Embryology of the Heart

Tube Formation

The heart is the first organ to function within an embryo. It starts to function at the beginning of the fourth week when the nutritional and oxygen requirements of the growing embryo can no longer be met by diffusion from the placenta. The heart initially forms from two tubes located bilaterally (on either side) of the trilaminar embryo in the cranial (head) region.

When looking down at this early embryo you can see multiple blood islands dispersed throughout the embryo. These will form the early blood vessels. At the most cranial end of the embryonic disc these blood islands are actually the primitive heart tube. From the side you can see one of the heart tubes and heart cavity developing in this position.

Clinical Correlations
The cardiac precursor cells migrate anteriorly towards the midline and fuse into a single heart tube.
If this migration event is blocked, cardia bifida results where the two heart primordia remain separated. During fusion, the heart tube is patterned along the anterior/posterior axis for the various regions and chambers of the heart.

Cardiac Looping

At this stage the tube already has minor constrictions within it, indicating sections of the heart tube that will form parts of the adult heart. The most caudal (tail end) segment of the heart tube is the sinus venosus which will later become the ends of the major veins carrying blood to the heart as well as parts of the atria. The next segments are the primitive atrium and primitive ventricle which will become the atria and ventricles of the adult heart. Cranial to these segments are the bulbus cordis, most of which will become the right ventricle, and the truncus arteriosus which forms the pulmonary and aortic trunks carrying blood away from the heart. This tubular heart undergoes a process of looping during week four of development to form a shape that resembles that of the adult heart. It initially forms a C-shape (with the convex portion of the C situated on the right side of the embryo) and then an S-shape. Eventually the atria are brought backwards and upwards so that they lie cranially and behind the ventricles.

Clinical Correlations
Abnormalities of Cardiac Looping
Dextrocardia: heart lies on the right side of the thorax instead of left, is caused by the heart looping to the left instead of right Situs Invertus:
A complete reversal of asymmetry in all organs Occurs in 1/7000 individuals Associated with normal physiology, although there is a slight risk of heart defects

Atrial and Ventricular Septation

1. Division of atrio-ventricular canal

Cells from the dorsal and ventral (back and front) walls of the heart grow and form two protrusions called the endocardial cushions. These grow towards each other and fuse to form the left and right atrioventricular canals.

Endocardial cushions and heart defects

Because of their location, abnormality in the endocardial cushion formation contribute to many cardiac malformations, including atrial and ventricular septal defects and defects involving the great vessels (transposition of great vessels and tetralogy of Fallot). Since the cells populating the conotruncal cushions include neural crest cells and since crest cells also contribute extensively to development of head and neck, abnormalities in these cells produced by teratogenic agents or genetic causes often produce craniofacial defects in the same individual.

2. Early atrial septation

Within the primordial atrium a septum (the septum primum) grows towards the endocardial cushions. The space between the cushions and septum is known as the foramen primum. As the foramen primum decreases in size a second opening forms in the septum: the foramen secundum.

3. Atrial and ventricle septation (Week 5)

A second septum (septum secundum) develops on the right of the septum primum.

4. Atrial and ventricle septation (Week 6)

A primordial muscular ridge exists in the floor of the ventricle. As the left and right ventricles grow, their medial (midline) walls fuse to form the interventricular septum.

Outflow tract septation

5. Development of the conotruncal ridges

Within the bulbus cordis and truncus arteriosus, which form the outflow tract, small ridges develop. They are continuous throughout the outflow tract and form a spiral shape.

6. Division of the outflow tract forms the aorta and pulmonary trunk

As these ridges fuse they create a spiral shaped septum throughout the outflow tract. The original outflow tract is therefore separated into both the aorta and pulmonary trunk.

Valvular defects
1. Valvular stenosis of pulmonary artery or aorta when the semilunar valves are fused for a variable distance.
Valvular stenosis of pulmonary artery: trunk is narrow or atretic, patent foramen ovale is the only outlet Valvular stenosis of aorta: fusion of thickened valves may be so complete that only a pinhole opening remains. Size of aorta itself is normal

2. Aortic valvular atresia: aorta, LV and LA are underdeveloped. Accompanied by open ductus arteriosus which delivers blood into aorta.

