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J R Levick

Publications and source records attributed to J R Levick.

At least 91 records · Page 5Linked to original sources

Microfibrillar meshwork of the synovial lining and associated broad banded collagen: a clue to identity.

The surface layer of synovial interstitium lining the rabbit knee was studied by transmission electron microscopy. Over a distance of 2-3 microns normal to the surface the interstitium contained a network of fine microfibrils (diameter 9.3 (0.7) nm, mean (SEM] which was quite dense in places (fractional area of projection 0.189 (0.023], and stained with ruthenium red. Periodic collagen fibrils were relatively scanty and fine (diameter 32 (2) nm) in this surface layer. Broad cross-striated bundles occurred in association with the microfibrils and B cells. These fibrous long spacing bundles (FLS) had a single period of 92.8 (2.8) nm with a broad dark band (37.6) (1.8) nm--so called 'zebra collagen'. Both the periodicity of the FLS and the morphological characteristics of the microfibrils are typical of type VI collagen, a widespread constituent of soft connective tissues. The functional importance of the inner microfibril network is likely to be mechanical, biochemical (glycosaminoglycan and glycoprotein entrapment), and to a very minor degree hydraulic resistance.

Actin Cytoskeleton↗

Pressure induced deformation of the interstitial route across synovium and its relation to hydraulic conductance.

The ease with which fluid passes across the synovial lining (i.e., the lining's hydraulic conductance) is enhanced when intraarticular fluid pressure (IAP) is raised acutely to pathological levels in rabbit knees. A structural basis for this pathophysiological change was sought by morphometry of synovial sections from rabbit knees fixed in situ at less than or equal to 5 cm H2O and 25 cm H2O IAP. Light and electron microscopy showed that the main structural changes induced in areolar synovium by raising IAP to 25 cm H2O were (1) a reduction in synovial thickness to 56% control value; (2) an increase in the area of interstitium exposed at the synovial surface (3) an increased proximity of the synovial capillaries to the joint lumen, the mean distance of capillaries from the surface falling from 8.9 +/- 0.5 microns (n = 391) to 3.3 +/- 0.3 microns (n = 92: p less than 0.001). The capillary profiles showed slight compression under 25 cm H2O IAP, but no collapse. The ratio of interstitial area to thickness is the geometric factor governing hydraulic conductance. The maximum change in interstitial area/thickness was 6.8 times for the blood-joint barrier. A change of this magnitude accounts partly (but not fully) for the experimentally observed conductance changes; and it highlights the importance of capillary depth as a factor governing exchange in joints.

Animals↗

Hypoxia and acidosis in chronic inflammatory arthritis; relation to vascular supply and dynamic effusion pressure.

The chronically inflamed joint is usually chronically hypoxic and acidotic, and this is due partly to a high synovial metabolic rate, partly to reduced synovial capillary density and capillary "burial" under thickened synovium, and partly, in the end stages, to a chronically reduced blood flow. In addition, recent work indicates that prolonged flexion or strong muscular contraction around a chronically inflamed joint (knee) can exacerbate the biochemical abnormalities, by transiently raising intraarticular pressure to such high levels as to further impair synovial blood flow. The resulting unphysiological internal environment is presumably detrimental per se to the joint's well being, though precisely how requires more explicit investigation. The possibility that the subsequent reperfusion during joint relaxation is itself a damaging, radical generating process represents an additional exciting, albeit still contentious development.

Acidosis↗

Synovial capillary distribution in relation to altered pressure and permeability in knees of anaesthetized rabbits.

1. The hydraulic conductance of the synovial lining of the rabbit knee increases greatly at intra-articular pressures (IAP) above 9 cmH2O. A structural cause was sought by fixing synovium in situ at less than or equal to 5 cmH2O IAP (ten animals) or 25 cmH2O IAP (five animals) and examining histological sections morphometrically. 2. The synovial lining was found to be a highly deformable sheet of very vascular connective tissue, with 47 x 10(3)-73 X 10(3) capillaries per cm2 section. 150-260 cm2 endothelial surface per cm3 tissue and a vascular volume of 2.4-5.7%. 3. The thickness of the lining averaged 14-19 microns at low IAP and was reduced at high IAP; in suprapatellar synovium, where changes were most marked, thickness fell by 24-47%. The loose subsynovial space expanded. 4. The average distance separating capillary near-edges from the joint cavity approximately halved from 3.75 and 7.47 microns at low IAP (harmonic and arithmetical means respectively) to 1.82 and 3.35 microns at high IAP. Capillaries remained patent and their number density did not change significantly at high IAP. 5. It is concluded that a reduction in the extravascular path length for fluid exchange contributes to the increase synovial conductance at high IAP, but the path length changes were not sufficient to account fully for the conductance changes.

