Heart Development Flashcards
Where do the first blood cells arise? Are these different from hematopoeitic stem cells?
First blood cells arise in blood islands on the wall of the yolk sac (mesoderm)- this population is transitory
Definitive hematopoeitic stem cells are derived from mesoderm surrounding the aorta in a site near the developing mesonephric kidney called the AGM
What is the major hematopoietic organ in the fetus from month 2-7?
Liver
Yolk sac mesoderm forms the first blood cells at day 17 and finishes by day 60. The liver primordia is colonized beginning at day _____ and continues until birth. The AGM begins hematopoietic processes at day _____ prior to contributing to liver colonization
23; 27-40
[bone marrow also hematopoietic at 10.5 weeks]
Process by which cells of the primary heart field are induced by the underlying pharyngeal endoderm to form cardiac myoblasts and blood islands that will form blood cells and vessels
Vasculogenesis
Blood cells may only belong to what lineage prior to colonization of the liver?
Myeloid
____________ = common precursor for vessel and blood cell formation that are formed in blood islands of yolk sac
Hemangioblasts
What is the difference in fate of hemangioblasts at the center of blood islands vs at the periphery?
Central hemangioblasts form hematopoietic stem cells (precursors of all blood cells)
Peripheral hemangioblasts differentiate into angioblasts (precursors to blood vessels)
______ = formation of blood vessels by sprouting from existing vessels
Angiogenesis
_____ = existing blood vessel splits into 2
Intussusception
What is the AGM region?
Aortic-gonadal-mesonephric region
Where definitive hematopoietic stem cells are programmed from hemogenic endothelial precursor cells
[hematopoietic stem cells appear at day 27 and disappear from AGM by day 40]
What is the major difference between intraembryonic vasculogenesis and extraembryonic vasculogenesis?
Intraembryonic vasculogenesis involves coupling with hematopoiesis (because it all starts with the blood islands)
All other de novo blood vessel formation occurs SEPARATE from hematopoeisis
Extraembryonic vasculogenesis begins around day 17 when extraembryonic ______ and _______ mesoderm differentiate into either hematopoietic progenitors or ___________ precursor cells. The primary function is to meet immediate need for blood cells
Splanchnic; chorionic
Endothelial
What are the 2 major mechanisms of vascular plexus expansion
Angiogenesis
Intussusception
______ are characterized by abnormal blood vessel and lymphatic capillary growth
Angiomas
What type of angioma is characterized by excessive growth of capillaries?
Capillary hemangioma
What type of angioma is characterized by excessive growth of venous sinuses?
Cavernous hemangioma
Generation of ______ _______ forms 2 bilateral primary heart fields which eventually fuse, thereby creating linear primary heart tube
Precardiac mesoderm
By day 18 of heart development, the lateral mesoderm of the primary heart tube has ______ and _______ components, and the latter will give rise to almost all heart components
Somatopleure; splanchnopleure
Early endocardial cells separate from the mesoderm to create paired heart tubes; what process occurs to bring the paired heart tubes together into a single tube?
Lateral embryonic folding
What structures eventually unite to form a horseshoe shaped endothelial lined tube surrounded by myoblasts, forming the cardiogenic region?
Blood islands
The intraembryonic cavity over the cardiogenic region of the primitive heart will later develop into what structure?
Pericardial cavity
What structures form from blood islands that appear bilaterally and close to midline of the embryonic shield?
Dorsal aortae
All heart structures come from embryonic _______ _______, except for neural crest cells which are ________
Splanchnic mesoderm; ectoderm
When does the primary heart field form
Around day 19 (range of 16-18)
Where is the primary heart field located?
Splanchnic layer of lateral plate mesoderm, cranial to neural folds (these are progenitor heart cells which migrated from the epiblast - aka the area just cranial to the primitive streak)
As progenitor cells migrate from the epiblast to form the primary heart field, they are specified on both sides from lateral to medial to become what heart structures?
Atria
Left ventricle
Most of right ventricle
The primary heart field appears around day 19. When does the secondary heart field appear?
