The pulmonary circulation is normally one of low resistance and pulmonary blood pressure is only about one eighth of systemic blood pressure. Pulmonary hypertension (when mean pulmonary pressure reaches one fourth of systemic levels) is most frequently secondary to structural cardiopulmonary conditions that increase pulmonary blood flow or pressure (or both), pulmonary vasculary resistance or left heart resistance to blood flow . These include the following:

Chronic obstructive or intestitial lund disease: Patients with emphysema have hypoxia as well as destruction of lung parenchyma and hence have fewer alveolar capilaries. This causes increased pulmonary arterial resistance and secondarily pressure.

Antecedent congenital or acquired heart disease; Pulmonary hypertension occurs in patients with mitral stenosis for example because of an increase in left atrial pressure that leads to an increase in pulmonary venous pressure and consequently to an increase in pulmonary artery pressure.

Recurrent thromboemboli

Patients with recurrent pulmonary emboli may have pulmonary hypertension primarily owing to a reduction in the functional cross-sectional area of the pulmonary vascular bed brought about by the obstructing emboli, which in turn leads to an increase in pulmonary vascular resistance.

Uncommonly pulmonary hypertension is encountered in patients in whom all known causes of increased pulmonary pressure are excluded and this is referred to as primary or idiopathic pulmonary hypertension.

Pathogenesis

The endothelial cells in the lungs contribute in important ways to the dynamic regulation of pulmonary blood flow and pulmonary vascular resistance. Dysfunction of pulmonary vascular endothelial cells plays a central part in the vascular responses of both idiopathic (primary) and secondary pulmonary hypertension.

In secondary forms of pulmonary hypertension, endothelial cell dysfunction is produced nby the process initiating the disorder, such as the increased shear and mechanical injury associated with left to right shunts or the biochemical injury produced by fibrin in thromboembolism. In primary pulmonary hypertension, endothelial dysfunction is idiopathic in most cases but is sometimes associated with autoimmune disorders, toxic substances, and perhaps specific genetic determinants. Decreased elaboration of prostacyclin, decreased production of nitric oxide and increased release of endothelin all promote pulmonary vasconstriction. Also decreased elaboration of prostacyclin and nitric oxide promotes platelet adhesion and activation. Moreover endothelial activation.

Finally , production and release of growth factors and cytokines induce the migration and replication of vascular smooth muscle cells and elaboration of extracellular matrix.

Some patients with pulmonary hypertension have a vasospastic component; in such patients, pulmonary vascular resistance can be rapidly decreased with vasodilators. Pulmonary hypertension has also been reported after ingestion of certain plants or medicines, including the leguminous plant Crotalaria spectabilis, indigenous to the topics and used medicinally in bush tea; the appetite depressant agent aminorex olive oil; and most recently the antiobesity drugs fenfluramine and phentermine. It has been suggested that such substances may act through endothelial dysfunction, by enhancing pulmonary vasoconstriction.

Clinical Course

Although secondary forms can occur at any age, primary pulmonary hypertension is most common in women who are 20 to 40 years of age and is also seen ocasionally in young children. Clinical signs and symptoms of both the primary and the secondary forms of vascular scelerosis become evident only with advanced arterial disease. In cases of primary disease , the presenting features are usuallyu dyspnea and fatigue but some patients have chest pain of the anginal type. In the course of time severe respiratory distress, cyanosis, and right ventricular hypertrophy occur and death from decompensated cor pulmonale often with superimposed thromboembolism and pneumonia usually ensues with 2 to 5 years in 80% of patiens. Continuous therapy with vasodilators (e.g., calcium channel blockers or inhaled nitric oxide) and antithrombotic medications (e.g., warfarin, prostacyclin, and thromboxane receptor blockers), however, appears to improve the outcome in certain patients.