SYNOVIAL FLUID COMPOSITION

INTRODUCTION
• Synovial fluid is a thick, stringy fluid found in the cavities of synovial
joints.

• With its egg-like consistency ("synovial" partially derives from ovum,

Latin for egg), synovial fluid reduces friction between the articular
cartilage and other tissues in joints, to lubricate and cushion them
during movement.

• The inner membrane of synovial joints is called the synovial

membrane and secretes synovial fluid into the joint cavity.

• This fluid forms a thin layer (roughly 50 μm) at the surface of

cartilage.
 SYNOVIAL JOINT
• Plasma constituents that enter
joint fluid must cross a double-
barrier membrane.

• First, the endothelial lining of the

capillaries is traversed followed by
movement through a matrix that
surrounds synovial cells.

• This ultrafiltrate is combined with

a mucopolysaccharide
(hyaluronate) synthesized by the
synovium.
 Synovial fluid electrolytes
• The distribution ratio of most electrolytes between
synovial fluid and serum is 1.

• The average ratio of total anions of serum to total

anions of synovial fluid is 1.99.

• Ionic calcium ratios are approximately 1.18.

• This higher ratio is thought to be due to the base

combining power of mucin for calcium.
 Secretion of Synovial Fluid
 Synovial tissue is composed of connective tissue that lacks a
basement membrane.
 There are two main types of synovial lining cells:
o Type A cells are macrophage-like and have primarily a
phagocytic function which is important to remove microbes and
the debris that results from normal wear and tear in the joint.
o Type B cells are fibroblast-like and produce hyaluronate, which
accounts for the increased viscosity of synovial fluid.
• Other cells found in the synovium include antigen-presenting
cells called dendritic cells and mast cells.
• Synovial tissue also contains fat and lymphatic vessels,
fenestrated microvessels, and nerve fibers derived from the
capsule and periarticular tissues.
 Secretion of Synovial Fluid
• Synovial fluid is made of hyaluronic acid and lubricin,
proteinases, and collagenases.

• Normal synovial fluid contains 3-4 mg/ml hyaluronate

(hyaluronic acid), a polymer of disaccharides composed
of D-glucuronic acid and D-N-acetylglucosamine joined
by alternating beta-1,4 and beta-1,3 glycosidic bonds.

• Synovial fluid also contains lubricin secreted by

synovial cells. It is chiefly responsible for so-called
boundary-layer lubrication, which reduces friction
between opposing surfaces of cartilage. It may also
have a role in synovial cell growth.
 FUNCTIONS
Synovial fluid is believed to have two main functions:

 To aid in the nutrition of articular cartilage by acting as a

transport medium for nutritional substances, such as
glucose.

• Articular cartilage has no blood, nerve, or lymphatic supply.

 Supplying oxygen and nutrients to and removing carbon

dioxide and metabolic wastes from the chondrocytes within
articular cartilage.

• Glucose for articular cartilage chondrocyte energy is

transported from the periarticular vasculature to the
cartilage by the synovial fluid.
 FUNCTIONS
 To aid in the mechanical function of joints by
lubrication of the articulating surfaces.

• Lubrication reduces frictional resistance between

bearing surfaces by keeping them apart.

• During movement, the synovial fluid held in the

cartilage is squeezed out mechanically to maintain a
layer of fluid on the cartilage surface.

• The lubricating properties of synovial fluid on articular

cartilage are due to the presence of hyaluronate or
mucin and a glycoprotein in it.
Physical Characteristics of Normal
Synovial Fluid
• Normal synovial fluid is clear, pale yellow, viscid,
and does not clot.

• Volume: The amount of fluid contained in joints is

usually small. The knee joint normally contains up
to 4 mL of fluid.

An increase in synovial fluid enough to aspirates is

due to some disease.
 Clotting
• Normal synovial fluid: Do not clot

• Clotting of synovial fluid means fibrinogen is

present:

1.Damaged synovial membrane

2.Traumatic tap
 Color and clarity:
• Normal synovial fluid is colorless and clear.
• Other appearances may indicate various disease
states.