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Ultrastructure of transport pathways in stressed synovium of the knee in anaesthetized rabbits.

1. The hydraulic conductance of the synovial lining of a rabbit knee increases greatly when intra-articular pressure (IAP) is raised above approximately 9 cmH2O (yield point). To investigate the cause, synovium was fixed in situ by perfusion at controlled IAP and prepared for transmission electron microscopy. Micrographs of synovium fixed below yield pressure (atmospheric pressure and 5 cmH2O IAP, ten joints) and above it (25 cmH2O IAP, five joints) were analysed by morphometry. 2. The discontinuous cellular lining consisted of fibroblast-like cells (67%) and macrophage-like cells (33%) separated by interstitium-filled gaps. Interstitium formed 26-36% of the surface below yield pressure. Depending on sample site the surface gaps averaged 1.9 +/- 0.2 to 2.4 +/- 0.2 microns wide below yield pressure (mean +/- S.E.M. throughout). Above yield pressure the mean gap width increased by 42-64% (P less than 0.05, analysis of variance). 3. The qualitative and quantitative composition of the lining varied with distance below the surface. In a plane 5 microns deep, the intercellular distances and interstitial area fraction were almost double those at the surface. Classic periodic collagen fibrils (diameter 50 +/- 3 nm) abounded at 5 microns depth whereas the surface interstitium was richer in Ruthenium Red-staining microfibrils (diameter 9.3 +/- 0.7 nm) associated with 93 nm period fibrous long-spacing bundles. 4. Averaging over all the tissue between the surface and the 5 microns deep plane, the mean interstitial volume fraction was 0.61 +/- 0.05 at 5 cmH2O and 0.67 +/- 0.02 at 25 cmH2O (n.s.). 5. Capillary fenestrae (8.5 +/- 1.1 per fenestrated profile) and intercellular junctions were unaltered at high IAP. The tortuosity of the capillary-to-joint cavity path was 1.50 +/- 0.01 below yield pressure and 1.86 +/- 0.24 at 25 cmH2O (n.s.). 6. Intra-articular tracers (ferrocyanide, ferritin and glycogen) permeated synovial interstitium without evidence of preferential pathways. Ferrocyanide delineated the capillary intercellular junction as a permeable channel. Ferritin and glycogen were phagocytosed by the macrophages. 7. In suprapatellar areolar synovium, the most extensive and most altered tissue, the ratio of interstitial area to path length increased maximally 4.1 times between 5 and 25 cmH2O IAP. This represents a substantial contribution to the physiologically estimated rise in interstitial conductance (14 x) but does not wholly explain it.

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Interaction of plasma colloid osmotic pressure and joint fluid pressure across the endothelium-synovium layer: significance of extravascular resistance.

Fluid exchanges between blood and a synovial joint cavity across two membranes in series--synovial capillary wall (fenestrated) and synovial intima (modified connective tissue). The relation between transsynovial absorption of intraarticular Krebs solution (flow Qs) and plasma colloid osmotic pressure pi p was investigated in rabbit knees perfused at constant blood pressure. Intraarticular pressure Pj was independently controlled. Linear relations between transsynovial flow and plasma colloid osmotic pressure established that transsynovial flow obeys the Starling hypothesis. However osmotic conductance, dQs/d pi p, increased 3.9 times when Pj was raised from 6 cm H2O or subatmospheric pressure to 18 cm H2O--the "yield phenomenon." Comparison of the effects of pi p and capillary pressure revealed no major change in the osmotic reflection coefficient of the blood-joint barrier to albumin upon raising Pj. The large increase in osmotic conductance was predicted quantitatively by a previous model (prediction 3.8 X) based on increases in extravascular (intimal) conductance as a function of extravascular pressure. It is argued that capillary endothelium is not the sole significant hydraulic resistance in this pathway. In the terminology of Intaglietta and de Plomb (1973) synovial capillaries are functionally intermediate between "tubes" and "tunnels."

Absorption↗

Synovial fluid--its mass, macromolecular content and pressure in major limb joints of the rabbit.

