Pulmonary hypertension

In normal lungs the pulmonary arterial pressure is about 20/8mmHg (compared with typical
systemic artery systolic/diastolic pressures of 120/80 mmHg) and the mean pulmonary artery
pressure is 1215mmHg. Pulmonary hypertension is defined as a mean pulmonary artery
pressure >25 mmHg at rest. Hypertension occurs as a result of hypoxaemia and chronic lung
disease, when it is often referred to as cor pulmonale, but in some cases there is no demonstrable
cause and this is termed primary pulmonary hypertension.

What is pulmonary hypertension?

The right ventricle pumps blood returning from the body into the pulmonary arteries to the lungs
to receive oxygen. The pressures in the lung arteries (pulmonary arteries) are normally
significantly lower than the pressures in the systemic circulation. When pressure in the
pulmonary circulation becomes abnormally elevated, it is referred to as pulmonary hypertension,
pulmonary artery hypertension, or PAH.
Pulmonary hypertension results from constriction, or stiffening, of the pulmonary arteries that
supply blood to the lungs. Consequently, it becomes more difficult for the heart to pump blood
forward through the lungs. This stress on the heart leads to enlargement of the right heart and
eventually fluid can build up in the liver and other tissues, such as the in the legs.
Classification of pulmonary hypertension

In the conventional classification, pulmonary hypertension, which is also called pulmonary
arterial hypertension, is divided into two main categories:
1) primary pulmonary hypertension (not caused by any other disease or condition)
2) secondary pulmonary hypertension (caused by another underlying condition).
Secondary pulmonary hypertension is much more common than primary pulmonary
hypertension.

A newer classification of this condition is based on the main underlying cause of pulmonary
hypertension. This system classifies the condition based on whether it is due to:
Pulmonary hypertension from a variety of causes, some known and others unknown, such as:
drug-induced pulmonary artery hypertension,
pulmonary artery hypertension associated with collagen vascular diseases, HIV,
and schistosomiasis (a parasitic infection), and
pulmonary arterial hypertension of unknown cause (idiopathic pulmonary arterial
hypertension)
Pulmonary arterial hypertension from left-sided heart disease, often referred to as
pulmonary venous hypertension, including thickening of the heart muscle, decrease heart
pump function, and disorders of the heart valves
Pulmonary arterial hypertension associated with lung disease and or persistent drop in
oxygen levels (hypoxia) including:
COPD (chronic obstructive pulmonary disease),
sleep apnea,
pulmonary fibrosis, and
living at high elevations
Pulmonary arterial hypertension from blood clotting disorders that deliver clots to the
lung (pulmonary emboli) or are formed directly in the lung arteries (pulmonary thrombosis),
also known as chronic thromboembolic pulmonary hypertension;
Pulmonary arterial hypertension from miscellaneous causes with unclear multifactorial
mechanisms; including diseases such as:
sarcoidosis,
tumor obstruction,
metabolic disorders (glycogen storage disease), and
kidney failure

What causes pulmonary hypertension?
There are many causes of pulmonary hypertension. Often more than one mechanism is involved
in a specific disease process. This can also change as the disease progresses.
Hypoxic pulmonary vasoconstriction is the process in which the lung vessels narrow in
attempt to divert blood from poorly functioning segments of the lung. For instance,
when pneumonia develops, a portion of lung becomes inflamed and works poorly in
performing the functions of the lung (to add oxygen and remove carbon dioxide from the
blood). This process diverts blood from these poorly working areas and sends it to better
functioning lung tissue. However, a problem develops when all the blood has a low oxygen
level (hypoxia). This causes constriction of the vessels on the pulmonary arterial side and
hence raises the pressure.
Remodeling of blood vessels also occurs in some diseaseswhereby the inner lining
(lumen) of the vessel becomes narrowed due to inappropriate growth of the tissue within
and around the vessel. Masses and scarring from other diseases can compress and narrow
vessels causing increased resistance to flow resulting in elevation of pressures.
In a fairly common parasitic infection in the Middle East (schistosomiasis), the blood
vessels in the lung become blocked by the parasites causing pulmonary artery hypertension.
Some substances cause constriction of the blood vessels. Pulmonary hypertension has
been rarely reported with the use of anti-obesity drugs, such as dexfenfluramine (Redux)
and Fen/Phen. These medications have seen been removed from the market. Some street
drugs such as, cocaine and methamphetamines can cause severe pulmonary hypertension.
Some diseases raise pulmonary pressures to cause pulmonary artery hypertension for
unclear reasons. Perhaps an unknown toxin or chemical effects the blood vessels by causes
constriction or inappropriate growth of the tissue within or around the vessel. For example,
there is a condition known as portopulmonary hypertension that is result of liver failure.
When these individuals receive a liver transplant, the pulmonary hypertension disappears
suggesting that the failing liver is unable to clear some biochemical that leads to pulmonary
artery hypertension.
Low-oxygen conditions. High altitude living, obesity, and sleep apnea can also lead to the
development of pulmonary hypertension.

