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Tetralogy of Fallot

Definition:
Tetralogy of Fallot (TOF) is an abnormality of the heart and major blood vessels, which may be found in babies.

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It’s one of the most complex heart problems, as there are four different abnormalities (hence the term ‘tetralogy’):

•A large ventricular septal defect – one of the more serious types of hole in the heart, in which there is a connection between the two main pumping chambers of the heart (ventricles)

•Narrowing of the pulmonary valve (pulmonary stenosis) – this means the heart has to work harder to pump blood into the lungs to collect oxygen

•Right ventricular hypertrophy – thickening of the muscle wall of the right ventricle

•A displaced aorta – the major blood vessel that takes blood out of the heart and directs it around the body

Although these are the main problems, every child is different and there may be all sorts of other abnormalities.

Tetralogy of Fallot occurs in approximately 400 per million live births.

It was described in 1672 by Niels Stensen, in 1773 by Edward Sandifort, and in 1888 by the French physician Étienne-Louis Arthur Fallot, for whom it is named.

Symptoms:
Tetralogy of Fallot symptoms vary, depending on the extent of obstruction of blood flow out of the right ventricle and into the lungs. Signs and symptoms may include:

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You may click to see different pictures of Tetralogy of Fallot

*A bluish coloration of the skin caused by blood low in oxygen (cyanosis)

*Shortness of breath and rapid breathing, especially during feeding

*Loss of consciousness (fainting)

*Clubbing of fingers and toes — an abnormal, rounded shape of the nail bed

*Poor weight gain

*Tiring easily during play

*Irritability

*Prolonged crying

*A heart murmur

Tet spells
Sometimes, babies with tetralogy of Fallot will suddenly develop deep blue skin, nails and lips after crying, feeding, having a bowel movement, or kicking his or her legs upon awakening. These episodes are called “Tet spells” and are caused by a rapid drop in the amount of oxygen in the blood. Toddlers or older children may instinctively squat when they are short of breath. Squatting increases blood flow to the lungs. Tet spells are more common in young infants, around 2 to 4 months old.

Seek medical help if you notice that your baby has the following symptoms:

*Difficulty breathing

*Bluish discoloration of the skin

*Passing out or seizures

*Weakness

*Unusual irritability

If your baby becomes blue (cyanotic), immediately place your child on his or her side and pull the knees up to the chest. This helps increase blood flow to the lungs.

Causes:–
The cause of TOF isn’t fully understood. While a baby is in the womb, something interferes with the development of the heart and major blood vessels.

Its cause is thought to be due to environmental or genetic factors or a combination. It is associated with chromosome 22 deletions and DiGeorge syndrome.

Specific genetic associations include:

JAG1[4]
NKX2-5[5]
ZFPM2[6]
VEGF[7]
It occurs slightly more often in males than in females.

Embryology studies show that it is a result of anterior malalignment of the aorticopulmonary septum, resulting in the clinical combination of a VSD, pulmonary stenosis, and an overriding aorta. Right ventricular hypertrophy results from this combination, which causes resistance to blood flow from the right ventricle.

Although no specific single genetic abnormality has yet been found to explain every case, genetics often do play a part in these types of malformations (known as conotruncal abnormalities). In some children, a particular genetic problem can be identified, such as DiGeorge syndrome, where a small piece of chromosome 22 is lost or deleted.

Some researchers have suggested that TOF is caused by an autosomal recessive gene that has yet to be identified and which has variable penetrance (that is, it doesn’t always cause disease).

However, this is far from proven and TOF has also been linked to environmental factors such as certain medications or alcohol taken by the mother while pregnant.

Whatever the cause, in those families who have a child with TOF, the risk of a second child being born with the condition is only increased very slightly.

Risk factors:-
While the exact cause of tetralogy of Fallot is unknown, several factors may increase the risk of a baby being born with this condition. These include:

*A viral illness in the mother, such as rubella (German measles), during pregnancy

*Maternal alcoholism

*Poor nutrition

*A mother older than 40

*A parent with tetralogy of Fallot

*Babies who are also born with Down syndrome or DiGeorge syndrome

Diagnosis:-
The abnormal “coeur-en-sabot” (boot-like) appearance of a heart with tetralogy of Fallot is easily visible via chest x-ray, and before more sophisticated techniques became available, this was the definitive method of diagnosis. Congenital heart defects are now diagnosed with echocardiography, which is quick, involves no radiation, is very specific, and can be done prenatally.

