Chapter 12: Congenital Heart Disorders Flashcards
What is a congenital heart disease?
Congenital heart disease is a general term used to describe abnormalities of the heart or great
vessels that are present from birth.
Where does most congenital disorders arise from ?
Most such disorders arise from faulty embryogenesis during gestational weeks 3 through 8, when major cardiovascular structures form and begin to
function.
The most severe anomalies are incompatible with intrauterine survival.
Congenital heart defects compatible with embryologic maturation and birth generally affect individual
chambers or discrete regions of the heart, with the remainder of the heart developing relatively
normally.
Examples are infants born with a defect in :
- septation (“hole in the heart”),
- such as atrial septal defect (ASD) or a ventricular septal defect (VSD),
- stenotic valvular lesions, or with
- abnormalities in the coronary arteries.
Some forms of congenital heart disease produce
clinically important manifestations soon after birth, which are frequently brought on by the
change from fetal to postnatal circulatory patterns (with reliance on the lungs for oxygenation birth, rather than the placenta as in intrauterine life).
Approximately half of congenital
cardiovascular malformations are diagnosed in the first year of life, but some mild forms may
not become evident until adulthood (e.g., ASD).
With an incidence of approximately 1% (estimates range from 4 to 50 per 1000 live births),
- *congenital cardiovascular** defects are among the most prevalent malformations and are the
- *most common type of heart disease among children**. [24]
T or F
True
The incidence is higher in premature
infants and in stillborns
TABLE 12-2 – Frequencies of Congenital Cardiac Malformations
in desceding order
- Ventricular septal defect : 42%
- Atrial septal defect: 10%
- Pulmonary stenosis :8 %
- Patent ductus arteriosus: 7%
- Tetralogy of Fallot
- Coarctation of the aorta
- Atrioventricular septal defect
- Aortic stenosis
- Transposition of the great arteries
- Truncus arteriosus
- Total anomalous pulmonary venous connection
- Tricuspid atresia
The number of individuals who have survived with congenital heart disease into adulthood is
increasing rapidly and is presently estimated at nearly 1 million individuals in the United States. [25]
Many of those with congenital heart disease have benefited greatly from rapid advances in the surgical and interventional repair of various structural heart defects.
Nevertheless, such repairs may not restore the heart to normal; in such instances, patients may
suffer from arrhythmias or ventricular dysfunction, and require additional surgery. [26] Other
factors that impact the long-term outcome include risks associated with the use of prosthetic
materials and devices, [27] such as substitute valves or myocardial patches, and maternal risks
associated with childbearing.
The diverse malformations seen in congenital heart disease are caused by errors that occur
during cardiac development; thus, a brief review how the heart normally forms is in order before
discussing the specific defects
Suffice it to say that the earliest cardiac precursors originate in ________________
lateral
mesoderm
Suffice it to say that the earliest cardiac precursors originate in lateral
mesoderm and move to the mid-line in two migratory waves to create a crescent of cells
consisting of the first and second heart fields by about _____________
day 15 of development
Suffice it to say that the earliest cardiac precursors originate in lateral
mesoderm and move to the mid-line in two migratory waves to create a crescent of cells
consisting of the______________ by about day 15 of development
first and second heart fields
Each
heart field is marked by the expression of different sets of genes; for example, the first heart
field expresses the transcription factors ________
TBX5 and Hand1,
Each
heart field is marked by the expression of different sets of genes; whereas the second heart field
expresses the transcription factor ______________
Hand2 and fibroblast growth factor-10.
Both first and second fields contain
multipotent progenitor cells that can produce all of the major cell types of the heart;
endocardium, myocardium, and smooth muscle cells.
As an aside, there is considerable interest
in the therapeutic potential of such early cardiac progenitors, which could conceivably be used
to regenerate portions of the adult heart that are damaged or otherwise dysfunctional.
FIGURE 12-3 Human cardiac development, emphasizing the three sources of cells.
- A, Day 15. First heart field (FHF) cells (shown in red) form a crescent shape in the anterior embryo with second heart field (SHF) cells (shown in yellow) near the FHF.
- B, Day 21. SHF cells lie dorsal to the straight heart tube and begin to migrate (arrows) into the anterior and posterior ends of the tube to form the right ventricle (RV), conotruncus (CT), and part of the atria (A).
- C, Day 28. Following rightward looping of the heart tube, cardiac neural crest cells (shown in
blue) also migrate (arrow) into the outflow tract from the neural folds to septate the outflow
tract and pattern the bilaterally symmetric aortic arch arteries (III, IV, and VI). - D, Day 50. Septation of the ventricles, atria, and atrioventricular valves (AVV) results in the
appropriately configured four-chambered heart. Ao, aorta; AS, aortic sac; DA, ductus
arteriosus; LA, left atrium; LCA, left carotid artery; LSCA, left subclavian artery; LV, left
ventricle; PA, pulmonary artery; RA, right atrium; RCA, right carotid artery; RSCA, right
subclavian artery; V, ventricle.
Even at this very early stage of development, each heart field is destined to give rise to particular portions of the heart.
Cells derived from the first heart field mainly give rise to _________,
the left ventricle
Even at this very early stage of development, each heart field is destined to give rise to particular portions of the heart.
Cells derived from the second heart field give rise to the what?
- outflow tract,
- right ventricle,
- and most of the atria.
What happens by day 20 in the development of heart?
By day 20, the initial cell crescent develops into a beating tube, which loops to the right
When do the heart chambers begin to form?
begins to form the heart chambers by day 28
Aside from the start of formation of the heart chambers on day 28, what else are the critical events that occur?
Around this time, two
other critical events occur:
- (1) cells derived from the neural crest migrate into the outflow tract, where they participate in the septation of the outflow tract and the formation of the aortic arches; and
- (2) the extracellular matrix (ECM) underlying the future atrioventricular canal and outflow tract enlarges to produce swellings known as endocardial cushions
This process
depends on the delamination of a subset of endocardial cells, which invade the ECM and
subsequently proliferate and differentiate into the mesenchymal cells that are responsible for
valve development.
What happens by day 50 in the development of the heart?
By day 50, further septation of the ventricles, atria, and atrioventricular valves produces the four chambered heart.
The proper orchestration of these remarkable transformations in the development of the heart depends on a network of transcription factors that are regulated by a number of signaling pathways, particularly the
- Wnt,
- VEGF,
- bone morphogenetic factor,
- TGF-β,
- fibroblast growth factor,
- and Notch pathways.
Because a heart is a mechanical organ, what else play an important role in its development aside from the growth factors and genes?
It should also be remembered that the heart is a mechanical organ that is exposed to flowing blood from its earliest stages of development.
It is likely that hemodynamic forces play an
important role in cardiac development,just as theyinfluence adaptations in the adult heart such
as hypertrophy and dilation.
How does micro-RNAs play critical roles in cardiac development?
In addition, specific micro-RNAs play critical roles in cardiac development by coordinating patterns and levels of transcription factor expression
Many of the genetic defects that affect heart development are \_\_\_\_\_\_\_\_\_\_\_\_\_ that cause partial loss of function in one or another required factor, which are often transcription factors (discussed below).
autosomal dominant mutations
Thus, even relatively minor changes in the activity of
one of the many factors necessary for normal development can lead to defects in the final
product, the fully developed heart.
It can be imagined (but is unproved) that transient
environmental stresses during the first trimester of pregnancy that alter the activity of these
same genes might give rise to defects resembling those produced by inherited mutations.
