Pleural Effusion — Harrison's 22e

Anatomy & Normal Physiology

• Fluid enters the pleural space from parietal pleural capillaries and from lung interstitium via the visceral pleura (or from the peritoneal cavity via diaphragmatic defects).
• Fluid is removed by parietal pleural lymphatics, which can absorb up to 20× the normal rate of formation.

Diagnostic Approach

Light's Criteria (Exudate if ≥1 criterion met):

These criteria misidentify ~25% of transudates as exudates — particularly in diuretic-treated heart failure and hepatic hydrothorax (pseudoexudates). When protein criteria are borderline, a serum-PF albumin gradient > 1.2 g/dL or serum-PF protein gradient > 3.1 g/dL can identify pseudoexudates (100% sensitivity in CHF, 99% in hepatothorax). Elevated PF cholesterol combined with elevated LDH also favors a true exudate.

Disease-Specific PF Tests (Table 305-2):

Causes

Transudative Effusions

1. Congestive heart failure (most common cause overall)
2. Cirrhosis (hepatic hydrothorax)
3. Nephrotic syndrome
4. Peritoneal dialysis
5. Superior vena cava obstruction
6. Myxedema
7. Urinothorax

Exudative Effusions

• Bacterial (parapneumonic / empyema) — most common exudative cause in the US
• Tuberculosis
• Fungal, viral, parasitic

• Pulmonary embolism
• GI disease: esophageal perforation, pancreatic disease, intraabdominal abscess, diaphragmatic hernia, post-abdominal surgery, endoscopic variceal sclerotherapy, post-liver transplant
• Collagen vascular disease: rheumatoid pleuritis, SLE, drug-induced lupus, Sjögren syndrome, granulomatosis with polyangiitis (Wegener's), Churg-Strauss
• Post-CABG
• Asbestos exposure
• Sarcoidosis, uremia, Meigs' syndrome, yellow nail syndrome
• Drug-induced: nitrofurantoin, dantrolene, methysergide, bromocriptine, procarbazine, amiodarone, dasatinib
• Trapped lung, radiation therapy, post-cardiac injury syndrome
• Hemothorax, chylothorax, ovarian hyperstimulation syndrome, pericardial disease
• Iatrogenic injury

Key Individual Effusion Types

1. Heart Failure (Transudate)

• Mechanism: elevated left atrial/pulmonary venous pressure → increased interstitial fluid → overwhelms parietal lymphatics.
• Thoracentesis is indicated if effusions are not bilateral/comparable in size, patient is febrile, or pleuritic chest pain is present.
• PF NT-proBNP > 1500 pg/mL supports CHF etiology.

2. Parapneumonic Effusions (PPE) / Empyema (Exudate)

• Found in up to 50% of community-acquired pneumonia; most common exudative cause in the US.
• Most PPEs are reactive (culture-negative). In ~10%, infection sets in → complicated PPE or empyema (fibrinopurulent/grossly purulent fluid).
• Aerobic bacteria: acute febrile illness, pleuritic chest pain, leukocytosis.
• Anaerobic: subacute, weight loss, mild anemia, aspiration history — may have large effusion with minimal parenchymal infiltrate.
• Free-flowing fluid confirmed by lateral decubitus CXR, CT, or ultrasound.
• Drainage indications (any of the following):
  • Loculated fluid on imaging
  • PF pH < 7.20 or PF glucose < 60 mg/dL
  • Positive Gram stain or culture
  • Gross pus (empyema)
• Options: thoracentesis, tube thoracostomy, VATS (video-assisted thoracoscopic surgery).
• Intrapleural fibrinolytics (t-PA + DNase) used for loculated/complex parapneumonic effusions.

3. Malignant Effusion (Exudate)

• Second most common cause of exudative effusion.
• Most common primaries: lung > breast > lymphoma.
• Diagnosed by PF cytology (positive in ~60%) or pleural biopsy. Thoracoscopy improves yield.
• PF glucose < 60 mg/dL and pH < 7.30 → poor prognosis, reduced pleurodesis success.
• Management: therapeutic thoracentesis, pleurodesis (talc most effective), indwelling pleural catheter (IPC) for trapped lung or recurrent effusion.

4. Tuberculous Pleuritis (Exudate)

• Lymphocyte-predominant exudate; often in young patients in endemic areas.
• Diagnosis: PF adenosine deaminase (ADA) levels, PF culture (positive in <40%), or pleural biopsy.
• Treated with standard anti-TB regimens; glucocorticoids may reduce acute symptoms.

5. Pulmonary Embolism (Exudate or Transudate)

• Present in up to 30% of PE cases; usually small.
• Can be transudative or exudative.
• Diagnosis with CT pulmonary angiography or V/Q scan.

6. Hepatic Hydrothorax (Transudate)

• Cirrhosis with ascites → fluid migrates through diaphragmatic defects → usually right-sided.
• Diagnosed by injecting Tc-99m sulfur colloid intraperitoneally — if detected in pleural space, confirms hepatic hydrothorax.
• Treatment: sodium restriction, diuretics, TIPS; recurrent cases may need IPC.

7. Chylothorax

• Milky fluid; PF triglycerides > 110 mg/dL confirms diagnosis.
• Causes: thoracic duct disruption (trauma, surgery, malignancy).
• Treatment: low-fat diet/TPN, octreotide, surgical ligation/pleurodesis.

Management Summary

Physical Examination of Pleural Effusion

Symptoms (Pre-examination Context)

• Small effusions (<500 mL) are often asymptomatic
• Dyspnoea — the cardinal symptom, typically appearing once fluid exceeds ~500 mL
• Pleuritic chest pain — sharp, worse on inspiration; or referred pain to the ipsilateral shoulder
• With massive effusions (>1.5–2 L): haemodynamic compromise, orthopnoea, inability to lie flat

1. INSPECTION

The examination finding that best correlates with presence of a pleural effusion is asymmetric chest wall expansion (lag on affected side). — Washington Manual

2. PALPATION

3. PERCUSSION

"Auscultatory percussion" (percussing while listening with the stethoscope) may be more sensitive and specific for detecting pleural effusion than standard percussion alone. — Rosen's

4. AUSCULTATION

Comparison Table: Classical Physical Signs

Key Differentiating Points

• Effusion vs. Consolidation: The critical distinction is fremitus — decreased in effusion, increased in consolidation. Egophony is localised to the upper border of the effusion (not throughout), whereas in consolidation it is present throughout the consolidated area.
• Effusion vs. Atelectasis: Both cause dullness and absent breath sounds, but in atelectasis the trachea/mediastinum shifts toward the affected side; in effusion it shifts away.
• >200 mL of fluid is needed before physical signs become detectable; imaging (CXR, ultrasound, CT) is more sensitive for smaller volumes.