THE STRUCTURE AND FUNCTION WITH PARTICULAR REFERENCE OF SYNOVIAL JOINTS, TO THE MECHANISM OF THEIR LUBRICATION by MICHAEL STAFFORD PIPER M.D., University of B r i t i s h Columbia, 1968 A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE i n the Department of Anatomy We a c c e p t t h i s required t h e s i s as c o n f i r m i n g t o the standard THE UNIVERSITY OF BRITISH COLUMBIA JUNE, 1972 In p r e s e n t i n g t h i s thesis an advanced degree at the L i b r a r y I in p a r t i a l the U n i v e r s i t y s h a l l make i t freely f u l f i l m e n t o f the of B r i t i s h available for requirements Columbia, I agree for that r e f e r e n c e and s t u d y . f u r t h e r agree t h a t p e r m i s s i o n f o r e x t e n s i v e copying o f this thesis f o r s c h o l a r l y purposes may be granted by the Head o f my Department o r by h i s of this representatives. It thesis for financial i s understood that copying o r p u b l i c a t i o n gain s h a l l written permission. Department o f The U n i v e r s i t y o f B r i t i s h Vancouver 8, Canada Colui not be allowed without my (ii) ABSTRACT The years. s t r u c t u r e and p h y s i o l o g y o f s y n o v i a l j o i n t s has been s t u d i e d f o r Recent advances i n t e c h n o l o g y and i n v e s t i g a t i v e t o o l s have enabled workers t o g r e a t l y e l u c i d a t e the n a t u r e o f these remarkably joints. This t h e s i s p r e s e n t s a review o f the l i t e r a t u r e d e a l i n g w i t h the morphology and p h y s i o l o g y of d i a r t h r o d i a l joints. development and the gross s t r u c t u r e c a r t i l a g e and s y n o v i a l membrane. f l u i d are presented. the b i o c h e m i s t r y As In a d d i t i o n , features of a r t i c u l a r some o f the f e a t u r e s o f The r e s u l t s o f r e c e n t investigation into and m e t a b o l i s m o f a r t i c u l a r c a r t i l a g e a r e d i s c u s s e d . the main f u n c t i o n o f s y n o v i a l j o i n t s i s t o p r o v i d e p a i n l e s s , t r o l l e d motion, much i n t e r e s t has r e c e n t l y lubrication i n these j o i n t s . nature of j o i n t l u b r i c a t i o n i s presented, This forces c o n c e r n i n g the and a t h e o r y o f l u b r i c a t i o n i s proposed. t h e o r y was developed from the r e s u l t s o f a t e c h n i q u e o f synovianalysis conducted on a s e r i e s o f 61 samples o f s y n o v i a l samples were c o l l e c t e d from a s e r i e s o f h o s p i t a l p a t i e n t s . of p a t i e n t s suffered comprised o f p a t i e n t s rheumatoid The fluid. One group from rheumatoid a r t h r i t i s , w h i l e a second group was s u f f e r i n g from c o n d i t i o n s not associated with arthritis. samples were s u b j e c t e d electrodes, measured. con- f o c u s e d on the mechanism o f A review o f the l i t e r a t u r e enhancement by e l e c t r i c a l r e p u l s i v e The The e m b r y o l o g i c a l o f these j o i n t s i s p r e s e n t e d as i s a d i s c u s s i o n o f the l i g h t and e l e c t r o n m i c r o s c o p i c synovial functional to analysis using and the c o n c e n t r a t i o n s In a d d i t i o n , i n the s y n o v i a l fluid cation sensitive of i o n i z e d sodium and potassium were sodium and p o t a s s i u m c o n c e n t r a t i o n s samples u s i n g glass a spectrophotometer. were measured (iii) As fluid a result samples significantly It synovial fluid part, investigations, from p a t i e n t s lower i s concluded electrical in of these concentration that the of rheumatoid repulsive with forces rheumatoid found arthritis of i o n i z e d lower may acting within seen that the synovial contained a sodium. concentration arthritis the c a r t i l a g e a t t r i t i o n i t was result synovial i n this Sydney o f sodium ions i n a diminution joints, and in of explain, disease. M. Professor Friedman and Head Department o f Anatomy University of B r i t i s h (Supervisor) Columbia (iv) TABLE OF CONTENTS THE STRUCTURE AND FUNCTION OF SYNOVIAL JOINTS, WITH PARTICULAR REFERENCE TO THEIR MECHANISM OF LUBRICATION. Page No. Introduction Embryology o f S y n o v i a l 1 Joints Gross Anatomy o f S y n o v i a l 4 Joints B l o o d and Nerve Supply o f S y n o v i a l 6 Joints L i g h t and E l e c t r o n M i c r o s c o p y o f S y n o v i a l Synovial Membrane and S y n o v i a l 8 Joints 13 Fluid 18 Biochemistry of A r t i c u l a r Cartilage 25 Metabolism of A r t i c u l a r C a r t i l a g e 28 Lubrication of Synovial 30 Conclusion Bibliography Joints " 37 39 (v) LIST OF TABLES Page No. I. II. Sex and Age o f E x p e r i m e n t a l Sample 33 Sodium and P o t a s s i u m I o n C o n c e n t r a t i o n s i n Synovial Fluid o f Rheumatoid and Non-Rheumatoid P a t i e n t s Measured w i t h Glass Electrodes III. 34 Sodium and P o t a s s i u m C o n c e n t r a t i o n i n S y n o v i a l F l u i d of Rheumatoid and Non-Rheumatoid P a t i e n t s Measured w i t h t h e IV. V. Spectrophotometer 35 S y n o v i a l pH i n Rheumatoid and Non-Rheumatoid P a t i e n t s 35 Serum E l e c t r o l y t e s (by Flame P h o t o m e t r y ) i n Rheumatoid and Non-Rheumatoid P a t i e n t s 36 (vi) ACKNOWLEDGEMENT tion I would like of this thesis. surgeons t o acknowledge the assistance I n p a r t i c u l a r I would like given me t o thank i n the preparathe and r a d i o l o g i s t s a t t h e Vancouver G e n e r a l H o s p i t a l assistance i n obtaining synovial for h i s technical assistance. Dr. S y d n e y M. F r i e d m a n his d i r e c t i o n and support. fluid samples, In addition, f o r the opportunity orthopaedic for their and Dr. G e r f r i e d appreciation t o conduct Gebert i s expressed t o t h i s work, and f o r THE STRUCTURE AND FUNCTION OF SYNOVIAL JOINTS, WITH PARTICULAR REFERENCE TO THE MECHANISM OF THEIR LUBRICATION X INTRODUCTION "The F a b r i c o f the J o i n t s i n the Human Body i s a S u b j e c t so much the more e n t e r t a i n i n g , as i t must s t r i k e everyone that considers i t a t t e n t i v e - l y w i t h an Idea o f f i n e m e c h a n i c a l C o m p o s i t i o n . Where-ever the M o t i o n o f one Bone upon a n o t h e r i s r e q u i s i t e , t h e r e we f i n d an e x c e l l e n t f o r r e n d e r i n g t h a t M o t i o n s a f e and f r e e : Apparatus We s e e , f o r I n s t a n c e , t h e e x t r e m i t y o f one Bone moulded i n t o an o r b i c u l a r C a v i t y , t o r e c e i v e the Head o f a n o t h e r , i n o r d e r t o a f f o r d i t an e x t e n s i v e P l a y . Both a r e c o v e r e d w i t h a smooth e l a s t i c C r u s t , t o p r e v e n t m u t u a l A b r a s i o n ; connected w i t h s t r o n g L i g a m e n t s , t o p r e v e n t D i s l o c a t i o n ; and e n c l o s e d i n a Bag t h a t c o n t a i n s a p r o p e r F l u i d d e p o s i t e d t h e r e , f o r l u b r i c a t i n g the Two c o n t i g u o u s Surfaces. So much i n g e n e r a l . " thus w r o t e W i l l i a m H u n t e r , i n 1743 i n a r e m a r k a b l e e s s a y ; "Of the S t r u c t u r e and D i s e a s e s o f A r t i c u l a t i n g C a r t i l a g e s ( 1 ) " . H i s o b s e r v a t i o n s , r e c o r d e d over two hundred y e a r s ago, were e x t r e m e l y a c u t e ; i n f a c t , h i s d e s c r i p t i o n o f t h e b l o o d s u p p l y o f j o i n t s , the " C i r c u l u s Articuli V a s c u l o s u s " has p e r s i s t e d t o the p r e s e n t t i m e . That the s y n o v i a l j o i n t s c o m p r i s e d a unique body t i s s u e easily a c c e s s i b l e t o i n v e s t i g a t i o n l e d e a r l y anatomists t o t h e i r study. Thus, w i t h t h e i n t r o d u c t i o n o f t h e m i c r o s c o p e , the unique h i s t o l o g i c a l appear- ance o f the a r t i c u l a r c a r t i l a g e s was e s t a b l i s h e d , and c a r t i l a g e was known t o have a h i g h m a t r i x t o c e l l r a t i o ( 2 ) . Much i n f o r m a t i o n on the n a t u r e o f s y n o v i a l j o i n t s has been accumul a t e d i n r e c e n t y e a r s , and i t i s the purpose o f t h i s paper t o r e v i e w - 2 these findings. As an introduction to"these discussions embryology of synovial j o i n t s . that of c a v i t a t i o n . I s h a l l f i r s t review the One i n t e r e s t i n g aspect of t h i s f i e l d i s As the limb buds develop as s o l i d mesenchymal pro- trusions, the concept of c e l l death providing c a v i t i e s at the s i t e of j o i n t s has been developed. Teratologists have recently proposed that much pre-natal pathology r e s u l t s from inappropriate c e l l death and question those factors which are active i n the " c o n t r o l l e d c e l l ' death" seen i n j o i n t formation. ( 3 ) Despite the great v a r i a t i o n i n gross structure of synovial j o i n t s , t h e i r general morphology i s b a s i c a l l y s i m i l a r and these features are discussed. Recently developed i n j e c t i o n techniques and auto-radiography have c l a r i f i e d the patterns with regard of c i r c u l a t i o n about j o i n t s , p a r t i c u l a r l y to the osseous c i r c u l a t i o n , and mention of these findings and some discussion of t h e i r c l i n i c a l s i g n i f i c a n c e w i l l be made. (4) With regard to the fine structure of synovial j o i n t s , the introduc- t i o n of the electron microscope has been of great s i g n i f i c a n c e . The f i n d - ings of a number of investigators are included i n t h i s discussion, as w e l l as conclusions reference reached as a r e s u l t of these studies. i n this regard Particular i s made to the u l t r a s t r u e t u r e of the synovial membrane and implications regarding the functions of the various cells within this structure. The structure of the matrix of a r t i c u l a r c a r t i l a g e has greatly limited studies as t o i t s biochemical makeup and metabolism. However, the development of new techniques and modification of old ones has, i n the past two decades, yielded much of this The