uric acid metabolism

Question 1

what are purines?

Answer 1

nitrogenous bases in DNA and RNA
-adenosine, guanosine, inosine

Question 2

what does HPRT do?

Answer 2

-involved in purine salvage pathway to convert hypoxanthine and guanine into nucleotides

Question 3

explain purine catabolism pathway?

Answer 3

xanthine oxidase converts hypoxanthine to xanthine and xanthine to uric acid

Question 4

is urate soluble

Answer 4

relatively insoluble and always on the brink of forming crystals

Question 5

what happens to uric acid in kidney

Answer 5

most reabsorbed in PCT

Question 6

what is fractional exretion of uric acid?

Answer 6

10% - uric acid blood level kept high

Question 8

how are purines produced

Answer 8

-de novo synthesis (bone marrow)
-salvage pathway (recyled from existing purine bases using HPRT -less energy intensive)

Question 9

what happens in Lesch-Nyhan syndrome?

Answer 9

-HPRT deficiency thus cant use salvage pathway so de novo pathway goes into overdrive and produces bare uric acid as a result
-X-linked recessive

Question 10

features of Lesch-nyhan?

Answer 10

-hyperuricaemia
-developmental delay
-gouty arthritis
-self-mutilation

Question 11

how are causes of hyperuricaemia divided

Answer 11

1) increased urate production
2) decreased urate excretion

Question 12

causes of decreased urate excretion?

Answer 12

-renal failure
-barters syndrome
-lead poisoning
-thiazides

Question 13

causes of increased urate production?

Answer 13

-dietary intake
-genetic disorders
-cell turnover (TLS)

Question 14

what crystals found in gout

Answer 14

monosodium urate

Question 15

what are acute and chronic gout called respectively

Answer 15

acute = podagra
chronic = tophaceous

Question 16

epidemiology of gout?

Answer 16

males > females
common in postpubertal men and post-menopausal women

Question 17

pathology of gout

Answer 17

precipitation of crystals due to solubility dropping forming needle shaped crystals that launch inflammatory attack of neutrophils & macrophages at joint

Question 18

what are tophi?

Answer 18

deposition of urate cyrstals on skin or joint (yellow)

Question 19

what joint affected in acute gout

Answer 19

1st MTP - big toe

Question 20

what shouldnt be done in acute gout

Answer 20

dont lower urate levels - this can precipitate attack

Question 21

management of acute gout?

Answer 21

-NSAIDs (1st line)
-colchicine
-glucocorticoids

Question 22

mechanism of colchicine

Answer 22

inhibits microtubule assembly needed for motility of neutrophils

Question 23

management of chronic gout?

Answer 23

-manage hydration & risk factors
-allopurinol
-procenocid (uric acid excretion increased)

Question 24

mechanism of allopurinol?

Answer 24

xanthine oxidase inhibotor

Question 25

side effects allopurinol

Answer 25

-bone marrow suppresion
-GI
allergic rxns
hepatotoxicity

Question 26

what does allopurinol interact with

Answer 26

azathioprine
mercaptopurine

Question 27

gout under polarised light

Answer 27

negatively birefringent needle shaped crystals (blue perpendicular to compensator filter axis)

Question 28

pseudogout under polarised light

Answer 28

positively birefringent rhomboid shaped crystals

Question 29

who does pseudogout present in

Answer 29

osteoarthritis patients (chondrocalcinosis)

Question 30

crystals in pseudogout

Answer 30

calcium pyrophosphate

Question 31

joints affected in pseudogout

Answer 31

all over. commonly knee