Primary Pulmonary Hypertension
Primary pulmonary hypertension has no identifiable underlying cause. Primary pulmonary
hypertension is also referred to as idiopathic pulmonary hypertension. Primary pulmonary
hypertension is more common in young people and more common in females than males.
Primary pulmonary hypertension is an unusually aggressive and often fatal form of pulmonary
hypertension. Whereas it is known that the arterial obstruction is caused by a building up of the
smooth muscle cells that line the arteries, the underlying cause of the disease has long been a
mystery.
A genetic cause of the familial form of primary pulmonary hypertension has been discovered. It
is caused by mutations in a gene called BMPR2. BMPR2 encodes a receptor (a transforming
growth factor beta type II receptor) that sits on the surface of cells and binds molecules of the
TGF-beta superfamily. Binding triggers conformational changes that are shunted down into the
cell's interior where a series of biochemical reactions occur, ultimately affecting the cell's
behavior. The mutations block this process. This discovery may provide a means of genetic
diagnosis and a potential target for the therapy of people with familial (and possibly also
sporadic) primary pulmonary hypertension.

How common is pulmonary hypertension?
There are no clear statistical data on the prevalence of pulmonary hypertension. Since pulmonary
hypertension is seen in multiple different conditions, it is perhaps better to look at the prevalence
in each condition. It is fairly common in patients with heart failure, COPD, and sleep apnea. It
occurs in 7% to 12% of patients with collagen vascular disease and in less than 5% of HIV
patients.
Signs and symptoms
Many people with pulmonary hypertension may have no symptoms at all, especially if the
disease is mild or in the early stages.
Pulmonary hypertension symptoms may include:
Shortness of breath that worsens with activity
Other common complaints are cough,fatigue, dizziness, and lethargy.
With the advancement of the condition and ensuing right heart failure, shortness of breath
may become worse and retention of fluid in the body may increase (due to failure of the
heart to pump blood forward) resulting in swelling the legs.
People may also complain of chest pain and angina.
Depending on the underlying associated disease, pulmonary artery hypertension can have
other manifestations. For example, characteristic skin changes seen in scleroderma, or the
signs of liver disease seen in portopulmonary hypertension.
Signs of pulmonary hypertension may include:
Rapid breathing
hypoxia (low oxygen level in the blood)
swelling in the legs.

Diagnosis
Because pulmonary hypertension may be caused by many medical conditions, a complete
medical history, physical exam, and description of your symptoms are necessary to rule out other
diseases and make the correct diagnosis. During the physical exam, your health care provider
will:
listen for abnormal heart sounds such as a loud pulmonic valve sound, a systolic murmur of
tricuspid regurgitation, or a gallop due to ventricular failure.
examine the jugular vein in the neck for engorgement.
examine the abdomen, legs, and ankles for fluid retention.
examine nail beds for bluish tint.
look for signs of other underlying diseases that might be causing pulmonary
hypertension.
Blood tests:
o Complete metabolic panel (CMP): Examines liver and kidney function
o Autoantibody blood tests, such as ANA, ESR, and others: Screens for collagen
vascular diseases
o Thyroid stimulating hormone (TSH): A screen for thyroid problems
o HIV: A screen for human immunodeficiency virus
o Arterial blood gases (ABG): Determines the level of oxygen in arterial blood.
o Complete blood count (CBC): Tests for infection, elevated hemoglobin, and
anemia
o B-type natriuretic peptide (BNP): A marker for heart failure
Doppler echocardiogram: Uses sound waves to show the function of the right ventricle, to
measure blood flow through the heart valves, and then calculate the systolic pulmonary
artery pressure.
Chest X-ray: Shows an enlarged right ventricle and enlarged pulmonary arteries.
6 minute walk test: Determines exercise tolerance level and blood oxygen saturation level
during exercise.
Pulmonary function tests: Evaluates for other lung conditions such as chronic obstructive
pulmonary disease and idiopathic pulmonary fibrosis among others.
Polysomnogram or overnight oximetry: Screens for sleep apnea (results in low oxygen
levels at night).

