Gout Flashcards
Define Gout.
Gout is a type of arthritis and is a clinical manifestation of hyperuricaemia resulting in the deposition of mono sodium urate monohydrate crystals in and around the joints causing acute inflammation and tissue damage.
What is hyperuricaemia caused by?
Either caused by an increase in production of uric acid and / or reduced excretion.
What is the prevalence and incidence of Gout in the UK?
The prevalence of gout in the UK is 2.49%.
The incidence in the UK is 1.77 per 1000 people a year
What is the US prevalence of Gout?
3.9%
What age is Gout more prevalent?
Men between 30-60 years
Women after menopause
Very rare under the age of 20
Will Gout always occur when a patient has hyperuricaemia?
No, Gout is a clinical manifestation of hyperuricaemia and does not develop in every patient.
Alternatively there are incidents where a patient has normal uric acid levels but suffers from gout attacks.
Therefore, the risk of developing is higher then uric acid levels are higher.
What is the ratio of prevalence of men and women who develop Gout?
4.3 : 1
What are some of the risk factors for Gout?
Obesity, High blood pressure and/or Diabetes
Having a close relative with gout (family history)
Kidney problems
Eating foods that cause a build-up of uric acid, such as red meat, offal and seafood
Drinking too much beer or spirits
Briefly describe the pathophysiology of Gout?
Gout occurs when there is an increase in uric acid levels. Uric acid is produced as an end product of purine metabolism.
Hypoxanthine is converted Xanthine and then to Uric acid by a single enzyme Xanthine Oxidase. The kidneys are responsible for the majority of excretion of uric acid - 2/3 in the urine, whilst the other 1/3 is excreted in the faeces facilitated by bile. When the kidneys are working normally they work very specifically to ensure the uric acid range in the blood is very controlled, however when there is either an overproduction of uric acid (over-producers) or the kidneys are not working properly (under-excreters) the levels of uric acid build up in the blood, potentially leading to the development of Gout.
Describe the overall reabsorption and excretion amounts of uric acid.
When Uric Acid is first filtered in the glomerular, 90-100% of the uric acid is reabsorbed in the proximal tubule.
50% is then actively secreted in the distal tubule.
40-45% is post secretory reabsorbed. 5-10% of the original glomerular load is excreted.
Of those who develop Gout, what percentage is due to being over-producers and what percentage is due to being under secretors.
10% of patients with Gout are due to the increased rate of synthesis of purine precursors of uric acid.
90% is due to the reduced elimination of uric acid y the kidney.
State the differences in aetiology of primary and secondary Gout.
Primary Gout has no singular identifiable cause other than possibly genetic predisposition.
Secondary Gout is the type of Gout caused by another condition or factor that affects the levels of uric acid in the body.
State some foods that have a high purine content and hence result in over production.
Red meat
Offal
Sea food
What are some of the conditions that can cause over production of purine precursors?
Neoplasia
Psoriasis
Haemolytic anaemias
Cell lysis due to chemotherapy
Enzyme defects leading to increased synthesis (Xanthine Oxidases)
What are some of the contributing factors that can result in uric acid under excretion?
Hyperuricaemia
Alcohol
Drugs affecting kidney reabsorption
What are some other independent factors that lead to Gout development?
Triggers- physical stress
Joint trauma- tight shoes, hill walking, hiking, history of joint trauma
Hypertension
Obesity
Hypertriglyceridemia
What are some drugs that can affect renal function and hence excretion of UA?
Diuretics - especially thiazide (due to volume depletion and reduced tubular excretion.
Other drugs include:
Aspirin
Ciclosporin
Omeprazole
Ethambutol
Pyrazinamide
Niacin
Didanosine
Levodopa
Cytotoxics
How does hyperuricaemia then contribute to a reduction in UA excretion?
High circulating levels of UA results in a high urate loading passing through the kidney. This then results in an increase of urate reabsorption to avoid the dumping of insoluble urate into the urinary tract.
