Gout Flashcards
Define uric acid
bio active end product of human purine metabolism
How is gout caused? and levels?
hyperuricemia w/ greater than 6.8mg/dL in serum=> combination or single faulty one
1) urate overproduction
2) urate underexcretion
What plays a key role in urate excretion?
OATs play central role in excretion of urate by kidney
How does gout cause an inflammatory response?
accumulation of monosodium urate at levels to cause precipitation of crystals resulting in a response
How does monosodium urate crystals lead to the inflammatory response?
activates NLRP3 inflammasome that processes and generates IL-1B, IL-18 and IL-33
Once gouty inflammation is present, how does it proceed?
local WBCs induces influx of neutrophils into joint that are activated by urate crystals causing more inflammation
Describe chronic and tophaceous gout
low level inflammation allows macrophages to continue to produce cytokines and proteases leading to more cartilage and bone destruction
What transporter is most important in resorption of urate from proximal tubule ultrafiltrate?
URAT1
What transporter is most important in secretion?
OAT1 and OAT3 move urate from interstitium to epithelial cell interior
What diseases are associated with underexcretion of urate?
renal insufficiency;
dehyrdration/volume depletion;
lactic acidosis;
ketoacidosis
In acute gout, what determines the effectiveness of Tx?
how quickly Tx is initiated
Individuals who are hyperuricemic should be screened for what?
HTN, coronary artery disease, diabetes, obesity, alcoholism
What is hyperuricemia associated with?
serum creatinine; BMI; age; BP; alcohol
How do urate levels change with age?
low in childhood and increase in men at puberty and women at menopause
Environmental factors associated with gout?
alcohol (beer); diet (seafood, red meat)
protective=> milk and yogurt
What are the genetics of gout?
inherited factors affecting serum urate levels through renal urate clearance but urate transporter polymorphisms are likely altered
What are the 3 stages of gout?
asymptomatic hyperuricemia;
acute and intercritical gout;
chronic gouty arthritis
Based on gender and age, when is the first gout attack likely to happen?
men at 40-60y/o and women after age 60
asymptomatic hyperuricemia lasts up to 20 years before initial attack of gout
How does the gout attack typically manifest?
monoarticular w/ predominance in 1st metatarsophalangeal joint causing abrupt and painful onset
What is most useful in Dx of acute and chronic gout?
Ultrasound
Untreated or undertreated gout leads to chronic gout. How is this characterized?
development of tophi and progressive joint damage
What conditions is gout associated with?
obesity; hypertriglyceridemia; glucose intolerance and metabolic syndrome (HTN, atherosclerosis, hypothyroidism)
What is associated with hyperuricemia and gout?
renal insufficiency
What is the difference in chronic vs acute hyperuricemia in how it can affect kidneys?
chronic=> urate nephropathy
acute=> uric acid nephropathy=> tumor lysis syndrome
