Block III: Congenital malformations (conf 4) Flashcards
1
Q
WHat is the main purpose of the heart?
A
oxygenate blood by delivering deoxygenated blood into the lungs for oxygenation
2
Q
from where does SVC and IVC drain blood from?
A
upper body, head and neck; lower trunk and lower limbs
3
Q
what vessels carry oxygenated blood from arch of aorta into head and upper limbs?
A
Brachiocephalic a.
Left common carotid a.
Left subclavian a.
4
Q
explain the circulation of blood (in adult)
A
- deoxygenated blood enters the right atrium through IVC and SVC
- From the right atrium, passes through the tricuspid valve into the right ventricle
- From right ventricle passes through the pulmonary valve into th epulmonary trunk and into the lungs to be oxygenated.
- blood enters the heart again, oxygenated through the pulmonary veins into the left atrium.
- From left atrium enters through the mitral valve into the left ventricle.
- From left ventricle goes through the aortic valve into the aortic arch and goes through whole body by braciochephalic artery, left common carotid artery, left subclavian artery and the descending aorta.
5
Q
What structure in the cadaver remains that we had infoldings that closed?
A
linea alba
6
Q
explain the segmentation of the heart tube
A
unsegmented tube covered by a segmented tube
7
Q
What are the 3 main concepts of the development of heart?
A
- It all starts with an unsegmented tube
- Followed by invagination of the laminar structure of the embryo
- And by rotation of the (“primordial heart”) tube.
8
Q
where is the heart before the cranio-caudal folding? (hint: se me sale el corazon por la boca, garganta colorá)
A
anterior to the oropharyngeal membrane
9
Q
where does heart tube incorporate with the cranio-caudal folding?
A
coelomic cavoty into the pericardial cavity
10
Q
when does the formation of the cardiac loop occur?
A
22-24 days
11
Q
explain the cardiac loop?
A
ventricules are originally above atriums, they rotate to the front and down into the right and the atriums are originally below the ventricles but they move posterior and left. Thus, atriums are on top and ventricles on the bottom
12
Q
Where does primary heart field develop ?
A
develops cranial to the neural pliegues
13
Q
where does the primary heart field comes from?
A
from neural crest
14
Q
explain how does the primary heart field develops
A
Progenitor heart cells lie in the epiblast, immediately adjacent to the cranial end of the primitive streak. From there, they migrate through the streak and into the visceral layer of lateral plate mesoderm where some form a horseshoe-shaped cluster of cells.
15
Q
what do progenitor heart cells form?
A
These cells form portions of the atria and the entire left ventricle
16
Q
How does the secondary heart field form and what structures they form?
A
Cells reside in the visceral (splanchnic) mesoderm ventral to the pharynx. They form The right ventricle and outflow tract (conus cordis and truncus arteriosus) and the atria at the caudal end of the heart.
17
Q
what is the venous pole?
A
big vessels that enter and exit heart
18
Q
What is the outflow tract?
A
allows heart to be connected to the rest of the body
19
Q
What is the master gene of heart development?
A
NKX2.5 gene
20
Q
What activates the cascade of heart differentiation?
A
Secretion of BMP 2.4, crescent and cerberus by the endoderm produces inhibition of WNT genes and activation of NKX2.5 gene
21
Q
What secretes BMP2.4?
A
secreted by the endoderm and lateral plate mesoderm; transforming growth factors B
22
Q
What does WNT inhibitor genes secrete?
A
crescent and cerberus; inhibiting neural crest by inhibiting WNT 3a and WNT 8 which are secreted by neural tube
23
Q
Who secretes WNT?
A
secreted by the endoderm in the anterior half of the embryo
24
Q
What is syndromic?
A
congenital malformations
25
Which valves appear first?
tricuspid and mitral
26
What is the foramen ovale?
space between septum secundum and endocardial cushion
27
which is the potential anatomical space?
foramen ovale
28
why does the flap valve close?
due to first breath and low pressure in the right side
29
What is the purpose of the coronary sinus?
