Gout Flashcards
(39 cards)
What is gout
Result of increased uric acid in the blood and results in deposition of monosodium urate crystals in the synovial fluid or tissue, including the kidneys
Uricase, which convers uric acid to the more soluble allantoin, is absent in humans (but can be given when you are expecting increased purine degradation, as in chemo)
synoviocytes uptake urate crystals and release PGs, lysosomal enzymes, and IL-1, attracting neutrophils and macrophages and causing inflammation
What is defined as hyperuricemia?
Serum urate > or equal to 6.8 mg/dL
What factors are associated with increased serum urate concentrations?
primary (overproduction or underexcretion of uric acid):
Age
Serum creatinine/BUN
male gender
blood pressure
body weight (urate production correlates with surface area)
alcohol intake (increases purine catabolism in the liver)(lactic acid increases and competes with uric acid for excretion by kidneys)
certain foods (meat)
When does incidence of gout for men and women equal out?
After women reach menopause, their uric acid levels increase. 50% of new cases in older age groups are in women
What is the pathway from guanylic acid and adenylic acid to monosodium urate?
purine degredation pathway
guanylic acid, adenylic acid –> inosinic acid –purine nucleoside phosphoylase–> hypoxanthine –xanthine oxidase–> xanthine –xanthine oxidase–> uric acid –high concentration–> monosodium urate crystals
what is the purine salvage pathway?
hypoxanthine-guanine phosphoribosyltransferase converts hypoxanthine + PRPP (phosphoribosyl pyrophosphate) –> GMP, IMP, AMP
decreased HGPRTase results in increased hypoxanthine oxidation to uric acid
secondary gout
uric acid increases due to cell death and lysis, resulting in release of nucleic acid:
chemotherapeutic agents
myelo- and lymphoproliferative disorders
polycythemia vera and anemia
psoriasis
How is uric acid excreted?
2/3 daily production is excreted in kidneys
1/3 eliminated through GI tract by enzyme degradation
90% of filtered uric acid is reabsorbed in the proximal and distal tubules (enhanced by conditions which enhance sodium reabsorption, such as dehydration)
how to determine if someone is an overproducer of uric acid?
measure urine uric acid over 24 hours
>1000mg excretion on regular diet = overproducer
how to determine if someone is an underexcretor of uric acid?
purine free diet for 3-5 days
measure urine uric acid over 24 hours
What are some drugs that can induce hyperuricemia?
diuretics (thiazides and loops) nicotinic acid salicylates ethanol cyclosporine pyrazinamide levodopa ethambutol cytotoxic drugs urate lowering therapies
What is the clinical presentation of gout?
Rapid and localized onset of excruciating pain and inflammation, with peak severity within 12-24 hours
Untreated attacks can last from 3-14 days
Fever, intense pain, erythema, warmth, swelling, and inflammation
First metatarsophalangeal joint involvement = podagra
Asymptomatic between attacks
What are tophi?
monosodium urate crystals that deposit in cartilage, tendons, synovial membranes, and elsewhere
can result in bone destruction
why is gout common in the lower joints?
lower temperature within those joints, and high intraarticular urate concentration (synovial effusions are likely in weight bearing joints during the day, but at night the water is reabsorbed from the joint leaving behind supersaturated monosodium urate)
how is gout diagnosed?
gold standard - visualization of urate crystals from the joint or tophi through aspiration
acceptable - clinical diagnosis through Sx (pain, swelling, erythema, big toe involvement, monoarticular, inflammation within one day, asx between episodes, hyperuricemia, tophi, joint damage on xray)
long term complications of gout?
uric acid nephrolithiasis (uric acid less soluble in acidic urine w/pH acute renal failure –> common with ALL, CLL, CML patients
chronic - long term deposition of crystals within renal sys –> proteinuria –> common with HTN, DM, atherosclerosis
tophaceous gout - joint destruction, pain, and nerve compression syndrome
Explain why probenicid may precipitate an acute attack of gout
probenicid needs to get into the tubule before it can compete with uric acid for reabsorption at the uric acid transporter (URAT-1); probenicid enters the tubule through organic acid transporter (OAT1,3) where it competes with uric acid; may cause a short term increase in uric acid serum concentration bc it is unable to be excreted properly
Explain why thiazide diuretics may precipitate an acute attack of gout
thiazides interfere with uric acid excretion and thereby increases the serum uric acid
Explain why aspirin may precipitate an acute attack of gout
low dose aspirin (+nicotinic acid) is secreted by OAT wth uric acid, leading to an increase in uric acid conc and gout attack
high dose aspirin is filtered by the glomerulus and competes with uric acid at URAT, leading to increased uric acid excretion
Lifestyle adjustments for people with symptomatic gout and asymptomatic hyperuricemia
Reduce dietary purines: meat, seafood, alcohol, cheese
Reduce fructose-containing products: energy drinks, soft drinks
Increase: fluid intake to reduce risk of nephrolithiasis
Increase: consumption of low-fat or nonfat dairy products
Rest joint for 1-2 days and avoid heat
Encourage weight loss
colchicine
alkaloid from crocus plant
immunosuppressant
relieves pain and inflammation
binds and stabilizes tubulin to inhibit microtubule polymerization, impairing neutrophil chemotaxis and degranulation and phagocytosis; also inhibits the synthesis of LTB4
GI side effects (diarrhea), bone marrow suppression (aplastic anemia, thrombocytopenia), neuromuscular toxicity (myopathy, rhabodmyolysis)
Metabolism by CYP3A4, renal excretion
NSAIDS (indomethacin; not aspirin)
inhibit PG synthesis
inhibit urate crystal phagocytosis
less toxic than colchicine
oxaprozin
increases urate excretion in urine
corticosteroids
oral prednisone or intra-articular triamcinolone
