L3.

Development of the Heart

Most Prevalent Abnormalities: o Produce 2 kinds of disorders: Mix of O2 poor systemic blood with O2 rich pulmonary blood e.g. septal defects, patent ductus arteriosus Narrowed valves or vessels that greatly increase workload of the heart e.g. coarctation of the aorta Tetralogy of Fallot (both types) Heart and vascular defects account for 1% of malformations among live-born infants 8:1000 live births have one or more heart and circulatory defects This incidence is increased 10 times in humans: o 8% genetic factors o 2% environmental

1) Understand the basic development of the heart and great vessels Lecture Handout Heart is one of the earliest differentiating and functioning organs Develops from cardiogenic mesoderm o Which originally lies above cranial end of neural tube The angiogenic clusters coalesce forming right and left endocardial tubes Each tube is continuous cranially with a dorsal aorta, outflow tract and caudally with a vitelloumbilical vein, inflow tract By 21 days fusion is complete of the endocardial tubes= primitive heart tube Ventricular Primordia initially lies above the atria Mesoderm from foregut forms external layer of heart = primitive myocardium Layer of extracellular matrix: o Cardiac Jelly o Separates Endothelial heart tube and Myocardium Heart beats on day 22 Sinus venosus is where inflow occurs There are paired primitive atria Atrioventricular sulcus divides atria from the primitive ventricle (ONE) Primitive ventricle expands to become left ventricle Interventricular sulcus divides primitive ventricle from BULBUS CORDIS Bulbus Cordis is divided into: o Bulbus Cordis proximal portion forms right ventricle o Conus Cordis Outflow o Truncus Arteriosus Outflow Heart Looping: o As the primitive heart continues to develop, it lengthens o The ends are fixed, therefore it is forced to bulge and twist within the pericardial sac o From day 22 to 24, heart tube doubles in length Marieb 4 primitive chambers of the heart are the following: o Sinus Venosus: Receives all venous blood of embryo Becomes the smooth walled part of the right atrium and the coronary sinus 1

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Gives rise to SAN Atrium Becomes pectinate muscle-ridged parts of atria Ventricle Gives rise to left ventricle Bulbus Cordis Bulbus Cordis + truncus arteriosus give rise to pulmonary trunk, first part of aorta and most of right ventricle Heart undergoes rightward looping Ventricle moves caudally and atrium cranially Midline septum forms and splits the bulbus cordis into: Pulmonary trunk Ascending Aorta After second month few changes occur

2) Describe embryonic folding of the heart Septum formation in atrio-ventricular canal o At the end of 4th week 2 swellings of mesenchymal tissue arise o Atrio-ventricular endocardial cushions o Appear at the inferior and superior border of the atrio-ventricular canal o Endocardial cushions grow and fuse together o At this stage there is no direct communication between atria and ventricles o Blood flows from common atrium into left ventricle then into right ventricle o During septation of the ventricles, the atrioventricular canal must shift to the right to communicate with right ventricle in addition to left ventricle Atrial Partitioning o Begins with appearance of septum primum at day 28 o This is a crescent of tissue that grows from the dorsal wall of the atrium towards the endocardial cushions o The ostium formed by free edge of septum primum is the ostium Primum o Before septum primum fuses with endocardial cushions, perforations appear in upper portion of septum primum Perforations coalesce to form ostium secondum o A septum secondum now starts to grow o It does not fuse with the endocardial cushions o The free edge of septum secondum forms foramen ovale o Blood is shunted through the foramen ovale between the 2 atria as foetal lungs are not developed Formation of ventricles o By end of 4th week 2 ventricles begin to expand o New cardiac muscle (myocardium) is added to outside of ventricles o IVS is the trabeculated muscle o Endocardial cushion membranous part of ventricles, atrioventricular canals Partioning of the outflow tract Aorta and pulmonary trunk o Septum forms from two pairs of swellings which grow from the walls of the outflow tract o Right and left bulbar ridges

2 spiral mesodermal ridges grow from the inner walls of the truncus arteriosus and bulbus cordis, twist around each other and fuse to form a spiral aorticpulmonary septum These fuse in the midline and also with the top of the muscular ventricular septum Therefore the aorta connects with the left ventricle and the pulmonary trunk with the right ventricle

