Flashcards in Hyperuricaemia and Gout Deck (22):
What is Urate?
salt of Uric acid
with the nitrogenous base belonging to the group of purines
How is Urate produced?
Uric acid is the end product of purine metabolism in primates
Other purines: Caffine, adenine
How is Uric acid excreted?
Through the urine
Low concentration in plasma normally
What 4 sources make the pool of purine nucleotides?
Breakdown of tissue nucleotides (Tumour lysis syndrome)
Salvage pathway (HGPRT deficiency)
Endogenous synthesis (Phosphoribosyl pyrophosphate=PRPP)
what is the pathway of pool of purine nucleotides?
Pool of purine nucleotides--->Free purines--->Uric acid--->Renal failure
What level of uric acid is hyperuricaemia?
It has to be greater than 0.38nm
caused by an overproduction of uric acid
or under secretion of uric acid
no gout without crystal depostition
silent without disease
How do we diagnose Gout?
Physical exam (PE)
Medical history (Hx)
Synovial fluid aspiration
Aetiology of gout
Urate crystals inside joints causing problems at the extremeties
Macrophages attach crystals but cannot dissolve them
Result:Inflamed and painful joints
4 gout stages?
1.High uric acid- No symptoms
4.Advanced gout-Chronic Arthritis
Where are purines in the diet come from?
The breakdown of ingested nucleic acids
Where does purine synthesis occur?
Mainly in the liver
What occurs in the Salvage pathway for a source of purines?
In the salvage pathway it reuses free purine bases
2 main enzymes used:
Hypoxanthinie Guanine phosphoribosyltransferase (HGPRT)
Purines are used for:
Nucleic acid synthesis
Purines oxidised to uric acid (urate), firstly transfered to xanthinine then transformed to uric acid
Where does the uric acid go?
to kidneys,3/4 excreted.
also to gastrointestinal gut, metabolised by bacteria (uricolysis) due to lacking the enzyme uricase (breaks down uric acid)
What is Lesh Nyhan Syndrome?
x linked recessive disorder
Increased synthesis of purine nucleotides
leading to gout and Hyperuricaemia
What is Von Gierke's disease?
Accumulation of G6P
Which is transformed into ribose 5 phophate, promoting gout
What other conditions can lead to Hyperuricaemia?
Associated with the overproduction of cells:
-Other solid tumours
- Cytotoxic tumours
-Alcohol (lactate build up)
-Aspirin (inhibits renal secretion)
where does 75% of urate travel to?
Using drugs can cause what secretion?
Renal and tubular secretion
Reduced renal clearance of urate can be due to?
Volume depletion (not drinking enough)
Low doses of salicylates (reduces distal tuble secretion)
1.Anti inflammatory drugs (NSAIDs)
2.Increased renal clearance (probenccid)
3.Xanthine oxidase inhibitor (Allopurinal)
Major factor is renal clearance by kidney