SYNOVIAL FLUID AND SYNOVIUM
Synovium Structure | Type A and B Synoviocytes | Hyaluronic Acid | Boundary and Fluid Film Lubrication
SYNOVIUM STRUCTURE
Critical Must-Knows
- Synovium lacks basement membrane - unique feature allowing bidirectional diffusion for joint nutrition
- Type A synoviocytes are macrophage-like (CD68+) and remove debris via phagocytosis
- Type B synoviocytes are fibroblast-like and synthesize hyaluronic acid for synovial fluid viscosity
- Hyaluronic acid (MW 3-4 MDa) provides non-Newtonian viscosity for lubrication
- Boundary lubrication (lubricin/PRG4) prevents solid-solid contact at low speeds; fluid film lubrication at high speeds
Examiner's Pearls
- "Normal synovial fluid is acellular (under 200 WBC/μL) with no organisms on Gram stain
- "Septic arthritis: over 50,000 WBC/μL with over 75% neutrophils, positive culture
- "Inflammatory arthritis: 2,000-50,000 WBC/μL, rheumatoid factor may be present
- "Lubrication mechanisms differ by speed: boundary (static/low speed) vs fluid film (high speed)
Clinical Imaging
Imaging Gallery




Critical Synovial Fluid and Synovium Exam Points
Synovium Structure
Synovium lacks basement membrane - unique feature among body membranes. The intima (lining layer) is 1-3 cells thick with Type A (macrophage-like) and Type B (fibroblast-like) synoviocytes. Subintima is vascular connective tissue.
Hyaluronic Acid Function
Hyaluronic acid (hyaluronan) is a high molecular weight (3-4 MDa) glycosaminoglycan synthesized by Type B synoviocytes. Provides non-Newtonian viscosity: high viscosity at low shear (shock absorption), low viscosity at high shear (ease of movement).
Lubrication Mechanisms
Two lubrication modes: (1) Boundary lubrication by lubricin (PRG4) adsorbed to cartilage surface prevents solid-solid contact at low speeds. (2) Fluid film lubrication by pressurized synovial fluid separates surfaces at high speeds.
Synovial Fluid Analysis
Normal synovial fluid: Clear, yellow, viscous, acellular (under 200 WBC/μL). Septic arthritis: Purulent, over 50,000 WBC/μL, over 75% PMNs, positive culture. Crystal arthropathy: Monosodium urate (gout, negative birefringence), calcium pyrophosphate (pseudogout, positive birefringence).
TYPE ABTYPE AB - Synoviocyte Functions
Memory Hook:TYPE AB blood types remind you: Type A cleans (macrophage), Type B builds (fibroblast)
HYALURONICHYALURONIC - Hyaluronic Acid Properties
Memory Hook:HYALURONIC = HY molecular weight gives LUBRICation
BOUNDARYBOUNDARY - Lubrication Mechanisms
Memory Hook:BOUNDARY keeps cartilage surfaces apart at the boundary between static and moving
Overview and Introduction
The synovium is a specialized mesenchymal tissue that lines the non-cartilaginous surfaces of synovial joints. It produces synovial fluid, which provides nutrition to avascular articular cartilage and enables nearly frictionless joint motion through sophisticated lubrication mechanisms.
Synovial fluid is a dialysate of plasma enriched with hyaluronic acid (hyaluronan), a high molecular weight glycosaminoglycan that provides unique viscoelastic properties essential for joint function.
Synovium Anatomy and Histology
Macroscopic Anatomy
Location and distribution:
- Lines joint capsule, intra-articular ligaments, and bone surfaces not covered by cartilage
- Does NOT cover articular cartilage or menisci
- Extends to bone-cartilage junction (tidemark region)
- Forms synovial folds (plicae) and villi that increase surface area
Macroscopic appearance:
- Thin membrane (0.1-0.3 mm thickness)
- Smooth, glistening surface
- Pink to pale red color (vascular)
- Highly vascular and innervated
Microscopic Structure
The synovium has two distinct layers:
1. Intima (Lining Layer):
- Thickness: 1-3 cell layers (20-40 micrometers)
- Cell types: Type A and Type B synoviocytes
- NO basement membrane - unique feature allowing bidirectional diffusion
- Intercellular gaps: Allow molecules up to 10-20 nm to pass freely
- Function: Synovial fluid production, nutrition of cartilage, debris removal
2. Subintima (Sublining Layer):
- Structure: Loose connective tissue rich in blood vessels, lymphatics, and nerves
- Three subtypes based on predominant tissue:
- Fibrous (collagenous) - most common, near capsule
- Areolar (loose connective tissue) - most common, near bone
- Adipose (fat tissue) - near fat pads
- Function: Vascular supply, immune surveillance, structural support
Understanding the lack of basement membrane is critical - this allows efficient nutrient exchange for avascular cartilage.
