Gout Flashcards
What is gout and hyperuricaemia?
This is the most common inflammatory arthritis and is caused by an inflammatory response to monosodium urate crystals which from in the presence of high serum urate levels
What is the classical evolution of hyperuricaemia and gout?
There is a period of asymptomatc hyperuricemia there is then a period where acute flares of pain occur which are bridged by painless intercritical segments this will eventually progress to advanced bout where the painless intercritical segments have become painful intercritical segments
What are the epidemiological features of gout?
It is more common in maori and pacific than Asian and European
It is also more common in men than women and prevalence has been increasing
Incidence increases in women after menopause
What are the factors which increase the risk of gout?
Beer
Red meat
Seafood
Fructose
What are the factors which decrease the risk of gout?
Low fat dairy
Coffee
Cherries
Vitamin C
What are the Co-morbidities associated with gout?
Gout is associated with an increased risk of metabolic syndrome the development of type 2 diabetes and an increase in the risk of acute myocardial infarction
What are the acquired causes of urate overproduction?
A high purine diet
Fructose ingestion
Disorders associated with high cellular turnover
Alcohol intake
What are the genetic causes of urate overproduction?
HPRT deficiency
PRS superactivity
What are the acquired causes of uric acid underexcretion?
Metabolic syndrome
Diuretic use
Renal disease
Lactae or ketones
What are the genetic causes of uric acid under excretion?
This is mostly the result of complex genetic interactions rather than simply the actions of a single gene but some of the genes implicated are
SLC2A9
ABCG2
URAT1
Variants in urate transporters
Uromodulin mutations
Genes involved in carbohydrate metabolism
How does renal transport of uric acid occur?
There are proteins which both actively secrete and reabsorb uric acid in the nephron
What can induce the formation of MSU crystals?
Urate supersuspension pH Temperature Joint trauma or debris Proteins like IgM, IgG and collagen
What is the role of innate immunity in acute gout?
Uric acid results in the formation of MSU crystals these cause neutrophil/monocyte activation which can lead to phagocytosis and removal of the crystrals as well as the release of proinflammatory mediators
What is the role of IL-1 and the NLRP3 inflammasome in acute gout?
These play a role in the initiation phase of acute gout with the inflammasome recognizing the crystal and IL-1 regulating the inflammation which results
What occurs in the resolution phase of acute gout?
There is protein coating of the crystals Phagocytosis of apoptotic neutrophils Anti-inflammatroy signalling pathways Macrophage differentiation Anti-inflammatory cytokines such as TGF-Beta and IL-10