Rheum #1: Osteoarthritis

Front 1

What is the most common type of arthritis?

Thinking about the natural history, what areas of the body does it tend to affect? How does this differ from the other kind of arthritis?

Back 1

Most common= Osteoarthritis (OA)

Affects: DIP, PIP, cervical and lumbar spine, hip, knee. MCP is spared (as is wrist, elbow, ankle).

In RA (rheumatoid), MCP is affected!

Front 2

What is the biggest risk factor for OA?

Who is at higher risk of developing OA (women or men)?

Back 2

Aging= greatest risk factor (after 75 yrs, 80% of people have OA)

F>M (genetic predisposition for nodal OA0.

Front 3

A patient with bothersome joints asks you "Doc, how can I prevent the progression of OA"?

You say...

Back 3

Exercise and losing weight are the only things that prevent progression of OA

(obesity = big risk factor, puts stress on weight bearing joints. Muscle weakness & decreased used risk factor).

Front 4

What 2 main changes do you see in a knee with OA compared to a normal knee?

Back 4

1) Loss of articular cartilage (*Hallmark*)
2) Eburnation, i.e. Reactive sclerosis (formation of new bone in areas of OA)

Front 5

What is Eburnation? What is an osteophyte?

Back 5

Eburnation= bony sclerosis (hardening) at areas of cartilage loss.

Osteophyte= bone spurs (bony projections that form along joint margin).

Front 6

What type of arthritis does this person have? How can you tell? What are the names of the swellings?

Back 6

Osteoarthritis- you can tell because DIP and PIP affected, but MCP is spared.

PIP nodules = Bouchard's
DIP nodules = Heberden's

Front 7

What does this knee x-ray show?

Back 7

Osteoarthritis- note the reactive sclerosis (increased bone formation) and lateral joint space narrowing (loss of articular cartilage).

*similarly seen on xray of the hip (subchondral sclerosis and osteophytes or bony spurs).

Front 8

Why does it not cause pain when cartilage rubs against itself? Where do the chondrocytes get nutrients from?

Back 8

Cartilage= avascular and not innervated

Nutrients and waste removal through synovial fluid.

Front 9

What is the composition of the extracellular matrix? What is the main type of collagen in the articular cartilage?

Back 9

Fluid (mainly water)
Proteins (only 20-40%)
- collagen type II
- proteoglycans
- non collagenous proteins (fibronectin, anchorin, etc.)

Front 10

What is the function of articular cartilage? (4 main things)

Back 10

1. Cushions joint surfaces (against shock)
2. Lubrication/ friction-free movement of joints
3. Stabilizes joint
3. Compresses joint (help exchange nutrients)

Front 11

What is the structure of an aggrecan? What happens to aggrecan's in OA?

Back 11

Made up of hyaluronate which has multiple core proteins linked to it. Each core protein contains keratin sulfate or chondroitan sulfate.

Aggrecans can cross link to other PGs and collagen--> resilience and cushioning. Negative charges of Aggrecan's cause repulsion & give cartilage stiffness.

Aggrecan's and PGs are decreased in OA --> brittle cartilage.

Front 12

What is the composition of synovial fluid? Why is it that giving systemic medication (ex: antibiotics) in the setting of infection of the joint can easily reach the joint?

Which of the above tubes corresponds to OA synovial tap?

Back 12

Synovial fluid- ultrafiltrate of plasma, water, and proteins (lubricin). Does not have basement membrane (drugs can easily reach).

OA- clear, transparent fluid. RA- turbid, inflammatory effusion (due to increased cells)

Front 13

Osteoarthritis is a dynamic process that reflects a balance between ______ and _____.

What does this image show? What is the pink color staining for?

Back 13

Balance between Destruction and Repair
Destruction = softening of cartilage, exposure of fragmented bone
Repair= new growth of cartilage, bone formation

Image shows normal articular cartilage with chondrocytes in a sea of matrix. Pink= proteoglycans.

Front 14

What does this histopath image show?

Back 14

Cartilage has been destroyed (note cracks in surface).

Chondrocytes undergo "clonal proliferation" to make collagen and PGs, thus balancing destructive forces.

Front 15

What main biochemical changes occur in OA?

What about the metabolic changes (ex: matrix degrading enzymes)?

Back 15

Biochemical: Decrease in PGs and increase in H2O --> ↑ stiffness, ↑ permeability, ↓ lubrication

Metabolic: Increased MMPs (ex: collagenase), ↓ TIMPs (MMP inhibitors), ↑ aggrecanase (breaks down PGs)

Front 16

What are MMPs? TIMPs? and Aggrecanase 1?