Synovial Fluid Composition and Properties
Synovial Fluid Components
Normal synovial fluid characteristics:
- Volume: 0.3-3.5 mL in knee (varies by joint size)
- Color: Clear to pale yellow (straw-colored)
- Viscosity: High (due to hyaluronic acid)
- Clarity: Transparent (can read newsprint through it)
- Cell count: Under 200 WBC/μL (under 25% neutrophils)
Composition:
1. Plasma dialysate (base fluid):
- Water: 85%
- Electrolytes: Similar to plasma (Na+, K+, Cl-, Ca2+, Mg2+)
- Glucose: 90-100% of plasma glucose (50-100 mg/dL)
- Small molecules diffuse freely from blood
2. Hyaluronic acid (key component):
- Concentration: 3-4 mg/mL (0.3-0.4%)
- Molecular weight: 3-4 million Daltons (3-4 MDa)
- Source: Synthesized by Type B synoviocytes
- Function: Provides viscosity and elasticity
3. Lubricin (PRG4):
- Glycoprotein: 227 kDa molecular weight
- Source: Synthesized by Type B synoviocytes and chondrocytes
- Function: Boundary lubrication, prevents cartilage adhesion
- Concentration: 50-400 micrograms/mL
4. Proteins:
- Total protein: 1-2 g/dL (one-third of plasma protein concentration)
- Albumin: Predominant protein (passes through synovial membrane easily)
- Immunoglobulins: IgG, IgM, IgA present in lower concentrations than plasma
- Enzymes: Collagenase, hyaluronidase (at low levels normally)
5. Cells:
- Total WBC: Under 200/μL (mostly mononuclear)
- Cell types: Monocytes, lymphocytes, synoviocytes (shed from intima)
- No RBCs in normal fluid
Normal synovial fluid is essentially a plasma ultrafiltrate enriched with hyaluronic acid and lubricin.
Joint Lubrication Mechanisms
Two Primary Lubrication Mechanisms
Joints achieve remarkably low friction (coefficient 0.001-0.01) through two complementary mechanisms that operate under different conditions:
1. Boundary Lubrication:
- Active when: Static loading, low sliding speeds, high loads
- Mechanism: Lubricin adsorbed to cartilage surface prevents solid-solid contact
- Lubricant: Lubricin (PRG4) - glycoprotein
- Coefficient of friction: 0.01-0.02
2. Fluid Film Lubrication:
- Active when: High sliding speeds, low to moderate loads
- Mechanism: Pressurized synovial fluid separates opposing cartilage surfaces
- Lubricant: Synovial fluid (water + hyaluronic acid)
- Coefficient of friction: 0.001-0.005
3. Additional mechanisms (contribute but less dominant):
- Weeping lubrication: Fluid exudes from cartilage matrix under load
- Boosted lubrication: HA macromolecules concentrate in gap, increasing viscosity locally
- Hydration lubrication: Hydrated phospholipid layers on cartilage surface
| Feature | Boundary Lubrication | Fluid Film Lubrication |
|---|---|---|
| Active condition | Low speed, high load | High speed, low-moderate load |
| Lubricant | Lubricin (PRG4) | Synovial fluid (HA + water) |
| Mechanism | Adsorbed molecular layer | Pressurized fluid film |
| Friction coefficient | 0.01-0.02 | 0.001-0.005 |
| Example activity | Standing, static loading | Walking, running |
The two mechanisms work together to provide lubrication across the full range of joint activities.
