Heart Development Flashcards
How and when does vasculogenesis happen, what is it coupled with?
blood vessels made from mesenchyme
Coupled with hematopoiesis
Hematopoiesis begins at Day 17 in mesoderm
What do hemangioblasts form and what do they form?
-Hemangioblasts form hematopoietic and endothelial precursor cells, form blood islands and early BVs, blood islands lengthen and come together, forming initial vascular network
What fills immediate need for blood cells?
-precursor cells form embryonic erythrocytes and macrophages
What are definitive hematopoietic stem cells?
Definitive hematopoietic stem cells are programmed from hemogenic endothelial cells in AGM region
- Form at day 27, disappear from AGM at Day 40
- programming in liver allows these cells to generate full spectrum of myeloid and lymphoid cell lineages, populate lymph organs and bone marrow
What are embryonic hematopoietic stem cells?
in developing liver, generate embryonic erythrocytes, macrophages and megakaryocytes
Sites of Hematopoiesis:
- Yolk sac mesoderm: starts at day 17 ends at 60, source of early rbcs and lymphocytes
- Liver Primordia: Colonized at Day 23- continues until birth
- AGM: begin day 27-40, colonize liver
- Bone Marrow: 10 weeks
major mechanisms by which the vascular plexus expands:
- Splanchnopleuric mesoderm is site of vessel formation by day 18
- endothelial precursor cells turn into endothelial cells then organize into vasculogenic cords
grows by
- continued proliferation of endothelial precursor cells
- angiogenesis
- intussusception
- recruitment of new mesodermal cells into walls of existing vessels
Describe angiomas
Abnormal blood vessels and lymphatic capillary growth via vasculogenesis
In infants, hemangiomas are benign and mostly endothelial cells
Capillary hemangioma
excessive formation of capillaries
Cavernous hemangioma
excessive formation of venous sinuses
What makes up the first heart field?
EPCs that are arranged in horse shoe shape within area of splanchnic mesoderm, with adjacent mesoderm
events leading to the formation of the early heart
Tubes
- With body folding, primary heart field becomes folded under embryo, pulls some endoderm inside to form foregut
- After this, EPCs differentiate and form two primitive endocardial tubes
- lateral sides of the embryo begin to move toward the midline and beneath embryo, bringing heart tubes together.
- Along with mesoderm, these tubes form simple tubular heart
- Heart tube dragged into thoracic region, forming a loop called the first aortic arch
Primitive Atrium?
between sinus venosus and ventricle, receives blood from sinus venosus
AV Region?
separates atrium from ventricle, lumen is called AV canal
Primitive ventricle
early left ventricle, delineated from future right ventricle via IV sulcus
Outflow tract:
portion between primitive ventricle and aortic sac
Aortic Sac?
contributes to great vessels, where arch blood vessels come together
Dorsal mesocardium?
suspends heart tube, ruptures and remnants form proepicardial organ
Epicardium?
formed from proepicardial, proepicardial cells migrate over surface of myocardium forming epicardium
cells important in helping to regulate cardiac looping
neural crest cells
Describe how a single cardiac tube is formed from the two primitive heart tubes
Atrium moves cranally and dorsally
Initial outflow tract forms future right ventricle
Distal end forms truncus arteriosus, conus arteriosus at cranial end
Second heart field forms to lengthen cardiac tube at both ends
Looping anomalies result in failure of mesoderm to rupture
List the three layers of the simple single heart tube and explain what are they and how they arise.
- Endocardium–inner epithelium continuous with blood vessels.
- Myocardium.
- Cardiac jelly– concentration of extracellular matrix between endocardium and myocardium.
Ventricular inversion?
the primitive ventricle folds to the right and the outflow tract ends up on the left with the outcome being a right-sided, left ventrical
Heterotaxia
abnormal left-right development of either some or all organs
Situs inversus
complete reverse symmetry of the heart and GI organs that is not fatal and may be asymptomatic
Situs ambiguous
reversal of some organs—this can be problematic
Visceroatrial heterotaxia
:condition whereby the heart and GI tract are asymmetrically arranged from one another , problems with flow, life threatening
development of the transverse sinus of the pericardium
Caudal remnants of transverse sinus form the proepicardial organ
Describe the primitive venous inflow into the sinus venosum and how these vessels are remodeled so it all
venous return enters the developing right atrium. Describe the structural features of the right atrium, formed
when the sinus venosus is incorporated into its wall.
venosus opening into the primitive atrium begins to shift toward the right atrium mainly due to cardiac looping
Left vitelline vein and left umbilical vein disappear
The left sinus venosus and left horn shift their connection to the right half of the common atrium because the expansion of the atria is more pronounced
most of the left common cardinal vein disappears. All that eventually remains of the left sinus horn becomes the coronary sinus
As the atrium enlarges, the sinus venosus now only opens into the future right atrium (sinoatrial orifice)
The right common cardinal vein becomes the superior vena cava while the right vitelline vein eventually becomes part of the inferior vena cava
Explain the role and formation of the endocardial cushion
formation of new connective tissue that occurs in the AV region and outflow tract.
MAkes the fibrous (membranous) portions of atrial and ventricular septum and conotruncal ridges of the outflow tract
The fibrous septa are formed by myocardial synthesis and secretion of specific molecules into cardiac jelly that then induce the formation, migration and proliferation of new mesenchymal cells derived from the endocardium called the endocardial cushion tissue (ECT).
