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Pathology > Osteoarthritis > Flashcards

Osteoarthritis Flashcards

1
Q

What is found in a synovial joint?

A

-Bone
-Fibrous joint capsule (& ligaments) - holds in place
-Hyaline articular cartilage - cushions when joint moves
-Synovium/synovial membrane - produces small amount of synovial fluid
-Synovial fluid - for lubrication - reduces friction

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2
Q

What is synovium/synovial membrane?

A

-CT between joint capsule & joint space - lines inner joint surface (excludes cartilage)
-Produces synovial fluid

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3
Q

Features of a healthy synovium?

A

-Thin lining layer facing joint space (1-2 cells thick) - contains macrophage-like synovial cells (synoviocytes type 1/A) & fibroblast-like synovial cells (synoviocytes type 2/B)
-Synovial sub-lining = loose CT w/ lots of blood vs, lymphatic vs, nerves, macrophages, fibroblasts

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4
Q

Structure of normal chondrocytes?

A

(Produce cartilage)

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5
Q

Normal synovial joint vs osteoarthritis synovial joint?

A

OA
-Subchondral bone cyst = fluid-filled space inside joint extending from a bones in joint
-Premature degeneration = become fragmented
-Bone of osteophyte = bone spurs - extra bits of bone that grow

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6
Q

Describe the process of cell & tissue changes in OA?

A

-Structural damage to cartilage = initial trigger to OA development
-Cytokines trigger synovial inflamm & bone remodelling
-Synovial inflammation = synovitis - synovial memb is thicken & inflamed

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7
Q

Describe the function of chondrocytes?

A

*Cartilage production (@ joints - articular cartilage)
*Role of chondrocytes = maintain extracellular matrix (ECM) & produce cartilage matrix

-Chondroblasts??? or chondrocytes - secrete type II collagen & other ECM components = aggrecan proteoglycans (cartilage specific) containing GAG sidechains
-Hyaluronic acid coats chondrocytes - to promote chondrocyte proliferation
-Articular cartilage ECM overall is made of: type II collagen fibres & interlocking mesh of fibrous proteins & proteoglycans, hyaluronic acid, & chondroitin sulfate
-Aggrecan binds hyaluronic acid

-In OA - pro-inf cytokines cause chondrocytes to secrete collagenases - which are MMPs (i.e., cartilage-degrading proteases) - these degrade newly synthesised molecules - so cartilage ECM degrades –> shown by N & C propeptide release from type II collagen
-Stimulates chondrocyte to release pro-inf cytokines = cycle - so stimulates further cartilage degradation

–> degradation of ARTICULAR cartilage

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8
Q

Role of matrix metalloproteinases (MMPs) - such as collagenases?

A

-Degrade/cleave aggrecan (a major proteoglycan in cartilage) - found in cartilage ECM
-Aggrecan contains water (so cartilage contains water - as aggrecan is a component of cartilage)
-Water causes cartilage to swell & expand = important for functions of cartilage
–> leads to loss of turgor of cartilage - so wilts - can’t exert its functions - i.e., symptoms of OA?

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9
Q

What changes occur to chondrocytes in early OA?

A

-Proliferate
-Become more active
-Form clusters
-Produce proteinases (e.g., MMPs)

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10
Q

What changes occur to extracellular matrix in early OA?

A

-Gradual loss of aggrecan
-Followed by type II collagen degradation
-Cracks develop in cartilage
-Termed fibrillation = finger-like projections in cartilage

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11
Q

What does the loss of balance mean in terms of the development of OA?

A

Balance in cartilage synthesis & cartilage degeneration is tipped further towards cartilage degeneration

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12
Q

What changes occur to cartilage in OA?

A

-Decreased swelling pressure of proteoglycans
-Altered collagen synthesis
-Decreased responsiveness of chondrocytes
-Loss of shock absorbing properties

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13
Q

Where do DAMPs come into OA?

A

-Degradation of cartilage = DAMPs release/cleaved off
-Triggers more inflammation
–> so further cartilage degradation
*e.g., of DAMPs = endogenous intracellular molecules released by activated or necrotic cells & ECM

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14
Q

What happens during OA inflammation?

