Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Musculoskeletal and Skin Pathology > Arthritis and Gout > Flashcards

Arthritis and Gout Flashcards

1
Q

What is podagra?

A

It’s gouty inflammation of the first metacarpal phalanx. It’s the most common place where gout begins.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Gout is predominant in which gender?

A

Men. However, women catch up after menopause, since estrogen plays a crucial role in excreting uric acid.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

In men, gout onset is most proprtional to what?

A

Uric acid level, with a sharp climb beyond 7

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

The majority of gout is due to overproduction or underexcretion?

A

Underexcretion in 90% of cases. Metabolic syndrome, renal disease, high BMI, or diuretic use can contribute.

Alcohol contributes to both overproduction and under excretion.

More than 2/3 of our uric acid is due to cycling of cellular nucleotides and nucleoproteins, meaning diet only has a limited impact in treating gout.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What test is key in determining gouty inflammation?

A

A white blood cell count greater than 2000 with 50-90% PMS.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What lab tests are key for arthritis?

A

ESR, CRP, and assess for peripheral blood leukocytosis (particularly if septic arthritis is suspected).

Joint fluid can be analyzed. X-ray’s will show erosion due to chronic inflammation at the joint.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What can precipitate a gout attack?

A

Climbing uric acid, or a sudden drop (which releases crystals of MSU from pre-formed deposits)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How does gout cause inflammation?

A

MSU crystals phagocytosed by monocytes, activated into macrophages and activates the inflammasome, activation of caspase-1, released and active IL-1beta. THis triggers endothelial activation and recruits neutrophils to the site

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What cytokines are released by inflammasome?

A

All are in the IL-1 family.

IL-1beta, IL-18, IL-33.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the 3 components of the inflammasome?

A

nalp3, asc, and pro-caspase1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

CPPD Deposition caused usually by what?

A

Overproduction of pyrophosphate, leading to calcium phyophosphate dihydrate (CPPD) crystal deposition

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Four major causes of CPPD?

A

Hemochromatosis
Hypophosphatasia (cannot break down phosphates)
Hypomagnesemia (needed as a phosphatase cofactor)
Hyperparathyroidism (excessive calcium available)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What’s pseudogout?

A

an ACUTE arthritic attack, similar to gout, but usually occurs in larger joints such as the knee, wrist, or shoulder rather than big toe.

Dx: Rhomboidal shaped, positively birefringent crystals in joint fluid

Diagnosis is usually suggestive of chondrcalcinosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Four major factors to memorize with CPPD Arthritis

A
  1. Usually it’s asymptomatic
  2. It can cause acute, pseudogout like attacks
  3. Can be associated with widespread OA, particularly OA in atypical joints
  4. It produces chronic low grade inflammation, that can result in RA-like MCP joint enlargement
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the four main contributors to RA?

A
  1. Genetics.. People with certain types of HLA-DR have a shared epitope that predisposes them
  2. Hormones (females more commonly suffer from RA)
  3. Smoking

Note: It’s a T cell disease, but recruits local cells (synovial fibroblasts), and synovitis, with proliferation of the synovium. Can resemble a benign, locally invasive tumor.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is rheumatoid factor?

A

an IgM directed to the IgG Fc portion. someone sensitive for RA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is CCP?

A

Anti-Cyclic Citrullinated Peptide

Seen in early RA, that may still be RF negative

Same SENSITIVITY as RF, but more SPECIFIC; RF can be false positive in patients with Hep C.

CCP correlates with overall disease activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How does late RA present in the hand?

A

Ulnar deviation and MCP subluxation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the swan neck deformity?

A

Hyperextension of PIP, flexion of DIP. Common in RA.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the Boutiniere deformity?

A

PIP flexion, hyperextension of DIP. Common in RA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the 7 criteria for RA, and rules for diagnosis?

A
  1. Morning stiffness for greater than an hour.
  2. Symmetrical arthritis.
  3. At least 3 swollen joints.
  4. Involvement of the wrist, MCP, PIP
  5. Rheumatoid nodules
  6. Positive RF
  7. X-ray changes typical of RA in hand/wrist.

3, 4, 5, and one other are needed for diagnosis!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Which 3 RA criteria are mandatory for diagnosis?

A
  1. At least 3 swollen joints
  2. Involvement of wrist, MCP, PIP
  3. Rheumatoid nodules
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the periodontitis hypothesis?

A

RA patients are twice as likely as OA patients to have moderate to severe periodontitis.
PD patients and RA patients have a shared HLA DR*B1 genetic risk, and are both high risk for being smokers

Anti-CCP antibodies are common in PD patients irrespective of RA. Does PD perpetuate or initiate RA???

