Gout Flashcards
What is gout?
This is a common disorder or uric acid metabolism
Monosodium urate crystals are deposited in soft tissues
What are monosodium urate (MSU) crystals usually coated by and why are they coated?
Coated by serum proteins (apoE or apoB)
Coating inhibits the binding of MSU crystals to cell receptors
What can trigger a gout attack?
- Uric acid levels elevate 20 years before the onset of gout
- The presence of urate crystals alone is not enough
Gout may be triggered by:
- release of uncoated crystal (partial dissolution of microtophus due to changing serum urate levels)
- precipitation of crystals in a supersaturated microenvironment
What occurs after a gout attack has been triggered?
- make urate interacts with the intracellular and surface receptors of local dendritic cells and macrophages –> activates immune system
- interaction may be enhanced by binding of IgG
- MSU triggers receptors (TLRs and NALP3 inflammasomes) and receptors expressed on myeloid cells = production of IL-1
- cascade of pro-inflammatory cytokines
- neutrophil phagocytosis = burst of inflammatory mediators
How do the crystals contribute to the pain and inflammation in gout?
The crystals are long and thin
Pierce the neutrophils = lysis
Release of contents from neutrophils attracts more WBCs and increases immune cells present
this causes the inflammation and pain
Why does pH become lowered and what effect does this have?
Neutrophils release acid when phagocytosed/lysed
Lowering of pH results in more crystal precipitation
What is podagra? How often is it seen in gout?
inflammation of the 1st MTP joint
Seen in 50% of gout cases
What is the onset of gout like? How long does it last?
Onset is usually sudden and intensity peaks at 8-12 hours
- usually occurs 2-3am when body temp is low
1st attacks will resolve within 2 weeks and will not require treatment
How does gout often present? what joints does it most often affect etc?
Common in men >30
Acute monoarticular in 90% of cases
Affects smaller, lower extremity joints
Joint will be red, hot, tender, and pain starts acutely and at night time
What happens if a person has multiple gout attacks that go untreated?
- attacks become polyarticular
- more proximal and upper extremity joints are involved
- attacks are more frequent and long-lasting
- chronic polyarticular arthritis almost symmetrical
- can affect other synovial structures
What are the main differences between an acute gout attack and chronic tophaceous gout?
Acute gout:
- phagocytosis of crystals
- cell swelling + inflammasome activation
- cytokines production + vasodilation
- neutrophil + monocyte influx
Chronic tophaceous gout:
- packaging of MSU crystals
- resolution of inflammation
- inactivation of inflammatory cytokines
- neutrophil death by NETosis
What are tophi? What % of cases do they develop in?
Urate crystals in soft tissues
Foreign body type giant cell reaction to the deposited crystals
Develop in 50% of patients with untreated gout
At what point is uric acid considered saturated?
At 6.8mg/dL
- often due to insufficient excretion rather than overproduction (90%)
How is gout diagnosed?
> 6 out of 11 variables
SF analysis:
- inflammatory
- WBC count >2000/uL
- predominance of polymorphonuclear neutrophils
- urate crystals will be needle-like + high negatively birefringent
Serum uric acid:
- if higher than 11 mg/dL - should be treated
X-rays/US:
- soft tissue swelling/increased blood flow
- maintenance of joint space
- erosion outside joint capsule
- erosions have overhanging edges (rat-bite)
Dual energy computed tomography (DECT)
What is the pharmacological treatment for acute gout?
- NSAIDs
- start with highest dose for 2-3 days
- taper down over 2 weeks
- gout symptoms should be gone for 2 days before stopping treatment - Colchicine (stops cell division)
- Corticosteroids
- if NSAIDs/colchicine cannot be used - IL-1 biologicals:
- Rilanocept, canakinumab, anakinra
- reduces length of attacks + recurrences
- used for severe + frequent attacks
