The synovial fluid is an ultradialysate of plasma. Therefore, the composition of the fluid can reflect either a transudative or exudative etiology. In the case of suspected infection, synovial fluid analysis is key to diagnosing joint pathology and, if possible, should be collected prior to the administration of antibiotics. Although most joints have minimal capacity for additional synovial fluid, the knee can contain as much as 100cc. However, the patient can experience pain with a small volume of fluid accumulation if that fluid developed rapidly over a short period of time.

Description of Tests

 

Synovial Fluid Classification

 

Quick Reference Table

 

 

DESCRIPTION OF TESTS

There are many studies that can be performed on synovial fluid and the following are of the highest yield (2,13).
Cell count and differential

Results of this test guide the physician in assessing the degree of inflammation or purulence. Ranges for different types of arthritis are provided below. Some overlap exists, and other key tests described usually allow for further discrimination of the specific etiology.

Gram Stain

The sensitivity of gram stain in septic arthritis is 50-75% for non-gonococcal infection, but only 10% for gonococcal arthritis. The specificity of a positive gram stain is very high (2)

 

Culture

Allows for confirmation in the diagnosis of septic arthritis, and allows for specific organism identification. Results are not immediately available.

 

Crystal Analysis

Crystal induced arthritis and septic arthritis may be difficult to distinguish clinically, and one should always look for the presence of crystals.

 

Chemistries

Protein and glucose measurements help discern a transudative vs. exudative etiology. Serum levels should be checked for reference.

 

String Test (4)

Synovial fluid is placed between the thumb and index finger and then drawn apart. Normal synovial fluid is viscous, and if the length of the string exceeds 3 cm, this suggests a noninflammatory state. Inflammatory or purulent fluid results in breakdown of hyaluronate chains, which results in lower fluid viscosity (and string will be less than 3 cm). It should be noted that this test is rarely performed due to universal precautions.

 

Mucin Clot Test (14)
Acetic acid is added to synovial fluid in a test tube, and the hyaluronate in the fluid polymerizes forming a white clot. The clot is fragile in infected and inflammatory states, and when one shakes the tube, the clot will break. In noninflammatory fluid, the clot remains firm.
 

Based on the results of these studies, synovial fluid can be classified as normal, traumatic, inflammatory, and infected. However, it is important to note that there is overlap between the categories. These groupings will guide in the diagnosis of the joint pathology.

SYNOVIAL FLUID CLASSIFICATION

Normal synovial fluid contains the following (10):

  • Electrolytes
  • Non electrolytes (glucose, uric acid)
  • Albumin and globulins
  • Mucin (glycoprotein containing hyaluronic acid responsible for the viscosity)
  • Blood cells
  • Debris

 

Based on these characteristics, synovial fluid can be broken down into:

 

Normal Fluid

Quantity: Average is 1.1cc. Range: 0.13 to 3.5 cc.

Appearance / Clarity: Clear and colorless (one should be able to read a newspaper through the fluid)

Viscosity: Very viscous

Cell count: Average 63; Range: 13-180.

Differential:

  • Red blood cells: Zero
  • Percent polymorphonuclear leukocytes: Average: 6.5%; Range 0-25
  • Lymphocytes: Average: 24.6%; Range 0-78
  • Monocytes: Average: 6.5%; Range 0-25

Mucin clot: Good

Crystals : None

Uric acid: Same as in plasma

Glucose level difference versus plasma: Within 10 mg/100ml of plasma concentration

 

Traumatic Fluid

Appearance / Clarity: Clear to slightly turbid

Viscosity: Mildly reduced

Leukocytes / cubic cm: 300-3000

Percent polymorphonuclear: 0-30%

Glucose level difference versus plasma: <20 mg/100ml

Mucin clot: Good to fair

 

Differential Diagnosis :

  • Traumatic arthropathy
  • Degenerative joint disease
  • Oesteochondromatosis
  • Osteochondritis dissecans

 

Inflammatory Fluid

Appearance / Clarity: Slightly turbid to turbid

Viscosity: Moderately reduced

Leukocytes / cubic cm: 3000-50,000

Percent polymorphoneuclear: 40-80%

Glucose level difference versus plasma: 10-40 mg/100ml

Mucin clot: Fair to poor

Crystals : May be present in gout and pseudogout. Note that septic and crystal induced arthritis

may coexist, and the presence of crystals does not exclude infection.

 

Differential Diagnosis:

  • Rheumatic fever
  • Systemic lupus erythematosus
  • Gouty arthritis
  • Pseudogout
  • Reiter's disease/spondyloarthropathy
  • Rheumatoid arthritis
  • Psoriatic arthritis

 

Crystals
The two types of crystals most commonly seen in synovial fluid are calcium pyrophosphate dihydrate (CPPD) and monosodium urate monohydrate (MSU) (16).

Crystal Types:
Monosodium urate monohydrate (MSU): These are the crystals that cause Gout. They exhibit negative birefringence under polarizing microscopy. Crystals are needle-shaped (monoclinic). Sensitivity of polarizing microscopy for gout is 90-95%, but is interobserver dependant (2). Patients may also have elevated serum uric acid levels (7.6-14.0 mg/dl) but normal levels can be seen in acute attacks (7).

Calcium Pyrophosphate Dihydrate (CPPD): These are the crystals that cause pseudogout. They exhibit weakly positive birefringence under polarizing microscopy and are rhomboid shaped. Sensitivity of polarizing microscopy in diagnosis is 75-80%, and is interobserver dependant (2). CPPD crystal deposition occurs with:
- Hereditary forms of pseudogout
- Acute pseudogout
- Metabolic disease such as hyperparathyroidism, hypothyroidism, diabetes mellitus, hemochromatosis, and gout

Infected Fluid (2,6,10,14)

Appearance / Clarity: Turbid to very turbid

Viscosity: Greatly reduced (similar to water)

Leukocytes / cubic cm: 15,000- >200,000

  • usually >50,000 and >100,000 is virtually diagnostic (14)

Percent polymorphoneuclear: 50-100%

  • > 90% almost always indicates infection (2)

Mucin clot: Poor to very poor

Glucose level difference versus plasma: >40 mg/100ml less than plasma

 

Differential Diagnosis

  • Tuberculous arthritis
  • Gonococcal arthritis
  • Non-gonococcal bacterial arthritis (most commonly staphylococcus aureus and streptococcus) (6)

QUICK REFERENCE TABLE

 

  Normal
Traumatic
Inflammatory
Infected
         
Clarity
 Clear Clear to slightly
turbid 		Slighty turbid to
turbid 		Turbid to very
turbid
         
Viscosity
 Very viscous Mildly reduced Moderately reduced Greatly reduced
         
WBC / mm3
13-180 300-3000 3000-50,000 15,000 - >200K
         
% polys
6.5 (0-25) 0-30 40-80 50-100
         
Glucose (diff vs plasma)
<10 mg/100ml
less than plasma		 <20 mg/100ml
less than plasma 		10-40 mg/100ml
less than plasma 		>40 mg/100ml less than plasma
         
Mucin Clot
Good Good to fair Fair to poor Poor to very poor
         
Crystals
 none   +/- CPPD / MSU  
         
Differential Diagnosis
  

-Traumatic arthropathy

- Degenerative joint disease

-Osteochondro-
matosis

-Osteochondritis dissecans

-Rheumatic fever

-Systemic lupus
erythematosus

-Gouty arthritis

-Pseudogout

-Reiter's disease/ spondyloarthropathy

-Rheumatoid arthritis

-Psoriatic arthritis

-Bacterial infection

-Tuberculosis arthritis

-Gonococcal arthritis

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