Cardiac Malformations
Cardiac malformations are caused by interplay of environmental and genetic causes. Examples of teratogens:
Classically, rubella virus and thalidomide Others: retinoic acid, alcohol

Other links: maternal diseases such as insulin dependant diabetes and hypertension

Chromosomal Defects
33% of children with chromosomal abnormality have a congenital heart malformation, with 100% incidence in trisomy 18(Edwards Syndrome) Cardiac malformations associated with genetic abnormality with craniofacial abnormalities such as DiGeorge, Goldenhar and Down Syndrome

Trisomy 18
Associated with VSD, ASD & coarctation of aorta

Trisomy 21
Associated with ASD & VSD

DiGeorge Syndrome

Associated with conotruncal malformations (tetralogy of Fallot, interrupted aortic arch, ventricular septal defect, and persistent truncus arteriosus)

Goldenhars

Associated with conotruncal heart defects

Embryonic circulation

Development of veins
Blood travels through the embryonic heart from the sinus venosus. There are three paired veins which form to drain into the sinus venosus:
Vitelline veins - return poorly oxygenated blood from the yolk sac Umbilical veins - carry well-oxygenated blood from the primordial placenta Common cardinal veins - return poorly oxygenated blood from the body of the embryo

The sinus venosus soon shifts to the right to be incorporated into the right atrium as there is a shift in the venous system from the left to the right side of the embryo. The inferior vena cava and superior vena cava form and drain into the sinus venosus. In the left atrium the four pulmonary veins form, which will return oxygenated blood from the lungs.

Development of Arteries
The dorsal aortae develop at the same time as the early heart tubes. These connect to the heart tubes prior to fusion via the first aortic arch arteries. Other arches develop, which go on to form the arteries of the head and neck. The dorsal aorta gives off branches which supply blood to the rest of the embryo:
Gut (ventral/front) branches Lateral (side) branches Intersegmental arteries

Fetal Circulation
As the embryo progresses to a fetus the vasculature is still remarkably different to that of the adult, including the presence of three vascular shunts:
foramen ovale - blood travels from the right atrium to the left atrium ductus venosus - blood from the umbilical vein bypasses the liver to enter the inferior vena cava ductus arteriosus - blood passes from the pulmonary trunk into the aorta

These shunts allow blood to bypass the lungs, liver and kidneys, whose functions are performed by the placenta while in utero.

 The movement of blood throughout the fetal circulation. The main flow of blood is as follows:
Placenta umbilical vein ductus venosus inferior vena cava right atrium foramen ovale left atrium left ventricle aorta hypogastric arteries umbilical arteries placenta.

Blood that passes from the right atrium to the right ventricle travels:
Right ventricle pulmonary trunk ductus arteriosus aorta

Fetal circulation

Circulatory changes at Birth

With birth, a change from parallel flow through the heart to a serial one gradually takes place. The following changes must occur:
The gas exchange takes place in the baby's lungs. By cutting the umbilical cord, the placental circulation system is switched off. The fetal heart shunts become closed.

Postnatal circulatory changes

RA pressure < LA pressure

Disappearance of placental resistence by cutting of umbilical cord

Pressure in aorta > truncus pulmonalis changes R->L to L->R

Contraction of the smooth musculature in the wall of the ductus arteriosus

1st breath, increase alveolar PO2 causes vasodilation

Clinical Correlations
Patent Foramen Ovale
Failure of the foramen ovale to close at birth, e.g., due to faulty development of the septum primum and/or septum secundum. This condition is usually physiologically insignificant.

Patent Ductus Arteriosus

Failure of the ductus arteriosus to close after birth. Patients with some heart anomalies can survive only if they have a patent ductus arteriosus. Administration of prostaglandins can delay the closure of the ductus arteriosus. Conversely, drugs that inhibit prostaglandin synthesis (e.g. with indomethacin) can sometimes be used to close the ductus arteriosus without surgery.

Anatomy of Heart
The circulatory system Blood vessels The heart Coronary circulation

The circulatory system

There are about 100 trillion cells in the human body. For each of these cells to survive and perform its function, each cell needs to receive nutrition, replenish oxygen and remove waste. The circulatory system performs these functions for the cells. The circulatory system is the major highway network in the body.
The arteries, veins and capillaries are the conduits. The blood is the transportation medium. The entire system is powered by the heart, the main pump.

