Gout Flashcards
What is gout?
Gout is an inflammatory arthritis which progresses from asymptomatic hyperuricaemia (elevated circulating uric acid levels). It is caused by deposition of urate crystals in the synovial fluid of joints bone and other tissues.
What enzyme is not present in humans to break down uric acid?
Uricase
What is the most common cause pf hyperuricemia?
Furosemide
What are the risk factors of gout?
Male Sex
Older age
Genetic factors (mainly reduced excretion of urate)
Metabolic syndrome
Obesity (reduced excretion of urate)
Hypertension (reduced excretion of urate)
Hyperlipidaemia (reduced excretion of urate)
Loop and thiazide diuretics (reduced renal excretion of urate)
Chronic Kidney Disease (reduced excretion of urate)
Osteoarthritis (enhanced crystal formation)
Dietary factors (increased production of uric acid)
• Excess purine-rich foods, fructose, sugar sweetened soft drinks
• Excess alcohol consumption, particularly beer
What causes hyperuricaemia?
1) Increase synthesis/incoming:
a. Enzymatic defects (decrease HGPRT) leads to Lesch-Nyhan syndrome
b. Increase cellular turnover (lymphopoliferative diseases, radiography)
c. Increase intake (dietary purines, ethanol)
2) Decrease Renal excretion
a. Renal failure
b. Drugs (thiazides/furosemides)
Excess consumption of alcohol
Overweight - increased amount of protein and fat intake
Lots of broken down purines in blood
How can asymptomatic hyperuricaemia occur?
Monosodic urate crystalisation occurs with molecule increasing crystak nucleation: collagen, chondroitin sulfate, proteoglycans —> increase of crystals –> tissue crystal deposition —> inflammation
What are the favouring factors for asymptomatic hyperuricaemia to occur?
Decreasing temperature pH Rapid decrease of urate serum levels Intra-articular dehydration Increased intra articular pressure Trauma
What are the 3 mechanisms of how inflammation in gout occurs?
1) Phagocytosis mediated by IgG - crystals precipitated by IgG but cannot digest. Therefore activation of macrophages by this pathway.
2) Phagocytosis mediated by toll like receptor (2 and 4). Crystal can activate the toll-like receptor directly, activate monocyte macrophages
3) Complement activation
What is the mechanism to produce IL-1 beta?
The general consensus is that maturation and release of IL-1β requires two distinct signals:
the first signal leads to synthesis of pro-IL-1β and other components of the inflammasome, such as NLRP3 itself;
the second signal results in the assembly of the NLRP3 inflammasome, caspase-1 activation and IL-1β secretion.
Caspase 1 activation –> Pro-ILb –> IL1-b
What is acute gout?
Sudden onset (frequently during the night)
Acute signs and symptoms of inflammation
5-10 days
Attack is singular and monoarticular
What is chronic gout?
- Lasts months or years
- acute attacks become more frequent and polyarticular (> 4 joints involved)
- Tophus (deposit of sodium urate around the joints in cartilage, bone, bursea, and subcutaenous tissue, in the external ear and kidney).
What would lab exams of gout show?
Increased ESR
Increased CRP
Increased WBC
Increased URICAEMIA
What is the treatment of gout?
Diet – INCREASE water intake and decrease protein intake. Decrease alcohol (has 2 negative effects: favours formation of MSU and causes dehydration which favovurs deposition of crystals)
Block Xanthine oxidase (modulates formation of urate crystals) or can give recombinant uricase
Most common: Allopurinol
Target IL-1
If patient has chronic gout need to couple with anti-inflammatory drugs
Most common: Anakinra
Il-1 cytokine regulates inflammatory process
Can block IL-1, disintegrate biological effect
Canakinumab
What is the management of gout?
NSAIDs (diclofenac, naproxen) - prescribe with PPI
Colchicine if NSAID is contraindicated
Corticosteroids - If NSAID and colchicine are contraindicated
Paracetamol for pain relief
How can you prevent gout?
Decrease body weight
Decrease alcohol intake
Decrease excessive consumption of foods rich in purines
Take regular exercise and stop smoking
Allopurinol
Second line: Febuxostat
