Gout

Question 1

What physiological phenomenon causes gout

Answer 1

Gout is caused by the build up and deposition of sharp needle-like crystals of monosodium urate in areas of slow blood flow like the joints and renal tubules

Question 2

What physiological phenomenon causes gout

Answer 2

Gout is caused by the build up and deposition of sharp needle-like crystals of monosodium urate in areas of slow blood flow like the joints and renal tubules

Question 3

Where does the uric acid come from

Answer 3

Purines and pyrimidines are both contain nitrogen atoms
Purines are key components of nucleic acids (found in DNA, RNA). When cells and the nucleic acids within those cells breakdown throughout the body, the purines are broken down into uric acid. Uric acid can be filtered out of the blood and then excreted into the urine

Question 4

Why can uric acid cause problems when its usualy dealt with automatically by the body

Answer 4

Uric acid has limited solubility in body fluids, it will manifest as hyperuricaema when the rate at which it is made exceeds solubility. Uric acid can lose an ion (at pH 7.4) to become urate, and this can combine with the sodium ion to become monosodium urate (i.e. the sharp needle link crystals).

Question 5

Which foods contain high, moderate and low amounts of purines

Answer 5

High - Offal, Game, Oily fish, Seafood, Meat and yeast extracts

Medium - Meat/poultry,
Mushrooms and mycoprotein,
Dried peas, beans and legumes,
Some vegetables – asparagus, cauliflower, spinach, Wholegrains

Low - Dairy, Eggs, Bread and cereals (except wholegrain), Pasta and noodles, Fruit and vegetables

Question 6

What are the risk factors for developing gout

Answer 6

Increased purine intake 
Overproduction of uric acid
Taking loop and thiazide diuretics 
Some medicines that can raise uric acid levels
Genetic predisposition
Obesity
Hypertension
Dyslipidaemia
Alcohol intake (leads to dehydration and subsequent causes decreased clearance of uric acid) 
Male gender

Question 7

Why are loop and thiazide diuretics associated with the development of gout

Answer 7

Loop and thiazide diuretics cause volume depletion and reduced tubular renal secretion of uric acid and are commonly associated with the development of gout

Question 8

Which medicines are known to raise uric acid levels

Answer 8

Aspirin
    Ciclosporin
    Cytotoxic medicines
    Diuretics (loop and thiazide)
    Ethambutol
    Levodopa
    Pyrazinamide
    Ribavarin and interferon
    Teriparatide

Question 9

What are the key symptoms of gout and which presents first

Answer 9

Crystals build up underneath the skins
Yellow or white bumps (tophi)
can damage joints
Gout usually affects the first metatarsal joint of the big toe – this is known as podagra.

Question 10

Where does the uric acid come from

Answer 10

Purines and pyrimidines are both contain nitrogen atoms
Purines are key components of nucleic acids (found in DNA, RNA). When cells and the nucleic acids within those cells breakdown throughout the body, the purines are broken down into uric acid. Uric acid can be filtered out of the blood and then excreted into the urine

Question 11

Why can uric acid cause problems when its usualy dealt with automatically by the body

Answer 11

Uric acid has limited solubility in body fluids, it will manifest as hyperuricaema when the rate at which it is made exceeds solubility. Uric acid can lose an ion (at pH 7.4) to become urate, and this can combine with the sodium ion to become monosodium urate (i.e. the sharp needle link crystals).

Question 12

Which foods contain high, moderate and low amounts of purines

Answer 12

High - Offal, Game, Oily fish, Seafood, Meat and yeast extracts

Medium - Meat/poultry,
Mushrooms and mycoprotein,
Dried peas, beans and legumes,
Some vegetables – asparagus, cauliflower, spinach, Wholegrains

Low - Dairy, Eggs, Bread and cereals (except wholegrain), Pasta and noodles, Fruit and vegetables

Question 13

What are the risk factors for developing gout

Answer 13

Increased purine intake 
Overproduction of uric acid
Taking loop and thiazide diuretics 
Some medicines that can raise uric acid levels
Genetic predisposition
Obesity
Hypertension
Dyslipidaemia
Alcohol intake (leads to dehydration and subsequent causes decreased clearance of uric acid) 
Male gender

Question 14

Why are loop and thiazide diuretics associated with the development of gout

Answer 14

Loop and thiazide diuretics cause volume depletion and reduced tubular renal secretion of uric acid and are commonly associated with the development of gout

Question 15

Which medicines are known to raise uric acid levels

Answer 15

Aspirin
    Ciclosporin
    Cytotoxic medicines
    Diuretics (loop and thiazide)
    Ethambutol
    Levodopa
    Pyrazinamide
    Ribavarin and interferon
    Teriparatide

Question 16

What are the key symptoms of gout and which presents first

Answer 16

Crystals build up underneath the skins
Yellow or white bumps (tophi)
can damage joints
Gout usually affects the first metatarsal joint of the big toe – this is known as podagra.

Question 17

What happens when gout attacks occur repeatedly

Answer 17

Repeat gout attacks can develop into chronic gout (type of arthritis with joint tissue destruction and deformity).

Chronic gout can also lead to a permanent build up of urate crystals tophi which form along the bones underneath the skin. Patients with chronic gout are also at increased risk of developing kidney stones (made of urate crystals) and urate nephropathy,

Question 18

WHat are the aims of treatment for gout and how do we

Answer 18

The aim of the treatment is relieve pain (and swelling) rapidly.
1st line treatment is NSAIDS and if they are not suitable then colchicine can be used. It is thought the mode of action relates to the migration of white blood cells – arresting the assembly of microtubules in neutrophils and inhibiting various cell functions. Colchicine takes around 6 hours to take actions versus 2 hours for an NSAID
If NSAIDS or colchicine contraindicated or ineffective = Corticosteroids

Question 19

What are the side effects and councelling points for colchicine

Answer 19

Common side effects include abdominal cramps, nausea and vomiting. Rarely, bone marrow suppression, neuropathy and myopathy can also occur.

Question 20

What is the aim of prophylaxis of gout

Answer 20

Aim of prophylaxis is to;
Maintain serum uric acid levels below the saturation point of monosodium urate; if serum urate is maintained below this level, crystal deposits dissolve

Question 21

How do we treat gout for prophylaxis pharmocologically

Answer 21

If a patient has 1 or more acute attaches within 12 months of an initial attack, uric acid lowering therapy will be required to prevent further flare-ups. In some patient groups it may be appropriate to start prophylaxis after the first attack – those with visible tophi, those with uric acid stones and those who need to continue on diuretics. The drugs we use are:
Allopurinol
Febuxostat
Uricosurics
Start medication 2-3 weeks after an acute attack has completely resolved.

Question 22

How does allopurinol work to treat gout

Answer 22

It inhibits the action of the enzyme xanthine oxidase, thus reducing the production of uric acid.

Question 23

How does Febuxostat work to treat gout

Answer 23

Febuxostat is a more selective and potent inhibitor of xanthine oxidase than allopurinol, and has no effect on other enzymes involved in purine or pyrimidine metabolism.

Question 24

How do Uricosurics work to treat gout

Answer 24

Uricosuric medicines that increase excretion of uric acid, have traditionally been used to manage gout but are less relevant clinically now

Question 25

How can a patient modify their lifestyle to help prevent gout attacks

Answer 25

Engaging with moderate physical exercise (not intense as this can raise uric acid levels due to increased cell turnover)
Lose weight gradually if overweight
Ensure purine intake is no more than 200mg/day
Men should restrict alcohol consumption to less than 14 units per week (updated recommended limit)
Men and women should have 3-alcohol free days/week