Synovial Fluid Analysis - Clinical Pathology
Classification of Synovial Fluid
| Parameter | Normal | Non-inflammatory | Inflammatory | Septic |
|---|---|---|---|---|
| Color | Clear/pale yellow | Yellow | Yellow/cloudy | Purulent/opaque |
| Clarity | Transparent | Transparent | Translucent/opaque | Opaque |
| Viscosity | High | High | Low | Very low |
| WBC count | under 200/μL | 200-2,000/μL | 2,000-50,000/μL | over 50,000/μL |
| PMN % | under 25% | under 25% | over 50% | over 75% |
| Culture | Negative | Negative | Negative | Positive (50-70%) |
Key diagnostic thresholds:
- Normal: Under 200 WBC/μL
- Non-inflammatory (OA, trauma): 200-2,000 WBC/μL
- Inflammatory (RA, gout, pseudogout): 2,000-50,000 WBC/μL
- Septic: Over 50,000 WBC/μL (classic), but can overlap with inflammatory
Septic Arthritis Diagnosis
Septic arthritis is a surgical emergency. Classic findings: WBC over 50,000/μL, over 75% PMNs, positive Gram stain or culture. However, WBC counts can overlap with inflammatory arthritis. Always correlate with clinical presentation (fever, acute monoarthritis). If suspicion is high, treat as septic until proven otherwise (washout and antibiotics).
Understanding synovial fluid classification guides diagnosis and management.
Pathophysiology of Synovial Diseases
Inflammatory Arthritis (Rheumatoid Arthritis)
Synovial pathology:
- Synovial hypertrophy: Intimal lining proliferates (10-20 cell layers thick vs normal 1-3)
- Pannus formation: Invasive synovial tissue (granulation tissue) erodes cartilage and bone
- Inflammatory infiltrate: Lymphocytes (T and B cells), plasma cells, macrophages in subintima
- Neovascularization: VEGF-driven angiogenesis brings more inflammatory cells
- Cytokine production: TNF-alpha, IL-1, IL-6 drive inflammation and joint destruction
Synovial fluid changes:
- High WBC count: 5,000-50,000/μL (inflammatory range)
- Neutrophil predominance: 50-75% PMNs
- Low viscosity: Hyaluronic acid degraded by hyaluronidase and free radicals
- Low complement: C3 and C4 consumed by immune complexes
- Rheumatoid factor: May be present
Osteoarthritis
Synovial pathology:
- Mild synovitis: Low-grade inflammation (not as severe as RA)
- Fibrosis: Subintimal fibrosis and thickening
- Cartilage fragments: Released into joint, phagocytosed by Type A synoviocytes
Synovial fluid changes:
- Low WBC count: 200-2,000/μL (non-inflammatory)
- Normal to decreased viscosity: HA molecular weight decreases over time
- Cartilage debris: May contain fragments
Septic Arthritis
Synovial pathology:
- Acute inflammation: Massive neutrophil infiltration
- Purulent exudate: Pus formation
- Cartilage destruction: Bacterial enzymes and neutrophil proteases degrade cartilage rapidly
- Vascular thrombosis: Can lead to bone infarction
Synovial fluid changes:
- Very high WBC count: Over 50,000/μL (often over 100,000)
- Neutrophil predominance: Over 75% (often over 90%)
- Positive culture: Staphylococcus aureus most common
- Low glucose: Bacteria consume glucose
- Very low viscosity: Complete HA degradation
Evidence Base
Hyaluronic Acid and Joint Lubrication
- Hyaluronic acid (3-4 MDa) provides non-Newtonian viscosity to synovial fluid
- Viscosity decreases with increasing shear rate (ideal for joint function)
- In osteoarthritis, HA molecular weight and concentration decrease
- Degraded HA impairs fluid film lubrication, increasing cartilage wear
Lubricin and Boundary Lubrication
- Lubricin (PRG4) provides boundary lubrication by adsorbing to cartilage surface
- Creates hydrated molecular brush that prevents solid-solid contact
- Lubricin-deficient mice develop precocious joint degeneration
- PRG4 mutations in humans cause CACP syndrome with early arthropathy
Synovial Fluid Analysis in Septic Arthritis
- Systematic review of diagnostic accuracy for septic arthritis
- Synovial fluid WBC over 50,000/μL: sensitivity 62%, specificity 92%
- Over 75% neutrophils: sensitivity 77%, specificity 73%
- Positive Gram stain: sensitivity 50%, specificity 99%
- No single test is definitive - clinical correlation essential
Basic Science Viva Scenarios
Practice these scenarios to excel in your viva examination
Scenario 1: Synovium Structure and Synoviocyte Types
"Describe the structure of the synovium. What are the two types of synoviocytes and what are their functions?"
