Gout Flashcards
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)