Consequently this results in a reduction of tubular secretion and an overall reduction in excretion.
What UA level is monosodium urate crystallisation most likely to occur?
When UA levels are persistently over 380 micromol/mL which is known as the solubility limit.
What is the pka of UA?
Uric acid is a weak acid with a pka of 5.8, meaning that at physiological pH it is ionised and able to form a salt (hence formation of monosodium urate.
When does crystallisation of monosodium urate crystals occur?
Once supersaturation has occurred, the solubility limit has been reached.
What is solubility influenced by?
Temperature
pH
Cation concentration
Articular dehydration and presence of nucleating agents
What are some examples of nucleating agents which influences solubility?
Non-aggregated proteoglycans
Insoluble collagens
Chondroitin
Do symptoms of Gout begin and soon as crystal formation occurs?
No, deposition and formation of monosodium urate crystals can occur for years before symptoms appear.
Usually symptoms only occur once the crystals have been shed into the bursa (which are small sacs of synovial fluid surrounding the joint), this then triggers an inflammatory reaction.
What are some of the precipitating factors that can cause shedding of these crystals?
Trauma
Dehydration
Rapid weight loss
Illness
Surgery
What is the effect of urate crystals presence on the immune response?
Initiates amplifies and sustains inflammatory responses by:
Humoral and cellular inflammatory mediators
Complement system
By triggering these inflammatory pathways this then results in:
Pro-inflammatory cascade of cytokines, chemotactic factors, TNF
Inflammatory cell accumulation (monocytes and mast cells in the early early stage, neutrophils in the late stage).
What is a crucial pro-inflammatory mediator involved in Gout?
IL-1B
State the 5 progressive stages of Gout.
Asymptomatic hyperuricaemia
Acute gouty arthritis
Interval gout/ Intercritical Gout
Chronic tophaceous Gout
Gouty nephropathy
Which joints are normally first affected by Gout?
90% of Gout first precipitates in one joint
80% of cases begin in the first metatarsophalangeal joint (big toe)
Other joints that can be affected:
Small joints of feet/ankles
Hands
Elbow
Knees
What are some of the first symptoms of Gout?
Severe pain with hot, red, swollen joints
Abrupt start, maximum intensity at 8-12 hours
Weight bearing is impossible
Erthyema
Synovitis
Increase in WBC (Leucocytosis)
Confusion in the elderly
When is a Gout attack most likely to happen?
Normally after a trigger such as alcohol or food
What happens if Gout is left untreated?
After 7 days it resolves itself
But there will be desquamation of the overlying skin (skin shedding)
Describe what occurs in the Intercritical Gout stage.
This is simply the time between Gout attacks.
This can be months to years without the patient experiencing any symptoms
Describe what occurs in the Chronic tophaceous Gout stage.
In this stage, which is normally 10 years plus after Gout diagnosis / of hyperuricaemia, there is the development of tophi.
Tophi are white deposits of monosodium urate crystals which appear as nodules on the joint.
These usually occur subcutaneously or in the periarticular areas.
What are some of the complications that can occur in Gouty nephropathy?
Due to crystal deposition around the renal tubules.
Complications include:
Interstitial nephritis
Proteinuria
Renal impairment
Renal stone formation
What are some of the complications of Gout in general?
Cardiovascular disease and cardiovascular mortality.
Chronic arthritis.
Chronic kidney disease.
Joint damage.
Reduced quality of life.
Renal stones.
Tophi.
When should Gout be suspected?
Rapid onset of severe pain together with redness and swelling in one or both metatarsophalangeal joints.
Tophi.
What may the assessment for Gout include?
Assessment of gout should include taking a medical history, examining the person, and measuring the serum urate level.
May also involve:
Joint fluid microscopy - presence of crystals and absence of infection (rule out septic arthritis)
Joint X-ray - rule out other causes
Standard bloods - RF, lipids, glucose