Scenario 2: Joint Lubrication Mechanisms
"Explain the mechanisms of joint lubrication. How do boundary lubrication and fluid film lubrication differ?"
Scenario 3: Synovial Fluid Analysis
"You aspirate synovial fluid from an acutely swollen knee. Describe how you would analyze the fluid and interpret the results."
Management Algorithm

SYNOVIAL FLUID AND SYNOVIUM
High-Yield Exam Summary
Synovium Structure
- •Intima: 1-3 cell layers thick (20-40 μm), NO basement membrane (unique feature for diffusion)
- •Subintima: vascular connective tissue (fibrous, areolar, or adipose types)
- •Type A synoviocyte: macrophage-like (CD68+), phagocytosis, 20-30% of intimal cells
- •Type B synoviocyte: fibroblast-like (vimentin+), synthesize HA and lubricin, 70-80% of intimal cells
Synovial Fluid Normal Composition
- •Volume: 0.3-3.5 mL in knee joint
- •Appearance: clear, pale yellow, transparent, highly viscous
- •WBC count: under 200/μL (under 25% neutrophils)
- •Hyaluronic acid: 3-4 mg/mL, 3-4 MDa molecular weight (provides viscosity)
- •Lubricin (PRG4): 50-400 μg/mL (boundary lubrication)
- •Protein: 1-2 g/dL (one-third of plasma)
Hyaluronic Acid
- •Glycosaminoglycan (NOT proteoglycan - no protein core)
- •Repeating disaccharides: D-glucuronic acid + N-acetyl-D-glucosamine
- •MW: 3-4 million Daltons (3-4 MDa) in normal SF
- •Non-Newtonian viscosity: high at low shear (shock absorption), low at high shear (ease of movement)
- •Synthesized by Type B synoviocytes (HAS1/2/3 enzymes)
- •Degraded in arthritis (lower MW and concentration) - impairs fluid film lubrication
Lubrication Mechanisms
- •Boundary lubrication: lubricin (PRG4) adsorbed to cartilage, active at low speed/high load, coefficient 0.01-0.02
- •Fluid film lubrication: pressurized SF separates surfaces, active at high speed, coefficient 0.001-0.005
- •Lubricin: 227 kDa glycoprotein, central mucin domain (hydrated brush), prevents solid-solid contact
- •PRG4 deficiency: CACP syndrome (camptodactyly-arthropathy-coxa vara-pericarditis)
- •Hydrodynamic: wedge film from sliding motion; Squeeze film: viscous resistance to rapid loading
Synovial Fluid Analysis
- •Normal: under 200 WBC/μL, clear, viscous
- •Non-inflammatory (OA): 200-2,000 WBC/μL, under 25% PMNs
- •Inflammatory (RA, gout): 2,000-50,000 WBC/μL, over 50% PMNs
- •Septic: over 50,000 WBC/μL, over 75% PMNs, positive culture (50-90%)
- •Gout: MSU crystals (needle, negative birefringence - yellow when parallel)
- •Pseudogout: CPP crystals (rhomboid, positive birefringence - blue when parallel)
- •Septic markers: glucose under 50% of serum, lactate over 10 mmol/L
Key Clinical Correlations
- •Septic arthritis: surgical emergency, treat if high suspicion (WBC counts overlap with inflammatory)
- •Rheumatoid arthritis: pannus formation (invasive synovium), low complement (C3, C4), ragocytes
- •Osteoarthritis: mild synovitis, HA degradation over time, cartilage fragments in SF
- •Viscosupplementation: exogenous HA injection to restore fluid film lubrication in OA
- •TB arthritis: lymphocyte predominance (not PMNs), culture on Lowenstein-Jensen (6-8 weeks)