Synovial fluid from rabbit elbow, shoulder, hip and knee was analysed to establish the normal levels of parameters relevant to fluid exchange viz. fluid mass per joint, hydraulic pressure, temperature, colloid osmotic pressure (COP), protein, albumin and glycosaminoglycan (GAG) concentrations. Fluid mass was greatest in the least congruous joint, the shoulder (43 +/- 4 mg), cf. 6 +/- 2 mg in the highly congruous hip. In the knee (24 +/- 4 mg) the mean thickness of the fluid layer was calculated to be 30 microns. Fluid pressure was subatmospheric in all joints (mean -2.8 +/- 0.4 cmH2O, elbow, to -5.7 +/- 0.3 cmH2O, knee), as in many other interstitial spaces. Colloid osmotic pressure was substantial (mean 11.4 +/- 0.9 cmH2O, shoulder, to 13.1 +/- 1.0 cmH2O, elbow), being 40-46% of serum level. Comparison of synovial fluid results with COP versus concentration curves in vitro indicated that the fluid's COP was primarily generated by its protein content (22-30 g l-1, 64% albumin) rather than GAG (4.0-5.8 g l-1). The GAG was 95% hyaluronate and 5% sulphated GAG. Algebraic summation of the hydraulic and colloid osmotic pressures of synovial fluid and serum indicated a net filtration gradient from blood to joint cavity. When serum COP was reduced by intravenous saline infusion, synovial fluid mass increased, in accordance with the ultrafiltration hypothesis of synovial fluid formation. The fluid's colloid concentration declined as volume increased. The relation was not a simple dilution curve, but indicated that the newly formed synovial fluid contained greater than or equal to 8 g protein l-1 (14.5% serum concentration); and that hyaluronate was entering the synovial cavity at a rate of greater than or equal to 6.5 micrograms h-1 per joint.

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Relation between trans-synovial flow and plasma osmotic pressure, with an estimation of the albumin reflection coefficient in the rabbit knee.

The volume of synovial fluid in a joint correlates inversely with plasma colloid osmotic pressure (COP). The inferred influence of plasma osmotic forces on trans-synovial flow was investigated directly here, in isolated perfused hindquarters of sixteen rabbits. Flow of intra-articularly infused Krebs solution across the synovial lining of the cannulated knee was recorded at controlled intra-articular pressure (18 cmH2O). Colloid osmotic pressure in the synovial microcirculation was varied by perfusion with oxygenated red cells resuspended in albumin solution or plasma from an extra-corporeal system at constant perfusion pressure. Studies in vitro showed that the COP versus concentration curve for commercial bovine albumin samples was variable and not reliably described by a widely used polynomial. The rate of trans-synovial absorption Qs was a positive linear function of intravascular COP pi p (r = 0.936, P less than 0.001, n = 83). The average slope dQs/d pi p was 0.20 microliter min-1 cmH2O-1 (S.E. +/- 0.01 microliter min-1 cmH2O-1), the slope depending on hydraulic conductance and osmotic reflection coefficient. Trans-synovial flow was a negative linear function of synovial capillary pressure (Pc). Absolute slope dQs/d pi p was on average only 78% of dQs/dPc in the same joint. The osmotic reflection coefficient of the blood-joint barrier to serum albumin was estimated from these slopes as 0.78-0.81 (S.E.M. +/- 0.06). Vascular perfusion with a hyperosmolar solution of glucose, sucrose or NaCl generated a transient, rapidly decaying osmotic absorption from the joint cavity, with a half-life of 17-60 s. A reversed osmotic transient occurred on reperfusion with isotonic fluid. It was concluded that the blood-joint barrier, which comprises fenestrated endothelium and synovial intima, approximates to an imperfect semipermeable membrane for albumin solutions, justifying the application of Starling's hypothesis to trans-synovial flow. For small solutes the tissues form a highly permeable but nevertheless slightly osmotically reflective membrane.

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Morphology of surface synoviocytes in situ at normal and raised joint pressure, studied by scanning electron microscopy.

