Synovial Fluid Analysis/Synovial fluid is defined as the collection of fluid confined within a joint space. Synovial fluid is physiologic and acts as a joint space lubricant of articular cartilage, and nutrient source through diffusion for surrounding structures including cartilage, meniscus, labrum, etc. Synovial fluid is produced as an ultrafiltrate of blood plasma and is primarily composed of hyaluronan, lubricin, proteinase, collagenases, and prostaglandins.[rx] Synovial fluid production is from fibroblast-like type B synovial cells. Physiologic changes in synovial fluid volume and content occur in response to trauma, infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।" data-rx-term="inflammation" data-rx-definition="Inflammation is the body’s response to injury, infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।">inflammation, and bacterial, fungal, or viral penetrance. When patients present with acutely painful joints with suspicion of infection, inflammation or non-inflammatory causes of effusion, synovial fluid aspiration and analysis is imperative to aid in diagnosis and direct treatment modality.
Synovial fluid, also called synovia is a viscous, non-Newtonian fluid found in the cavities of synovial joints. With its egg white-like consistency,[rx] the principal role of synovial fluid is to reduce friction between the articular cartilage of synovial joints during movement.[rx] Synovial fluid is a small component of the transcellular fluid component of extracellular fluid.
Structure of Synovial Fluid Analysis
The inner membrane of synovial joints is called the synovial membrane and secretes synovial fluid into the joint cavity.[rx] Synovial fluid is an ultrafiltrate from plasma and contains proteins derived from the blood plasma and proteins that are produced by cells within the joint tissues.[rx] The fluid contains hyaluronan secreted by fibroblast-like cells in the synovial membrane, lubricin (proteoglycan 4; PRG4) secreted by the surface chondrocytes of the articular cartilage and interstitial fluid filtered from the blood plasma.[5] This fluid forms a thin layer (roughly 50 μm) at the surface of the cartilage and also seeps into microcavities and irregularities in the articular cartilage surface, filling all empty space.[6] The fluid in articular cartilage effectively serves as a synovial fluid reserve. During movement, the synovial fluid held in the cartilage is squeezed out mechanically to maintain a layer of fluid on the cartilage surface (so-called weeping lubrication). The functions of the synovial fluid include:
- Reduction of friction — synovial fluid lubricates the articulating joints[rx]
- Shock absorption — as a dilatant fluid, that possesses rheopectic properties,[rx] becoming more viscous under applied pressure; the synovial fluid in diarthrotic joints becomes thick the moment shear is applied in order to protect the joint and subsequently, thins to normal viscosity instantaneously to resume its lubricating function between shocks.[rx]nutrient and waste transportation — the fluid supplies oxygen and nutrients and removes carbon dioxide and metabolic wastes from the chondrocytes in the surrounding cartilage
- Molecular sieving – pressure within the joint forces hyaluronan in the fluid against the synovial membrane forming a barrier against cells migrating into, or fluid migrating out of, the joint space. This function is dependent on the molecular weight of the hyaluronan.[rx]
Normal and Critical Findings of Synovial Fluid Analysis
Below we discuss normal and abnormal findings in native adult joints. It is important to note that cell count thresholds vary in joints with previous hardware such as post-traumatic fixation with hardware or in cases of previous joint replacement.
Native adult joint synovial fluid analysis [rx]
According to the American Rheumatologic Association guidelines
- Non-inflammatory <200 to 2000 WBC/mm^3
- Inflammatory >2000 to 50,000 WBC/mm^3
- Infectious > 50,000 WBC/mm^3
Differential with polymorphic nuclear cells (PMNs)
Crystal Analysis: Gout and Pseudogout
- Presence of monosodium urate crystals indicates a diagnosis of gout
- Presence of calcium pyrophosphate dihydrate crystals indicates a diagnosis of pseudogout
Gram stain and bacterial culture: synovial fluid aspirate is analyzed for gram stain and both aerobic and anaerobic culture to determine the presence of infection; the presence of any organism indicates abnormal findings.
Classification of Synovial Fluid Analysis
Synovial fluid may be classified into normal, noninflammatory, inflammatory, septic, and hemorrhagic:
| Normal | Noninflammatory | Inflammatory | Septic | Bleeding | |
| Volume (ml) | <3.5 | >3.5 | >3.5 | >3.5 | >3.5 |
| Viscosity | High | High | Low | Mixed | Low |
| Clarity | Clear | Clear | Cloudy | Opaque | Mixed |
| Color | Colorless/straw | Straw/yellow | Yellow | Mixed | Red |
| WBC/mm3 | <200 | <2,000[rx] | 5,000[rx]-75,000 | >50,000[rx] | Similar to blood level |
| Polys (%) | <25 | <25[rx] | 50[rx]-70[rx] | >70[rx] | Similar to blood level |
| Gram stain | Negative | Negative | Negative | Often positive | Negative |
Glucose (mg/dl) concentration in synovial fluid is nearly equal to serum.
