Pulmonary Vascular Disease & ARDS
Clots, high pressures, and the stiff, flooded lung
Pulmonary embolism: source and physiology
Where clots come from. Most pulmonary emboli arise from proximal deep veins of the leg (femoral, iliac). Virchow triad explains why they form: venous stasis (immobility, surgery, long travel), endothelial injury (trauma, surgery), and hypercoagulability (malignancy, pregnancy, estrogen, inherited thrombophilia). A large saddle embolus lodges at the pulmonary artery bifurcation and can cause sudden death.
- Proximal DVTFemoral or iliac vein
- EmbolizesThrough the right heart
- Lodges in pulmonary arteryDead space, V/Q → ∞
- RV strain, shockHypoxemia
Gas exchange. The occluded region is ventilated but not perfused: alveolar dead space, with V/Q → ∞. Blood diverted to the remaining lung overperfuses it, creating low-V/Q units, so hypoxemia develops with a widened A-a gradient. Hyperventilation blows off CO₂, so the classic ABG is respiratory alkalosis with hypoxemia.
Hemodynamics. A large clot burden abruptly raises pulmonary vascular resistance; the thin-walled RV dilates and fails (acute cor pulmonale), LV filling falls, and massive PE produces obstructive shock.
Infarction is the exception. The lung has a dual blood supply (bronchial arteries), so most emboli do not infarct tissue. Infarcts occur mainly when circulation is already compromised (e.g., heart failure) and are hemorrhagic, wedge-shaped, and pleural-based, explaining pleuritic pain and hemoptysis.
Recognizing and confirming PE
Presentation. Sudden dyspnea, pleuritic chest pain, tachypnea, tachycardia, and hypoxemia; massive PE adds hypotension and right heart strain. Because the picture is often nonspecific, risk stratify before testing.
- Wells scoreSets pretest probability
- Low probability → D-dimerNegative result excludes PE (sensitive, not specific)
- Otherwise → CT pulmonary angiographyGold standard; shows the filling defect
- Contrast contraindicated → V/Q scanRenal failure, pregnancy
ECG. The most common finding is sinus tachycardia. The classic S1Q3T3 pattern (S wave in lead I, Q wave and inverted T in lead III) reflects right heart strain and is specific but insensitive; also look for new right axis deviation and right bundle branch block.
Treatment principle. Anticoagulation stops propagation while endogenous fibrinolysis clears the clot; thrombolysis is reserved for massive PE with hypotension.
Nonthrombotic emboli and thrombus pathology
FAT BAT. An embolus need not be thrombus: Fat, Air, Thrombus, Bacteria, Amniotic fluid, Tumor.
| Embolus | Setting | Clues |
|---|---|---|
| Fat | Long-bone (e.g., femur) fracture, liposuction | 1–3 days later: hypoxemia/dyspnea, neurologic change, petechial rash |
| Air | Divers ascending too fast; central line insertion or removal | Gas bubbles occlude vessels (decompression sickness in divers) |
| Bacteria | Right-sided endocarditis (IV drug use) | Septic emboli: multiple nodules that may cavitate |
| Amniotic fluid | Labor and delivery | Sudden dyspnea, shock, DIC; fetal squamous cells in maternal lung vessels |
| Tumor | Malignancy invading veins | Tumor cells lodge in pulmonary vessels |
Lines of Zahn. Alternating pale layers of platelets and fibrin and dark layers of red cells show that a thrombus formed in flowing blood before death. Postmortem clots lack these lines, are not attached to the vessel wall, and settle into a gelatinous yellow "chicken fat" layer over a dark "currant jelly" layer.
Pulmonary hypertension and cor pulmonale
Definition and signs. Pulmonary hypertension is a mean pulmonary artery pressure above 20 mmHg at rest (the older cutoff was ≥25). It causes exertional dyspnea, a loud (sometimes palpable) P2, a right ventricular heave, and eventually cor pulmonale. Sustained pressure produces medial hypertrophy and intimal fibrosis of pulmonary arteries and even atherosclerosis of the pulmonary trunk.
| Group | Mechanism | Examples |
|---|---|---|
| 1: PAH | Disease of the pulmonary arterioles | Idiopathic/heritable (BMPR2), connective tissue disease, drugs, HIV |
| 2 | Left heart disease (most common overall) | LV failure, mitral valve disease |
| 3 | Lung disease or hypoxia | COPD, interstitial lung disease, sleep apnea, high altitude |
| 4 | Chronic thromboembolic | Recurrent or unresolved PE |
| 5 | Multifactorial | e.g., sarcoidosis, myeloproliferative disorders |
Idiopathic/heritable PAH. Classically a young woman. BMPR2, a TGF-β–family receptor that normally restrains vascular smooth muscle growth, carries an inactivating mutation (autosomal dominant, incomplete penetrance), so smooth muscle proliferates. Severe disease shows plexiform lesions: tufts of capillary-like channels within dilated arteries. Therapy targets three vasodilator pathways.
| Class | Example | Mechanism |
|---|---|---|
| Prostacyclin analog | Epoprostenol | ↑ cAMP → vasodilation; inhibits platelet aggregation |
| Endothelin receptor antagonist | Bosentan | Blocks endothelin-1 vasoconstriction; hepatotoxic |
| PDE5 inhibitor | Sildenafil | ↑ cGMP → vasodilation |
Cor pulmonale. Right ventricular hypertrophy and failure caused by lung or pulmonary vascular disease, by definition sparing the left heart. Chronic cor pulmonale follows COPD, interstitial disease, and hypoxic vasoconstriction; acute cor pulmonale follows massive PE. The clue is isolated right-sided failure: JVD, hepatomegaly, peripheral edema, and a loud P2.
Acute respiratory distress syndrome
Berlin definition. Onset within 1 week of a known insult; bilateral opacities; respiratory failure not explained by cardiac failure or fluid overload; and PaO₂/FiO₂ ≤300 on PEEP ≥5 cm H₂O. Severity is mild (201–300), moderate (101–200), or severe (≤100).
Pathogenesis. Sepsis (the most common cause), aspiration, pneumonia, trauma, or pancreatitis activates neutrophils and cytokines that injure the alveolar-capillary membrane (diffuse alveolar damage). Capillary permeability rises, protein-rich exudate floods the alveoli, and hyaline membranes (fibrin plus necrotic cell debris) line the alveolar walls as type I pneumocytes die and surfactant is lost. Type II pneumocytes proliferate during repair, and some patients progress to fibrosis.
- Lung insultSepsis, aspiration, trauma
- Diffuse alveolar damageCapillary permeability up
- Protein-rich exudateHyaline membranes
- Low compliance + shuntRefractory hypoxemia
Physiology and ventilation. Flooded, collapsed alveoli are perfused but not ventilated (intrapulmonary shunt), so hypoxemia is refractory to supplemental O₂, and the lungs are stiff. Low tidal volume ventilation (6 mL/kg ideal body weight, ARDSNet) limits barotrauma and volutrauma to injured alveoli, accepting permissive hypercapnia. Adequate PEEP reopens alveoli and reduces shunt, and prone positioning improves V/Q matching.