Joint Diseases - Cochran, Pfister, Cronin Flashcards Preview

FPP_MSS > Joint Diseases - Cochran, Pfister, Cronin > Flashcards

Flashcards in Joint Diseases - Cochran, Pfister, Cronin Deck (52)
1

Review the structure of synovial joints:

What type of cartilage is present? Is it vascular? How is it maintained?

What is the source of synovial fluid? Describe its composition.

(Synovial joints are encapsulated and fluid-filled to allow gliding movement)

Type 2 (car-two-lige), avascular. Maintained by chondrocytes.

Synovial cells lining the cavity produce the synovial fluid (in addition to serving phagocytic functions).

2

What physical exam findings are seen in inflammatory arthrites?

Morning stiffness > 1hr

Warmth, erythema (variable)

Synovitis (thickening, tenderness)

3

What lab findings are seen in inflammatory arthrites?

Elevated inflammatory markers (ESR/CRP), leukocytosis in blood. 

Imaging reveals erosion of bone.

Synovial fluid has WBC count >2000 and >50% neutrophils.

4

What is gout?

What is its most common etiology?

Gout results from hyperuricemia causing MSU (monosodium urate) crystals to deposit in joints.

90% of cases are due to underexcretion in feces/urine.

5

What is the source of most of the filtered load of uric acid?

What percentage of that load is usually excreted?

Cellular byproducts (nucleotides, nucleoproteins).

10% of filtered load is excreted.

6

Which groups are most susceptible to gout?

Why is it becoming more common?

Males have a higher prevalence (estrogen promotes renal excretion), and incidence is higher in non-white races.

It correlates with BMI, which is increasing.

7

What is podagra?

When is it usually seen?

Podagra is pain of the great toe resulting from MSU deposition there.

During acute gout attacks (mobilization of urate).

8

Distinguish between the optical properties of crystals in gout and pseudogout.

Gout: MSU crystals are flat and negatively birefringent.

Pseudogout: Calcium pyrophosphate crystals are rhomboid and positively birefringent.

9

Why are the distral extremities most susceptible to MSU crystal deposition?

Decreased temperatures in the extremity reduces relative solubility, leading to deposition.

10

Chronic gout is associated with renal failure and tophi. What are tophi?

Where can they form?

Tophi are white, chalky urate aggregates.

They can deposit in nearly any tissue, but especially deposit in skin, joints, cartilage and bone.

11

How does gout precipitate an inflammatory response?

MSU crystals are phagocytsed by APCs, which trigger inflammasomal IL-1β production.

12

Describe the prevalence and etiology of CPPD deposition disease (pseudogout).

Pseudogout mostly affects the elderly, and results usually from pyrophosphate overproduction.

13

What joints does CPPD deposition usually affect?

What is its pathognomonic radiological finding?

Larger joints than gout: knee, wrist, shoulder.

Chondrocalcinosis (calcificaiton of articular cartilage.

14

How can gout be treated?

Describe the role of NSAIDs and steroids in the treatment of gout.

Reducing urate production, increasing its excretion, and reducing inflammation/symptoms.

NSAIDs can be used for short term relief (indomethacin or naproxen, but not aspirin!). Same is true of steroids.

15

Colchicine

Describe its mechanism of action.

What are its uses?

Colchicine

Interferes with tubulin dimers to prevent microtubule formation. This inhibits neutrophil expansion/activation, reducing inflammation.

Used for treatment of acute gout attacks, as well as prophylactically in chronic gout (side effects are limiting)

16

Colchicine

Describe its pharmacokinetics.

What are its side effects and contraindications?

Colchicine

Orally administered, rapidly absorbed with large Vd. CYP3A4 metabolized. P-gp substrate.

Major GI disturbances (limits proliferative cells). Not for the elderly, those with hepatic or renal disease, or with 3A4/P-gp inhibitors.

17

What are some indications for prophylactic gout therapy?