The synovial surface in rabbit knees was examined by scanning electron microscopy (SEM) to define normal surface contour, cell shape, and interstitial exposure. Comparison was made between specimens excised before immersion fixation (I), fixed in situ by vascular perfusion (V) before excision, or fixed in situ under an effusion pressure of 5-25 cmH2O (E). The deeply convoluted appearance of rabbit areolar-muscular synovium fixed after excision (I) was found to be an artefact; areolar-muscular synovium fixed in situ (V) was much smoother. The well documented cobblestone contour of immersion fixed adipose synovium was present after fixation in situ, but may be exaggerated by the SEM preparative process. At higher magnification the synoviocytes showed evidence of considerable surface activity (smooth granules, larger cauliflower-like excrescences, thin lamelliform filopodia). Cell shape was variable but many synoviocytes extended long cytoplasmic processes along the surface, producing fibroblastoid and even stellate outlines. At an intra-articular pressure of 25 cmH2O (E) the cytoplasmic processes were elongated and branched, creating a highly dendritic outline. Also, the exposure of interstitium increased markedly at the higher pressure. It is concluded that extension of lengthy cytoplasmic processes is a feature of normal healthy synoviocytes, and that an increase in interstitial area with joint pressure contributes to the increased hydraulic permeability of synovium at raised pressure.

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An analysis of the permeability of a fenestra.

In this analysis of published data we evaluate the permeabilities of unit area of fenestral pathway to water and small solutes. These properties are then used to assess the functional significance of the fenestral diaphragm which, along with the glycocalyx and basement membrane, makes up the fenestral pathway. Endothelial hydraulic conductance and permeability to small lipophobic solutes increase with fenestral density in a variety of mammalian tissue. The increase in conductance per unit increment in fenestral area (Kfen) averages 0.38 micron X s-1 X mm Hg-1 (regression analysis). This value means that a single fenestra (diam 0.06 micron, area 0.003 micron2) has a greater conductance than 1 micron2 of continuous (skeletal muscle) endothelium. Similarly the diffusional permeability of unit fenestral area (Pfen) to B12 and inulin is high. But neither Kfen nor Pfen is as great as might be expected from the extreme thinness of the diaphragm (less than or equal to 5 nm). Pfen depends on diffusivity (D) and pathlength (delta chi): Pfen = D'/delta chi. D' depends on the fraction of the fenestral surface available for exchange and on restriction to diffusion. These relations were applied to test the view that the diaphragm, rather than the glycocalyx or basement membrane, is the major barrier to fluid and small solutes in the fenestral pathway. If this were turn, over 98 1/2% of the diaphragm's area would have to be totally impermeable in order to yield the observed values of Pfen--a result consequent upon the extreme thinness of the diaphragm. In this event there would be less than one equivalent pore (radius 5-11 nm) per diaphragm on average-which is incompatible with ultrastructural evidence. The resistance of a 5-nm-thick diaphragm containing one or more pores is not high enough to account for fenestral resistance. It is concluded that much thicker structures, such as the glycocalyx and/or basement membrane, and not the diaphragm, account for fenestral resistance to small-solute and water transport.

Animals↗

Flow through interstitium and other fibrous matrices.

This review examined the relation between interstitial hydraulic permeability and chemical composition, using porous matrix theory, and assessed the view that interstitial conductivity is governed by GAG concentration. Conductivity correlates negatively with both GAG and collagen concentration over a wide variety of tissues. Conductivities of GAG matrices in vitro, coupled with other quantitative considerations, indicate, however, that no single class of fixed fibrous element exists at a sufficiently high concentration to account by itself for the low conductivity in most tissues. It seems that the low interstitial conductivity arises from the combined interactive effects of three main classes of fibrous element: collagen fibrils, GAG and proteoglycan core protein. In most cases the proteoglycan complex plays a major role which is significantly amplified, however, by the collagen fibril network.

Aggrecans↗

Osmotic flows across the blood-joint barrier.

The effective osmotic pressure across the blood-joint barrier is a key factor controlling synovial fluid volume and joint effusions. The effect of plasma colloid osmotic pressure (COP) on trans-synovial flow was studied directly in rabbit knees expanded by intra-articular fluid infusion. The synovial microcirculation was perfused with blood of varying COP. Absorption of fluid from the joint cavity was a linear function of COP; but albumin COP was only 78% effective across the blood-joint interface. Hyperosmolar solutions of small solutes (e.g., glucose) generated transient osmotic flows across the blood-joint barrier, but far less effectively than albumin. The hydraulic permeability of synovium increased at pathological intra-articular pressures--a phenomenon of potential importance to effusion kinetics.

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Effect of fluid pressure on the hydraulic conductance of interstitium and fenestrated endothelium in the rabbit knee.