Treatment:-
Emergency management of tet spells:

Prior to corrective surgery, children with tetralogy of Fallot may be prone to consequential acute hypoxia (tet spells), characterized by sudden cyanosis and syncope. These may be treated with beta-blockers such as propranolol, but acute episodes may require rapid intervention with morphine to reduce ventilatory drive and a vasopressor such as epinephrine, phenylephrine, or norepinephrine to increase blood pressure. Oxygen is effective in treating spells because it is a potent pulmonary vasodilator and systemic vasoconstrictor. This allows more blood flow to the lungs. There are also simple procedures such as squatting and the knee chest position which increases aortic wave reflection, increasing pressure on the left side of the heart, decreasing the right to left shunt thus decreasing the amount of deoxygenated blood entering the systemic circulation.

Palliative surgery:
The condition was initially thought untreatable until surgeon Alfred Blalock, cardiologist Helen B. Taussig, and lab assistant Vivien Thomas at Johns Hopkins University developed a palliative surgical procedure, which involved forming an anastomosis between the subclavian artery and the pulmonary artery (See movie “Something the Lord Made”). It was actually Helen Taussig who convinced Alfred Blalock that the shunt was going to work. This redirected a large portion of the partially oxygenated blood leaving the heart for the body into the lungs, increasing flow through the pulmonary circuit, and greatly relieving symptoms in patients. The first Blalock-Thomas-Taussig shunt surgery was performed on 15-month old Eileen Saxon on November 29, 1944 with dramatic results.

The Potts shunt and the Waterston-Cooley shunt are other shunt procedures which were developed for the same purpose. These are no longer used.

Currently, Blalock-Thomas-Taussig shunts are not normally performed on infants with TOF except for severe variants such as TOF with pulmonary atresia (pseudotruncus arteriosus).

…

Total surgical repair:
The Blalock-Thomas-Taussig procedure, initially the only surgical treatment available for Tetralogy of Fallot, was palliative but not curative. The first total repair of Tetralogy of Fallot was done by a team led by C. Walton Lillehei at the University of Minnesota in 1954 on a 11-year-old boy. Total repair on infants has had success from 1981, with research indicating that it has a comparatively low mortality rate.

Total repair of Tetralogy of Fallot initially carried a high mortality risk. This risk has gone down steadily over the years. Surgery is now often carried out in infants one year of age or younger with less than 5% perioperative mortality. The open-heart surgery is designed (1) to relieve the right ventricular outflow tract stenosis by careful resection of muscle and (2) to repair the VSD with a Gore-Tex patch or a homograft. Additional reparative or reconstructive surgery may be done on patients as required by their particular cardiac anatomy

Prognosis:-
Untreated, Tetralogy of Fallot rapidly results in progressive right ventricular hypertrophy due to the increased resistance on the right ventricle. This progresses to heart failure (dilated cardiomyopathy) which begins in the right heart and often leads to left heart failure. Actuarial survival for untreated Tetralogy of Fallot is approximately 75% after the first year of life, 60% by four years, 30% by ten years, and 5% by forty years.

Patients who have undergone total surgical repair of Tetralogy of Fallot have improved hemodynamics and often have good to excellent cardiac function after the operation with some to no exercise intolerance (New York Heart Association Class I-II). Surgical success and long-term outcome greatly depends on the particular anatomy of the patient and the surgeon’s skill and experience with this type of repair.

Ninety percent of patients with total repair as infants develop a progressively leaky pulmonary valve as the heart grows to its adult size but the valve does not. Patients also may have damage to the electrical system of the heart from surgical incisions if the middle cardiac nerve is accidentally tapped during surgery. If the nerve is touched, it will cause abnormalities as detected by EKG and/or arrhythmias.

Long-term follow up studies show that patients with total repair of TOF are at risk for sudden cardiac death and for heart failure. Therefore, lifetime follow-up care by an adult congenital cardiologist is recommended to monitor these risks and to recommend treatment, such as interventional procedures or re-operation, if it becomes necessary.

The use of antibiotics is no longer required by cardiologists and varies from case to case.

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.