Day 20-21
What structures are formed from the secondary heart field?
Remainder of right ventricle Outflow tract (conus cordis, truncus arteriosus)
Where is the secondary heart field found?
Splanchnic mesoderm ventral to posterior pharynx
What regulates formation of secondary heart field
Neural crest cells - which control concentrations of FGFs in the area and pass the SHF in the pharyngeal arches as they migrate from the hindbrain to septate the outflow tract
What gives rise to the epicardium, interstitial cells and vasculature smooth muscle, and coronary vasculature?
Pro-epicardium
What are the 3 layers of the simple single heart tube?
Primordial myocardium (external layer)
Epicardium (visceral pericardium)
Endocardium (internal endothelial lining of the heart)
What forms the external layer (primordial myocardium) of the simple single heart tube
Splanchnic mesoderm surrounding the pericardial cavity (cardiac precursors of anterior/secondary heart field)
Which layer of the heart tube is derived from mesothelial cells that arise from external surface of sinus venosus and spread over myocardium?
Epicardium - often referred to as cardiac jelly
When is cardiac looping complete and what are the results?
Complete by day 28
Result is an S-shaped heart with atrium located dorsal to outflow part of heart
Outflow part of heart (bulbus cordis) leads to the aortic sac and aortic arch system
Internal septum begins to divide ventricle and later an internal septum will begin to divide the atria
__________ = broader proximal part of bulbus cordis
____________ = narrower distal part of bulbus cordis
[bulbus cordis is the outflow part of the heart]
Conus arteriosus
Truncus arteriosus
How is the transverse pericardial sinus formed during heart looping?
The central part of the dorsal mesentery degenerates (which was suspending the heart tube), forming TPS between the right and left sides of the pericardial cavity
What is the role of the secondary heart field in cardiac looping?
Cells from the secondary heart field are added to cranial end of the heart tube as it continues to elongate
This lengthening process is essential for normal formation of part of RV, outflow tract, and looping
What do the bulbus cordis and conus cordis become?
Bulbus cordis becomes trabeculated part of RV
Conus cordis forms outflow tracts of both ventricles
At first, circulation through the primordial heart is an ebb-and-flow type, but by the end of the 4th week coordinated contractions of the heart result in unidirectional flow.
Initially, the ______ acts as an interim pacemaker of the heart, the ______ _______ then takes over this function.
The SA node develops in the ______ week, located in the right wall of the RA.
Atrium; sinus venosus
____ is the most frequent positional defect of the heart where the embryonic heart tube bends to the left instead of to the right
Dextrocardia
When would dextrocardia be the least symptomatic?
If combined with situs inversus (transposition of abdominal viscera) because then organs match up with heart reversal
______ ______ = partial reversal of organs
Situs ambiguous
What condition is characterized by a right sided left ventricle of the heart but a normal GI arrangement; thus the left ventricle is hooked up to the pulmonary trunk instead of the aorta?
Visceroatrial heterotaxia
3 paired veins drain into the primordial heart of a 4 week embryo. What are they ?
Vitelline veins
Umbilical veins
Common cardinal veins
________ return poorly oxygenated blood from the umbilical vesicle to the sinus venosus after passing through the septum transversum
Vitelline veins
________ veins carry well-oxygenated blood from the chorionic sac of the placenta, running on each side of the liver to drain into the sinus venosus of the primordial heart of the 4 week embryo
Umbilical veins
The right umbilical vein disappears during week 7, leaving the left umbilical vein as the only vessel carrying oxygenated blood from the placenta to the embryo. The persistent caudal part of the left umbilical vein is connected to the IVC via what?
Ductus venosus - forms bypass through the liver, enabling most of the blood from the placenta to pass directly to the heart
What veins return poorly oxygenated blood from the body of the embryo to the heart - serving as the major venous drainage of the embryo?
Common cardinal veins
Describe structural features of RA when the sinus venosus is incorporated into its wall
Initially, the sinus venosus is a separate chamber of the heart and opens into the dorsal wall of the RA.
