Crystal Arthropathies Flashcards
Gout is a common disorder of…?
Uric acid metabolism (uric acid is a product of purine breakdown)
How many % of the population does gout affect?
1%
Is gout more common in males or females?
Why?
Males
Uric acid levels in the blood need to be elevated for about 20 years before onset of gout. The levels rise in men at puberty, but not until menopause in women, so women would have to be about 70-80 before onset of gout.
What crystals get deposited in soft tissues in gout?
Monosodium urate crystals
If gout is left untreated, what can it lead to? (2)
Joint destruction
Renal damage
Where do 50% of cases of gout start?
First MTP (big toe)
Presence of urate crystals in synovial fluid is not sufficient to cause flares of gouty arthritis - how is this explained?
Clumps (microtophi) of highly negatively charged and reactive monosodium urate crystals are normally coated with serum proteins (ApoE or B) – these proteins inhibit the binding of crystals to cell receptors, so they are inert.
What can trigger a gout attack?
Either a release of uncoated crystals, or a sudden large change in concentration
After a gout attack is triggered, what happens?
The naked crystals (not coated with serum proteins) interact with intracellular and surface receptors of dendritic cells and macrophages, activating the innate immune system.
This causes the production of IL-1, which initiates the production of a cascade of proinflammatory cytokines (e.g. IL-6, IL-8, and TNF-alpha).
Neutrophils phagocytose crystals and burst, releasing their intercellular contents.
This lowers the PH, due to release of lysosomes, and also leads to more inflammatory mediation production. A lower pH leads to more precipitation, which sets up the spiral.
Gout is unlikely before…?
30 years of age
How does gout usually present?
Acute monoarticular (90% of cases) Small lower extremity joints Podagra - inflammation of 1st MTP joint (50% of cases) Begins suddenly and reach maximum intensity with 8-12 hours
What joints are commonly affected? (4)
1st MTP (90% of individuals) = podagra
Ankle
Knee = gonagra
Elbow
What other complications of gout are there? (4)
Renal damage/stones
Deposition of crystals in cartilage (tophi) – ear, hands
Gout osteoarthropathy
Olecranon bursitis
What does the patient present with in terms of the joint history?
Red, hot, tender.
Pain starts acutely and usually at night.
Intermittent cycles – the first attacks resolve spontaneously in less than two weeks.
If gout is untreated…? (5)
Attacks become polyarticular
More proximal and upper extremity joints involved
Attacks more frequent and last longer
Chronic polyarticular arthritis almost symmetrical
Can affect other synovial structures
What can be seen on x-ray and on examination in gout?
Tophi
‘Rat bite’ erosions on x-ray
What are tophi? How many untreated patients do they develop in?
Urate crystals in soft tissues
50% after 10 years
What do these tophi look like on histology?
Foreign body-type giant cells seen (reaction to the deposited crystals)
The crystalline nature of this material is not obvious in formalin-fixed specimen as the crystals get washed out, but you can see some brown deposit
Macrophages (histocytes) wall off (palisading) the central crystals, and you get lymphocytes around this.
How many mg/dL of purines do we get from diet? How much is synthesised?
600mg/dL
Purine nucleotides and bases 300-600mg/dL, plus tissue nucleotide synthesis 300-600mg/dL
How do humans remove uric acid?
Renal excretion (600mg/dL) and faeces (200mg/dL)
When excretion is insufficient to maintain serum urate levels below what level does hyperuricemia develop?
6.8mg/dL
Is gout usually due to overproduction or under excretion?
What can cause this? (3)
Under excretion (90% of cases) Renal insufficiency, dehydration, thiazide diuretics
What foods are high in purines?
Beef, pork, lamb, seafood, beer, alcoholic beverages…
What are the gout risk factors? (6)
Male Age Obesity Ethnicity (Pacific Islanders) Genetics (polymorphisms) Kidney disease
