Essay On Heart Embryology Notes

How does the heart develop? What developmental abnormalities arise when this process is defective?

The heart, unlike other organs begins to function as soon as it has formed and it starts to beat and pump blood by day 22. The spontaneous contraction is initiated by the pacemaker region in the SAN which then spreads throughout the myocytes in a specific pattern and this leads to timely contraction of the atria and ventricles. The heart is derived from the lateral plate splanchiopleuric mesoderm that is cranial to the neural tube and from neural crest cells. The following key steps are important in forming a functional heart; the formation of a primitive heart tube and its blood vessels, the looping of the heart, separation of the pulmonary and systemic circulation and septation of the atria and ventricles. However due to the complexity in the processes that are required to form a functional heart, congenital cardiovascular defects often occur which accounts for 20% of all defects seen in newborns.

Heart formation begins when mesodermal cells from the cranial pole of the primitive streak (Cardiac progenitor cells) migrate cranially and laterally to form the left and right heart fields. At the end of the week 3 these mesodermal cells between the endoderm of the primary yolk sac and the splanchnic mesoderm proliferate in the cranial and lateral regions to form angiogenic clusters which join to form the cardiac crescent (primary heart field). Key cardiogenic signals are BMP and FGF which are secreted by the endoderm and induce the expression of cardiac specific transcription factors such as homeodomain protein Nkx2.5 and this stimulates a downward cascade of expression of various other transcription factors which leads to the expression of cardiac muscle specific proteins. The posterior limbs of the crescent, known as the endocardial tubes, fuse at the midline during rostral and lateral folding of the embryo and are positioned in the thorax. Through programmed cell death at the contact regions the 2 endocardial tubes form a single tube known as the primitive heart tube. Errors in the formation of the 2 separate endocardial tubes results in cardia bifida.

The primitive heart tube, suspended in the pericardial cavity, initially consists of a thin layer of endothelium but once formed mesenchymal cells from the mesoderm attach to the endothelium where it differentiates into the myocardium. The myocardium secretes a large amount of hyaluronic acid and proteoglycans to form another layer known as the cardiac jelly which seperates the myocardium from the endothelium. The epicardium surrounds the myocardium and is also derived from the splanchnic mesoderm.

Whilst the primitive heart tube is forming, inflow and outflow tracts are formed through the fusion of various tubes. The paried dorsal aortae,which is the primary outflow tract of the heart, are formed from the mesenchyme either side of the notochord and fuses with the superior end of the primitive heart tube. Folding of the embryo causes the paired dorsal aortae to from the dorsal ventral arch. The inflow tracts of the heart develop at the inferior end of the primitive tube and consist of the sinus venosus which is made up of the left and right sinus horns. Each of the sinus horns have three pairs of vessels draining into them; the vitelline veins drain the yolk sac, the cardinal veins drains the body and the umbilical veins brings oxygenated blood from the placenta.

Following this, on day 21 the primary heart tube undergoes rostro-caudal patterning and it becomes segmented into various chambers through a process of constrictions and expansions. Above the left and right sinus horns of the sinus venosus the first chamber to form is the primitive atrium which eventually gives rise to both the left and right atrium. Key signalling factors that leads to atrialisation is retinoic acid which was shown to induce the formation of atria in chick embryo. The retinoic acid induces the expression of the atrial myosin heavy chain AMCH1. Cranial to the primitive atrium is the ventricle which gives rise to the left ventricle and in this chamber there is selective expression of ventricular myosin heavy chain 1. Between the primitive atrium and the ventricle is an atrioventricular sulcus. The chamber above the ventricle, separated by the interventricular sulcus, is known as the bulbus cordis and its inferior region gives rise to the right ventricle whilst the superior region forms the conotruncus. The conotruncus becomes the outflow tracts, aortae and pulmonary arteries which arise eventually rise from the left and right ventricles. The primitive heart tube lengthens due to dorsal migration of mesodermal cells from the secondary heart field which adds to the cranial and caudal poles by proliferating. Cell lineage studies provide evidence for this process.

The next stage in heart development is the looping of the primary heart tube where the chambers of the heart are correctly positioned. Between days 23 to 28 differential proliferation causes the heart tube to elongate and causes the atria to migrate cranially to the ventricle. The ventricle enlarges and is shifted to the left whereas the bulbus cordis is positioned inferiorly and more to the right. The driving force that is responsible for the looping is due to the flow of the blood which results in cells in different regions of the heart to proliferate at different rates. The resulting change caused by the looping is the first sign of the left/right asymmetry. Further left and right differences are induced by the primitive node which causes differential gene expression; HAND1 gene is expressed in the left whereas HAND 2 is expressed in the right ventricle. If the primitive heart tube folds to the right instead of the left patients suffer from dextrocardia and this is caused by situs inversus.

The left/right asymmetry is also shown in the redistribution of the vessels connecting the primitive heart tube....

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