Crystal arthritis Flashcards
What is gout?
heterogeneous group of disease with deposition of monosodium urate (MSU) crystals occurs due to hyperuricemia
how can Gout manifest?
Gouty arthritis, Tophi, Gouty nephropathy, and Uric acid nephrolithiasis (kidney stones)
Whats is Gouty arthritis?
recurrent attacks of severe acute and chronic articular and periarticular inflammation
What is Tophi?
aggregated deposits of MSU in joints, bones, and soft tissues. Commonly in digits of hands and feet, olecranon bursa, extensor surface of forearm, Achilles tendon, and antihelix of ear
What is Gouty nephropathy?
renal interstitial, glomerular, and/or tubular deposition of MSU crystals
What are the stages of Gout?
Asymptomatic hyperuricemia (MSU above 7mg/dL), Acute Gouty arthritis, intercritical gout (asymptomatic intervals between attacks, Chronic Tophaceous Gout (Tophi occurs)
Describe an acute gouty arthritis attack
abrupt onset of an exquisitely painful, warm, red swollen joint often at night or early morning. Typically in MTP joint of great toe (podagra) followed by insteps, ankles, heals, knees, wrists, fingers, and elbows. Early attacks Spontaneously resolve in 3-10 days
T or F: gout is more common in men after the age of 30 than women
TRUE
What other medical conditions are often seen with gout?
alcohol abuse, obesity, insulin resistance syndrome, and hypertension
What 2 dysfuctions canlead to hyperuricemia?
increased production or decreased renal excretion of urate
What can does a 24h urinary excretion of >750mg/24h uric acid tell you in gout?
overproduction of uric acid
What can does a 24h urinary excretion of <750mg/24h uric acid tell you in gout?
underexcretion of uric acid
What is the cause of primary gout in most patients?
underexcretion of uric acid seen in 90% of patients
What is the steady state of uric acid?
urate produced + absorbed = urate excreted by kidney + GI tract
What are the 4 steps to Urinary uric acid excretion?
1) glomerular filtration, 2) pre secretory reabsorption in proximal tuble, 3) secretion back into the tuble, and 4) post secretory reabsorption.
What is the net reabsorption of filtered uric acid?
90%
What does the urate/organic anion exchanger (URAT1) do?
reabsorbs uric acid in exchange for tubular secretions and excretions of unwanted organic acids (lactate, acetoacetate, etc).
What drugs cause decreased renal excretion of uric acid?
nicotinate, pyrazinoate, diuretic and low-dose asprin by activating URAT1
What drugs cause increased renal excretion of uric acid?
probenecid, sulfinpyrazone, metaolite of losartan, and high-dose asprin by inactivating URAT1
What are 2 major proteins that extrude urine from epitelial cells into tubular urine?
ABCG2 and MPR4
T or F: MSU crystals in synovial fluid results in acute inflammation
TRUE
MSU crystal interaction with synovial lining cells results in what?
monocyte and mast cell activation via recognition of naked MSU crystals by TLR2 and TLR4
How do MSU crystals bring about IL-1beta?
engage caspase-1 activating NLRP3 inflammasome
What else do MSU crystals induce
release of THNF-alpha, IL-6, IL-8; activate complement; neutrophil recruitment and phagocytosis of crystals with ROS and lysosome release; prostaglandin synthesis
What are some causes of MSU crystalization (especially in the big toe)?
lower intra-articular temperature, minor trama, abnormal joint proteoglycans, changes in intra-articular pH, and resorption of fluid from the big toe at night
What 2 specific defects of purine metabolism can lead to gout?
increased phosphotibosyl pyrophosphate syntase activity (PRPP synthase) or a deficiency in hypoxanthine-guanine phophoribosyltransferase (HGPRT)
What sort of genetic inheritance of PRPP synthase and HGPRT defects display?
X-linked - lead to overproduction of uric acid
what does a complete HGPRT deficiency lead to?
Lesch-Nyhan syndrome (choreoathetosis, striking growth and mental retardation, spasticity, self-mutilation, and marked hyperuricemia with excessive uric acid production)
What nutritional advice could you give to someone with gout?
don’t eat meats, shellfish, limit fructose and alcohol? lose weight
What can be given to treat acute gouty attacks?
NSAIDS, cholchicine, or corticosteroids
why would colchicine work (just interesting in my opinion)?
binds intracellular tubulin => diminished PMN activity. May also block activation of NLRP3 inflammasome in monocytes
What can you give to an underexcretor for chronic treatment of gout?
a uricosuric (probenecid)
What can you give to an overproducer for gout?
a xanthine oxidase inhibitor (allopurinol or febuxostat)
What is the significance of HLA-B*5801?
allopurinol hypersensitivity (Asian prevalence)
What can you give IV for severe gout?
Pegylated-uricase
What do MSU crystals in PMNs look like?
needle shaped, and negatively birefringent (yellow when parallel to axis of red compensator
What does the synovial fluid look like in gout?
inflammatory (usually 20,000-100,000 leukocytes/mm^3) with predominance of neutrophils
what would hematologic evaluation show in gout?
elevated ESR, mild neutrophil leukocytosis, and possibly reactive thrombocytosis
What causes pseudogout (calcium pyrophosphate dihydrate deposition disease (CPDD)?
abnormal pyrophosphate (PPi) metabolism leads to CPPD crystals
What are the issues in abnormal PPi metabolism?
chondrocyte surface enzyme NTP pyrophosphohydrolase (makes NMP + PPi), or possibly abnormal ANKH transporter protein activity (transports PPi in chondrocytes)
How are CPPD crystals released into synovial fluid?
“shedding phenomenon” or “enzymatic strip mining” of preformed crystals in the cartilage matrix made from high extracellular PPi precipitating with Ca from cartilage
how can you treat CPPD?
anti-inflammatory drugs are pretty much it. You can’t really remove crystals like you can in gout
What do CPPD crystals look like?
rhromboid-shaped and positively birefringent (blue when parallel to red compensator)
What does the synovial fluid look like in CPPD?
inflammatory (usually 2,000-80,000 leukocytes/mm^3) with a predominance of neutrophils
What joints are most effected in CPDD?
large joints, most often the knee (less freq is qrist and ankle). MTP rarely involved
What are some epidemiologic associations with CPDD?
elderly, hyperparathyroidism, hemochromatosis, joint trama or prior joint surgery (risk factors in young), rare familial forms also exist
When might WBC and ESR be elevated in CPDD?
during an acute attack
what other studies can be helpful in looking for associated metabolic causes of CPDD?
serum Calcium, phosphorus, and iron studies