Resources:–
http://www.bbc.co.uk/health/physical_health/conditions/fallotstetralogy.shtml
http://en.wikipedia.org/wiki/Tetralogy_of_Fallot
http://www.drattawarsandeep.com/tetralogy_of_fallot.php
http://www.mayoclinic.com/health/tetralogy-of-fallot/DS00615/DSECTION

Tetralogy Of Fallot ( TOF )

Family copes with rare heart defect (bendbulletin.com)
Procedure replaces heart valve, avoids open-heart surgery (physorg.com)
Minorities Born With Heart Defects At Higher Risk Of Dying In Early Childhood Than Whites (medicalnewstoday.com)
A Guide to the Cardiac Catheter Procedure (brighthub.com)
The Adorable Kid Behind The VW Darth Vader Commercial Has A Pacemaker (gizmodo.com.au)
A Surgical Assistant with Hands Blessed by God: Vivien Thomas (3quarksdaily.com)
Darth Vader Super Bowl Commercial Star Is Six-Year-Old Heart Patient Max Pagehasm (sbnation.com)
Pint-size Vader from Super Bowl VW commercial unmasked (slashgear.com)
The Making of “The Force” Commercial (mymodernmet.com)

Thymoma

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Introduction
Thymoma, the most common neoplasm of the anterior mediastinum, originates within the epithelial cells of the thymus.

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The thymus is a lymphoid organ located in the anterior mediastinum. In early life, the thymus is responsible for the development and maturation of cell-mediated immunological functions. The thymus is composed predominantly of epithelial cells and lymphocytes. Precursor cells migrate to the thymus and differentiate into lymphocytes. Most of these lymphocytes are destroyed, with the remainder of these cells migrating to tissues to become T lymphocytes. The thymus gland is located behind the sternum in front of the great vessels; it reaches its maximum weight at puberty and undergoes involution thereafter.

In human anatomy, the thymus is an organ located in the upper anterior portion of the chest cavity just behind the sternum. The main function of the thymus is to provide an area for T cell maturation, and is vital in protecting against autoimmunity.

Etiology:-
The etiology of thymomas has not been elucidated; however, it has been associated with various systemic syndromes. As many as 30-40% of patients who have a thymoma experience symptoms suggestive of MG. An additional 5% of patients who have a thymoma have other systemic syndromes, including red cell aplasia, dermatomyositis, systemic lupus erythematous, Cushing syndrome, and syndrome of inappropriate antidiuretic hormone secretion.

History:-
The thymus was known to the Ancient Greeks, and its name comes from the Greek word ??µ?? (thumos), meaning heart, soul, desire, life – possibly because of its location in the chest, near where emotions are subjectively felt; or else the name comes from the herb thyme (also in Greek ??µ??), which became the name for a “warty excrescence”, possibly due to its resemblance to a bunch of thyme.

Galen was the first to note that the size of the organ changed over the duration of a person’s life.

Due to the large numbers of apoptotic lymphocytes, the thymus was originally dismissed as a “lymphocyte graveyard”, without functional importance. The importance of the thymus in the immune system was discovered in 1961 by Jacques Miller, by surgically removing the thymus from three day old mice, and observing the subsequent deficiency in a lymphocyte population, subsequently named T cells after the organ of their origin. Recently, advances in immunology have allowed the function of the thymus in T cell maturation to be more fully understood.

Function:-
In the two thymic lobes, lymphocyte precursors from the bone-marrow become thymocytes, and subsequently mature into T cells. Once mature, T cells emigrate from the thymus and constitute the peripheral T cell repertoire responsible for directing many facets of the adaptive immune system. Loss of the thymus at an early age through genetic mutation (as in DiGeorge Syndrome) or surgical removal results in severe immunodeficiency and a high susceptibility to infection.

The stock of T-lymphocytes is built up in early life, so the function of the thymus is diminished in adults. It is largely degenerated in elderly adults and is barely identifiable, consisting mostly of fatty tissue, but it continues to function as an endocrine gland important in stimulating the immune system.[8] Involution of the thymus has been linked to loss of immune function in the elderly, susceptibility to infection and to cancer.

The ability of T cells to recognize foreign antigens is mediated by the T cell receptor. The T cell receptor undergoes genetic rearrangement during thymocyte maturation, resulting in each T cell bearing a unique T cell receptor, specific to a limited set of peptide:MHC combinations. The random nature of the genetic rearrangement results in a requirement of central tolerance mechanisms to remove or inactivate those T cells which bear a T cell receptor with the ability to recognise self-peptides.

