Cartilage Flashcards
How do synovial joints aid in load transfer
Increases in compliance towards the distal end of the bones (compact bone in shaft → cortical bone → articular cartilage → fibrocartilage structures (in some joints). Increases surface area at joints for stress reduction.
Functions of hyaline cartilage
Distribute load effectively to protect underlying bone from high stress.
Maintain low friction to prevent wear and tissue loss
Structure of hyaline cartilage
Hyaline cartilage has very low cell count, with less than 10% of it being chondrocytes (maintain). The other 90% is ECM which consists of collagen type 2, proteoglycan molecules and water.
Collagen arrangement
The greatest proportion of collagen is in the superficial zone where they are arranged longitudinally, this helps to ensure resistance to surface friction and tension as well as act as superficial interstitial fluid support (doesn’t go in joint).
In the middle of the cartilage is the greatest proteoglycan concentration and the fibers are in a mesh type arrangement.
At the deepest layer (jut before subchondral bone) the collagen is aligned vertically to ensure it is anchored to the bone below.
Proteoglycans structure
Consist of a protein core with side changes of GAGs (glucose amino glycan side chains). Proteoglycans have a very high affinity to bine to hyaluronic acid, Therefore, they are then bound to a hyaluronic acid backbone referred to as a proteoglycan aggregate (aggrecan)
Proteoglycan repulsion
The GAG side chains are negatively charged meaning they reply each other which is why they appear bristle like. It also mean that during compression these sides chains will provide greater repulsion giving stiffness to the PG’s
How does the Donnan effect relate to Proteoglycans
Donnan effect = Immobile fixed charge density induces greater osmotic pressure in the tissue than its surroundings
Gags have a fixed charge density meaning water will flow into the cartilage which is why the ECM has such a high water concentration in hyaline cartilage.
Stiffness from aggrecan
The aggrecan promotes immobilisation of the PGs and the collagen mesh network confines these PG aggrecans via the interweaving of collagen fibrils. This allows for tension in the collagen fibers and thus increased stiffness.
Explain the result of the PG collagen network
The PG collagen network forms a porous, permeable solid swollen with interstitial fluid.
i.e They form a solid framework that is swollen with interstitial fluid
Porosity = fluid (pores/spaces) volume: total volume
This refers to the spaces between the solid components
Permeability (interaction between fluid and solid components)
Relates to the ease of fluid flow through the material that is inversely proportional to frictional drag
The permeability of the matrix is very low due to the PG-collagen solid matrix (only 50% of interstitial fluid can move)
Biphasic model of cartilage
- Interstitial fluid phase - Viscous interstitial fluid support the compressive load
- External compression increases internal stress, due to the pores the interstitial fluid is susceptible to frictional drag while moving through these pours. The fluid must navigate the twisting path of the solid the rate at which this occurs depends porosity and the permeability of the ECM
- When internal stress is greater than the swelling pressure the fluid flows out of the cartilage, the remove of this fluid then transfers compression stress to solid components
- Elastic solid phase
- PG’s and collagen
Creep and stress relaxation
- Creep - With a constant stress, it will strain over time
- The external stress is balanced by the solid and osmotic swelling pressure after water has moved into the joint space. (Equilibrium is met)
- Stress relaxation - Constant strain applied and maintained
- Some fluid into joint space but the rest will be redistributed through the solid causing equilibrium and therefore relaxation
Matrix response to compression at different strain rates
- Low strain rate
- Water has time to exudate
- Water exudation is a direction outcome of the resistance to fluid flow given by the matrix porosity, frictional resistance increases with increasing velocity of compression
- High strain rate
- Not enough time for fluid to navigate through the poris tissue
- Significate lateral distortion and classical elastic response
Therefore the solid component is effecting this strain rate which is why increasing strain rate will provide increased stiffness
Structure of hyaline and fibrocartilage
Hyaline has increases in proteoglycans meaning there is greater osmotic swelling pressure causing the increase in water levels. More resistance to compression
Hyaline consists of collagen type 2 and fibro consisting of collagen type 1.
Function of hyaline and fibrocartilage
Fibrocartilage is much better at resisting tension (high modulus) due to collagen type 1 fibres (larger cross-sectional area) and their alignment. But is much more deformable under compressive and shear forces. Hyaline cartilage has a much greater concentration of proteoglycans meaning it can draw more water into the cartilage allowing for better resistance from compressive forces. The PG collagen interaction would also resist shear forces.
Hyaline has a higher modulus and ultimate stress for compression and shear with fibro having a greater modulus for tensile.
Fibro has lower modulus for shear but higher ultimate stress for shear than hyaline.
3 types of lubrication
- Fluid film, lubrication
- Thin layer of fluid separates articular surfaces
- Viscosity of this fluid is important, needs to have high viscosity (slow fluid flow)
- Increased pressure in the fluid provides support to the load
- Needs to be >3 x surface roughness to reduce friction
- Boundary layer lubrication
- Surfaces protected by a boundary lubrication (molecules that adhere to the surface), prevents contact of articular surfaces but not as effective as fluid film.
