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Flashcards in Gout Deck (51):
1

what type of an arthritis is gout?

a crystal arthritis

2

clinical syndrome of gout

monosodium urate (MSU) crystal deposition

3

physiologic syndrome of gout

hyperuricemia

4

hyperuricemia

excess urate in the plasma that may or may not result in precipitation of uric acid crystals. >6.8 mg/dl

5

most common form of inflammatory arthritis?

gout

6

who does gout mostly affect?

middle aged men

7

why doesn't gout affect pre-menopasual women?

estrogen promotes renal uric acid excretion

8

risk factors for gout

obesity, metabolic syndrome, hypertension, insulin resistance, purine rich diet, alcohol

9

role of PRPP synthase

conversion of ribose 5P to PRPP

10

role of PRPP in gout

increased activity leads to increased PRPP (X linked mutation) that leads to increased uric acid (hyperuricemia)

11

HGPRT role

catalyzes single step salvage reaction for guanine and hypoxanthine.

12

HGPRT in gout

enzyme deficiency leads to higher levels of guanine and hypoxanthine --> hyperuricemia

13

uricase

enzyme not present in humans, catalyzes the conversion of uric acid to soluble allantion, leading to lower levels of uric acid

14

recombinant uricase used for gout treatment

pegloticase

15

xanthine oxidase role

catalyzes oxidation of hypothanxine to xanthine and xanthine to uric acid

16

xanthine oxidase in gout

inhibition decreases uric acid level

17

drugs targeting XO

allopurinol & febuxostat

18

circulating uric acid

urate anion

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limit of solubility for serum urate anions

6.8mg/dL

20

where is uric acid produced?

liver (from degradation of purine compounds)

21

sources of urate production

not direct (always from liver metabolism of purine compounds).
dietary intake, tissue nucleic acids, endogenous purine synthesis

22

urate excretion

GI (1/3) and renal (2/3)

23

URAT1 (urate/organic anion exchanger)

highly urate specific anion exchanger (organic anions) that is responsible for the reabsorption of filtered urate

24

where is URAT1?

on the luminal membrane of proximal renal tubular epithelial cells.

25

stimulation of URAT1

increased irate absorption and hyperuricemia

26

inhibition of URAT1

decreased irate absorption, hypouricemia

27

drug that inhibits URAT1 and causes more uric acid secretion in urine (uricosuria)

probenecid

28

is hyperuricemia more likely due to overproduction or under excretion?

90% underexcretion

29

causes of irate overproduction

primary and secondary hyperuricemia

30

primary hyperuricemia

inherited defects in regulation of purine nucleotide synthesis (HGPRT deficiency and PRPP synthetase super activity)

31

secondary hyperuricemia

dietary consumption, increased nucleic acid turnover (MPNs), accelerated ATP degradation

32

causes of irate underexcretion

kidney disease , medications, stimulation of URAT1

33

how does alcohol affect homeostasis of urate pool?

overproduction: increases plasma concentration of purines due to liver metabolism
underexcretion: stimulates URAT1 via increased lactic acid fro fermentation, dehydration inhibits excretion

34

pathogenesis of gout-basic version

uric acid crystals are mobilized and shed into synovial fluid, which causes a very strong inflammatory response

35

pathogenesis of gout- detailed version

crystal phagocytosis by synovial cells leads to the activation of the NALP3 inflammasome, which releases IL-1B, which binds to IL1 in synovial cells, which activates NF-kB which in turn increases secretion of cytokines that cause neutrophil activation and acute inflammation

36

IL-1B

inflammatory cytokine produced and released by NALP3 inflammasome complex

37

MSU crystals and complement

crystals can directly activate the C5b-9 complex that leads to mediator production involved in systemic symptoms like fever, high white count, etc

38

how does gout spontaneously resolve?

mediators either undergo death/deactivation/differentiation and lose inflammatory function, or up regulation of anti-inflammatory cytokines, or increased vascular permeability leads to urate transport out/increased entry of anti-inflammatory molecules

39

asymptomatic hyperuricemia

elevation of serum urate concentration in absence of signs of gout. 2/3s of hyperurimic patients

40

acute gout

acute onset, maximal severity within 12-24 hrs. severe pain, redness, swelling, disability. monoarticular

41

which joints are most commonly affected in acute gout?

hallux and knee

42

hallux involvement in gout

podagra

43

pseudogout

crystals of calcium pyrophosphate

44

chronic tophaceous gout

chronic hyperuricemia with recurrent acute flares. persistence of synovial fluid crystals with low grade inflammation. presence of tophi and erosions

45

tophi

deposits of MSU crystals. nests of crystals enveloped by granuloma like chronic inflammatory response with macrophages and multi nucleated giant cells, encased by dense connective tissue

46

urolithiasis

uric acid kidney stones. precipitation of crystals in the collecting ducts and ureters

47

acute uric acid nephropathy

uric acid precipitation within the renal tubules or interstititum. causes acute renal failure

48

synovial fluid aspirate diagnostic of gout

needle shaped, negatively birefringent (yellow=parallel, blue=perpendicular)

49

treatment for acute gout

control acute inflammation with non steroidal anti-inflammatory meds, colchicine, glucocorticoids

50

colchicine

blocks activation of NALP3 inflammasome, inhibits neutrophil activation in response to crystals

51

treatment from chronic gout

decrease uric acid levels with XO inhibitors (allopurinol), uricase (pegloticase), and URAT1 agents (probencid) or via lifestyle modification (decreased purine intake)