Brainscape's Knowledge GenomeTM

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


See full index

BMS150 Test 2 > Crystal Arthropathies - Gout, CPPD (Rheumatology 3 - Week 5) > Flashcards

Crystal Arthropathies - Gout, CPPD (Rheumatology 3 - Week 5) Flashcards

1
Q

How many rings do pyrimidine bases have?

A

1

Examples: C, T (DNA only), U (RNA only)

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

How many rings do purine bases have?

A

2

Examples: A, G

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

How many carbons make up the sugar component of DNA and RNA?

A

5

Note: for RNA, it’s a 5-C ribose and for DNA it’s a 5-C deoxyribose

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

What do we call a sugar and base together?

A

nucleoside

Example: adenosine (adenine + ribose sugar)

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

What do we call a nucleoside (base + sugar) and 1-3 phosphates?

A

nucleotide

Example: adenosine triphosphate (ATP)

Note: nucleotides are the building blocks used in DNA and RNA synthesis

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

What is the nucleoside name for cytosine?

A

cytidine

Note: notice the “ine” ending of the bases changing to “dine” endings for pyramidine nucleosides

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

What is the nucleoside name for thymine?

A

thymidine

Note: notice the “ine” ending of the bases changing to “dine” endings for pyramidine nucleosides

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

What is the nucleoside name for uracil?

A

uridine

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

What is the nucleoside name for adenine?

A

adenosine

Note: notice the “ine” ending of the bases changing to “sine” endings for purine nucleosides

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

What is the nucleoside name for guanine?

A

guanosine

Note: notice the “ine” ending of the bases changing to “sine” endings for purine nucleosides

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

What is the nucleoside name for xanthine?

A

xanthosine

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

What is the nucleoside name for hypoxanthine?

A

inosine

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

What are the two pathways for purine nucleotide biosynthesis?

A

1) de novo pathway
2) salvage pathway

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

Describe the de novo pathway for purine nucleotide biosynthesis

A

“Adding things onto an activated ribose (PRPP) to make a completely new base”

After we have that ribose and make that base, we have a nucleotide, because the phosphates are already attached (on the activated ribose)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe the salvage pathway for purine nucleotide biosynthesis

A

Again, you have the activated ribose with the phosphates (PRPP), but you also already have a pre-formed base in your body (can be from diet or products from cell turnover)

We put the PRPP and base together, and we get a nucleotide

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

What molecule is used to transfer an N (nitrogen) to PRPP in de novo synthesis?

A

glutamine

Recall: “amine” = nitrogen containing

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

True or False: Inosine monophosphate (IMP) can be used to make AMP or GMP

A

True

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

How do ATP and GTP levels influence GMP and AMP synthesis?

A
  • when ATP levels are high, you make GMP (ATP makes GMP)
  • when GTP levels are high, you make AMP (GTP makes AMP)

Note: we can refer to this as reciprocal control

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

What is a disadvantage of the de novo pathway?

A

It uses a lot of energy because we’re making bases from scratch.

Therefore, helpful that we also have the salvage pathway.

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

What are two important enzymes for the salvage pathway?

A

1) hypoxanthine-guanine phosphoribosyl transferase (HGPRT)

2) adenine phosphoribosyltransferase (APRT)

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

What reaction does HGPRT catalyze?

A

addition of phopsphoribose (sugar + P) from PRPP to:

  • hypoxanthine to make IMP
  • guanine to make GMP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What reaction does APRT catalyze?

A

addition of phosphoribose (sugar + P) from PRPP to:

  • adenine to make AMP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the pathway used for pyrimidine nucleotide synthesis?

A

1) de novo pathway

Remember: “de novo” means making from scratch (completely new)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Describe the de no pathway for pyrimidine nucleotide synthesis

A
  • make an intermediate pyrimidine ring first
  • then attaching a ribose-5-P (via PRPP)

Note: this is opposite to purines, where the ring is constructed directly onto the ribose-5-P

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the substrates used for the ring in the de novo pathway in pyrimidine nucleotide biosynthesis?

A

1) carbamoyl phosphate
2) aspartate

Note: carbamoyl phosphate is made from glutamine + ATP + HCO3-

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

How do we make CTP?

A
  • phosphorylate UMP to make UTP
  • UTP is aminated to CTP (N supplied by glutamine)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

How do we make dTMP?

A
  • phosphorylate UMP to make UDP
  • UDP converted to dUMP
  • dUMP is methylated to dTMP (via folate coenzyme/B9 coenzyme)

recall: folate = vitamin B9

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

True or False: IMP, AMP, and GMP are examples of monophosphates

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What do nucleotidases do?

A

Remove phosphates from nucleotides to release nucleosides

Recall: nucleoside = sugar + base

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What does cytosine get degraded into?

A

cytosine –> uracil –> alanine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What does thymine get degraded into?

A

thymine –> aminoisobutyrate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What do purines (guanine and adenine) get degraded into?

