Synovial Fluid Analysis

Analysis of synovial fluid can aid in the diagnosis of joint disorders.

Analyte	Normal Value
volume	< 4 mL
appearance	clear and colorless
viscosity	high
mucin clot	good
fibrin clot	none
glucose	((blood glucose) - (synovial fluid glucose)) < 10 mg/dL
total protein	25-30% * (serum protein level)
uric acid	approximately same as serum
pH	approximately same as serum
WBC per µL	< 200 per µL
% neutrophils	< 25%
cultures	negative

where:

• For glucose concentrations, serum and joint fluid specimen should be drawn after the patient has fasted for at least 4 hours.

• An elevated joint total protein is > 2.5 g/dL. > 4.5 g/dL indicates moderately severe inflammation

Changes seen in joint fluid with inflammation:

(1) increased white blood cells

(2) decreased viscosity

(3) presence of a fibrin clot

(4) increased difference in glucose concentrations between synovial fluid and serum

(5) increased total protein

Differential diagnosis of joint disorders:

(1) noninflammatory (degenerative or traumatic)

(2) hemorrhage (coagulopathy or traumatic)

(3) infectious septic

(4) infectious nonseptic (virus, chlamydia, Borrelia burfdorferi, etc.)

(5) crystal-associated (urate, calcium pyrophosphate dihyrdrate)

(6) autoimmune (rheumatoid arthritis, systemic lupus erythematosus)

Diagnosis	appearance	viscosity	mucin clot	fibrin clot
non-inflammatory	clear, straw colored	high	good	negative (usually)
hemorrhagic	bloody or xanthochromic	variable	variable	negative (usually)
septic	turbid, yellow	decreased	poor	positive
nonseptic infectious	turbid, yellow	decreased	fair to poor	positive
crystal	turbid, yellow	decreased	fair to poor	positive
autoimmune	turbid, yellow	decreased	fair to poor	positive

Diagnosis	WBC count	% neutrophils	crystals in PMNs
non-inflammatory	rarely > 2000 per µL	rarely >75% neutrophils	negative
hemorrhagic	<= WBC of peripheral blood	usually < 50%	negative
septic	usually > 2000 per µL	usually >75% neutrophils	negative
nonseptic infectious	> 200	usually < 75%	negative
crystal	> 200, often high	usually > 75%	positive
autoimmune	> 200, often high	usually < 75%	negative

Crystal associated arthropathy:

(1) uric acid: needle shaped, negative birefringence

(2) pseudogout (calcium pyrophosphate dihydrate): needle shaped, positive birefringence

(3) exclude corticosteroid crystals from joint injections

(4) exclude cholesterol crystals (notched plates) caused by old hemorrhage

Diagnosis	difference glucose in serum and fluid	joint total protein	ESR (peripheral blood)
non-inflammatory	< 10 mg/dL		normal
hemorrhagic	< 25 mg/dL	may be similar to serum	normal
septic	increased	> 2.5 g/dL	increased
nonseptic infectious	variable
crystal	variable
autoimmune	variable		increased

Diagnosis	Gram stain	culture	infectious serology	immune serology (RF, ANA)
non-inflammatory	negative	negative	negative	negative
hemorrhagic	negative	negative	negative	negative
septic	positive	positive	positive	negative
nonseptic infectious	negative	negative	positive	negative
crystal	negative	negative	negative	negative
autoimmune	negative	negative	negative	positive

Joint Disorder	Key Changes in Synovial Fluid	Causes of False Positive or Negative Diagnosis
septic	purulence with positive Gram stain and/or culture	recent antibiotic therapy; nonsterile specimen collection
infection-related, nonseptic	positive serology, viral culture	failure to select test for causative organism
autoimmune	lymphocytic response, positive serology (ANA, RF, other)	recent immuno-suppressive therapy
crystal-associated	urates, pyrophosphates, etc under polarized light	crystals from injected drugs; cholesterol crystals from old hemorrhage
hemorrhage (trauma, coagulopathy)	bloody	traumatic tap
degenerative arthritis	clinical history and exclusion of other conditions

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Purpose: To use synovial fluid analysis in the diagnosis of joint disorders.