Heart Development Flashcards
what is Vasculogenesis
Process of making blood vessels directly from mesenchyme
Process of Extraembryonic vasculogenesis, what cells accomplish this and when does it begin
begins day 17 in mesoderm next to the endoderm yolk sac wall
this process is coupled with hematopoiesis (blood cell formation)
hemangioblasts differentiate to created Hematopoietic progenitor cells and endothelial precursor cells
these cells make blood islands that lengthen and connect to make vascular network
3rd week have vascularized yolk sac wall, connecting stalk, and chronic villi
what are eventual sites of hematopoiesis
yolk sac, liver aortic gonadal mesonepheric (AGM) region, lymph organs, and bone marrow
what do Embryonic hematopoietic cells do and when do they appear
appear day 17 and then populate the developing liver by dau 23 to make embryonic erythrocytes, macrophages, and megakaryocytes
what do definitive hematopoietic stem cells do
programmed hemogenic endothelial cells of the dorsal aorta in the aortic-gonadal-mesonephric (AGM) region
these cells seed the liver day 30 and make myeloid (fetal and adult erythrocytes) and lymphoid cell lineages
then finally they go out to populate the lymph organs and bone marrow
when does the AGM region appear and disappear
appears day 27 and then disappears by day 40 after seeding the liver
Intraembryonic vasculogenesis
with the exception of the AGM region, blood vessel formation within the embryo is not coupled with hematopoiesis
starts by day 18, vessel formation occurs in the intraembryonic splanchopleuric mesoderm
subset of these cells differenticate into endothelial precursor cells to proliferate and differentiate into endothelial cells making the angioplastic plexus
this also occurs in the paraxial mesoderm as well due to migration of the EPCs
what are the four ways the angioplastic plexus grows and spreads
1) continued proliferation of endothelial precursor cells
2) angiogenesis, the budding and sprouting of new vessesl from existing ones
3) intussusception: splitting of a existing vessel
4) recruitment of new mesodermal cells into walls of existing vessels
what are Angiomas and how are they caused
benign tumors from vascular or lymphatic vessels
caused abnormal growth from the vasculogenic process stimulated by abnormal levels of angiogenic factors
Capillary hemangioma
excessive growth from a small capillary network
Cavernous hemangioma
excessive growth of a venous sinus
Hemangiomas of infancy
benign tumors made mostly of endothelial cells
not immediate threats but deepending on the degree and site of growth can lead to clinical complications
can regress over the years though
First Heart field
first seen with the formation of EPCs clusters that are arranged in a horseshoe shape within the cardiogenic area of intraembryonic splanchnic mesoderm
also called the cardiac crescent
intraembryonic coelom lies dorsal to the first heart field
how does anterior/posterior folding affect the primary heart field
the primary heart field and coelom become folded beneath the embryo pulling in endoderm to help form the foregut
the limbs of the first heart field now lie ventral to the foregut and dosal to the coelom
Meanwhile the EPCs differentiate into endothelial cells making the primitive endocardial tubes
How does the lateral folding affect the primary heart field
brings the two forming heart tubes together, thus the endocardial heart tubes fuse at the midline with the adjacent cardiogenic mesoderm to form a simble tubular heart
then the heart sinks into the pericardial cavity
the cranial ends of the developing dorsal aorta are dragged ventrally to make a loop making the first aortic arch
what three blood vessels get blood to the primitive heart
Common cardinal veins
Vitelline veins
Umbilical veins
What does the primary heart tube wall consist of
Endocardium (inner epithelium continuous with blood vessels) Myocardium Cardiac jelly (concentration of extracellular matrix between endocardium and myocardium)
when does blood first flow through the primitive heart and when is the first rhythmic contraction
rhythmic contraction begins day 22
blood flow starts about day 24
goes from sinus venosus to the outflow tract
Morphologically the heart consists of what 5 structures when first beginning contraction
Sinus venosus: right and left sinus horns, draining into each horn is umbilical horn, vitelline vein (blood from gut), and common cardinal vein (venous blood from head and trunk)
Primitive atrium: region between vsinus venosus and ventricle
Atrioventricular region: area seperating primitive atrium and primitive ventricle
Primitive ventricle: early left ventricle, delineated from future right ventricle by construction of interventricular sulcus
Outflow tract: portion between primtive ventricle and aortic sac
Aortic sac or root: eventually become the great vessels.
