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20 Cards in this Set
- Front
- Back
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What is hyperuricemia?
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plasma monosodium urate concentration higher than 7 mg/dL (men) or 6 mg/dL (women)
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What is gout?
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both genes and environment factors (obesity and hypertension) contribute to precipitation of monosodium urate in synovial joints, typically manifests late in life
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What is the term for monosodium urate crystals?
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tophi
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What happens to urate crystals (tophi) after their are deposited on articular cartilage?
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neutrophils and macrophages phagocytize the crystals → cell lysis → inflammatory response and release of lysosomal enzymes → joint damage
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What is the major source of nucleotides in the American diet?
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meat
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Which is more soluble, urate or uric acid? What influences the solubility?
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urate is more soluble than uric acid, dependent on the concentration of urate and sodium (more sodium → less soluble) and on temperature (higher temp. → more soluble)
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What are the upsides and downsides to urate?
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limited solubility and excretion, but it is an antioxidant
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How is 98% of filtered urate reabsorbed into the blood (from the PCT of the nephron)?
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urate anion transporter
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How are organic anions, including 50% of the filtered urate, returned to the lumen of the PCT of the nephron?
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organic anion pump
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Overall, what percentage of total urate is excreted in urine?
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8-12%
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What happens to urate in the blood when there is an increase in organic acids, such as lactate, keton bodies, aspirin, etc?
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the organic anion pump operates near Vmax, an increase in organic acids results in an accumulation of urate in the serum due to competetive inhibition
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Which is least soluble in urine, urate or uric acid?
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uric acid
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Which compound is more commonly found in kidney stones, urate or uric acid?
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uric acid
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What is the cause of primary gout?
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increased production of uric acid
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What is the cause of secondary gout?
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decreased renal excretion of urate
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What are causes of hyperuricemia gout?
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decreased efficiency of purine salvage (HGPRT), overactive PRPP synthetase, increased purine degradation, increased cell death
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What is Lesch-Nyhan syndrome?
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<1% HGPRT function, genetic disorder, results in premature gout, kidney stones, low IQ, cerebral palsy, self mutilation
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How does overactive PRPP synthetase cause hyperuricemia?
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increased production of purines = increased degradation (salvage only recycles 90%)
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What is tumor lysis syndrome?
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group of metabolic complications (hyperuricemia, renal failure) that can occur after treatment of cancer, caused by the breakdown of products of dying cancer cells
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How is gout treated?
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Allopurinol (suicide inhibitor) - xanthine oxidase converts xanthine (in allopurinol) to alloxanthine (xanthine oxidase inhibitor
Rasburicase - prevents tumor lysis syndrome Febuxostat - non-purine inhibitor of xanthine oxidase |