24
Q

What organism forms the basis for Periodontitis hypothesis?

A

Porphyromonas gingivalis in PD creates peptidyl arginine deiminase (PAD)… this creates citrulline from arginine, creating neo-epitopes…. People with HLA-DR*B1 are more likely to form these anti-CCP antibodies.

25
Q

What systemic issues are associated with RA?

A

Sjogren’s, CVD, Diabetes, Neuropathies particularly in hands, rheumatoid vasculities, rheumatoid pleuritis with effusion (exudate and low glucose), interstitial fibrosis in lung with nodules… Caplan’s syndrome with rheumatoid pneumoconiosis

Chronic inflammation can result in atherosclerosis

26
Q

Who is most affected by gout?

A

Elderly men and postmenopausal women

27
Q

What role do NSAIDs have in Gout?

A

Indomethacin, naproxen, ibuprofen can be given to treat gout within the first 24 hours, but DO NOT give Aspirin…. it is a uricosuric agent and if given in high doses (rather than low) it will increase uric acid levels in the blood.

28
Q

What role do Steroids have in Gout?

A

Symptomatic relief in patients that can’t take NSAIDs… only used short term.

29
Q

Colchicine

A

Is an anti-mitotic, that arrests cells in G1 and interferes with microtubules in neutrophils, preventing their activation and migration.

Symptomatic relief; this does not affect uric acid excretion!!

Oral.

Rapid absorption, deposits in tissues and complexes with tubulin (large volume of distribution)

Processed by CYP450s, and a substrate for p-glycoproteins

Can also undergo enterohepatic recirculation

Causes GI side effects bc it affects rapid proliferating GI cells… narrow therapeutic window.

If you take a p-glycoprotein inhibitor (cyclosporin) or if a CYP3A4 inhibitor (grapefruit), it can increase dose. CONTRAINDICATED.

Do not give in elderly or patients with hepatic or renal disease

Treats acute gout attacks, but can also be used prophylactically

Do not give with p-glycoprotein or cyp3a4 inhibitors as the toxicity can be life threatening

30
Q

Allopurinol

A

Blocks xanthine oxidase, needed to generate uric acid

Plasma uric acid concentration decreases, and crystals can dissolve

An analog for hypoxanthine. Converted to oxypurinal (Still biologically active) by aldehyde oxidoreductase

Allopurinal is active, half life 1-2 hours
Oxypurinal is still active, half like 18-30 hours

Can cause hypersensitivity (higher risk if given with ACE inhibitor, TZ diuretics, amoxicillin), acute gout attack by mobilizing stores of uric acid, or also ppt a gout attack if combined NSAID or colchine

Some patients get a skin rash.

Used prophylaxis, but don’t give in an acute gout attack

Oral to prevent hyperurecemia in chronic gout… also treats tophaceous deposits, renal urate stones, gouty nephropathy… Also give as prophylaxis in patients who have hyperurecemia secondary to anti-neoplastic therapy or hematological disorders

Will prevent metabolism of other drugs normally metabolized by XO (azathioprine, mercaptopurine)

31
Q

Pegloticase

A

PEGylated (polyethylene glycol) recominate form of uricase… uricase urate-oxidase enzyme

Uricase is absent in humans, but this enzyme can convert uric acid to allantoin (soluble and easily excretable)

IV every two weeks with long half life

Can have infusion rxns, an immune response, but is used to prophylactically treat acute gout flare in chronic refractory gout

32
Q

Probenecid

A

Uricosuric agent (agent that increases rate of uric acid excretion)

Orally given, dose-dependent half life

Also binds plasma proteins

Does not work in patients with renal insufficiency, and contraindicated in patients with uric acid kidney stones, some GI side effects

Used in chronic gout, but not if there is kidney disease or if someone is overproducing uric acid since this can result in urate kidney stones

Aspirin decreases its effectiveness, oxypurinol will be cleared more easily if on probenecid (increasing dose needed of allopurinal)… loop diuretics will be less effective, but have higher serum concentrations and be more toxic

33
Q

Uriosuric Agent mechanism

A

Increases uric acid extreion by competing with renal tubular acid transporter so that less urate is reabsorbed…. OAT = organic acid transporter

34
Q

NSAID therapy in RA… what are the goals?

A

Pain relief. Large doses with long durations. This can lead to GI problems and renal damage. Does NOT effect the progression of the disease!

35
Q

Etanercept

A

Recombinant fusion protein that is binds the TNF-alpha receptor… prevents TNF-alpha from binding.