information. function of synovial j o i n t s , to paraphrase Hunter, i s to provide - 3 controlled painless v i d e d muscles design motion and g r a v i t y for stability. o f the limbs. f o r motion However, synovial joints that greatest source of controversey with a discussion lubrication; of and, as a r e s u l t lubrication enhancement end, n a t u r e has ligaments and i t i s t h e mechanism has p r o v i d e d of the various and To t h i s the greatest i n recent mechanisms of research by m o n o v a l e n t architectural of lubrication interest years. This proposed conducted pro- as w e l l thesis as t h e concludes to account this cations within year, in for this a theory synovial fluid. - 4 Embryology of S y n o v i a l J o i n t s Fore and hind limb buds appear i n the human embryo at four weeks of age as outgrowths of p r i m i t i v e mesenchyme. (5, 6, 7) W i t h i n a few days, a c e n t r a l core of mesenchyme condenses to become what i s termed the "blastema". The blastema subsequently becomes f u r t h e r condensed i n t o c h o n d r i f i c a t i o n centers, one f o r each s k e l e t a l element. That part of the blastema which remains f o l l o w i n g segmentation i s c a l l e d the " i n t e r z o n e . " These are located at the s i t e s o f future j o i n t s , and are continuous w i t h the perichondrium surrounding the c a r t i l a g i n o u s models of the bones. (8) At about f i v e and one h a l f weeks (embryo 11-17 mm) the interzone has f u r t h e r d i f f e r e n t i a t e d i n t o a three layered s t r u c t u r e w i t h two chondrogenic layers sandwiching a loose middle l a y e r . (9) The chondrogenic layers are continuous w i t h the perichondrium of the neighbouring s k e l e t a l segment. The intermediate layer i s continuous w i t h the adjacent e x t r a - > blastemal mesenchyme, which has become v a s c u l a r i z e d at t h i s stage and i s r e f e r r e d to as the " s y n o v i a l mesenchyme", ( s i x and one h a l f weeks - 25 mm). (6, 8, 9, 10) At t h i s stage the outer layers of the s y n o v i a l mesenchyme have begun to d i f f e r e n t i a t e i n t o the fibrous capsule, w h i l e deeper layers are d i f f e r e n t i a t i n g i n t o s y n o v i a l membrane and the i n t r a capsular s t r u c t u r e s . (9) Most authors agree that the s y n o v i a l space begins t o develop at about the s i x week stage of growth as minute spaces i n the s y n o v i a l mesenchyme and the loose middle layer of the interzone. These small spaces subsequently coalese to form the j o i n t c a v i t y . (6, 8, 11, 12) i s some dispute as to how c a v i t a t i o n a c t u a l l y comes about. However, there Some f e e l that c a v i t a t i o n i s an a c t i v e process accomplished by c e l l u l a r p r o l i f e r a t i o n o f . - 5 the lining tissue (9, 13). Others i n d i c a t e t h a t c a v i t a t i o n i s the r e s u l t of c e l l death i n t h e i n t e r z o n e under g e n e t i c c o n t r o l . ( 3 , 6, 14) Recent w o r k e r s have s u g g e s t e d t h a t i n t r a u t e r i n e movement i s e s s e n t i a l t o the p r o c e s s o f c a v i t a t i o n . ( 1 1 , 12) As c a v i t a t i o n p r o c e e d s , the s y n o v i a l s u r f a c e i s a t f i r s t rough and r a g g e d , but towards the end o f the embryonic p e r i o d a smooth i n t i m a l l i n i n g appears o v e r l y i n g the v a s c u l a r s u b s y n o v i a l l a y e r . the j o i n t s have r e a c h e d a d u l t configuration. By e l e v e n weeks - 6 Gross Anatomy of S y n o v i a l Joints A j o i n t or a r t i c u l a t i o n i s formed where two meet one a n o t h e r . (15, l a r g e l y d e t e r m i n e d by i n the cartilaginous The c h a r a c t e r and their function. j o i n t s e x i s t as the s u r f a c e s of the bones are a d i s c of f i b r o c a r t i l a g e . j o i n t s are j o i n t s and surfaces are another. the articular cartilage b a s a l l a y e r of the The "articular and Lining and diar- c o n t i g u o u s bony are not attached to one The lamella." are bound t o one of a dense c o n n e c t i v e t i s s u e bones n e a r the i n n e r s u r f a c e of the case f i r m l y bound t o a n o t h e r by cuff. p e r i p h e r y of the c a p s u l e are f i b r o u s c a p s u l e and a r t i c u l a r margins i s a s y n o v i a l membrane. a Generally articular seen. t o p r e v e n t e x c e s s i v e or abnormal movements of the the by and i s white f i b r o c a r t i l a g e . A v a r i a b l e number of t h i c k e n i n g s i n the ligaments act The i s c a l c i f i e d and bones of s y n o v i a l a r t i c u l a t i o n s c a p s u l e i s a t t a c h e d t o the surface. connected i s u s u a l l y h y a l i n e , however, i n the articular cartilage fibrous capsule c o n s i s t i n g and r e f e r r e d t o as s y n o v i a l or articular cartilage the u n d e r l y i n g bone, the articular sterno-manubrial have common c h a r a c t e r i s t i c s . of membranous bone the eventually pubic symphysis. covered w i t h a r t i c u l a r c a r t i l a g e The epiphysis These j o i n t s a l l o w some degree of m o t i o n , A l l o t h e r j o i n t s i n the body are t h r o d i a l j o i n t s , and inferior temporary and covered w i t h h y a l i n e c a r t i l a g e seen Primary seen where the found i n the median p l a n e of the body - the intervertebral the cartilaginous. such they are are f i b r o u s as e p i p h y s e a l p l a t e between the As Secondary c a r t i l a g i n o u s be syndesmosis of the be body s t r u c t u r e of j o i n t s Thus, j o i n t s may S e c o n d l y , j o i n t s may d i a p h y s i s of g r o w i n g bones. ossify. are 17) s u t u r e s between c r a n i a l bones, or the tibiofibular joint. and 16, or more bones o f the These joints. a t t a c h i n g to This h i g h l y s p e c i a l i z e d the structure encloses a potential amount o f " S y n o v i a " The joint capsule (the true j o i n t or "Synovial cavity fibrocartilaginous the space may disc. periphery, is a small Fluid". be d i v i d e d , c o m p l e t e l y articular at their space) w i t h i n which These discs or incompletely, by a are u s u a l l y attached but are not covered with to s y n o v i a l mem- brane. Synovial joints motion permitted surfaces, the i n them. the muscles joints' are further c l a s s i f i e d This according i s determined t h a t a c t upon the j o i n t , e x c u r s i o n by the c a p s u l e and to the kind of by t h e shape of the and t h e l i m i t s ligaments. articular placed on - 8 B l o o d and Nerve S u p p l y o f S y n o v i a l J o i n t s I n o r d e r t o u n d e r s t a n d the b l o o d s u p p l y t o s y n o v i a l j o i n t s , one must c o n s i d e r two s y s t e m s . The f i r s t i s the a n a s t o m o t i c network of v e s s e l s s u r r o u n d i n g and s u p p l y i n g the s o f t t i s s u e s ; t h a t i s the l i g a m e n t s , and synovium. The second system i s t h a t w h i c h s u p p l i e s the capsule epiphyseal r e g i o n and hence the s u b c h o n d r a l bone. Generally speaking the b l o o d s u p p l y t o l o n g bones i n a p a r t i c u l a r species i s remarkably constant. A s y s t e m i c v e s s e l u s u a l l y runs p a r a l l e l t o the l o n g a x i s o f the bone, and g i v e s a n u t r i e n t a r t e r y w h i c h e n t e r s diaphysis. the T r a n s v e r s e l y a r r a n g e d v e s s e l s form a n a s t o m o t i c networks around the j o i n t s , and a r e the o r i g i n o f v e s s e l s s u p p l y i n g the e p i p h y s e a l metaphyseal r e g i o n s . system although supplying i t . The venous s y s t e m tends t o p a r a l l e l the and arterial t h e r e a r e u s u a l l y more v e i n s d r a i n i n g a bone t h a n arteries T y p i c a l l y a s i n g l e d i a p h y s e a l a r t e r y e n t e r s the n u t r i e n t foramen and r a m i f y s i n the marrow c a v i t y . O c c a s i o n a l l y there are two n u t r i e n t a r t e r i e s , as i n the human femur ( 1 , 1 5 ) . The e p i p h y s e s and d i a p h y s e s smaller nutrient a r t e r i e s . for the m e t a p h y s i s and one a l l y d e s c r i b e d by H u n t e r . A r t i c u l i V a s c u l o s i a s " , and o f l o n g bones a r e s u p p l i e d by numerous These r a m i f y i n t o two a n a s t o m o t i c s y s t e m s , f o r the e p i p h y s i s . one These systems were o r i g i n - He r e f e r r e d t o the c h a n n e l s as "The Circulus l i k e n e d them t o the v e s s e l s o f the m e s e n t e r y . The m e t a p h y s e a l v e s s e l s can be s e e n t o a r i s e d i r e c t l y f r o m the circulus a r t i c u l i v a s c u l o s u s , w h i l e the e p i p h y s e a l v e s s e l s a r i s e from v a s c u l a r a r c a d e s l y i n g on the n o n - a r t i c u l a r p a r t o f the e p i p h y s i s . (4) I t has been p o s t u l a t e d t h a t t h i s d i f f e r e n t o r i g i n o f e p i p h y s e a l and m e t a p h y s e a l a r t e r i e s may (18) account f o r the d i f f e r e n c e i n b l o o d p r e s s u r e found i n the two systems. - 9The b l o o d s u p p l y o f the m e t a p h y s i s changes between f o e t a l and a d u l t life. (19j 20, 21) I n the f o e t u s , the metaphysis n u t r i e n t a r t e r y a l o n e , w h i l e i n the a d u l t , the p e r i p h e r a l two f i f t h s the m e t a p h y s e a l a r t e r i e s of the m e t a p h y s i s , b e i n g s u p p l i e d by the n u t r i e n t a r t e r y . i s s u p p l i e d by the supply the c e n t r a l t h r e e f i f t h s This s i t u a t i o n e x i s t s (22) still i n the " g r o w i n g end" of l o n g bones. I n the " n o n - g r o w i n g e n d " e v e n t u a l l y a l l b l o o d derives arteries. from the m e t a p h y s e a l L i k e w i s e t h e r e i s a change i n the b l o o d s u p p l y of e p i p h y s e s . infant, (up t o one y e a r ) , metaphyseal v e s s e l s p i e r c e the In the cartilaginous e p i p h y s e a l p l a t e and thus