PLEURAL FLUID ANALYSIS

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thoracentesis pleural fluid analytic tests

• Pleural fluid analysis is often indicated to diagnose causes of pleural effusions.
• Pleural fluid is obtained via thoracentesis, a procedure performed (often at bedside with sterile techniques) by inserting a needle into the pleural cavity to drain out as much fluid as possible to both relieve discomfort (therapeutic benefit) and obtain pleural fluid for analysis.
• The first step in the analysis is to determine whether the fluid is transudative or exudative using the Light’s criteria.
• Additional information can be obtained via pleural fluid gross appearance, cell count with differential, glucose level, pH level, cytology, tumor markers, microbiology, and other tests.

transudate vs. exudate


• Pleural effusions can be either transudative or exudative, depending on the underlying pathophysiological mechanism:
   Transudate: fluid that is forced out of the capillary into the pleural space due to either an increase in intravascular hydrostatic pressure (e.g. in heart failure, cirrhosis) or a decrease in intravascular osmotic pressure (e.g. in nephrotic syndrome). Fluid can also enter the pleural space from the peritoneal, retoperitoneal, cerebrospinal space, or infusion via central venous catheter
   Exudate: fluid with high protein content leaked into the pleural space across the highly permeable capillary membrane as a result of inflammation (e.g. malignancy, infection, autoimmune disorders, etc) but is not adequately drained by the lymphatic system due to various causes such as blockage or injury
• Light's criteria is routinely used to differentiate between these 2 types of pleural fluid. Protein and lactate dehydrogenase (LDH) levels in pleural fluid are compared with the corresponding serum levels (proteins and LDHs are used as surrogates for enzymatic activities of malignant and inflammatory cells, which are the pathological factors of exudative pleural effusions).
• Per Light's criteria, to be classified as “exudate”, 1 of the 3 criteria must be met:
   1) pleural protein/serum protein level is greater than 0.5
   2) pleural LDH/serum LDH level is greater than 0.6
   3) pleural LDH is greater than 2/3 of upper limit of serum LDH

pleural fluid gross appearance
TRANSUDATE

✿ Increased intravascular hydrostatic pressure
  ✧ heart failure
  ✧ central venous obstruction
    ☼ superior vena cava syndrome
    ☼ brachiocephalic vein obstruction (hemodialysis)

✿ Decreased intravascular osmotic pressure
  ✧ nephrotic syndrome
  ✧ hypoalbuminemia

✿ Intra-abdominal leak
  ✧ hepatic hydrothorax
  ✧ peritoneal dialysis
  ✧ urinothorax (gu tract obstruction / injury)
  ✧ glycinothorax (perforated bladder wall)


✿ Decreased pleural pressure
  ✧ atelectasis

✿ Cerebrospinal leak
  ✧ thoracic spinal surgery
  ✧ malpositioned ventriculoperitoneal shunt
  ✧ ventriculopleural shunt

✿ Iatrogenic
  ✧ malpositioned or leaked central venous catheter

EXUDATE

✿ Pulmonary diseases
  ✧ lung infection
    ☼ bacterial pneumonia / abscess
    ☼ tuberculosis
    ☼ viral pneumonia (flu, covid)
    ☼ fungal infection
    ☼ parasitic infection
  ✧ asbestosis / mesothelioma
  ✧ lung malignancy
  ✧ acute respiratory distress syndrome
  ✧ chest trauma
  ✧ diaphragmatic hernia

✿ Cardiovascular diseases
  ✧ pulmonary embolism or infarct
  ✧ pulmonary vein stenosis s/p afib ablation
  ✧ aortic dissection or aneurysm rupture

✿ Gastrointestinal diseases
  ✧ liver infection (abscess, viral hepatitis)
  ✧ cholecystitis / cholangitis
  ✧ splenic abscess or infarct
  ✧ subphrenic abscess / pleurobiliary fistula
  ✧ esophageal perforation
  ✧ acute pancreatitis
  ✧ pancreaticopleural fistula
  ✧ pancreatic pseudocyst rupture

✿ Obstetric-gynecologic diseases
  ✧ ovarian hyperstimulation syndrome
  ✧ post partum pleural effusion
  ✧ meigs' syndrome
  ✧ endometriosis

✿ Iatrogenic
  ✧ cardiothoracic or upper gi surgery
  ✧ malpositioned or leaked central venous catheter
  ✧ malpositioned feeding tube
  ✧ chest radiation therapy
  ✧ lung radioablation therapy
  ✧ esophageal sclerotherapy


✿ Autoimmune disorders
  ✧ rheumatoid arthritis
  ✧ systemis lupus erythematosus
  ✧ mixed connective tissue disease
  ✧ eosinophilic granulomatosis w/ polyangiitis
  ✧ granulomatosis w/ polyangiitis
  ✧ ig-g4 related disease
  ✧ behcet syndrome
  ✧ familial Mediterranean fever

✿ Systemic infiltrative diseases
  ✧ metastatic malignancy
  ✧ lymphoma / leukemia
  ✧ plasma cell dyscrasias (mm, waldenstrom)
  ✧ extramedullar hematopoiesis
  ✧ amyloidosis
  ✧ sarcoidosis
  ✧ uremia
  ✧ severe hypothyroidism

✿ Lymphatic diseases
  ✧ yellow nail syndrome
  ✧ lymphagioleiomyomatosis
  ✧ lymphagiectasia

✿ Drugs
  ✧ amiodarone
  ✧ nitrofurantoin
  ✧ dasatinib
  ✧ interleukin 2
  ✧ methotrexate
  ✧ clozapine
  ✧ ergot alkaloids
  ✧ phenytoin

✿ Other
  ✧ drowning
  ✧ electrical burns
  ✧ capillary leak syndromes

gross appearance, cell count, chemistry


• Additional tests can be done to further characterize exudative fluid and to determine etiologies including cell count with differential, glucose, pH, cytology, tumor markers, microbiology, amylase, NT-proBNP, triglyceride, cholesterol, among others.

pleural fluid gross appearance
pleural fluid cell count
pleural fluid chemistry

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