Pathology of pulmonary hypertension

Abstract

There are similarities in the pathological features of pulmonary hypertension of varying etiologies in infants and children. Abnormalities in growth and development of the peripheral pulmonary arteries related to abnormal extension of muscle into normally non-muscular peripheral arteries, medial hypertrophy of proximal normally muscular arteries and a reduction in the number of small arteries relative to alveoli occur in infants with congenital heart defects as well as lung parenchymal and hypoxia-induced lung disease. These features are also seen in infants with unexplained pulmonary hypertension. The pathology of thromboembolic pulmonary hypertension is usually distinguished by thrombi, recalanized vessels and lack of uniformity of pathological changes. In most cases of advanced pulmonary vascular disease as in the setting of a congenital heart defect, connective tissue disease, portal hypertension or when the etiology is unexplained, obliterative changes are prevalent and the ‘plexiform lesion’ is a common feature. Venous changes are prevalent with congenital heart defects causing left sided obstruction, and occlusive changes can occur primarily in veins in patients with unexplained pulmonary hypertension. The ability of continuous intravenous prostacyclin to arrest progression, and even induce regression of structurally advanced pulmonary vascular disease in some cases, has led to rethinking how pathological material can be useful in clinical decision making. The presence of occlusive changes and particularly plexiform lesions was thought to represent irreversible disease, but the observation that ongoing cellular proliferation and connective tissue synthesis occurs, even in advanced lesions thought to represent end stage ‘burnt-out’ diseases, led to re-evaluation of the potential of biologically reversing the disease process. Clinical material, cultured cells and studies in experimental animals provide insights into cellular mechanisms which lead to the progression of vascular changes. Our laboratory focused on the increased activity of an endogenous vascular elastase (EVE) and expression of the glycoproteins tenascin and fibronectin in the pathobiology of pulmonary hypertension. These studies suggested ways to prevent progression and induce regression of advanced pulmonary arterial changes.