Rheol.

Acta 10, 2-7 (1971)

].

From the Bio-engineemng Group ]or the Study o/Human Joints, University o/Leeds (England)

The rheology of synovial fluid*)

B y P. C. S e l l e r , D. D o w s o n and V. W r i g h t

With 4 figures and 3 tables

(Received August 14, 1970)
Introduction e x p l a i n e d v a r i o u s l y : - t h a t protein serves as
Biochemically, s y n o v i a l fluid m a y be re- a ' g o b e t w e e n ' to allow hyaluronic acid to
g a r d e d as a d i a l y s a t e of blood p l a s m a to which adsorb to a r t i c u l a r cartilage (4), t h a t p r o t e i n
is a d d e d v a r y i n g a m o u n t s of a p r o t e i n / m u c o - helps to a b s o r b the h y d r o g e n bonding poten-
p o l y s a c c h a r i d e c o m p l e x (1). This m u c o p o l y - t i a l i t y in the h y a l u r o n i c acid chain (5).
saccharide, h y a l u r o n i c acid, was first isolated T h e rheology of synovial fluid has b e e n
a n d identified in 1934 (2) a n d has since b e e n the subject of m u c h work, which follows the
f o u n d to consist of r e p e a t i n g disaccharide t h r e e general aspects of the rheology of
groups, each containing e q u i m o l a r p r o p o r - p o l y m e r solutions, i. e, the viscosity of syn-
tions of glucuronic acid a n d N - a c e t y l g l u c o s a - ovial fluid u n d e r single-shear a n d m u l t i - s h e a r
mine, w i t h h y d r o x y l end groups. T h e struc- r a t e conditions, a n d the visco-elastic b e h a v -
ture compared with other glycosaminoglycans iour in conditions of oscillatory shear rate.
is s h o w n in fig. 1.
O420~
r co?. o ! ,o 1 Hyaluronic acid concentrates and intrinsic vis-
cosity
OH OH Most of the w o r k done in the 1950's at-
t e m p t e d to correlate the pathological involve-
m e n t of s y n o v i a l joints w i t h the concentra-
tion of h y a l u r o n i c acid a n d its degree of poly-
merisation using capillary v i s c o m e t e r s (6-8).
I n osteoarthrosis t h e h y a l u r o n i c acid concen-
t r a t i o n in the s y n o v i a l fluid a p p e a r e d to be
, cjo~ cH2",
es~ 1 decreased a n d t h e degree of p o l y m e r i s a t i o n
diminished as i n d i c a t e d b y intrinsic viscosity.
"0 0 0

Shear rate dependence

OH NHAC
c~o. .2coso~.
OH NNAc
Fig. 1. The disaccharide repeating units of gIycosamino-
glyeans (we are grateful to Dr. J. Pal/rey for the use of
this figure)
H y a l u r o n i c acid is a polyelectrolyte, h a v -
ing a high n e t n e g a t i v e charge a n d a molec-
ular weight in excess of 1 million in s y n o v i a l
fluid. T h e complexes f o r m e d w i t h p r o t e i n
exist as v o l u m i n o u s , r a n d o m l y coiled particles
w i t h a d i a m e t e r 0.5# (3) a n d h a v e been
*) Paper presented to the British Society of Rheology
Conference on Rheology in Medicine and Pharmacy,
London, April 14-15, 1970.
, However, later work has shown that synovial fluid is
a pseudoplastic (shear-thinning) fluid, both in the nor-
mal and pathological states (10, 11), and that, in the
case of shear dependent fluids, extrapolation to zero
shear rate must precede extrapolation to zero concen-
tration in order to derive the intrinsic viscosity (12, 13).
Some of the interesting data of Bloch and Dinten]ass
(10) have been graphed in fig. 2. Hence, it can be seen
that viscometric data over a range of shear rates is
important and is particularly relevant in that the shear-
rate in a synovial joint is varying continuously.
Elasticity
In 1953, it was shown that bovine synovial fluid has
elasticity (14) and this was attributed to the hyaluronic
acid content of the fluid. However, it was not until the
1960's that the viscoelastic properties of synovial fluid
or hyaluronic acid solutions were investigated in greater
detail (15-17). In addition, the 'normal-force' effect has
also been investigated (18, 19).
 Seller et al., The rheology o/synovial fluid 3

10;o~ 1o" ~o~ ~ o ) ~ . , 1o' ,o" 1o-' 1o" 1o),oc ,1o ~.

