Introduction

Severe chronic pulmonary hypertension develops in patients with congenital cardiovascular abnormalities, patients with thromboembolism, interstitial lung diseases, collagen-vascular disorders, patients with sickle cell disease and in a group of diseases summarized under the rubric of primary pulmonary hypertension [1–3]. Although the prevalence of severe pulmonary hypertension in the population is not known, there are estimates that the prevalence of primary pulmonary hypertension (PPH) is 1–2 per million people. The use of the term ‘primary pulmonary hypertension’ continues to produce confusion among patients, physicians and insurance providers. Attempts should be made to change the nomenclature. Recently, our group has made such an attempt [4]. One of the many vexing aspects of PPH and other forms of plexogenic pulmonary arteriopathy is the multifactorial aetiology of such diseases.

Figure 4.1 demonstrates that a familial genetic disposition to high blood flow, elevated shear stress, collagenvascular diseases, liver cirrhosis and portal hypertension, viral infections and appetite suppressant drugs [5–13] can all lead to the same histopathological pattern. How is this possible? Is there a common pathomechanism that can explain such a multifaceted aetiology? In search of a ‘unifying’ hypothesis, we arrived at the concept of ‘misguided angiogenesis’.

Pathobiology

Vasoconstriction or increased blood flow, and therefore increased shear stress, causes vascular injury, and either this vascular injury carries inflammatory features [14] or there is endothelial cell proliferation, autonomously triggered in the pulmonary precapillary arteries, that causes obliteration of most of the precapillary arterioles and severe pulmonary hypertension (Figure 4.2).