Crystal Arthopathy

Question 1

GOUT

1. define
2. cause
3. disorder
4. gender

Answer 1

1. acute inflammatory arthritis
2. uncoated monosodium urate crystals in soft tissue
3. uric acid metabolism
4. MEN - higher uric acid levels naturally

Question 2

podagra

Answer 2

Gout involving the BIG TOE

Question 3

Incidence in the population of gout

Answer 3

1% in population

Question 4

Clinical features of gout

Answer 4

• EXTREMELY PAIN (most painful disorder known to man)
• red
• HOT
• swelling
• 1st MTP foot =50% cases
• monoarticular= 90% cases

Question 5

Which joints are most commonly affected in gout

Answer 5

DISTAL + SMALL JOINTS

• lowest temp = crystallisation occurs more easily
• less synovial fluid = more concentrated uric acid

Question 6

progression of gout (if untreated)

Answer 6

• polyarticular
• spread more proximal (to knees)
• gout attacks increase in freq + intensity
• affects bone - rat bites erosion +

Question 7

Why are you unlikely to see gout under age 30

Answer 7

require >20years raised uric acid levels
men- onset = puberty
women- onset = menopause

(therefore gout seen in:
men 40-60s
women 60-70s)

Question 8

TOPHI

1. define
2. sites
3. time for tophi to develop in gout
4. when tophi develops

Answer 8

1. FORIEGN BODY-TYPE GIANT CELL REACTION to urate crystals deposition
2. white smooth deposits -ears + hands + elbows + feet
3. > 10years
4. untreated gout (50% patients)

Question 9

Histology of tophi

look at a slide

Answer 9

LAYERS

1. core/centre uric acid
2. macrophage + dendritics
3. fibrotic material
4. Calcification - wall off infection

Question 10

pathophysiology of gout

Answer 10

1. uncoated urate crystals (foreign material) - NEUTROPHILS - lysis (crystals=sharp)
2. cytokine cascade - IL1 -triggers more neutrophils
3. acid lysosomes- decrease pH - crystallation occurs more easily
4. spiral of gout attacks

Question 11

Is the presence of gout crystals in the synovial fluid enough to trigger a gout attack?

Answer 11

NO
-need to have UNCOATED crystals (stim. immune response
OR
-sudden large increase in uric acid

Question 12

How does the body normally die with mono-sodium urate crystals

Answer 12

-serum proteins -apoB/E- COAT crystals - inert

Question 13

what is the saturation point

1. define
2. define by uric acid

Answer 13

1. point at which all the lipoprotiens are saturated- unable to coat any more crystals - therefore crystals precipitate into soft tissues - GOUT
2. saturation point = 6.8mg/dl

Question 14

Complications of untreated gout

Answer 14

1. joint destruction
2. renal damage - urate excess cannot be excreted - KIDNEY STONES
   (3. tophi)

Question 15

4 Cause of gout

Answer 15

DISORDER OF URIC ACID METABOLISM

1. overproduction of uric acid
2. disorders involving high cell turnover (invovles purines)
3. overconsumption purine rich foods
4. impaired excretion of purines

Question 16

what is uric acid the metabolite of?

Answer 16

purine

Question 17

PURINE CYCLE
input
output

Answer 17

input =600mg/d =diet
=300-600mg/d= new purine synthesis in body

output=600mg/d -kidneys -urine
=200mg/d -intestines-faeces

use in body = purine nucleotide bases for DNA/RNA

Question 18

Dietary sources of purine

Answer 18

beer, shellfish, porte, red wine, beef , lamb

Question 19

Use of purines in body

Answer 19

nucleotide bases

Question 20

Main method by which uric acid is excreted

Answer 20

renal excretion

Question 21

Main cause of hyperuricaemia

Answer 21

90% patients - impaired renal excretion - excess urate stores in the body

Question 22

2 genetic conditions linked to gout

Answer 22

CAUSE OVERPRODCUTION OF URIC ACID

1. Lesch Nyhan syndrome
2. von wilke’s disease (G6Pase deficiency)

Question 23

Enzyme involved in purine metabolism

Answer 23

XANTHIANE OXIDASE

1. hypoxathine -xanthine
2. xanthine -uric acid

Question 24

Use of this medication to treat hypertension if patient also suffers gout should be avoided

