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Pleural Effusion

Pleural fluid provides surface tension between the visceral and parietal pleura and assures close apposition and mechanical coupling between lung and chest wall. It also serves as a lubricant preventing friction between pleural surfaces. Pleural fluid is continuously renewed. An ultrafiltrate of plasma moves from capillaries in the parietal pleura into the pleural space. Excess fluid is normally drained by lympatics in the parietal pleural. In a healthy person, the volume of pleural fluid around both lungs is approximately 0.26 mL per kg of body weight. A healthy adult weighing 75 kg would have approximately 10 mL of pleural fluid. Between 10 and 20 mL of fluid is produced per day.

The most common causes of pleural effusion are congestive heart failure, pneumonia, cancer, cirrhosis with ascites, and coronary artery bypass graft. Effusions can be classified into transudates and exudates based on the results of laboratory tests.

 

Test

Sensitivity for Exudate

Specificity for Exudate

Pleural/serum protein >0.5

86

84

Pleural/serum LDH >0.6

90

82

Pleural LDH>0.66x serum ULN

82

89

Pleural cholesterol >60 mg/dL

54

92

Pleural cholesterol >43 mg/dL

75

80

Pleural/serum cholesterol >0.3

80

81

Pleural fluid protein >2.9 g/dL

NA

NA

Serum – pleural albumin <1.2 g/dL

87

92

 

The first 3 criteria are known as Lights criteria. These criteria classify nearly all exudates correctly, but they misclassify approximately 20% of transudates as exudates. Misclassification is most commonly seen in patients on long term diuretic therapy for congestive heart failure because dieresis concentrates pleural fluid protein and LDH.

Normal pleural fluid is clear straw-colored fluid with a low protein concentration of ~1 g/dL and an alkaline pH of 7.60 to 7.66. Pleural fluid is more alkaline than blood because of its higher bicarbonate concentration. A small number of red blood cells (~40/uL0 and which blood cells (~150/uL) are normally present. White blood cells mostly consist of macrophages and lymphocytes.

Pleural fluid LDH >1000 IU/L suggests empyema, malignant effusion, rheumatoid effusion or pleural paragonimiasis.

A pleural fluid glucose <60 mg/dL or a pleural fluid: serum glucose ratio <0.5 may be seen in effusions caused by cancer, tuberculosis, empyema, esophageal rupture and lupus or rheumatoid pleuritis. Very low pleural glucose concentration below 30 mg/dL further restricts diagnostic possibilities to rheumatoid pleurisy or empyema. When a pleural pH value is not available, a pleural fluid glucose below 60 mg/dL can be used to identify complicated parapneumonic effusions.

Normal pleural fluid pH ranges between 7.60 and 7.66. Transudates usually have a pH between 7.45 and 7.55 while exudates have an even lower pH in the range of 7.30 to 7.45. Most bacterial infections result in a pH in the exudative range. One exception is infection with Proteus which produces an alkaline pH between 7.45 and 8.0. A pleural fluid pH of <7.30 is associated with a limited number of diseases including esophageal rupture, tuberculosis, rheumatoid disease, malignancy and pneumonia. Some experts have suggested that a pH>7.4 may be sufficient evidence to rule out a diagnosis of tuberculosis. Very low pleural pH of <6.0 is virtually diagnostic of esophageal rupture. In patients with malignant pleural effusion, pleural fluid pH<7.3 indicates reduced survival and is a contraindication for pleurodesis.

Pleural fluid pH is useful to evaluate the prognosis of effusions associated with pneumonia.  A pleural fluid pH >7.3 suggests that resolution is possible with medical therapy alone. A pH <7.2 suggests that a more complicated effusion or empyema requiring surgical drainage has probably formed. Pneumonia due to Proteus species is the exception to this rule because these bacteria produce urease that converts urea to ammonia, making the fluid alkaline (pH 7.45–8.0).

Pleural fluid pH should be measured with a blood gas analyzer and not with litmus paper or a pH meter, because both of the latter methods result in falsely elevated values.  Pleural fluid for pH measurement should be collected anaerobically in a heparinized syringe and analyzed within one hour of collection.

Studies suggest that pleural fluid levels of NT pro-BNP are elevated above 1300 ng/L in effusions due to congestive heart failure. 

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