Cyanotic heart defect pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-In-Chief: Keri Shafer, M.D. [2], Atif Mohammad, M.D.; Kalsang Dolma, M.B.B.S.[3]

Overview[edit | edit source]

Pathophysiology[edit | edit source]

Tetrology of Fallot[edit | edit source]

• It is understood that tetralogy of fallot is the result of improper positioning of the outlet septum.^[1][2][3]
• In the normal heart, the outlet septum is an indistinguishable component of the crista supraventricularis that communicates with the septomarginal trabeculae to divide the right and left ventricular cavities.
• In Tetralogy of Fallot, proper ventricular septation is perturbed by anterocephalad displacement of the outlet septum relative to the septomarginal trabecula.
• The direct consequence of this misalignment is an overriding aortic orifice and a ventricular septal defect, resulting in an intracardiac right to left shunt of blood.
• In addition, anterocephalad displacement of the outlet septum indirectly predisposes the pulmonary trunk to stenosis in the setting of septoparietal trabecular hypertrophy.
• Together, the displacement of the outlet septum coupled with the hypertrophic arrangement of the septoparietal trabeculae account for the three anatomical cardinal defects in Tetralogy of Fallot - aortic dextroposition, interventricular communication (VSD), and pulmonary stenosis.
• The fourth defect - right ventricular hypertrophy - is a hemodynamic consequence of these three morphologic changes, as the right ventricle physiologically adapts to the increased resistance of a stenotic pulmonary trunk.

Total Anomalous Pulmonary Venous Connection[edit | edit source]

• In this condition,the right side of heart is receiving blood both from pulmonary and systemic circulation.^[4][5]
• There is a mixing of oxygenated pulmonary venous blood with deoxygenated blood from systemic circulation.
• The mixing of blood could occur at three levels i.e. supracardiac, infracardiac and cardiac.
• In the former two the mixing occurs outside the heart and in latter inside the heart (right atrium)

Transpostion of Great Arteries[edit | edit source]

• In the TGA the aorta arises from the morphologic right ventricle via a subaortic infundibulum and the pulmonary artery arises from the morphologic left ventricle, without a subpulmonary infundibulum.^[6][7][8][9]
• These ventriculoarterial connection is known as ventriculoarterial discordance.
• As a consequence, there is a a fibrous continuity between the mitral and pulmonary valve, but no continuity between the tricuspid and aortic valve.
• The abnormal origin of the great arteries results in an altered spiral relationship.
• Therefore, the aorta and pulmonary artery run parallel to each other
• In normal heart thus the circulation is in series.
• However, in transposition of the great vessels circulation is in parallel

Truncus Arteriosus[edit | edit source]

• In truncus arteriosus, the pulmonary arteries are connected to the aorta.
• A decrease in PVR at birth causes a left to right shunt with evidence of congestive heart failure.
• These patients have a very high incidence of pulmonary hypertension and vascular disease.

Tricuspid Atresia[edit | edit source]

• In tricuspid atresia, there is no continuity between the right atrium and right ventricle. Blood from superior vena cava and inferior vena cava is forced across intra atrial connection into the left heart.
• As a consequence, oxygen saturation in the left atrial blood is diminished.

Hypoplastic Left Heart Syndrome[edit | edit source]

• In patients with hypoplastic left heart syndrome, the left side of the heart is unable to send enough blood to the body.
• As a result, the right side of the heart must maintain the circulation for both the lungs and the body.
• The right ventricle can support the circulation to both the lungs and the body for a while, but this extra workload eventually causes the right side of the heart to fail.

Genetics[edit | edit source]

• Genes involved in the pathogenesis of tetralogy of fallot include:^{[10][11][12][13][14][15][16]}
  • The cellular processes that underlie cardiogenesis are extensively regulated in the developing heart.
  • Proper cardiac development requires the complex orchestration of cardiac transcription factors and signaling pathways in a spatiotemporal specific manner.
  • Previous genetic studies demonstrated that mutations in numerous genes encoding cardiac transcription factors and cell signaling proteins have a role in the development of Tetralogy of Fallot.
  • Specifically, heterozygous mutations in NKX2-5, HAND1, TBX5, and GATA4 have been reported in familial forms of disease.
  • Many of these single gene mutations result in haploinsufficiency and suggest a dose dependent relationship between genetic expression and disease.
  • While the mechanistic basis of this relationship is currently poorly understood, it is hypothesized that disruption of the direct protein-protein interactions that allow these transcription factors to work synergistically impedes the activation of downstream targets and signaling pathways central to cardiac morphogenesis.
  • In addition, recent whole-exome sequencing investigations have introduced a novel role for epigenetic dysregulation in the pathogenesis of Tetralogy of Fallot.
  • Aberrant epigenetic modifications are thought to provide an alternative mechanism to perturb normal spatiotemporal expression of these essential developmental genes.

• Genetic mutations associated with total anomalous pulmonary venous connection include:^[17][18]

Associated Conditions[edit | edit source]

• Conditions associated with tetralogy of fallot include:^{[19][20][21][22]}
  • Left superior vena cava
  • Anomalies of the mitral valve
  • Anomalies of the tricuspid valve
  • Stenosis of the left pulmonary artery, in 40% of patients
  • A bicuspid pulmonary valve, in 40% of patients
  • Right sided aortic arch, in 25% of patients
  • Coronary artery anomalies, in 10% of patients
  • An atrial septal defect, in which case the syndrome is sometimes called a pentalogy of Fallot.
  • An atrioventricular septal defect
  • Partially or totally anomalous pulmonary venous return
  • Forked ribs and scoliosis
  • Associated abnormalities include cleft lip, cleft palate, hypospadias, skeletal and craniofacial abnormalities.

• Conditions associated with total anomalous pulmonary venous connection
  • Patent foramen ovale
  • Atrial septal defect
  • Patent ductus arteriosus
  • Pulmonary hypertension
• Conditions associated with TGA include:
  • Ventricular septal defect
  • Pulmonary stenosis
  • Left atrioventricular valve regurgitation (tricuspid or systemic)
  • Complete heart block
• Conditions associated with truncus arteriosus include:
  • DiGeorge syndrome

Gross Pathology[edit | edit source]

On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

Microscopic Pathology[edit | edit source]

On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

References[edit | edit source]

Template:WikiDoc Sources