Pulmonary Arterial Hypertension (PAH) is a severe, progressive condition impacting blood vessels within the lungs. It leads to elevated blood pressure in the arteries carrying blood from the heart to the lungs, a critical pathway for oxygen uptake. Understanding its development and impact on the lungs and heart is important for comprehending its widespread implications.
Understanding Pulmonary Arterial Hypertension
Pulmonary hypertension (PH) describes high blood pressure in the pulmonary arteries, the blood vessels connecting the heart to the lungs. These arteries transport deoxygenated blood from the right side of the heart to the lungs for oxygen uptake, then oxygenated blood returns to the left side of the heart for systemic circulation.
Pulmonary Arterial Hypertension (PAH) is a specific form of PH, categorized as Group 1 by the World Health Organization. In PAH, small arteries within the lungs become narrow, thick, or stiff. This structural change impedes blood flow, causing pressure to build up and forcing the heart to exert more effort to pump blood into the lungs.
Changes in Lung Blood Vessels
Vascular remodeling, a hallmark of PAH, involves significant structural changes in the pulmonary arteries. Their walls thicken, stiffen, and narrow, reducing space for blood flow and directly contributing to increased pressure within the pulmonary circulation.
Remodeling affects various layers of the vessel wall, including proliferation of smooth muscle cells (media) and thickening of the inner lining (intima). These changes can form complex lesions within the pulmonary arteries, further obstructing blood flow. The increased resistance in these remodeled vessels directly elevates pulmonary artery pressure.
Cellular and Molecular Contributors
Structural changes in PAH result from complex cellular and molecular dysfunctions. Endothelial cells, forming the inner lining of blood vessels, become dysfunctional, leading to an imbalance in substances regulating vessel constriction and dilation.
This often involves overproduction of vasoconstrictors like endothelin-1, which narrow vessels, and reduced production of vasodilators like nitric oxide and prostacyclin, which relax them. Smooth muscle cells also exhibit excessive proliferation and migration, contributing to artery wall thickening and stiffening.
Inflammation also contributes to PAH progression, as immune cells infiltrate the vascular wall and release signaling molecules promoting remodeling. Genetic factors, particularly BMPR2 gene mutations, are identified in many PAH cases, impairing signaling that affects cell growth and function. This interplay of cellular proliferation, signaling imbalances, inflammation, and genetic predispositions drives pathological changes in pulmonary arteries.
Strain on the Heart
Increased pressure within the pulmonary arteries burdens the right side of the heart. The right ventricle, pumping blood to the lungs, must work harder to overcome elevated resistance in the stiffened, narrowed pulmonary vessels. This sustained workload causes adaptive changes, initially increasing its muscle mass, a process known as hypertrophy.
While initially compensatory, this hypertrophy can become maladaptive, leading to the right ventricle becoming enlarged and weakened. Eventually, it may fail to effectively pump blood, resulting in right heart failure. This failure is a major factor in PAH progression and severity. Right ventricular dysfunction can also indirectly affect the left side of the heart and other organ systems due to reduced blood flow and systemic congestion.