4/18 Crystal Joint Disease - Corbett Flashcards
crystal induced arthropathies
definition
epidemiology
cause
2 types
recurrent episodes of pian and joint infl
- premenopause: M >> F (due to effect of estrogen on urate excr)
- higher age of onset in F
- strong correlation with hyperuricemia
- risk: age, metabolic syndrome, diet (alc)
cause: crystals within joint space, deposition of crystals in soft tissue
- gout : monosodium urate monohydrate (MSU)
- pseudogout : calcium pyrophosphate (CPP)
what causes hyperuricemia?
uric acid (urate) is end product of purine degradation
- adenosine → inosine → hypoxanthine → xanthine [ADA, PNP, xanthine oxidase]
- guanosine → guanine → xanthine [PNP, guanine deaminase]
- xanthine → URIC ACID [xanthine oxidase]
hyperuricemia: serum urate conc greater than solubility (> 6.8 mg/dl) → crystal formation!
- either due to overprod or underexcr of urate
purine catabolism enzyme deficiencies
1. adenosine deaminase def → SCID (severe combined immunodef syndrome)
- blocks ribonucleotide reductase via excess dATP buildup
2. purine nucleotide phosphorylase def → immune deficiency syndrome (not as bad as ADA def)
hyperuricemia
- overproduction by liver
- underexcretion by kidney (70% of excretion)
- underexcretion by gut (30% of excretion)
renal uric acid excretion
- most uric acid not bound to protein → freely filtered at glom
- almost all reabsorbed in PCT
- resecreted, then reabsorbed again
- net 10% of filtered urate secreted/excreted
***other anions will use urate as “trade” for reabs (ex. lactate, butyrate, ncotinate, salicylate, PZA, thiazide diuretics, alcohol metabolites will be secreted using urate as reabs currency
apical
URAT1 : picks up urate from filtrateOAT10
- targeted by: probenecid, losartan
-
mutations: familial hypouricemia
- exercise-induced ARF
- kidney stones
- OAT4
- OAT10
basolat
- Glut9a
factors promoting hyperuricemia
link between hyperuricemia and gout
hyperuricemia is linked to gout BUT DOES NOT CAUSE IT
some other predisposing factors
- trauma/irritation
- prior disease
- lower temp (foot, helix of ear)
gout triggers
- infection, IV contrast media, acidosis, surgery/trauma, diuretic tx, chemotx start
primary gout
vs
secondary gout
90% primary gout
- exact cause of hyepruricemia unknown (prob underexcretion of uric acid)
- age/weight gain/genetics
- thiazide/loop diuretics, low dose baby aspirin, cyclosporine A
10% secondary gout (often high cell turnover)
- known underlying disease → incr uric acid
- myeloprolif diseases or tx
- renal failure/tubular disorders
- lead poisoning
- congenital enzymatic defects (ex. HGPRT def)
- high cell turnover (myeloprolif issues, lymphoma, exfoliative psoriasis), genetic disorders, tumor lysis, chemotx
crystals coated w protein = nonreactive
- crystals act as “danger signals” → IL1 and other cytokines released → lysosomal enzymes released
- inflammasome activation phase
- amplification phase
- resolution phase
- intercritical gout
key pathological features
- dense PMH infiltration in synovium
- MSU crystals in synovial fluid/tissue
-
tophi are pathognomonic for chronic gout
- large agg of urate crystals → intense infl infiltrate
- articular cartilage, periarticular tendons/ligaments/soft tissue
- helix of ear, olecranon processes, IP joints
- over osteoarth Herberden’s/Bouchard’s nodes
tophaceous gout
acute gout vs advanced gout
key sx
acute
- rapid onset, max sx intensity at 8-12h
- commonly monoarticular (MTP joint first, ankle/heel/knee/wrist)
- joints RED, hot, tender
advanced
- interattack interval shortens
- attacks become more polyarticular (more proximal and UE affected; more joints, less pain)
- greater risk for kitney stones
- assoc with metabolic syndrome (DM, HTN, low HDL)
key physical exam
key ddx
definitive dx of gout
- monoarticular
- inflammation → ltd ROM
- key ddx*: SEPTIC JOINT or pseudogout
- see slide
- definitive dx?*
aspirate the joint, look for crystals → strongly negatively birefringent (yellow when parallel, blue when perpendicular)
gout tx
acute attack : symptom control
- NSAIDs, corticosteroid
- colchicine
- tx to control hyperuricemia is contraindicated during acute attack
prevention of recurrence/chronic sequellae
- XO inhibitors (allopurinol)
- uricosuric agents
psuedogout
calcium pyrophosphate deposition (CPPD)
- onset typically over 50; incr incidence w age
- almost exclusively in articular tissues (fibrocartilage and hyaline cartilage)
- patellofemoral, radiocarpal jts are 2 most common
- most common cause of chondrocalcinosis
cartilage calcification
causes
chrondrocyte phenotype alteration
- ECM altered → imbalance b/w inhibitors and promineralization factors
- dysreg’d incorganic pyrophosphate and inorganic phosphate metabolism
altered resps to growth factors, infl cytokines, mediators
- “stressed” chondrocytes create more ATP → incr extracellular PPi production!
ANKH mutations
- ANKH stimulates cellular transport of inorg phosphates
- mutation in AD familial chondrocalcinosis, severe articular CPPD → degenerative arthropathy
- sporadic chondrocalcinosis (ass w aging)
algorithm for joint crystal disease