s u p p l y the b a s a l p a r t of the e p i p h y s i s . After one y e a r of age the e p i p h y s e a l p l a t e becomes i m p e r v i o u s t o t h e s e metaphyseal vessels, and i s s u p p l i e d s o l e l y by the e p i p h y s e a l v e s s e l s . Thus i t can be seen t h a t l o n g bones, the b l o o d s u p p l y o f the e p i p h y s e a l p a r t and hence t h e s u b c h o n d r a l r e g i o n i s of v a r i a b l e depending upon the age of the bone and the s i t e be of r e l e v a n c e of s t u d y . T h i s f a c t may of the (19) The r o l e of the s u b c h o n d r a l e p i p h y s e a l v e s s e l s a r t i c u l a r c a r t i l a g e w i l l be d i s c u s s e d l a t e r , of the e p i p h y s i s now deserves i n the n u t r i t i o n of however, the v a s c u l a r anatomy mention. Many e p i p h y s e a l n u t r i e n t a r t e r i e s arise from the c i r c u l u s a r t i c u l i and anastomose w i t h i n the e p i p h y s e s immature s k e l e t o n some branches of l o n g bones. In the pass d i r e c t l y to the s u b c h o n d r a l a r e a the c a r t i l a g i n o u s growth . p l a t e ( e p i p h y s e a l p l a t e ) , epiphyseal arteries of origin, i n c o n s i d e r i n g the e t i o l o g y of a v a s c u l a r n e c r o s i s c a p i t a l femoral e p i p h y s i s . vasculasis (23) but the m a j o r i t y of pass towards the a r t i c u l a r and n o n - a r t i c u l a r of the surfaces of the e p i p h y s i s . As t h e s e e p i p h y s e a l n u t r i e n t a r t e r i e s e p i p h y s i s a d j a c e n t t o the m e t a p h y s i s pass from t h a t p a r t of towards the a r t i c u l a r s u r f a c e , the they - 10 f e e d i n t o a number o f a r t e r i a l arcades w h i c h s u b s e q u e n t l y f u r t h e r r a d i a t i n g a r t e r i e s . (15) give r i s e to T h i s p a t t e r n of the a r t e r i a l s u p p l y of the e p i p h y s i s i s s i m i l a r t o the p a t t e r n o f the v a s c u l a r s u p p l y seen i n the c a r t i l a g i n o u s e p i p h y s e a l p r e c u r s o r . (24) The a n a l o g y between a v a s - c u l a r n e c r o s i s o f the f e m o r a l head i n a d u l t s (25) and t h a t seen f o l l o w i n g r e d u c t i o n o f a c o n g e n i t a l l y d i s l o c a t e d h i p (26) i s e a s i l y s e e n . I t has been n o t e d t h a t the d i s t r i b u t i o n o f e p i p h y s e a l a r t e r i e s i s not r e l a t e d t o the t r a b e c u l a r a r c h i t e c t u r e o f the bone. (27) t h e t r a b e c u l a e i s known t o be v a r i a b l e depending upon the f o r c e s o p e r a t i v e i n v a r i o u s c o n d i t i o n s . (28) e p i p h y s e a l a r t e r i e s appears r e m a r k a b l y The The p a t t e r n o f biomechanical However, the d i s t r i b u t i o n o f constant. terminal epiphyseal a r t e r i o l e s which emanate from the anasto- m o t i c a r c a d e s i n the c e n t r a l p a r t of t h e e p i p h y s i s r a d i a t e towards the s u b c h o n d r a l bony p l a t e w h i c h s u p p o r t s the c a r t i l a g e . Here they s i n u s o i d a l loops a b u t i n g a g a i n s t the b a s a l c a r t i l a g e l a y e r s . form These a r e s i m p l e s i n u s o i d s not a t a l l l i k e the d i l a t e d , v a r i c o s e s i n u s e s seen on the m e t a p h y s i a l s i d e o f the growth p l a t e . (23) O c c a s i o n a l l y these sub- c h o n d r a l loops can be seen t o r e a c h i n t o the c a l c i f i e d zone o f c a r t i l a g e , but o n l y v e r y r a r e l y i n t o the more s u p e r f i c i a l zones o f u n c a l c i f i e d cartilage. The (4) s i n u s o i d a l network i n the immediate s u b c h o n d r a l a r e a o f the e p i p h y s i s tends t o be p a r a l l e l t o the a r t i c u l a r c a r t i l a g e . anastomosis i s s e p a r a t e d This v a s c u l a r from the most b a s a l l a y e r o f the c a r t i l a g e c a l c i f i e d zone o f c a r t i l a g e ) by a t h i n p l a t e o f bone. As has been men- t i o n e d t h i s bony p l a t e i s o c c a s i o n a l l y seen t o be p e r f o r a t e d by v a s c u l a r c h a n n e l s w h i c h e x t e n d i n t o the c a l c i f i e d zone of the cartilage. (the small articular T h i s f i n d i n g l e n d s c r e d e n c e t o the s u g g e s t i o n t h a t the a r t i c u l a r c a r t i l a g e d e r i v e s a t l e a s t p a r t o f i t s n u t r i t i o n from the sub- «» c h o n d r a l c i r c u l a t i o n . (29) discussed The n u t r i t i o n o f a r t i c u l a r c a r t i l a g e w i l l be i n more d e t a i l s u b s e q u e n t l y . The v e i n s d r a i n i n g t h e s i n u s e s w i t h i n t h e e p i p h y s e s , a l t h o u g h h a v i n g a r a d i a t e p a t t e r n s i m i l a r t o t h e a r t e r i e s , do n o t accompany t h e a r t e r i e s . They tend t o be more numerous t h a n t h e a r t e r i e s and d r a i n t o t h e c i r c u l u s a r t i c u l i vasculosis. J o i n t s have a b a s i c p a t t e r n o f n e r v e s u p p l y . The branches t o them a r i s e , e i t h e r d i r e c t l y o r i n d i r e c t l y , from the nerves which supply the o v e r l y i n g s k i n and t h e muscles w h i c h move t h e j o i n t . l a r nerve supplies a f a i r l y joint. Each major a r t i c u - l a r g e and r e l a t i v e l y c o n s t a n t p o r t i o n o f t h e There a r e r e g i o n a l d i f f e r e n c e s , i n t h a t c e r t a i n p a r t s o f each j o i n t a r e more h e a v i l y s u p p l i e d w i t h n e r v e f i b e r s t h a n a r e o t h e r regions. These p a r t s a r e u s u a l l y t h o s e most s u b j e c t t o d e f o r m a t i o n d u r i n g movement o f t h e j o i n t and t h e g r e a t e r number o f f i b e r s have a g r e a t e r concentration of p r o p r i o c e p t i v e endings. (30) A r t i c u l a r n e r v e s have a common b a s i c p a t t e r n , and c o n t a i n b o t h m y e l i n a t e d and n o n - m y e l i n a t e d f i b e r s . A l l myelinated f i b e r s are afferent u s u a l l y c a r r y i n g i m p u l s e s from endings o f t h e R u f f i n i t y p e . corpuscles are a l s o seen, u s u a l l y i n the f i b r o u s capsule. Pacinian Some o f t h e s m a l l e r a f f e r e n t m y e l i n a t e d f i b e r s end i n s i m p l e o r f r e e nerve e n d i n g s i n the c a p s u l e and a r e f e l t t o be s i m p l e p a i n receptors. Many p f t h e n o n - m y e l i n a t e d f i b e r s a r e p o s t g a n g l i o n i c fibers supplying sympathetic t h e smooth muscle o f t h e a r t i c u l a r v e s s e l s . Some n o n - m y e l i n a t e d f i b e r s end i n f r e e n e r v e endings and c a r r y a f f e r e n t p a i n impulses. The m a j o r i t y o f b o t h m y e l i n a t e d and n o n - m y e l i n a t e d f i b e r s a r e found i n t h e f i b r o u s c a p s u l e , .the s y n o v i a l membrane i t s e l f b e i n g v e r y p o o r l y s u p p l i e d w i t h p a i n f i b e r s . (31) Many o f the fibers These supply the blood brane, and thereby temperature of evidence the One That one overlying lead joints. to of of failure i n the of flow of the are capsule through the and supply innervated nerve. procedures This vasomotor fibrous joints nerve a joint articular nerves skin i n distended common s u p p l y characteristic other vessels c o n t r o l blood i s , each r e g i o n least may of the in articular joint. to The pathological by to synovial one of nerve elevated joints is (32) joints is overlap. is supplied overlapping denervate vasosensory. s y n o v i a l mem- overlying skin. pattern designed and and by at innervation painful arthritic - 13 L i g h t and E l e c t r o n M i c r o s c o p y o f A r t i c u l a r C a r t i l a g e In r o u t i n e h i s t o l o g i c a l preparations o f a r t i c u l a r c a r t i l a g e s d r o c y t e s a r e seen t o l i e i n l a c u n a e d i s t r i b u t e d i n t r a c e l l u l a r m a t r i x . (33) young c a r t i l a g e . chon- w i t h i n an abundant h y a l i n e The c h o n d r o c y t e s a r e s p a r c e , even i n v e r y (34, 35) E a r l y m i c r o s c o p i s t s d e f i n e d f o u r d i s t i n c t zones i n a d u l t a r t i c u l a r c a r t i l a g e , and d e s c r i b e d d i f f e r e n c e s i n t h e s p a t i a l arrangement as w e l l as the c e l l u l a r morphology i n these z o n e s . (34) Zone I , t h e s u p e r f i c i a l o r t a n g e n t i a l s t r a t u m c o n s i s t s o f f l a t t e n e d or markedly ovoid c e l l s l y i n g adjacent t o the s u r f a c e w i t h the long a x i s o f the c e l l s p a r a l l e l t o t h e a r t i c u l a r m a r g i n . T h i s a r e a has a l s o been r e f e r r e d t o as t h e " g l i d i n g zone". (36) I n Zone I I , t h e i n t e r m e d i a t e o r t r a n s i t i o n a l s t r a t u m , a r e plump and o v a l and d i s t r i b u t e d the chondrocytes i n a random f a s h i o n . Zone I I I i s r e f e r r e d t o as t h e deep o r r a d i a t e s t r a t u m . i n t h i s zone tend t o be s m a l l and r o u n d . The c e l l s They a r e a r r a n g e d i n s h o r t , i r r e g u l a r columns p e r p e n d i c u l a r t o t h e a r t i c u l a r s u r f a c e . The b a s a l l a y e r o r Zone I V i s the c a l c i f i e d s t r a t u m , and l i e s t o t h e s u b c h o n d r a l bony p l a t e . and irregular with pyknotic On h e m a t o x y l i n adjacent I n t h i s a r e a t h e c e l l s tend t o be s m a l l nuclei. and e o s i n s t a i n t h e c a l c i f i e d s t r a t u m i s s e p a r a t e d from t h e more s u p e r f i c i a l l a y e r s by a t h i n wavy b l u e l i n e . The n a t u r e o f t h i s b a s o p h i l i c a r e a i s unknown; i t has been c a l l e d t h e " t i d e m a r k " . mention w i l l be made o f t h e v a r i a t i o n s Further found i n t h e c h o n d r o c y t e s o f d i f f e r - ent zones, p a r t i c u l a r l y w i t h r e g a r d t o s t u d i e s w i t h t h e e l e c t r o n m i c r o