A

-Is known as synovitis - inflamm of synovium
-Involves innate imm resp
-Involves: DAMP-TLR signalling, complement system, CPB, macrophages & mast cells

  1. DAMPs from fragmented cartilage - bind PRRs
  2. DAMPs in synovia - taken up by macrophages
    = triggers inflammatory resp
    -Get inc. blood flow
    -Swelling
    -Pain - synovium is soft tissue so has nerves = where feel pain - but cartilage which is degraded has no nerves - so no pain here
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15
Q

What are the molecular mediators of OA inflammation?

A

-Cytokines - TNFα, IL-1β, IL-6, IL-18 & IL-21
-Chemokines & their recs
-Growth factors - TGFβ
-Adipokines (in fat/adipose tissue) - leptin, adiponectin, visfatin & resistin
-Prostaglandins (part of inflammatory cascade) & leukotrienes
-Neuropeptides (trigger pain) – bradykinin, substance P

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16
Q

Why are ultrasounds use for diagnosing OA?

A

-Good for detecting osteophytes (hallmark) & assessing joint space & cartilage integrity
-Detect blood flow where is pain - indicates level of inflamm

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17
Q

What are some constitutional risk factors of OA?

A

-Ageing
-Heredity
-Gender
-Hormonal status (menopause)
-Metabolic Bone disease e.g., Paget’s

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18
Q

What are some local risk factors of OA?

A

-Trauma

*Knee
-Obesity
-Quadriceps weakness (less stability of joint = more cartilage fractures)
-Joint laxity/malalignment

*Hip
-Developmental dysplasia (joint abnormalities)
-Occupation (kneel down a lot?)

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19
Q

How does ageing link to OA?

A

-As age collagen becomes less effective - ageing collagen = get wrinkles

-Non-enzymatic crosslinking of collagen occurs with ageing = alters cartilage - & resulting changes reduce ECM synthesis by chondrocytes
-Ageing-associated changes affecting articular tissues promote development of osteoarthritis

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20
Q

Hypotheses of ageing & OA?

A

-Reduced muscle mass &increased fat mass alter joint loading - can cause ageing-related inflammation
-Elevated levels of reactive oxygen species can cause oxidative damage & disrupt of cell signalling
-Chondrocytes have reduced levels of ECM gene expression (switch off) & can undergo cellular senescence with age

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21
Q

Statistics of ageing & OA?

A

-Most prominent OA risk factor
-Ageing-associated processes promote OA development BUT ageing & OA are separate!!!

1/3 women & almost 1/4 men between 45-64 = treated for OA –> rises to almost half of people aged 75 & over

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22
Q

Is OA genetic (hereditary)?

A

-Big risk factor - especially for in hands & hips
-Accounts for 60% hand & hip OA & 40% of knee OA

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23
Q

What can be said about the genetic link to OA?

A

Polygenic (many genes involved) - related to changes in many genes

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24
Q

Give an example of genetic mutations linked to hand OA?

A

-Mutation in aggrecan gene - AGC1

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25
Q

What can mutation in aggrecan gene - AGC1 - lead to in hand OA?

A
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26
Q

What can genes are linked to hip OA?

A

-GDF5
-DIO2
-SMAD3

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27
Q

What can GDF5, DIO2 & SMAD3 genes linked to hip OA cause?

A

-GDF5 = Bone morphogenetic protein, joint development
-DIO2 = Thyroid metabolism
-SMAD3 = TGF-β signalling, maintenance of articular cartilage

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28
Q

How does being female influence OA?

A

-Women = 60% of hip & knee replacements
-Marked incidence of knee OA at menopause
-Oestrogen levels on the decline
-Chondrocytes have oestrogen receptors
-Oestrogen deficiency favours OA
-HRT improves symptoms

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29
Q

How does obesity link to OA - statistics?

A

-Overweight = x2.5 more likely to develop OA
-BMI hip & knee replacements = 28.7-30.9

30
Q

How can obesity influence OA?

A

-Altered biomechanics
-Excessive loading affects cartilage & subchondral bone
–> leads to joint degeneration
-Accelerates OA process

31
Q

What can reduce risk of OA if are overweight & why?

A

-Exercise
-Weight loss
-Low-fat diet
–>
-clinically beneficial
-pain reduction
-improved joint function

32
Q

Give the science behind how obesity can lead to OA?

