Mechanism of disease: Pulmonary hypertension

Extract: Pulmonary hypertension (PH) was previously termed primary (idiopathic or of unknown origin, i.e., spontaneous) or secondary (as a result of another disorder) pulmonary hypertension. It is now clear, however, that many of the entities labeled as secondary pulmonary hypertension resemble primary pulmonary hypertension in both their histopathological features and their response to treatment. For this reason, the World Health Organization (WHO) has recently classified PH into five groups on the basis of their proposed underlying mechanism. Group I in this classification, designated pulmonary arterial hypertension, is the focus of this overview. Pulmonary arterial hypertension (PAH) is defined as a sustained elevation of the pulmonary arterial pressure to greater than 25 mmHg at rest or greater than 30 mmHg following exercise, with a mean pulmonary-capillary wedge pressure (an indirect measure of left atrial pressure) of less than 15 mmHg. The entities within the category of PAH include idiopathic pulmonary arterial hypertension (IPAH; formerly, primary pulmonary hypertension), PAH associated with collagen vascular disease (e.g., in limited systemic sclerosis), portal hypertension (high pressure in the vessel that carries blood from the intestines to the liver), congenital left-to-right intra-cardiac shunts, infection with the human immunodeficiency virus (HIV), and persistent pulmonary hypertension of the newborn. The histological appearance of lung vessels in each of these conditions is similar: intimal fibrosis (formation of fibrous material in the inner lining of the blood vessel), increased medial thickness, pulmonary arteriolar occlusion (block of arterioles [the vessels that join the arteries and capillaries] in the lung), and plexiform (web-like) lesions predominate.