hyperurecemia/gout
Terms
undefined, object
copy deck
- hyperurecemia
- result fr uric acid overprodxn, impaired renal clearance of uric acid or combo
- upper limit of normal
- 7mg/dl (uricase mtd)
- gout
-
dz that is characterized by recurrent acute attacks of urate crystal-induced arthritis
- incl tophi - tophi
- deposits of monosodium urate in and around the joints and cartilage and in the kidneys as well as uric acid nephrolithiasis
- serum uric acid level rises
- risk of developing gout inc
- gout pts serum uric acid level
- > 7mg/dl
- uric acid
-
end product of purine metabolism
-produced from both dietary and endogenous sources
- formation results from the conversion of adenine and guanine moieties of nucleoproteins and nucleotides - xanthine oxidase
- enzyme that converts xanthine to uric acid -> reduces serum uric acid level while inc renal excretion of more soluble oxypurine precursors-> dec the risk of uric acid stones and nephropathy
- uric acid via kidneys excretion
-
300-600mg/day
2/3's of total uric acid - uric acid via gi tract excretion
- 100-300mg/day
- bodies total uric acid content
- 1-1.2g
- daily turnover rate of uric acid content
- 600-800mg
- urine ph
- 1-5
- poorly soluble free acid
- uric acid
- exists as monosoium urate salt
- uric acid
- primary hyperurecemia and gout
- result fr an innate defect in purine metabolism or uric acid excretion
- enzymatic defect
- pt's with hyperurecemia and gout
- ex of enzymatic defect
-
HGPRT
PRPP - HGPRT
- hypoxanthine-guanine phosphoribosyltransferase
- PRPP
-
phosphoribosyl-1-pyrophosphate
synthetase excess - classified as overproducers or underexcretors of uric acid
- primary hyperurecemia and gout
- overproducers
- synthesize abnormally large amts of uric acid and excrete excessive amts-more than 800-1000mg daily on an unrestricted diet or more than 600 mg daily on a purine-restricted diet
- underexcretors
-
90% of pts
produce normal or nearly normal amts of uric acid but excrete less than 600 mg daily on a purine restricted diet
-slightly inc miscible urate pool - pathway of uric acid
- glomerulus ->proximal convoluted tubule ->distal tubule
- proximal tubule
- here approx 99% if uric acid is reabsorbed into the bloodstream.
- glomerulus
- uric acid is filtered and enters proximal tubules
- distal tubule
-
uric acid is secreted
about 75% of the amt secreted is reabsorbed therefore almost all urinary uric acid is excreted at the distal tubule - hematological
- assoc with inc nucleic acid turnover and breakdown of uric acid
- hematological causes
-
lymphoproliferative disorders
myeloporliferative disorders
hemolytic anemia
hemoglobinopathies - hyperuricemia
- reduced renal clearance of uric acid
- asa and other salicylates
- inhibit tubular secretion of uric acid at low doses
- uricosuria
- high doses of asa and other salicylates
- inc uric acid conc by enhancing nucleic acid turnover and excretion
- cytotoxic drugs
- ethambutol and nicotinic acid
- inc uric acid conc
-
cyclosporine
pyrazinamide
levodopa - dec renal urate clearance
- ethanol
- alters uric acid metabolism by inc uric acid producxn thru an inc in adenine nucleotide catabolism and by suppressing renal uric acid excretion as a result of lactate inhibition of renal tubular uric acid secretion
- examples of conditions that may cause hyperuricemia
-
diabetic ketoacidosis
psoriasis
chronic lead poisoning - gouty arthritis
- monosodium urate crystals are deposited in the synovium of involved joints
- inflam response to mono-na urate crystals
- leads to an attack of acute gouty arthritis
- sx of acute gouty arthritis
-
redness
warmth
tenderness - tophi or tophaceous deposits
- deposits of monosodium urate crystals
- lead to joint deformity and disability
