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The first system to develop due to the growing embryo's ever-increasing metabolic demands is the cardiovascular system. Initially, simple diffusion of necessary nutrients is sufficient but eventually becomes inadequate to supply oxygen and nutrients. Cardiac development is a complicated interplay of molecular communication, ensuring the proper formation of structures and spatial configuration changes in the appropriate timing. Interference with this process, whether genetic or environmental, leads to the formation of congenital heart diseases.

zA significant majority of congenital heart defects occur due to genetic mutations that interfere with cardiac development. Other conditions are also associated with abnormalities in the various developmental stages, often due to the influence of teratogens such as alcohol, rubella, etc. Chromosomal lesions (as those found in DiGeorge syndrome or Holt-Oram syndrome) are also noted to contribute to congenital heart disease development. The number one genetic cause of congenital heart disease is trisomy 21, which often manifests itself as endocardial cushion defects.The significant features of congenital heart disease can follow one or more elements of the following classifications: malformations causing shunting (right-to-left or left-to-right) or malformations causing an obstruction. Shunts are abnormal communications between systemic circulation (the left heart) and the pulmonary circulation (the right side).

zA significant majority of congenital heart defects occur due to genetic mutations that interfere with cardiac development. Other conditions are also associated with abnormalities in the various developmental stages, often due to the influence of teratogens such as alcohol, rubella, etc. Chromosomal lesions (as those found in DiGeorge syndrome or Holt-Oram syndrome) are also noted to contribute to congenital heart disease development. The number one genetic cause of congenital heart disease is trisomy 21, which often manifests itself as endocardial cushion defects.The significant features of congenital heart disease can follow one or more elements of the following classifications: malformations causing shunting (right-to-left or left-to-right) or malformations causing an obstruction. Shunts are abnormal communications between systemic circulation (the left heart) and the pulmonary circulation (the right side). The term shunt refers to abnormal communication between vascular structures, and these shunts permit non-physiologic blood flow along pressure gradients. Blood flowing from the right side of the heart to the left side is termed a “right-to-left” shunt, while blood flowing from the left side of the heart to the right side is a “left-to-right” shunt. Right-to-left shunt implies the circulation of deoxygenated blood (i.e., blood that has yet to reach the pulmonary system) to the systemic circulation. Patients with a right to left shunts present with cyanosis and at increased risk for paradoxical embolism and the associated complications like infarction and abscess formation. In contrast, left-to-right shunts do not present with cyanosis since the systemic circulation still receives oxygenated blood. However, the increase in pulmonary blood load from the left-to-right shunt leads to profound pathological responses, partly due to the pulmonary system being a “low-pressure” system incapable of withstanding the increased pressure.The pulmonary arteries typically respond to the increased blood flow and pressure via hypertrophy and vasoconstriction. Eventually, pulmonary vascular resistance approaches systemic levels, creating a shunt reversal (now right-to-left) to distribute deoxygenated blood into the systemic system. The name given this condition of shunt reversal is Eisenmenger syndrome. Once pulmonary hypertension develops, the congenital heart condition progresses beyond irreparability.

The term shunt refers to abnormal communication between vascular structures, and these shunts permit non-physiologic blood flow along pressure gradients. Blood flowing from the right side of the heart to the left side is termed a “right-to-left” shunt, while blood flowing from the left side of the heart to the right side is a “left-to-right” shunt. Right-to-left shunt implies the circulation of deoxygenated blood (i.e., blood that has yet to reach the pulmonary system) to the systemic circulation. Patients with a right to left shunts present with cyanosis and at increased risk for paradoxical embolism and the associated complications like infarction and abscess formation. In contrast, left-to-right shunts do not present with cyanosis since the systemic circulation still receives oxygenated blood. However, the increase in pulmonary blood load from the left-to-right shunt leads to profound pathological responses, partly due to the pulmonary system being a “low-pressure” system incapable of withstanding the increased pressure.The pulmonary arteries typically respond to the increased blood flow and pressure via hypertrophy and vasoconstriction. Eventually, pulmonary vascular resistance approaches systemic levels, creating a shunt reversal (now right-to-left) to distribute deoxygenated blood into the systemic system. The name given this condition of shunt reversal is Eisenmenger syndrome. Once pulmonary hypertension develops, the congenital heart condition progresses beyond irreparability. The most commonly associated left-to-right shunts include atrial septal defect, ventricular septal defect, patent ductus arteriosus, and atrioventricular septal defects. Common right-to-left shunts include Fallot’s tetralogy, transposition of the great arteries, persistent truncus arteriosus, total anomalous pulmonary venous connection, and tricuspid atresia.Calreticulin is a Ca (2 +) - binding chaperone and is found in the endoplasmic reticulum. Studies reveal that it is a fundamental substance in the complex process of cardiac development. An alteration of the calreticulin function will cause cardiac disorders such as hypertrophy and dilated cardiomyopathy.