A synovial cavity is separated from plasma by synovial intima in series with capillary endothelium. Because 20% of the intimal surface is bare interstitium, the system is a convenient model for the study of passive transport through serial endothelial and interstitial layers. Here hydraulic flow across the composite barrier was investigated in forty-seven knees of isolated, blood-perfused rabbit hindquarters, at intra-articular pressures between 4 and 30 cmH2O. In order to measure barrier conductance at constant intra-articular pressure, pressure on the opposite side of the barrier was varied, i.e. capillary blood pressure (PC). Capillary pressure was changed by alteration of vascular perfusion pressures, and the resulting changes in rate of absorption of Krebs solution from the synovial cavity (QS) were recorded. Trans-synovial absorption was a negative linear function of PC at each joint pressure, in verification of the applicability of Starling's hypothesis to this system. The hydraulic conductance of the blood-joint barrier was calculated as dQS/dPC. Conductance was independent of intra-articular pressure below 9 cmH2O and was 0.12 +/- 0.015 microliter min-1 mmHg-1 (mean +/- S.E. of mean). Barrier conductance increased as a curvilinear function of intra-articular pressure above 9.4 cmH2O (yield pressure). At 30 cmH2O conductance averaged 0.60 +/- 0.06 microliter min-1 mmHg-1, a 5-fold increase. A hyperbolic curve relating net barrier conductance to joint pressure was predicted from the hypothesis that interstitial conductance increases as a monotonic function of intra-articular pressure above yield pressure (Appendix). The data were in reasonable agreement with the theoretical hyperbola. Interstitial conductivity (3 X 10(-7)-7 X 10(-7) cm4 s-1 N-1 below yield pressure) and mean endothelial conductance (1.1 X 10(-4)-1.4 X 10(-4) cm3 s-1 N-1) were evaluated and compared with values in other tissues. Synovial endothelium contains on average 0.25 fenestrae micron-1 circumference. The conductance of a single fenestra was calculated to be 2.3 X 10(-13) cm5 s-1 N-1. Interstitial resistance accounted for roughly half the total resistance below yield point: therefore dQS/dPC should not be equated with 'capillary filtration capacity' in tissues with dense or fenestrated capillary beds. Large inconsistencies between interstitial conductivity and glycosaminoglycan concentration are noted, and mechanistic explanations of increases in conductivity with joint pressure are offered.

Animals↗

Morphometry of the ultrastructure of the blood-joint barrier in the rabbit knee.

The ultrastructure of the barrier to water and solute exchange between blood and a synovial cavity was studied morphometrically in five rabbit knees. The synovial surface consisted of 80% synoviocytes and 20% interstitium in direct contact with synovial fluid. The surface intercellular gaps were wide (0.1-5.5 microns). A rich network of capillaries lay just beneath the surface, the commonest (modal) depth of the capillary perimeter being 5 microns at its nearest point. Of these capillaries, 91% were fenestrated in adipose synovium, 44% in areolar synovium and 21% in posterior synovium; the remainder were continuous capillaries. The number of fenestrae per fenestrated capillary was low (approximately 0.5 micron-1, circumference: approximately 6 microns-2). The fenestrae (width 52 nm; membrane thickness 3-4 nm) occupied approximately 1% of the fenestrated endothelial surface-area. Nuclear segments and intercellular junctions were roughly twice as frequent in continuous capillaries as in fenestrated capillaries of the same circumference, indicating that continuous endothelial cells are of smaller surface area than fenestrated cells. The basement membranes of continuous and fenestrated synovial capillaries were relatively thick (98 and 110 nm respectively), perhaps supporting the synovial endothelium during joint motion. In both fenestrated and continuous capillaries the nuclei were preferentially oriented away from the synovial surface (92 and 67% respectively), which presumably facilitates exchange with the surface.

Animals↗

An analysis of the effect of synovial capillary distribution upon trans-synovial concentration profiles and exchange.

