Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
45 Cards in this Set
- Front
- Back
|
what is the offending structure in gout?
|
monosodium urate crystals
|
|
|
why is gout exclusively a disease of humans?
|
b/c we lack uricase enzyme (seen in other animals) which breaks catabolizes uric acid (urate)
|
|
|
how is uric acid formed?
|
elimination of excess nucleic acid purines and nitrogenous waste productes
|
|
|
what is more important in the pathogenesis of hyperuricemia in gout: dietary sources of urate or endogenous overproduction?
|
endogenous overproduction
|
|
|
what is the rate-limiting rxn in urate formation? what enzyme catalyzes it? where does it occur?
|
PRPP + Glutamine --> Inosinic Acid
catalyzed bye PRPP aminotransferase primarily in the liver |
|
|
what is the defect in Lesch-Nyhan syndrome and what are the consequences?
|
HGPRTase deficiency --> no purine (really, hypoxanthine and guanine) salvage --> increased urate production
|
|
|
the biochemical hallmark of gout is __
|
hyperuricemia
|
|
|
in general terms what is primary hyperuricemia?
|
an idiopathic or inborn error of metabolism leading ONLY to hyperuricemia
|
|
|
in general terms, what is 2'ary hyperuricemia?
|
an acquired or inborn error of metabolism leading to a spectrum of diseases, one of which is gout
|
|
|
more than 95% of the pts w/ gout have __
|
primary hyperuricemia
|
|
|
T/F: In primary gout, there is a problem with renal excretion of urate
|
TRUE (but the main problem is overproduction of MSU)
|
|
|
what is the cause of saturnine gout?
|
lead nephropathy in "moonshine" drinkers leads to decreased urate excretion
|
|
|
what molecules compete w/ urate for secretion along the nephron with overingestion leading to hyperuricemia?
|
lactate (metabolic acidosis)
ketogenic acids (ketosis) salicylate ingestion |
|
|
after filtration in the glomerulus, how is urate resorbed?
|
by active transport, primarily in the proximal tubule
|
|
|
why are synovial joints a site of crystal formation?
|
uric acid becomes less soluble with:
lower body temps repetitive trauma increased or decreased hydrostatic pressure rapid change in serum concentration |
|
|
describe the acute inflammatory cascade in gout.
|
1. MSU crystals precipitate in joint
2. IgG binds to crystals 3. Complement binds to crystals or are activated by inflammatory response --> amplifier 4. PMNs bind to crystals via Fc receptor of immunoglobulin 5. PMNs phagocytize crystals |
|
|
what happens after PMNs phagocytize the MSU crystals?
|
there is lysosomal mediated cell rupture, or the actual crystal pierces the membrane leading to spilling of the PMN cytoplasmic contents into the synovial fluid which amplifies the inflammatory response
|
|
|
what is crystal chemotactic factor?
|
a glycopeptide released from PMNs after exposure to MSU crystals --> attracts other PMNs to the synovial fluid
|
|
|
what is podagra?
|
gout of the first MTP joint
|
|
|
what is the typical presentation of gout?
|
severe monoarticular arthritis lasting days to weeks
|
|
|
T/F: Actue gout can be precipitated by physical stress
|
TRUE
|
|
|
how do you dx gout?
|
observing negatively birefringent (yellow crystals), needle-shaped MSU crystals engulfed by PMNs in a synovial fluid aspirate
|
|
|
what is the major extraarticular manifestation of gout?
|
nephrolithiasis
|
|
|
what are some common chronic diseases assoc w/ gout?
|
EtOHism
obesity HTN CAD hypertriglyceridemia |
|
|
T/F: Extracellular MSU crystals seen in a joint aspirate are diagnostic of gout
|
FALSE
|
|
|
T/F: elevated serum uric acid is pivotal in the diagnosis of gout
|
FALSE. It is of little value.
|
|
|
what are some supportive lab studies seen in gout?
|
CBC (left shift to PMNs)
ESR CRP |
|
|
what are typical ranges of WBC counts in synovial aspirates in gout?
|
20-80K
can mimic septic arthritis |
|
|
what are tophi?
|
cystalline deposits of urate (chalk-like)
|
|
|
how do tophi appear on x-ray?
|
radiolucent
|
|
|
what is the treatment of acute gout?
|
rest
ice NSAIDs oral corticosteroid COLCHICINE intraarticular aspiration/steroid injection |
|
|
in reality is ice used to treat acute gout?
|
no, b/c they can't stand pressure or moving the joint
|
|
|
what is the MOA of colchicine?
|
Inhibits PMN microtubular function and migration
|
|
|
what is the MOA of probenecid?
|
inhibits reabsorption of uric acid in the PCT
|
|
|
for whom is probenecid contraindicated?
|
pts w/ hx of renal stones or elevated urinary urate excretion rates b/c probenecid may promote stone formation
|
|
|
how does allopurinol block purine degradation?
|
it inhibits xanthine oxidase and blocks purine degradation at RLS.
|
|
|
what is pseudogout?
|
acute arthritis caused by calcium pyrophosphate deposition disease (CPPD) crystal induced inflammation
|
|
|
if you see pseudogout in a pt < 50, what should you do?
|
look for assoc disease such as:
hyperPTH hypothyroidism hemochromatosis ochronosis (pigmented cartilage from alkaptonuria) gout |
|
|
how do you dx pseudogout?
|
rhomboid crystals that are weakly-postively birefringent (blue) engulfed by PMNs
|
|
|
T/F: attacks of pseudogout are slower in onset and not as severe as gout
|
TRUE
|
|
|
what joints are commonly affected by pseudogout?
|
knee, wrist, elbow, shoulder, pubic symphysis
|
|
|
what is an x-ray finding in severe pseudogout?
|
chondrocalcinosis (linear or punctate radiodensities in the cartilage of tendons and ligaments)
Basically mineralization of fibrocartilage and articular cartilage (like meniscus) |
|
|
how do you Rx pseudogout?
|
joint aspiration and NSAIDs
|
|
|
gout-like clinical pattern, periarticular calcium on radiograph, absence of other arthritic causes and observation of purple rounded inclusions in PMNs -->
|
apatite arthritis
|
|
|
how can you distinguish corticosteroid arithritis flare from iatrogeneic infection?
|
steroid flare will occur in hours, the infection won't manifest for a few days
|
