19. Crystal arthropathies (Robson) Flashcards
What is gout?
Where defective metabolism - poor renal excretion - of uric acid results in arthritis
What is the prevalence of gout?
1% of the population
What are the different facto categories that result in the onset of gout?
Environmental
Dietary
Genetic
Is gout more common in men or women?
Men
Why is gout more common in men?
Because men have higher levels of uric acid then females
When does the level of uric acid rise in men?
In boys - around the age of puberty
When does gout present in men?
Around the age of thirty
How long does it take for the onset of gout to occur?
About 20 years after the uric acid levels rise
How does gout occur?
Uric acid flares and crystalises to form monosodium urate crystals - these crystals can then be attacked by the immune system and arthritis in the form of gout forms
What are the crystals that are formed in gout?
Monosodium urate crystals
Where are the crystals deposited in gout?
Deposited in the soft tissues - joints, articular capsule, tendons, ligaments, cartilage
When does the level of uric acid increased in women?
Around the age of the menopause
What is the most common site of gout in an individual and why?
The big toe - the first metataral joint
Because it is slightly colder than the rest of the body and has a slightly lower pH due to reduced perfusion - the favourable conditions for the development of gout
When can gout result in joint destruction?
If it is untreated and there are repeated attacks of gout at the same joint
What is the main organ concerned with the formation of gout and why?
Kidney
Sufficient renal excretion of uric acid is not occurring
How is uric acid produced?
By the breakdown of purines - metabolism of purines results in the production of uric acid
When is uric acid present in an individual?
Uric acid is present in everyone at all ages in the form of the monosodium urate crystals - but does not cause a problem because it is inert
Why do monosodium urate crstals not normally result in gout?
Uric acid is normally inert
How are monosodium urate crystals made inert?
The crystals are coated by proteins - these are apolipoproteins that are highly negative and this hides the crystals from the immune system
If the monosodium urate crystals are inert, why does gout occur?
If there is an increased level of crystals that are forming - large change in concentration then there can be too great a level for the serum protein to coat them all
What is the saturated level of the crystals to be coated by the proteins?
68mg/dl
What are the conditions required for the precipitation of the crystals from uric acid?
Low temperature - a drop of two degrees compared to normal
Reduced pH
What is the main white blood cell involved in gout?
Neutrophils
Which receptor on neutrophils is activated by the non-coated crystals?
IL1
What is the mode of action of the neutrophils to the gout crystals and what does this result in?
Neutrophils are phagocytic and they ingest the crystals - the crystal then pops/bursts the neutrophil from within and all the contents is exposed into the environment
What is the effect of the bursting of neutrophils on the surrounding environment and why?
Lowers the pH - release of very acidic lysosomes
What is the effect of the bursting neutrophils on crystal formation?
The bursting of neutrophils lowers the pH - this is favourable for the precipitation of crystals - more crystals from - recruits more neutrophils - cycle continues
What is ‘podagra’?
Inflammation of the first MTP joint in gout - the most common joint that is affected - 50% of cases
Is gout mono or poly articular?
Monoarticular - 90% of cases
What is the first symptomatic period of gout?
Begins suddenly and there is a maximum intensity of pain within the first 8-12 hours
How intense is the maximum intensity of pain in patients with gout?
So intense that these patients cannot even take the weight of a sheet over the affected foot
How long does the first flare of gout normally last for?
Normally resolves within about 2-3 weeks - provide painkillers and inflammation goes and everything calms down - no other treatment required for the first attack
What are the types of joints commonly affected by gout?
Tends to stay out in the periphery and in the smaller joints
Other than joints, what else can be affected by gout?
Organs e.g. kidney
Bursa
How does the affected joint present in a patient with gout?
Red
Hot
Exquisitely tender
Pain starts acutely and usually at night
Why does the pain from gout usually start at night ?
Usually starts around 2am because of circadian rhythm - this is when you are the coldest
How will gout present throughout someones life after the first attack?
Very variable - some people will have just one attack - some people will have a progressive form which gets worse each time and becomes polyarticular
How does untreated gout progress?
Attacks can become polyarticular
More proximal and upper extremity joints involved
Attacks become more frequent and last for longer
Polyarticular and will become almost symmetrical
What are ‘tophi’?