Fig. 2. Plots of viscosity as a function of shear rate in various fluids. A, C = post-traumatic, B ~ torn menis-
cus, D = non-specific arthritis, E, F ~ osteoarthrosis, I, K = rheumatoid arthritis, J ~ gout, G, H, L ~ solu-
tions of hyaluronic acid (after Bloch and Dinten/ass)

Lubrication
fluid time to cover and possibly i m p r e g n a t e
The bulk rheologieM behaviour of synoviM the surface of the cartilage.
fluid m a y be of possible i m p o r t a n c e in A series of experiments were p e r f o r m e d
eharacterising joint disease, b u t its impor- in which 3 different types of cartilage and 3
tance in terms of joint lubrication is limited. different t y p e s of synovial fluid were used -
U n d e r normM conditions the frictionM forces normal, soft (showing mild fibrillation) a n d
between sliding cartilage surfaces, lubricated osteoarthrosie cartilage, and thick, normM
with synovial fluid, are v e r y low, typical and " w a t e r y " (from a p a t i e n t with r h e u m a t -
values for the coefficient, of friction being oid arthritis) synovial fluid. The results of
0.002-0.01 (20-22). U n d e r e x t r e m e conditions shear stress after 1 see and 5 rain or recipro-
of starved lubrication these values can reach cating motion are shown in tables 2 and 3.
0.1 or more. I t will be observed t h a t in all eases the shear
We have p r o d u c e d evidence to show t h a t stress was greater at 5 rain t h a n it was at
low friction is associated with a full film of I sec. With normM fluid the more degenerate
lubricant, either synovial fluid or a deriva- the cartilage the higher was the shear stress
tive, separating completely the surfaces, and and this difference was more p r o n o u n c e d in
t h a t high friction results from thin films and the early phase. With n o r m a l cartilage the
loeMised b o u n d a r y friction due to asperity more w a t e r y the synoviM fluid the greater
contact (22). was the shear stress and this difference was
I n a series of experiments we used a recip-
r o t a t i n g friction machine to measure the Table 1
coefficient of friction between cartilage and
glass, the moving p a r t being a flat glass plate. disease author concentration intrinsic
T h e reciprocating motion at an amplitude ~ viscosity
of l cm completed the full cycle in 2 sec, dl/gm
giving a m a x i m u m sliding speed of 3 cm/sec.
The specimen was held at one end of a piv- post-mortem Bollet (8) 0.182 69.3@- 4.2
oted arm so t h a t it could be loaded against Stafford (9) 0.24 @-0.09 81.0@- 6.8
the glass plate while the other end of the arm normal Stafford (9) 0.41 j-0.10 73.0@-11.0
c o n t a c t e d the force transducer which re-
corded the frictional force at the cartilage- osteo- Sundblad (6) 0.146@-0.014 27.2:[: 2.2
arthrosis Fletcher (7) 0.110 42.0
glass interface and displayed this on a chart Bollet (8) 0.190 49.8
recorder. The accuracy of the recording was Stafford (9) 0.120@-0.470 56.0@-13.3
0.1 ~ 0.002 kg. The cartilage specimen was
rheumatoid Sundblad (6) 0.150~-0.005 26.0@- 1.1
cut in such a w a y t h a t the bone remained Fletcher (7) 0.072 38
a t t a c h e d to give good backing, the contact Bollet (8) 0.096 37.6
area being t r i m m e d to 0.13 cm. Thus when Stafford (9) 0.070@-0.029 54.0@-11.0
a load of 1.8 kg was applied, the nominM traumatic Sundblad (6) 0.101@-0.008 41.0@- 1.2
contact pressure was 14 kg/em. SynoviM fluid Bollet (8) 0.067 32.5
was deposited on the glass plate and several Stafford (9) 0.110@-0.042 45.0~_ 8.7
minutes were allowed with the cartilage in rneniscal Sundblad (6) 0.175-~0.017 29.4:~: 1.6
light contact with the fluid. This allowed the "infective" Sundblad (6) 0.153~0.020 18.5@_ 1.G
1"
4 Rheologica Acta, Band 10, Heft 1 (1971)

