Pulmonary hypertension

Definition

• Normal pulmonary pressure: ~1/8th of systemic pressure (low resistance circuit)
• Pulmonary hypertension: pulmonary pressure becomes ≥1/4th of systemic pressure

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Classification

Primary (Idiopathic) Pulmonary Hypertension

• Uncommon; diagnosis of exclusion
• Most cases are sporadic or familial (autosomal dominant)

Secondary Pulmonary Hypertension (most common)

Etiology:

1. Chronic obstructive or interstitial lung disease: destruction of lung parenchyma → ↓ alveolar capillaries → ↑ pulmonary vascular resistance → ↑ arterial pressure
2. Recurrent pulmonary emboli: ↓ functional cross-sectional area of pulmonary vascular bed → ↑ vascular resistance
3. Antecedent heart disease: e.g. mitral stenosis → ↑ left atrial pressure → ↑ pulmonary venous pressure → pulmonary arterial hypertension
4. Congenital left-to-right shunts

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Pathogenesis

Underlying cause: pulmonary endothelial and/or vascular smooth muscle dysfunction

Primary (familial) pulmonary hypertension:

• BMPR2 gene mutation (codes for receptor of bone morphogenetic proteins in TGF-β superfamily)
• BMPR2 normally inhibits proliferation → mutation → abnormal endothelial and smooth muscle proliferation
• Sporadic: serotonin transporter gene (5-HTT) polymorphism → ↑ expression on smooth muscle → proliferation

Secondary pulmonary hypertension:

• Underlying disorder → mechanical/biochemical endothelial injury → ↓ vasodilators + ↑ vasoconstrictors
• Cytokine and growth factor production

Pulmonary arterial hypertension (shared final pathway):

• VSM dysfunction → vessels stiffen and thicken (fibrosis) → ↑ BP in lungs → ↑ right heart workload → right ventricular hypertrophy (cor pulmonale) → cardiac decompensation and failure

Pulmonary venous hypertension:

• Left heart failure → pooling of blood in lungs → pulmonary edema and pleural effusions
• By retrograde flow → also leads to pulmonary arterial hypertension

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Morphology

• Large elastic arteries: atheromas (similar to systemic atherosclerosis)
• Medium-sized muscular arteries: intimal + medial thickening → narrowed lumen
• Small arteries and arterioles: wall thickening → near-obliteration of lumen
• Primary PH only: plexogenic pulmonary arteriopathy → network of capillaries inside dilated, thin-walled small arteries

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Clinical Features

Primary PH:

• Develops at young age; more common in women
• Symptoms: fatigue, syncope, dyspnea on exertion, chest pain
• → Respiratory insufficiency + cyanosis → death from right-sided heart failure within 2–5 years

Secondary PH:

• May develop at any age
• Clinical picture reflects the underlying disease (respiratory insufficiency + right-sided heart strain)

💡 High-yield: Primary PH = BMPR2 mutation; young women; syncope + dyspnea; plexogenic arteriopathy; death in 2–5 yr. Secondary PH = COPD, recurrent emboli, mitral stenosis, shunts. Both → cor pulmonale. Venous PH = left heart failure → pulmonary edema.