If left untreated, the increased pulmonary vascular resistance will eventually lead to right heart failure and death.
Late findings include swelling of the extremities, edema and ascites (which are signs of right heart failure).
In disease that is refractory to medical therapy, an atrial septostomy may be used palliatively or as a bridge to lung transplantation.
As PAH progresses and chronically elevated pulmonary arterial pressures result in right heart failure; swelling of the legs and other areas of the body (edema), fluid buildup in the abdomen (ascites) develop as late symptoms.
Genetic variants or mutations in bone morphogenic protein receptor 2 (BMPR2) account for approximately 75-80% of cases of heritable PAH.
Other types of genes coding for proteins involved in BMPR2 signaling have also been implicated as causes of heritable PAH, such as activin A receptor type-2-like-1 ACVRL1, Endoglin (ENG), SMAD genes encoding for SMAD transcription factors involved in downstream BMPR2 signaling and cell growth including Smad1, Smad4 and Smad9.
[1] KCNK3 encodes for a potassium channel which regulates membrane potential across cells thus controlling vascular tone.
The subcategory is characterized by severe hypoxemia, capillary congestion and prominent post-capillary venule thickening.
[1] The smooth muscles in the tunica media also extend more distally than normal, encroaching upon the capillary bed.
Infiltration of inflammatory cells, proliferation of fibroblasts and disruptions in collagen architecture result in adventitial thickening and remodeling.
[1] Pathogenic and inappropriate platelet activation coupled with endothelial injury leads to formation of micro-thrombi.
And PAH also involve the characteristic plexiform lesions which are growths in the walls of the arterioles consisting of dilated blood vessels which communicate with the bronchial artery and vaso vasorum.
[1] As pulmonary hypertension persists and worsens the right ventricle undergoes compensatory changes such as concentric hypertrophy of the heart muscle and changes in the microcirculation.
However, with prolonged pulmonary hypertension, with the right ventricle pumping against elevated right heart pressures, the hypertrophy becomes maladaptive with microvascular rarefaction, and fibrosis.
[4] Echocardiography is the preferred screening test in the diagnosis of PAH as it accurately estimates pulmonary pressures.
Pulmonary function testing in PAH may show an obstructive or restrictive defect, and the diffusion capacity of carbon monoxide (used as a surrogate for gas exchange in the alveoli) is reduced.
[1] The N-terminal prohormone of brain natriuretic peptide (NT pro-BNP) may be monitored in those with PAH and is prognostic.
[1][2] Supportive care in those with PAH involves using diuretics as needed for fluid overload, supplemental oxygen for hypoxemia, following a low sodium diet, an exercise program (such as walking), and routine immunizations.
[1][2] PDE5 inhibitors (including sildenafil and tadalafil are used to dilate blood vessels by inhibiting the degradation of Cyclic guanosine monophosphate (cGMP).
[2] Endothelin receptor antagonists cause vasodilation as well by blocking the action of the potent vasoconstrictor and vascular smooth muscle cell proliferation activator endothelin-1.
PGI2 activates adenylate cyclase to convert adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP), cAMP inhibits proliferation of smooth muscle cells in the pulmonary artery walls, and causes relaxation of smooth muscle cells thus acting as a vasodilator.
[2][1][4] In those who have a sustained vasodilator response as determined during the right heart catheterization (approximately 10% of those with PAH are responders), long acting calcium channel blockers nifedipine, diltiazem or amlodipine are indicated.
[1][4] In disease that is refractory to medical therapy, an atrial septostomy may be used palliatively or as a bridge to lung transplantation.