Hyperuricaemia and Gout

Question 1

What is Urate?

Answer 1

salt of Uric acid

with the nitrogenous base belonging to the group of purines

Question 2

How is Urate produced?

Answer 2

Uric acid is the end product of purine metabolism in primates
Other purines: Caffine, adenine

Question 3

How is Uric acid excreted?

Answer 3

Through the urine

Low concentration in plasma normally

Question 4

What 4 sources make the pool of purine nucleotides?

Answer 4

Dietary Purine
Breakdown of tissue nucleotides (Tumour lysis syndrome)
Salvage pathway (HGPRT deficiency)
Endogenous synthesis (Phosphoribosyl pyrophosphate=PRPP)

Question 5

what is the pathway of pool of purine nucleotides?

Answer 5

Pool of purine nucleotides—>Free purines—>Uric acid—>Renal failure

Question 6

What level of uric acid is hyperuricaemia?

Answer 6

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

Question 7

How do we diagnose Gout?

Answer 7

Physical exam (PE)
Medical history (Hx)
Synovial fluid aspiration
X ray
Blood test

Question 8

Aetiology of gout

Answer 8

Urate crystals inside joints causing problems at the extremeties
Macrophages attach crystals but cannot dissolve them
Result:Inflamed and painful joints

Question 9

4 gout stages?

Answer 9

1. High uric acid- No symptoms
2. Acute flares
3. Intercritical periods
4. Advanced gout-Chronic Arthritis

Question 10

Where are purines in the diet come from?

Answer 10

The breakdown of ingested nucleic acids

Question 11

Where does purine synthesis occur?

Answer 11

Mainly in the liver

Question 12

What occurs in the Salvage pathway for a source of purines?

Answer 12

In the salvage pathway it reuses free purine bases
2 main enzymes used:
Adenine phosphoribosyltransferase
Hypoxanthinie Guanine phosphoribosyltransferase (HGPRT)

Question 13

Purines are used for:

Answer 13

Nucleic acid synthesis
Metabolic reactions
Purines oxidised to uric acid (urate), firstly transfered to xanthinine then transformed to uric acid

Question 14

Where does the uric acid go?

Answer 14

to kidneys,3/4 excreted.
also to gastrointestinal gut, metabolised by bacteria (uricolysis) due to lacking the enzyme uricase (breaks down uric acid)

Question 15

What is Lesh Nyhan Syndrome?

Answer 15

x linked recessive disorder
Increased synthesis of purine nucleotides
leading to gout and Hyperuricaemia

Question 16

What is Von Gierke’s disease?

Answer 16

Accumulation of G6P

Which is transformed into ribose 5 phophate, promoting gout

Question 17

What other conditions can lead to Hyperuricaemia?

Answer 17

Associated with the overproduction of cells:

• Lymphoma
• Other solid tumours
• Cytotoxic tumours
• Alcohol (lactate build up)
• Aspirin (inhibits renal secretion)

Question 18

where does 75% of urate travel to?

Answer 18

kidney

Question 19

Using drugs can cause what secretion?

Answer 19

Renal and tubular secretion

Question 20

Reduced renal clearance of urate can be due to?

Answer 20

Volume depletion (not drinking enough)
Diuretics
Low doses of salicylates (reduces distal tuble secretion)

Question 21

Gout therapies?

Answer 21

1.Anti inflammatory drugs (NSAIDs)
2.Increased renal clearance (probenccid)
3.Xanthine oxidase inhibitor (Allopurinal)
Major factor is renal clearance by kidney

Question 22

What does renal failure cause?

Answer 22

Renal stones

raised plasma urate