Chapter 13 embryology
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