What happens to the levels of these enzymes in patients with OA?

Back 16

MMP= matrix metalloprotinase, ex: collagenase, which degrade matrix (downregulated)

TIMPs= tissue inhibitors of MMPs (downregulated)

Aggrecanase 1= enzyme that breaks down proteoglycans. (upregulated in OA)

Front 17

What do you see in this slide? Do you suspect that this is an early or end stage OA? Is it painful?

Back 17

Loss of articular cartilage, from end stage OA. Note the sclerotic bone below and barely any pink-staining PGs.

Bone rubbing against bone = painful (has nerves). Gross image of OA (note worn off cartilage)

Front 18

T or F

OA has an inflammatory process?

How is cartilage repaired?

Back 18

True! Not as great as RA (rheumatoid arthritis), however.

Mechanisms:
1) IL-1 and TNFa promote cartilage degradation (↑MMP synthesis, chondrocyte apoptosis)

Repair-
2) IL-1 ra and TIMP (antagonize IL-1 and MMP), counteract the degradation.
3. Growth factors repair cartilage (IGF-1 and TGF-B).

Front 19

What is the role of NO in the pathogenesis of OA? What is the role of IGF-1 and TGF B?

Back 19

NO inhibits aggrecan synthesis and enhances PG (proteoglycan) activity

IGF-1 and TGF-B = growth factors (promote cartilage repair)

Front 20

OA is different from aging. Compare the following:

Proteoglycan concentration
Chondrocyte proliferation
Metabolic activity
Subchonral bone thickness
Cartilage hydration

Back 20

PG conc. ↓ in OA, no change in Aging
Chondrocyte proliferation ↑ in OA, no change in Aging
Metabolic activity ↑ in OA, no change in Aging
bone thickness ↑ in OA (from ebnuration), no change in Aging

↑ cartilage hydration in OA (↑ in H2O), ↓ in Aging

Front 21

What are some symptoms that a person with OA might complain of? What are some signs you would identify on physical exam?

Back 21

Sxs- pain with use, temporary morning stiffness, limited ROM. No inflammation

Signs- crepitus, bony hypertrophy and tenderness, malalignment

Front 22

What might you find on laboratory data from a patient with OA (ex: ESR, RF, synovial fluid)? What about radiographic imaging?

Back 22

ESR and RF are both normal. Non inflammatory (clear, yellow, viscous) synovial fluid.

Radiography shows osteophytes (bone spurs) and joint space narrowing. Subchondral cysts and bone spurs may be seen. Sclerosis and malalignment.

Front 23

What would you grade the picture on the top left as? What about the picture on the bottom right?

Back 23

Grading system for OA (1-4): Grade I= mild change, Grade 4= large osteophyte, severe joint space narrowing, sclerosis and bony deformities

*also note the grading scale for the hip

Front 24

A purulent synovial effusion with low glucose and high white count >75% PMNs suggests what type of condition?

What about a cloudy, yellow watery fluid that has elevated white count with >50% PMNs?

Back 24

Purulent and low glucose-- septic joint, needs treatment asap

Cloudy and watery- inflammatory fluid

(normal= clear, colorless, <200 WBCs)

Front 25

If someone presents with arthritis in area not associated with OA you have to presume that it is from a secondary or systemic cause.

What factors might lead to secondary OA?

What about systemic OA?

Back 25

Secondary OA: joint injury, osteonecrosis, gout, septic arthritis, RA in an area

Systemic: Hemochromatosis (↑ Fe deposition), Hyperpara (↑ Ca2+), Wilson's disease (↑ Cu2+), Gout, Acromegaly (overgrowth of structurally unsound cartilage), Amyloidosis, Ehler Danlos

Front 26

What is the common intermediate from which prostaglandins arise?

What is the difference between COX-1 and COX-2 in terms of their physiologic effects?

Back 26

Phospholipid --> Arachadonic Acid

COX-1: has physiologic effects in terms of platelet aggregation, protection of gastric mucosa

COX-2: induced by IL-1 and TNFa, causes inflammation

Front 27

How do selective COX-2 inhibitors work?

What are the adverse side effects associated with use of a typical (non-selective) NSAID?

Back 27

They are not able to bind active site of COX-1 but able to bind active site (side pocket) of COX-2, thus selectively inhibiting that enzyme.

Non-selective: decreased platelet aggregation, increased bleeding time

Front 28

Patients with OA can receive intra-articular injections of _____.

Back 28

Hyaluronan (and steroids)

Can stimulate endogenous hyaluronan production, and inhibits release of Arachadonic acid.