what is the function of the Dorsal mesocardium and what does it become as an adult
suspends the heart tube but eventually ruptures forming the transverse sinus as an adult
remenants are the proepicardial organ
Cardiac Looping
reverses the atrial and ventricle positions as the heart tube lengthens
atrium moves cranially and dorsally now locatedbetween outflow tract and dorsal pericardial wall
ventricle bends left and superior and dorsally to the outflow tract
what does the initial outflow tract form, what does myocardium at the cranial end form, and what does the distal most end of the outflow tract form
initial outflow: right ventricle
cranial end myocardium: conus arteriosus (outflow portion of both ventricles)
distal end outflow: forms the truncus arteriosus (aorta and pulmonary artery)
how does the lengtheining of the cardiac tube occur during cardiac looping
accomplished by the development of a second heart field that forms at both ends of the rupturing dorsal mesocardium
Neural crest cells, pharyngeal arch mesoderm, and pharyngeal arch endoderm help maintain the cardiogenic mesoderm proliferation and proper myocardial cell specification
Looping anomalies: Ventricular inversion
primitive ventricle folds to the right and the outflow tract ends up on the left generating a rightsided left ventricle
Looping anomalies: two forms of Heterotaxia
any abnormal left right development of either some or all organs (often seen in immobile cilia syndrome and Kartagener syndrome
Situs inversus: complete reverse symmetry of the heart and GI organs that is often asymptomatic
Situs ambiguous: reversal of some organs.. can be problematic
-Visceroatrial hererotaxia: heart and GI tract are asymetrically arranged from one other. this affects the inflow and outflow tract development which can be life threatening
what happenss to the left side of the embryonic vessels and sinuses as the heart grows and loops
sinus venosus opening into the primitive atrium begins shifting to the right due to the looping, growth, and hemodynamics
left vitelline vein and left umbilical vein disappear
left sinus venosus and left horn shift their connection to the right half of the common atrium (since atria expansion bigger on the left side of common sinus opening) this helps with net shifit in amount of blood return to right side
left common cardinal vein then disappears
left sinus horn becomes the coronary sinus
what happens as the atrium enlarges on the right side?
sinus venosus now only opens to the future right atrim via the sinoatrial orifice
right sinus horn and right common cardinal veins are incorporated into the posterior wall of the expanding right atrium
right common cardinal vein becomes the superior vena cava
Right vitelline vein becomes part of the inferior vena cava
Right umbilical vein is lost
pair of tissue flaps develop on either side of the developing opening of the coronary sinus (left and right atrial venous valves)
what happens to the left and right valvular folds
Left valvular fold becomes incorporated into the interarterial septum
Superior right vavlular fold disappears
inferior part of right valvular fold becomes valve of inferior vena cava
small fold of left sinus horn makes valve of the coronary sinus
What is the crista terminalis
junction between the pectinate (rough) part of the right atrium and the smoothed wall (sinus venarum- part of sinus venosus incorporated into atria)
what does the SA node and AV node come from
SA node comes from a portion of the right sinus horn and right common cardinal vein
AV node comes from the similar tissue in the root of the left sinus horn
what are the two aspects important in septa formation
Differential growth (however this does not fully close off a lumen)
Endocardial cushion tissue: connective tissue in the AV region that makes the fibrous portions of atrial and ventricular septa and conotruncial ridges
How does the Atrioventricular septum develop
superior and inferior endocardial cushions fuse at the midline to form the atrioventricular septum
subsequent growth up and down from the AV septum contributes to the atrial and ventricular septa as well
cushion cells also provide mesenchyme needed for anchoring the heart valves and contribute to the cardiac skeleton
leflets are freed fromthe walls by cavitation and remodeling of the ventricular myocardium and remnants help form the chordae tendinae and papillary muscles
what are the conotruncal ridges and what do they contribute to
found in the outflow tract that are part ECT and neural crest cell derived
they divide the conus arteriosus so blood from the LV and RV go out different vessels
also contributes to the fibrous portion of the interventricular septum
also divides the truncus arteriosus to make aorta and pulmonary arteries via formation of the aorticpulmonary septum
What is critical about the septum between the atrium and how is this problem solved
must be leaky since the left side of the atrium needs the blood so that the left side of the heart doesnt become hypoplastic
also since the lungs have not developed or uninflated the heart can push all the blood through the lungs therefore create two septum in the atria
Septum Primum and its other contributers and the holes it has
touching of the outflow tract to the atrium during cardiac looping that induces septum I formation
sickle shaped extends from the atrial wall toward the AV septum
also recieves contribution from the dorsal mesenchymal protrusion (DMP) or spina vestibuli (a mesodermal projection emanating from the caudal dorsal mesocardium
the hole in the septum primum near the AV septum called the ostium primum however cushion tissue and DMP forms near the AV and blocks this hole
a new hole will form in septum primum toward the cranial end of the septum called the ostium secundum
Septum secundum
as the atria contiunues to expand a additional sickle shaped and much thicker septum grows toward the AV region
this will overlap the ostium secundum but as the septa secundum grows it never fully covers the lumen and leaves an opening called the foramen ovalis (ovale)
this makes the septuum primum act as a one way flutter valve allowing for right atrial blood to enter the left atrium but not let the flow go in the opposite direction
