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Synovial Fluid Analysis

The most important reason for performing joint fluid analysis is to rule out septic arthritis. Synovial fluid analysis can demonstrate local inflammatory response, infection and the presence of crystals. Synovial fluid effusions are classified into five general etiologic categories: noninflammatory responses, inflammation, sepsis, crystal induced and hemorrhage.The most common diseases associated with each category are summarized in the following table.

Effusion

Diseases

Noninflammatory

osteoarthritis, trauma, osteochondritis, pigmented villonodular synovitis, sickle cell disease, neuropathic

Inflammation

rheumatoid arthritis, SLE, Reiters syndrome, ankylosing spondylitis, ulcerative colitis, psoriasis

Infection

bacteria, fungi, mycobacteria

Crystal

gout, pseudogout

Hemorrhage

trauma, hemophilia, hemangioma, pigmented villonodular synovitis, anticoagulant therapy, tumors

The following tests can be performed on synovial fluid.

  • Visual examination
  • Cell Count
  • Gram stain & culture
  • Polarizing microscopic crystal exam

Normal synovial fluid is a clear, yellowish fluid and transparent enough to read newsprint through. The following table summarizes the typical laboratory findings for each category of joint disease.

Test

Normal

Non-inflam

Inflam

Sepsis

Crystal

Hemo

Clarity

Clear

Slightly turbid

Turbid

Turbid

Turbid

Bloody

Color

Yellow

Yellow

Yellow

Gray -green

Yellow-milky

Red-Brown

Viscosity

High

Reduced

Low

Low

Low

Reduced

Mucin clot

Firm

Firm to friable

Friable

Friable

Friable

Friable

Clotted

no

occasional

occasional

often

occasional

yes

WBC/uL

0 - 200

0 - 2000

2000 - 100,000

50,000 - 200,000

500 - 200,000

50 - 10,000

%Polys

<25

<30

>50

>90

<90

<50

Glucose difference

0 - 10

0 -10

0-40

20-100

0-80

0-20

Crystals

Absent

Absent

Absent

Absent

Present

Absent

Culture

Sterile

Sterile

Sterile

Positive

Sterile

Sterile

Synovial fluid protein concentration is usually 25% of serum (1-3 g/dL). Synovial fluid glucose is normally within 10 mg/dL of plasma glucose. Neither synovial fluid glucose nor protein provides much useful diagnostic information.

White cell counts (WBC) are normally less than 200/uL with fewer than 25% neutrophils. A WBC count of 2,000/uL and a neutrophil count of 75% serve as useful cutoff points to distinguish inflammatory from noninflammatory disease. However, there is much overlap in synovial fluid WBCs between the inflammatory, crystal-induced, and sepsis categories. WBC is greater than 50,000/uL in 70% of patients with septic arthritis, 15% with gout, 10% with pseudogout, and 4% with rheumatoid arthritis.

Acute septic arthritis is usually caused by bacterial infection of the joint. Tuberculosis and fungi are less commonly involved. Infection can occur by hematogenous spread, direct innoculation during surgery or trauma or from osteomyelitis. Septic arthritis is usually characterized by an acute onset of monoarticular joint pain. Staph aureus is responsible for the majority of cases of bacterial infection. Neisseria gonorrhea is common in adolescents and young adults. E. coli is most commonly seen in neonates. Other gram positive rods are associated with immunocompromised patients.

Birefringent crystals are found in the synovial fluid of >90% of patients with acutely inflamed joints. Crystal identification aids in the diagnosis of joint disease. Monosodium urate crystals are seen in gouty fluids. Urate crystals are mainly needle-shaped and strongly doubly refractile, and may be found within leukocytes. Calcium pyrophosphate crystals are present in chondrocalcinosis. Calcium pyrophosphate dehydrate crystals usually appear as rhomboids and tend to be small, measuring between 1 and 20 um. They are smaller than cholesterol crystals and lack the corner notch. They differ from monosodium urate in that they form very small rhomboids, short rods, or rectangles. With polarized light, they are weakly birefringent and appear yellow when aligned with the compensator axis. This polarization pattern is the opposite of monosodium urate crystals.  They are associated with degenerative arthritis. Cholesterol crystals may also be observed as bright square or rectangular plates.

Specimen requirement for cell count and differential is 1 mL of synovial fluid transferred to a lavender top (EDTA) tube. Bacterial cultures require 2-3 mL of fluid in a yellow top tube.

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