Brings low O2 blood from myocardium to right atrium for caval circulation (blood circulation of whole body/systemic)
30
What happens if foramen ovale closes too early?
results in problem where all blood will go into the left atrium
31
how does heart loops?
ventrally; heart goes from tubular structure into a four chamber structure with valves
32
when are congenital heart defects produced?
when developmental processes that mediate heart transformation are disrupted
33
what is the incidence of congenital heart defects in stillborns?
10%
34
what is the prevalence of congenital heart defects?
1% of live born infants. It makes up for the largest category of human birth defects.
35
what are the co-morbidities of congenital heart defects?
30% of heart defects occur in infants with other major malformations
33% of newborns with a chromosomal defect also have a heart defect
36
What are some examples of syndromes that can be accompanied by heart malformations?
Edwards Syndrome (Trisomy 18), Down Syndrome (Trisomy 21), golderhay syndrome (oculoauroculovertebral spectrum), DiGEORGE SYNDROME
37
What is the etiology of congenital heart defects?
Approximately 2% of heart defects are due to environmental agents, but most are
caused by a complex interplay between genetic and environmental influences;
(multifactorial causes); ie. idiopathic
38
What are some cardiovascular teratogens?
Rubella virus, Thalidomide, Retinoic acid (Accutane), Alcohol
* Insulin-dependent diabetes and hypertension of the mother has also been linked to cardiac defects.
39
What is the percentage of distribution of congenital defects by sex?
varon - 52%
hembra- 46%
intersex - 3%
40
cuales son los municipios con mayor numero de casos de defectos congénitos por densidad poblacional?
San juan (242), bayamon (125), ponce (106), carolina (53) y caguas (53)
41
Cual es la prevalencia de defectos congenitos por municipio por cada 1000-10000 nacimientos?
Maricao, guayanilla, cataño, hormigueros, yauco, peñuelas, maunabo, quebradillas, hatillo, santa isabel
contaminantes etc, fabricas, sistema electrico, farmaceuticas, industrias, health professionals shortage areas, monsanto
42
cual es la condicion congenita mas comun en puerto rico?
VSD (ventricular septal defect) and ASD secundum (atrial septal defect)
43
what is the international coding of disease?
numbers that doctor puts as diagnosis to get paid
44
NKX2.5 gene on chromosome 5q35 has been linked to:
Atrial Septal Defects (secundum type)
Tetralogy of Fallot
Atrioventricular conduction delays in an autosomal dominant fashion
45
What is the function of TBX5 gene of chromosome 12q24.1?
It has a DNA binding motif known as ‘the T box’.
It plays an important role in heart septation.
linked with holt-oram syndrome
46
What si the holt-oram syndrome?
-One of a group of the so-called ‘heart–hand syndromes’
-Upper limb malformations and atrioseptal defects (ASDs).
-Defects in the muscular portion of the interventricular septum may also occur
47
what is the frequency and classification of halt-oram?
Autosomal dominant trait with a frequency of 1/100,000 live births
48
What is an example that cardiac malformations coexists?
tetralogy of fallot
49
By what can ASDs also be accompanied?
ASDs can result in a common atrium chamber, which are usually accompanied by defects in mitral and tricuspid valves.
50
By what can VSDs also be accompanied?
VSDs can result in a common ventricle chamber, which are usually accompanied by TGAs. ASDs and TGAs can also coexist.
51
By what can PTAs also be accompanied?
PTA co-exists with VSDs
52
What is the common feature of cardial congenital malformations?
The common feature is poor oxygenation, change from aerobic to anaerobic metabolism, acidosis, and eventual death in severe cases. Some minor defects resolve after birth while others can be compatible with life, some may require repair later in life. mix of blood
53
What is the most common form of ASD?
Patent oval foramen; mix of oxygenated and deoxygenated blood between atriums
54
What is small isolated patent oval foramen?
no clinical significance; but if there are other defects (e.g. pulmonary stenosis or atresia), blood is shunted through the oval foramen into the left atrium and produces cyanosis (dark bluish or purplish coloration of the skin and mucous membranes = deficient oxygenation of the blood).
