Pulmonary Hypertension Program - Children's Hospital Boston

300 Longwood Avenue
Boston, MA 02115
(617) 355-6000

Clinical Services (Pulmonary Hypertension Program):

About Pulmonary Hypertension

Pulmonary hypertension simply means higher than normal pressure in the blood vessel that connects the right-sided pumping chamber (the "right ventricle") with the lungs. That blood vessel is called the "pulmonary artery". Like most diseases, pulmonary hypertension can range in severity from mild to severe.

The pulmonary arterial pressure is higher than normal because the very small blood vessels in the lung are either smaller in diameter than normal, or there are fewer of them. Actually, in many patients both of these abnormalities occur. Because the resistance to blood flow is increased, more pressure is required to push blood through the lungs. Here is a highly-simplified diagram (there are actually millions of tiny arteries in the lungs) to show this:

There are several reasons why the number of arteries is reduced: In some cases, fewer arteries develop as the lung grows. Also, the intima (called the linking of the arteries) is so thick that very tiny pulmonary arteries are blocked off. Some tiny arteries are blocked by small blood clots which form in the artery.

The muscle in the walls of the arteries (called the "media") is also thicker than normal. This increased thickness is due to an increased number and/or size of cells (muscle cells and other types) in the intima and media. There is also an increased amount of "matrix protein" in between the cells.

Pulmonary arteries contain a special type of muscle called smooth muscle. When this smooth muscle contracts, the diameter of the small arteries decreases (called vasoconstriction). To what extent pulmonary hypertension is caused by vasoconstriction, versus the other abnormalities described above, varies from patient to patient.

What causes abnormalities of the pulmonary arteries?

We do not know what causes these abnormalities of pulmonary blood vessels. We have learned many factors that may play a role in causing this "pathological remodeling", but are just beginning to learn which ones are important, and how they fit together. A few of these factors are:

1. Low oxygen levels within the lung, as can occur at high altitudes, with certain types of lung disease, and with certain breathing disorders, causes vasoconstriction and increased thickness of the pulmonary arteries. This is a common cause of pulmonary hypertension.

2. Increased pressure and increased blood flow in the pulmonary arteries, as can occur with certain malformations of the heart, or abnormal function of the left side of the heart, can cause pathological remodeling. We do not understand exactly how increased pressure and flow cause pathological remodeling.

3. Within the body substances are normally produced which cause the smooth muscle within the pulmonary arteries to contract ("vasoconstrictors") or relax ("vasodilators"). An imbalance in these substances may cause abnormal constriction of the small pulmonary arteries, and abnormal growth of the cells in the arteries. Because many of these factors are produced in the cells which line the arteries ("endothelial" cells), it seems likely that abnormal endothelial cells can lead to pulmonary hypertension. 4. Cells in the lung also produce substances called growth factors. Platelet derived growth factor (PDGF) and transforming growth factor beta (TGF-B) ) are two examples of growth factors that researchers think may be involved in causing pulmonary hypertension. Either too much or too little of these important substances could cause pathological remodeling in blood vessels.

5. Abnormalities in a few genes have been discovered which predispose to pulmonary hypertension. Abnormalities in the "BMPR2" (bone morphogenetic protein receptor 2) gene are related to pulmonary hypertension, especially the variety which runs in families. It is unknown how abnormal function of this gene causes pulmonary hypertension, although we have reason to think that PDGF may be involved. Mutations in the "ALK1" gene also appear to be related to development of pulmonary hypertension although, as is the case with BMPR2, we don't know how this gene acts to cause pathological remodeling. There are doubtlessly many other genetic abnormalities related to pulmonary hypertension yet to be discovered.

6. Although the details are as yet sketchy, it appears that inflammation can cause or worsen pulmonary hypertension. We think this because a number of inflammatory disorders, such as scleroderma and sarcoidosis are associated with pulmonary hypertension. Also, inflammatory cells are sometimes seen near or in pulmonary arteries with pulmonary hypertension, even without other inflammatory disease being present.

7. A few environmental exposures can cause pulmonary hypertension. The drugs fenfluramine and dexfenfluramine ("Fen-phen") are associated with pulmonary hypertension. How they cause pulmonary hypertension is unknown.

8. Blood clots which form in the legs or other parts of the body can break away and travel to the lungs. If large enough, a clot can cause pulmonary hypertension to develop very suddenly. Many small clots, migrating to the lungs over a long period of time (months or years) can cause slowly developing, yet severe, pulmonary hypertension. (These clots are different from the clots which form in very small pulmonary arteries in patients with pre-existing pulmonary hypertension.)



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