LOCO Revision4 Flashcards
State 5 symptoms of OA [5]
Joint pain with use
Morning stiffness lasting <30 mins
Crepitus on motion
Joint instability or buckling
State a non-pharmological adjunct for OA pain relief [1]
Transcutaneous electrical nerve stimulation (TENS)
Pharmacological managementfor OA
COME BACK
- Start with oral analgesics &/ or topical NSAIDs
- Where paracetamol or topical NSAIDs are ineffective then substitute with oral NSAID/COX-2 inhibitor
- Intra-articular injections; Corticosteroid injections
OA
Why are only three intra-articular injections (corticosteroid injections) recomended?
If prescribe too much: softens cartilage which can cause further problems
State 6 surgical interventions for OA [6]
Arthroscopic lavage
Arthroscopic lavage plus debridement
Microfracture
Mosiacplasty (osteochondral transplant)
Chondrocyte grafts
Joint replacement
Explain mechanism of arthroscopic lavage plus debridement treament for OA
Needs to be large joint
Camera inserted into joint; assess damage for inflammation and pieces of cartilage that have worn off and leaving exposed bone
Wash out synovial fluid and get rid of floating bits of cartilage
Debridement: tidies up exposed & frayed areas; remove cartilage
Healthy on L, OA on R
Explain mechanism of Arthroscopic washout and debridement plus microfracture [2]
Same mechanism as arthroscopic washout and debridement
After debridement: have area of exposed bone: drilling into subchondral bone and bone marrow pluripotent stem cells
Stimulates repair of articular cartilage
Cartilage recovers within 4-6 months
Explain the MoA of chondrocyte grafting
Take chondrocytes from other areas of the body (e.g. costochondral joint)
Grow chondrocytes in culture
Place in graft and get more hyaline cartilage
OA treatment
Explain MoA of mosaicplasty (osteochondral grafting) [1]
Take undamaged cartilage from less weight bearing regions plus the underlying bone and move to OA region
Describe mechanism of osteotomy [1]
Realignment of joint surfaces
Treatment for OA
Which IL can you target / block to treat OA? [1]
IL-1 blockage
OA treatment
Adalimumab targets which cytokine? [1]
TNF inhibition
OA diagnosis
State 4 things assess for OA when using X-ray? [4]
LOSS:
- Loss of joint space
- Osteophytes
- Subarticular sclerosis
- Subchondral cysts
How do you distinguish OA from RA? [2]
- by the pattern of joint involvement: OA is unilateral, RA is bilateral
- the absence of systemic features and marked early morning stiffness that occur in rheumatoid arthritis
OA
Heberdens nodes occur at which joint space? [1]
DIPs
State three locations of chondrocytes for chondrocyte grafting [3]
Rib costochondral process
Non damaged part of joint
Also cartilage implants from young individuals available
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
Main IL associated with gout? [1]
IL-1
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.
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
Explain how uric acid is produced & how hyperuricaemia can occur [3]
High purine diet (e.g. meat) creates dietary purines
- Excess purines are metabolised to uric acid
- 70% is excreted via urine; 30% excreted in faeces
- If excretion is insufficient then uric acid becomes saturated and crystals start forming (90% of patients have excess urate crystals because uric acid is not excreted in urine)
State 3 variables that increase liklihood of gout
Hypertension: then placed on thiazide diuretic causes increased Ca2+ levels
Male
Obesity
Increasing age
Serum acid level more than 5.88mg / dL
What score in gout diagnositic criteria suggests gout? [1]
Score > 6
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).
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.
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.
What does this x-ray of a gout patient show? [1]
Rat bite erosions
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.
Explain the three mechanisms of gout development [3]
Purine overproduction:
* This occurs when there is increased cell turnover or lysis of cells leading to release of purines and breakdown to uric acid.
* Causes include myelo- or lymphoproliferative disorders, psoriasis and use of chemotherapy agents.
Increase purine intake:
* There are several foods and beverages that are rich in purines and increase the risk of developing gout.
* These include seafood (i.e. anchovies, sardines), red meat, alcohol and fructose-rich beverages.
Decreased uric acid secretion:
* Uric acid is predominantly renal excreted so anything that affects the kidneys can increase the risk of developing gout.
