Pleural Effusion-General

Physiology

Pleural Space Cell Content

  • Pleural space normally contains 75% macrophages + 23% lymphocytes

Etiologies of Various Pleural Space Pressure States

PLEURAL SPACE

CXR Findings

  • Typical CXR Finding = Pleural Effusion with Contralateral Shift of Mediastinum
  • CXR Finding in Presence of Trapped Lung, Fixed Mediastinum, or Co-Existent Atelectasis = Pleural Effusion with Ipsilateral Shift of Mediastinum (or Midline Mediastinum)

Pleural Fluid Criteria

General Comments

  • LDH Ratio and Total Protein Ratio are Necessary from Light’s Criteria
    • The pleural LDH <66% criterion does not add more in discriminative value
  • Cut-Off Values for LDH and Total Protein Ratios: since there is not a discrete cut-off between values of LDH and total protein, the specified cut-off values give high sensitivity but lower specificity (ie: you will detect all true exudates, but you may misclassify some transudates as exudates, as in diuresed congestive heart failure cases)

Transudate (see Pleural Effusion-Transudate, [[Pleural Effusion-Transudate]])

  • LDH Ratio <0.6
  • Total Protein Ratio <0.5
  • Pleural LDH <66% of Upper Limit of Normal Range for Serum LDH
  • Pleural Cholesterol <55-60 mg/L
  • Pleural/Serum Cholesterol Ratio: normal
  • Serum-Pleural Albumin Gradient (SPAG) >1.2 g/dL
    • If fluid clinically appears to be a transudate and SPAG >1.2, but Light’s criteria suggest exudate, fluid can be assumed to be a transudate (albumin is lower MW than other proteins and crosses capillary walls more easily)

Exudate (see Pleural Effusion-Exudate, [[Pleural Effusion-Exudate]])

  • General Comments: pleural effusion is considered exudative if it meets any one of the following criteria, although LDH ratio and total protein ratio are the best criteria
  • LDH Ratio >0.6
  • Total Protein Ratio >0.5
  • Pleural LDH >66% of Upper Limit of Normal Range for Serum LDH
  • Pleural Cholesterol >55-60 mg/dL
  • Pleural/Serum Cholesterol Ratio: elevated
  • Serum-Pleural Albumin Gradient (SPAG) <1.2 g/dl
    • If fluid clinically appears to be a transudate and SPAG >1.2, but Light’s criteria suggest exudate, fluid can be assumed to be a transudate (albumin is lower molecular weight than other proteins and crosses capillary walls more easily)

Bloody Effusion (see [[Pleural Effusion-Bloody Effusion]])

  • RBC Count >100k

Hemothorax (see [[Pleural Effusion-Hemothorax]])

  • Pleural Hct >50% of Serum Hct

Chylothorax (see [[Pleural Effusion-Chylothorax]])

  • Pleural Fluid Triglyceride: elevated
    • Trig >100 mg/dL: diagnoses chylothorax (chylothorax fluid clears with addition of ethyl ether)
    • Trig <50 mg/dL: rules out chylothorax
    • Trig 50-110 mg/dL: perform lipoprotein analysis for chylomicrons to diagnose chylothorax
  • Pleural Fluid Chylomicron: seen

Pseudochylothorax (Cholesterol Pleurisy) (see [[Pleural Effusion-Pseudochylothorax]])

  • Elevated cholesterol (>200 mg/dL), but no triglycerides or chylomicrons

Empyema (see [[Pleural Effusion-Parapneumonic]])

  • Pus in the pleural space (with or without a positive gram stain)

Pleural Fluid pH

  • Routine measurement of pleural pH is recommended only in patients with parapneumonic effusions
  • Technique: collect blood aerobically in heparinized syringe (similar to ABG collection technique)
    • Sample left open to air (or with sir bubble in the syringe) can have increase in pH due to loss of CO2 into the air
  • In general, pleural fluid pH correlates with pleural fluid glucose
    [Potts DE, Willcox MA, Good JTJ, et al: The acidosis of low-glucose pleural effusions. Am Rev Respir Dis 1978; 117:665-671]

Pleural Fluid Cholesterol

  • Cholesterol is always very high (>200 mg/dL) in Pseudochylothorax (see [[Pleural Effusion-Pseudochylothorax]])

Pleural Fluid Triglycerides

  • Trig >100 mg/dL: diagnoses chylothorax (chylothorax fluid clears with addition of ethyl ether)
  • Trig <50 mg/dL: rules out chylothorax
  • Trig 50-110 mg/dL: perform lipoprotein analysis for chylomicrons to diagnose chylothorax

Pleural Fluid Amylase

  • Increased Pleural Fluid Amylase
    • Esophageal Perforation (see Esophageal Perforation, [[Esophageal Perforation]])
      • Amylase originates from salivary source
      • Typically increased in pleural fluid within 2 hrs of perforation
    • Pancreatico-Pleural Fistula: pleural fluid amylase is typically very high (>4000 IU/mL)
    • Malignancy
      • Approximately 10% of malignant effusions (due to non-pancreatic malignancy) have mildly elevated pleural amylase
      • Pleural amylase in these cases is of the salivary isoenzyme type

Pleural Fluid Adenosine Deaminase (ADA)

  • ADA is released from activated lymphocytes
  • ADA is >45 U/mL in almost all patients with TB pleuritis
    • However, elevated ADA can also seen in empyema, lymphoma, leukemia, and RA
  • ADA may be less useful in Asians
  • ADA is a sensitive marker for TB pleuritis even in the setting of HIV
    [Baba K, Hoosen AA, Langeland N, et al: Adenosine deaminase activity is a sensitive marker for the diagnosis of tuberculous pleuritis in patients with very low CD4 counts. PLoS One 2008; 3:e2788]

Pleural Fluid ANA

  • Pleural Fluid ANA: positive at >1:40 titer
    • High Negative Predictive Value for Diagnosis of Lupus Pleuritis: positive pleural ANA is present in all cases of lupus pleuritis -> negative pleural ANA suggest that lupus pleuritis is not the etiology of the effusion
    • Low Specificity for Diagnosis of Lupus Pleuritis: positive pleural ANA can also be seen in 11-27% of other effusions -> importantly, neither the titer of ANA, ratio between pleural and serum ANA, nor pattern of staining increase the specificity of the pleural ANA test for lupus pleuritis
  • Pleural/serum ANA ratio is >1 (with pleural ANA >1:160) in SLE

Pleural Fluid RF

  • Pleural titer >1:320 is seen in RA (this is usually higher than the concomitant serum titer)

Pleural Fluid Complement

Pleural Fluid Immunocytometry

  • Positive in Lymphoma-Associated Exudates (see Lymphoma, [[Lymphoma]])

Pleural Fluid Mesothelial Cells

  • Decreased Pleural Fluid Mesothelial Cells
  • Increased Pleural Fluid Mesothelial Cells

Pleural Fluid Interferon Gamma

  • Elevated in TB pleuritis

Pleural Fluid TB PCR

  • May be useful in diagnosis of TB pleuritis
  • However, these tests have low sensitivity, often comparable to that of cultures alone

References

  • Baba K, Hoosen AA, Langeland N, et al: Adenosine deaminase activity is a sensitive marker for the diagnosis of tuberculous pleuritis in patients with very low CD4 counts. PLoS One 2008; 3:e2788