Crystal Arthritis (gout and pseudogout) Flashcards
enzymatic pathway for production of uric acid
Hypoxanthine –> xanthine –> uric acid
via xanthene oxidase
allopurinol, febuxostat target
xanthene oxidase
describe normal uric acid handleing in the kidney
Filtered at glomerulus (100%)
reabs by: URAT-1 → GLUT9 → circulation (98%)
secreted by OAT → urine (5-10%)
What is uricase
enzyme that normally breaks down urate
epidemiology of gout
purine rich diet (red meat, seafood)
alcohol (beer) abuse
Men > women
older people
In general how do you get hyperuricemia?
make too much uric acid or don’t get rid of enough
**the later is the cause of hyperuricemia in 90% of cases
congenital causes of hyperuricemia?
- HGPRT deficiency (Lesch-Nyhan syndrome)–> surplus substrate (PRPP)
- G6PD deficiency (interferes with renal excretion)
- Fructose-1-phosphae adolase deficiency
- Phyosphoribosyl-pyrophosphate synthase overactivity
secondary causes of increased uric acid production
increased cell turnover • leukemia/lymphoma • tumor lysis syndrome • treating psoriasis • sickle cell disease, etc
What drugs cause decreased secretion of uric acid
o Thiazide and loop diuretics
o Low dose aspirin/salicylates: blocks secretion
o Ethanol
o Cyclosporine
also, Nicotinic acid, Pyrazinamide and Ethambutol
how does DM lead to hyperuricemia
enhances uric acid reabs
pathophys of gout
hyperuricemia –> uric acid ppt and forms crystals
–> Urate crystals are recognized as a foreign substance by macrophages, fibroblasts, and mast cells and activate NLRP3 inflammasome → release of IL-1Beta → neutrophils influx into joint and are activated → IL-8, TNF released + neutrophil cell lysis → INFLAMMATION
Presentation of gout
Sudden onset of agonizing pain, swelling ad redness of first MTP joint
Raised serum uric acid levels (>6.8 mg/dL)
Trophi (more with chronic)
Leuckocytosis
Gout can occur at any time but is often precipitated by
- too much food or alcohol (beer in particular)
- dehydration
- starting a diuretic
- illness or stress
in skin and around joints = Smooth white deposits
trophi
Elicits a granulomatous reaction = macrophages
chronic gout
–> erosive arthritis
What other clinical conditions are seen with gout?
- nephrolithiasis
- lead poisoning (produces interstitial nephritis which interferes with uric acid secretion )
- HTN and CAD
What conditions are necessary for uric acid nephrolithiasis to form
inc uric acid excretion
decreased urine volume
low urine pH
risk factors for gout
age obesity metabolic syndrome alcoholism chronic diuretic or low dose aspirin use
Where do the CPP deposit in CPDD dz?
cartilage»_space;> tendons, ligaments, bursa
pathophys of CPDD dz
CPP crystals recognized as foreign substance → activate NLRP3 inflammasome → IL-1B released → neutrophils move into joint and are activated → INFLAMMATION
Familial CPPD linked to mutation in …
ANHK gene
**seen in pts <55 yo
What joints does CPDD effect?
KNEE
(rarelt affects MTP)
chronic CPDD: wrists, elbows, hip
= joints less likely affected by OA
Assc diseases to consider when pt presents with CPDD
younger: hemachromatosis
polder: hyperparathyroidism
How is the diagnosis of CPDD made?
detecting rhomboidal, WEAKLY birefringent, intracellular crystals in joint fluid
