Term
| What is the difference between gout and hyperuricemia? |
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Definition
| Hyperuricemia is elevated uric acid in the blood, while gout is the actual deposition of uric acid crystals, usually due to purine metabolism |
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Term
| What are the major clinical manifestations of gout? |
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Definition
- recurrent acute arthitic attacks
- destructive crystals in the joints (TOPHI)
- uric acid stones - urolithiasis
- renal impairment - gouty nephropathy |
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Term
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Definition
Gout in the big toe, first place inflammation is seen.
Crystals deposit at plasma levels >7%. Less soluble at low temp, lower pH. |
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Term
| What is urate load derived from? |
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Definition
guanylic acid (GMP)
inosinic acid (IMP)
adenylic acid (AMP)
Lack uricase to easily excrete uric acid.
At the end of the day, gout is an inborn error of purine metabolism
Important enzymes: PRPP synthetase/aminotransferase, Xanthine oxidase, HGPRT |
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Term
| How is uric acid handled in the proximal tubules? |
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Definition
Both secreted and reabsorbed in the proximal tubule
Urate is reabsorbed in exchange for lactate |
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Term
| What are inborn causes of gout? |
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Definition
- Increased production caused by: increased PRPP synthetase, decreased HGPRT (salvage), excess intake from food and alcohol
- Decreased excretion due to a secretary disorder, HTN, renal failure. Decreased secretion = increased plasma levels
- If salvage pathways are inhibited, everything is converted to uric acid |
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Term
| What is the direct phase/cellular phase of gout? |
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Definition
- Monocytes recognize urate crystals --> phagocytosis. Inflammasome activation --> release of IL-1. IL-1 releases other cytokines and chemokines through NFkB
- Migration of neutrophils --> engulfs crystals --> lysosomal cell tell |
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Term
| What is indirect phase/humoral phase of gout? |
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Definition
- urate crystals activate classical or alternative complement
- C3a and C5a act as chemotactic factors --> neutrophil attraction.
- Kinin system activation --> formation of bradykinin leads to pain and inflammation |
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Term
| What cells are the most important in gout? |
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Definition
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Term
| What drugs are used for the acute treatment of gout? |
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Definition
- NSAIDs - PG inhibitors, stop neutrophils
- Colchicine - irreversible inhibitor of tubulin in the PMN. Decreases neutrophil movement and IL-1. Neutrophils and PMN cannot merge. GI side effects.
- Steroids |
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Term
| What is the site of action of Probenacid/Benemid? |
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Definition
Uricosuric agent - Blocks both sites of reabsorption in the proximal tubule. Few side effects, but drugs that block secretion interact w/ probenecid (ASA, penicillin, diuretics)
Can cause preciptiation out of tissues --> acute attach. Often given WITH colchicine for this reason. |
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Term
| What drugs are xanthine oxidase inhibitors? |
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Definition
| Inhibit Xanthine oxidase, one of the final steps in the conversion to uric acid. Leads to feedback inhibition. |
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Term
| How does Allopurinol work? |
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Definition
| Allopurinol is a hypoxanthine analog, competitively inhibits xanthine oxidase --> oxipurinol (metabolite, long half life). Excretion is renal. |
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Term
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Definition
| Uloric/febuxostat - non-purine. More potent, liver metabolism. Less toxic than allopurinol, but more expensive. |
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