A 27-year-old woman comes to the office due to exertional dyspnea over the past 3 months. The patient initially had shortness of breath during exercise but now becomes dyspneic with routine activities. She has had no cough, fever, or leg swelling but has noticed increased fatigue over this time. The patient does not use tobacco, alcohol, or illicit drugs. Vital signs are within normal limits. Physical examination reveals a loud pulmonic component of S2 but is otherwise unremarkable. Chest x-ray is normal. Echocardiography shows elevated pulmonary artery systolic pressure and right ventricular hypertrophy. Left ventricular structure and function are normal. Which of the following patterns of chemical mediators is most likely present in this patient's pulmonary arteries?

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Quizplus · Accepted Answer

11ec160b_3b49_b3f2_9249_8d9b16b1b028_MD0001_00 This young woman with progressive dyspnea and fatigue and a loud pulmonic component of S2 on physical examination likely has pulmonary arterial hypertension (PAH). PAH results from progressive remodeling of the small- and medium-sized pulmonary arteries/arterioles. Endothelial dysfunction leads to an increase in vasoconstrictive, proproliferative mediators (eg, endothelin, thromboxane A2) and a decrease in vasodilative, antiproliferative mediators (eg, nitric oxide, prostacyclin). The relative imbalance of these mediators leads to vasoconstriction and smooth muscle proliferation with intimal thickening of the vascular walls; consequently, there is increased pulmonary vascular resistance and elevated pulmonary arterial pressure. Over time, the right ventricle is unable to pump against the increased afterload, and right-sided heart failure develops. Medical therapy for PAH targets the mediator imbalance created by endothelial dysfunction. Endothelin receptor antagonists (eg, bosentan) are used to reduce vasoconstriction, while prostacyclin analogues (eg, epoprostenol) and nitric oxide-enhancing agents (eg, sildenafil) are used to promote vasodilation. All of these agents help reduce tissue proliferation. (Choices B, C, D, and E) These changes in the levels of prostacyclin, thromboxane, and nitric oxide are not consistent with the changes that occur in PAH. Educational objective: Pulmonary arterial hypertension results from endothelial dysfunction that leads to an increase in vasoconstrictive, proproliferative mediators (eg, endothelin, thromboxane A2) and a decrease in vasodilative, antiproliferative mediators (eg, nitric oxide, prostacyclin). The relative imbalance in these mediators leads to vasoconstriction and intimal-wall thickening with a consequent increase in pulmonary vascular resistance.

A 27-Year-Old Woman Comes to the Office Due to Exertional