- Synovial fluid viscosity
Normal
- Normal
- Traumatic pain, swelling, stiffness, or reduced movement. সহজ বাংলা: জয়েন্টের প্রদাহ।" data-rx-term="arthritis" data-rx-definition="Arthritis means joint inflammation causing pain, swelling, stiffness, or reduced movement. সহজ বাংলা: জয়েন্টের প্রদাহ।">arthritis
- Degenerative (Osteo) pain, swelling, stiffness, or reduced movement. সহজ বাংলা: জয়েন্টের প্রদাহ।" data-rx-term="arthritis" data-rx-definition="Arthritis means joint inflammation causing pain, swelling, stiffness, or reduced movement. সহজ বাংলা: জয়েন্টের প্রদাহ।">arthritis
- Pigmented villonodular synovitis
Normal or decreased
- Systemic lupus erythematosus
Decreased
- Rheumatic fever
- arthritis: Rheumatoid arthritis is an autoimmune joint disease causing infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।" data-rx-term="inflammation" data-rx-definition="Inflammation is the body’s response to injury, infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।">inflammation, pain, and swelling. সহজ বাংলা: রোগপ্রতিরোধ ব্যবস্থার ভুল আক্রমণে জয়েন্টের প্রদাহ।" data-rx-term="rheumatoid arthritis" data-rx-definition="Rheumatoid arthritis is an autoimmune joint disease causing inflammation, pain, and swelling. সহজ বাংলা: রোগপ্রতিরোধ ব্যবস্থার ভুল আক্রমণে জয়েন্টের প্রদাহ।">Rheumatoid arthritis
- Gout
- Pyogenic (Septic) arthritis
- Tubercular arthritis
- Less of lubrication in joints
Pathology
Many synovial fluid types are associated with specific diagnoses
Noninflammatory (Group I)
- Osteoarthritis, degenerative joint disease
- Trauma
- Rheumatic fever
- Chronic gout or pseudogout
- Scleroderma
- Polymyositis
- Systemic lupus erythematosus
- Erythema nodosum
- Neuropathic arthropathy (with possible hemorrhage)
- Sickle-cell disease
- Hemochromatosis
- Acromegaly
- Amyloidosis
Inflammatory (Group II)
- Rheumatoid arthritis
- Reactive arthritis
- Psoriatic arthritis
- Acute rheumatic fever
- Acute gout or pseudogout
- Scleroderma
- Polymyositis
- Systemic lupus erythematosus
- Ankylosing spondylitis
- Inflammatory bowel disease arthritis
- Infection (viral, fungal, bacterial) including Lyme disease
- Acute crystal synovitis (gout)
Septic (Group III)
- Pyogenic bacterial infection
- Septic arthritis
Hemorrhagic
- Trauma
- Tumors
- Hemophilia/coagulopathy
- Scurvy
- Ehlers-Danlos syndrome
- Neuropathic arthropathy
Indications of Synovial Fluid Analysis
The synovial fluid aspirate should be analyzed for[rx]:
- Complete blood count (CBC) with differential (white blood cell [WBC], polymorphonuclear leukocytes)
- Crystal examination of synovial fluid
- Culture and Gram staining of synovial fluid
- Viscosity (RA: expect decreased viscosity and poor mucin clot formation)
- Glucose
- Low level of synovial-fluid glucose is suggestive of an infected joint, but low glucose levels are present in only about 50% of patients with septic joints and can also occur in rheumatoid arthritis
- Fasting glucose levels are usually reduced to less than half of the simultaneously obtained blood levels
- The presence of crystals cannot exclude septic arthritis with certainty.[8] Septic arthritis occurs concurrently with gout or pseudogout in less than 5% of cases.
Septic Arthritis
- Joint fluid appears cloudy or purulent
- Cell count with WBC greater than 50,000 is considered diagnostic for septic arthritis. However, lower counts may still indicate infection (not sensitive)[rx]
- Prosthetic joint with WBC greater than 1100 is considered septic
- Gram stains only identify infective organism one-third of time
- Glucose less than 50% of serum level
Non-Inflammatory Synovial Fluid
- Contains less than 60 to 180 cells per mL, most of which should be mononuclear
- Synovial fluid is considered to be non-inflammatory if it contains less than 2000 cells/mL, but most samples of synovial fluids from pts with osteoarthritis contain less than 500 cells per ml.