s c o p e . M e n t i o n s h o u l d be made now, however, o f t h e l i g h t m i c r o s c o p i c of t h e i n t r a c e l l u l a r m a t r i x o f a r t i c u l a r cartilage. appearance - 14 I t has been known f o r many y e a r s t h a t c a r t i l a g e c o n t a i n s f i b e r s imbedded w i t h i n the ground s u b s t a n c e and responsible at l e a s t p a r t i a l l y f o r the s t i f f n e s s of the m a t r i x . (37) suggested that c o l l a g e n Benninghoff, i n formed bundles a r r a n g e d i n a r c a d e s . t h e s e b u n d l e s were anchored i n the c a l c i f i e d s t r a t u m and towards the s u r f a c e collagen t h r o u g h the r a d i a t e s t r a t u m . ran He 1925, felt that vertically At the t r a n s i t i o n a l zone the f i b e r s t u r n e d o b l i q u e l y t o f o l l o w the t a n g e n t i a l o r i e n t a t i o n of superficial layer. They t h e n t u r n e d down, r u n n i n g p e r p e n d i c u l a r l y t h r o u g h the r a d i a l zone t o become anchored a g a i n i n the c a l c i f i e d These " B e n n i n g h o f f a r c a d e s " can be demonstrated u s i n g phase m i c r o s c o p y . (30) back zone. contrast However, r e c e n t e l e c t r o n m i c r o s c o p i c s t u d i e s have i n d i - c a t e d a f a r more random o r i e n t a t i o n of the The the e l e c t r o n m i c r o s c o p e has fibers. r e c e n t l y been used e x t e n s i v e l y a t t e m p t t o c l a r i f y the n a t u r e of a r t i c u l a r c a r t i l a g e . i n an These s t u d i e s shed l i g h t on the o r g a n i z a t i o n o f the e x t r a c e l l u l a r m a t r i x , as w e l l i n d i c a t i n g the s o u r c e of the components of the m a t r i x . studies with greater indicated a v a r i a t i o n i n the s i z e of the f i b e r s found w i t h i n the m a t r i x , and c o n f i r m e d t h i s . (40, 41, 42, 43) to a o f the " g l i d i n g c a r t i l a g e s " . E a r l y s t u d i e s w i t h the e l e c t r o n m i c r o s c o p e (39) has as In a d d i t i o n , the s c a n n i n g e l e c t r o n m i c r o s c o p e have c o n t r i b u t e d u n d e r s t a n d i n g o f the n a t u r e o f the s u r f a c e have subsequent work I n t r a c e l l u l a r d i f f e r e n c e s are also n o t e d i n the s p e c i f i c zones o f the c a r t i l a g e . E l e c t r o n m i c r o g r a p h s of the s u p e r f i c i a l or t a n g e n t i a l s t r a t u m show i t t o e x t e n d t o a depth of 200 t o 600 m i c r a , b e i n g t h i c k e r a t the of the c a r t i l a g e where i t b l e n d s w i t h the p e r i c h o n d r i u m . the c a r t i l a g e i s c o v e r e d w i t h a l a y e r of f i n e f i b e r s and three micra i n depth. The periphery surface filaments of about S c a n n i n g e l e c t r o n m i c r o g r a p h s of t h i s s u r f a c e layer - 15 have l e d some i n v e s t i g a t o r s adsorbed this hyaluronic concept. layer show as the acid. (45) to believe (44) Light microscopists referred "lamina splendens". elements o f the the typical collagen periodicity surfaces and are arranged at oblique or are tightly the deeper packed w i t h layers. fine In remainder angles relatively the narrow t o one little zones region seen r u n n i n g between c o l l a g e n - b u n d l e s . The of the reticulum, flattened secretory the layers. vacuoles filamentous f i b r i l s In These than fibers those their and a r e randomly seen larger cell 64 OA* of more a b u n d a n t , The of i n the and containing superficial chondrocytes membrane n o t results arranged from seen fine and material matrix. classic and have zone. fibers less The and fine I. rough those endo- apparatus collagen of fibers to 600A" a r e tendency to form cell of to 0 ground a scalloped the from A number (41) I t i s suggested to appearance. seen. bundles are appearance that wall with substance filamentous f i b r i l s i n Zone with of i n appearance amorphous zone have merging are markedly (47) 300 cells 100X beaded developed fibers compared a number similar r a n g i n g from of the G o l g i of material. i n this large vesicles also poorly small, stratum) a diameter articular m a t r i x as a characteristic the e x t r a c e l l u l a r a g a i n the are of individual a periodicity a relatively Zone I I , ( t h e t r a n s i t i o n a l a periodicity ance are seen t o the o f Zone I d i f f e r apparently devoid a diameter These intervening There the m i t o c h o n d r i a are sacs They have strata) of m a t r i x s u r r o u n d i n g the and chondrocytes They have of superficial (tangential another. i n diameter w i t h 40A* d i a m e t e r of small e l l i p s o i d deeper plasmic forms fibrils 12OA to this running p a r a l l e l this filamentous fibers layer have c o r r o b o r a t e d o f Zone I o f 64 OX. i n bundles right to a (46) fibrous 35 OA i t corresponds Biochemical studies The about that this is seen. to appear- to discharge - 16 their contents. endoplasmic (41) reticulum, many v e s i c l e s . These The very In findings producing s i m i l a r to of The dense preparation the of calcified necrotic, and separated matrix. The mentioned healthy istic cells (1), 1743, and this have been ute (4) to the good from calcified above, of i t was has that deposits of the the of the actively radiate strata, is a be larger slightly (41) i s random sections to there the appears cartilage s i m i l a r to c a r t i l a g e matrix by appear matrix. a narrow a homogenous of Zone I I I ; t h a t i n immature nourishment wall that seen. those of organelles. chondrocytes involved with f i b e r s have again are the been confirmed described zone of suggested the to rough 47) perpendicular calcified m a t r i x has cells tend are of"Zone for e l e c t r o n microscopy. cell those complex cells collagen they this i n the by Golgi 42, Zone I I I , in ultra-thin of sections 38, arrangement extensive a number resemble organelles In less these (37, the f i b e r s running surrounded however, As Their z o n e , many are Again chondrocytes calcium of developed of mitochondria are that 640A\ b u t state of slightly number picture of w e l l developed collagen. Zone I I . 1 II with The the of a preponderance a well large p e r i o d i c i t y of (47) as particularly that large quantity t o most w o r k e r s some o b s e r v e r s surface. Zone a (400A t o 800S). diameter be well addition protein, is a electron microscopic although to as indicate characteristic in There cells zone i n recent synthesis. but chondrocytes. these are or appearance. However, the the character- (47) aneural (48) depths of u n c a l c i f i e d i s they have times. hinder calcified wall i s , electron-dense c a r t i l a g e was the degenerate appear n e c r o t i c . in protein animals The In IV and avascular Cartilage felt They d i s a p p e a r not to early channels contribin life. - 17 The one n u t r i t i o n o f a r t i c u l a r c a r t i l a g e w i l l be d i s c u s s e d l a t e r , however f u r t h e r note as t o t h e dynamics o f t h e c h o n d r o c y t e s h o u l d be made a t t h i s time. A l t h o u g h m i t o t i c f i g u r e s have been d e s c r i b e d i n t h e c a r t i l a g e o f immature a n i m a l s they a r e n o t seen i n n o r m a l a r t i c u l a r c a r t i l a g e from mature a n i m a l s . ( 4 1 , 4 2 , 4 7 , 49) under c o n d i t i o n s M i t o t i c f i g u r e s a r e o c c a s i o n a l l y seen o f l a c e r a t i v e i n j u r y (42) o r c o m p r e s s i o n . ( 5 0 ) animals c a r t i l a g e c e l l s w i t h i r r e g u l a r shaped n u c l e i a r e o c c a s i o n a l l y and were once thought t o r e p r e s e n t a m i t o t i c d i v i s i o n . studies with In older seen, In recent years t r i t i a t e d t h y m i d i n e , ( a n i n d i c a t o r o f DNA r e p l i c a t i o n ) have shown t h a t a zone o f c h o n d r o c y t e p r o l i f e r a t i o n e x i s t s a d j a c e n t t o t h e zone o f c a l c i f i c a t i o n u n t i l t h e onset o f m a t u r i t y . (51) These f i n d i n g s w o u l d tend t o i n d i c a t e t h a t t h e c e l l count o f a r t i c u l a r c a r t i l a g e would d i m i n i s h w i t h a g i n g . T h i s seems t o be t r u e i n t h e case o f r a b b i t s and c a t t l e , b u t s t u d i e s w i t h human a r t i c u l a r c a r t i l a g e have f a i l e d t o show a s i m i l a r f a l l i n c e l l c o u n t . (35) I n view of the f r e - quency o f c e l l death seen on e l e c t r o n m i c r o s c o p i c s t u d i e s , these f i n d i n g s are as y e t u n e x p l a i n e d . - 18 S y n o v i a l Membrane and S y n o v i a l The Fluid unique n a t u r e o f d i a r t h r o d i a l j o i n t s i s a f u n c t i o n o f b o t h t h e h y a l i n e c a r t i l a g e found a t t h e a r t i c u l a t i n g ends o f bones, and t h e s y n o v i a l membrane. Normal s y n o v i a l membrane c a n be thought o f as c o n - s i s t i n g o f two p a r t s : a t h i n i n n e r l i n i n g bounding t h e j o i n t space and r e f e r r e d t o as t h e s y n o v i a l i n t i m a , and a s u p p o r t i v e the s u b i n t i m a o r s u b s y n o v i a l As discussed derived (52). l a y e r r e f e r r e d t o as tissue. i n t h e embryology o f j o i n t s , t h e s y n o v i a l membrane i s from t h e embryonic mesenchyme o f t h e o r i g i n a l s k e l e t a l b l a s t e m a The r e g e n e r a t i o n o f s y n o v i a l membrane f o l l o w i n g t o t a l synovectomy i n d i c a t e s t h a t i t i s r e a l l y a m o d i f i e d form o f m e s o t h e l i u m . (53) The f u n c t i o n o f s y n o v i a l membrane i s f e l t t o be t w o - f o l d . Certain c e l l s appear t o have a p h a g o c y t i c f u n c t i o n and t h e s t r u c t u r e i s a l s o responsible f o r the production of synovial f l u i d . (54) These phenomena w i l l be d i s c u s s e d more f u l l y . Grossly t h e s y n o v i a l membrane c a n be seen t o l i n e t h e i n n e r of d i a r t h r o d i a l j o i n t s . I t i