Pleural Effusion-General

Physiology

Pleural Space Cell Content

Pleural space normally contains 75% macrophages + 23% lymphocytes

Etiologies of Various Pleural Space Pressure States

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

Decreased Pleural Fluid Complement
- Rheumatoid Arthritis (RA) (see Rheumatoid Arthritis, [[Rheumatoid Arthritis]])
- Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus, [[Systemic Lupus Erythematosus]])

Pleural Fluid Immunocytometry

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

Pleural Fluid Mesothelial Cells

Decreased Pleural Fluid Mesothelial Cells
- Rheumatoid Arthritis (RA) (see Rheumatoid Arthritis, [[Rheumatoid Arthritis]])
- Tuberculosis (see Tuberculosis, [[Tuberculosis]])
Increased Pleural Fluid Mesothelial Cells
- Radiation Pleuritis (see Radiation Pleuritis, [[Radiation Pleuritis]])

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