A

-Adipose tissue (fat) - secretes adipokines & cytokines
-Adipose tissue - can promote low-grade inflamm
-Obese adipose tissue contains - M1 macrophages, DCs, T & B cells, neutrophils
-Adipocytes & imm cells - secrete cytokines (IL-6, TNFα, VEGF)
-TNFα & IL-6 inhibit ECM production (proteoglycans & type II collagen) & upreg MMP expression - break down cartilage

33
Q

What are some molecules expressed higher or lower in obesity & what do they do?

A

-Leptin- expression inc = cartilage destruction &
inc. IL-6 & CXCL8 expression in synovium

-Resistin- expression inc. = increased release of MMPs & cartilage destruction = synovial inflammation

-Visfatin- expression inc. = increased MMPs & ADAMTS release from articular chondrocytes –> synovial inflamm & bone erosion

-Adiponectin - expression dec. = cartilage destruction & synovial inflamm

34
Q

What in terms of previous joint injury may increase risk to OA?

A

-Compression, torsion & shear = causes of injury
-Damage: ligaments, cartilage, muscle
–> can cause: pain, joint mal-alignment, locking

35
Q

How can occupation link to OA?

A

-Knee OA - higher in people who squat & kneel in their jobs
-Hip OA - linked to prolonged lifting & standing
-Hand OA - higher in people whose jobs need manual dexterity

36
Q

How does joint abnormality/morphology link to OA - statistics?

A

e.g., abnormal hip shape = 1/10 hip replacements in adults - & in over 60s = for 1/3 of hip replacements

37
Q

What is arthritis?

A

-Disorder affecting joints
-Symptoms generally = joint pain & stiffness

38
Q

Types of arthritis?

A

-Non-inflammatory
-Inflammatory

39
Q

Tree-like diagram to show arthritis types?

A
40
Q

Define OA?

A

= clinical syndrome of joint pain accompanied by varying degrees of functional limitation & reduced quality of life
-Most common form of arthritis
-Major cause of disability

41
Q

Clinical features of OA?

A

-Joint pain worse with use
-Pain worse in evening
-Rest pain/night pain
-Morning stiffness < 30mins
-Functional limitation/reduced quality of life

-Bony swelling
-Muscle wasting (esp. quadriceps)
-Deformity
-Palpable crepitus on movement
-Restricted painful movement

42
Q

Sites of body typically affected by OA?

A
43
Q

Names of OA joint ‘deformities’?

A
44
Q

Why is OA a ‘whole-organ’ disease of joint?

A

Affects:
-Cartilage
-Bone
-Synovium
-Joint capsule
-Ligaments
-Muscles

45
Q

Summarise what OA causes.

A

-Gradual loss of cartilage,
-Development of bony spurs (osteophytes)
-Development of subchondral bone cyst & sclerosis (thickening & whitening of bone)

46
Q

What is shown radiographically for OA? - image = normal knee x-ray here

A

-Joint space narrowing
-Osteophyte = bony spurs hang over edge due to cartilage loss
-Subchondral sclerosis - whiter & more dense/thick bone
-Subchondral cysts
-Get bone rubbing on bone when all cartilage degraded

47
Q

What may be some differential diagnoses that x-ray can exclude before concluding OA?

A

-Fracture
-Paget’s disease
-Pseudogout
-Avascular necrosis

48
Q

What may be some differential diagnoses that x-ray cannot help exclude before diagnosing OA?

A

*Ligament/meniscal problems
*Inflammatory arthritis
e.g.,
-Rheumatoid
-Gout
*Tumour
*Infection

49
Q

What must be satisfied to give a diagnosis of OA?

A

-Persistent joint pain with use
-Age 45 & over
-Any morning stiffness <30mins
(No x-ray required)

50
Q

What will blood tests show if have OA?

A

-Often normal
-Just used to exclude differential diagnoses

51
Q

Society statistics for OA?

A

*8.75 million over 45 in UK have OA
*3/4 report constant pain
*20% report depression & anxiety
*1/3 retire early, give up work, reduce hours

-2 million GP consultations per year for OA
-Over 100,000 knee replacements a year now
-36 million working days lost

52
Q

What are the 5 myths about OA - i.e., societal/previous perceptions that are not true?

A

1 = OA is an inevitable result of ageing
2 = OA is just ‘wear & tear’ of articular cartilage
3 = OA inevitably leads to decline & eventually joint replacement
4 = exercise is harmful & wears joint out more quickly
5 = joint replacement is the only effective treatment

53
Q

Why is OA not just an inevitable result of ageing?