Note: purine degradation is more relevant to today’s lecture on gout (compared to pyrimidine degradation)

A

guanine/adenine –> xanthine –> uric acid

Note: uric acid is eventually excreted in urine, and elevated levels (hyperuricemia) can lead to GOUT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What enzyme converts hypoxanthine to xanthine, and then xanthine to uric acid?

** POTENTIAL TEST QUESTION **

A

xanthine oxidase

34
Q

What do we call the condition characterized by joint inflammation due to the deposition of urate crystals?

A

Gout

35
Q

Gout can be due to ____________ (underexcretion/overexcretion) or ______________ (underproduction/overproduction) or uric acid, leading to hyperuricemia.

A

underexcretion or overproduction

Note: underexcretion = more common

36
Q

True or False: Hypouricemia can also lead to gout

A

False.

Only hyperuricemia can lead to gout

37
Q

In gout, immune cells mount an inflammatory response to what type of crystal deposited in the joints?

A

monosodium urate crystals

38
Q

True or false: Gout is also known as gouty arthritis

A

True

39
Q

What are tophi?

A

Nodular masses of monosodium urate crystals

Other descriptors:
- large, inflammatory bodies that surround areas of crystal deposition
- form foreign-body giant cells
- consist of macrophages and lymphocytes
- occur in articular cartilage, ligaments, tendons, and bursae
- can invade joint and surrounding soft tissues, kidney, earlobes, fingertips

40
Q

Uric acid stones (aka “kidney stones”) is referred to as what?

A

Urolithiasis

(or sometimes nephrolithiasis, depending on location of stones)

41
Q

Humans lack what enzyme that can degrade uric acid?

A

uricase

Note: because we can’t degrade it, we rely on excreting it (but sometimes this doesn’t work as we want because uric acid is readily reabsorbed back into the body)

42
Q

What are modifiable risk factors of gout?

A
  • diets high in alcohol (beer has a lot of purines)
  • diets high in meat (especially organs)
  • high asparagus consumption
43
Q

What are non-modifiable risk factors for gout?

A
  • male sex
  • decreased renal excretion
44
Q

What percent of the general population has gout?

A

1-4%

Note: 10-20% of the population of the Western hemisphere has hyperuricemia, but not all develop gout

45
Q

What might cause increased uric production?

A
  • enzyme defects (i.e., xanthine oxidase) in metabolism of uric acid
  • cancers (i.e., leukemia)
46
Q

What might cause decreased uric acid excretion?

A
  • idiopathic (meaning we don’t know why, it’s just happening)
  • chronic kidney disease
47
Q

_____________ phagocytose urate crystals and release chemokines that attract ____________

A

Macrophages,
neutrophils

48
Q

Complement activation via the ____________ pathway also contributes to neutrophil recruitment

A

alternative

49
Q

Phagocytosis by macrophages results in the activation of what?

A

inflammasome

Note: this leads to secretion of IL-1 and chemokines/other cytokines… all of which attracts more neutrophils

50
Q

Spontaneous remission (of acute gout) can occur after how long?

A

Days to weeks

51
Q

What are some characteristics of CHRONIC gout?

A
  • chronic arthritis/chronic inflammation
  • development of tophi/urate crystals encrust the articular surface of the joint, forming deposits in the synovium
  • synovium becomes hyperplastic, fibrotic, and thickened with inflammatory cells (i.e.., pannus formation)
  • destruction of underlying cartilage leads to bone erosion
  • in severe cases, a fibrous or bony ankylosis can form, resulting in loss of joint function
52
Q

What is the pathognomonic hallmark of gout?

A

tophi

53
Q

90% of affected individuals experience acute attacks in what common locations?

A
  • 1st metatarsal-phalangeal joint ***
  • insteps (top part of foot) **
  • knees**
  • ankles
  • heels
  • wrists
  • elbows
54
Q

True or False: lower limbs are more often affected than upper limbs

A

True

55
Q

True or False: acute gout attacks are relatively pain-free

A

False

Acute gout attacks may be excruciatingly painful as joints become inflamed (redness, swelling)

If untreated, acute gouty arthritis may last for hours to weeks

56
Q

True or False: In the absence of appropriate therapy, gout attacks recur at shorter intervals and frequently become polyarticular.

A

True

57
Q

What is Lesch-Nyhan Syndrome?

A

A syndrome that can lead to hyperuricemia via:

  • deficiency of HGPRT (leading to accumulation of hypoxanthine and guanine, which ultimately break down into uric acid)
  • PRPP also accumulates and stimulates production of purine nucleotides, which ultimately break down into uric acid

Hyperuricemia –> leads to urolithiasis and gouty arthritis

usually presents with severe neurological problems

58
Q

Calcium pyrophosphate crystal deposition disease (CPPD) is also known as what?

A

pseudogout

59
Q

What is the prevalence of CPPD/pseudogout in those older than 85 years?