Atrioventricular (AV) region
separates the atrium from ventricle
Superior (dorsal) and inferior (ventral) endocardial cushions fuse at midline to form
he atrioventricular (AV) septum
cushion cells provide
mesenchyme needed for anchoring the heart valves and also contribute to the cardiac skeleton
tricuspid and bicuspid valves themselves appear to form from the
ECT ,done by septa (wall) formation in atria, ventricles, and outflow tract through the formation of new tissue and differential growth
Conus arteriosus is divided so
blood from LV and RV go out different vessels
barrier between atria that must be leaky, two septa created:
- . Septum primum (septum I)
- first septum
- hole called foramen primum
- extends from atrial wall toward the AV septum
- receives a contribution from the dorsal mesenchymal protrusion - Septum secundum (septum II)
- much thicker septum called septum secundum grows toward the AV region
- overlaps the ostium secundum
- opening remains known as foramen ovale
Summarize the changes in blood flow between the two atrial chambers after birth
- pulmonary circulation opens and increases blood flow through lungs and return into left atrium.
- This increases the blood pressure in the left atrium
- easier for the RV to pump blood into lungs, therefore, RV and RA pressures decrease at birth
Differentiate between the muscular and membranous
interventricular septum
interventricular septum ,
made of a muscular part (from ventricular wall) and a fibrous part (from cushion tissue)
Explain the partitioning of the primordial ventricle
To separate ventricle into right and left side and still get blood from atrium into both ventricular sides, there is a shift of AV canal toward right side
- through a process called myocardialization, whereby the outer myocardial wall is thinned as some myocardial cells begin to be replaced by cushion cells in specific areas and there is further remodeling through apoptosis
- conotruncal septum that divides the outflow track, formed by conotruncal ridges
Explain the roles of endocardial and neural crest-derived cushion tissue in partitioning the conus arteriosus and
truncus arteriosus
- Cells of the spiraling ridges are derived from migrating neural crest cells and from the endocardial-derived cushion tissue. The result is the pulmonary artery is connected with RV and aorta is connected to LV.
- Proximal root of the outflow tract (i.e., conus arteriosus) is eventually incorporated into each ventricle as the ventricles overgrow the conus
- Spiraling ridges at the truncus/conus junction provide primordia for semilunar valves of aorta and pulmonary trunk
Explain the role of right and left conotruncal ridges in forming the membranous portion of the interventricular
Septum
- conotruncal septum that divides the outflow tract.
- In the upper truncus, the ridges project into lumen from right & left sides.
- As the ridges approach the ventricle, the ridges come off at different angles and spiral downward.
- By the time the swellings reach the ventricle, they are turned 180 degrees and are perfectly parallel to the interventricular septum.
- Cells of the spiraling ridges are derived from migrating neural crest cells and from the endocardial-derived cushion tissue.
Ventricular septal defects
- Failure of proper closure by abnormal or inadequate fibrous tissue is the cause 95% of the time
- RV hypertrophies due to increased work load
- V pressure builds and exceeds the left side, so now a right to left shunt develops
- Eventually die of cardiac failure if not addressed
Persistent truncus arteriosus
- failure of contruncal ridge formation and fusion
- The pulmonary artery arises some distance away above the undivided truncus
- Undivided truncus overrides both right & left ventricle.
- mixing of oxygenated and deoxygenated blood within truncus so it can present with low degree of cyanosis
- leads to pulmonary congestion, RV hypertrophy
Tetralogy of Fallot
- Conotruncal ridges form off midline leading to unequal division of pulmonary trunk and aorta
- VSD (missing fibrous portion). ‘
- Pulmonary infundibular stenosis.
- Overriding aorta.
- RV hypertrophies in the fetus because of the small pulmonary opening
- VSD (missing fibrous portion). ‘
Transposition of great vessels
- conotruncal ridges fail to spiral.
- Consequence: pulmonary artery is connected to the LV and the aorta to RV. Survive only because of existing shunts such as VSD, ASD
- Even with shunts, expected survival is only 3 years
Pulmonary valvular atresia
- Semilunar valves are fused leading to RV hypoplasia.
- Patent foramen ovale then forms only outlet for blood on right side to get to the left side.
- Ductus arteriosus is always patent and is only route for blood to get to lungs.
- May require transplant depending on degree of RV hypoplasia.
Aortic valvular stenosis
- leads to hypertrophy of LV and eventually to cardiac failure and pulmonary hypertension
- Can be congenital, due to infection or degenerative
- more in males
Bicuspid aortic valve
- regurgitation or later, to a form of stenosis
- Initially asymptomatic but eventual leads to LV hypertrophy
Aortic valvular atresia
- If valves are completely fused the LV is underdeveloped
- A wide ductus arteriosus forms because it is the only way O2-enriched blood from placenta can get into left side
- Leads to RV hypertrophy during fetal period.
Tricuspid atresia
- obliteration of right AV orifice
- underdeveloped right ventricle, hypertrophy of left ventricle, and patent ductus arteriosus
- Can be corrected surgically if RV is not too under developed. Otherwise they may require a transplant
Hypoplastic left ventricle
- the LV is underdeveloped with absent or small bicuspid and aortic valves
- The ascending portion of the aorta is underdeveloped and there’s a patent ductus arteriosus and/or foramen ovale.
- The heart is basically working as a univentricular heart with the RV doing all the work.
- Surgical and medical interventions improve outcomes, but most die after 5 years
Fetal cardiac blood flow
- bulk of the blood entering from the IVC is shuttled through the foramen ovale into the left atrium
- Hence the LA receives the oxygenated blood that is transferred to the LV and out into fetal systemic arterial side
- Blood exiting the RV re-enters the systemic arterial side via the ductus arteriosus with only about 11-13% actually going through the pulmonary arteries to reach the developing lungs