The left horn of the sinus venosus becomes the coronary sinus; the right horn is incorporated into the RA wall as the sinus venarum
The remainder of the anterior internal surface of the RA have rough trabeculated appearance
________ = represents the cranial part of right SA valve that demarcates smooth and rough portions of right atrium
Crista terminalis
What is the external division that corresponds to the internal crista terminalis?
Sulcus terminalis
_________ =smooth part of wall of right atrium
Sinus venarum
The sinoatrial orifice is the entrance to the smooth walled part of the right atrium. It is flanked on each side by a valvular fold (right and left venous valves) that fuse dorsocranially to form the _______ _______
Septum secundum
Initially the right and left valves are large, but when the right sinus horn is incorporated into the right atrial wall, left venous valve and septum spurium fuse with developing atrial septum
At that point the superior portion of the right venous valve disappears entirely and the inferior portion of the right venous valve develops into what 2 structures?
Valve of IVC
Valve of coronary sinus
What are the 2 major processes by which cardiac septa are formed?
Cushion tissue formation
Differential growth
Describe cushion tissue formation as it relates to cardiac septation
2 actively growing masses of tissue approach each other until they fuse, dividing the lumen into 2 separate canals
Describe differential growth as it relates to cardiac septation
Active growth of a single tissue mass that continues to expand until it reaches the opposite side of the lumen
Is septum secundum muscular or membranous
Muscular
What forms the muscular part of the interventricular septum
Myocytes from both left and right primordial ventricles (later increased in size by active proliferation of myocytes in septum)
What forms membranous septa portion of AV septum?
Endocardial cushions
[AV endocardial cushions form on dorsal and ventral walls of AV canal from ECM as well as NCCs. Cushion tissue is invaded by mesenchymal cells during week 5, causing cushion tissue to fuse and form septum]
Describe origin of outflow tract in proximal region vs. distal region
Proximal region - derived from secondary heart field
Distal region - derived from neural crest
Describe partitioning of the outflow tract
Begins with growth of 2 opposing truncoconal ridges into the lumen; ridges meet in the middle and completely divide the lumen into 2 separate passageways
Final septum forms a spiral path which creates spiral pattern of ascending aorta with the pulmonary trunk in the final pattern
What is the inductive stimulus for endocardial cushions to lose their epithelial character and become transformed into mesenchymal cells which then migrate into cardiac jelly?
Degradation of adherons
During what week of development does atrial partitioning occur?
5th week
What are the 3 openings found in the early atrial partitioning?
Interatrial foramen primum
Interatrial foramen secundum
Foramen ovale
Space between leading edge of septum primum and endocardial cushion forming a right to left atrial shunt
Interatrial foramen primum
Space that forms at cephalic end of septum primum through apoptosis and continues the right to left atrial shunt after the foramen primum closes with the fusion of the septum primum with the endocardial cushion
Interatrial foramen secundum
The foramen ovale is a right to left atrial shunt that forms within which part of the interatrial septum?
Septum secundum
Describe unidirectional blood flow between the 2 developing atrial chambers
From sinus venosus –> primordial atrium –> AV canal –> primordial ventricle –> bulbus cordis + truncus arteriosus –> aortic sac –> pharyngeal arches –> dorsal aorta
What controls the blood flow from the sinus venosus into the primordial atrium?
Sinuatrial valves
Describe the interatrial septum primum
Downward growth from roof of primordial atrium to endocardial cushion separating it into left and right chambers
[foramen primum will be located in between its free edge and endocardial cushions, serving as a shunt that enables blood to pass from right to left atrium]
What forms to the right of the septum primum and from dorsal to ventral part of the atrium, gradually overlapping the foramen secundum in the septum primum?
Interatrial septum secundum
[this forms an incomplete partition, leaving the foramen ovale]
What pressure changes in the heart cause the foramen ovale to close at birth?
Pressure in left atrium increases as blood returns from lungs; eventually septum primum is pressed against septum secundum and adheres, so that foramen ovale becomes fossa ovalis
What secondary heart field derived structure may also be referred to as the vestibular spine or spina vestibuli?
