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Locomotor 2 > Normal and Abnormal joints the pathogenesis of OA > Flashcards

Normal and Abnormal joints the pathogenesis of OA Flashcards

1
Q

what type of cartilage is the articular cartilage made out of

A

hyaline cartilage

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2
Q

Name the components of synovial capsule

A
  • articular cartilage
  • synovium (synovial membrane)
  • fibrous capsule
  • ligaments
  • synovial fluid within joint cavity
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3
Q

What makes up the articular capsule

A
  • Fibrous capsule and synovial membrane
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4
Q

what does the articular cartilage allow for

A
  • gives a smooth and slippery surface reducing friction between the articulating surfaces
  • helps absorb impacts protecting the underlying bone
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5
Q

what does the articular capsule do

A
  • holds the articulating bones together

- it is fibrous

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6
Q

Describe hyaline cartilage

A
  • caps the ends of bones in synovial joints
  • smooth, slippery and very low coefficient of friction
  • deeper layer merges with subchondral bone via a calcified cartilage layer
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7
Q

What is the properties of the articular cartilage dependent on

A
  • Elastic and resilience

- properties depend on the composition of the extracellular matrix

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8
Q

What maintains and synthesis the extracellular matrix

A

Chondrocytes

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9
Q

describe the layers of articular cartilage

A

Superficial zone

  • resting reserve cartilage
  • small flattened chondrocytes that are parallel
  • the reserve cells gradually move into the middle zone

Middle/transitional zone

  • chondrocytes become more active
  • go back into the cell cycle and are proliferating
  • become bigger and more rounded

Deep/radial Zone

  • become more rounder
  • hypertrophy
  • form columns = end up with daughter cells underneath each chondrocytes

calcified

  • chondrocytes undergo lysis and die leaving an empty hole
  • they die they release cellular contents into the ECM
  • become calcified
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10
Q

what does chondrocytes do

A

Chondrocytes regulate both synthetic and catabolic processes

- they establish a specialised microenvironment and are responsible for ECM around them

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11
Q

How much of the volume do chondrocytes make up

A
  • less than 5% of total volume of cartilage
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12
Q

describe how the shape, size and number of chondrocytes change

A

Superficial/tangential - flatter, smaller and in greater density

Intermediate/transitional - rounder, larger and sparser - more metabolically active

Deep/radial - stacked up as they have proliferated.

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13
Q

what does chondrocytes sit in

A

lacuna space

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14
Q

describe characteristics of chondrocytes

A
  • low number of mitochondria as they have a low oxygen consumption
  • cell division is low - occurs in response to injury or disease
  • deep chondrocytes have prominent endoplasmic reticulum and golgi apparatus
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15
Q

why do deep chondrocytes have prominent endoplasmic reticulum and Golgi apparatus

A

Responsible for protein synthesis and sulphation of mucopolysaccharrides that form proteoglycan side chains

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16
Q

what makes the ECM of cartilage

A

chondrocytes

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17
Q

describe the ECM matrix of cartilage

A
  • up to 80% water
  • Collagen (mainly type II)
  • contains proteoglycans that draw water into the cartilage
  • lacks blood and lymphatic vessels
  • no nerve supply
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18
Q

what is the role of collagen type II in the ECM of cartilage

A

Network of fibrils, give overall framework and shape of cartilage

Makes pockets filled with proteoglycan complexes

Collagen fibres - right up edges of lacunae

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19
Q

what is the role of proteoglycans in the ECM of cartilage

A
  • these draw water into cartilage and regulate compressibility
  • these are between the gaps in the chondrocytes in the middle zone
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20
Q

how does the ECM get nutrients and metabolites

A
  • Survival and synthetic activity depends on diffusion of nutrients and metabolites through matrix therefore there is more oxygen present in the superficial and middle zone
  • Fine balance of anabolism and catabolism
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21
Q

What other collagen is present in the ECM of cartilage

A

II(Main type), IX, X(present in the deeper zone) and XI

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22
Q

describe the collagen direction in the superficial, intermediate and deep zones of articular cartilage

A

Superficially - parallel with surface highest tensile properties allows gliding

Intermediate - criss-crossed oblique allows compression – proteoglcyans in the pockets

Deep - perpendicular to surface follow stacks of chondrocytes

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23
Q

descirbe where type II collagen is and what percentage it makes up

A

Type II collagen 90-95%

- Present in all layers but more in superficial layers

24
Q

describe type X collagen and where it is

A

Type X collagen

Higher levels in calcified deeper layers

25
Q

how much of dry weight is the collagen in the articular cartilage

A

40-70% of dry weight

- forms a 3D network of fibrils

26
Q

what do most proteoglycans exist as

A

aggregates such as aggrecan

27
Q

How much of dry weight do proteoglycans form in articular cartilage

A

15-40% of dry weight

28
Q

describe aggregates of proteoglycans

A
  • core protein

- GAG side chains (glycosaminoglycan)

29
Q

describe the characteristic of proteoglycans

A
  • has many negative charges
  • highly hydrophilic
  • trap water forming ground substance
  • contributes to shock absorbing properties
30
Q

what is the core protein in proteoglycans

A

hyaluronan

31
Q

define GAGs and name some examples

A

GAGs linear polysaccharides of repeating disaccharide units

  • Keratin sulphate (KS)
  • Chondroitin sulphate (CS)
32
Q

what is the primary tissue that is lost in Oestoarthritis

A
  • the articular cartilage

- everything else is secondary damage after you have lost and damaged the articular cartilage