s a t t a c h e d t o t h e margins o f the a r t i c u l a r c a r t i l a g e s , and t h e s u b i n t i m a b l e n d s w i t h t h e i n t r a - a r t i c u l a r The surface periosteum. membrane o f t e n may be redundant and thrown i n t o f o l d s or v i l l i . The b l o o d s u p p l y o f t h e s y n o v i a l membrane, as w e l l as t h a t o f t h e fibrous capsule, derives from t h e c i r c u l u s a r t i c u l i v a s c u l o s i s . Generally s p e a k i n g t h e r e i s an a r t e r i a l network l y i n g j u s t beneath t h e s u b i n t i m a as i t blends w i t h the contiguous periosteum. arcades This gives r i s e t o a r t e r i a l ' w h i c h pass t h r o u g h t h e s y n o v i a l membrane and appear t o b r a n c h i n t o c a p i l l a r y beds a t t h e j u n c t i o n between i n t i m a and s u b i n t i m a . ( 5 5 , 4) Under t h e l i g h t m i c r o s c o p e s y n o v i a l membrane c a n be c l a s s i f i e d on the b a s i s o f t h e predominant s t r u c t u r e o f t h e s u b i n t i m a l c o n n e c t i v e t i s s u e . Thus, depending upon the site of origin of the synovium i t may be fibrous, fibro-areolar, areolar, areolar-adipose or adipose. (33, 55) The synovial intima has a characteristic appearance composed of a layer of cells varying in depth from one to four imbedded in a matrix of ground substance. The intimal cells have frequent branching c e l l processes with a finely granular cytoplasm which extend to the surface of the synovial membrane and to other cells. One of the characteristic features of the synovial intimal cells is that although they are more numerous on the surface of the synovial membrane, they do not form a continuous unbroken layer as on an endothelial surface. (55, 56) The intimal cells are generally ellipsoid in shape with an oval nucleus. The synovial intima lies on a meshwork of subintimal connective tissue, with numerous capillaries just below the lining surface. (57) The sub- intimal portion of the synovial membrane also has a characteristic c e l l population. About three percent of the subintimal cells are mast cells, and tend to occupy the region between the intima and subintima. Also within the subintima is a collection of unclassified connective tissue cells, predominantly fibroblasts. (56) Collagen fibers provide the major structural support for the subintima, and, to a lesser degree, the intima. Electron microscopy has contributed greatly to the study of the synovial membrane, both with regard to the nature and function of the synovial cells, and to the relationship between the cells and the surrounding matrix.. The light microscopic impression that synovial cells did not form a complete lining of the joint cavity has been confirmed by electron microscopy. (47, 58) Thus the subintima is not exposed to the joint space, although intimal cells and their surrounding matrix are bathed in synovial fluid. is the absence of a basement membrane in synovial membrane. Also noticeable - 20 The n a t u r e o f the s y n o v i a l i n t i m a l c e l l s has w i t h the e l e c t r o n m i c r o s c o p e . and Two been g r e a t l y e l u c i d a t e d types have been d i s t i n g u i s h e d ; types A B c e l l s ; the A c e l l s b e i n g more f r e q u e n t . p h o l o g i c a l d i s t i n c t i o n between the two (58) The fundamental mor- types o f c e l l s i n t h a t type A c o n t a i n prominent G o l g i complexes and many smooth w a l l e d v a c u o l e s , cells but l i t t l e rough e n d o p l a s m i c r e t i c u l u m , w h i l e type B c e l l s are r i g h l y endowed w i t h e n d o p l a s m i c r e t i c u l u m , but G o l g i systems and are s c a n t y . B, and Despite smooth w a l l e d v a c u o l e s the f a c t t h a t type A c e l l s are more f r e q u e n t despite t h e i r morphological than t y p e d i f f e r e n c e s , most a u t h o r s t e n d t o agree t h a t the d i f f e r e n t types do not r e p r e s e n t d i s t i n c t populations of cells, but r a t h e r v a r i a n t s whose morphology i s dependent upon f u n c t i o n a l a c t i v i t y . This concept i s s u p p o r t e d by the f a c t t h a t i n t e r m e d i a t e c e l l types w e l l endowed w i t h b o t h rough e n d o p l a s m i c r e t i c u l u m and G o l g i complexes are found. A l s o , i n some p a t h o l o g i c a l c o n d i t i o n s t h e r e may one c e l l t y p e over a n o t h e r . The f i n d i n g of two be a p r o l i f e r a t i o n o f (47) types o f c e l l s i n s y n o v i a l i n t i m a has led to a g r e a t e r i n s i g h t i n t o the f u n c t i o n o f t h e membrane, and much i n t e r e s t centered around the p r o d u c t i o n o f s y n o v i a l f l u i d . Of p a r t i c u l a r i s the s o u r c e o f s y n o v i a l mucin or h y a l u r o n i c a c i d . shown t o produce h y a l u r o n a t e i n v i t r o and glucuronic contributes, S y n o v i a l membrane has i n v i v o . (54, 59) c o l l o i d a l i r o n t e c h n i q u e s w i t h e l e c t r o n m i c r o s c o p y , i t has h y a l u r o n i c a c i d i s produced i n the G o l g i complex and m a t r i x and of T h i s c o i l e d macromolecule i s r e s p o n s i b l e f o r the v i s c o u s n a t u r e of s y n o v i a l f l u i d , and at l e a s t p a r t i a l l y , to j o i n t l u b r i c a t i o n . interest This i s a s u l f a t e - free mucopolysaccharide containing equimolar concentrations a c i d and N - a c e t y I g l u c o s a m i n e . (54, 56) has been Using been shown t h a t transported the j o i n t c a v i t y by the l a r g e smooth w a l l e d v a c u o l e s . t o the I t seems s i n c e the G o l g i complex and smooth w a l l e d v a c u o l e s are the characteristic f e a t u r e s o f t y p e A c e l l s , i t i s t h e s e c e l l s w h i c h are m a i n l y r e s p o n s i b l e for hyaluronic acid synthesis. (60) I n a d d i t i o n t o the p r o d u c t i o n of h y a l u r o n i c a c i d , the type A a r e a c t i v e i n removing s u b s t a n c e s from the s y n o v i a l f l u i d . These c e l l s a r e a c t i v e i n p h a g o c y t o s i n g b o t h s m a l l p a r t i c u l a t e m a t t e r , and o b j e c t s such as c e l l fragments and e r y t h r o c y t e s . The cells also larger (61) f i n d i n g o f l a r g e amounts o f rough e n d o p l a s m i c r e t i c u l u m i n the less frequent type B c e l l s has i n d i c a t e d t h a t t h e s e c e l l s are engaged i n the m a n u f a c t u r e o f p r o t e i n . actively A l t h o u g h a l m o s t a l l the p r o t e i n found i n s y n o v i a l f l u i d i s f e l t t o d e r i v e from the plasma, two p e r c e n t o f t h i s p r o t e i n i s found i n the s y n o v i a l f l u i d f i r m l y bound t o h y a l u r o n i c a c i d . (56, 62) I t has f l u i d p r o t e i n may been s u g g e s t e d t h a t t h i s s m a l l f r a c t i o n ' o f s y n o v i a l a r i s e from the s m a l l p o p u l a t i o n o f type B c e l l s . (47, 58) The m a t r i x of the s y n o v i a l i n t i m a has varying electron density. a m o t t l e d appearance, w i t h C o l l a g e n w i t h c h a r a c t e r i s t i c 640^ i s s e e n , as w e l l as v e r y f i n e f i b r i l l a r y f i b e r s . periodicity I n areas o f synovium where the i n t i m a l c e l l s a r e t h r e e t o f o u r deep, a rough d i v i s i o n between s u p e r f i c i a l , m i d d l e and deep zones can be made. Generally speaking, i t i s i n the deep zone t h a t most of the banded c o l l a g e n i s found, w h i l e the finer f i b e r s are s e e n i n the more s u p e r f i c i a l zones w i t h the g r a n u l a r amorphous matrix. The (47, 58) electronmicroscopic appearance of the s u b s y n o v i a l i n t i m a depends l a r g e l y upon the n a t u r e o f the a r e a or a d i p o s e ) . ( i . e . fibrous, areolar I n a l l v a r i e t i e s , f i b r o b l a s t s , mast c e l l s and phages a r e f o u n d . One t i s s u e or s u b - t i s s u e macro- c h a r a c t e r i s t i c f e a t u r e o f the s u b i n t i m a v a s c u l a r i t y , w i t h many a r t e r i o l e s and capillaries. The i s i t s high capillaries extend - 22 i n t o the i n t i m a , and i n f a c t may be s e p a r a t e d a t h i n band o f i n t i m a l m a t r i x . (47) only There i s a v a r i a b l e amount o f banded c o l l a g e n p r o v i d i n g the framework o f t h e Any from the j o i n t space by subintima. d i s c u s s i o n o f the s y n o v i a l membrane must i n c l u d e a c o n s i d e r a t i o n of s y n o v i a l f l u i d . 