Name some non-pharmacological treatment measures.

If attacks are frequent, disabling, or are associated with urate stones, nephropathy, or tophi (chronic).

Dietary adjustment (no alcohol, rich foods). Discontinue meds that block urate secretion (OAT).

18

Allopurinol

Describe its mechanism of action.

What are its indications?

Allopurinol

Metabolized to oxypurinol > blocks xanthine oxidase > reduces urate production.

For prevention of primary hyperuricemia.

19

Allopurinol

Describe its pharmacokinetics.

What are its side effects and contraindications?

Allopurinol

Prodrug activated by aldehyde oxidoreductase. 1-2hr half-life, but metabolite lasts 18-30hrs.

Can cause hypersensitivity reaction and may provoke acute gout attacks.

20

Febuxostat

Describe its mechanism of action.

Contrast it with Allopurinol.

Febuxostat

Inhibitor of XDH/XO.

Binds both oxidized and reduced form of XO. More potent, better for patients with renal failure, but with higher side effects (eg cardiovascular).

21

Pegloticase

Describe its mechanism of action.

What are its indications?

Pegloticase

Recombinant & PEGylated uricase; converts urate to allantoin.

For treatment of chronic refractory gout.

22

Pegloticase

Describe its pharmacokinetics.

What are its adverse effects?

Pegloticase

IV administration (big molecule!), biweekly. Long lasting.

Infusion site reactions and immune response to PEG portion. May provoke gout flares.

23

Probenecid

Describe its mechanism of action.

What are its indications?

Probenecid

Uricosuric: Competes with OAT/URAT1 to increase urate excretion.

For treatment of chronic gout, except in overproducers & those with kidney disease.

24

Describe the etiology of rheumatoid arthritis.

What are some of its risk factors?

Type IV hypersensitivity (T-cell, with some B involvement) directed against synovial joints.

Smoking, HLA-DR4, being female. (infections, stress?)

25

Describe the pathology of rheumatoid arthritis.

(talk about open-ended...)

Chronic inflammation of the synovium along with papillary synovial cell hyperplasia causes formation of a pannus, cartilage destruction, and joint ankylosis.

26

What are rheumatoid nodules?

A clinical finding in rheumatoid arthritis resulting from fibrinoid vascular necrosis. They are firm, round, and develop usually on skin subjected to pressure.

NOTE: Histology reveals palisaded inflammation.

27

How does the patient history in rheumatoid arthritis differ from that of osteoarthritis?

Rheumatoid arthritis is symmetrical, involves morning stiffness lasting >1hr, and lasts for weeks.

28

What is rheumatoid factor (RF)?

What are some other blood factors seen in rheumatoid arthritis?

RF is an IgM directed against the Fc portion of IgG.

CCP is seen in some cases of RF- rheumatoid arthritis.

29

Summarize some diagnostic criteria for RA diagnosis.

Morning stiff >1hr

Symmetrical arthritis

At least 3 swollen joints

Wrist, MCP, PIP involvement

Rheumatoid nodules

RH+

Confirming X-ray

30

Summarize the effects of RA on the cardiovascular system.

Summarize the effects of RA on the pulmonary system.

Patients with RA are at an increased risk of cardiovascular events, presumably due to inflammation-mediated atherosclerosis.

RA is associated with interstitial fibrosis, nodules, Caplan's syndrome (pneumoconiosis), and pleuritis with "low-glucose exudate".

31

What are the goals of treatment of RA? 

What role do NSAIDs play?

Relieve inflammation, slow/stop joint damage, reduce pain and improve function.

NSAIDs are a good first-line treatment to reduce inflammation and pain, but the large doses and long course results in side effects.

32

Etanercept

What is its mechanism of action?

What are its indications?

Etanercept

It is a soluble TNFa receptor, bound to IgG Fc. It therefore inihibits TNFa to reduce inflammation.

Used in many stages of RA: Moderate, severe, juvenile, early...? In addition to many other inflammatory conditions.

