Chemical Patholgy 1 - Uric acid metabolism Flashcards Preview

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Flashcards in Chemical Patholgy 1 - Uric acid metabolism Deck (21)
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1

Recall 3 roles of purines

1. Base in DNA
2. 2nd messengers for cAMP
3. Form part of ATP

2

Recall the pathway of purine catabolism

Purines --> hypo-xanthine --> xanthine --> uric acid
Xanthine oxidase is involved in the production of both xanthine and urate

3

Recall the renal handling of urate

Urate is fairly insoluble
It is freely-filtered at the Bowman's capsule
Bizzarely: it is both reabsorbed and re-excreted in the proximal convoluted tubule!

4

Name one disorder of inborn error of purine
metabolism

Lesch Nyhan Syndrome

5

What is the inheritance pattern of Lesch Nyhan syndrome

X-linked

6

How does Lesch-Nyhan syndrome first present?

With developmental delay at 6-12 months

7

What is the mutation that causes Lesch-Nyhan syndrome?

HPRT - an enzyme that is key in purine recycling
Since there is no feedback inhibition on dinovosynthesis of purines, plasma urate increases a LOT

8

What are the symptoms of Lesch-Nyhan syndrome?

Choreform movements, spasticity and UMN signs with mental retardation
Self-mutilation in 85% :-( They bite their lips and digits with a great deal of force

9

What type of crystals cause gout?

Monosodium urate

10

What are the 2 clinical forms of gout?

Acute - "podagra"
Chronic - "tophaceous"

11

How should acute gout be treated?

Key thing is to reduce inflammation
1. NSAIDs
1b. Colchicine (this is 2nd line, if NSAIDs contra-indicated)
1c. Glucocorticoids (if all else fails!!)
Nb: if you try to correct urate in the acute phase, you can actually make it worse!!

12

How should chronic gout be treated?

Need to manage the hyperuricaemia
1. Hydration (water!)
2. Reverse the factors driving urate up
3. Allopurinol
4. Probenecid

13

What prescription drug can drive urate up?

Thiazide diuretics

14

What is the mechanism of action of allopurinol?

Inhibits xanthine oxidase

15

What is the mechanism of action of probenecid?

Increases renal excretion of urate

16

Recall one very important drug interaction to avoid when prescribing gout drugs

Allopurinol and azothioprine
The intermediary of azothioprine = mercaptopurine - which needs xanthine oxidase to be catabolised

17

Recall the diagnostic approach for gout

1. History and examination should be sufficient
2. If not clear: TAP effusion

18

How can gout crystrals be visualised?

View effusion material under polarised light - use RED filter

19

How can gout and pseudogout crystals be differenitated under the microscope?

Gout crystals = negatively birefringent (BLUE - this is perpendicular to compensator)
Pseudogout crystals - positively birefringent (red)

20

Which other condition predisposes to pseudogout?

Osteoarthritis

21

How long does pseudogout last?

1-3 weeks

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