How do you differentiate between transudative and exudative causes of pleural effusion in an adult patient without a clear history of liver disease or heart failure?

Differentiating Transudative from Exudative Pleural Effusion

Measure pleural fluid protein first: if <25 g/L it's a transudate, if >35 g/L it's an exudate; for values between 25-35 g/L, apply Light's criteria using simultaneous serum and pleural fluid protein and LDH measurements. 1

Initial Pleural Fluid Analysis

Step 1: Pleural Fluid Protein Measurement

• If serum protein is normal:
  • Pleural fluid protein <25 g/L → Transudate 1
  • Pleural fluid protein >35 g/L → Exudate 1
  • Pleural fluid protein 25-35 g/L → Proceed to Light's criteria 1

Step 2: Light's Criteria (When Protein is Borderline)

An effusion is exudative if it meets ANY ONE of the following: 2, 3

• Pleural fluid/serum protein ratio >0.5
• Pleural fluid/serum LDH ratio >0.6
• Pleural fluid LDH >0.67 (or >67%) of the upper limit of normal for serum LDH

Performance characteristics: Light's criteria have 98% sensitivity and 72% specificity for identifying exudates 2, 3

Addressing "Pseudoexudates" (False Exudates)

Common pitfall: Light's criteria misclassify 25-30% of transudates from heart failure or cirrhosis as exudates, creating "pseudoexudates" 4

When to Suspect a Pseudoexudate:

• Light's criteria suggest exudate BUT clinical picture strongly suggests heart failure or cirrhosis 4

Corrective Tests:

Use albumin gradient to reclassify: 2

• Serum albumin minus pleural fluid albumin >1.2 g/dL → True transudate (correctly reclassifies ~80% of pseudoexudates)
• Pleural fluid/serum albumin ratio <0.6 → True transudate 2

Use NT-proBNP for heart failure: 2, 3

• Pleural fluid or serum NT-proBNP >1500 μg/mL → Heart failure-related transudate
• Sensitivity 92-94%, specificity 88-91% 2

Alternative Criteria When Serum Samples Unavailable

If you cannot obtain simultaneous serum samples: 3

• Pleural fluid LDH >67% of upper limit of normal for serum → Exudate
• Pleural fluid cholesterol >55 mg/dL → Exudate 4, 3

Additional Diagnostic Clues from Fluid Appearance

Visual Inspection: 1

• Serous/clear: Can be either transudate or exudate
• Turbid/milky: Centrifuge the sample
  • If supernatant clears → Empyema (cell debris)
  • If remains turbid → Chylothorax or pseudochylothorax (high lipid content)
• Bloody: Check hematocrit
  • Pleural fluid hematocrit >50% of peripheral blood → Hemothorax (usually malignancy, PE, trauma, asbestos)
  • Pleural fluid hematocrit <1% → Blood not clinically significant

Common Causes by Category

Transudates (>80% are heart failure): 2, 5

• Congestive heart failure (most common)
• Liver cirrhosis with ascites
• Nephrotic syndrome
• Peritoneal dialysis
• Hypoalbuminemia

Exudates: 2, 3, 6

• Malignancy (26% of exudates)
• Pneumonia/parapneumonic effusion
• Tuberculosis
• Pulmonary embolism
• Autoimmune disorders (rheumatoid arthritis, lupus)

Critical Caveat About Imaging

Ultrasound and CT cannot replace biochemical analysis for transudate-exudate differentiation 2, 3, 7

• Anechoic effusions on ultrasound can be either transudate or exudate 2, 7
• Septations on ultrasound are 95% specific for exudate but not sensitive 7
• Imaging provides adjunctive information only; biochemical analysis is mandatory 2

Recommended Thoracentesis Protocol

Send pleural fluid for: 3

• Protein and LDH (with simultaneous serum samples)
• Cytology (diagnostic in 60% of malignant effusions)
• pH (if infection suspected)
• Gram stain and culture (in both sterile vials AND blood culture bottles)
• AAFB stain and TB culture