16th c e n t u r y , who The t e r m " s y n o v i a " was f i r s t used by P a r a c e l s u s i n the l i k e n e d i t s appearance t o egg w h i t e . (56, 62) Synovial f l u i d has been d e f i n e d as " a p r o t e i n c o n t a i n i n g d i a l y s a t e o f b l o o d p l a s m a , t o w h i c h m u c i n , s e c r e t e d by the s y n o v i a l c e l l s , w a t e r d i f f u s e s through t h e s y n o v i a l t i s s u e spaces i n t o the l a r g e r s p a c e , the j o i n t c a v i t y " . (62) t o 7.8. tissue Grossly, s y n o v i a l f l u i d i s c l e a r , pale y e l l o w , v i s c i d , and does not c l o t . f r o m 7.39 i s added as t h e plasma I t i s w e a k l y a l k a l i n e , w i t h a pH of (63) The c h a r a c t e r i s t i c v i s c o s i t y o f s y n o v i a l f l u i d i s p r o v i d e d by u r o n i c a c i d , a s u l f a t e - f r e e mucopolysaccharide. polymerized molecule of equimolar N-acetylglucosamine This i s a long chained p r o p o r t i o n s of g l u c u r o n i c a c i d h a v i n g a m o l e c u l a r w e i g h t o f about one hyal- and million. H y a l u r o n i c a c i d c o n t e n t i n normal s y n o v i a l f l u i d i s a p p r o x i m a t e l y 3.6 milli- grams p e r gram. (17) V a r i o u s f u n c t i o n s f o r h y a l u r o n i c a c i d i n s y n o v i a l f l u i d have been p r o posed. I t i s operative i n maintaining lubrication i n j o i n t s . T h i s can be s e e n when h y a l u r o n i d a s e i s i n t r o d u c e d i n t o a j o i n t and r a p i d breakdown o f a r t i c u l a r c a r t i l a g e r e s u l t s . (64, 65) h y a l u r o n a t e a c i d may joint. i n some way I t has a l s o been suggested' t h a t the m a i n t a i n the w a t e r b a l a n c e w i t h i n the (56) Normal s y n o v i a l f l u i d c o n t a i n s about one t h i r d the p r o t e i n found i n serum (2.5 grams p e r 100 m i l l i l i t r e s ) , w i t h a h i g h e r a l b u m i n - g l o b u l i n ratio. A l b u m i n forms 75 p e r c e n t o f the p r o t e i n . The p e r c e n t a g e o f a l p h a - 23 and b e t a g l o b u l i n i s s i m i l a r t o t h a t found i n serum, w h i l e t h e p e r c e n t a g e of a l p h a - 2 g l o b u l i n and gamma g l o b u l i n i s l e s s . F u r t h e r m o r e , a l l serum p r o t e i n s w i t h a m o l e c u l a r w e i g h t i n excess o f 160,000 a r e e x c l u d e d synovial joints. from Of p a r t i c u l a r i m p o r t a n c e i s the absence o f f i b r i n o g e n , p r o t h r o m b i n , t h r o m b i n , and t h r o m b o p l a s t i n . These l a r g e m o l e c u l a r w e i g h t p r o t e i n s are e x c l u d e d from j o i n t s by the p r e f e r e n t i a l p e r m e a b i l i t y o f the c a p i l l a r y membrane and the ground s u b s t a n c e o f the s y n o v i a l membrane. (17) Thus s y n o v i a l f l u i d w i l l not clot. S y n o v i a l f l u i d n o r m a l l y c o n t a i n s a s m a l l c e l l u l a r component, r a n g i n g up t o 200 w h i t e c e l l s per m i l l i l i t r e . The m a j o r i t y o f the n u c l e a t e d c e l l s w i t h i n s y n o v i a l f l u i d a r e p h a g o c y t e s , w i t h monocytes b e i n g the most p r e valent. The normal low p o p u l a t i o n o f p o l y m o r p h o n u c l e a r l e u k o c y t e s (about 2 p e r c e n t ) l e a d s t o the s u s p i c i o n o f i n f e c t i o n when any h i g h e r l e v e l i s f o u n d . (66) Red b l o o d c e l l s are v e r y r a r e i n normal f l u i d and a r e f e l t t o r e s u l t from trauma. I n o r g a n i c m a t e r i a l s such as n o n - p r o t e i n n i t r o g e n and g l u c o s e t e n d t o r e f l e c t serum l e v e l s , b o t h b e i n g s l i g h t l y lower i n s y n o v i a l f l u i d . Similar- l y , e l e c t r o l y t e s t e n d t o be s l i g h t l y lower i n s y n o v i a l f l u i d t h a n t h e serum, (62) and a f u r t h e r d i s c u s s i o n o f the c o n c e n t r a t i o n s o f sodium and will potassium follow. A number o f enzymes have been found i n s y n o v i a l f l u i d , and c o n s i d e r a b l e e f f o r t i s p r e s e n t l y b e i n g expended i n an a t t e m p t t o c o r r e l a t e abnormal enzyme l e v e l s w i t h a r t i c u l a r c a r t i l a g e damage i n v a r i o u s j o i n t d i s e a s e s . A number o f dehydrogenases, t r a n s a m i n a s e s and phosphotases have been measured i n s y n o v i a l f l u i d , however t h e i r l e v e l o f a c t i v i t y seems t o c o r r e l a t e w i t h t h e number of l e u k o c y t e s found i n the s y n o v i a l One fluid. o f the f e a t u r e s o f s y n o v i a l f l u i d i s i t s tendency t o accumulate - 24 as a r e s u l t of pathology. Synovianalysis i s a great aid i n diagnosing various forms of a r t h r i t i s and i n assessing the e f f i c a c y of treatment. (66) - 25 Biochemistry of Articular Cartilage F u n c t i o n being so c l o s e l y recently In been expended i n t o addition, new metabolism of high matrix The to light lar matrix ing features have chondrocyte, cell structure, the much e f f o r t biochemical nature enabled researchers in spite of to limitations microscopic Biochemically, one of cartilage hyperhydrated state, m e a s u r i n g up to 80%. (as a mineral but polysaccharides. articular tein 507o content tical It cartilage Over with of is that cult to separate saccharide. is has This Much o f to largely dependent of of hydroxylysine. appears to of the the chains of although the the intracellu- most the is not cartilage has content tightly bound, b e i n g bound t o elastic there interest- the water combination with It ( 7 0 ) to of the the muco- behaviour content. and may be a ( 6 9 ) of 907, of to the be from the a complex i n t e r a c t i o n chondroitin sulfates and iden- slightly proved extremely cartilage pro- diffi- protein between polythe collagen ( 7 1 ) component o f molecular weight attached i m p o s e d by c o m p o s i t i o n appears articular b e due of content in articular collagens, The p r o t e i n p o l y s a c c h a r i d e s organic cartilage. the upon the w a t e r The a m i n o a c i d collagen water the water been suggested that other the this form a g e l dry weight mucopolysaccharide side fibrils. felt collagen. increased quantity its proportion of is the of is ( 6 7 , 68) large crystal) of determine characteristics been d e s c r i b e d . i n bone, has ratio. and e l e c t r o n have to clarifying techniques the related side core varies the cartilages. macromolecules, a number o f protein articular make up chains consisting of considerably sulfated in i size majority These of of the complexes a protein rest are core polysaccharides. and amino a c i d of the high to which is Although content, the - 26 b a s i c u n i t i s thought t o be about 4000S 1 ong w i t h about 60 s i d e c h a i n s . (72, The polysaccharide 73) p o l y s a c c h a r i d e s i d e c h a i n s a r e composed o f r e p e a t e d "glycosaminoglycan" (GAG) units. Three o f these d i m e r i c u n i t s have been described i n a r t i c u l a r c a r t i l a g e ; chondroitin-4 s u l f a t e , s u l f a t e , and k e r a t i n s u l f a t e . (73) macromolecule may The range between 50 and The p r o t e i n p o l y s a c c h a r i d e s dimeric chondroitin-6 number o f s a c c h a r i d e u n i t s i n a 50,000. are n o t d i f f u s e l y d i s t r i b u t e d c a r t i l a g e , but a r e found i n h i g h e s t c o n c e n t r a t i o n i m m e d i a t e l y t h e c e l l s . (74) I n a d d i t i o n the t h r e e g l y c o s a m i n o g l y c a n s d i s t r i b u t e d w i t h i n the c a r t i l a g e . throughout surrounding are differently As mentioned i n the d i s c u s s i o n o f the u l t r a s t r u c t u r e o f c a r t i l a g e , the c o n c e n t r a t i o n o f c e l l p r o t e i n p o l y s a c c h a r i d e s i s markedly d e c r e a s e d i n the s u p e r f i c i a l or g l i d i n g s t r a t a . (40) K e r a t i n s u l f a t e i s found p r i m a r i l y i n the i n t e r t e r r i t o r i a l r e g i o n s i s between the v a r i o u s s t r a t a ) . c o n c e n t r a t i o n s but may (that O t h e r w i s e , k e r a t i n s u l f a t e i s i n low be found t o i n c r e a s e w i t h o l d age. Chondroitin-6 s u l f a t e i s t h e most p r e v a l e n t of the t h r e e glycosaminogens found i n a r t i c u l a r c a r t i l a g e , w i t h chondroitin-4 s u l f a t e having a high concentration i n the embryonic p e r i o d but d e c r e a s i n g w i t h a d v a n c i n g age. The p r o t e i n p o l y s a c c h a r i d e s a r e f e l t t o be i m p o r t a n t (75) i n providing much o f the r e s i l i e n c y o f a r t i c u l a r c a r t i l a g e - perhaps by m a i n t a i n i n g the s p a t i a l o r i e n t a t i o n o f the c o l l a g e n f i b e r s . Some o t h e r o r g a n i c m a t e r i a l s are found i n s m a l l q u a n t i t i e s i n a r t i c ular cartilage. S i a l i c a c i d , probably i n the form of s i a l o p r o t e i n , likely e x i s t s i n c o m b i n a t i o n w i t h the p r o t e i n p o l y s a c c h a r i d e complexes. (76) In a d d i t i o n t h e r e a r e low c o n c e n t r a t i o n s of l i p i d s of c a r t i l a g e . (77) The n a t u r e and found w i t h i n the m a t r i x f u n c t i o n of t h i s m a t e r i a l i s unknown. Also, a number these w i l l With o f enzymes be d i s c u s s e d regard concentration of and unbound in the i s similar (68, 7 8 ) , w i t h sulfates concentration of sulfated the c o n c e n t r a t i o n polyanionic found w i t h i n under the metabolism of of electrolytes fluids the been t o t h e i n o r g a n i c components cellular bound have two serves cartilage. found First, i n other the as Also, the intra- concentration (understandably polysaccharides). o f sodium, w h i c h matrix. to that high, cartilages; of a r t i c u l a r cartilage, exceptions. are very the a r t i c u l a r there the p r i n c i p a l i n view i s an of increase cation for - 28 Metabolism of A r t i c u l a r C a r t i l a g e U n t i l f a i r l y r e c e n t l y , measurements o f r e s p i r a t o r y a c t i v i t y had i n d i c a t e d t h a t a r t i c u l a r c a r t i l a g e had a v e r y low m e t a b o l i c activity. How- e v e r , subsequent s t u d i e s p o i n t e d out the v e r y low c e l l mass o f c a r t i l a g e , and s u g g e s t e d t h a t the r a t e o f m e t a b o l i c of other t i s s u e s . Most of the g l y c o l y t i c enzymes have been demonstrated i n a r t i c u l a r c a r t i l a g e , and only minimally a c t i v i t y per c e l l approached t h a t i n a d d i t i o n , c a r t i l a g e has a f f e c t e d by p e r i o d s o f oxygen d e p r i v a t i o n . l a c t i c a c i d has In a d d i t i o n , been found i n h i g h c o n c e n t r a t i o n i n the t i s s u e . f i n d i n g s have s u g g e s t e d t h a t the m e t a b o l i c tent with i t s avascular developed. been shown t o be c h a r a c t e r , and These a c t i v i t y of c a r t i l a g e i s c o n s i s - t h a t the a n a e r o b i c pathway i s w e l l (79) I n a d d i t i o n , e a r l y i n v e s t i g a t o r s a l s o thought t h a t the were " i n e r t " and at m a t u r i t y , had l i t t l e synthetic a c t i v i t y . chondrocytes However, subsequent i n v e s t i g a t i o n s u t i l i z i n g r a d i o s u l f a t e uptake showed a r a p i d r a t e of turnover f o