3) Explain the importance of the endocardial cushions and the separation of the atria and ventricles Because of the location of the atrioventricular canals in the endocardial cushions, o They can contribute to many cardiac malformations e.g. atrial septal and ventricular septal defects

4) Recognise the following congenital heart defects dextrocardia, atrial and ventricular septal defects, persistent TA, tetralogy of Fallot, Coaraction Dextrocardia o Primitive heart tube folds to the left o Mirror image of normal looping o Occurs when all organ systems are reversed situs inversus o Situs Inversus occurs in 1:7000 of ppl Ventricular Septal Defect o Superior part of interventricular septum fails to form o Blood mixes between the 2 ventricles o More blood is shunted from left to right because left ventricle is stronger o 1 in 500 births Coarctation of the Aorta o A part of the aorta is narrowed increasing the workload of the left ventricle o Occurs 1 in 1500 births Tetralogy of Fallot o Multiple defects o Pulmonary trunk is too narrow and pulmonary valve is stenosed o Results in hypertrophied right ventricle o Ventricular septal defect o Aorta opens from both ventricles o Baby becomes cyanotic within minutes of birth

Acyanotic Heart Lesions Congenital heart disease: a group of cardiac diseases with a left right shunt or left heart abnormality Make up about 1/3 of congenital heart diseases Acyanotic heart lesions with left to right shunts include: o Atrial Septal Defects o VSD ventricular septal defects o Persistent Ductus Arteriosus o AV canal defects Atrial Septal Defects o 7: 10,000 births 3

2:1 prevalence in females versus males Primum Atrial Septal Defect Ostium Primum is patent because septum primum has not fused with endocardial cushions The cushions are responsible for forming a portion of septum primum o Secundum Atrial Septal Defect Short septum primum does not overlap foramen ovale. Hence there is communication between right and left atrium A LARGE ASD with left-to-right shunt resulted in: Pulmonary HT and inc pulmonary arterial pressures This led to right-left shunt resulting in right ventricular hypertrophy A SMALL ASD (probe patient) A probe can be passed from one atrium to the other Ventricular Septal Defect o Are the most common type of cardiac defects accounting for 25% of congenital heart disease o Many small VSD will close spontaneously (30-50%) o Isolated VSD are detected with an incidence of 12:10,000 o About 90% of VSD are in membranous septum and 10% in muscular septum o A massive left to right shunting of blood results in pulmonary hypertension Patent Ductus Arteriosus o Connects the descending aorta to the main pulmonary trunk near the origin of the left subclavian o Normal post-natal closure results in fibrosis which becomes the ligamentum arteriosum o Small PDA does not increase risk for heart failure but does carry a risk for bacterial endocarditis o Defects that cause large differences between aortic and pulmonary pressures may cause inc blood flow through ductus, preventing normal closure Valvular Stenosis o Pulmonary Pulmonary trunk narrow or atretic o If atresia patent, foramen ovale only outlet from right side. Ductus arteriosus only access to pulmonary circulation o Aortic valvular Atresia The LA, LV and aorta are underdeveloped + patent ductus arteriosus which delivers blood to the aorta Coarctation of the Aorta o 10-15%of congenital heart disease o Constriction may be above or below the ductus arteriosus (pre-ductal, post ductal) o In pre-ductal types, ductus arteriosus persist allowing blood flow o In post ductal collateral circulations must be established for proper perfusion of body and legs o Diagnosis: Young adults may be asymptomatic Can get hypertension + dec lower extremity pulses Causes systemic HT and secondary left ventricular hypertrophy with heart failure o Treatment Considered for patients with gradients greater than 30mmHg on cardiac catheter Balloon angioplasty

