Gout

Question 1

What is uric acid?

Answer 1

-biologically active end product of human purine metabolism

Question 2

Serum urate conc. determined by?

Answer 2

-balance between urate production and elimination; hyperuricemia results from urate overproduction, urate underexcretion, or a combination of both

Question 3

Specific organic anion transporters (OATs)?

Answer 3

-identified as playing a central role in the excretion of urate by the kidney

Question 4

Hyperuricemia?

Answer 4

-serum urate levels greater than 6.8mg/dL, the limit of its solubility in serum

Question 5

Gout pathogenesis

Answer 5

-requires the accumulation of monosodium urate at levels sufficient to drive the precipitation of crystals, resulting in the initiation of an inflammatory response

Question 6

Monosodium urate crystals activate what?

Answer 6

NLRP3 (NALP3) inflammasome, a multimolecular cytosolic complex that processes and generates interleukin-1β (IL-1β), IL-18, and IL-33

Question 7

What does the initiation of gouty inflammation by local white blood cells do?

Answer 7

-induces an influx of neutrophils into the joint; when these neutrophils encounter urate crystals, they become activated and propagate further inflammation

Question 8

Low level inflammation?

Answer 8

-present in chronic gout and tophaceous gout; macrophages continue to produce cytokines and proteases, thereby facilitating cartilage and bone destruction

Question 9

Treat acute gout?

Answer 9

-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

Question 10

Before starting a urate-lowering agent, a patient should?

Answer 10

be treated with low-dose colchicine or an NSAID in an attempt to prevent further attacks

Question 11

Patient should take lowest does to keep urate level below?

Answer 11

6.8mg/dL - preferably below 6mg/dL

Question 12

Urate-lowering agents?

Answer 12

allopurinol, febuxostat, pegloticase

Question 13

Hyperuricemic individuals should be screened for?

Answer 13

• HTN
• CAD
• diabetes
• obesity
• alcoholism
• these conditions should be managed in patients with asymptomatic gout

Question 14

Gout: epidemiology

Answer 14

• 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

Question 15

Gout: environmental factors

Answer 15

-alcohol consumption (beer)
-red meat
-seafood
Proactive foods: milk, yogurt

Question 16

Gout: Genetics

Answer 16

• 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

Question 17

3 stages of gout?

Answer 17

asymptomatic hyperuricemia
acute and intercritical gout
and chronic gouty arthritis

Question 18

Asymptomatic Hyperuricemia

Answer 18

-lasts up to to 20 years before the initial attack of gout or nephrolithiasis

Question 19

First gout attach occurs?

Answer 19

-at age 40 to 60 in men and after age 60 in women

Question 20

Drugs that raise serum urate levels and predispose to gout?

Answer 20

diuretics

Question 21

Most attacks of gout, especially early in the course, are?

Answer 21

-monoarticular, with a predilection for the first metatarsophalangeal joint (podagra) and have a characteristic abrupt and painful onset

Question 22

DDX for gout?

Answer 22

infectious arthritis or other crystal-induced synovitis, particularly pseudogout

Question 23

How to diagnose acute and chronic gout?

Answer 23

ultrasonography

Question 24

Untreated Gout?

Answer 24

-characterized by the development of tophi and progressive joint damage

Question 25

Conditions associated with gout?

Answer 25

- 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

Question 26

Primary Hyperuricemia and gout

Answer 26

-caused by decreased renal uric acid excretion in more than 90% and overproduction of urate in less than 10% of affected patients

Question 27

Secondary Hyperuricemia and gout

Answer 27

- 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

Question 28

Is asymptomatic hyperuricemia treated?

Answer 28

usually no | -but search for cause/associated conditions

Question 29

Treat episodes of acute gouty arthritis?

Answer 29

-with colchicine, NSAIDs, adrenocorticotropic hormone, and systemic or intra-articular steroids

Question 30

Prophylaxis against acute gout attacks?

Answer 30

-colchicine or NSAIDs can be effective but does not change the underlying process in the absence of concomitant urate-lowering therapy

Question 31

Lowering serum urate levels?

Answer 31

-Xanthine oxidase inhibitors and uricosurics

Question 32

Urate lowering therapy after single attack?

Answer 32

debatable

Question 33

refractory tophaceous gout treatment?

Answer 33

Uricases such as pegloticase

Question 34

Targeted serum urate level?

Answer 34

<6mg/dL

Question 35

Prophylixas for gout at least 6 months after urate lowering drugs using?

Answer 35

colchicine, NSAIDs, or less preferably, systemic steroids

Question 36

Major issue with patients who have gout?

Answer 36

Long-term compliance with the treatment regimen

Question 37

Lifestyle/management of what to help with gout?

Answer 37

- decrease alcohol | - manage obesity and hyperlipidemia