Week 2: Normal Cartilage Structure and Joint Function

Question 1

The use of ASA and NSAIDs in RA is disease modifying (Y/N?)

Answer 1

No- they reduce the inflammation but do not alter disease course

Question 2

NSAIDS are more efficacious than ASA in RA management

Answer 2

No- their dosing is easier b/c longer t1/2, but they seem to be equally efficacious

Question 3

Are the doses required for ASA analgesia & antipyretic activity higher or lower than the dose required for anti-inflammation?

Answer 3

Lower. A higher dose is required as an anti-inflammatory

Question 4

Reasons why NSAIDs are GI irritants?

Answer 4

• directly irritate the muosa
• pH dependent partiioning to the gastric epithelium (it gets trapped in the cell because of pH tricks…acidic outside cell makes it easy to get to the cell, then neutral inside cell makes it hard to get out)
• systemic effect of blocking COX-1 decreases mucus and bicarb secretion (via decrease in PGE) and increases acid secretion (messes with the usual regulation)

Question 5

Is tylenol or aspirin more anti-inflammatory?

Answer 5

Tylenol is more antiinflammatory, ASA is more anti-coagulant, both are anti-pyretic

Question 6

Are COX-2 inhibitors better than non-selective NSAIDs for symptomatic management of RA?

Answer 6

No difference in clinical efficacy

Question 7

Composition of articular cartilage

Answer 7

Cartilage is composed of 70% water, 20% collagen II, 2-10% proteoglycans and less than 5% salts.

Question 8

What is the structure of proteoglycans?

Answer 8

Proteoglycans consist of a single hyaluronic acid molecule to which extended core proteins are attached non-covalently and the proteins have chondroitin sulphate and keratin sulphate chains covalently bound to them. The hyaluronic acid is soluble in water and acts as a viscosity-increasing agent.

Question 9

What supplements are chondroitin sulfate and keratin sulfate?

Answer 9

keratin sulfate= glucosamine sulfate

Question 10

What is the mechanims of renal toxicity with NSAID use?

Answer 10

PG are important for kidney function…. they allow the kidney to maintain GFR. Without PGs GFR can be reduced.

Question 11

What do type A and type B synovioctyes do?

Answer 11

A: monocyte derived, eat things

B: mesenchyme derived (fibroblast-like) secrete synovial fluid

Question 12

What is a difference between fibrocartilage and elastic/hyaline cartilage?

Answer 12

Fibrocartilage has no perichondrium

Question 13

What heals ok:

• ruptured ACL
• meniscus
• MCL/LCL
• articular cartilage
• tendon

Answer 13

Ruptured ACL/PCL is exposed to synovial fluid which inhibits clotting so it doesnt heal very well. No spontaneous healing

meniscus is fibrocartilage which is avascular so it doesn’t heal well

MCL and LCL are extraarticular and can heal with fibrin clot

articular cartilage doesnt heal except in the very young. It may heal as fibrocartilage instead of hyaline cartilage

tendon heals ok- it’s got a good blood supply, it just takes forever to heal and is never quite as good as the original

Question 14

Tendons are generally _______articular except ____

Endotenon contains

Answer 14

extraarticular, except long head of biceps tendon, popliteus

blood and nerves

Question 15

What is a bone bruise?

Answer 15

Injury to the subchondral bone- can be seen on MRI and correlates with poorer outcome & increased likelihood of developing OA

Question 16

Where is the tide mark in articular cartilage? What is the significance?

Answer 16

Cartilage may heal as fibrocartilage deep to this point

Question 17

What are the layers of articular cartilage?

Answer 17

Question 18

WHat is the lubricating component in synovial fluid?

Answer 18

lubricin- secreted by synoviocytes

Question 19

Compared to normal aging, what is the hydration of articular cartilage with OA? Chondrocyte # and activity?

Answer 19

more hydration, cartilage is asymmetrically worn with progressive fibrillation, more chondrocytes, more active

Question 20

OA pathophys

Answer 20

articular cartilage is damaged, responds inappropriately by secreting more MMPs (MMP1, MMP3, MMP13) than matrix, ends up building bone spurs because it is unable to repair cartilage.

IL-1 is involved- released by chondrocytes and autostimulates them

Question 21

Why don’t we say “tendonitis” anymore?

Answer 21

Because there doesn’t seem to be inflammation involved- the tendon becomes disordered and there are more vessels, but not much inflammation therefore doesn’t respond well to NSAIDs

Question 22

What are the general stages of embryological joint formation?

Answer 22

Embryological joint formation stages

1. Homogenous interzone
   a. Undifferentiated mesenchymal cells
2. 3 layer interzone
   a. The 3 layers develop into articular surfaces, menisci, cruciate ligaments, collateral ligaments
3. Early liquefaction of middle layer
4. Full separation and joint cavitation

Question 23

What is the pathogenesis of tendinopathy?

Answer 23

• tendinosis cycle (inadequate repair → tenocyte death→ further reduction in collagen + matrix → predisposition to further injury), tissue damage can be advanced by the time pain arrives

Question 24

What kind of imaging do you do for tendinopathy? What is the treatment usually?

Answer 24

US is first line, treatment is NOT NSAIDs and physio (relative rest–> strengthening)

Question 25

What is the enthesis?

Answer 25

The connective tissue between the tendon and bone

Question 26

What are the four general ways to get OA?

Answer 26

Ways to get OA:
• Abnormal force on normal cartilage (e.g.meniscectomy, ACL laxity)
• Normal force on abnormal cartilage (e.g. crystals, secondary in RA)
• Normal force on normal cartilage with stiff subchondral bone (Pagets)
• Normal force on normal cartilage with weakened subchondral bone (osteomalacia)

Question 27

What are the four classic OA radiographic findings? What would the knee look like in OA vs. RA

Answer 27

OA radiographic findings:
• Subchondral sclerosis
• Decreased joint space
• Osteophyte
• Subchondral cysts

In knee, more likely to be medial narrowing of joint space in OA. In RA the whole space will be narrowed (concentric narrowing). RA has peri0articular osteopenia where OA has subchondral sclerosis

Question 28

What is the general Tx for OA?

Answer 28

• Education, physio
• 1) Tylenol 2) NSAIDs
• Nutraceuticals (glucosamine doesn’t harm, no clear evidence it helps) (it is part of keratin sulfate)
• Cortisone injection
• Viscosupplementation

Surgery (debridement, lavage ==> arthroplasty)

Question 29

How to mitigate the GI effects of NSAIDs

Answer 29

• GI- mucous inhibition ***take with food***use misoprostol***use PPI***use COX-2 (celecoxib)

Question 30

Where does the hepatotoxicity of tylenol come from?

Answer 30

When overdose, NAPQI builds up. toxic intermediate.

Question 31

What is each radiographic modality good for:

• MRI
• CT
• Bone scintgraphy
• US
• DEXA

Answer 31

• MRI study of choice for soft tissue
• CT or plain study of choice for bone
• Bone scintigraphy for occult fractures, osteomyelities, metastases, avascular necrosis
o Can do 3 phases 1) blood flow 2) blood pool 3)delayed phase (2-24 hrs)
• US good for tendon tears
• Bone densitometry (DEXA) for osteoporosis (gives T-score (comparison with peak BMD) and Z-score (comparision with age+ gender mean)

Question 32

Which site is most involved in ankylosing spondylitis

Answer 32

the enthesis calcifies (?)