Table 2. Shear stress (kg/sq cm) with normal fluid such an experiment are shown in fig. 3. In
previous studies using the standard Reynolds
cartilage after lifting equation for parallel linkage, an iso-viseous
1 sec 5 rain incompressable fluid and a circular contact
we obtained results which demonstrated t h a t
normal 0.35 0.65 the surface of the cartilage played an essential
soft 0.1 1.0
very soft 0.2 3.0 part in prolonging the squeezing out of the
fluid from between the surface, and that a
squeeze film action was an important feature
Table 3. Shear stress (kg/sq ore) with normal cartilage of lubrication in synovial joints.
Further studies using scanning electron
synovial after lifting microscopy have shown t h a t surface aggrega-
fluid 1 sec 5 rain tion of hyaluronic acid protein complex can
form on cartilage surfaces and give enhanced
tacky 0.015 0.023
normal 0.02 0.5 Squeeze film effecf~
watery 0.15 1.0 ~oed
5ynovial ~ ] Ariicu/ar

particularly pronounced after 5 min. The Recl)~rocati'ng

motion ~ "~" ""~ . . . . . ~ I~S S .....
difference in shear stress between tacky and
watery fluid after 1 sec was tenfold, whereas 1. Wrung-out cortilaqe
after 5 min it was nearly 50 fold. These & I 59ueezefilm time I
results demonstrate clearly that both the Mosimum value ~ ~ f h e ca~Ioyeslider - ~ B o u n d a r y fn'd/on
of fridion ot 9 " ~r Nthis ~ ~ has again been
nature of the lubricating fluid and of the boundarylubri" [
cation condl~ions [
Tpointondl~enllf~efr/'ction
[lowered / f o r c e increoses
reodTed
articulating surfaces are important in deter-
Lowfndionfqrce ~ J gradTlally
mining shear stress. whenafluidf{Im~
seporot~ cad/lo~e end closi
- -_.
9Time ~ - >
In a further series of experiments speci-
mens of cartilage were positioned in the re-
ciprocating friction machine and the cartilage 2. Fully saturated cortilaqe
lowered on to a pool of synovial fluid so squeeze ~#'lm
t h a t complete soaking and absorption oc- I ti~ ~ Ful/w~nq-
curred. When the specimen was loaded 'el ~,~e~, y . r opphe~lood
against the reciprocating plate and friction l~l~hmeott~/t~ n~V
plotted against time, the frictional force rose
steadily until a limit was reached when a
maximum amount of fluid had been wrung 0.~ N 'h _rf?o. ,
s o ; : ~ i/f~.ll.,.i,~9-o~,t
out from the cartilage at that load. In these
squeeze film the abovepraph con be
experiments, the value of friction at any ~ time of t3 redrawn b2puHing
stage during the wringing out process was ; ~ _ @
points(~(~) &0 at
the~amezero
called the "boundary value" of friction at
t h a t stage of wring out. To obtain squeeze
film results at any stage, the cartilage spec-
imen was lifted clear of the glass plate to Time
allow synovial fluid to enter the space be- 10Squeeze film time ]E
tween the surfaces, friction readings being time after lift ' ' "
recorded. After a short run with the cartilage Fig. 3. Squeeze film effects shown diagrammatically
fully saturated, the friction reading was
taken to be the first "boundary value". The
cartilage was momentarily lifted from the lubrication (fig. 4). The adsorbed "structures"
plate and the motion of the plate continued of complex, whilst providing a boundary
until the friction values became greater than lubrication mechanism, when asperities con-