Blood vessels

Connection of vessels

The Heart
The heart is a hollow muscle that pumps blood throughout the blood vessels by repeated, rhythmic contractions. It is found in all animals with a circulatory system The vertebrate heart is principally composed of cardiac muscle and connective tissue. Cardiac muscle is an involuntary striated muscle tissue found only in this organ and responsible for the ability of the heart to pump blood. The average human heart, beating at 72 beats per minute, will beat approximately 2.5 billion times during an average 66 year lifespan. It weighs approximately 250 to 300 grams (9 to 11 oz) in females and 300 to 350 grams (11 to 12 oz) in males.

Human heart
The adult human heart has a mass of between 250 and 350 grams and is about the size of a fist. It is located anterior to the vertebral column and posterior to the sternum. It is enclosed in a double-walled sac called the pericardium. The superficial part of this sac is called the fibrous pericardium.
This sac protects the heart, anchors its surrounding structures, and prevents overfilling of the heart with blood.

The outer wall of the human heart is composed of three layers.

The outer layer is called the epicardium, or visceral pericardium since it is also the inner wall of the pericardium. The middle layer is called the myocardium and is composed of cardiac muscle which contracts. The inner layer is called the endocardium and is in contact with the blood that the heart pumps. Also, it merges with the inner lining (endothelium) of blood vessels and covers heart valves.

Pericardium
Clinical correlations:
Pericarditis Pericardial effusion Constrictive pericarditis

Surface anatomy
The heart is demarcated by:
A point 9 cm to the left of the midsternal line (apex of the heart) The seventh right sternocostal articulation The upper border of the third right costal cartilage 1 cm from the right sternal line The lower border of the second left costal cartilage 2.5 cm from the left lateral sternal line.

Chambers of the heart

The human heart has four chambers, two superior atria and two inferior ventricles.
The atria are the receiving chambers The ventricles are the discharging chambers.

Valves of the heart

Functions to seperate the chambers of the heart:
Tricuspid valves: 3 cusps, provides connection between RA and RV Pulmonary valves: provides continuation between RV and pulmonary trunk Mitral valves: 2 cusps, provides a connection between the LA and the LV Aortic valves: provides continuation between LV and ascending aorta (rise to coronary arteries)

Cardiac valves

Clinical correlations
Valve disease caused by:
Incompetence from poorly functioning valves Stenosis, a narrowed orifice caused by valves inability to open fully

Examples:
Mitral valve disease Aortic valve disease Infections of right side valves

Cardiac auscultation

Heart sounds
The noises generated by the beating heart and the resultant flow of blood through it (specifically, the turbulence created when the heart valves snap shut). In healthy adults, there are two normal heart sounds often described as a lub and a dub (or dup), that occur in sequence with each heartbeat.
These are the first heart sound (S1) and second heart sound (S2), produced by the closing of the AV valves and semilunar valves respectively. In addition to these normal sounds, a variety of other sounds may be present including heart murmurs, adventitious sounds, and gallop rhythms S3 and S4.

Heart murmurs are generated by turbulent flow of blood, which may occur inside or outside the heart.
Murmurs may be physiological (benign) or pathological (abnormal). Abnormal murmurs can be caused by stenosis restricting the opening of a heart valve, resulting in turbulence as blood flows through it. Abnormal murmurs may also occur with valvular insufficiency (or regurgitation), which allows backflow of blood when the incompetent valve closes with only partial effectiveness. Different murmurs are audible in different parts of the cardiac cycle, depending on the cause of the murmur.

Blood Pathway
The pathway of blood through the human heart consists of a pulmonary circuit and a systemic circuit. Deoxygenated blood flows through the heart in one direction, entering through the superior vena cava into the right atrium and is pumped through the tricuspid valve into the right ventricle before being pumped out through the pulmonary valve to the pulmonary arteries into the lungs. It returns from the lungs through the pulmonary veins to the left atrium where it is pumped through the mitral valve into the left ventricle before leaving through the aortic valve to the aorta.