Given IV or SubQ, takes 1-2 weeks to start, with a half life of 3 days

Infusion rxns, higher risk of infection in patients immunosuppressed, can cause lymphomas in children or adolescent patients

Originally for severe RA, now approved for early

36
Q

Infliximab

A

IgG monoclonal antibody

Binds to soluble and transmembrane TNF-alpha… still prevents its interaction with its receptor

IV infusion, every 2-6 weeks

Infusion rxn, fever, chest pain, changes (up or down) BP

Higher risk of infection if immunosuppressed, and lymphoma risk in children/adolescents

Moderate to severe RA

More versatile than Etanercept, since it binds soluble and bound TNF… rather than just the bound receptor

37
Q

Tocilizumab

A

A humanized antibody that binds to soluble or membrane-bound IL-6 receptors. THis inhibits IL-6 mediated signaling via these receptors

Given IV every 4 weeks

Alters lipid profile, infusion rxn, infection risk

Used in patients with moderate to severe active RA, and who have had an inadequeate response to one or more TNF antagonists

38
Q

Tofacitinib

A

A tyrosine kinase inhibitor that blocks Janus Kinase (JAK), downstream of cytokine activtion of the STAT-JAK pathway.

Able to be given orally.

Metabolized mostly by CYP3A4 but also CYP2C19

Infection risk, increases cholesterol

Used in moderate to severly active RA, or patients that are intolerant to methotrexate

39
Q

Anakinra

A

Blocks IL-1 receptor

40
Q

Abatacept

A

Blocks T cell activation

41
Q

Rituximab

A

Blocks B cells by targeting CD20

42
Q

Most common joint disorder?

A

Osteoarthritis

43
Q

Pathogenesis of osteoarthritis is predominantly due to what?

A

A degenerative disorder of the articular cartilage such that chondrocytes do not respond to biomechanical and biologic stresses appropriately… rather than remodeling, they allow the matrix to break down.

It is not a chiefly inflammatory process, although the name suggests so. Structural changes to the bone are secondary to the chondrocyte dysfunction.

44
Q

What are the two purposes of cartilage

A
  1. Provide friction-free movement. This is thanks to synovial fluid serving as lubricant.
  2. Absorb shock and weight.
45
Q

How does cartilage biochemically achieve its goals?

A
  1. It gains its elasticity and resilient response to compression from its dense concentration of proteoglycans
  2. It gains its high tensile strength due its presence of type II collagen
46
Q

What are causes of secondary osteoarthritis?

A
  1. Trauma
  2. Congenital deformities
  3. Ochronosis (a blue/black discoloration of tissues, seen with alkaptonuria, from exposure to certain substances such as carbon-rich oils)
  4. Hemochromatosis
  5. Marked obesity
47
Q

Does primary osteoarthritis have a cause?

A

Not a clear cause. Damage begins however many years before presentation, which is typically in the 50s and 60s.

48
Q

How many joints involved in OA?

A

IT is generally an oligoarticular disease, with joints of the hands, knees, hips, and spine more commonly affected.

Knees and hands are generally worse in women.

Hips are generally worse in men.

49
Q

Signs and Symptoms of OA?

A
  1. Deep, aching pains… worse with prolonged use of joint. Apparent by end of day
  2. Morning stiffness
  3. Crepitus (grating, popping in the joint)
  4. Impaired range of motion
  5. Heberden nodes (these are prominent osteophyytes at the DIP joints)… Classic presentation in women.
  6. Impingement on spinal formaina, causing nerve root compression and radicular pain, muscle spasm, muscle atrophy, and neurologic deficits

DIP is classic OA, PIP is classic RA

50
Q

What happens to cartilage during OA?

A

Early: Granular-appearing cartilage surface; this is called chondromalacia.

Late: Full-thickness portions are cartilage are lost, exposing subchondral bone plate. Additionally, subchondral bone becomes eburnated (polished and ivory) due to sanding away of its surface once it’s exposed

51
Q

What’s eburnation?

A

The sanding away and subsequently ivory like appearance of subchondral bone after cartilage in joint is lost during OA.

52
Q

What are joint mice and rice bodies?

A

These are small cartilage and subchondral bone fragments that form loose bodies in the joint space due to fractures during OA

53
Q

What are subchondral cysts?

A

Regions in bone articulation that image darkly on X ray. This is because small fracture gaps in the subchondral regions of the bone form fibrous walled (subchondral) cysts that are filled with synovial fluid after the potential space is broken into.

54
Q

What are osteophytes?

A

Bone spurs, they occur usually at the margin of the joint. They can lead to nerve and nerve root compression, muscle atrophy and pain

55
Q

What is the goal of treatment of OA

A

Symptomatic treatment. Joint replacement is good at particular joints that are severely degraded. Otherwise, disease progression is usually unable to be slowed or halted with therapy.

Musculoskeletal and Skin Pathology (10 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions