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MBBS II MSS > L15 - Inflammatory and Degenerative Joint Disorders > Flashcards

L15 - Inflammatory and Degenerative Joint Disorders Flashcards

1
Q

What is the structure of synovium?

A

vascular tissue with an inner layer of 2 types of synovial cells:

1) Type A: macrophage-like cells
2) Type B: make proteins (especially hyaluronic acid of synovial fluid)

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2
Q

What is the composition of synovial fluid?

A

Synovial fluid = ultrafiltrate of blood plasma:

  • Contains hyaluronic acid, proteinase, collagenases, prostaglandins
  • No red blood cells / clotting factors / haemoglobin
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3
Q

What are the 2 functions of cartilage?

A
  1. Distribute load over bone surfaces

2. Provide a low-friction surface over which bone can move

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4
Q

How do nutrients enter cartilage?

A

Avascular, no basement membrane
» water can pass freely in and out and enter in 2 ways:

1) Subchondral
2) Diffusion from synovial fluid

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5
Q

Describe the movement of nutrients from synovial fluid?

A

2 phases:

1) Weight loading pushes water and nutrients OUT
2) Remove weight load means water and nutrients move back into matrix of cartilage

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6
Q

Describe the composition of cartilage?

A

chondrocytes and matrix

Cartilage is composed of cells called chondrocytes ( 1% - 2% of tissue volume) within a matrix (98% - 99% of volume).

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7
Q

What is the role of chondrocytes?

A

Produce extracellular matrix constituents:

1) Type II collagen = scaffold
2) Proteoglycan (up to 200 large aggrecan) = trap water
3) Hyaluronic acid = backbone for aggregan to bind to, give compressive stiffness, inhibit calcification, absorb and rebound

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8
Q

What dictates the composition of the matrix in cartilage?

A

Continually turning over by balance between:

1) Matrix metalloproteinases (MMP): physiological resorption of macromolecules, collagen; Break down (degrade) proteoglycans synthesized by cells
2) Inhibitors of tissue metalloproteinases (TIMP) 

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9
Q

List the 6 organized zones of cartilage.

A

1) Lamina splendens
2) Tangential zone
3) Transitional and radial zone
4) Tidemark
5) Calcified cartilage
6) Subchondral bone

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10
Q

What are the properties of Lamina splendens?

A

outermost layer:

1) Collagen parallel to surface
2) Resists tension
3) Glucose can diffuse in
4) Hyaluronic acid cannot escap

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11
Q

Compare Tangential zone vs Transitional and radial zone of articular cartilage?

A

Tangential = Flat, elongated chondrocytes

Transitional and radial zone = Typical, stacked chondrocytes + Collagen radiates inward to act as anchor

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12
Q

What is the function of Tidemark zone in cartilage?

A

Boundary between transitional and calcified zones

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13
Q

Describe how calcified cartilage and subchondral bone are attached?

A

Junction between calcified cartilage zone and subchondral bone is irregular to hold cartilage in place.

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14
Q

What is the morphology of chondrocytes in calcified cartilage zone?

A

Contains chondrocytes in a dark staining matrix due to increased mineral content

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15
Q

What is the pathological basis of OA?

A

Degeneration with imbalance between cartilage synthesis and degeneration:

Too much breakdown and/ or too little synthesis, with an inflammatory component

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16
Q

Compare primary and secondary OA.

A

Primary = without primary initiating cause, usually olg age, poor posture, trauma, occupation

Secondary = predisposing condition, such as previous trauma, developmental deformity, or underlying systemic disease such as ochronosis, hemochromatosis, or marked obesity

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17
Q

What are the histological features of OA?

A

Fibrillation (appear granular)

clefting,

cellular proliferation,

eburnation (loss of cartilage) and a nonspecific synovitis

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18
Q

What are the radiological features of OA?

A

Loss of joint surface, irregular erosion of cartilage

Osteophyte formation

Subchondral sclerosis

Loose bodies (broken bits of cartliage)

Subchondral cyst formation

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19
Q

What are the 4 mechanisms that lead to OA?

A

1) Abnormal loading leading to disruption of normal cycle of nutrient supply
2) Disturbed regulation of matrix formation by stromeolysin
3) Repair process fails to reproduce the normal balance of mature tissue compounds
4) Remodelling of join to adapt to abnormal weight distribution

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20
Q

Explain how fibrillation of cartilage occurs in OA?

A

Abnormal nutrient supply cycle:

  • Underloading causes poor diffusion from synovial fluid&raquo_space; poor chondrocyte nutrition and poor matrix formation
  • Overloading obliterates joint space, fluid movement stagnates&raquo_space; chondrocyte death and poor matrix formation

> > Splitting of cartilage matrix and loss of collagen II framework = Fibrillation

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21
Q

Explain how matrix formation is poorly regulated in OA?

A

Stromeolysin (matrix metalloproteinase) disturbs regulation of matrix formation

Cleave collagen II&raquo_space; lose framework and cause fibrillation, erosion, cracking

Cleave Aggrecan&raquo_space; Matrix swelling, loss compressive and tensile stiffness&raquo_space; abnormal loading

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22
Q

Explain how remodelling of joint aggravates OA?

A

Repair process fails to reproduce normal balance of mature tissue compounds:

Chondrocytes respond to damage only by proliferating to increase enzymes, growth factors

> > matrix degradation + abnormal distribution, composition of matrix

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23
Q

What leads to subchondral sclerosis?

A

Abnormal joint remodelling&raquo_space; increased matrix degradation&raquo_space; fibrous tissue formation beneath cartilage

interferes with chondrocyte nutrition

24
Q

What forms in the fingers in OA?

A

Osteophyte formation to stabilize the joint

1) Distal interphalangeal joint = Heberden’s nodes
2) Proximal interphalangeal joint = Bouchard’s nodes

25
Q

Explain the formation of subchondral cyst?

A

Loss of cartilage (bare bone)

> > high pressure from joint pushes synovial fluid into subchondral area

> > form cyst in bone where pressure is lower

26
Q

Describe the effect of OA on the spine?

A

Sclerosis of endplate of vertebral body with osteophyte formation may compress the nerve

27
Q

Define Rheumatoid arthritis?

A

Rheumatoid arthritis (RA) is a systemic, chronic inflammatory autoimmune disease affecting many tissues but principally attacking the joints.

causes nonsuppurative proliferative synovitis that frequently progresses to destroy articular cartilage and underlying bone&raquo_space; resulting disabling arthritis.

28
Q

Prevalence of RA?

A

RA is a relatively common condition, with a prevalence of approximately 1%

three to five times more common in women than in men.

peak incidence is in the second to fourth decades of life, but no age is immune.

29
Q

Describe the effects of RA on joints?

A

A progressive symmetrical synovitis with pain and stiffness which may lead to deformity and destruction of the joints

30
Q

What is the revised criteria of RA?

A

definite RA requires:

1) Confirmed presence of synovitis in at least 1 joint
2) No alternative diagnosis for the observed arthritis

3) Total score of at least 6 from the individual scores in 4 domains:
1. Number, site of involved joints (range 0-5)
2. Serological abnormalities (range 0-3)
3. Elevated acute-phase response (range 0-1)
4. Symptom duration (2 levels: range 0-1)

31
Q

What is the root of pathogenesis of RA? List some environmental risk factors.

A

genetic risk factors + environment + abnormal immune system = autoimmune cytokine-mediated inflammation

Environmental factors: smoking, bacteria, dust or silica exposure

32
Q

Explain the interaction between genetic and environmental factors in RA? (2 prong attack)

A

1) - Susceptibility gene (HLA)&raquo_space; Failure of tolerance and unregulated lymphocyte activation
2) -Environmental factor&raquo_space; Enzymatic modification (citrullination) of self protein

1 + 2 = T and B cells response to self-antigens

33
Q

What type of inflammation cause RA?

A

cytokine-mediated inflammation

Dendritic cells and APCs, CD4+ T cells, Macrophages

34
Q

Explain how immune system contributes to RA? **

A

CD4+ cells activate cytokine- mediated immunity:

1) Activate Dendritic cells and APCs to present citrullinated proteins to lymphocytes&raquo_space; AutoAb vs citrullinated collagen, vimentin
2) Increase Macrophage infiltration, produce TNFα and IL1 to stimulate fibroblasts to produce more enzymes to destroy cartilage&raquo_space; attract more monocytes through chemotaxis

> > Osteoclast(macrophage)-dependent bone destruction, acute destructive inflammatory synovitis

35
Q

Explain how minor joint damage can exacerbate RA?

A

minor trauma increases the expression of citrullinated proteins in normal healthy joints

Osteoclasts express enzymes that increase citrullination of collagen II

More ‘tagged’ for attack by autoantibodies

36
Q

What is Rheumatoid factor?

A

Rheumatoid Factor = serum IgM or IgA autoantibodies that bind to against Fc portion of IgG

37
Q

What are the predictable X-ray appearances of RA?

A

1) Inflammation of subchondral bone = osteopenia of juxtaarticular bone
2) Inflammation of synovium = hyperaemia
3) Pannus = bone erosions
4) Joint space narrowing
5) Soft tissue swelling

38
Q

What cytokine can be targeted in RA treatment?

A

pronounced macrophage infiltration with release of TNFα

> > thus TNFα antagonists have proved beneficial

39
Q

What are the clinical manifestation of RA and explain each one?

A
  1. Triggering immune system = Fatigue, malaise, weight loss
  2. Activ. of immune cells and inflam. cytokines = Joint pain, swelling, stiffness, Limited range of motion
  3. Activation of synovial and cartilage by tissue-damaging enzymes = Joint damage, erosions, joint space narrowing
40
Q

What are the 4 unique hallmarks of Ankylosing spondylitis/ Seronegative Spondyloarthropathies?

A

1) Pathologic changes that begin in the ligamentous attachments to bone rather than in the synovium
2) Involvement of the sacroiliac joints, with or without arthritis in other peripheral joints
3) Absence of rheumatoid factor (hence the designation seronegative)
4) Association with HLA-B27

41
Q

What are the histological features of Ankylosing spondylitis?

A

Endochondral ossification takes place in articular cartilage or IV disc (Bamboo spine)

42
Q

Symptoms of ankylosing spondylitis? What people are affected?

A

Young adult males present with pain and morning stiffness of back

43
Q

What is the root cause of gout?

A

excessive amounts of uric acid within tissues and body fluids from overproduction and/or under-excretion

> > Chalky white Monosodium urate crystals precipitate from supersaturated body fluids

> > acute inflammatory reaction

44
Q

What are some causes of gout?

A

Primary = Enzyme defects

Secondary = Chronic renal disease, Inborn errors of metabolism, Increased nucleic acid turnover (e.g. leukemia)

45
Q

What is the role of inflammasome in gout?

A

intracellular sensors that detection of foreign antigen

> > stimulation leads to production of the cytokine IL-1&raquo_space; cause local accumulation of neutrophils and macrophages in joints and synovial membranes

> > release chemofactors (i.e. Leukotriene B4) and lysosomes to destroy cells

46
Q

Histological features of acute gout?

A

acute inflammation: edema, congestion, dense neutrophilic infiltrate synovium and synovial fluid

Needle-shaped monosodium urate crystals

47
Q

Can serum uric acid levels be used to dx gout?

A

No

30% patient have normal serum uric acid, test not sensitive enough

48
Q

What happens during the intermediate stage of gout?

A

Diffuse deposits seen due to deposition of monosodium urate crystals in body

particularly kidneys and periarticular region. Deposits lead to bone erosion.

49
Q

What is a pathognomonic for gout?

A

Tophi

= large aggregations of urate crystals surrounded by lots of lymphocytes, macrophages, and foreign-body giant cells

50
Q

What are the 2 presentations of CPPD?

A

CALCIUM PYROPHOSPHATE DIHYDRATE (CPPD)

  1. Acute synovitis that mimics gout (pseudogout)
  2. Chronic pyrophosphate arthropathy which mimics OA
51
Q

Explain the formation of CPPD cyrstals in pseudogout?

A

replicating / damaged cells (e.g. osteoarthritis) release ATP = converted to pyrophosphate and AMP

  • pyrophosphate is normally converted by alkaline phosphatase to inorganic phosphate.
  • Under influence of growth promoting factors complexes with calcium to form rhomboidal CPPD from cartilage into joint space
52
Q

Radiological changes of pseudogout? Epidemiology?

A

Calcification of cartilage and menisci

seen in:
10-15% persons aged 65-75

30-60% persons aged >85

53
Q

Why is CPPD often associated with OA?

A

OA contains replicating or damaged cells which release ATP&raquo_space; AMP + Pyrophosphate

OA&raquo_space; abnormal balance of growth factors

54
Q

Which joints do Pseudogout affect more?

A

Radiocarpal joints - Wrist

Glenohumeral joints - Shoulder

Midtarsal joints - Middle of foot

55
Q

What is pannus formation in RA?

A

Vascularized granulation tissue

56
Q

List some difference between gout and pseudogout?

A

Crystal- type and color, shape
Joint location
Tophi vs no tophi
Different root cause

MBBS II MSS (31 decks)

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