The Crystal Arthropathies Flashcards
Gout is a disorder of metabolising which substance? [1]
What does this mean has deposition in soft tissue? [1]
Uric acid metabolism disordered: causes monosodium urate crystals get deposited in soft tissues
How long are uric acid levels elevated for before onset of gout?
What ages are uric acid levels being raised (to cause gout) in men [1] and women [1]?
Uric acid levels elevated for 20years before onset of gout
Uric acid in men rise at puberty and peak age of onset is between 40-60 years
In women uric acid rises at menopause peak age of onset is between 60-80 years
How does the body handle raised uric acid levels and crystals normally? [1]
What does this mean with regards to cause of gout attack? [1]
They coat them in serum proteins, specifically apolipoprotein E to make them inert
Therefore, the presence of monosodium urate crystals in synovial fluid is NOT enough to cause flares of gouty arthritis/attack
Describe the pathophysiology of gout
Sudden increase in the number of crystals and the body isn’t able to respond by coating crystals with serum proteins
Uncoated crystals in the joint that triggers an attack.
Naked urate crystals are then believed to interact with intracellular and surface receptors of local dendritic cells and macrophages, serving as a danger signal to activate the innate immune system
This interaction may be enhanced by immunoglobulin G (IgG) binding.
(Triggering of these receptors, including Toll-like receptors, NALP3 inflammasomes, and the triggering receptors expressed on myeloid cells (TREMs) by MSU) results in the production of interleukin (IL)–1, which in turn initiates the production of a cascade of pro-inflammatory cytokines, including IL-6, IL-8, neutrophil chemotactic factors, and tumour necrosis factor (TNF)–alpha
Neutrophil phagocytosis leads to another burst of inflammatory mediator production
Describe the role of neutrophils in gout pathogenesis
- Sudden increase in MSU uncoated crystals cause neutrophils to enter synovial fluid
- Neutrophils phagocytose MSU crystals, and macrophages that detect crystals release IL-1
- .The structure of MSU crystals cause neutrophil to be pierced, lyse and die
- Contents of neutrophil released: proteins, etc which bring more white blood cells in, and production of pro-inflammatory cytokines
- Acid released from neutrophils lowers pH, makes crystals precipitate even more: attack will start of pain, etc
- This inflammation from neutrophil phagocytosis is also aided by massive release of IL-1 from original macrophages that come into contact with crystal, which initiates a cascade of release of other cytokines like TNF-alpha, IL-6, IL-8, etc.
Main IL associated with gout? [1]
IL-1
State 5 reasons why an acute flare of gout may occur [5]
Factors that that lead to increased levels of serum uric acid:
- consumption of beer or liquor, overconsumption of foods with high purine content
- trauma
- haemorrhage
- dehydration
- medications that elevate levels of uric acid.
Gout is commonly [monoarticular / polyarticular]?
Which joints are commonly affected and why?
Gout is commonly monoarticular
Small lower extremity joints: these areas are colder and lower pH
What is a podagra? [1]
gout which affects the joint located between the foot and the big toe; metatarsophalangeal joint.
Describe the time profile of of gout onset [3]
Gout is episodic
* it appears in acute attacks, which will settle down and disappear after approximately 2 weeks
* may not have another attack for 2-5 years,
* may never have an attack again at all (which is also dependent on diet, genetics, medications, etc).
(It is essentially a remitting-relapsing condition, similar to MS)
Which joints are most commonly affected in gout?
Lower joints more common
Explain a complication of gout in another organ [1]
Renal damage and kidney stones:
- Chronic urate nephropathy in patients with chronic tophaceous gout can result from the deposition of urate crystals in the medullary interstitium and pyramids, resulting in an inflammatory reaction that can lead to fibrotic changes.
Gout is common in patients with which syndrome? [1]
metabolic syndrome
presence of these associated disorders can lead to coronary artery disease, these problems should be sought and treated in patients diagnosed with gout.
Importantly, ask about a history of peptic ulcer disease, renal disease, or other conditions that may complicate the use of the medications used to treat gout.
How does a gout attack commonly present? [4]
Joint:
* Hot
* Red
* Tender
* Pain is acute and at night
Describe progession of gout if disease state is left untreated [5]
- Attacks become poly-articular
- More proximal and upper extremity joints involved
- Attacks more frequent and last longer
- Chronic poly-articular arthritis almost symmetrical
- Can affect other synovial structures
Describe the pathogenesis of gout tophi [1]
Where are they commonly found? [1]
In a chronic state, the neutrophils present die, the monosodium urate crystals are packaged and walled off into tophi which continue to grow/expand into hard lumps known as tophi.
Commonly found in: extensor surface joints, especially the elbows, knees, and Achilles tendons.
What does this x-ray of a gout patient show? [1]
Rat bite erosions
What is gouty tophi? [1]
nodular masses of monosodium urate crystals deposited in the soft tissues of the body
Describe the histology of tophi [2]
Large aggregates of urate crystals surrounded by lymphocytes, macrophages and foreign body giant cells
Ring around nodes ./ tophi of palisade of histocytes (macrophages in tissue), T lymphocytes & super macrophages
What are the 11 factors used in diagnosis of gout? [11]
probs dont need to know
How does synovial fluid gout appear? [1]
If did a smear of gout synovial fluid what cell type would be present? [1]
White & iridescent - although not always present like this if there arent enough crystals
There is also a predominance of polymorphonuclear neutrophils (PMNs).