- Mixed lubrication
- Combination of both
Bearing fucntion of articular surfaces
An increases in compression will increase frictional force (Ff). However, the friction between the articulating cartilage surfaces is mainly dependent on the solid phase (biphasic). Meaning that the coefficient of friction between the articulating cartilage surface can be maintain at very low levels if the fluid phase is maintained. To do this:
- Dynamic loading rather than constant loading and relative motion between articulating surfaces.
Age related changes to hyaline cartilage
Can be grouped by changes to chondrocytes, GAGs and calcification
Chondrocytes - Decrease in proliferation and synthetic capacity of chondrocytes. Meaning that synthesis of ECM is slowed down and decreased
GAGs - Change in GAGs quality and type as well as decrease in concentration. Decrease in size of aggrecan. This then causes a net decreases in osmotic swelling pressure and therefore H2O retention
Calcification - Calcification of ECM (different forces due to decrease in osmotic swelling pressure). Tide mark moving into deep zone (tidemark is the line marking the border between calcified cartilage and non calcified). Replacement of the lower calcified cartilage by bone
Change in loading patterns for hyaline cartilage
Cartilage health is promoted by loading patterns meaning alter loading can causes compositional changes.
- Excessive impact load (high strain rate)
- Inadequate time for fluid distribution allowing for stress relaxation
- Prolonged static load
- Fluid exudation and stress transferred onto solid
- Absence of load
- Inadequate stimuli for chondrocytes. No ECM maintenance therefore decrease in proteoglycan number and quality.
- Change in distribution of load (ligament injury) or rate of load
- Cartilage is slow to adapt
Types of load alter chondrocyte metabolism
Chondrocytes response positively to intermittent hydrostatic pressure. Via a process of mechanotransduction aggrecan and type 2 collagen will be produced. However when exposed to increase shear stresses normal components of ECM are not produced. Instead increases release of proinflammatory mediator, decreased aggrecan and type 2 collagen expression and induce molecular changes that can lead to apoptosis.
Pathological changes to hyaline cartilage
- Altered lubricant (amount and quality)
- Bearing surface failure
- Impulsive load can lead to acute tear
- Mechanical ware can result in interfacial ware or fatigue wear
- Altered chondrocyte activity
- Disruption of collagen - PG matrix
- Altered subchondral bone stiffness. Hyaline protects subchondral bone so without hyaline there is abnormal loading.
Altered loading cycle
Altered chondrocyte metabolism (abnormal remodelling) → altered ECM (collagen PG) meaning decreases tensile resistance and stiffness with increases in porosity (decreased ability to retain water) → altered mechanical behaviour (decreased stiffness, increases permeability which leads to decreased hydrostatic pressure meaning more load shift to solid matrix) → abnormal chondrocyte stimuli
Why does cartilage have inability to repair
- Avascular (diffusion is slower) and aneural (lack of nociception to promote protection)
- Low cellular density
- Low metabolic activity
- Inability to migrate to site of injury
OA risk factors
age, obesity, previous injury, female, genetic inheritance, nutritional factors.
Functions of the meniscus
- Load distribution and decrease stress
- Shock absorption
- Joint stability
- Proprioception (anterior and posterior horns are innervated)
- Lubrication
The aim to protect the articular cartilage
Internal structure of meniscus
-Outer zone
- Fibroblast like cells
- Long cell extension (communication)
- Collagen type 1 (resist tensile forces)
- Inner zone
- Fibro chondrocytes
- Collagen percentage is more type 2 than one
- Proteoglycans are greatest in the inner 2/3
(compression)
- Superficial zone
- Progenitor cells (repair)
Vascularisation and innervation in the outer 1/3 only (horns)
Collagen alignment in meniscus
Anisotropic, collagen fibres orientate with the local axis of stress
Circumferential fibres resist the tension in the outer zone (collagen type 1
Radial fibres transfer the force onto the circumferential
Much higher modules of elasticity to tensile forces (greater relative stiffness) when compared to compression and shear
Changes with ageing in menisci
Earliest changes occurred predominantly along the inner rim, anterior horns of both menisci were less effected by age and OA
- Decreased cell density (die with age)
- Abnormal PGs and altered mix of PGs
- Increases in collagen fibril diameter and amount of collagen (birth to 30)
- Cross linkages of collagen (stiffness against tensile)
- Calcification
Pathological changes at the menisci
Can be difficult to differentiate from aging.
- Abnormal cellularity, cell hypertrophy and abnormal cell clusters
- Changes in PG’s
- Separation of ECM
- Tears
- Either traumatic or degenerative
- Radial tears most common in young adults (inner most part towards outer)
- longitudinal may progress to bucket handle
- Calcification
- Fraying
