Gout

Question 1

Define uric acid

Answer 1

bio active end product of human purine metabolism

Question 2

How is gout caused? and levels?

Answer 2

hyperuricemia w/ greater than 6.8mg/dL in serum=> combination or single faulty one

1) urate overproduction
2) urate underexcretion

Question 3

What plays a key role in urate excretion?

Answer 3

OATs play central role in excretion of urate by kidney

Question 4

How does gout cause an inflammatory response?

Answer 4

accumulation of monosodium urate at levels to cause precipitation of crystals resulting in a response

Question 5

How does monosodium urate crystals lead to the inflammatory response?

Answer 5

activates NLRP3 inflammasome that processes and generates IL-1B, IL-18 and IL-33

Question 6

Once gouty inflammation is present, how does it proceed?

Answer 6

local WBCs induces influx of neutrophils into joint that are activated by urate crystals causing more inflammation

Question 7

Describe chronic and tophaceous gout

Answer 7

low level inflammation allows macrophages to continue to produce cytokines and proteases leading to more cartilage and bone destruction

Question 8

What transporter is most important in resorption of urate from proximal tubule ultrafiltrate?

Answer 8

URAT1

Question 9

What transporter is most important in secretion?

Answer 9

OAT1 and OAT3 move urate from interstitium to epithelial cell interior

Question 10

What diseases are associated with underexcretion of urate?

Answer 10

renal insufficiency;
dehyrdration/volume depletion;
lactic acidosis;
ketoacidosis

Question 11

In acute gout, what determines the effectiveness of Tx?

Answer 11

how quickly Tx is initiated

Question 12

Individuals who are hyperuricemic should be screened for what?

Answer 12

HTN, coronary artery disease, diabetes, obesity, alcoholism

Question 13

What is hyperuricemia associated with?

Answer 13

serum creatinine; BMI; age; BP; alcohol

Question 14

How do urate levels change with age?

Answer 14

low in childhood and increase in men at puberty and women at menopause

Question 15

Environmental factors associated with gout?

Answer 15

alcohol (beer); diet (seafood, red meat)

protective=> milk and yogurt

Question 16

What are the genetics of gout?

Answer 16

inherited factors affecting serum urate levels through renal urate clearance but urate transporter polymorphisms are likely altered

Question 17

What are the 3 stages of gout?

Answer 17

asymptomatic hyperuricemia;
acute and intercritical gout;
chronic gouty arthritis

Question 18

Based on gender and age, when is the first gout attack likely to happen?

Answer 18

men at 40-60y/o and women after age 60

asymptomatic hyperuricemia lasts up to 20 years before initial attack of gout

Question 19

How does the gout attack typically manifest?

Answer 19

monoarticular w/ predominance in 1st metatarsophalangeal joint causing abrupt and painful onset

Question 20

What is most useful in Dx of acute and chronic gout?

Answer 20

Ultrasound

Question 21

Untreated or undertreated gout leads to chronic gout. How is this characterized?

Answer 21

development of tophi and progressive joint damage

Question 22

What conditions is gout associated with?

Answer 22

obesity; hypertriglyceridemia; glucose intolerance and metabolic syndrome (HTN, atherosclerosis, hypothyroidism)

Question 23

What is associated with hyperuricemia and gout?

Answer 23

renal insufficiency

Question 24

What is the difference in chronic vs acute hyperuricemia in how it can affect kidneys?

Answer 24

chronic=> urate nephropathy

acute=> uric acid nephropathy=> tumor lysis syndrome

Question 25

Alcohol use, lead intox and cyclosporine Tx cause what?

Answer 25

hyperuricemia and gout

Question 26

90% of cases involving primary hyperuricemia is associated with what?

Answer 26

decreased renal uric acid excretion

10% overproduction

Question 27

Acute gouty arthritis can be treated with what?

Answer 27

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