Dorsal mesenchymal protrusion
Formation of the dorsal mesenchymal protrusion is critical for what processes?
Formation of AV mesenchymal complex
Atrial septation
Determining location of where pulmonary veins drain into the heart
Describe cyanosis
Blueish skin tone due to O2 sats less than 90%
May be due to mixing of oxygenated with deox blood
Manifested by clubbing of fingers, blue nail beds and lips, fatigue
What is the most commone ASD
Foramen ovale
Consequences of patent foramen ovale
A small isolated patency is not problematic but if other defects like pulmonary stenosis or atresia are present, blood is shunted through the ovale into the left atrium and produce cyanosis
Most common causes of atrial septal defects
Excessive resorption of tissue around foramen secundum or hypoplastic growth of septum secundum
Less common is d/t lack of union between endocardial cushions and septum primum
4 types of ASDs
Ostium secundum defect
Endocardial cushion defect with ostium primum defect
Sinus venosus defect
Common atrium (septum absent)
What is the dorsal mesenchymal protrusion derived from
Splanchnic mesoderm in SHF
How do developing ventricles gain access to AV canal?
When partitioning of truncus arteriosus is nearly complete, semilunar valves begin to develop from 3 sweelings of subendocardial tissue around orifices of aorta and pulmonary trunk (NCCs also contribute)
How is the outflow tract divided so that the aorta and pulmonary trunk are connected to the appropriate ventricles?
Membranous part of IV septum merges with aorticopulmonary septum and thick muscular part of IV septum
The bulbar and truncle ridges undergo 180 degree spiraling that results in spiraling of aorticopulmonary septum when the ridges fuse - this divides the bulbus cordis into 2 arterial channels: ascending aorta and pulmonary trunk
What 3 major tissue structures are required to separate the right and left ventricle?
Right bulbar ridge
Left bulbar ridge
Endocardial cushion
How does the interventricular foramen eventually close
Bulbar ridges of IV septum fuse with endocardial cushions
IV septal defects most frequently occur in the ____ portion of the septum
Membranous
Why are IV septal defects associated with left to right acyanotic shunting? What symptoms are seen?
Because pressure is higher in left ventricle
Right ventricular hypertrophy, pulmonary hypertension, dyspena, cardiac failure in infancy
What condition develops if septation of outflow tract by truncoconal ridges is asymmetricl, narrowing either the aorta or pulmonary artery?
Aortic or pulmonary stenosis
What is the root cause of tetralogy of fallot?
Abnormal NCC migration - division of truncus arteriosus is unequal and pulmonary trunk is stenotic
What are the characteristics of tetralogy of fallot?
PROVE mnemonic
Pulmonary stenosis, right ventricular hypertrophy, overriding aorta, ventricular septal defect
What is the most common single cause of cyanotic heart disease in neonates?
Transposition of great vessels
Characteristics of transposition of great arteries pathology
Failure of IV septum to form = 3 chambered heart
Atria empty through common valve or 2 separate AV valves into single ventricular chamber; aorta and pulm trunk arise from ventricle
What type of defect always accompanies persistent truncus arteriosus?
VSD
Describe persistent truncus arteriosus
Failure of truncal ridges and aorticopulmonary septum to develop normally and divide the truncus arteriosus into aorta and pulm trunk
So there is a single arterial trunk that arises from the heart and supplies the systemic, pulm, and coronary circulation
[caused by developmental arrest of outflow tract, semilunar valves, and aortic sac during days 31-32]
What malalignment defect causes both the aorta and pulm trunk to exit via the right ventricle due to insufficient shifting of AV septum or cardiac looping?
Double outlet right ventricle
The ductus arteriosus is a fetal structure that later becomes what?
Ligamentum arteriosum
The foramen ovale is a fetal structure that later becomes what?
Fossa ovalis
The ductus venosus is a fetal structure that later becomes what?
Ligamentum venosum
The umbilical vein is a fetal structure that later becomes what?
Ligamentum teres
The umbilical arteries are fetal structures that later become what?
Medial umbilical ligaments