A

30-60%

Note: prevalence of CPPD increases with age

60
Q

True or False: Most cases of CPPD/pseudogout are sporadic

A

True

However, other causes may include:
- genetic component (autosomal dominant)
- hyperparathyroidism
- hemochromatosis
- diabetes
- hypothyroidism
- some medications (not well defined)

61
Q

Where do the calcium pyrophosphate crystals deposit?

A

in the matrix of the menisci & connective tissue of the joint

62
Q

True or False: Similar to gout, in CPPD, macrophages phagocytose the crystals, neutrophils are recruited, and rupturing induces this inflammatory process to continue

A

True

63
Q

How does CPPD/pseudogout present clinically?

A
  • can be asymptomatic or can mimic osteoarthritis or rheumatoid arthritis
  • asymmetric
  • monoarticular or polyarticular
  • commonly affects KNEES
  • less common sites: wrists, shoulders, elbows, ankles
  • eventually, 50% patients have significant joint damage (therefore affecting mobility)
64
Q

What is the standard treatment for CPPD/pseudogout?

A

no therapy is effective in preventing damage

mostly symptomatic treatment (i.e., pain management)

65
Q

Why do we do synovial fluid analysis?

A
  • can let us know if we’re dealing with septic arthritis (emergency), gout, pseudogout, hemarthroses, or rheumatic joint diseases

Note: hemarthrosis and gout should also be managed “semi-urgently”

  • also distinguishes between an acute flare of gout or pseudogout and septic arthritis
66
Q

When does a synovial fluid analysis have poor sensitivity and specificity?

A

When it’s more difficult to visualize crystals (aka during the time in between flares)

67
Q

When would you conduct a synovial fluid analysis?

A

Suspicion of:

  • infectious arthritis
  • flare of crystal arthritis
  • hemarthrosis (blood in the joint)
  • monoarthritis with or without a prior history of arthritis of other joints
  • trauma to a joint (with effusion)
68
Q

What does a synovial fluid analysis analyze? (Hint: 3 C’s)

A

1) CRYSTALS (what type?)

2) CELLS (if there’s blood in the joint, we’ll see more RBCs, whereas if there’s inflammation there may be neutrophils/lymphocytes)

3) CULTURE (if there’s microorganisms, would indicate that it’s septic)

69
Q

What would normal results be for a synovial fluid analysis?

A

Cells: less than 200ul (low)

Crystals: Negative

Culture: Negative

70
Q

Synovial fluid analysis results for a patient with gout:

A

Cells: greater than 2000ul (high, but not as high as septic)

Crystals: Birefringent, needle-shaped**

Culture: Negative

71
Q

Synovial fluid analysis results for a patient with pseudogout:

A

Cells: greater than 2000ul (high, but not as high as septic)

Crystals: Birefringent, cuboidal**

Culture: Negative

72
Q

Synovial fluid analysis results for a patient with septic arthritis:

A

Cells: greater than 50, 000 (very high)

Crystals: Negative

Culture: Positive**

73
Q

Synovial fluid analysis results for a patient with hemarthrosis:

A

Cells: lots of RBCs**

Crystals: Negative

Culture: Negative

74
Q

What are some treatment options for gout?

A
  • corticosteroids (to target inflammation; specific for gout = colchicine)
  • analgesics (pain relief; i.e., NSAIDs such as aspirin) - most common treatment
  • allupurinol (decrease uric acid production)
  • uricosurics, such as probenecid and sulfinpyrazone (increase uric acid excretion)
75
Q

What is the mechanism of colchine (corticosteroid/anti-inflammatory) for gout?

A

Binds to tubulin and prevents microtubule polymerization

Recall: microtubules are like “highways”, so when we block these highways/prevent them from forming, you block the migration of leukocytes (mainly neutrophils), thereby decreasing inflammation

Dosage to terminate an acute attack (just FYI): 1-1.2 mg every hour until attack abates or until diarrhea

76
Q

True or False: Colchine cannot be used as a prophylactic

A

False

Colchine, taken prophylactically, can reduce frequency of attacks

Dose (FYI): 0.5mg/day for 3-4 days/week

77
Q

What is the mechanism of allopurinol for treatment of gout?

A

it’s a competitive inhibitor of xanthine oxidase

(thereby decreasing production of uric acid)

Note: CANNOT stop an acute attack, but can reduce frequency of attacks

78
Q

What is the mechanism of uricosurics for treatment of gout?

A

Block tubular reabsorption of uric acid, thereby increasing excretion

79
Q

Can allopurinol precipitate an attack of gout at the beginning of therapy?

A

Yes (because immune system is getting used to the change)

aspirin typically given at beginning of allopurinol therapy

80
Q

Can uricosurics precipitate an attack of gout at the beginning of therapy?

A

Yes (immune system is getting used to change)

81
Q

True or false: uricosurics can be taken prophylatically

A

True

BMS150 Test 2 (10 decks)

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