This is the deposition of the crystals in and about the synovial joint - so in the soft tissue and the synovial fluid etc.
How can gout be recognised on an x-ray?
Tophi
Joint erosions - ‘rat bites’
Where do joint erosions occur in gout?
Do not occur right at the joint - are at the insertion of the articular capsule - called ‘rat bites’ and have overhanging edges
Are tophi only visible on n x-ray?
No - occur in the soft tissues so will be able to see them under the skin
In what percentage of people with gout do tophi occur?
In 50% of these people
When do tophi occur?
Occur after 10 years of gout
What will be visible on a biopsy of gout?
Tophi will be visible as a nodule - histocytes surround the crystals and then lymphocytes surround this -forms a nodule
What are histocytes?
These are macropahges that are not located in the bloodstream
Why will the crystals not be physically present on a biopsy?
Crystals are present in the nodules but they are soluble - will be washed out during the procedures of the biopsy
How do humans normally remove uric acid from the system?
70% in urine
30% in faecal matter
Where is uric acid obtained from?
Small amount is obtained fro the diet
Majority is produced by metabolism of purines
Which foods result in a high uric acid consumption?
Meat - beef, pork, lamb
Alcohol (yeast) - bear, red wine
Seafood - tuna
Other that food, what are other risk factors for the development of gout?
Thiazide diuretics !! Dehydration Renal insufficiency Male gender Increasing age Increased fructose intake eg. in drugs
What are the different causes of hyperuricemia that can lead to gout?
Joint inflammation Kidney or bladder stones Nephropathy CV disease Metabolic syndrome
What is hyperuricemia?
High levels of uric acid
What is the appearance of the synovial fluid in someone that has gout?
Will be packed full of neutrophils - white and creamy
Will also look slightly shiny - glisten when held up to the light -presence of crystals
What is the appearance of the crystals in gout?
These are sharp, needle like and very shiny
Is hperuricemia diagnostic for gout and why?
No - 5-8% of the population have naturally elavated serum uric acid levels anyhow (and still do not have gout)
Not just requirement of hyperuricemia - also need cold temperature and low pH
How will gout show on a doppler ultrasound?
There will be an increased blood flow
Why and how does joint damage occur in gout?
RANKL is stimulated
RANKL stimulates the production and proliferation of osteoclasts and osteoclast precursors - erosion of bone
Which inflammatory cytokines are involved in gout?
IL1
TNF-alpha
IL6
(RANKL)
Give four drug groups that can be used in the treatment of acute gout
NSAIDs
Colchicine
Corticosteroids
IL1 biologicals
Also change in diet
What is colchicine?
Antimitotic - this stops cell division and stops the proliferation of the neutrophils
Why is colchicine not so commonly used anymore?
Has a narrow therapeutic window and also has a risk of toxicity
Four treatments of chronic gout are?
Allopurinol
Probenecid
Rasburicase
Altered diet
What is pseudogout?
Deposition of calcium salts in soft tissues - if these come into contact with exposed bone then they can precipitate
What are the calcium salts involved in psuedogout?
Calcium pyrophosphate dihydrate crystals
What is the most commonly affected joint in peudogout?
The knee
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What is the appearance of the crystals in pseudogout?
Short and stubby - not as shiny
What is chondrocalcinosis?
Calcification within the soft tissue
How does chondrocalcinosis appear on an ultrasound?
Appears as an extra line below the normal surface
What is the age group that is affected by pseudogout?
The elderly
Two immune cells that are present around gout nodule/tophi are?
Histocytes
Lymphocytes (surround histocytes)
Mechanism of action of colchicine is?
Anti-mitotic - inhibition of the proliferation of neutrophils
Mechanism of action of allopurinol?
Blocks xanthine oxidase (reduced production of uric acid)
Mechanism of action of probenecid?
Increases excretion of uric acid
Mechanism of action of rasburicase?
Catalyses converstion of uric acid to allantoin
What is the shape of the crystals in pseudogout?
Rhomboid shaped crystals
What do the crystals in pseudogout look like?
Short and stubby and not as shiny
Treatment for pseudogout is?
NSAIDs
