Pulmonary arterial hypertension (PAH) is a progressive disease caused by narrowing or tightening (constriction) of the pulmonary arteries, which connect the right side of the heart to the lungs. By definition, PAH is characterised by an increase in mean pulmonary arterial pressure (PAP) to ≥25 mmHg at rest, and a mean primary capillary wedge pressure of ≤15 mmHg. As PAH develops, blood flow through the pulmonary arteries is restricted and the right side of the heart becomes enlarged due to the increased strain of pumping blood through the lungs. It is this strain on the heart and decrease in blood to the left heart and systemic circulation through the lungs that leads to the common symptoms of PAH, such as breathlessness, fatigue, weakness, angina, syncope, and abdominal distension.
The increase in pulmonary vascular resistance observed in patients with PAH is related to a number of progressive changes in the pulmonary arterioles, including:
The most prominent histological feature of PAH is a thickening of the three cellular layers (the intima, media, and adventitia) that line the blood vessels, which is due to a process of cell enlargement termed hypertrophy. Other changes include development of plexiform lesions (focal proliferations of endothelial and smooth muscle cells that are a classic characteristic of PAH), and in situ thromboses.