Iodine, thymus and immunity:-
Iodine has important actions in the immune system. The high iodide-concentration of thymus suggests an anatomical rationale for this role of iodine in immune system.

Phases of thymocyte maturation:-
The generation of T cells expressing distinct T cell receptors occurs within the thymus, and can be conceptually divided into three phases:

1.A rare population of hematopoietic progenitor cells enter the thymus from the blood, and expands by cell division to generate a large population of immature thymocytes.

2.Immature thymocytes each make distinct T cell receptors by a process of gene rearrangement. This process is error-prone, and some thymocytes fail to make functional T cell receptors, whereas other thymocytes make T cell receptors that are autoreactive. Growth factors include thymopoietin and thymosin.

3.Immature thymocytes undergo a process of selection, based on the specificity of their T cell receptors. This involves selection of T cells that are functional (positive selection), and elimination of T cells that are autoreactive (negative selection).

Anatomy:–
The thymus is of a pinkish-gray color, soft, and lobulated on its surfaces. At birth it is about 5 cm in length, 4 cm in breadth, and about 6 mm in thickness. The organ enlarges during childhood, and atrophies at puberty. Unlike the liver, kidney and heart, for instance, the thymus is at its largest in children. The thymus reaches maximum weight (20 to 37 grams) by the time of puberty. It remains active only until puberty. Then with growing age, it starts to shrink. The thymus gland of older people is scarcely distinguishable from surrounding fatty tissue. As one ages the thymus slowly shrinks, eventually degenerating into tiny islands of fatty tissue. By the age of 75 years, the thymus gland weighs only 6 grams. In children the thymus is grayish-pink in colour and in adults it is yellow.
Presentation:-
Peak incidence of thymoma occurs in the fourth to fifth decade of life; mean age of patients is 52 years. No sexual predilection exists. Although development of a thymoma in childhood is rare, children are more likely than adults to have symptoms. Several explanations for the prevalence of symptoms in children have been proposed, including the following: (1) children are more likely to have malignancy, (2) lesions are more likely to cause symptoms by compression or invasion in the smaller thoracic cavity of a child, and (3) the most common location for mediastinal tumors in children is near the trachea, resulting in respiratory symptoms.

Four cases of patients who presented with severe chest pain secondary to infarction or hemorrhage of the tumor have been reported. Cases of invasion into the superior vena cava resulting in venous obstruction have also been reported.2 The clinician should be aware of these rare presentations of a thymoma.

The thymus will, if examined when its growth is most active, be found to consist of two lateral lobes placed in close contact along the middle line, situated partly in the thorax, partly in the neck, and extending from the fourth costal cartilage upward, as high as the lower border of the thyroid gland. It is covered by the sternum, and by the origins of the sternohyoidei and sternothyreoidei. Below, it rests upon the pericardium, being separated from the aortic arch and great vessels by a layer of fascia. In the neck, it lies on the front and sides of the trachea, behind the sternohyoidei and sternothyreoidei. The two lobes differ in size and may be united or separated

Problem:-
No clear histologic distinction between benign and malignant thymomas exists. The propensity of a thymoma to be malignant is determined by the invasiveness of the thymoma. Malignant thymomas can invade the vasculature, lymphatics, and adjacent structures within the mediastinum. The 15-year survival rate of a person with an invasive thymoma is 12.5%, and it is 47% for a person with a noninvasive thymoma. Death usually occurs from cardiac tamponade or other cardiorespiratory complications.

Frequency:-
Thymoma, the most common neoplasm of the anterior mediastinum, accounts for 20-25% of all mediastinal tumors and 50% of anterior mediastinal masses

Two primary forms of tumours originate in the thymus.

Tumours originating from the thymic epithelial cells are called thymomas, and are found in about 10-15% of patients with myasthenia gravis. Symptoms are sometimes confused with bronchitis or a strong cough because the tumor presses on the recurrent laryngeal nerve. All thymomas are potentially cancerous, but they can vary a great deal. Some grow very slowly. Others grow rapidly and can spread to surrounding tissues. Treatment of thymomas often requires surgery to remove the entire thymus. Tumours originating from the thymocytes are called thymic lymphomas.

Radiation Induced:-
People with enlarged thymus glands, particularly children, were treated with intense radiation in the years before 1950. There is an elevated incidence of thyroid cancer and leukemia in treated individuals.

Resources:
http://emedicine.medscape.com/article/193809-overview
http://en.wikipedia.org/wiki/Thymus