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Flashcards in Gout Deck (30):

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?

Red meat


What are the factors which decrease the risk of gout?

Low fat dairy
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
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
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


What occurs in chronic tophaceous gout?

The MSU crystals are walled off by a ring of immune cells, primarily macrophages and surrounded by a fibrotic capsule


What occurs to oesteoclastogenesis in gout?

In chronic gout this becomes disordered with there being the presence of cells in the synovial fluid capable of rapid differentiation and an increased presence at the tophus


What are the Key checkpoints in gout pathogenesis?

Hyperuricaemia (caused by either overproduction of urate or more commonly underexcretion of uric acid) this is followed by formation of MSU crystals which may lead to Acute gout followed by resolution of the acute gout attack or to chronic gout and tophus formation


How does the overproduction of urate occur?

This may be acquired due to a high purine diet, fructose ingestion, alcohol intake or disorders associated with high cellular turnover
Or it may be due to genet causes like HPRT deficiency or PRS superactivity


How does the under excretion of uric acid occur?

This may be acquired through metabolic syndrome, diuretic use, renal disease or lactate and ketone presence
Or it may be linked to genetic causes such as urate transporter mutations or carbohydrate metabolism mutations


What are the features of the acute gout phase?

There is a principal role played by NALP3 and IL-1beta
There is inflammasome activation, the presence of innate immune cells and other resident cells within the joint there are also soluble mediators of inflammation


What are the features of the resolution of acute gout attacks?

Protein coating of crystals, anti-inflammatory cytokines and signalling pathways as well as macrophage differentiation


What are the features of chronic gout and tophus formation?

Macrophage activation and granuloma formation
Oesteoclast activation


How can gout be detected/visualised?

Plain radiography
Ultrasonography (where a thickening of the double contour zone is observed)
Dual energy CT which can detect the chemical composition of urate


How is gout treated?

Treatment of the acute flare is done by NSAIDs, Colchine, Prednisone Intra-articular corticosteroid, ACTH and IL-1 inhibitors
Prophylaxis against acute flares is treated with NSAIDs, Colchine and IL-1 inhibitors
Urate lowering therapy for chronic gout uses Xanthine oxidase inhibitors, uricosuric agents and Uricase


Who should be treated with urate lowering therapy?

Those who have an established diagnosis of gout and more than 2 attacks a year or those who have tophi on examination and imaging, CKD2 or worse or those who have past urolithiasis


What is the target concentration for uric acid with urate lowering therapy?

0.36 mmol/L


What is Allopurinol?

This is a pill which only needs to be taken once daily, has no requirement for fluid intake advice and is effective regardless of how the high levels of uric acid have been caused


What are the therapeutic options for allopurinol intolerant patients?

Uricosuric agents which promote urate excretion in the kidney however the fluid retention can then be a problem for people who have comorbid conditions
Or there may be methods which allow desensitization of the patient to allopurinol


Is dietary advice a good way to treat gout patients?

No as low purine diets are commonly unpalatable and they are only moderately effective at lowering serum urate