55
what is probe patent oval foramen?
(present in up to 25% of people) – probe can be passed from one atrium to the other through the oval fossa; results from incomplete adhesion between the flaplike valve of the oval foramen and the septum secundum after birth (usually of no clinical significance unless combined with other cardiac defects).
56
What is ostium secundum ASDs?
It includes defects of the septum primum and secundum
57
why does patent oval foramen occur?
results from absorption of the septum primum during the formation of the foramen
secundum (the resulting short septum primum will not close the oval foramen).
58
why does large oval foramen occur?
Large oval foramen can also occur because of defective development of the septum secundum (a normal septum primum will not close the abnormal oval foramen at birth).
59
why does large ostium secundum ASDs occur?
Large ostium secundum ASDs may occur because of a combination of excessive resorption of the septum primum and a large oval foramen.
60
explain the clinical consequence of ostium secundum ASDs
Ostium secundum ASDs are well tolerated during childhood; symptoms such as pulmonary hypertension usually appear in the 30s or later (closure of the ASD is
carried out with open heart surgery – mortality rate is less than 1%).
61
Which is the most serious form of the ASD group?
Common atrium (cortriloculare biventriculare)
62
what happens in Common atrium (cortriloculare
biventriculare?
no septums dividing atriums, thus cannot have functioning valves (they are open); mix of blood
63
by what is cortriloculare biventriculare associated with? and what other malformation is present in this condition?
attachment of mitral and tricuspid valves to the interventricular septum in the same anatomical plane.
A cleft mitral leaflet is almost always present with this condition
64
What are the clinical consequences of cortriloculre biventriculare?
Severe cyanosis, hypoxia, cardiac failure in early infancy, but also reported cases of people who live through adulthood
65
what mostly co-exists with ASDs?
mitral and tricuspid valve defects
66
What is the most common form of VSDs?
Membranous VSD
67
What is memebranous VSD?
Incomplete closure of the IV foramen results from failure of the membranous part of the IV septum to develop. (“endocardial cushions” do not form)
68
What is muscular VSD?
excessive cavitation of myocardial tissue during formation of the ventricular walls and the muscular part of the IV septum; Swiss cheese VSD – produced when there are multiple small defects within the muscular part of the IV septum.
69
WHat are the clinical consequences of VSDs?
Large VSDs with excessive pulmonary blood flow and pulmonary hypertension result in dyspnea (difficulty breathing) and cardiac failure early in infancy
70
where does VSD occurs?
May occur in any part of the IV septum.
71
what happens with small VSDs?
Small VSDs close spontaneously (30-50%) during the 1st year.
72
WHat is single or common ventricle VSD?
absence of the IV septum; both atria empty through a common valve or two separate AV valves into a single ventricular chamber (aorta and pulmonary trunk arise from the
single ventricle).
73
What are the clinical consequences of single/common ventricle VSD?
Single ventricle is usually accompanied by Transposition of the Great Arteries; some patients die during infancy from congestive heart failure, but others may survive until early adult life
74
Patent Ductus Arteriosus (PDA) results from?
compensatory mechanism due to ASD or VSD or both, compensatory mechanism to oxygenate and distribute blood
75
By what does the heart tube consists in the beginning?
the heart tube consists of the myocardium (wall of heart) and endocardium (lining of tube) separated by a layer of extracellular matrix (ECM).
76
Where do endocardial cushions form?
in the atrioventricular canal and in the outflow tract as expansions of the ECM.
77
how does endocardial cushions form?
Cells migrate into the cushions and proliferate: In the atrioventricular (AV) canal, these cells are derived from the endocardium whereas in the outflow tract, they are derived from neural crest cells.
78
WHat is persistent truncus arteriosus (PTA)?
aorticopulmonary septum does not develop; pulmonary trunk and aortic trunk are fused still
79
what other malformation is accompanied with PTA?
VSD, blood mixed so i have to compensate
80
What is the function of the pulmonary valve?
This is the valve separating the right ventricle and the pulmonary artery. The pulmonary artery carries oxygen-poor blood to the lungs.
81
What is pulmonary stenosis?