* Causes include diuretics (i.e. furosemide), acute kidney injury, chronic kidney disease, ACE inhibitors and diabetes mellitus
State two drug classes that could cause decreased uric acid secretion [2]
Name a disease that could cause high turnover of cells and therefore increased purine production [1]
Diuretics: Loop and Thiazide like
psoriasis
Dual energy CT is used to assess measures
RA
OA
OP
Gout
Gout: detects uric acid levels
Explain if presence of hyperuricemia is diagnostic? [1]
What level of uric acid found would indicate treatment is immediately needed? [1]
No: because 5-8% of population have elevated serum uric acid levels (>7mg/dL (0.07mg/ml))
If higher than 11mg/dL (0.11mg/ml) should be treated
How would you treat acute gout / gout attack? [4]
NSAIDs:
* Start with highest dose for 2-3 days & taper down over 2 weeks
Colchicine:
* 2nd line (narrow therapeutic window and risk of toxicity)
Corticosteroids
* For those that can’t use NSAID or colchicine
IL1 biologicals
* Rilonacept, canakinumab, anakinra
* Reduces length of attack and reoccurrences
* Used for patients who have severe and frequent flares
How long should gout symptoms be absent for before stopping NSAID treatment for gout? [1]
2 days
Which IL1 biologicals can be used to treat acute gout? [3]
Rilonacept, canakinumab, anakinra
What type of diet is recommended for gout patients? [2]
Low purine diet AND diet high in vitamin C
What x-ray findings are present in gout patients? [1]
Rat-bite erosions form on the main shaft of the bone where tendons are inserting/joint capsule is inserting
Describe a new technique for visualising gout [1]
Dual energy computed tomography (DECT): able to detect the uric acid crystals deposited in the joint & soft tissue
Describe the pathogenesis of rat-bite erosions
rat-bite erosions are due to osteoclasts eroding the bone in joints with gout
TNF-alpha, IL-1, etc will convert synovial macrophages to osteoclasts
The crystals tend to get lodged in the deeper folds of the joint capsule, meaning the osteoclasts will attack the shaft of the bone
Why are IL-1 biologicals not as useful for treating gout than RA? [1]
have to be used daily, yet with gout flares they are only used acutely for short periods of time. Only used if a patient has severe and frequent flare due to their extreme cost.
Describe how you treat chronic gout [5]
Allopurinol:
* Blocks xanthine oxidase, which is responsible from converting xanthine (which comes from purines in the diet) to urate
Febuxostat:
* non-purine selective inhibitor of xanthine oxidase
uricosuric:
* increases uric acid excretion
Probenecid:
* increases the secretion of uric acid
* fewer side effects than allopurinol.
Rasburicase:
* Catalyses conversion of uric acid to allantoin
Which ARB can be used to treat chronic gout? [1]
Losartan
Describe the pathogenesis of pseudogout [2]
Deposition of calcium pyrophosphate in and around joints onto the surface of the articular cartilage and the fibrocartilage:
- Release of calcium pyrophosphate crystals into the joint space
- followed by neutrophils, macrophages etc phagocytosing the crystals: cytokine release and inflammation.
- The crystals are not as shiny or sharp/needle like, meaning they don’t cause NETosis and the attack is much milder, with a slower onset.
Where is a common place for pseudogout to occur? [2]
Explain why [1]
Wrist and the elbow due to big amounts of fibrocartilage that can be deposited with CPP.
Which cell type is primarily involved in pseudogout CPP formation? [1]
Chondrocytes are the principle cell involved in the formation and deposition of CPP.
What would the shape, size and birefringence of pseudogout crystals be like? [3]
Shape
* rhomboid
Size:
* small (0.5 - 10 microns)
Birefringence:
* weakly positive on plane-polarised light
Which is the most commonly affected joint by pseudogout? [1]
Knee is most commonly affected joint but can affect any joint
Decribe the difference in gout and pseudogout:
- Crystal structure & appearance
- Symptoms
- Joint most commonly affected
Crystals:
* MSU very shiny under polarised light & needle like
* CPP crystals are not as shiny and are rhomboid shaped
Symptoms
* gout: has very painful acute attacks that come on sudden
* pseudo gout: more slowly progressing
Joint:
* Gout: 1st MTP joint
* Pseudogou: knee or wrist
How do cholesterol crystals present under magnification? [1]
Monohydrate cholesterol crystals are identified on the basis of their geometric plates with notched corners
Synovial fluid clearly shows the milky appearance.
Describe how cholesterol crystals are made [1]
Defective drainage of synovial fliud back into the venous system due to synovitis, local destruction, increased permeability of synovial membrane to LDL and HDL & intraarticular bleeding
Which joint in the hand is commonly affected by gout? [1]
carpometacarpal joints
Describe the appearance of aspiration fluid of gout [4]
No bacterial growth
Needle shaped crystals
Negatively birefringent of polarised light
Monosodium urate crystals
