Joint Fluid Interpretation

Synovial fluid, often referred as joint fluid, is located in all joints or diarthroses. At the synovial joints, the bones are covered by articular cartilage and are separated from each other by a small cavity that contains the synovial fluid. Together, all these anatomic elements form the joint, which is enclosed in the articular capsule. Inside these capsules are specialized secretory cells termed synoviocytes (types A and B), which produce the components of the synovial fluid (eg, matrix constituents, hyaluronic acid and salts, collagens, fibronectin for the intimal interstitium and synovial fluid).^[1]The synoviocytes also contribute to the local production of cytokines, small-molecule mediators of inflammation, and proteolytic enzymes that degrade the extracellular matrix, therefore being key components of the inflammatory rheumatoid arthritis pathways that affect joints.^{[2, 3]}Together, the cartilages and the synovial fluid protect the bones, reducing the friction between them during movement. Synovial fluid also provides the nutrients and lubrication for the joints.

Biochemically, the synovial fluid is an ultrafiltrate of plasma across the synovial membrane enriched with various compounds produced by the synoviocytes. In normal physiological conditions, the biochemical composition of the synovial fluid is similar to that of plasma. In pathological conditions, laboratory evaluation of synovial fluid provides information about the pathology of the condition affecting the joint (eg, arthritis).^[4]

Similar to other body fluids, common laboratory evaluation of synovial fluid involves the following three steps

Physical examination of synovial fluid (eg, appearance, to include color, viscosity, other physical characteristics)
Chemical analysis (eg, glucose, total protein level, uric acid)^[5]
Microscopic evaluation (eg, cell count and differential count, crystal identification)

In addition, synovial fluid can be subjected to microbiologic, serologic, and cytologic laboratory evaluations.

Typical characteristics of synovial fluid

The characteristics of normal synovial fluid are as follows:

Appearance: Clear
White blood cell (WBC) count: Less than 200 cells/µL
Polymorphonuclear neutrophils (PMNs): Less than 25%
Viscosity: High
Glucose level: Similar to that of the patient’s serum glucose level

The following are typical characteristics of synovial fluid in noninflammatory conditions (eg, osteoarthritis, trauma):

Appearance: Clear, yellow
WBC count: Less than 2000 cells/µL
PMNs: Less than 25%
Viscosity: High
Glucose level: Similar to that of the patient’s serum glucose level

Collection and testing

Synovial fluid is collected via arthrocentesis (needle aspiration). The collected volume depends on the size of the joint and the necessary tests. Generally, the volume of the synovial fluid within a joint is only of few milliliters, but it can significantly increase in the presence of inflammation.

Depending on the test, different types of preservatives are required, as follows:

Sterile heparinized tubes for microbiology testing
Heparinized (Green-top tubes) or EDTA tubes (Lavender-top tubes) for cell count
No preservatives for most chemistry tests
NaF for glucose testing

Powder preservatives or powdered gloves should not be used for sample collection as they can introduce particulates that could interfere with the synovial crystal analysis. Additionally, centrifugation, separation, and sample evaluation should be done as so as possible to avoid changes in synovial crystals

Indications and result interpretation

Indications include evaluation of inflammation, infections, trauma and degenerative diseases of the joints.

The aspect, biochemical composition, and microscopic content of synovial fluid change with different diseases, conditions, or medications.

Conditions associated with changes in the appearance of synovial fluid

In normal conditions, synovial fluid is colorless or faint yellow and clear, and it can form viscous strings of 4-6 cm (owing to polymerization of hyaluronic acid). (The word synovial comes from the Latin word for egg/egg white.)^[4]

The color and clarity of synovial fluid can change in different medical conditions, as follows:

Inflammatory diseases of nonimmunologic origin: Cloudy/turbid, dense yellow with crystals
Septic conditions: Cloudy, yellow-green, more viscous, positive culture
Hemorrhagic conditions (eg, trauma, traumatic aspiration): Cloudy, reddish, low viscosity, with WBC count equal to the blood count
When a high number of crystals are present: Milky/cloudy

The viscosity of synovial fluid can change in different medical conditions. In arthritis, the viscosity of synovial fluid is decreased because of decreased production and polymerization of hyaluronic acid. Viscosity can be empirically evaluated by forming a string of synovial fluid between the tips of the fingers. A string of 4-6 cm is considered normal. The mucin clot test can be used to evaluate viscosity, but it has little diagnostic information and is rarely used.^{[4, 6]}

Conditions associated with changes in the biochemical composition of synovial fluid

For accurate interpretation of synovial fluid laboratory results, serum samples should be concomitantly evaluated. In normal circumstances, the biochemical composition of synovial fluid is similar to that of serum. Therefore, the concentration of most of the analytes of synovial fluid is the same as that in serum.

Glucose is routinely measured in synovial fluid, and the glucose concentration in synovial fluid should be similar to that of serum. For accurate interpretation of glucose concentration in synovial fluid, serum samples should be concomitantly evaluated. Glucose is significantly decreased in inflammatory (eg, immunologic disorders, lupus, scleroderma, ankylosis, crystal-induced gout and pseudogout, rheumatoid arthritis) and septic joint diseases. To avoid obtaining a falsely decreased glucose concentration, samples used for glucose evaluation should be collected in NaF tubes to prevent rapid glycolysis and should be tested within 1 hour after collection.^{[4, 6]}

Total protein concentration in synovial fluid is lower than in serum, usually one third of that in serum. However, this concentration increases in inflammatory and hemorrhagic disorders.^{[4, 6]}

Uric acid is measured for evaluation of gout (uric acid is significantly elevated in gout), and identification of a high number of uric acid crystals in synovial fluid confirms the diagnosis of gout.^{[4, 6, 7]}

Microscopic evaluation of crystals in synovial fluid

The presence of monosodium urate (MSU) crystals is associated with gout and reflects impaired metabolism of uric acid due to genetic defects, liver diseases, alcoholism, high-purine‒content diet, chemotherapy, or impaired renal excretion of uric acid in renal diseases. MSU crystals are needle-shaped and have negative/yellow birefringence in compensated polarized light.

Calcium pyrophosphate (CPP) crystals are associated with pseudogout, which is characterized by degenerative arthritis, cartilage calcification, and increased calcium endocrine disorders. These crystals are rhombic-shaped and have positive/blue birefringence in compensated polarized light.^{[4, 6]}

Cholesterol crystals can be found in patients with hyperlipoproteinemia and rheumatoid arteritis. They are rhombic and have negative/yellow birefringence in compensated polarized light.^{[4, 6]}

Corticosteroids crystals can be formed and detected posttreatment with intra-articular injections of anti-inflammatory corticosteroids. They are flat, small, and have different shapes and can have both positive/blue and negative/yellow birefringence in compensated polarized light.^{[4, 6]}

Calcium phosphate crystals (apatite) are associated with degeneration and calcification of cartilage and osteoarthritis. They are coffin-lid‒shaped and have no birefringence in compensated polarized light.^{[4, 6]}

Calcium oxalate crystals can be seen in patients with renal diseases on dialysis. They are shaped like envelopes or pyramids and have negative/yellow birefringence in in compensated polarized light.^{[4, 6]}

Cell counts in synovial fluid

WBC count is one the most frequent tests performed on synovial fluid. Normally, synovial fluid contains less than 200 cells/µL (WBC). This count increases significantly in infections and inflammation.^{[8, 9]}Gram stain and culture can be used for differential diagnosis.^[4]