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Subject: Crystal Identification, Synovial Fluid
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Synovial fluid, often referred to as “joint fluid,” is a viscous liquid found in the joint cavities. Synovial membranes line the joints, bursae, and tendon sheaths. The function of the synovial fluid is to lubricate the joint space and transport nutrients to the articular cartilage.
The aspiration and analysis of synovial fluid may be done to determine the cause of joint disease, especially when accompanied by an abnormal accumulation of fluid in the joint (effusion). The joint disease may be crystal-induced, degenerative, inflammatory, or infectious. Morphologic analysis for cells and crystals, together with Gram stain and culture, help in the differentiation.
Normal synovial fluid is a clear, pale yellow, viscous liquid that does not clot. When a synovial membrane is inflamed for any reason, the WBC count in the synovial fluid increases.
In a rough fashion, one can classify this fluid into four groups.
Noninflammatory effusions (group I) occur when the WBC count is normal or minimally increased, as in traumatic arthritis or degenerative joint disease. Only rarely will such fluid have WBC counts of >2,000 cells/mm3.
Noninfectious mildly inflammatory effusions (group II) with WBC counts rarely >5,000 cells/mm3 occur in SLE and scleroderma.
In noninfectious acute inflammatory effusions (group III) characteristic of classic rheumatoid arthritis, gout, pseudogout, and rheumatic fever, the WBC count varies from 5,000 to 25,000 cells/mm3 but may exceed 50,000 or even 100,000 cells/mm3.
In the inflammatory effusions caused by infection (group IV), the WBC count commonly varies from 25,000 to >100,000 cells/mm3. As the WBC count becomes elevated, the percentage of polymorphonuclear leukocytes generally increases, the hyaluronate becomes degraded, and the synovial fluid sugar falls.
Examination of synovial fluid for crystals is facilitated by having a microscope with polarizing filters and a quarter waveplate (also known as a “red compensator”). Birefringence is a term used to describe the optical property associated with certain transparent crystals in which the speed of propagation of light along the major and minor axes of the crystal differs, causing the plane of polarized light to be rotated.
Detection of birefringent crystals is facilitated by use of two plane polarizing filters, one between the light source and the sample, and the other between the sample and the observer's eye. When the polarized filters are crossed, the background appears dark, and birefringent material, including a variety of crystals, appears brighter than the background.
Several types of crystals have been found in synovial fluids (Table 16.26). The two most important are monosodium urate (MSU), characteristic of gouty effusions, and calcium pyrophosphate dihydrate (CPPD), characteristic of the effusions of pseudogout (crystal deposition disease). Other crystals such as calcium hydroxyapatite, calcium oxalate, cholesterol, and corticosteroid esters may also be associated with inflammatory effusions.
Crystals that cause inflammation are usually 0.5 to approximately 20 μm in length, sparingly soluble in water, and capable of being phagocytized. At the peak of inflammation, most are intracellular.
Normal range: absent (no crystals present).
+, positive birefringence; −, negative birefringence; 0, no axis.
Crystals are best seen in fresh, wet-mount preparations examined with polarizing light.
Hydroxyapatite complexes (diagnostic of apatite disease) and basic calcium phosphate complexes can be identified only by EM; most cases are suspected clinically but never confirmed.
EDTA, ethylenediaminetetraacetic acid; PMN, polymorphonuclear neutrophil.
Source: Judkins SW, Cornbleet PJ. Synovial fluid crystal analysis. Lab Med. 1997;28:774. With permission from American Society for Clinical Pathology and ASCP Press.
According to the American College of Radiology, synovial fluid analysis should be undertaken in the febrile patient with an acute flare of established arthritis (e.g., RA, osteoarthritis) to rule out superimposed septic arthritis.
Repeated aspiration and synovial fluid analysis may be used to monitor the response of septic arthritis to treatment and may also be valuable for diagnosis of some cases of gout in which the initial aspirate does not have detectable crystals.
Positive identification of crystals provides a definitive diagnosis of joint disease.
Powdered anticoagulants such as oxalate are themselves crystalline; their use may cause confusion, masking the presence of synovial fluid crystals definitive for the disease.
Substantial variability has been noted among hospital laboratories in the ability to properly identify the presence or absence of MSU and CPPD crystals in synovial fluids. Studies of the performance of different hospital laboratories on the same synovial fluids suggest that MSU crystals are more easily detected than CPPD crystals.
MSU crystals: reported sensitivity ranges from 63 to 78%; specificity from 93 to 100% (positive likelihood ratio of 14 for a diagnosis of gout).
CPPD crystals: reported sensitivity ranges from 12 to 83%; specificity from 78 to 96% (positive likelihood ratio of 2.9 for a diagnosis of CPPD-associated arthritis).
The stability of crystals in synovial fluids is studied by many at different temperatures. CPPD crystals dissolved significantly, and MSU crystals were detectable up to weeks but became smaller and less numerous. As storage time increased, new artificial crystals developed in the form of star-shaped arrays, plate-like structures, and positive birefringent Maltese crosses. Synovial fluid should be evaluated within 1 hour of collection.