33
Q

Describe what happens once the articular cartilage has been damaged in osteoarthritis

A
  • articular cartilage fails and undergoes necrosis and cracking so the underlying bone is exposed
  • bone undergoes changes and starts to form an osteophyte
  • the osteophyte irritates the synovial membrane causing inflammation within the synovial membrane
  • inflammation causes a failure in the production of hydrolyrunic acid
  • lowers them viscosity of the synovial fluid
34
Q

what is an osteophyte

A

a bony projection associated with the degeneration of cartilage at joints

35
Q

what increases your risk of osteoarthritis

A

Extrinic and biomechanics factors

  • high BMI
  • past joint injury
  • physical activity levels

Intrinsic factors

  • infection
  • past joint surgery
  • congenial abnormalities

Systemic factors

  • post menopausal hormone replacement therapy
  • genetic
  • increasing age
  • female gender
  • diet
  • bone mineral density
36
Q

describe the role of pro inflammatory cytokines in the pathophysiology of osteoarthritis

A

when chondrocytes become stressed they release pro inflammatory cytokines that lead to an inflammatory response in the rest of the joint

  • pro inflammatory cytokines increase the production of matrix proteases reducing the amount of aggrecan and collagen type II that is made
  • areas are not replaced with new extracellaurl matrix so you end up with an area of cartilage that is not replaced
  • IL-1, 6, 17 and TNF alpha are the inflammatory cytokines that also create local inflammation in the synovium
37
Q

What are the inflammatory markers that create inflammation int eh synovium

A
  • IL-1, 6, 17 and TNF alpha are the inflammatory cytokines that also create local inflammation in the synovium
38
Q

what is synovitis secondary to

A

Synovitis secondary to established bone and cartilage pathology

Once it sets in it drives further inflammatory damage to adjacent bone and cartilage

39
Q

What is the major cause of pain and loss of function in osteoarthritis

A
  • synovitis caused by pro inflammatory cytokines
40
Q

what gene is involved in the cause of osteoarthritis

A

HMGB2

41
Q

what does HMGB2 stand for

A 
HMGB2 = high
mobility group
protein 2
(chromatin 
Protein)
42
Q

where is HMGB2 expressed and what does it do

A

HMGB2 uniquely expressed in the superficial zone chondrocytes
- supports chondrocyte survival and regulates the specific differentiation status of superficial zone cells, including progenitor cells

43
Q

what does loss of HMGB2 lead to

A
  • leads to superficial zone cell death means that there is less reserve cells so fewer chondrocytes that can replace damaged chondrocytes further down
  • loss of progenitor cells,
  • reduced synthesis of ECM components
44
Q

what are the three phases of degeneration macroscopically of the articular cartilage

A

Fibrillation

Erosion and Cracking

Eburnation

45
Q

describe the three phases of degeneration macroscopically of the articular cartilage

A

Fibrillation
- it becomes rougher so you get free edges to the surface of the articular cartilage and then it becomes rougher and you start to get these cracks this is fibrillation

Erosion and Cracking

  • synovial fluid goes underneath the cracks
  • this pushes the cracks further apart and peels the cartilage of the bone

Eburnation
- this is when you lose a bit of cartage completely and it breaks of becoming a loose body in the synovial fluid

46
Q

what are the microscopic changes of osteoarthritis

A
  • Chondrocyte necrosis in superficial layers
  • focal clumsy or clones of chondrocytes due to increased local proliferation
  • change to fibrocartilage from hyaline
47
Q

describe how the hyaline cartilage changes to fibrocartilage in osteoarthritis

A
  • Type 1 collagen rather than type II
  • reduces thickness of articular cartilage
  • thickening of calcified cartilage merging with subchondral bone
48
Q

describe biochemically what happens in osteoarthritis

A
  • In early stages of OA the articular cartilage thickens and swells due to increased amount of water
  • loss of proteoglycans makes it less compressible
  • therefore water moves in and out faster due to the less amounts of proteoglycans
  • collagen network breaks down as enzymes are released from stressed chondrocytes and synovial membrane cells
  • cartilage softens and progresses to fibrillation
49
Q

what does chondromalacia stand for

A
  • the means that the cartilage softens and progresses to fibrillation
50
Q

What enzymes are released from stressed chondrocytes

A

MMPs, collagenases and ADAMTS

51
Q

what does CSPC stand for

A

chondrocyte stem/progenitor cell

52
Q

what is the difference between early OA and late OA

A

Early OA
- characterised by loss of superficial zone and changes to the ECM of the articular cartilage and cell clusters emerge

Late stage OA
- characterised by continued loss of ECM and chondrocyte hypertrophy

53
Q

what happens once the bone is exposed

A
  • micro fractures of trabecular
  • increased osteoblastic activity and new bone formation
  • surface undergoes focal pressure necrosis - subarticular cysts
  • vascular engoregement, slows blood flow and there is bone marrow oedema
54
Q

What is subchondral sclerosis

A

Subchondral sclerosis is the hardening of the bone just below the cartilage surface. It shows up in the later stages of osteoarthritis

55
Q

what are the therapeutic targets in early OA

A

Cartilage stem/progenitor cells (CSPCs) could help regenerate joint resurfacing,

ECM production and chondroprotection

Locomotor 2 (30 decks)

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