Right heart catheterization: Measures various heart pressures (ie, inside the pulmonary
arteries, coming from the left side of the heart), the rate at which the heart is able to pump
blood, and finds any leaks between the right and left sides of the heart.
Ventilation perfusion scan (V/Q scan): Looks for evidence of blood clots along the
pathway to the lungs.
Pulmonary angiogram: Looks for blood clot blockages in the pulmonary arteries.
Chest CT scan: Looks for blood clots and other lung conditions that may be contributing
to or worsening pulmonary hypertension.

Treatments

Medications
Many different types of medications are available to treat pulmonary hypertension. Treatment
choices, such as those listed below, depend on the severity of pulmonary hypertension, the
likelihood of progression, and individual drug tolerance.
Oxygen replaces the low oxygen in your blood.
Anticoagulants or "blood thinners" decreases blood clot formation so blood flows more freely
through blood vessels.
Diuretics or "water pills" removes extra fluid from the tissues and bloodstream, which
reduces swelling and makes breathing easier.
Potassium replaces potassium (an essential nutrient) that may be lost with increased urination
when taking diuretics.
Inotropic agents improves the hearts pumping ability.
Vasodilators lowers pulmonary blood pressure and may improve the pumping ability of the
right side of the heart.
Bosentan helps block the action of endothelin, a substance that causes narrowing of lung
blood vessels. These medications require monthly labwork to monitor liver function.
Epoprostenol dilates pulmonary arteries and helps prevent blood clots from forming.
Sildenafil relaxes pulmonary smooth muscle cells, which leads to dilation of the pulmonary
arteries.

Surgical therapies
Pulmonary thromboendarterectomy: If present, a large clot in the pulmonary artery
may be surgically removed to improve blood flow and lung function.
Lung transplantation: Currently, this is the only cure for primary pulmonary
hypertension. Transplantation is reserved for advanced pulmonary hypertension that is
not responsive to medical therapy. The right side of the heart will generally return to
normal after the lung/lungs have been transplanted. About 1,000 lung transplants are
performed annually in the United States. Many people are on the waiting list, yet a
shortage of donors is the major limiting factor. Your health care provider will discuss
transplantation if it is an appropriate treatment option for your condition.
Prognosis
Generally, the prognosis of pulmonary varies depending on the underlying condition that is
causing it. For idiopathic or familial pulmonary hypertension, the overall prognosis depends on
the severity and whether treatment was instituted. The statistics show a survival of about 3 years
in idiopathic pulmonary hypertension without any therapy. Some of the other factors may
indicate even poorer prognosis which include severe symptoms, age of onset greater than 45
years, evidence of right sided heart failure, and failure to respond to treatment. For patients with
idiopathic pulmonary hypertension who get started on treatment and respond to it, the prognosis
is better. Studies are underway to determine optimal treatment regimens.
Conclusion

Pulmonary hypertension is a rare lung disorder in which the arteries that carry blood from the
heart to the lungs become narrowed, making it difficult for blood to flow through the vessels. As
a result, the blood pressure in these arteries called pulmonary arteries rises far above normal
levels. Pulmonary hypertension occurs in individuals of all ages, races, and ethnic backgrounds
although it is much more common in young adults and is approximately twice as common in
women as in men.






References
http://my.clevelandclinic.org/disorders/pulmonary_hypertension/
http://www.medicinenet.com/pulmonary_hypertension/
http://www.ucsfhealth.org/conditions/pulmonary_hypertension
Bourke, S.J. Lecture Notes on Respiratory Medicine. 6
th
Edition. Blackwell Publishing, 2003.