r a t l e a s t the s u l f a t e d p o l y s a c c h a r i d e m a t r i x . (80) I t appears now component of the t h a t the c h o n d r o c y t e s a r e i n v o l v e d i n a " c o n t i n u a l complex p a t t e r n o f a c t i v i t y d i r e c t e d e n t i r e l y ( o r a l m o s t e n t i r e l y ) t o s y n t h e s i s , maintenance and degradation t h a t compose the i n t r a c e l l u l a r m a t e r i a l " . (81) o f the macromolecules I t has been shown t h a t the c h o n d r o c y t e i s c a p a b l e o f the s y n t h e s i s o f the p r o t e i n o f both the p r o t e i n polysaccharide and c o l l a g e n , the s y n t h e s i s o f the p o l y s a c c h a r i d e p o l y m e r i z a t i o n ) , and the s u l f a t i o n o f the p o l y s a c c h a r i d e . (82, 83) o f the q u a l i t a t i v e and q u a n t i t a t i v e i n f o r m a t i o n on the m e t a b o l i c o f a r t i c u l a r c a r t i l a g e has been d e r i v e d from the use s p e c i f i c t o the macromolecules s y n t h e s i z e d . degradation r a t e s can be d e t e r m i n e d . (and i t s Much activity of i s o t o p i c t r a c e r s Thus both s y n t h e s i s and From these s t u d i e s a number o f con- - 29 e l u s i o n s have been r e a c h e d . The r a t e o f s y n t h e s i s o f the macromolecules has been found t o be more r a p i d i n immature a n i m a l s but a f t e r an d e c l i n e remains f a i r l y c o n s t a n t throughout l i f e . (49) A number o f a n t i m e t a b o l i t e s can be seen t o i n h i b i t t h i s s y n t h e s i s . n e t s y n t h e s i s o f macromolocules has initial I n a d d i t i o n , the been shown t o i n c r e a s e i m m e d i a t e l y following lacerative injury to a r t i c u l a r c a r t i l a g e . increase i n synthesis i n o s t e o a r t h r i t i c j o i n t s . A l s o , t h e r e i s an (84) Normal c a r t i l a g e shows no n e t g a i n i n m a t r i x volume, d e s p i t e the r a t e of s y n t h e s i s of i t s c o n s t i t u e n t macromolecules. t i v e s y s t e m has R e c e n t l y , a degrada- been d e s c r i b e d c a p a b l e o f s p l i t t i n g the p r o t e i n p o l y - s a c c h a r i d e a t o r n e a r t h e s u g a r - p r o t e i n band s i t e . been r e f e r r e d t o as " c a t h e p s i n - D " , a l y s o s o m a l One such p r o t e a s e has enzyme found b o t h i n t r a and I t has been p r o p o s e d t h a t t h e c a p a c i t y of b o t h r a t e s o f s y n t h e s i s and e x t r a c e l l u l a r l y . (85, 86) degradation s u g g e s t s the p r e s e n c e of an a c t i v e i n t e r n a l r e m o d e l l i n g (81, high system. 86). That the c h o n d r o c y t e s o f a r t i c u l a r c a r t i l a g e a r e m e t a b o l i c a l l y a c t i v e r a t h e r t h a n i n e r t has become o b v i o u s . However, c o n t r o v e r s y s t i l l as t o the s o u r c e o f n u t r i t i v e m a t e r i a l s f o r t h i s a c t i v i t y . exists Most e a r l y i n v e s t i g a t o r s , n o t i n g the a v a s c u l a r i t y o f the t i s s u e , s u g g e s t e d t h a t s y n o v i a l f l u i d was the o n l y s o u r c e o f n u t r i t i o n f o r c a r t i l a g e . the Although m i c r o v a s c u l a r c h a n n e l s have been demonstrated p e r f o r a t i n g the bony p l a t e and e n t e r i n g the p o o r l y c a l c i f i e d b a s a l zone o f immature c a r t i l a g e c h a n n e l s cannot be i d e n t i f i e d i n mature a n i m a l s . (40, 87) Most c u r r e n t i n v e s t i g a t o r s f e e l t h a t n u t r i t i v e m a t e r i a l s d i f f u s e t h r o u g h the from the s y n o v i a l f l u i d b a t h i n g the c a r t i l a g e s u r f a c e . these matrix - 30 Lubrication of Synovial Joints As H u n t e r n o t e d i n 1743, the prime f u n c t i o n o f s y n o v i a l j o i n t s i s t o " r e n d e r m o t i o n s a f e and f r e e " and t h a t t h i s f u n c t i o n was a c c o m p l i s h e d by a "bag that contains a proper f l u i d deposited there contiguous s u r f a c e s " . (1) f o r l u b r i c a t i n g t h e two This p a r t i c u l a r l y f r i c t i o n - f r e e movement, found t o have a c o e f f i c i e n t o f f r i c t i o n o f about 0.013, (88) has f a s c i n a t e d b o t h e n g i n e e r s and b i o l o g i s t s f o r y e a r s , and t h e s o u r c e o f t h i s efficient lubrication i s s t i l l highly controversial. extremely The h i g h l y viscous n a t u r e o f s y n o v i a l f l u i d has been n o t e d , and has been f e l t t o add g r e a t l y t o t h e l u b r i c a t i o n o f s y n o v i a l j o i n t s . ( 8 9 , 90) A number o f t h e o r i e s have been proposed i n an a t t e m p t t o e x p l a i n t h e phenomenon o f j o i n t l u b r i c a t i o n . "Hydrodynamic l u b r i c a t i o n " was s u g g e s t e d when t h e i n c o n g r u i t y o f j o i n t s u r f a c e s was n o t e d . (91) two r i g i d surfaces In this system, s e t a t an a n g l e t o one a n o t h e r were seen t o produce a wedge-shaped gap. When one s u r f a c e moves t a n g e n t i a l l y t o t h e o t h e r t h e viscous s y n o v i a l f l u i d i s drawn i n t o t h e d i m i n i s h i n g gap, and a p r e s s u r e i s developed w i t h i n the f l u i d s u f f i c i e n t t o support the v e r t i c a l l o a d . p r o p o s a l was a t t a c k e d on t h e b a s i s This t h a t hydrodynamic l u b r i c a t i o n i s n o t s u i t e d t o r e c i p r o c a t i n g movement, as seen i n p h y s i o l o g i c a l c o n d i t i o n s . (88) A l s o , the high pressures to which a r t i c u l a t i n g j o i n t s are subjected t o i n normal w e i g h t b e a r i n g l e d t o the development o f t h e t h e o r y o f "boundary l u b r i c a t i o n " as a p p l i e d t o s y n o v i a l j o i n t s . I n t h i s model, t h e l u b r i c a n t ( f o r example t h e h y a l u r o n a t e o f s y n o v i a l f l u i d ) has an for the s o l i d s u r f a c e s . affinity Movement t a k e s p l a c e between mono-molecular l a y e r s of adherent l u b r i c a n t . (88) T h i s model i s t h e o r e t i c a l l y a t t r a c t i v e , how- e v e r i n v i t r o e x p e r i m e n t s have found t h i s f o r m o f l u b r i c a t i o n a c t i n g a t o n l y v e r y l i g h t l o a d s . (92) • - 31 The t h e o r y o f "weeping l u b r i c a t i o n " r e l a t e d to t h e l u b r i c a t i o n mechanism. (93) the n u t r i t i o n of c a r t i l a g e The porous n a t u r e of a r t i c u l a r age e n a b l e s i t t o t a k e up l u b r i c a t i n g f l u i d ; w i t h t h e a p p l i c a t i o n load the f l u i d i s squeezed out and p r o v i d e s a f l u i d cartil- of a film for lubrication. ( 9 3 , 94) Most i n v e s t i g a t o r s f e e l that "elastohydrodynamic l u b r i c a t i o n " i s a c t i v e i n p e r i o d s o f r a p i d m o t i o n w i t h l i g h t l o a d s , as i n t h e swing phase o f walking. ( 9 2 , 9 5 , 96) T h i s m o d i f i c a t i o n o f t h e hydrodynamic d e v e l o p e d when i t was s e e n t h a t f o r c e s w i t h i n an e l a s t i c d e f o r m a t i o n o f the c a r t i l a g e . g e n e r a t e a t h i c k e r wedge o f l u b r i c a t i n g s y n o v i a l j o i n t s c o u l d produce This d e f o r m a t i o n cartilages can be seen t o f l u i d . (95) As mentioned i n t h e d i s c u s s i o n o f t h e u l t r a s t r u c t u r e c a r t i l a g e , scanning theory of a r t i c u l a r e l e c t r o n m i c r o g r a p h s have shown the s u r f a c e o f t h e s e t o be r e l a t i v e l y r o u g h . (97) Thus has d e v e l o p e d t h e combined theory of "boosted l u b r i c a t i o n " f o r a r t i c u l a r c a r t i l a g e s . t h e o r y s u g g e s t s t h a t as p r e s s u r e i s a p p l i e d across ( 9 2 , 97) This a j o i n t , o p p o s i n g peaks o f c a r t i l a g e meet, and between t h e s e peaks boundary l u b r i c a t i o n i s a c t i v e . P o o l s o f s y n o v i a l f l u i d accumulate i n t h e d e p r e s s i o n s As t h e p r e s s u r e between t h e p e a k s . r i s e s , w a t e r and o t h e r low m o l e c u l a r w e i g h t s u b s t a n c e s d i f f u s e between the pores o f the c a r t i l a g e and c o l l e c t i o n s hyaluronate r i c h f l u i d a r e g e n e r a t e d . (94) vides a modified f l u i d f i l m f o r further of v i s c o u s , This h i g h l y v i s c o u s f l u i d l u b r i c a t i o n . (92) A r e c e n t s t u d y measured t h e t h i c k n e s s o f s y n o v i a l f l u i d f i l m s h e a l t h y and a r t h r i t i c j o i n t s . I t was n o t e d t h a t b o t h f l u i d i n thickness w i t h the a p p l i c a t i o n f i l m was always c o n s i d e r a b l y l e s s . pro- films of l o a d , but that the a r t h r i t i c from decreased fluid F u r t h e r m o r e , t h e t h i c k n e s s o f the f l u i d f i l m from d i s e a s e d j o i n t s c o u l d be made t o approach t h a t o f normal fluid - 32 by t h e a d d i t i o n o f sodium c h l o r i d e . The d i f f e r e n c e i n t h e t h i c k n e s s o f t h e f l u i d f i l m s was f e l t t o be due t o a d i f f e r e n c e i n t h e number o f e l e c t r i c a l r e p u l s i v e f o r c e s adsorbed o n t o n e g a t i v e l y charged s u r f a c e m o l e c u l e s . (98) To date t h e o n l y r e c o r d e d measurements o f s y n o v i a l f l u i d are electrolytes t h o s e w h i c h have been o b t a i n e d u s i n g flame p h o t o m e t r y . ( 6 2 , 66) These values correspond t o the t o t a l c o n c e n t r a t i o n of the e l e c t r o l y t e i n q u e s t i o n . However, r e c e n t advances i n the use of c a t i o n s e n s i t i v e g l a s s electrodes have e n a b l e d i n v e s t i g a t o r s t o measure t h e i o n i z e d f r a c t i o n o f v a r i o u s electrolytes i n biological fluids. the ( 9 9 , 100) I t has been s u g g e s t e d t h a t c a t i o n i c f r a c t i o n o f these e l e c t r o l y t e s represent t h e i