the first "boundary value". The friction force tact, also enhance the conventional squeeze
reached was called the second "boundary film time, as shown by theoretical analysis
value". Another squeeze film test was done, (23). This analysis demonstrates that the
reaching and exceeding the second boundary squeeze film time is not dependent on the
value, as before. The experiment proceeded viscosity of the synovial fluid but on the
in this way until the limiting friction force viscosity of the solvent (the dialysate), which
at full wring-out was reached. Results from approximates to t h a t of water.
 Seller et al., The rheology o/synovial fluid
Fig. 4. Scanning electron microscopy showing surfi~ce aggregation of hyaluronic acid protein complexes on
cartilage surfaces
Acknowledgements
We would like to t h a n k the Arthritis & Rheumatism
Council, Reckitt & Sons, and the West Riding Medical
Trust for financial support of the work described in this
article.
Summary
A review has been undertaken of the rheological
properties of synovial fluid in which the viscosity of
synovial fluid under single-shear and multi-shear rate
conditions, and the visco-elastic behaviour in conditions
of oscillatory shear rate have been described. Synovial
fluid is a pseudo-plastic (shear-thinning) fluid, both in
normal and pathological conditions. The fluid exhibits
elasticity and a normal-force effect. The low friction in
joints is associated with a full film of lubricant which
separates the surfaces and high friction results fl'om t h i n
films of localised boundary friction due to asperity con-
5
tacts. A series of experiments with varying types of
cartilage and synovial fluid have suggested t h a t the
nature of the lubricating fluid and the articular surfaces
are i m p o r t a n t in determining shear stress during re-
ciprocating motion. Scanning electron microscopy has
confirmed the suggestion t h a t surface aggregation of
hyaluronie acid-protein complex can give enhanced
lubrication.
Zusammen/assung
1. Synovialfliissigkeit ist eine nicht-newtonsehe struk-
turvikose Flfissigkeit, deren gesamt-rheologisehe Eigen-
sehaften bei Menseh und anderen Lebewesen g u t doku-
mentiert worden sind. Wir h a b e n uns d a m i t beschgftigt,
ihre Sehmiereigenseh~ften in normalen u n d kranken
menschliehen Gelenken zu untersuchen, Folgende Fak-
toren sind fiir den Sehmiermeehanismus beachtet wor-
den:
6 Rheologiea Acta, Band 10, Heft 1 (1971)
1. Die Arbeitsbedingungen (Belastungen und Ge-
schwindigkeiten)
2. Die Schmierflfissigkeit (Synovialflfissigkeit)
3. Die GelenkoberflEchen (Gelenkknorpel).
Talysur[s-Diagramme von Abdriicken von mensch-
lichen Gelenken haben gezeigt, dab im Vergleich mit
maschinengefertigten Lagern diese sehr rauh sind. Dieses
konnte mit elektronenmikroskopischen Aufnahmen ge-
zeigt werden. Untersuchungen mit einer reziprok arbei-
tenden Reibungsmaschine haben beim Gleiten von Knor-
pel auf Glas, geschmiert mit einer Synovialflfissigkeit,
eine Schmierfilmzeit gezeigt, die die theoretisch errech-
nete nnd auch die ffir l~eopren-Gummi mit Ehnlicher
Beschaffenheit wie Gelenkknorpel bei weitem fibertraf.
Daraus haben wir geschlossen, dab wires hier mit einem
in der Technik unbekannten Schmiermechanismus zu
