Gout Flashcards
What is uric acid?
-biologically active end product of human purine metabolism
Serum urate conc. determined by?
-balance between urate production and elimination; hyperuricemia results from urate overproduction, urate underexcretion, or a combination of both
Specific organic anion transporters (OATs)?
-identified as playing a central role in the excretion of urate by the kidney
Hyperuricemia?
-serum urate levels greater than 6.8mg/dL, the limit of its solubility in serum
Gout pathogenesis
-requires the accumulation of monosodium urate at levels sufficient to drive the precipitation of crystals, resulting in the initiation of an inflammatory response
Monosodium urate crystals activate what?
NLRP3 (NALP3) inflammasome, a multimolecular cytosolic complex that processes and generates interleukin-1β (IL-1β), IL-18, and IL-33
What does the initiation of gouty inflammation by local white blood cells do?
-induces an influx of neutrophils into the joint; when these neutrophils encounter urate crystals, they become activated and propagate further inflammation
Low level inflammation?
-present in chronic gout and tophaceous gout; macrophages continue to produce cytokines and proteases, thereby facilitating cartilage and bone destruction
Treat acute gout?
-nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, corticosteroids, or adrenocorticotropic hormone. The effectiveness of treatment depends more on how quickly the therapy is initiated than which agent is used
Before starting a urate-lowering agent, a patient should?
be treated with low-dose colchicine or an NSAID in an attempt to prevent further attacks
Patient should take lowest does to keep urate level below?
6.8mg/dL - preferably below 6mg/dL
Urate-lowering agents?
allopurinol, febuxostat, pegloticase
Hyperuricemic individuals should be screened for?
- HTN
- CAD
- diabetes
- obesity
- alcoholism
- these conditions should be managed in patients with asymptomatic gout
Gout: epidemiology
- hyperuricemia is common, and directly associated with serum creatinie, BMI, age, bp, alcohol
- low in childhood, increase in men at puberty and women at menopause
- prevalence (1-15%) with increase in recent years
- due to Western diet and obesity
Gout: environmental factors
-alcohol consumption (beer)
-red meat
-seafood
Proactive foods: milk, yogurt
Gout: Genetics
- rare forms of early hyperuricemia and gout have genetic/metabolic basis
- runs in families, inherited factors factors affecting serum urate levels through renal urate clearance
- Recent genome-wide association studies have identified polymorphisms in several candidate genes encoding urate transporters in the renal proximal tubules as determinants of serum urate levels and the risk of gout
3 stages of gout?
asymptomatic hyperuricemia
acute and intercritical gout
and chronic gouty arthritis
Asymptomatic Hyperuricemia
-lasts up to to 20 years before the initial attack of gout or nephrolithiasis
First gout attach occurs?
-at age 40 to 60 in men and after age 60 in women
Drugs that raise serum urate levels and predispose to gout?
diuretics
Most attacks of gout, especially early in the course, are?
-monoarticular, with a predilection for the first metatarsophalangeal joint (podagra) and have a characteristic abrupt and painful onset
DDX for gout?
infectious arthritis or other crystal-induced synovitis, particularly pseudogout
How to diagnose acute and chronic gout?
ultrasonography
Untreated Gout?
-characterized by the development of tophi and progressive joint damage
Conditions associated with gout?
- obesity, hypertriglyceridemia, glucose intolerance and the metabolic syndrome, hypertension, atherosclerosis, and hypothyroidism
- renal insufficiency
- Hyperuricemia is a common cause of nephrolithiasis, and rarely, chronic hyperuricemia may cause urate nephropathy and acute hyperuricemia may lead to uric acid nephropathy in the tumor lysis syndrome
- Alcohol use, lead intoxication, and cyclosporine treatment
Primary Hyperuricemia and gout
-caused by decreased renal uric acid excretion in more than 90% and overproduction of urate in less than 10% of affected patients
Secondary Hyperuricemia and gout
- usually related to decreased renal urate clearance as a direct or indirect consequence of the primary disease process
- Four known specific inborn errors of purine metabolism with overproduction of urate account for less than 1% of cases of secondary hyperuricemia and gout
Is asymptomatic hyperuricemia treated?
usually no
-but search for cause/associated conditions
Treat episodes of acute gouty arthritis?
-with colchicine, NSAIDs, adrenocorticotropic hormone, and systemic or intra-articular steroids
Prophylaxis against acute gout attacks?
-colchicine or NSAIDs can be effective but does not change the underlying process in the absence of concomitant urate-lowering therapy
Lowering serum urate levels?
-Xanthine oxidase inhibitors and uricosurics
Urate lowering therapy after single attack?
debatable
refractory tophaceous gout treatment?
Uricases such as pegloticase
Targeted serum urate level?
<6mg/dL
Prophylixas for gout at least 6 months after urate lowering drugs using?
colchicine, NSAIDs, or less preferably, systemic steroids
Major issue with patients who have gout?
Long-term compliance with the treatment regimen
Lifestyle/management of what to help with gout?
- decrease alcohol
- manage obesity and hyperlipidemia