Stenosis, or narrowing, occurs when the valve cannot open wide enough; it can be repaired
82
What is persistent atrioventricular canal?
atrioventricular channels never closed; occurs very early on. upper and lower portion of heart are completely communicating (endocardial cushion defect)
83
what cushions participate in the formation of the septum in the atrioventricular canal?
superior endocardial cushion
lateral cushion
inferior endocardial cushion
84
what does the endocardial cushion also participates?
formation of the membranous portion of the interventricular septum and in closure of the ostium primum. In a developing heart sonogram, you look for “the cross sign”
85
What are the 4 components of the tetralogy of fallot?
Pulmonary stenosis
Overriding aorta – positioning over the VSD instead of over the left ventricle
Ventricular septal defect (VSD)
Hypertrophy of the right ventricle - hay q llegar al lado izq a arteria pulmonar, al pulmon, so lado derecho va a trabajar mas fuerte
86
what compensatory mechanism is present in teratology of fallot present?
Patent ductus arteriosus
87
Why does tetralogy of fallot occur?
due to unequal partitioning of the truncus arteriosus
88
What is the chromosomal def of Digeorge sequence syndrome?
22q11 deletion syndrome
89
where does DiGeorge syndrome malformation originate?
abnormal neural crest development
90
What are the characteristics/malformations of DiGeorge?
1. Cardiac malformations involving the outflow tract, such as Persistent Truncus Arteriosus and Tetralogy of Fallot.
2. Thymic hypoplasia - a specialized primary lymphoid organ of the immune system
3. Parathyroid dysfunction - hypocalcemia
4. Facial atypia (facis)
* small ears with squared upper ear
* hooded eyelids
* cleft lip and/or palate
* asymmetric crying facies
* small mouth, chin, and side areas of the nose tip
* flaccid muscles
5. mental retardation
91
What is the embryological basis of neural crest celss (for tetralogy of fallot purposes?
origin of neural crest cells in the hindbrain and their migration through pharyngeal arches 3, 4, and 6 to the outflow tract of the heart. In this location, they contribute to
septation of the conus cordis and truncus arteriosus.
92
What is dextrocardia?
heart rotates to the left instead of right; A condition where the heart lies on the right side of the thorax instead of the left and it occurs when the heart loops to the left instead of the right.
93
By what is dextrocardia induced?
The defect may be induced during gastrulation, when laterality is established, or
slightly later when cardiac looping occurs.
Dextrocardia occurs with situs inversus, a complete reversal of asymmetry in all organs, or may be associated with laterality sequences (heterotaxy) in which only some organ positions are reversed
94
What can happen in heterotaxy?
- Slight risk of heart problems
- Left-sided laterality: polysplenia (muchos brazos)
- Right-sided laterality: hypoplastic spleen or asplenia
95
What is transposition of great arteries?
body–heart –body (without being routed to the lungs for oxygen except for mixing of blood through PDA or blood flowing backwards. blood no llegó al pulmón porque lado derecho e izq no se estan comunicando. you can only exchange blood in patent ductus arteriosus
96
What are some causes of transposition of great arteries?
- Conal growth hypothesis: aorticopulmonary septum and spiral growth
- Arrested migration of neural crest cells
97
What is the clinical consequence of transposition of great arteries?
Without surgical correction of the transposition, these infants die within a few months
98
Where does ASD, VSD, TGA develop from?
PHF [primary heart field] (days 16–18); it is supposed to form the 4 chambers of heart
99
What is the origin of ASD, mitral/tricuspid valve defects (mitral insufficiency and tricuspid atresia)?
AVC endocardial cushions (days 26–35)
100
What tissue is responsible of dextrocardia?
heart tube, was supposed to have laterality and looping
101
Where does tetralogy of fallot and TGA come from?
SHF (days 22-28) secondary heart field
102
explain
Magnetic resonance image of a fetus demonstrating exteriorization of the heart (*) from its normal position within the thorax (t). An omphalocele can also be seen (arrow). Extrabacion de aorta occurs due to lack of closure of lateral foldings