Coronary circulation
There are two major coronary arteries: the right and the left.These two arteries branch out of the aorta immediately after the aortic valve. The right coronary artery splits into the marginal branch, which feeds blood into the right ventricle, and the posterior interventricular branch, which supplies the left ventricle. The left coronary artery is notably larger than the right coronary artery because it feeds the left heart, which, as a result of it's more powerful contractions, requires a more vigorous blood flow. The left coronary artery splits into the anterior interventricular branch and a circumflex branch. The anterior interventricular branch runs towards the apex of the heart, providing blood for both of the ventricles and the ventricular septum. The circumflex branch, on the other hand, follows the groove between the left atrium and the left ventricle, providing blood supply to both of these chambers until it reaches and joins with the right coronary artery in the posterior of the heart.

 Coronary artery disease caused by:

Stenosis or occlusion

Results in myocardial infarct or ischemic heart disease

Innervation of Heart
The heart is innervated by parasympathetic and sympathetic fibers. The medulla is the primary site in the brain for regulating sympathetic and parasympathetic outflow to the heart and blood vessels. The hypothalamus and higher centers modify the activity of the medullary centers and are particularly important in regulating cardiovascular responses to emotion and stress (eg, exercise, thermal stress). Parasympathetic innervation of the heart is controlled by the vagus nerve. To be specific, the vagus nerve acts to lower the heart rate. The right vagus innervates the sinoatrial node. Parasympathetic hyperstimulation predisposes those affected to bradyarrhythmias. The left vagus when hyperstimulated predisposes the heart to atrioventricular (AV) blocks.

Physiology of the heart

Electrical conduction system Mechanical events of cardiac cycle Cardiac output

The function of the heart

The human heart is actually two pumps in one.
The right side receives oxygen-poor blood from the various regions of the body and delivers it to the lungs. In the lungs, oxygen is absorbed in the blood. The left side of the heart receives the oxygen-rich blood from the lungs and delivers it to the rest of the body

The electrical conduction system

Heart's electrical system includes three important parts:
S-A node (sinoatrial node) known as the heart's natural pacemaker, the S-A node has special cells that create the electricity that makes your heart beat. A-V node (atrioventricular node) the A-V node is the bridge between the atria and ventricles. Electrical signals pass from the atria down to the ventricles through the A-V node. His-Purkinje system the His-Purkinje system carries the electrical signals throughout the ventricles to make them contract. The parts of the His-Purkinje system include:
o His Bundle (the start of the system) o Right bundle branch o Left bundle branch o Purkinje fibers (the end of the system)

Cardiac cycle
Consists of three important events: 1. The generation of electrical activity as the heart auto-rhythmically depolarizes and repolarizes 2. Mechanical activity: consisting of systole and diastole 3. Directional flow of blood through the heart chambers

Cardiac cycle
Atrial pressure remains low throughout the cardiac cycle, with minor fluctuations. The aortic pressure curve remains high the entire time, with moderate fluctuations The ventricular pressure curve fluctuates dramatically, because ventricular must be below the low atrial pressure to allow the AV valve to open for filling and to force aortic valve open to allow emptying, it must be above the aortic pressure during systole.

 During periods of isovolumetric ventricular contraction and relaxation, ventricular pressure is above the low atrial pressure and below the high aortic pressure, so all valves are closed and no blood enters or leaves the heart. End-diastolic volume is the volume of blood in the ventricle when filling is complete at the end of diastole. End-systolic volume is the volume of blood remaining in the ventricle when ejection is complete at the end of systole. Stroke volume is the volume of blood pumped out by each ventricle at each heart beat.

Cardiac output and its control

Cardiac output: the volume of blood ejected by each ventricle each minute, is determined by heart rate X stroke volume Heart rate: varied by altering the balance of parasympathetic and sympathetic influence on the SA node. Stroke volume: depends on
1. Intrinsic control: The extent of ventricular filling, with an increased end-diastolic volume resulting in a larger stroke volume by means of the length-tension relationship (Frank-Starling law of the heart) 2. Extrinsic control: The extent of sympathetic stimulation resulting in increased contractility of the heart

 Preload: workload imposed on the heart before contraction begins = extent of filling Afterload: workload imposed on the heart after contraction begins = arterial BP

References
Grays Anatomy for Students, 2nd edition Human physiology, From Cells to Systems, 7th edition Langmans Medical Embryology, 11th edition