C - Uric Acid Metabolism (E) Flashcards
name 3 purines
adenosine
guanosine
inosine
describe purine catabolism (4 steps with enzymes)
purines
–>
hypo-xanthine
–> (xanthine oxidase)
xanthine
–> (xanthine oxidase)
urate
why don’t animals get gout
they have a uricase enzyme that breaks down gout
plasma conc of urate in men / women
men 0.12 - 0.42
women 0.12 - 0.36
how is uric acid handled in the kidney
reabsorbed in PCT then resecreted later down the tubule
around 90% reabsorbed
2 types of purine synthesis
de novo pathway (from scratch)
salvage pathway (using other molecules)
when does the de novo pathway predominate
BM - making so much DNA that it needs de novo
everywhere else its salvage as its less energy
what is the rate limiting step of purine synthesis
PAT enzyme step
why is the PAT enzyme step rate limiting
has negative feedback from other steps
another key enzyme in purine metabolism
HPRT (sometimes called HGRT)
why is HPRT important
main enzyme of salvage pathway
what is complete HPRT deficiency called
Lesch Nyhan syndrome
PC of Lesch Nyhan syndrome at birth
normal at birth
PC of Lesch Nyhan syndrome at 6 months
developmental delay
PC of Lesch Nyhan syndrome at 1 year
choreiform movements
PC of Lesch Nyhan syndrome after 1 year
spasticity
mental retardation
self mutilation (85%) - bite lips / digits
key metabolic disturbance in Lesch Nyhan syndrome
hyperuricaemia (gout)
why do you get hyperuricaemia in Lesch Nyhan syndrome
no HPRT –> no negative feedback on PAT –> increased de novo pathway action –> increased synthetic pathway action –> lots of urate production
how can disorders of hyperuricaemia be classified
increased urate production
- primary / secondary
decreased urate excretion
- primary / secondary
primary causes of increased urate production
lesch nyhan syndrome
partial HPRT deficiency
glycogen storage disorders
fructose intolerance
PRPP synthetase over activity
secondary causes of increased urate production
myeloproliferative disorders
lymphoproliferative disorders
carcinomatosis
chronic HA
Gaucher’s disease
severe psoriasis
primary causes of decreased urate excretion
FJHN
- familial juvenille hyperuricaemic nephropathy
secondary causes of decreased urate excretion
CKD
Bartter’s syndrome
Down’s
lead poisoning
thiazide diuretics
aspirin
T or F
de novo pathway predominates over salvage pathway in most tissues
F
T or F
xanthine oxidase oxidises xanthine to uric acid
T
T or F
HPRT is deficient in Lesh Nyhan syndrome
T
T or F
PAT is the rate limiting enzyme
T
what crystals are present ingout
monosodium urate crystals
needle shaped
what is acute gout called
podagra
what is chronic gout called q
tophaceous
prevalence of gout in M or F
M 3%
F 0.6%
which M / F get gout
post menopausal F or post pubertal M
what does tophaceous gout look like
creamy cottage cheese looking lumps
what are the exceptions to the rule that only post pubertal men get gout
Lesch Nyhan syndrome
familial juvenille hyperuricaemic nephropathy
what does gout look like
red, shiny skin over a lump
+++ painful
PC of acute gout
rapid build up of pain
affected joint is red, hot, swollen
what % of first site joints is the MTP
50%
in how many cases is the MTP joint involved either as first or later joint
90%
2 aims of Tx of gout
reducing inflammation
managing the hyperuricaemia
Tx of acute gout
1st NSAIDs
2nd colchicine
3rd glucocorticoids (pred)
what should you NOT try to Tx in acute gout
the plasma urate conc - can worsen precipitations of gout crystals
how do you treat the hyperuricaemia after the acute attack of gout
drink plenty of water
reverse any factors increasing the urate
allopurinol (reduce synthesis of urate)
probenecid (uricosuric - increases renal excretion)
how does allopurinol reduce synthesis of urate
xanthine oxidase inhibitor
which drug can you NOT co prescribe with allopurinol
azothioprine
why is allopurinol CI if pt is taking azothioprine
increases bone marrow toxicity
T or F
allopurinol should be used acutely
F
T or F
NSAIDS are 1st line in acute attacks
T
T or F
colchicine lowers urate levels
F
T or F
allopurinol lowers urate levels by inhibiting HPRT
F
T or F
allopurinol lowers urate levels by inhibiting xanthine oxidase
T
how is gout Dx if any clinical uncertainty
tap effusion
view under polarised light
use red filters
how does gout look under polarised light
negatively birefringent needle shaped crystals
how does pseudogout look under polarised light
positively birefringent rhomboid shaped crystals
what compound are the crystals in pseudogout
calcium pyrophosphate dihydrate
who gets pseudogout
osteoarthritis pts
prognosis of pseudogout
self limiting in 1-3 weeks
