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Body Fluid Panel

The serous body cavities are mesothelial lined potential spaces surrounding the lungs, heart and abdomen. Normally, they contain a small amount of fluid that is an ultrafiltrate of plasma. When production and resorption of this ultrafiltrate are not balanced, fluid may accumulate, resulting in an effusion. Effusions may be classified as transudates or exudates. Transudates are usually bilateral and arise from either increased capillary hydrostatic pressure or decreased oncotic pressure secondary to congestive heart failure, fluid overload, cirrhosis or hypoalbuminemia. Exudates are usually unilateral and result from increased capillary permeability or decreased lymphatic resorption associated with infection, autoimmune disease, pancreatitis or cancer.

Several laboratory tests are helpful in distinguishing transudates from exudates including pH, total protein, lactate dehydrogenase (LD), amylase, glucose, white cell count and differential. Only one of these values has to fall into the exudate range for the effusion to be classified as an exudate. Large chemistry panels should not be ordered on body fluids.

Light’s criteria have been widely used to classify pleural and pericardial fluid as a transudate or an exudate.

Light’s Criteria

Lab Test Transudate Exudate
Appearance Clear, pale yellow Turbid, bloody
Fluid total protein 3.0 g/dL or less >3.0 g/dL
Fluid/serum protein <0.5 >0.5
Fluid/serum LD <0.6 >0.6
Fluid LD <0.67 x ULN serum >0.67 x ULN serum
Cholesterol <45 mg/dL 45 mg/dL or greater
Specific gravity <1.015 >1.015

 

Exudates typically have higher protein concentration and LD activity and lower pH and glucose values than transudates. The protein concentration of an exudate usually exceeds 3 g/dL. Exudate LD activity is greater than 0.67 times the upper limit of normal for serum.

Pleural Effusions

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 alb <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.

Chylous Pleural Effusions

Chylous pleural effusions usually result from disruption or obstruction of the thoracic duct and are typically described as exudative lymphocytic pleural effusions with a milky appearance. Identifying chylothorax is important in determining the etiology of pleural effusion.

Chylothorax is defined according to Light’s criteria as a turbid pleural effusion with triglycerides >110 mg/dL and cholesterol <200 mg/dL. A milky appearing pleural fluid should always be investigated for chylothorax. Not all chylothorax is exudative, with 20% of cases being transudative. A non-milky appearance should not be used as a criterion to rule out a chylous effusion.

An important distinction should also be made between chylothorax and pseudo-chylothorax based on cholesterol and triglyceride concentrations. Pseudochylothorax is the accumulation of cholesterol crystals in a chronic effusion. It may be seen in patients with rheumatoid pleurisy or tuberculosis. Pleural fluid cholesterol is >200 mg/dL and triglyceride <50 mg/dL.

Approximately 15% of patients with chylothorax have pleural fluid triglyceride levels below 110 mg/dL, primarily due to perioperative fasting and malnourishment. In cases of suspected chylous effusion with triglycerides less than 110 mg/dL, the specimen can be sent to a reference laboratory for lipoprotein electrophoresis. The presence of chlyomicrons in the fluid supports the diagnosis of chylothorax.

Peritoneal Fluid

The criteria for classifying transudates and exudates in pleural and pericardial fluids are often misleading when applied to peritoneal fluid (ascites). Transudative processes may produce a peritoneal fluid protein level in the exudate range. Calculation of a serum to ascites albumin gradient (SAAG) is a more physiologically appropriate test. It is calculated as the serum albumin concentration minus the peritoneal fluid albumin. A high SAAG of 1.1 or greater indicates that ascites contains very little albumin and is related to portal hypertension, usually due to cirrhosis. A low SAAG <1.1 indicates that the concentration of albumin in ascites is similar to the plasma concentration. A low SAAG indicates that ascites is being produced by an extra-hepatic source such as by cancer, infection, pancreatitis or the nephrotic syndrome. SAAG is difficult to interpret when the serum albumin concentration is less than 2.2 g/dL.

Ascites fluid with an amylase level more than 3 times the serum value is usually caused by pancreatitis, pancreatic pseudocyst or trauma. Elevated bilirubin may indicate biliary tract injury. Elevated cholesterol in ascites fluid has been associated with malignancy. Elevated alkaline phosphatase has been associated with bowel injury.

Spontaneous bacterial peritonitis (SBP) is bacterial infection of the peritoneal tissues without any identificable secondary source of infection. It occurs in patients with cirrhosis of the liver, nephrotic syndrome and in immunocompromised patients. It is identified in 10 to 30% of patients hospitalized with ascites and mortality can approach 30%. Many patients do not manifest symptoms such as abdominal pain, fever or encephalopathy at the time of presentation. Therefore, it is recommended that all patients with cirrhosis and ascites undergo a paracentesis at the time of admission to assess for SBP. The diagnosis is based on a neutrophil count of 250/uL or greater. An elevated PMN count alone is sufficient to establish the diagnosis as peritoneal fluid and blood cultures are often negative.

Cell Counts

Total leukocyte and RBC counts are of limited value in body fluid analysis except when diagnostic peritoneal lavage is performed. Normally, less than 10,000 RBCs/uL are present in pleural, pericardial and peritoneal fluids. Pleural and pericardial fluids usually have less than 1000 WBC/uL while peritoneal fluid has less than 500 WBC/uL. RBC counts >100,000/uL in pleural fluid are suggestive of malignancy, trauma, or pulmonary infarct. Lavage fluids usually have less than 50,000 to 100,000 RBCs/uL and less than 200 WBC/uL. Higher RBC and WBC cell counts in lavage fluids are consistent with hollow organ perforation.

Source RBC Normal Range WBC Normal Range
Pleural <10,000/uL <1000/uL
Pericardial <10,000/uL <1000/uL
Peritoneal <10,000/uL <500/uL
Lavage <100,000/uL <200/uL

 

According to the literature related specifically to nephrology and dialysis, normal peritoneal dialysis fluid should contain less than 50 WBC/uL and have fewer than 15% neutrophils. A fluid should be considered suspicious for bacterial infection, when the total WBC count is >100/uL and the percentage of neutrophils exceeds 50%, Common nonbacterial causes of neutrophilia in dialysis fluids include infectious diarrhea, active colitis, menstruation or ovulation, and pelvic inflammatory disease. A Gram stain should also be performed, but the sensitivity for bacterial peritonitis is only 50%. However, a positive gram stain is predictive of culture results in 85% of cases.

Differential count is performed to determine the predominant cell type present in the fluid, which can suggest certain diseases. Reference ranges have not been established. Increased numbers of neutrophils are seen with exudates caused by bacterial infection, infarction, cancer or pancreatitis.   Increased numbers of lymphocytes are associated with viral infections, tuberculosis, lymphoproliferative disorders, congestive heart failure, and cirrhosis. Eosinophils are increased in infections, neoplasms, chronic renal failure, pneumothorax, pulmonary infarction and parasitic infestations. Plasma cells are present in rheumatoid arthritis, cancer, tuberculosis, and multiple myeloma.

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