tun haben, der ,,untersttitzte Schmierung" genannt
wird und der durch EinschluB und Anreichernng yon
Fliissigkeit zustande kommt. Es wird angenommen, dab
Synovialfifissigkeit yon den Unebenheiten eingeschlos-
sen und unter Belastung ein Dialysat herausgepreBt
wird und dabei eine Flfissigkeit mit einer viel h6heren
Konzentration an ttyaluronsEnre-EiweiBkomplex zu-
rficklEBt. Mit elektronenmikroskopischen Aufnahmen
konnte diese Fliissigkeit nachgewiesen werden; und
weitere Experimente zeigten, dab der Komplex sich in
einer Schichten-Struktur anordnet, die unter Belastung
zusammenbricht und dabei einen Schutzfilm auf dem
Gelenkknorpel bildet.
In einer Reihe von Experimenten konnte beim Mes-
sen der Schubbelastung eines normalen Knorpels mit
verschiedenen Synovialfliissigkeiten gezeigt werden, dab
die Schubkraft nach dem Entlasten des Knorpels und an-
schlieBend einer Sekunde reziproker Bewegungen mit zEh-
fl/issiger Synovialfliissigkeit 0,015 kg/cm ~, und mit einer
w~Brigen Synovialfliissigkeit im Vergleich 0,15 kg/cm 2
betrug; nach einer Bewegungsdauer yon 5 min wurden
entsprechende Zahlenwerte yon 0,023 und 1,0 kg/cm 2
gefunden. Eine Reihenuntersuchung mit normaler
Synovialflfissigkeit nnd verschiedenen Arten yon Knor-
pel haben gezeigt, dab die Schubbelastung in einem
osteoarthritisch verEnderten Knorpel 6mal so groB ist
wie f/ir einen normalen Knorpel. Daraus konnten wit
einen ,,Leistungsfaktor" errechnen und verschiedene
Kombinationen yon Knorpel und Synovialflfissigkeit
betrachten. Es ist deutlich, dab nach kurzer Zeit die
Eigenschaft der Synovialflfissigkeit die Leistung ent-
scheidend bestimmt und dab zu einem spEteren Zeit-
punkt die Beschaffenheit des Knorpels mehr an Bedeu-
tung gewinnt. Daraus wird gefolgert, dab Versagen des
Schmiermechanismus in einigen FEllen die Abnfitzung
eines menschlichen Gelenkes hervorrufen und f6rdern
kSnnte, vergleichbar mit der Abnfitzung eines mechani-
schen Lagers dnrch Abrieb, AdhEsion oder Ermiidung.
Re/erences
1) Davies, D. V., Proc. Inst. Mech. Eng. 181, (3J),
25 (1967).
2) Meyer, K. and J. W. Palmer, J. Biol. Chem. 107,
629 (1934).
3) Ogston, A. G. and J. E. Stanier, Biochem. J. 49,
585 (1951).
4) Linn, F. C. and E. L. Radin, Arth. Rheum. 11,
674 (1969).
5) Rogers, H. S., Flow properties of blood and other
biological systems. Proceedings of an informal meeting
between the Faraday Society and the British Society of
Rheology, ed. A. L. Copley and G. Stansby, S. 287
(Oxford 1960).
6) Sundblad, L., Acta Soc. med. Upsalien 58, 113
(1953).
7) Fletcher, E., J. H. Jacobs and R. L. Markham,
Clin. Sci. 14, 653 (1955).
8) Bollet, A. J., J. Lab. Clin. Med. 48, 721 (1956).
9) Sta~ord, C. H., W. Niedermeier, H. L. Holley and
W. Pigman, Ann. Rheum. Dis. 23, 152 (1964).
10) Bloch, B. and L. Dintenfass, Australian and
New Zealand J. Surg. 33, 108 (1963).
11) Davies, D. V., Fed. Proc. 25, 1069 (1966).
12) Fox, T. C., V. G. Fox and P. J. Flory, J. Amer.
Chem. Soc. 73, 1901 (1951).
13) Pearson, G. P., Bull. Brit. Soc. Rheol. 12, 12
(1969).
14) Ogston, A. G. and J. E. Stanier, J. Physiol. 66,
342 (1953).
15) Negami, S., M. Sc. Thesis, Lehigh University,
Bethlehem, Pennsylvania, U.S.A. (1964).
16) Balazs, E. A., Fed. Proc. 25, 1817 (1966).
17) Gibbs, D.A., E. W. Merrill, K . A . Smith and
