Pulmonary Hypertensions: A Mechanistic Analysis

Pulmonary hypertension (PH), an increased blood pressure in the arteries of the lungs, is a condition classified by five distinct pathophysiologic mechanisms. According to a recent paper published by Scott Friedman and Bruce Andrus of the Geisel School of Medicine at Dartmouth, the World Health Organization has repeatedly reevaluated this potentially life-threatening affliction in order to create a systemic diagnostic approach leading to more specific, effective treatment options. The paper presents five distinct mechanisms unique to those afflicted with obesity, of which any may be present in an afflicted patient.

Obesity is the strongest risk factor for the first of these mechanisms: obstructive sleep apnea (OSA). OSA is marked by a disordered sleep-breathing pattern. It is typically associated with daytime somnolence and can lead to multiple systemic failures. Treatment with continuous positive airway pressure can lead to moderately improved pulmonary artery pressures; however, any combination of OSA with a co-morbid condition contributing to hypoxemia can lead to severe degrees of PH.

Obesity hypoventilation syndrome (OHS) is the second component linking obesity and its co-morbidities to PH. The condition involves chronic hypoventilation and hypoxemia in the patient with sleep disordered breathing. Although distinct from OSA, OHS is nonetheless significantly related to obesity, evidenced by its prevalence and strongly linear relationship to the body-mass index (BMI). The chronic hypoxemia seen in patients with OHS is reversible in many cases; however, OHS is consistently seen as involving more severe degrees of PH than is OSA.

Anorexigen use is also thought to precipitate PH, specifically through two mechanisms that lead to vasoconstriction. The drug inhibits a specific membrane potassium channel, which causes the blood vessel to contract. Anorexigen use also contributes to an excess of serotonin and its precursor, 5-HT, which initiate a similar response. This third mechanism of PH is unique to those afflicted with obesity, and is not typically reversible following the removal of the drug.

A fourth mechanism, cardiomyopathy of obesity, involves an eccentric ventricular hypertrophy (dilation without wall thickening) and diastolic heart failure in those suffering from severe obesity. Two mechanisms are thought to explain the influence of cardiomyopathy of obesity on PH; triglyceride excess and increased volume pressure on the left ventricle collectively cause damage to myocardial cells and elicit a negative physiologic response. As stated by the authors, the most effective method of relief for this mechanism is weight loss.

Chronic thromboembolic disease is the fifth and final unique mechanism that frequently begets PH in obese patients. In this case, PH arises from a blockage of an artery in the lungs and the subsequent distortion of the pulmonary vessels that ensues. Presently, additional mechanisms that give rise to PH are under investigation. Nevertheless, the current mechanisms and proposed models allow for a refined view of pulmonary hypertension and a more effective method for diagnosis and treatment.

Scott E. Friedman and Bruce W. Andrus, “Obesity and Pulmonary Hypertension: A Review of Pathophysiologic Mechanisms,” Journal of Obesity, vol. 2012, Article ID 505274, 9 pages, 2012.

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