what happens to septum I and II after a baby takes their first breath
pulmonary circulation opens up and increases blood flow to the lungs, this process increases pressure in the left atrium and decreases pressure in RV and RA
the higher pressure on the left vs the right side drives septum I against septum II resulting in a functionally closed septum and eventually seals shut within 3 months of birth
if it does not fuse the patent foramen ovalis (ovale) may cause issues in the future
Three types of Atrial septal defects
Ostium II or high atrial septal defect: hole in atrial septum caused by either excessive absoprtion of septum I forms an overly large ostium II or Inadequate development of septum II
Common atria: no septa are formed
Ostium I defect or low atrial septal defect: failure of up growth of AV cushion tissue from AV septum and DMP to fill ostium primum
initial left to right shunting because of increased blood flow returning from the lungs and decreased pulmonary resistance
however as time leads on an increased blood flow to lungs leads to pulmonary damage and resistance (pulmonary congestion) RV hypertorphy and eventually congestive heart failure
as the RV hypertrophies a right to left shunt begins and cyanosis appears
can go many years unnoticed depending on degree of severity because of the lower atria pressures
cyanosis
refers to bluish coloration of skin due to the presence of deoxygenated blood mixing with oxygenated blood
can be seen via clobbing of fingers and bluish fingernail beds and lips
individual also fatigues easily
patients have an oxygen saturation of below 90 percent
how much blood actually goes through to the pulmonary circulation in a fetus
11-13 percent
this is due to the foramen ovale and the ductus arteriosus
how is the ventricular septation created
formation of the interventricular septum is made of a muscular part (ventricular wall) and a fibrous part (from cushion tissue of AV cushion and proximal conotruncal ridges
mechanism of partitioning outflow tract
Aortic arch VI ataches RV to lungs
Aortic arch III and IV connects LV to rest of body
1) shift of AV canal toward right side so that the fusing of the AV cushions meet near the region of the forming interventricular septum.. done via myocardialization (outer myocardial wall is thinned and replaced by cushion cells and futrther apoptosis for remodeling)
2) new cushion tissue forms in outfow tract called conotruncal ridges that spiral down the ventricular septum and fuse to form the conotruncal septum
as this spirals down it makes a 180 degree turn and become parallel with the interventricular septum (these are derived from migrating neural crest cells and endocardial derived cushion tissue. the resut is pulmonary artery connected with RV and aorta connected with LV
3) complete ventricular septation requires fusion of the conotruncal ridges with each other and then with the interventricuar septum and coincident with downgrowth of cushion tissue from the AV septum
4) Proximal root of the outflow tract is eventually incorporated into each ventricle s the ventricle overgrows the conus . spiraling ridges at the truncus/conus junction provide primordia for semilunar valves or aorta and pulmonary trunk
Ventricular septal Defects
failuure of proper closure by abnormal or inadequate fibrous tissue
starts as a left to right shunt but becomes cyanotic sometime after birth
RV hypertrophies enough so RV pressure builds up and exceeds the left side thus needing a right to left shunt to develop
will die of cardiac failure if not addressed
how does double outlet right ventricle occur
shift fails of the AV canal both aorta and pulmonary artery exit the right ventricle
lead to cyanosis and breathlessness and murmur
Persistent truncus Arteriosus
failure of contruncial ridge formation and fusion, pulmonary artery arises some distance away above the undivided truncus and causes a VSD due to the fibrousportion
mixing of left and right ventricle contents giving rise to low degree cyanosis
RV hypertrophy and increased right ventricular pressure and eventual more severe cyanotic condition
Tetralogy of Fallot
Conotruncal ridges form off center leading to unequal division of pulmonary and aorta
VSD (missing fibrous portion)
Pulmonary infundibular stenosis
Overriding aorta
RV hypertrophies in the fetus due to the small pulmonary opening
increases RV pressure over LV resulting in right to left shunting of blood and leads to cyanosis
Transposition of great vessels
Conotruncal ridges fail to spiral
pulmonary artery is connected to the LV and the aorta to the Right
survival due to shunts such as VSD, ASD, patent ductus arteriosus
life expectency is 3 years without surgery
Pulmonary valvular atresia
Semilunar valves are fused leading to RV hypoplasia
Patent foramen ovale then forms as the only outlet for blood on right side to get to left
Patent ductus arteriosus to get blood to lungs
need surgery to open pulmonary valve if the RV is not too weak
can have a VSD and become a univentricular heart
Aortic Vavlular stenosis
leads to hypertrophy of the LV and eventually cardiac failure and pulmonary hypertension, can be congenital, due to a fever, or degenerative
Bicuspid aortic valve
only two leaflets rather than 3 are formed or three formed but two are fused
leads to regurgitation or later to form a stenosis
starts asymptomatic but eventual leads to LV hypertrophy
associated with aortic aneurysm
Aortic Valvular atresia
valves are completely fused the LV is underdeveloped (hypoplastic)
wide ductus arteriosus forms to get oxygen rich blood to the left side
RV hypertrophy and blood must go back through a ASD to the right side from the left
needs surgery for survival
Tricuspid Atrestia
Obliteration of the right AV orifice and fusion of the tricuspid vavles associated with a patent foramen ovale
VSD, and underdeveloped right ventricle and a hypertrophy left ventricle and patent ductust arterisus
can be corrected based on the RV weakness
most likely transplant
Hypoplastic keft ventrice
LV is underdeveloped with absent or small bicuspid and aortic valve
ascending portion of aorta is underdeveloped and there is a patent ductus arteriosus and foramen ovale
univentricular heart with the right ventricle
need surgery
