Pulmonary Arterial Hypertension: Understanding the Causes

Pulmonary arterial hypertension (PAH) is a complex and serious condition characterized by abnormally high blood pressure in the arteries of the lungs. Understanding the causes of PAH is crucial for early diagnosis and effective treatment. The condition can be classified into multiple categories based on its origin and underlying triggers.

1. Idiopathic Pulmonary Arterial Hypertension

The first category includes idiopathic PAH, which means the cause is unknown. Despite extensive research, no specific trigger can be identified in these cases, making it a diagnosis of exclusion.

2. Heritable and Drug-Induced PAH

Some cases of PAH are linked to genetic factors and are considered heritable. These often run in families and may be associated with specific gene mutations. Additionally, certain drugs and toxins can act as triggers for PAH, especially in individuals with a predisposition to the condition.

3. Associated Conditions and Diseases

PAH can also be associated with other medical conditions. These include connective tissue disorders, portal hypertension due to liver disease, congenital heart defects, and schistosomiasis, a parasitic disease common in certain parts of the world.

4. Left Heart Disease-Related PAH

Another major group involves PAH related to left heart disease. This includes dysfunction of the left ventricle—both systolic and diastolic impairments—as well as valvular heart disease. Structural abnormalities such as congenital or acquired obstructions in the left ventricular inflow or outflow tracts can also contribute to elevated pulmonary artery pressure.

5. Lung Diseases and Hypoxia-Induced PAH

Chronic lung diseases are a significant cause of pulmonary hypertension. These include interstitial lung disease, mixed obstructive and restrictive lung disorders, and sleep-related breathing disorders such as sleep apnea. Other contributing factors include alveolar hypoventilation, prolonged exposure to high altitudes, and developmental abnormalities of the lungs.

6. Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Chronic blood clots in the pulmonary arteries can lead to a unique form of PAH known as chronic thromboembolic pulmonary hypertension. In CTEPH, old blood clots do not dissolve naturally and instead cause persistent blockages, increasing pressure in the pulmonary circulation.

7. Multifactorial and Rare Causes

Some cases of PAH arise from rare or less understood mechanisms. Blood disorders such as chronic hemolytic anemia and myeloproliferative diseases may contribute to PAH. Additionally, systemic conditions like sarcoidosis, lymphangioleiomyomatosis, and pulmonary histiocytosis are associated with the disease. Metabolic disorders including glycogen storage diseases and thyroid dysfunction can also play a role in the development of pulmonary hypertension.