Uric Acid Metabolism

Question 1

Purines?

Answer 1

Adenosine
Guanosine
Inosine

Question 2

Purine catabolism

Answer 2

Purine to Hypo-Xanthine

Hypo-xanthine to Xanthine = Xanthine Oxidase

Xanthine to Urate = Xanthine Oxidase

Urate to Allantoin = Uricase which humans don’t have, hence urate builds up in plasma and needs exreting

Question 3

Why do women get gout less than men?

Answer 3

Lower plasma urate concentration

Question 4

Which joint does gout classically attack?

Answer 4

MTP, Low temperature joint hence buildup of uric acid crystals

90% of all cases

50% 1st MTP

Question 5

What is the rate limiting step of de novo purine synthesis?

Answer 5

PAT = PRPP Amidotransferase

PPRP to 5-phosphoribosyl-1-amine

Question 6

What is HPRT

Answer 6

Main enzyme of the salvage pathway of purine metabolism

Question 7

HPRT Deficiency

Answer 7

Lesch Nyhan Syndrome

Neuro signs + Self-mutliation

Frank Gout

Normal at birth, delay at 6m

X-Linked

Question 8

Secondary causes of decrease in urate excretion

Answer 8

Raised cell turnover in cancer, myeloproliferative diseases or severe psoriasis

Question 9

Primary causes of decreased urate excretion

Answer 9

Familial Juvenile Hyperuricaemic Nephropathy

Question 10

Secondary causes of decreased urate excretion

Answer 10

CKD
Bartter’s
Saturnine Gout = lead poisoning
Diuretics

Question 11

How is urate excreted renally

Answer 11

PCT -> only 10% excreted, 90% reabsorbed maybe due to anti-oxidant properties

Question 12

Which electrolyte imbalances are associated with Thiazide Diuretics

Answer 12

Low Sodium

High glucose, Ca, Urate

Question 13

Gout

Answer 13

Crystal Arthropathy
Monosodium Urate crystals
3%M 0.5% F

Question 14

Podagra

Answer 14

Acute gout in one foot

Question 15

Tophaceous Gout

Answer 15

Chronic Gout in soft tissues

Classically peri-articular or earlobes (tophi)

Question 16

Gout investigation

Answer 16

Negatively birefringent needles of monosodium urate under polarised light microscopy

Parallel = yellow/red
Perpendicular = blue

Question 17

Acute gout management

Answer 17

NSAIDs (Diclofenac)
Colchicine
Glucocorticoids

Question 18

Chronic Gout management

Answer 18

Hydration
Allopurinol
Reversing causative factors (ie. beer, port)

Question 19

When are NSAIDs contraindicated

Answer 19

Peptic Ulcer
Severe Asthma
CKD

Question 20

How does Colchicine work?

Answer 20

Inhibits tubulin polymerisation = no microtubule assembly = no neutrophil migration to site of inflammation

Question 21

Allopurinol MOA

Answer 21

Xanthine Oxidase inhibitor = less urate production

Question 22

Probenecid

Answer 22

Uricosurics, a class of drug that enhances tubular urate excretion

Question 23

Allopurinol contraindications

Answer 23

Azathioprine, as they counteract one another with regards to bone marrow turnover

Azathioprine metabolite = mercaptopurine which is metabolised by xanthine oxidase, hence allopurinol can raise this to toxic levels

Question 24

Pseudogout

Answer 24

Pyrophosphate crystals
Positively birefringent

Parallel = blue 
Perpendicular = Red/yellow