- The most common cause of non-inflammatory effusions of the knee (synovial fluid white blood cell count less than 2000 cells/mcL) is osteoarthritis; other causes include osteonecrosis, Charcot arthropathy, sarcoidosis, amyloidosis, hypothyroidism, and acromegaly. Inflammatory arthritis (synovial fluid white blood cell greater than 2000 cells/mL) can be caused by infection, autoimmune disease, and crystal-induced arthritis. Aspiration of dark brown serosanguinous fluid should raise the possibility of pigmented villonodular synovitis.
Inflammatory Synovial Fluid
Greater than 2000 leukocytes/mL
- Traumatic: Less than 5000 (w/RBCs)
- Toxic Synovitis: 5000 to 15,000 and less than 25% polymorphs
- Acute Rheumatic Fever: 10,000 to 15,000 and 50% polymorphs
- JRA 15,000 to 80,000 and 75% polymorphs
Greater 50,000 leukocytes/mL;
- Although other diseases including trauma, may produce WBC cells in joint fluid, levels greater than 50,000/mm3 are usually due to infectious arthritis.
- Usually causes most intense synovial fluid leukocytosis, w/ 50,000 to 200,000 cells/mL and usually over 90% PMNs
- Lower leukocyte counts are more common early in course of bacterial arthritis and in patients with disseminated gonococcal infection
- Non-infectious conditions such as gout, pseudogout, acute rheumatic fever, reactive arthritis, and RA can cause a markedly inflammatory synovial effusion. Finding of greater than 90% PMNs despite relatively low total leukocyte count should prompt concern about infection or crystal-induced disease. However, the presence of crystals cannot exclude septic arthritis with certainty[rx]
Septic arthritis 80,000 to 200,000 and greater than 75% polymorphs
- In synovial fluid WBC count and percentage of polymorphonuclear cells from arthrocentesis are the most powerful predictors for septic arthritis. The LR is increased as the synovial fluid WBC count increased.
- For counts greater than 50,000/microL (LR, 7.7; 95% CI, 5.7-11.0) and for counts greater than 100,000/microL (LR, 28.0; 95% CI, 12.0-66.0). On the same synovial fluid sample, a polymorphonuclear cell count of at least 90% suggests septic arthritis with an LR of 3.4 (95% CI, 2.8-4.2), while a PMN cell count of less than 90% lowers the likelihood (LR, 0.34; 95% CI, 0.25-0.47)[5]
Procedures
Arthrocentesis is the process by which synovial fluid collection occurs by penetrating the joint space through aspiration. This procedure should be done under sterile procedural conditions and performed by a physician with intimate knowledge of the involved anatomy. Sterility is essential not only to prevent transmission of infection but also to ensure accurate fluid analysis. Ultrasound technology may be useful in ensuring correct needle placement but is often unnecessary. Fluoroscopy and CT guided arthrocentesis can also provide utility for deeper joints including shoulder and hip. Once indications are met for arthrocentesis, aspiration site is selected and marked. The literature documents the safe entry portals thoroughly for the shoulder, elbow, wrist, hip, knee, and ankle. The site is then prepped and draped in the usual sterile fashion using antiseptics that include one or a combination of alcohol, betadine, and/or chlorhexidine. Local anesthetic can be used to create a cutaneous/subcutaneous wheel for local pain control. Next, a large gauge, sharp needle, typically 18 gauge (or smaller if a smaller joint in being aspirated), is inserted into the joint attached to a minimum 10 cc syringe. A spinal needle may be an option for deeper joints or patients with anatomy complicated by obesity. On obtaining access to the joint, negative pressure should be maintained in the syringe until an adequate amount of synovial fluid is collected. The fluid should then be transferred to a sterile specimen collection cup and sealed for transport to the laboratory for analysis. The syringe may be emptied and reattached to the indwelling needle repeatedly, minimizing needle entry points. Once the procedure is complete, the antiseptic should be cleaned off the skin, site dried, and pressure and a soft dressing applied for local hemostasis. No activity modifications or changes in weight-bearing status are necessary following the procedure, in the absence of other pathology. Compressive ace bandage dressings often aid in the prevention of fluid reaccumulation.
References
- https://www.ncbi.nlm.nih.gov/books/NBK532279/
- https://www.ncbi.nlm.nih.gov/books/NBK537114/
- https://www.ncbi.nlm.nih.gov/books/NBK274/
- https://www.ncbi.nlm.nih.gov/books/NBK557805/
- https://www.ncbi.nlm.nih.gov/books/NBK378787/
- https://www.ncbi.nlm.nih.gov/books/NBK470229/
- https://www.ncbi.nlm.nih.gov/books/NBK518967/
- https://en.wikipedia.org/wiki/Synovial_fluid