• Loss of clarity : crystals, increased cellularity,

infective, cartilage debris

• E.g. Yellow/clear (non inflammatory effusions),

yellow/cloudy (inflammatory processes), white/
cloudy (crystals); and red brown (hemorrhage).
 Physical Characteristics of Normal
Synovial Fluid
• Viscosity: Synovial fluid is very viscous due to its high
concentration of polymerized hyaluronate.
• A string test can be used to evaluate the level of synovial fluid
viscosity. After removing the needle or cap from the syringe,
synovial fluid is expressed into a test tube one drop at a time.
• Normal synovial fluid will form a “string” approximately 5 cm
long before breaking.
• In addition, the fluid may cling to the side of the test tube rather
than running down to the bottom.
• Low viscosity of synovial indicates the presence of an
inflammatory process.
 Physical Characteristics of Normal
Synovial Fluid
• Temperature – 32 degree Celsius (peripheral
joints are cooler than core body temperature).

• pH – 7.4
 Indications
• Suspected septic arthritis
– Any febrile person with unexplained inflammatory fluid ->
presumed septic joint
– Even with acute flare of arthritis (e.g., RA), should rule out septic
joint

• Suspected crystal-induced arthritis

– Gout or pseudogout diagnosis largely made with microscopic
examination
– Diagnosis requires negative Gram stain/culture

• Unexplained joint or bursa swelling

– Largely to permit classification into inflammatory vs
noninflammatory categories
– Diagnosis made along with history & physical.
 BIOCHEMICAL EXAMINATION
• Protein: Synovial fluid contains all proteins found in plasma,
except various high–molecular weight proteins.
• These high–molecular-weight proteins include fibrinogen,
beta 2 macroglobulin, and alpha 2 macroglobulin, and can
be absent or present in very low amounts.

• Most commonly used serum protein procedures can be

used to measure synovial fluid protein.
• The normal range for synovial fluid protein is 1–3 g/dL.

• Increased synovial fluid protein levels are seen in ankylosing

spondylitis, arthritis, arthropathies that accompany Crohn
disease, gout, psoriasis, Reiter syndrome, and ulcerative
colitis.
 BIOCHEMICAL EXAMINATION
• Glucose: Synovial fluid glucose levels should be interpreted
using serum glucose levels.
• A fasting specimen should be used or at least one 6–8 hours
postprandially.

• Normally, synovial fluid glucose levels are less than 10

mg/dL lower than serum levels.

• Joint disorders that are classified as infectious demonstrate

large decreases in synovial fluid glucose and can be as much
as 20–100 mg/dL less than serum levels.
• Other groups of joint disorders demonstrate a less of a
decrease in synovial fluid glucose, 0–20 mg/dL
 BIOCHEMICAL EXAMINATION
• Uric acid: Synovial fluid uric acid normally ranges from 6 to 8
mg/dL.

• The presence of uric acid in synovial fluid is helpful in diagnosis

gout.

• Usually, crystal identification is used for this determination, but

synovial fluid uric acid levels may be performed in laboratories
that do not have a light polarizing microscope.

• Lactic acid: Lactic acid is rarely measured in synovial fluid but can
be helpful in diagnosing septic arthritis.
 Lactate levels in the synovial fluid have the highest
diagnostic potential for predicting septic arthritis.

• Normally, synovial fluid lactate is less than 25 mg/dL but can be

as high as 1000 mg/dL in septic arthritis.
 BIOCHEMICAL EXAMINATION
• Enzymes: Alkaline phosphatase, acid phosphatase,
lactic dehydrogenase, and other enzymes are present
in detectable quantities.

• Synovial fluid to serum ratios of these and other

enzymes vary with the presence of articular disease.

• Enzymes enter the synovial fluid directly from the

plasma or may be produced locally by the synovial
membrane or released by synovial fluid macrophages.
 BIOCHEMICAL EXAMINATION
• Lactate dehydrogenase: Lactate dehydrogenase (LD)
can be elevated in synovial fluid, while serum levels
remain normal.

