Medical Archive

Introduction

Pathobiology

• Endothelial dysfunction
  • ?Vasoconstrictive, proproliferative mediators (e.g., endothelin, TXA2)
  • ?Vasodilative, antiproliferative mediators (e.g., NO, prostacyclin)

Diagnosis and classification

• Physical exam
  • RV heave (or parasternal heave), which is an impulse palpated immediately to the left of the sternum that suggests RV enlargement.
  • S2: loud pulmonary component
  • S3: d/t RV volume overload, best heard at the left lower sternal border on end-inspiration.
• Echo
  • Dilated coronary sinus�
    • D/t dilation of the right atrium.
    • M/c cause is ?right-sided heart pressure secondary to pulmonary hypertension.

Group 1 – PAH, which can be idiopathic, or d/t drugs, HIV, or connective tissue diseases
Group 2 – PH d/t LHD
Group 3 – PH d/t chronic lung disease or hypoxemia
Group 4 – PH d/t chronic thromboembolic disease
Group 5 – PH d/t other causes (eg, hematologic, systemic disorders)

Pulmonary hypertension as a comorbid disease

Pulmonary arterial hypertension PAH

• Heritable PAH
  • Inactivating mutation in BMPR2 gene. ?In 20-40yrs women
  • Predisposes affected individuals to excessive endothelial and smooth muscle cell proliferation.
  • An insult (e.g., infection, drugs) is thought to then activate the disease process. 
• Pulmonary vasculature endothelial dysfunction results in �?vasoconstrictors (eg, endothelin) and �?vasodilators (eg, NO and prostacyclins).
  • Connective tissue disease (eg, RA, SS)
  • HIV infection 

Pulmonary Hypertension Associated with Left Heart Disease

1. PCWP > 12mmHg
2. Pulmonary venous congestion
3. Remodeling
   • Over time, occurs with ?smooth muscle cell proliferation ? endothelin-mediated pulmonary arteriolar vasoconstriction
   • Less extensive than in PAH ? partially reversible with treatment of the LHF.
4. ?pulmonary capillary and arterial pressure

Pulmonary Hypertension Associated with Lung Disease

• Destruction of lung parenchyma (eg, COPD)
  • Emphysematous obliteration of the vasculature 
• Lung inflammation/fibrosis (eg, interstitial lung diseases)
• Hypoxemic vasoconstriction (eg, obstructive sleep apnea, living in high altitude).

PH Associated with Chronic Thromboembolic Disease

Other disorders affecting the pulmonary vasculature

Sarcoidosis

Sickle cell disease

Schistosomiasis

Pharmacologic treatment of PAH

Prostanoids

Inhibits platelet aggregation
S/E: flushing, jaw pain.

Epoprostenol
Inhaled prostacyclins
Oral treprostinil (an extended release formulation)
Selexipag

Endothelin receptor antagonists

ERAs target ET-1
Hepatotoxic – monitor LFTs
e.g., bosentan

Nitric oxide pathway

Combination therapy