Congenital Heart Defects/Disease (CHD) Flashcards
Congenital Heart Defects/Disease (CHD)
- CHD are a class of heterogeneous defects/diseases
- = structural abnormalities of the heart or great vessels
- CHD are the most common birth defect in newborns
What causes Congenital Heart Defects?
- Large proportion have no family history of CHD
- Only 20-35% cases can be traced to a known cause
- 3-5% monogenic
- 8-10% chromosomal
- 3-25% copy number variants
- 2% environmental causes (maternal diabetes, smoking, alcohol etc)
- Infections e.g. rubella
80% are considered multifactorial
* Possibly multiple causes e.g. environment/other factors
Variation in CHD phenotypes
* Family members with the same genetic mutation may present with different
CHD
Environmental Factors
- Example:
- Diabetic mother: almost three-fold
increased risk of CHD. - In mice, hyperglycemic conditions
(increased blood glucose) inhibits EMT
required for cushion development. - Hyperglycemia inhibits the release of VEGF
- Leads to retention of PECAM-1 in
endocardial cells so can’t undergo EMT
[PECAM is a cell adhesion molecule on endothlital cells, but endothelial cells need to differeinatie into mesenychmal cells to form cushions, so PECAM would normally detach from it, for them to change, but hypercemia, keeps the PECAM so now the endothelial cells are stuck and stagnant and cannot change its state]
- Hypoxia (low oxygen) → VEGF Increase
==> (lack of oxygen from defective
angiogenesis (new blood vessel
formation)) increases the release of VEGF
and therefore inhibits endocardial
cushion formation.
Excess VEGF keeps cells in an endothelial state, preventing them from transitioning into mesenchymal cells → again, no proper endocardial cushions.
[ VEGF helps cells detach but Excess VEGF → Overstimulates endothelial cells and reinforces their endothelial state, preventing them from transitioning into mesenchymal cells (bad for EMT and cushions)]
Causes of CHD
Major types of heart defects
1. Acyanotic
* Defect/s that result in L to R shift in blood flow [WRONG WAY]
* though Normal pulmonary blood flow [lungs get enough blood]
=> some of the oxygenated blood from the left side (LA/LV) leaks back into the right side (RA/RV) instead of going straight to the body.
==> still reaches the body
- Cyanotic
==> some deoxygenated blood bypasses the lungs and enters the aorta, going to the body without getting oxygenated.
maybe a hole to mix with oxygenated blood in the left heart
== body less oxygen
* Defect/s that result in Cyanosis = blue discolouration of the extremity skin/mucous
membrane (fingers, lips)
* Due to reduced oxygen saturation of systemic blood - Other: dependent on severity
* Heterotaxy = Abnormal arrangement of organs, including the heart
- Spectrum of CHD
- Dextrocardia: disruption of L-R patterning
= Heart is on the right side instead of the left, caused by disruption in Left-Right (L-R) body patterning
Atrial Septal Defect (ASD)
A hole in the septum between the atria.
Causes blood to flow from the left atrium (higher pressure) to the right atrium (lower pressure).
Leads to increased blood flow to the lungs (pulmonary overcirculation).
Atrioventricular Septal Defect (AVSD)
A defect in the atrioventricular septum.
==> high pressure in the left side of the heart (especially the left ventricle) causes blood to be pushed back into the right side, increasing pulmonary blood flow—just like ASD does. This leads to pulmonary overcirculation, which can strain the lungs and heart over time.
Partial vs. Complete AVSD:
1. Partial (Incomplete) AVSD:
Similar to an atrial septal defect (ASD).
There’s a hole in the atrial septum, but the ventricular septum is intact.
The AV valves (mitral & tricuspid) may be slightly abnormal but still separate.
Complete AVSD:
No proper septal formation (both atrial and ventricular septa are affected).
One large AV valve instead of two separate mitral and tricuspid valves.
Blood mixes freely between all four chambers, leading to severe pulmonary overcirculation and heart failure if untreated.
Can be partial (like ASD) or complete (no septal formation, one common AV valve).
Requires surgery to correct.
Patent Ductus Arteriosus (PDA)
The ductus arteriosus (a fetal blood vessel connecting the pulmonary artery to the aorta) fails to close after birth.
Blood from the aorta (higher pressure) flows into the pulmonary artery, increasing lung circulation.
Transposition of the Great Vessels (TGV)
The aorta and pulmonary artery are switched.
==> outflow tract defect
The aorta arises from the right ventricle (instead of the left), and the pulmonary trunk arises from the left ventricle (instead of the right).
==> deoxygenated blood is sent straight to the body instead of going to the lungs to get oxygenated.
This leads to parallel circulation, where deoxygenated blood keeps circulating in the body.
Requires surgical intervention
?? This means oxygenated blood keeps cycling back to the lungs without ever reaching the body.
That’s why TGV is fatal unless there’s a shunt (ASD, VSD, or PDA) to mix oxygenated and deoxygenated blood.
.
Tetralogy of Fallot (TOF)
The most common cyanotic heart disease.
Consists of 4 malformations:
1. Pulmonary stenosis – narrowing of the pulmonary outflow tract.
==> narrowed, less blood is able to go to the lungs to get oxygenated.
- Ventricular septal defect (VSD) – hole between ventricles.
=> some deoxygenated blood is pumped into the aorta and out to the body,
=> Less oxygenated blood in circulation → cyanosis. - Overriding aorta – aorta positioned over the VSD, receiving blood from both ventricles.
=> aorta ends up sending a mix of oxygenated and deoxygenated blood to the body. - Right ventricular hypertrophy – thickening of the right ventricle due to increased workload.
Results in cyanosis (blue skin) due to reduced oxygen in systemic circulation.
==> becomes stiff and less efficient, making it harder for the heart to pump blood properly.