33

Etanercept

Describe its pharmacokinetics.

What are its adverse effects?

Etanercept

IV/SubQ (big molecule...). 1-2wk onset from subQ, >3d half-life.

Injection reactions, infection susceptibility, and occasionally lymphomas. (same as adalimumab)

34

Adalimumab

Describe its mechanism of action.

What are its therapeutic indications?

Adalimumab

Monoclonal IgG against TNFa.

For active RA (and other inflammatory conditions)

35

Adalimumab

Describe its pharmacokinetics.

What are its adverse effects?

Adalimumab

SubQ, given every other week.

Injection reactions, infection susceptibility, and occasionally lymphomas. (same as etanercept)

36

Tocilizumab

Describe its mechanism of action.

What are its therapeutic indications?

Tocilizumab

Monoclonal antibody; binds to IL-6 receptors (membrane-bound or soluble!)

For adult patients with severe RA. (wiki says: juvenile too)

37

Tocilizumab

Describe its pharmacokinetics.

What are its adverse effects?

Tocilizumab

IV admin (4 weeks) or SubQ (2 weeks). This makes no sense.

Injection site reactions, infection susceptibility, and increases in lipid profiles.

38

Tofacitinib

Describe its mechanism of action.

What are its indications?

Tofacitinib

It is a JAK inhibitor; blocks expansion of immune cells.

For methotrexate-intolerant RA patients, and other inflammatory conditions.

39

Tofacitinib

Describe its pharmacokinetics.

What are its adverse effects?

Tofacitinib

Oral administration. Metabolized by 3A4 > 2C19.

Infection susceptibility, cholesterol increase.

40

Define osteoarthritis.

A progressive joint disorder caused by (mostly) non-inflammatory cartilage loss. "Wear and tear". Characterized by bony spurs and subchondral cysts.

41

Summarize the typical osteoarthritis patient history.

Morning stiffness <30min. Stiffness after inactivity, pain with use. Crepitus and joint locking. No fever/warmth/erythema.

42

Describe the course of injury to the joints in early and late stage osteoarthritis.

Early stages: The superficial layers are destroyed leading to fibrillation and cracking of the matrix. This is somewhat offset by chondrocyte action.

Late stages: Fuller cartilage loss, eburnation of underlying bone, subchondral sclerosing and cyst formation. Osteophytes.

43

Where do osteophytes generally develop?

What is the name given to osteoarthritis of the IP joints?

At the margins of articular surfaces of worn joints.

DIP: Heberden nodes. PIP: Bouchard nodes.

44

What are some secondary causes of osteoarthritis?

Trauma, deposition diseases, and a boatload of other developmental and metabolic diseases.

45

Why is osteoarthritis accompanied by mild-to-moderate swelling around a joint?

Distinguish between hallux valgus, genu varus, and genu valgus.

Osteophyte formation can cause mild inflammation.

Hallux valgus is a bunion (lateral deviation of great toe). Genu varus is bowlegging, genu valgus is knocking knees.

46

Describe synovial fluid findings in osteoarthritis.

Describe radiographic findings in osteoarthritis.

Translucent and non inflammatory. Viscous?

Joint space narrows, osteophytes form. Subchondral bone changes eg cysts, sclerosis.

47

What is the mechanism of action of Anakinra?

BRM: blocks IL-1R

48

What is the mechanism of action of abatacept?

BRM: inhibits T-cell activation

49

What is the mechanism of rituximab?

BRM: antibody directed against CD20 antigen (anti B-cell)

50

What is azathioprine?

A nucleotide analog that disrupts DNA synthesis; an immunosuppressant used in rheumatoid arthritis.

51

What is Leflunomide?

A DMARD which inhibits Dihydroorotate dehydrogenase >> immunosuppression.

52

Hydroxychloroquine, mother fucker! What is it!

An antimalarial which can apparently also be used for lupus and RA.