Pathophysiology of Gout + Hyperuricaemia Flashcards
What is hyperuricaemia?
Increased uric acid levels in the body
Increased intake or production or purines
Impaired excretion of uric acid by kidneys
What is gout?
Inflammatory arthritis associated with chronic hyperuricaemia, deposition of intra-articular sodium urate crystals, inflammation + pain
What are the different classifications of hyperuricaemia?
Renal overload
Overproduction
Extra-renal underexcretion type
Renal underexcretion
Combined type
What is the dominant cause of hyperuricaemia?
Underexcretion of urate
What is primary gout a result of?
Environment
What is secondary gout a result of?
Another medical condition/use of drugs
What are examples of drugs that raise serum (urate)?
Diuretics
Cyclosporin
Levodopa
Salicylates (low dose)
What are examples of drugs that lower serum (urate)?
Ascorbic acid
Oestrogens
Losartan
Salicylates (high dose)
Describe the pathogenesis of acute gout
Monosodium urate crystals forms from excessive hyperuricaemia
Recognised by phagocytes + ingested
High conc quickly increases Na+
H2O influx = swelling
Restoration with K+
K+ too low = excess production IL-1
Inflammatory response = GOUT
What are the characteristics of gouty arthritis?
Sudden onset
Middle aged males
Severe pain
Distal joints
Intense inflammation
Recurrent episodes
What is the environment contribution?
Diet
Alcohol
Adiposity + insulin resistance
How does diet contribute?
Purine-free diet reduced blood uric acid levels massively
How do alcohol contribute?
Increases uric acid production by net ATP degradation to AMP
How does adiposity + insulin resistance contribute?
Increased resistance associated with hyperuricaemia
How colchicine work?
Inhibits recruitment + actions of neutrophil leucocytes
Reduces production of pro-inflammatory TNFalpha