A

-OA = common, complex disorder
-Not just 1 disease
-Multiple risk factors
-Differs between sites

-Incidence of OA does inc. w/ age but ageing & OA are separate

54
Q

Why is OA not just ‘wear & tear’ of articular cartilage?

A

OA = metabolically active, dynamic repair process - affecting all joint tissues (cartilage, bone, synovium, capsule, ligaments, muscle)

*Get tissue loss - cartilage microfracture, fragments break off, pitting & abrasion of cartilage = localised articular/hyaline cartilage loss
–> in response - get reactive changes: remodelling of bone, new bone formed (osteophyte), synovitis, reabsorption of necrotic fractured subchondral bone

-Input of trauma (or maybe not) - however - OA is not the result of this trauma - but instead the result of an abnormal/non-functional repair process - repair doesn’t occur as should do

55
Q

Compare prior & current OA views in terms of OA being due to joint ‘wear & tear’?

A

Current view = OA is not inevitable

56
Q

Why is it not true that OA leads to decline & eventually joint replacement?

A

-Outcomes = variable
-Progressive decline is not inevitable
-Radiographic improvement = rare
-Symptoms often episodic not persistent
-Varies according to site
-Hands: Improvement in pain/function is common
-Knees: “Rule of thirds”:
One-third mild symptoms/improve
One-third moderate/stay the same
One-third severe/progress

57
Q

Why is the view that exercise is harmful & wears the joint out more quickly, false?

A

-Disuse - can cause tissue atrophy
-Physiological loading or ‘use it or lose it’ - can allow for health’
-Extreme loading (overuse) - can cause tissue damage
–> is a scale - which is why light exercises are recommended e.g., aerobic exercise & quadriceps strengthening (physio)
–> should improve pain, quality of life, balance
-> adherence = issue

58
Q

Why is the view that joint replacement is the effective treatment?

A

-This = reductionist
-OA = should be considered more holistically as image shows - holistic assessment

59
Q

What other management options are there for OA - other than joint replacement?

A

-Build from inside to outside

60
Q

Give some common beliefs regarding OA.

A

-‘Nothing much can be done to help’
-‘It’s not safe for someone like me to exercise’
-‘If I exercise my joints will wear out even quicker’
-‘Rest is best’

61
Q

What should be the take home messages to challenge the myths?

A

-Not an inevitable consequence of aging
-Not just “wear and tear”
-It involves the whole joint
-Decline and joint replacement is not inevitable, -symptoms often improve
-Effective non-surgical treatment is available
-Exercise is good
–>strengthening muscles takes load off the joint and reduces intra-articular pressure

62
Q

What are some appropriate exercises for people with OA?

A

-Swimming
-Cycling
-Walking
-Aqua classes
-Tai chi

63
Q

What are some analgesic drugs for OA?

A

-These = adjunctive to core treatments
-Paracetamol first-line - regular dosing may be required, but at lowest dose possible
-Topical NSAIDs considered for knee or hand OA

64
Q

What is not recommended for OA?

A

-Do not offer Glucosamine or Chondroitin based products for managing OA

-NICE - “No evidence to support the use of GS in hip or knee OA”

65
Q

What to do if paracetamol/topical NSAIDs are ineffective or insufficient?

A

Oral NSAID, COX-2 inhibitor or opioid

66
Q

What are some other non-pharmacological treatment?

A

-Hand therapy: joint protection
-Supports and braces
-Heat and cold
-Walking aids
-Footwear

67
Q

How effective are intra-articular injections?

A

Improve pain and function for up to 6 weeks (knee) but evidence poor quality

68
Q

When is joint replacement therapy used?

A

-Mainly for hip & knee OA
-Symptoms significantly impact quality of life
-Symptoms refractory to non-surgical treatment
-Patients should have been offered at least core non-surgical treatments

69
Q

What are DMOADs (Disease-Modifier Osteoarthritis Drugs)?

A

-Altering intracellular communication - inhibit macrophage effect - & so lower degradation

70
Q

What is not recommended for OA?

A

-Do not offer arthroscopic lavage unless is clear history of mechanical locking
-Weighing benefits & harms evidence does not support use of arthroscopy for knee OA

Pathology (7 decks)

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