pulmonary hypertension (ph) summarized.docx

7/27/2019 Pulmonary hypertension (PH) summarized.docx

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Pulmonary Hypertension

What is pulmonary hypertension?

Pulmonary hypertension is an abnormal elevation of the pressure in the blood vessels of the

lungs. In fact, it could be called the high blood pressure of the lungs. In normal lungs, thepressure in the blood vessels is about one-quarter of the pressure in the arteries of the body and

can temporarily adapt to increased pressures that occur during exercise. Pulmonary hypertension

is defined as a mean pulmonary artery pressure >25 mmHg at rest. In pulmonary hypertension,

the small arteries in the lungs are too narrow, so the pressure rises in these vessels. As a result,

the right side of the heart, which pumps blood into the lungs, has to pump against a higher

resistance to blood flow. This makes it more difficult to pump the blood through the lungs,

particularly when increased flow is needed, as when a patient exercises.

Classification of pulmonary hypertension

Pulmonary hypertension was previously divided into 2 categories, primary and secondary,depending on whether a specific cause could be identified. In 1998, the World Health

Organization (WHO) proposed a clinical classification of pulmonary hypertension into 5 main

groups on the basis of similarities in pathophysiology, clinical presentation, and therapeutic

options. This classification was later revised in Venice in 2003 and again in Dana Point in 2008

to further clarify classifications.

In all groups, the average pressure in the pulmonary arteries is 25 mmHg or higher. The pressure

in normal pulmonary arteries is 820 mmHg at rest.

(Note that group 1 is called pulmonary arterial hypertension (PAH) and groups 2 through 5 are

called pulmonary hypertension. However, together all groups are called pulmonary

hypertension.)

Group 1, PAH, is further divided into the following 4 subgroups:

Subgroup 1 - Idiopathic PAH (IPAH)

Subgroup 2 - Heritable PAH, including those withBMPR2 andALK2 gene mutations

Subgroup 3 - Drug- and toxin-induced PAH (Aminorex, fenfluramine derivatives, and

toxic rapeseed oil have been identified as definite risk factors for PAH.[5]

)

Subgroup 4 - Conditions with known localization of lesions in the small pulmonary

arterioles, including collagen-vascular disease (scleroderma/CREST syndrome),

congenital left-to-right shunts, portopulmonary hypertension, HIV-associated pulmonary

hypertension, schistosomiasis, and chronic hemolytic anemia

Subgroup 5Persistant pulmonary hypertension of the newborn

Group 2, pulmonary hypertension owing to left-sided heart disease, consists of left-sided

myocardial and valvular diseases and extrinsic compression of the pulmonary veins (eg, tumors)

and pulmonary veno-occlusive disease.
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Group 3, pulmonary hypertension owing to lung diseases and/or hypoxia, consists of diseases

that cause inadequate arterial oxygenation. Such conditions include lung disease (eg, chronic

obstructive pulmonary disease [COPD] and interstitial lung disease), impaired respiration (eg,

obstructive sleep apnea [OSA]and alveolar hypoventilation disorders), and long-term exposure

to high altitude.

Group 4 is chronic thromboembolic pulmonary hypertension (CTEPH)

Group 5, pulmonary hypertension with unclear or multifactorial etiologies, is further divided

into the following 4 subgroups:

Subgroup 1 - Hematologic disorders, including myeloproliferative disorders

Subgroup 2 - Systemic disorders, including sarcoidosis, pulmonary Langerhans cell

histiocytosis, lymphangioleiomyomatosis, neurofibromatosis, and vasculitis

Subgroup 3 - Metabolic disorders, including glycogen storage disease, Gaucher disease,

and thyroid disorders

Subgroup 4 - Miscellaneous conditions, including tumor obstruction, mediastinal fibrosis,

and chronic renal failure on dialysis

On the basis of information adapted from the executive summary of the world symposium on

Primary Pulmonary Hypertension in Evian, France, in 1998, pulmonary hypertension may be

divided into the following functional classes:

Class IThese are patients with pulmonary hypertension but without resulting limitation of

physical activity; ordinary physical activity does not cause undue dyspnea or fatigue, chest

pain, or near-syncope.

Class II These are patients with pulmonary hypertension resulting in slight limitation ofphysical activity; they are comfortable at rest, but ordinary physical activity causes undue

dyspnea or fatigue, chest pain, or near-syncope

Class IIIThese are patients with pulmonary hypertension resulting in marked limitation of

physical activity; they are comfortable at rest, but even less-than-ordinary activity causes undue

dyspnea or fatigue, chest pain, or near-syncope

Class IV These are patients with pulmonary hypertension who are unable to perform any

physical activity without symptoms; these patients manifest signs of right-sided heart failure;

dyspnea or fatigue may even be present at rest, and discomfort is increased by any physical

activity

What causes pulmonary hypertension?

