**4. Pathophysiology**

PAH is a proliferative vasculopathy which is histologically characterized by endothelial and smooth muscle cell proliferation, medial hypertrophy, fibrosis and in-situ thrombi of the small pulmonary arteries and arterioles.[13], [14]

**Genetic mutations** — Predisposition to pulmonary vascular disease may be related to genetic mutations in the bone morphogenetic protein receptor type II (BMPR2), activin-like kinase type 1, and/or 5-hydroxytryptamine (serotonin) transporter (5HTT) genes. Abnormal BMPR2 may play an important role in the pathogenesis of IPAH, with up to 25 percent of patients with IPAH having abnormal BMPR2 structure or function. [15], [16], [17]