Recent morphometric studies of synovium lining the rabbit knee showed that capillaries extend to greater than 200 microns below the synovial surface; that a proportion of the superficial capillaries are fenestrated; and that the numerical density of the capillaries varies with depth ( Knight & Levick , 1983, 1984). Such observations raised the question 'Down to what depth do capillaries contribute significantly to the diffusional flux of a small extracellular solute (e.g. sulphate) into the joint cavity?' This problem was addressed by a mathematical model of trans-synovial diffusion. The periarticular tissue was considered as a stack of thin slices (delta chi = 2.5 microns), each of known depth and capillary population. An expression for interstitial concentration normal to the surface was derived from the Fick diffusion equations and the mass-balance equation for each slice. Morphometric values were substituted into the area and distance terms of the Fick equation. A range of values was explored for two permeability terms, namely Df/Di (diffusivity across unit fenestral matrix relative to that across unit interstitial matrix) and PS/Q (permeability-surface area product/blood flow for synovial fenestrated capillaries); the ranges lay between the estimated extreme values. Steady-state concentrations and transcapillary fluxes at each depth were obtained by iterative calculation on a microcomputer. The thickness of tissue from which 80% of the joint influx arose (T0.8) was 7-13 microns for diffusion-limited transcapillary exchange (PS/Q = 0.05; Df/Di = 1-0.3); or 9-17 microns for flow-limited exchange (PS/Q = 5; Df/Di = 1-0.03) in areolar synovium, which is the most extensive tissue. The relative independence of the results from the permeability conditions was due to the dominant effect of a peak in capillary density just below the synovial surface. The resistance of the capillary endothelial wall as a fraction of total blood-joint barrier resistance was calculated to be 0.18-0.80 in areolar synovium under conditions of diffusion-limited exchange.

Animals↗

The influence of blood pressure on trans-synovial flow in the rabbit.

Fluid exchange across the synovium lining the cavity of extended knees was studied in twenty rabbit hindquarters. The isolated hindquarters were perfused with blood from an extracorporeal pump-oxygenator system at controlled arterial pressure (PA) and venous pressure (PV). Intra-articular pressure (PJ) was set at 18 cmH2O in most experiments. The rate of trans-synovial absorption of Krebs solution (QS), measured by a drop-counter, was a negative linear function of PA (70-160 mmHg) and of PV (2-42 cmH2O). The sensitivity of exchange to venous pressure ( dQS / dPV , mean -0.25 +/- 0.03 microliter min-1 mmHg-1) was greater than its sensitivity to arterial pressure ( dQS /dPA, mean -0.17 +/- 0.02 microliter min-1 mmHg-1). The ratio of the slopes, ( dQS / dPV )/( dQS /dPA), indicated the pre- to post-capillary vascular resistance ratio. From this ratio and PA, PV, synovial capillary pressures PC were calculated by the equation of Pappenheimer & Soto - Rivera (1948). Trans-synovial absorption rate was a negative linear function of PC. This observation supports the application to the synovial cavity of Starling's hypothesis for fluid exchange between interstitial spaces and plasma (Starling, 1896). The slope dQS /dPC equalled the net hydraulic conductance of the blood-joint barrier (synovium plus capillary endothelium), and averaged -0.425 +/- 0.025 microliter min-1 mmHg-1 at PJ = 18 cmH2O. When PJ was subatmospheric, as is common in extended normal joints, fluid exchange (measured indirectly as dPJ /dt) was only approximately 1/4 as sensitive to blood pressure as at PJ = 18 cmH2O. This observation supported the view that the conductance of the blood-joint barrier depends on PJ.

Absorption↗

The density and distribution of capillaries around a synovial cavity.

The interpretation of trans-synovial fluxes requires a knowledge of the number of capillaries present around the joint cavity, and their depths below the surface of the joint lining. Measurements of capillary numbers, depths and dimensions were therefore carried out by light microscopy on synovial tissue sections from five rabbit knees. In addition the surface area of synovial tissue lining the joint was estimated, and the thickness of the synovium measured. Synovial capillary density was found to be uneven, with respect to both anatomical location in the joint cavity and depth below the synovial surface. The large area of synovium over areolar or adipose tissue was highly vascular (67000-83000 capillaries X cm-2 section; mean intercapillary distance 35-55 micron; 228-329 cm2 endothelium X cm-3 synovium). The small area of synovium over tendons was of very low vascularity (2000 capillaries X cm-2 section). From these data and a previous estimate of net filtration capacity, mean synovial endothelial conductivity was estimated as approximately 16 X 10(-7) cm X s-1 X mmHg-1. The depth distribution of the capillaries was extremely skewed, with a sharp peak at 6-11 micron depth. The rapid decay in capillary density at depths greater than 6-11 micron was partly due to an uneven density of capillaries within the synovium itself; and partly due to a lower density in subsynovial tissues. It was concluded that most synovium has a rich capillary bed which is very superficially located and that the depth of periarticular tissue which is effective in exchange processes with the joint cavity is less than 25 microns.

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