• Synovial fluid LD levels are usually increased in RA,

infectious arthritis, and gout.

• The neutrophils that are increased during the acute

phase of these disorders contribute to this increased
LD level.
 BIOCHEMICAL EXAMINATION
• Complement levels: Normal synovial fluid complement
levels in humans are approximately 10% of the serum
values.
• In the inflamed joint synovial fluid complement levels
will vary. The long-term patterns of variation have
some prognostic value in human rheumatoid arthritis
patients.
• Rheumatoid factor (RF) is an antibody to
immunoglobulins.
• RF is present in the serum of most patients with RA,
whereas just more than half of these patients will
demonstrate RF in synovial fluid.
 CLINICAL IMPORTANCE

• Synovial fluid analysis is a well-established

procedure in the evaluation of joint disease.

• The purpose of synovial fluid analysis is to

determine the presence of arthritis and to place a
fluid into one of several categories.

• Appropriate treatment of joint disease depends on

proper identification of disease.
Practice Questions
Q1) Which of the following cells in the synovium
increases the viscosity of synovial fluid?
a) Type A cells (macrophage-like)
b) Type B cells (fibroblast-like)
c) mast cells
d) dendritic cells
 key: b
a) Type A is derived from blood monocytes, and it removes the wear-and-
tear debris from the synovial fluid.
b) Type B produces hyaluronan. Synovial fluid is made of hyaluronic acid
and lubricin, proteinases, and collagenases. Synovial fluid
contains lubricin (also known as PRG4) as a second lubricating
component, secreted by synovial fibroblasts
c) & d).
– Normally Synovial Fluid has .. NO leukocytes (white blood cells)
NO red blood cells NO plasma clotting factors NO culture (no
bacteria) NO chondrocytes
– In pathologic fluids, chondrocytes, osteoblasts, and osteoclasts may
be seen.
Q2) Which test can be used to evaluate the level
of synovial fluid viscosity?
a) String test
b) Gram staining
c) Coagulation test
d) Illumination test
key: a
a) String sign is used for the measure of viscosity
– 1-2 inches ; When a drop is taken between the thumb and finger as
in pinching and then they are separated, the drop forms a string
till 1-2 inches
b) Gram stain is used to distinguish and classify bacterial species into
two large groups
c) Cogulation test is used to assess blood clotting function.
d) The Illumination & Visibility Testing Laboratory is used for
conducting photometric measurements and human visual
performance
Q3) The presence of uric acid in synovial fluid is
helpful in diagnosis of:
a) Gout
b) Rheumatoid arthritis
c) Septic arthritis
d) Osteoarthritis
key: a
a) Gout arthritis is caused by the deposition of crystals
of uric acid in a joint.

b) Rheumatoid arthritis (RA) is an autoimmune disease

c) Septic arthritis is a penetrating injury delivers germs

directly into the joint.

d) Osteoarthritis is a degenerative disorder of joints.

Q4) In which joint condition does the synovial
fluid examination shows WBC count more
than 50,000 per ml?
a) Osteoarthritis
b) gout
c) trauma
d) gonococcal septic arthritis
key: d
a) Osteoarthritis is the degenerative disease

b) Gout arthritis is caused by the deposition of crystals of uric acid

in a joint.

c) Trauma does not elevate the WBC count

d) Synovial fluid white blood cell count in patients with septic

arthritis is usually greater than 50,000 per mm.
Q5). The highest diagnostic potential for
predicting septic arthritis in synovial fluid is:

a) Acetate
b) Lactate
c) Pyruvate
d) Uric acid
key: b
a) Normally, synovial fluid glucose levels are less than 10 mg/dL
lower than serum levels. So, Acetate will be not increased.
b) The highest concentrations of lactate occurred in non-
gonococcal septic synovial fluids. Lactate levels in the synovial
fluid have the highest diagnostic potential for predicting septic
arthritis.
c) Normally, synovial fluid glucose levels are less than 10 mg/dL
lower than serum levels. So, pyruvate will be not increased.
d) The presence of uric acid in synovial fluid is helpful in
diagnosis gout.