E. A. Balazs, Biopolymers 6, 777 (1968).
18) Davies, D. V. and A. J. Pal/rey, J. Biomech. 1,
79 (1968).
19) Vos, R. and F. Theyse, Lubrication and Wear in
Joints, pp. 29-34. ed. V. Wright, Sector (London 1969).
20) McCutchen, C. W., Wear 5, 1 (1962).
21) ],inn, F. C., J. Biomech. 1, 193 (1968).
22) Walker, P. S., D. Dowson, M. D. Longfield and
V. Wright, Ann. Rheum. Dis. 27, 512 (1968).
23) Unsworth, A., D. Dowson, and V. Wright, Ann.
Rheum. Dis. (1970).
Discussions
A. Silberberg (Rehovot/Israel) :
Is there no degradation of these high molecular
weight hyaluronic acid molecules in the joint particu-
larly if it is correct that the films are squeezed down to
the small dimensions suggested ?
Molecular weight determined from intrinsic viscosity
of a polyelectrolyte would not be very meaningful unless
the conditions under which it was determined (ionic
strength PH) were carefully investigated.
V. Wright (Leeds, England):
The amount of degradation of hyaluronic acid mole-
cules in vivo has never been investigated, and it remains
a possibility that this could be considerable. This
would be a difficult experiment to set up in that there is
some depolymerisation of hyaluronic acid as soon as it is
removed from the body.
We agree entirely that the molecular weight deter-
mination from intrinsic viscosity of a polyeleetrolyte
would not be very meaningful without speeifying the
conditions under which it was determined, although this
could be done, knowing the various constants in the
Mark-Houwink equation together with the ionic strength.
We have not however done any work on the determina-
tion of molecular weight from intrinsic viscosity data.
A. T. Pal/rey (London, England):
Could the speaker give rather more detail about the
technical procedures in the preparation of material for
the scanning electron mieroscope? Could yon also say
how big you think the trapped pools are - what is their
average diameter and thickness ?
D. Dowson (Leeds, England) :
Specimens of cartilage from the load bearing region
of the femoral condyles were cut in the form of disc
0.65 cm diameter and 0.2 cm thick and used in the re-
 Seller et al., The rheology o~ synovial fluid
eiprocating friction machine. They were p u t into the
specimen holder and layed in a pool of synovial fluid on
a glass plate for pre-soaking. A load of 1.8 kg, giving a
nominal contact pressure of 5.4 kg/cm, was applied to
the cartilage and the sliding action was started. After the
required sliding time, the specimen was lifted from the
glass plate at the centre of its stroke and immediately
lowered into a small t r a y containing Arcton 22 which
was held at a temperature just above its freezing point
of -- 160 ~ b y surrounding it with liquid nitrogen. I n
this way ultra-rapid freezing was obtained. The speci-
mens were then dried in a Pearce-Edwards tissue drier
7
at a b o u t -- 50 ~ After drying the specimens came free
from the glass plate leaving no trace of residue. The
surfaces of the cartilage were then coated with a b o u t
500 A of silver and examined in the Stereoscan.
The trapped pools are 20-50 ~ in diameter.
Authors' address:
Prof. Dr. D. Dowson, Prof. Dr. V. Wright and P . C .
Seller
Bio-engineering Group for the Study of H u m a n Joints,
University of Leeds (England)