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What is hyperuricemia?
Increased levels of MSU (monosodium urate)
How is MSU stored in cells?
What is the main cause of gout?
High MSU in the blood caused by increased intake of purines from meat and seafood
What is the pKa of uric acid?
Which is more polar and soluble, urate or uric acid?
What is the max concentration for uric acid?
What is the max concentration for MSU?
What are the two factors that determine the solubility of urate?
- 1) Temperature (lower temp = precipitate)
- 2) concentration (>Ksp = precipitate)
Where do the majority of urate crystals (tophi) deposit and why?
The feet because of the lower temperature
What is the downside and upside or uric acid?
- Down = low solubility and low excretion
- Up = antioxidant, help with cancer
When excreted, where does the MSU leave?
Does MSU participate in the formation of kidney stones?
No, but uric acid does
What is the best pH for someone at rish for uric acid stones?
Alkaline = more urate for solubility
What should a patient do to reduce possible kidney stones?
Drink fruit juice
What is primary gout?
Increased uric acid production (from purine degradation)
What is secondary gout?
decreased excretion of urate
What are the four main causes of increased uric acid production?
- 1) Lack of HGPRT or inhibition of HGPRT (he's got purine recycling trouble)
- 2) Overactive PRPP synthetase
- 3) increased purine degradation (AMP accumulation especially)
- 4) increased cell death
What syndrome is caused when HGPRT is below 1% normal levels?
How does Allopurinol resolve primary gout?
Causes xanthine oxidase to convert allopurinol to an inhibitor of xanthine oxidase so hypoxanthine and xanthine can be excreted instead of converted into uric acid
How does Rasburicase help with Tumor lysis syndrome?
It is a urate oxidase that converts uric acid to soluble form
How does pegloticase help tumor lysis syndrome?
Increased half-life over rasburicase
How does febuxostat function?
- non-purinol inhibitor of xanthine oxidase
- more effective than allopurinol but more expensive
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