r biologically a c t i v e p a r t ( 9 9 ) , and i t was e l e c t e d t o s u b j e c t s y n o v i a l f l u i d samples t o such an a n a l y s i s . I t was f e l t t h a t i f a r t h r i t i c f l u i d had l e s s biologically a c t i v e f o r c e s t h i s might a c c o u n t f o r t h e breakdown o f l u b r i c a t i o n found i n arthritic joints. Method S i x t y - o n e samples o f s y n o v i a l f l u i d were o b t a i n e d a t a r t h r o t o m y o r by a s p i r a t i o n , and t h e s e were d i v i d e d i n t o 2 g r o u p s . rheumatoid a r t h r i t i s . E l e v e n p a t i e n t s had The r e m a i n i n g f i f t y s u f f e r e d from c o n d i t i o n s n o t a s s o c i a t e d w i t h rheumatoid a r t h r i t i s ; the m a j o r i t y having arthrotomy of the knee f o r i n t e r n a l derangement o r f o r m i n i s c a l t e a r s . The mean age o f t h e r h e u m a t o i d group was 48.7, and t h e r e was a predominance non-rheumatoid of females. I n the group, t h e mean age was 35.4 and t h e r e were more m a l e s . - 33 TABLE I - Sex and Age o f E x p e r i m e n t a l Sample Rheumatoid Group 11 ( 7 f e m a l e , 4 male) Mean Age 48.7 Non-Rheumatoid Group 50 (15 f e m a l e , 35 male) Mean Age 35.4 61 Total The samples were a n a l y z e d f o r i o n i z e d sodium and p o t a s s i u m u s i n g flow- t h r o u g h e l e c t r o d e s c o n n e c t e d i n s e r i e s and s h i e l d e d i n a m e t a l b o x . The r e s u l t i n g e l e c t r o d e p o t e n t i a l s were r e a d on two V i b r o n E l e c t r o m e t e r s were c a l i b r a t e d d a i l y u s i n g weighed s t a n d a r d s . The samples were t o f u r t h e r a n a l y s i s u s i n g the Techtron Atomic A d s o r p t i o n which subjected Spectrophotometer and, when volume p e r m i t t e d , t h e pH o f the sample was d e t e r m i n e d . Results The mean c o n c e n t r a t i o n o f sodium i o n s i n t h e r h e u m a t o i d group was 139.0 mEq/litre. T h i s was compared t o a mean o f 148.9 m E q / l i t r e i n t h e non-rheumatoid g r o u p . concentrations 2.57 There was l i t t l e d i f f e r e n c e i n t h e p o t a s s i u m i o n i n t h e two g r o u p s , t h e mean l e v e l s b e i n g 2.52 m E q / l i t r e and mEq/litre respectively. - 34 TABLE I I - Sodium and P o t a s s i u m I o n C o n c e n t r a t i o n s i n Synovial Fluid of Rheumatoid and Non-Rheumatoid P a t i e n t s Measured w i t h G l a s s E l e c t r o d e s . [Na ] + Rheumatoid Group 139.0 mEq/1 (Range 135 mEq/1 - 146 mEq/1) ( S t a n d a r d D e v i a t i o n 3.16 mEq/1) Non-Rheumatoid Group 148.9 mEq/1 (Range 141 mEq/1 - 154 mEq/1) (Standard D e v i a t i o n 3.31 mEq/1) [K ] + Rheumatoid Group 2.52 mEq/1 (Range 1.6 mEq/1 - 2.8 mEq/1) ( S t a n d a r d D e v i a t i o n 0.41 mEq/1) Non Rheumatoid Group 2.57 mEq/1 (Range 1.8 mEq/1 - 3.0 mEq/1) ( S t a n d a r d D e v i a t i o n 0.49 mEq/1) When t h e samples were s u b j e c t e d t o a n a l y s i s u s i n g t h e s p e c t r o p h o t o meter, a s i m i l a r t r e n d was n o t e d . The r h e u m a t o i d group had a mean concen- t r a t i o n o f 130.7 m E q / l i t r e compared t o 135.7 m E q / l i t r e i n t h e nonr h e u m a t o i d group, w h i l e p o t a s s i u m c o n c e n t r a t i o n s were 4.3 m E q / l i t r e and 4.7 m E q / l i t r e . The l o w e r c o n c e n t r a t i o n s o f sodium seen u s i n g t h e s p e c t r o - photometer were f e l t t o be due t o b o t h t h e h i g h p r o t e i n c o n t e n t f l u i d , and t o a d i l u t i o n a l phenomenon. of the - 35 TABLE III Sodium Rheumatoid and P o t a s s i u m Concentrations and Non-Rheumatoid Patients i n Synovial Fluid of Measured w i t h t h e Spectrophotometer [Na] Rheumatoid Group 130.7 mEq/1 (Range 128 mEq/1 - 136 mEq/1) (Standard Non-Rheumatoid Group 135.7 mEq/1 Deviation 4.5 mEq/1) (Range 120 mEq/1 - 142 mEq/1) (Standard Deviation 5.4 mEq/1) [K] Rheumatoid Group 4.3 (Range 3.9 mEq/1 - 4.7 mEq/1) mEq/1 (Standard Non-Rheumatoid Group 4.7 mEq/1 analysis o f the synovial have a c o n s i s t e n t l y lower 7.10 a n d 7.42 r e s p e c t i v e l y . TABLE IV pH t h a n Synovial fluid pH showed the second Deviation group, t h e mean Non-Rheumatoid Group mEq/1) group t o levels being Patients pH Group mEq/1) 0.55 the rheumatoid mEq/1) pH i n R h e u m a t o i d a n d Non-Rheumatoid Rheumatoid 0.33 ( R a n g e 3.4 mEq/1 - 6.5 (Standard An Deviation Range 7.10 mEq/1 (6.9 mEq/1 - 7.3 mEq/1) 7.42 mEq/1 (7.25 mEq/1 - 7.53 mEq/1) - 36 The lytes question arose as to whether reflected differences the TABLE V levels i n a number found and of in synovial (By electro- Serum e l e c t r o l y t e patients, in synovial Serum E l e c t r o l y t e s Rheumatoid difference i n serum c o n c e n t r a t i o n s . determinations were a v a i l a b l e correlation with the and showed no fluid. Flame Non-Rheumatoid Photometry) in Patients. [Na] [K] Rheumatoid Group (Mean) 139 mEq/1 (Mean) 4.3 mEq/1 Non-Rheumatoid Group (Mean) 140 mEq/1 (Mean) 4.4 mEq/1 All of difference fluid the in above r e s u l t s were s u b j e c t e d the s o d i u m was two groups found to be i n glass highly to electrode statistical analysis. determinations of The synovial s i g n i f i c a n t . (p<0.0001) Discussion This paper mechanisms number of of was appear found to be the less electrical fluid films. fluid films could the addition years. active than those of This be to explain are (101) of active Fluid was made t o fluid of normal forces one seen i n rheumatoid films were films approach of electrolyte solutions. by fluid, for thickness (98) fact of That j o i n t s has boundary joint the possible arthritis. and responsible the the the be- When i t joints i t was a lubrication movement. from a r t h r i t i c synovial substantiated of in synovial i n d i f f e r e n t phases thickness repulsive these by attempt c a r t i l a g e wear i n recent that considerably that the an l u b r i c a t i o n mechanisms come o b v i o u s both represents was suggested maintenance that the normal of arthritic fluid films - 36a This s t u d y has significantly as may compared be due joints, The less may lower ly a diminution part, free repulsive i n the fluid samples concentration concentration the e l e c t r i c a l as bind the c o n c e n t r a t i o n from non-rheumatoid t o the h i g h e r in in i n synovial t o samples which lubrication shown t h a t - fluid sodium ions. film the c a r t i l a g e a t t r i t i o n patients. seen found sodium w i l l acting within fluid This is arthritics, difference i n rheumatoid (66) thickness. a r e s u l t of thinned sodium from rheumatoid of protein of ionized forces of ionized result in a a joint, Thus, subsequent- a breakdown i n films results. in arthritic and decrease This joints. may explain, - 37 CONCLUSION Advances i n t h e knowledge o f s y n o v i a l j o i n t anatomy and p h y s i o l o g y have p a r a l l e l e d s i m i l a r advances i n o t h e r b i o l o g i c a l f i e l d s . s y n o v i a l membrane h a s , i n the past, a t t r a c t e d the greatest Although the attention with r e g a r d t o t h e p a t h o g e n e s i s o f j o i n t d i s e a s e , new i n t e r e s t i s now b e i n g f o c u s e d on a l t e r a t i o n s i n a r t i c u l a r c a r t i l a g e . As i t i s on c a r t i l a g e i n t e g r i t y t h a t u s e f u l j o i n t f u n c t i o n depends, a breakdown i n t h i s integrity, e i t h e r mechanically or biochemically, r e s u l t s i n loss of function. Loss o f f u n c t i o n i n o n l y one o f t h e many s y n o v i a l j o i n t s o f t h e body c a n r e s u l t i n great l i m i t a t i o n o f an i n d i v i d u a l ' s c a p a c i t y . Thus a g r e a t e r understanding of t h e u l t r a s t r u c t u r e and m e t a b o l i s m o f s y n o v i a l j o i n t s and t h e changes that occur w i t h the i n t r o d u c t i o n o f pathology, i s leading basic and scientists c l i n i c i a n s c l o s e r t o an u n d e r s t a n d i n g o f t h e p a t h o g e n e s i s o f t h e v a r i o u s arthritidies. The c o m p l e x i t y o f t h e s e f i n d i n g s i s r e f l e c t e d by t h e r e c e n t l i t e r a t u r e d e a l i n g w i t h t h e p a t h o g e n e s i s o f r h e u m a t o i d a r t h r i t i s . (102, 103) T h i s paper i s an a t t e m p t t o r e v i e w t h e s t r u c t u r e and f u n c t i o n o f normal s y n o v i a l j o i n t s , w i t h p a r t i c u l a r r e f e r e n c e a s p e c t s o f t h e i r anatomy. t o the u l t r a s t r u c t u r a l I n a d d i t i o n , a review o f the c u r r e n t o f j o i n t l u b r i c a t i o n i s i n c l u d e d , and a t h e o r y o f d i s o r d e r e d derived is concepts lubrication, f r o m t h e r e s u l t s o f e x p e r i m e n t a l work c o n d u c t e d on s y n o v i a l fluid, presented. R e s e a r c h c o n t i n u e s i n many r e l a t e d f i e l d s , i n c l u d i n g of p r o s t h e t i c j o i n t s (106) (104, 105), reimplantation and t h e use o f a r t i f i c i a l l u b r i c a n t s . I t i s , however, t h r o u g h a g r e a t e r u n d e r s t a n d i n g o f t h e b a s i c rela- t i o n s h i p between t h e s t r u c t u r e and m e t a b o l i s m o f b i o l o g i c a l t i s s u e s and t h e i r u l t i m a t e f u n c t i o n t h a t answers t o many unanswered q u e s t i o n s w i l l be found. - 38 H u n t e r d e s c r i b e d t h e p e n u l t i m a t e r e s u l t o f a d i s e a s e d j o i n t i n 1743, and c o n c l u d e d : " a t l a s t t h e unhappy P e r s o n must submit t o E x t i r p a t i o n , a d o u b t f u l Remedy, o r wear out a p a i n f u l , though p r o b a b l y a s h o r t L i f e . " (1) His c o n c e r n was as a p p r o p r i a t e a t t h a t time as i t w o u l d be t o d a y . - 39 BIBLIOGRAPHY General 1. HUNTER, W., Of t h e S t r u c t u r e and D i s e a s e s o f A r t i c u l a t i n g P h i l . T r a n s . R. S o c . 42:514 2. Cartilages, (1743). 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