial cavity Oropharyngeal membrane pulls forward while the heart and pericardial cavity move to the cervical region, and then to the thorax due to brain growth and cephalic folding

Atrioventricular canal initially only gives access to the _______

The atrioventricular canal initially gives access only to the primitive left ventricle and is separated from the bulbis cordis by the bulbo (cono)ventricular flange.

Septum formation in common atrium What is the first portion of the septum primum

The crest

What happens when the left venous valve and the septum spurium fuse with the right side of the septum secundum

The free concave edge of the septum secundum begins to overlap the ostium secundum.

Eventually what disappears

The proximal part of the vitelline vein disappears

Arterial system aortic arches How do pharyngeal arches and vessels appear?

They appear in a cranial to caudal sequence Aortic sac contributes a branch to each new arch as it forms giving rise to a total of 5 pairs of arteries

What do WNT3α and 8 do in molecular regulation of cardiac development Where are they secreted from What are their inhibitors Where are the inhibitors produced

They are secreted by neural tube and must be blocked because they inhibit heart development Inhibitors are CRESENT and CEREBUS Inhibitors produced by endoderm cells adjacent to the heart forming mesoderm in the anterior half of the embryo

Formation of the cardiac septa What do the endocardial protrusions assist with?

They assist in the formation of atrial and ventricular (membranous portion) septa, the atrioventricular canals and valves, and the aortic and pulmonary channels

Abnormalities in endocardial cushion formation

They can cause cardial malformations, ASDs VSDs Also great vessel defects (such as transposition, truncus arteriosus and tetralogy of fallot)

Septum formation in the truncus arteriosus and conus cordis Cardiac neural crest cells originating in the edges of neural folds in the hindbrain region migrate where

They migrate through pharyngeal arches 3, 4 and 6 to the outflow region of the heart and invade and contribute to endocardial cushion formation in both the conus cordis and truncus arteriosus

When do progenitor cells migrate to the primitive streak during heart formation

They migrate to the primitive streak around day 16 and are specified on both sides from lateral to medial to become the different parts of the heart.

Molecular regulation of cardiac development TBX5

Transcription factor that contains DNA binding motif known as a T-box Expressed later than NKX2.5 Plays important role in separation

Overall 4th and 7th intercostal vein enter left supracardinal vein

Turns into hemizygous vein, in turn empties into azygos vein

Methods for septa formation are

Two actively growing masses of tissue approach each other until they fuse, dividing the lumen into two separate canals Active growth of a single tissue mass continues to expand until it reaches the opposite side of the lumen

Six primary lymph sacs. What are they

Two jugular- at junction of subclavian and anterior cardinal vein Two iliac- at junction of the iliac and posterior cardinal vein One retroperitoneal- near the root of mesentery One cisterna chyli-dorsal to the retroperitoneal sac

Septum primum facts

Two limbs extend toward the endocardial cushions in the atrioventricular canal Opening between this septum and the cushions the OSTIUM PRIMUM Along its edge, extensions of the superior and inferior endocardial cushions, thereby closing the ostium primum ----Note before closure completes, cell death produces perforations in the upper portion of this septum that will coalesce to form the ostium secundum, ensuring free blood flow from the right to left primitive atrium.

What forms ligamentum teres hepatis

Umbilical veins form it in lower margins of falciform ligament

What does BMP expression up regulate? The thing that it upregulates, what is it important for

Upragulates FGF8 Important for the expression of cardiac specific proteins.

PROX1

Upregulates lymphatic vessel genes and downregulates blood vessel genes

The entire system is patterened by guidance cues involving which factor

VEGF VEFG important for development of vasculature

What does VEFGC do to PROX1 expressing endothelial cells

VEGFC causes the PROX1 expressing endothelial cells to sprout from existing veins to initiate the growth of lymphatic vessels.

What gene is upregulated that serves as a receptor for the paracrine factor VEGFC

VEGFR3

When does the vascular system appear during embryonic development

Vascular system appears at the middle of the 3rd week

During vascular development, there are two mechanisms of blood vessel development. What are they

Vasculogenesis- vessels arise by coalescence of angioblasts-- Dorsal aorta and cardinal veins Angiogenesis-- vessels sprout from existing vessels. This forms the remainder of the vascular system

When the cardiac tube is formed, what specifies the venous portion?

