Uric Acid Metabolism Flashcards
Purines?
Adenosine
Guanosine
Inosine
Purine catabolism
Purine to Hypo-Xanthine
Hypo-xanthine to Xanthine = Xanthine Oxidase
Xanthine to Urate = Xanthine Oxidase
Urate to Allantoin = Uricase which humans don’t have, hence urate builds up in plasma and needs exreting
Why do women get gout less than men?
Lower plasma urate concentration
Which joint does gout classically attack?
MTP, Low temperature joint hence buildup of uric acid crystals
90% of all cases
50% 1st MTP
What is the rate limiting step of de novo purine synthesis?
PAT = PRPP Amidotransferase
PPRP to 5-phosphoribosyl-1-amine
What is HPRT
Main enzyme of the salvage pathway of purine metabolism
HPRT Deficiency
Lesch Nyhan Syndrome
Neuro signs + Self-mutliation
Frank Gout
Normal at birth, delay at 6m
X-Linked
Secondary causes of decrease in urate excretion
Raised cell turnover in cancer, myeloproliferative diseases or severe psoriasis
Primary causes of decreased urate excretion
Familial Juvenile Hyperuricaemic Nephropathy
Secondary causes of decreased urate excretion
CKD
Bartter’s
Saturnine Gout = lead poisoning
Diuretics
How is urate excreted renally
PCT -> only 10% excreted, 90% reabsorbed maybe due to anti-oxidant properties
Which electrolyte imbalances are associated with Thiazide Diuretics
Low Sodium
High glucose, Ca, Urate
Gout
Crystal Arthropathy
Monosodium Urate crystals
3%M 0.5% F
Podagra
Acute gout in one foot
Tophaceous Gout
Chronic Gout in soft tissues
Classically peri-articular or earlobes (tophi)
Gout investigation
Negatively birefringent needles of monosodium urate under polarised light microscopy
Parallel = yellow/red Perpendicular = blue
Acute gout management
NSAIDs (Diclofenac)
Colchicine
Glucocorticoids
Chronic Gout management
Hydration
Allopurinol
Reversing causative factors (ie. beer, port)
When are NSAIDs contraindicated
Peptic Ulcer
Severe Asthma
CKD
How does Colchicine work?
Inhibits tubulin polymerisation = no microtubule assembly = no neutrophil migration to site of inflammation
Allopurinol MOA
Xanthine Oxidase inhibitor = less urate production
Probenecid
Uricosurics, a class of drug that enhances tubular urate excretion
Allopurinol contraindications
Azathioprine, as they counteract one another with regards to bone marrow turnover
Azathioprine metabolite = mercaptopurine which is metabolised by xanthine oxidase, hence allopurinol can raise this to toxic levels
Pseudogout
Pyrophosphate crystals
Positively birefringent
Parallel = blue Perpendicular = Red/yellow
