Understanding Pulmonary Arterial Hypertension: Beyond High Blood Pressure

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• Pathology Overview of Pulmonary Arterial Hypertension
• Symptoms and Diagnostic Challenges
• Cellular Mechanisms and Proliferation
• The Inflammatory Component in PAH
• Historical Misconceptions and Treatment Implications
• Full Transcript

Pathology Overview of Pulmonary Arterial Hypertension

Pulmonary arterial hypertension is fundamentally a misnamed disease. Dr. Aaron Waxman, MD, emphasizes that the term focuses on high blood pressure, which is merely a symptom. The core pathology involves a complex process of vascular remodeling within the lungs.

This process causes thickening and stiffening of the lung's blood vessel walls. The increased stiffness creates significant resistance to blood flow. This elevated resistance is the true driver of the high pulmonary arterial pressure measured in patients.

Symptoms and Diagnostic Challenges

The primary symptom patients present with is shortness of breath on exertion. Dr. Anton Titov, MD, and Dr. Aaron Waxman, MD, discuss how this symptom is extremely common and non-specific. It does not point directly to PAH, making early diagnosis difficult.

Patients typically do not experience shortness of breath at rest in the early stages. This common complaint leads many individuals and doctors to initially suspect more common conditions like asthma or being out of shape. The disease's name further complicates understanding, as it describes a sign (hypertension) rather than the cause.

Cellular Mechanisms and Proliferation

The true cause of pulmonary arterial hypertension lies in abnormal cellular growth. Dr. Aaron Waxman, MD, explains that PAH is strikingly similar to a neoplastic, or cancer-like, process. There is uncontrolled proliferation of smooth muscle cells within the pulmonary vascular network.

Endothelial cells and endothelial-like cells also demonstrate abnormal growth in various lung vessel regions. This rampant cell proliferation is the central mechanism that leads to vessel wall thickening. It is this pathological change, not simple vasoconstriction, that defines the disease state.

The Inflammatory Component in PAH

Inflammation plays a critical role in the progression of pulmonary arterial hypertension. Dr. Aaron Waxman, MD, highlights the presence of increased inflammatory mediator molecules circulating in the blood. There is also a notable invasion of inflammatory cells into the pulmonary vasculature.

Beyond inflammation and cell growth, a fibrotic change occurs. Proliferation of connective tissue cells contributes to the scarring and stiffening of vessel walls. This combination of proliferation, inflammation, and fibrosis creates a highly complicated disease pathway.

Historical Misconceptions and Treatment Implications

Historical understanding of PAH incorrectly focused on vasoconstriction. Dr. Aaron Waxman, MD, notes that if constriction were the main problem, treatment would have been simple long ago. Vasodilators alone are insufficient because they do not address the underlying proliferative pathology.

The disease was named before its complex nature was fully understood. This is a common occurrence in medicine that can lead to persistent misconceptions. Dr. Anton Titov, MD, and Dr. Waxman's discussion underscores the need for treatments targeting cell proliferation and inflammation, not just pressure.

Full Transcript

Dr. Anton Titov, MD: Pulmonary hypertension is largely a misnomer. It is a result of lung blood vessel wall cells increasing in size and number. It is almost like cancer.

Top PAH expert explains. What is pulmonary arterial hypertension? How to recognize its symptoms? What causes pulmonary arterial hypertension?

Dr. Aaron Waxman, MD: The definition of pulmonary arterial hypertension is misleading. I wish we'd never called it pulmonary artery hypertension, because all it implies is that there is an increase in arterial blood pressure in the pulmonary artery. But increased arterial pressure is a sign of the disease; it is not the main problem in pulmonary arterial hypertension.

Pulmonary arterial hypertension is a pathologic process. It results in thickening and stiffening of the blood vessels inside the lung. Those vessels in the lung get stiffer, then they increase resistance to blood flow. This ultimately drives up pulmonary arterial pressure.

But it is the pathologic change that results in increased stiffness in lung blood vessels. It is increased resistance that imparts the pulmonary arterial hypertension disease state.

There is a difficult thing about pulmonary arterial hypertension—it is also a problem with all aspects of pulmonary vascular disease. The problem is that patients generally present simply with shortness of breath. It is usually shortness of breath that appears with physical exertion; there is no shortness of breath at rest.

Shortness of breath is a very common complaint. It is not specific to any disease.

People call the disease pulmonary arterial hypertension. It is the name that derives from symptoms and signs of pulmonary arterial hypertension. In reality, the causes of the disease are somewhere else.

We don't know what causes pulmonary arterial hypertension, but there are several associated disease states.

We have learned over the past 15–20 years the important discovery about pulmonary arterial hypertension. This is what causes the increased resistance in pulmonary blood vessels.

There is abnormal growth, or proliferation of cells. Pulmonary arterial hypertension is almost similar to a neoplastic process.

Dr. Anton Titov, MD: You see abnormal growth of smooth muscle cells in certain regions of the pulmonary vascular network. You see abnormal growth of endothelial cells and endothelial-like cells in different regions of the lung vascular network.

Dr. Aaron Waxman, MD: There is also a significant inflammatory component in pulmonary arterial hypertension. We see increased inflammatory mediator molecules that circulate in blood vessels. There is also almost an invasion of inflammatory cells in pulmonary arterial hypertension.

There is also proliferation of connective tissue cells. We also see fibrotic change. Pulmonary arterial hypertension is a very complicated disease; it is much like cancer.

Old thinking about pulmonary arterial hypertension focused on a vasoconstrictive process, but it is not about constriction of blood vessels in the lungs. Because if it was, it would have been easy to treat patients with pulmonary arterial hypertension many years ago.

It is certainly not the first time when the disease gets a name before its nature is understood. Then the name becomes somewhat misleading.

But it is very interesting to know that pulmonary arterial hypertension is a very complicated process. Proliferation of cells lies behind pulmonary arterial hypertension. Exactly!