Answer 24

DIURETICS (esp thiazide) - reduces urine output - reduce renal excretion of uric acid

Question 25

Diagnosis for definitive gout

Answer 25

Urate crystals present during acute attack

Question 26

Investigations to confirm gout diagnosis

Answer 26

1. synovial fluid analysis (+ under polarizing light) 2. serum uric acid analysis 3. x-ray 4. ultrasound

Question 27

Synovial fluid analysis in gout

Answer 27

- white + cloudy = infiltration of immune cells - esp neutrophils - sharp + shiny + highly negative + birefringent under polarizing light

Question 28

Appearance of neutrophils in gout

Answer 28

``` POLYMORPHONUCLEAR neutrophils (PMNs) -granules -release lytic enzymes under infection ```

Question 29

Serum uric acid levels

Answer 29

treat if >11mg/dL | NB - hyperuricaemia - NOT diagnostic - 5% pop have elevated uric acid levels and do not suffer from gout

Question 30

Radiological features of gout

Answer 30

1. soft tissue swelling 2. 'rat bites' (erosion with overhanging edges) 3. erosion OUTSIDE joint capsule 4. erosion with maintains of joint space *problem- changes are only seen after MULTIPLE GOUT ATTACKS solution - ultrasound - detect uric acid + soft tissue damage*

Question 31

Treatment for acute attack 1. aim 2. options

Answer 31

1.reduce pain 2.NSAIDs = 1st line treatment colchichine =2nd line corticosteroids=3rd line IL 1 blockers

Question 32

NSAIDs use for acute gout attacks

Answer 32

- high dose - 2 weeks - only stop once asymptomatic for 2 days

Question 33

2 Biological DMARDs which could be used for gout | +why are they not currently used

Answer 33

- Rilonacept - Anakinra - both IL1 blockers -IL1 is released during neutrophil lysis by urate crystals - reduce length + reoccurrence of attacks - currently not FDA approved due to £££££

Question 34

Colchichine 1. MOA 2. S.E

Answer 34

1.prevents microtubule formation - prevents mitosis .prevents neutrophil motility + activity (effect = anti-inflammatory in gout) 2. apalstic anaemia + alopecia + neutopenia

Question 35

Treatment of chronic gout 1. aim 2. 4 options

Answer 35

1. lowering uric acid levels - reduce gout attacks 2. diet + allupinrol + rasburicase + probenecid *probenecid -preferential - fewest SE*

Question 36

Allopurinol 1. MOA 2. S.E

Answer 36

1. blocks xanthine oxidase- reduces generation uric acid | 2. sever skin rashes

Question 37

Rasburicase 1. MOA 2. S.E

Answer 37

1.catalytic enzyme for conversion: xanthiane-urate-allantoin ALLANTOIN -more sol than urate - passes into urine 2.anaphylaxis

Question 38

Probenecid | 1.MOA

Answer 38

1.URICOSURIC - increase uric acid renal excretion -decrease serum uric acid

Question 39

PSEUDOGOUT 1. type of crystals 2. ass with which joint disorder 3. clinical presentation 4. incidence >85year olds

Answer 39

1. calcium pyrophosphate 2. OA 3. most cases are ASYMPTOMATIC 4. 50% of people >85years (esp women)

Question 40

Synvoial fluid analysis in pseudogout

Answer 40

- rhomboid + dull + weakly birefringement crystals | - white + mildly cloudy

Question 41

Imaging investigations in Pseudogout

Answer 41

X-ray or Ultrasound to observe CHONDROCALCINOSIS | calcium deposits on cartilage

Question 42

Joints in psuedogout vs gout

Answer 42

``` pseudogout = knees, wrists, ankles gout = 1st MTP joint, knees, wrists, fingers, olecranon bursae ```

Question 43

Treatment for pseudogout

Answer 43

NSAIDs + intra-articular corticosteroids