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Medicine Unit 5 > Pathogenesis of Osteoarthritis > Flashcards

Pathogenesis of Osteoarthritis Flashcards

1
Q

what is in the image

A

synovial joint

bone
fibrous joint capsule
hyaline articular cartilage
synovial membrane (synovium)
synovial fluid

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2
Q

healthy synovium

A

thin lining facing joint space, 1 to 2 cells thick
contains macrophage like cells called synoviocytes type 1/a and fibroblast like cells synoviocytes type2/b
synovial subliming is loose connective tissue with numerous blood and lymphatic vessels, nerves, scattered macrophages and fibroblasts

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3
Q

macrophage like cells

A

synoviocytes type 1 or type a

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4
Q

fibroblast like cells

A

synoviocytes type 2 or b

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5
Q

label top to bottom

A
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6
Q

label top to bottom

A
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7
Q

cell and tissue changes as a flow chart

A
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8
Q

matrix metalloproteinases

A

can degrade/ clear aggrecan

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9
Q

in early OA what occurs in the chondrocytes

A

proliferate
become more active
form clusters
produce proteinases

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10
Q

in early OA what occurs in the extracellular matrix

A

gradual loss of aggrecan
type 2 collagen degradation
cracks in cartilage
termed fibrillation

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11
Q

what is in the image

A

early OA

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12
Q

cartilage changes

A

decreased swelling pressure of proteoglycans
altered collagen synthesis
decreased responsiveness of chondrocytes
loss of shock absorbing properties

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13
Q

what is in the image

A

degradation of cartilage

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14
Q

what do DAMPs include

A

endogenous intracellular molecules
released by activated or necrotic cells and ECM

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15
Q

inflammation in OA

A

synovitis

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16
Q

how is synovitis detected

A

imaging
arthroscopy
histology

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17
Q

inflammation in OA

A

chronic
low grade
involves innate immune response

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18
Q

key components implicated in OA

A

DAMP-TLR signalling
complement system
CPB
macrophages
mast cells

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19
Q

cytokines in mediators of inflammation in OA

A

TNF alpha
Il-1 beta
Il-6
Il-18
Il-21

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20
Q

chemokine in inflammation mediation

A

growth factors
adipokines
prostaglandins and leukotrienes
neuropeptides

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21
Q

growth factors in inflammation mediation

A

TGF beta

22
Q

adipokines in mediating inflammation

A

leptin
adiponectin
visfatin
resistin

23
Q

neuropeptides in mediating inflammation

A

bradykinin
substance P

24
Q

what is in the image

A

grade 0 MCP synovitis

25
Q

what is in the image

A

grade 1 MCP synovitis

26
Q

what is in the image

A

grade 2 MCP synovitis

27
Q

what is in the image

A

grade 3 MCP synovitis

28
Q

constitutional risk factors

A

ageing
hereditary
gender
hormonal status
metabolic bone disease e.g. Pagets

29
Q

local risk factors

A

trauma
knee: obesity, quads weakness, joint laxity/ malalignment
hip: developmental dysplasia, occupation

30
Q

what is the most prominent risk factor for OA development

A

ageing

31
Q

ageing as a risk factor

A

reduced muscle mass
increased fat mass
alter joint loading
elevated levels of reatctive oxygen species can cause oxidative damage and disruption of cell signalling
chondrocytes have reduced levels of ECM gene expression
undergo cellular senescence with age

32
Q

hereditary risk factor

A

60% hand and hip
40% of knee

33
Q

inheritance

A

related to changes in multiple genes
polygenic
hip and knee OA have different genetic aetiologies

34
Q

hand OA

A

mutation in aggrecan gene, AGC1

35
Q

what is in the image

A

heberdens node
bouchards node

36
Q

genes associated with hip OA

A

GDF5
DIO2
SMAD3

37
Q

GDF5

A

bone morphogenetic protein
joint development

38
Q

DIO2

A

thyroid metabolism

39
Q

SMAD3

A

TGF beta signalling
maintenance of articular cartilage

40
Q

which gender has a greater risk

A

female

41
Q

gender as a risk factor

A

marked incidence of knee OA at menopause
oestrogen declining
chondrocytes have oestrogen receptors
oestrogen deficiency favours OA
HRT improves symptoms
precise mechanism unclear

42
Q

obesity as risk factor

A

overweight 2.5 times more likely to develop knee OA
altered biomechanics
subchondral bone
leads to joint degeneration
accelerates OA process

43
Q

how can exercise weight loss and low fat diet help

A

clinically beneficial
pain reduction
improved joint function

44
Q

obesity as risk factor, detail

A

adipose tissue secretes adipokines and cytokines
can promote low grade inflammation
obese adipose tissue has M1 macrophages, dendritic cells, T and B cells and neutrophils
secrete Il-6, TNF alpha and VEGF
TNF alpha and Il-6 inhibit production of proteoglycans and collagen 2
upreg MMP expresión

45
Q

leptin in obesity

A

expression increased
leads to cartilage destruction and increased il6, CXCL8 expression in synovium

46
Q

resistin in obesity

A

increased expression
increased MMP release
increased cartilage destruction
synovial inflammation

47
Q

visfatin in obesity

A

expression increased
increased MMPs and ADAMTS release from articular chondrocytes
synovial inflammation and bone erosion

48
Q

adiponetic in obesity

A

expression in obesity decreased
leads to cartilage destruction and synovial inflammation

49
Q

previous joint injury

A

injury caused y compression torsion shear
damaging the ligaments cartilage or muscles
resulting in pain joint Mal-alignment and locking

50
Q

occupation as risk factor

A

observed in occupations squatting and kneeling
hip OA with prolonged lifting and standing
hand OA in those with manual dexterity

51
Q

joint abnormality/morphology

A

one in 10 hip replacements in adults
one in 3 in people under 60

Medicine Unit 5 (14 decks)

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