Venous portion is specified by retinoic acid (RA)

How does the cephalic portion bend

Ventrally, caudally and to the right

Development of Sinus Venosus Each sinus horn receives blood from three important veins. What are those veins?

Vitelline (or omphalomesenteric vein) Umbilical vein Common cardinal vein

Vitelline arteries. What are they and what's the significance

Vitelline Arteries Initially a number of paired vessels supplying the yolk sac Fuse to form the arteries in the dorsal mesentery of the gut Represented by the celiac and superior mesenteric arteries in adults Inferior mesenteric arteries are derived from the umbilical arteries Celiac mesenteric arteries → supply derivatives of foregut Superior mesenteric arteries → supply derivatives of midgut Inferior mesenteric arteries → supply derivatives of hindgut

Vitelline veins. What does it do (they do)

Vitelline veins form a plexus around duodenum and passes through the septum transversum before entering the sinus venosus Course of veins interrupted by liver cords and an extensive vascular network called the hepatic sinusoids is formed Reduction of left sinus horn lead to blood from left side of liver rechanneled to right. Get enlargement of rt vitelline vein

5th week three main veins distinguished. What are they

Vitelline veins- Carry blood form yolk sac to sinus venosus Umbilical veins- Originate from chorionic villi. Carry oxygenated blood to embryo Cardinal veins- Drains body to embryo proper

What is Total anomalous pulmonary venous return (TAPVAR)

When pulmonary vein drains into other vessels or directly into the right atrium

Initially valves are large What happens when right sinus horn incorporated into wall of atrium

When the right sinus horn is incorporated into wall of atrium, the left venous valve and septum spurium fuse with teh developing atrial septum Eventually teh superior portion of the right venous valve disappears completely

Development of Sinus Venosus What forms the septum spurium

When the valves fuse dorsocranially, we get the septum spurium

Formation of the left atrium and pulmonary vein Within the dorsal mesenchyma protrusion (DMP) is what

Within the DMP is the developing pulmonary vein that is positioned in the LEFT atrium by the growth and movement of the DMP Remaining portion of DMP at the tip of the septum primum contributes to endocardial cushion formation in the atrioventricular canal

What is the dorsal aortae

a pair of longitudinal vessels formed by blood islands that are located bilaterally, parallel and close to the midline of the embryonic shield.

The anterior limb of the septum scandium extends downward to the septum in the...

atrioventricular canal

Network around duodenum

becomes portal vein

Dorsal and ventral cushions project further into the lumen and fuse resulting in complete division of the canal into right and left atrioventricular orifices by what week

by the 5th week.

Formation of vena cava system characterized by series of anastomoses between left and right in such manner that blood from left is channeled to right

cardinal vein formation

Arterial system aortic arches When do the pharyngeal arches form?

form during the 4th and 5th weeks of development Note: each pharyngeal arch as its own cranial nerve and artery

Obliteration of ductus arteriosus forms what

forms the ligamentum arteriosum

Septum formation in the truncus arteriosus and conus cordis What happens with the interventricular foramen with completion of conus septum

it shrinks

Formation of cardiac valves

mitral valves and tricuspid valves 1. proliferation of mesenchyme in AV orifice 2. The cords become hollowed out by bloodstream 3. The muscular tissue degenerates, replaced by dense CNT 4. A-V valves=CNT covered by endocardium connected to papillary muscles by chordae tendineae 5. Right=tricuspid valve Left=bicuspid (mitral) valves

What is left over by the septum secundum after formation

oval foramen or foramen ovale

Space between the free rim and muscular ventricular septum and the fused endocardial cushions permits communication between what

permits communication between two ventricles.

Desat blood from sup vena cava flows by way of right ventricle where

pulmonary trunk

One of each pair is assigned to the pulmonary and aortic channels Third tubercle appears in both channels Regarding semi lunar valves.Two prickles eventually hollow out at the upper surface and form the semi lunar valves

semi lunar valve formation

Right vitelline vein turns into

superior mesenteric vein Drains the primary intestinal loop Distal portion of left vitelline vein disappears

Primary heart field cells. where do they go

travel from atria, left ventricle and part of the right ventricle


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