- untreated gout -> tophi
- kidney involvement
- lead to renal impairment
- renal complications of hyperurecemia & gout
-
acute tubular obstruction
urolithiasis
chronic urate nephropathy - acute tubular obstruction
- develop 2ndary to uric acid preceipitation in the collecting tubules and ureters with subsequent blockage and renal failure
- urate oxidase (rasburicase)
- used in prophylaxis and trmt of hyperurecemia in peds w/ leukemia, lymphoma and solid tumor malignancies who are receiving anticancer therapy
- conversion of uric acid to allantoin
- 5x more soluble in urine than uric acid
- urolithiasis
- formation of uric acid stones in the urinary tract
- contributing factor to urolithiasis
- low urine pH
- chronic urate nephropathy
- urate deposits arise in the renal interstitium
- asymptomatic hyperuricemia
- elevated serum uric acid level but has no s/s of deposition dz
- deposition dz
-
arthritis
tophi
urolithiasis - acute gouty arthritis
- painful arthritic attacks
- pathogenesis of acute gouty arthritis
- monosodium salts -> articular tissue ->inflam rxn
- initial attack
-
abrupt
night or early am -> synovial fluid reabsorbed
involves a few joints - most common site of initial attack
- 1st metatarsophalangeal joint
- podagra
- attack at metatarsophalangeal joint
- common serum findings for acute gouty arthritis
-
leukocytosis
moderately elevated erythrocyte sedimentation rate - pseudogout
-
calcium pyrophosphate dihydrate crystal dz
septic arthritis - drug trmts
-
nsaids
indomethacin
naproxen
sulindac
colchicine
methyprednisolone acetate
prednisone
corticotropin
triamcinolone acetonide - colchicine
- relieves pain and inflam and ending acute attack
- moa colchicine
- impairs leukocyte migration to inflammed areas and disrupts urate deposition and the subsequent inflam response
- iv colchicine
- shld never be given IM or subcutaneously due to tissue irritation
- bone marrow depression
- colchicine therapy
- intracritical gout
- symptom free period after 1st attack
- inc urate productxn
-
high purine diet
obesity
alcohol comsumption - high purine diet
-
all meats
organ meats
seafood
beans
peas
asparagus - prophylaxis of acute gout attack
-
low doses colchicine
low dose nsaids - urate reducing drug therapy
-
uricosurics
xanthine oxidase inhibitor - uricosurics
- increse renal uric acid excretion
- zanthine oxidase inhibitor
- reduces uric acid production
-
probenecid
sulfinpyrazone -
uricosurics
preferred for underexcretors - long term uricosuric therapy
-
reduces teh incidence of gouty arthritis attacks
prevents formation of new tophi
helps resolve existing tophi - uricosuric moa
- blk uric acid reabsorption at the proximal convoluted tubule -> inc rate of uric acid excretion
- uricosuric indication
- reduce hyperurecemia for pt's excreting less than 600mg of uric acid per day
- not initiated during an acute gout attack
- uricosuric therapy
- maintain high fluid intake
- during uricosuric therapy to dec renal urate precipitation
- greatest potential risk of uricosuric drugs
-
-formation of uric acid crystals in urine
-deposition of uric acid in the renal tubules, pelvis or ureter causing renal colic or the deterioration of renal fxn - maintain an high alkaline irone volume
- take 1 g of sod bicarb 3-4x a day + high intake of fluid -> 2L/day
- c/i
- urinary tract stones
-
asa
salicylates - antagonize axn of uricosurics
- sulfinpyrazone
-
reduces platelet adhesiveness
cause bld dyscrasias - allopurinol moa
- long acting metabolite, oxypurinol, blk the final steps in uric acid synthesis by inhibiting xanthine oxidase
- allopurinol indicaions
-
doc for lowering uric acid levels in both underexcretors andoverproducers
preferred urate reducing agt - se of allopurinol
- exfoliative dermatitis