Pulmonary hypertension (PH) begins with inflammation and changes in the cells that line

pulmonary arteries. Other factors also can affect the pulmonary arteries and cause PH. For

example, the condition may develop if:


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The walls of the arteries tighten.

The walls of the arteries are stiff at birth or become stiff from an overgrowth of cells.

Blood clots form in the arteries.

These changes make it hard for the heart to push blood through your pulmonary arteries and intothe lungs. Thus, the pressure in the arteries rises, causing PH. Many factors can contribute to the

process that leads to the different types of PH.

Group 1 pulmonary arterial hypertension (PAH) may have no known cause, or the condition may

be inherited. Some diseases and conditions also can cause group 1 PAH. Examples include HIV

infection, congenital heart disease, and sickle cell disease. Also, the use of street drugs (such as

cocaine) and certain diet medicines can lead to PAH.

Many diseases and conditions can cause groups 2 through 5 PH (often called secondary PH),

including:

Mitral valve disease

Lung diseases, such as COPD (chronic obstructive pulmonary disease)

Sleep apnea

Sarcoidosis

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 theTGF-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.
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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 signs and symptoms may include:

Unusual fatigue

Shortness of breath

Chest pain

Loss of consciousness (or near-fainting episodes)

Swelling in the legs and ankles

Rapid breathing

Diagnosis

Because pulmonary hypertension may be caused by many medical conditions, a complete

medical history, physical exam, and description of symptoms are necessary to rule out other

diseases and make the correct diagnosis. Physical examination findings may include:

abnormal heart sounds such as a loud pulmonic valve sound, a systolic murmur of

tricuspid regurgitation, or a gallop due to ventricular failure.

Engorgement of jugular vein in the neck.

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.

Other tests may be done included:

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


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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.

ECG: This test may be done to record the electrical activity of the heart and show

changes in heart rhythm and wall thickness.

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 and the flow of blood.

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

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.

1. Calcium channel blocker therapy (CCB) such as nifedipine or diltiazem -acts on the vascular smooth muscle, dilating the pulmonary resistance vessels and

lowering the pulmonary artery pressure.

2. Prostacyclin therapy such as epoprostenol, treprostinil, and iloprost - dilates pulmonaryarteries and helps prevent blood clots from forming.

3. Endothelin receptor antagonists (ERAs) therapy such as bosentan, ambrisentan -blocksone of the proteins (endothelin) that constricts blood vessels in pulmonary hypertension

causing a reduction in pulmonary artery pressure.

4. Anticoagulants such as warfarin - prevent the formation of blood clots within the smallpulmonary arteries.

5. Cardiac glycosides such as digoxin - improves the hearts pumping ability.6. Diuretics such as furosemide, bumetanide and spironolactone - removes extra fluid from

the tissues and bloodstream, which reduces swelling and makes breathing easier.

7. Phosphodiesterase type 5 inhibitor therapy(PDE-5) such as sildenafil, tadalafil - relaxespulmonary smooth muscle cells, which leads to dilation of the pulmonary arteries.

8. Oxygen therapy - replaces the low oxygen in your blood.


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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 pulmonaryhypertension. 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.

Prognosis

Generally, the prognosis of pulmonary varies depending on the underlying condition that iscausing 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. PH is divided into five groups based on its causes and treatment options. In all groups, the

average pressure in the pulmonary arteries is 25 mmHg or higher. The pressure in normal

pulmonary arteries is 820 mmHg at rest. 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.


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References

1. Cleveland Clinic Foundation. Pulmonary Hypertension: Causes, Symptoms, Diagnosis,

Treatment [internet]. 2010 [cited 2013 September 12].

Available

from:http://my.clevelandclinic.org/disorders/pulmonary_hypertension/hic_pulmonary_hypert

ension_causes_symptoms_diagnosis_treatment.aspx

2. What causes Pulmonary hypertension? [internet]. 2013 [cited 2013 September 12]. Available

from:http://www.nhlbi.nih.gov/health/health-topics/topics/pah/causes.html

3. Schiffman, George et al. Pulmonary Hypertension. [internet]. 2011 [cited 2013 September

12]. Available from:

http://www.medicinenet.com/pulmonary_hypertension/page8.htm#what_is_the_life_expecta

ncy_for_pulmonary_hypertension

4. Benisty, Jacques I. Pumonary Hypertension [internet]. 2002 [cited 2013 September 14].

Available from:http://circ.ahajournals.org/content/106/24/e192.full.pdf+html

5. Kamangar, Nader et al. Etiology of Secondary Pulmonary Hypertension. Medscape[internet]. 2012 [cited 2013 September 12]. Available from:

http://emedicine.medscape.com/article/303098-overview#aw2aab6b2b2
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