C - Uric Acid Metabolism (E)

Question 1

name 3 purines

Answer 1

adenosine
guanosine
inosine

Question 2

describe purine catabolism (4 steps with enzymes)

Answer 2

purines
–>
hypo-xanthine
–> (xanthine oxidase)
xanthine
–> (xanthine oxidase)
urate

Question 3

why don’t animals get gout

Answer 3

they have a uricase enzyme that breaks down gout

Question 4

plasma conc of urate in men / women

Answer 4

men 0.12 - 0.42
women 0.12 - 0.36

Question 5

how is uric acid handled in the kidney

Answer 5

reabsorbed in PCT then resecreted later down the tubule
around 90% reabsorbed

Question 6

2 types of purine synthesis

Answer 6

de novo pathway (from scratch)
salvage pathway (using other molecules)

Question 7

when does the de novo pathway predominate

Answer 7

BM - making so much DNA that it needs de novo
everywhere else its salvage as its less energy

Question 8

what is the rate limiting step of purine synthesis

Answer 8

PAT enzyme step

Question 9

why is the PAT enzyme step rate limiting

Answer 9

has negative feedback from other steps

Question 10

another key enzyme in purine metabolism

Answer 10

HPRT (sometimes called HGRT)

Question 11

why is HPRT important

Answer 11

main enzyme of salvage pathway

Question 12

what is complete HPRT deficiency called

Answer 12

Lesch Nyhan syndrome

Question 13

PC of Lesch Nyhan syndrome at birth

Answer 13

normal at birth

Question 14

PC of Lesch Nyhan syndrome at 6 months

Answer 14

developmental delay

Question 15

PC of Lesch Nyhan syndrome at 1 year

Answer 15

choreiform movements

Question 16

PC of Lesch Nyhan syndrome after 1 year

Answer 16

spasticity
mental retardation
self mutilation (85%) - bite lips / digits

Question 17

key metabolic disturbance in Lesch Nyhan syndrome

Answer 17

hyperuricaemia (gout)

Question 18

why do you get hyperuricaemia in Lesch Nyhan syndrome

Answer 18

no HPRT –> no negative feedback on PAT –> increased de novo pathway action –> increased synthetic pathway action –> lots of urate production

Question 19

how can disorders of hyperuricaemia be classified

Answer 19

increased urate production
- primary / secondary
decreased urate excretion
- primary / secondary

Question 20

primary causes of increased urate production

Answer 20

lesch nyhan syndrome
partial HPRT deficiency
glycogen storage disorders
fructose intolerance
PRPP synthetase over activity

Question 21

secondary causes of increased urate production

Answer 21

myeloproliferative disorders
lymphoproliferative disorders
carcinomatosis
chronic HA
Gaucher’s disease
severe psoriasis

Question 22

primary causes of decreased urate excretion

Answer 22

FJHN
- familial juvenille hyperuricaemic nephropathy

Question 23

secondary causes of decreased urate excretion

Answer 23

CKD
Bartter’s syndrome
Down’s
lead poisoning
thiazide diuretics
aspirin

Question 24

T or F
de novo pathway predominates over salvage pathway in most tissues

Answer 24

F

Question 25

T or F xanthine oxidase oxidises xanthine to uric acid

Answer 25

T

Question 26

T or F HPRT is deficient in Lesh Nyhan syndrome

Answer 26

T

Question 27

T or F PAT is the rate limiting enzyme

Answer 27

T

Question 28

what crystals are present ingout

Answer 28

monosodium urate crystals needle shaped

Question 29

what is acute gout called

Answer 29

podagra

Question 30

what is chronic gout called q

Answer 30

tophaceous

Question 31

prevalence of gout in M or F

Answer 31

M 3% F 0.6%

Question 32

which M / F get gout

Answer 32

post menopausal F or post pubertal M

Question 33

what does tophaceous gout look like

Answer 33

creamy cottage cheese looking lumps

Question 34

what are the exceptions to the rule that only post pubertal men get gout

Answer 34

Lesch Nyhan syndrome familial juvenille hyperuricaemic nephropathy

Question 35

what does gout look like

Answer 35

red, shiny skin over a lump +++ painful

Question 36

PC of acute gout

Answer 36

rapid build up of pain affected joint is red, hot, swollen

Question 37

what % of first site joints is the MTP

Answer 37

50%

Question 38

in how many cases is the MTP joint involved either as first or later joint

Answer 38

90%

Question 39

2 aims of Tx of gout

Answer 39

reducing inflammation managing the hyperuricaemia

Question 40

Tx of acute gout

Answer 40

1st NSAIDs 2nd colchicine 3rd glucocorticoids (pred)

Question 41

what should you NOT try to Tx in acute gout

Answer 41

the plasma urate conc - can worsen precipitations of gout crystals

Question 42

how do you treat the hyperuricaemia after the acute attack of gout

Answer 42

drink plenty of water reverse any factors increasing the urate allopurinol (reduce synthesis of urate) probenecid (uricosuric - increases renal excretion)

Question 43

how does allopurinol reduce synthesis of urate

Answer 43

xanthine oxidase inhibitor

Question 44

which drug can you NOT co prescribe with allopurinol

Answer 44

azothioprine

Question 45

why is allopurinol CI if pt is taking azothioprine

Answer 45

increases bone marrow toxicity

Question 46

T or F allopurinol should be used acutely

Answer 46

F

Question 47

T or F NSAIDS are 1st line in acute attacks

Answer 47

T

Question 48

T or F colchicine lowers urate levels

Answer 48

F

Question 49

T or F allopurinol lowers urate levels by inhibiting HPRT

Answer 49

F

Question 50

T or F allopurinol lowers urate levels by inhibiting xanthine oxidase

Answer 50

T

Question 51

how is gout Dx if any clinical uncertainty

Answer 51

tap effusion view under polarised light use red filters

Question 52

how does gout look under polarised light

Answer 52

negatively birefringent needle shaped crystals

Question 53

how does pseudogout look under polarised light

Answer 53

positively birefringent rhomboid shaped crystals

Question 54

what compound are the crystals in pseudogout

Answer 54

calcium pyrophosphate dihydrate

Question 55

who gets pseudogout

Answer 55

osteoarthritis pts

Question 56

prognosis of pseudogout

Answer 56

self limiting in 1-3 weeks