Pulmonary Hypertension

Pathophysiology

1) increased arterial pressure in lungs 2) primary or idiopathic form occurs in absence of known precipitating causes 3) secondary form caused by – mitral stenosis, pulmonary venous occlusive disease, extreme obesity (Pickwickian syndrome), chronic hypoxemia, recurrent pulmonary embolism, kyphosis, infiltrative lung disease, chronic bronchitis, long periods at high altitude

Signs and Symptoms

1) insidious onset of dyspnea idiopathic form 2) right heart failure with venous distention of neck 3) peripheral cyanosis late in disease 4) palpable right ventricular heave (owing to cor pulmonale) 5) fatigue 6) syncope 7) hepatomegaly 8) ankle edema 9) tachypnea 10) nonproductive cough 11) chest pain

Characteristic Test Findings

Radiology – 1) scattered infiltrates consistent with hemorrhage and hemosiderosis on chest radiograph 2) enlarged central pulmonary arteries EKG – 3) right axis deviation with right ventricular hypertrophy Echocardiography – 4) right ventricular enlargement with decreased left ventricular size Laboratory – hypoxemia

Histology/Gross Pathology

1) early changes are reversible if underlying conditions are corrected (e.g., with heart surgery) 2) grade 1 – smooth muscle hypertrophy of arteries 3) grade 2 – intimal proliferation exists 4) grade 3 – intimal fibrosis has begun 5) grade 4 – dilation and thinning of pulmonary arteries with formation of nodular plexiform lesions 6) grade 5 – pulmonary artery rupture with hemorrhage into lung parenchyma 7) grade 6 – fibrinoid necrosis of arteries/arterioles

Associated Conditions

1) right-sided heart failure 2) generalized venous congestion 3) diet drugs fenfluramine and phentermine

Biochemistry

1) recurrent pulmonary embolism causes pulmonary hypertension through mechanical blockage of the arteries with resultant vasoconstriction and cytokine release 2) at birth the vasculature of the lungs thin and dilate as the lung moves to a high-volume/low pressure system from a low-volume/high pressure system in the fetus that shunts blood through the ductus arteriosus

Inheritance/Epidemiology

1) idiopathic pulmonary hypertension affects mostly women in the 20s and 30s 2) a few cases are familial with involved defect likely a trinucleotide repeat expansion on 2q31-32

Treatment

1) previously idiopathic from was relentlessly progressive and required heart-lung transplantation 2) new treatment regimens can at least slow the progression and includes – IV adenosine, IV prostacyclin, calcium channel blockers (nifedipine,diltiazem), anticoagulation, digoxin, diuretics, avoidance of strenuous activity

Tips for USMLE

1) isolated right-sided failure can occur in absence of left-sided failure 2) in pulmonary hypertension the right ventricular fraction does not increase with exercise as it would in a normal patient