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Cyanotic Heart Lesions 4

Cyanotic congenital heart disease: a group of cardiac diseases with a right to left shunt or RIGHT heart abnormality Persistent Truncus Arteriosus o Single Artery (truncus) arises from the heart supplying both aorta and pulmonary artery o A large VSD (ventricular septal defect) below the truncal valve allows mixing of right and left ventricular blood o Degree of cyanosis is variable o Presents with progressive heart failure o Continued aorta and pulmonary artery o Opening between ventricles Transposition of Great vessels o Aorta and pulmonary artery vessels have been switched o Opening between atria o Open ductus arteriosus o Conotruncal septum fails to follow spiral course runs straight down o Ex. Blue baby Immediate surgical intervention Catherterisation of fossa ovalis to inc mixing of pulmonary and systemic blood Buys time will infant can be operated at later date Tetralogy of Fallot o 4 lesions: Aorta shifted to the right and rises directly above ventricular septal defect RV hypertrophy due to high RV pressure Ventricular septal defect Narrow RV outflow (infundibular stenosis) Pulmonary stenosis Blood from both ventricles is pumped into the body Sometimes pulmonary valve is completely obstructed pulmonary atresia Cyanosis occurs as some oxygen-poor blood is pumped into the body o Cyanosis varies with degree of outflow obstruction and size of VSD o Cyanosis is caused by right to left shunting through the VSD o Correction: Early repair, unless patient is premature or low birth weight VSD is closed with patch Obstructing RV muscle is removed All other outflow tract abnormalities are addressed Tricuspid Atresia Total Anomalous pulmonary venous return

5) Describe foetal and neonatal circulation, and the adult derivatives of foetal vascular structures Foetus: o The foramen ovale connects the two atria and allows blood entering the right side of heart to bypass pulmonary circuit and collapsed non-functional fetal lungs o Ductus Arteriosus: Between pulmonary trunk and Aorta Baby: o Foramen ovale becomes fossa ovalis o Ductus Arteriosus Ligamentum Arteriosum (fibrous remnant)

Heart and Exercise

In people who exercise regularly heart increases in size and becomes a more efficient and powerful pump SV inc and resting HR dec Aerobic exercise helps clear fatty deposits from blood vessel walls, retarding atherosclerosis Regularity is important during exercise 30mins a day Intermittent vigorous exercise can cause: o MI o Push an unconditioned heart beyond its ability to respond to unexpected demands

Age-related Changes Sclerosis and thickening of valve flaps o Occurs where stress of blood flow is greatest (mitral valve) o Hence heart murmurs are more common in elderly people Decline in cardiac reserve: o Aged heart is less able to respond to both sudden and prolonged stressors that demand inc CO o Sympathetic control of heart becomes less efficient Amount of cAMP produced with age dec o HR becomes more variable and there is a decline in max HR Fibrosis of Cardiac Muscle o As a person ages more and more cardiac cells die and are replacedwith fibrous tissue o Heart stiffens and its filling for next heart beat is less efficient o Reduced SV o Nodes of the hearts conduction system become fibrosed with age o Inc incidence of arrhythmias Atherosclerosis o Hypertensive HD and Coronary artery occlusion inc risk of heart attack and stroke How is Foetus different from the neonate? Foetal haemoglobin Placenta Foetal Circulation Placental input and output o Baby Placenta Umbilical Arteries (internal Iliac arteries) Deoxygenated, high pressure o Placenta Baby Umbilical veins (becomes the ductus venosus) Oxygenated, low pressure Foetal Circulation Reduced pulmonary blood flow Ductus Arteriosus o Protects lungs against circulatory overload o Allows RV to strengthen o High pulmonary vascular resistance, low pulmonary blood flow o Carries moderately saturated blood Ductus Venosus (continuation of umbilical vein) o Connects umbilical vein to IVC o Flow regulated via sphincter o Conducts highly oxygenated blood Foramen Ovale 6

o Shunts highly oxygenated blood from RA to LA RV pumps 2/3 cardiac output

Adaptations at Birth Umbilical Vein: o Becomes the ligamentum teres (umbilicus to the liver) o The mesentery becomes the falciform ligament Ductus Venosus o Constricts so all the blood passes through the hepatic sinusoids Foramen Ovale o Decreased flow from placenta and IVC causes lower Pressure in RA o Dec pulmonary vascular resistance secondary to lung expansion o Inc in pulmonary blood flow raising LA pressure to higher than that of the IVC o Closes due to increase pressure in LA compared to RA Ductus Arteriosus o Closed by inc PO2 ligamentum arteriosum o Due to decreased pulmonary vascular resistance, Pulmonary Arterial pressure falls below systemic pressure and blood flow through the ductus arteriosus is diminished o Closing it o Bradykinin mediates closure o Prostaglandin E2 may reopen Ductus Arteriosus Umbilical Arteries o Constricts but some parts remain patent and supply the bladder