Life begins with DNA

Life ends with DNR

 Knowledge about gout/urate:
• BC 1500 Ebers papyrus
• BC 469 Hippocrates
• AD 150 Galen – gout is caused by
“debauchery, intemperance and a
hereditary trait”.
• AD 1683 Sydenham.
 DNA

ATP,ADP,AMP GMP,GDP,GTP
Adenosine Guanosine
ITP,IDP,IMP Purines
Inosine
Pentose Pentose
Hypoxanthine Guanine
Xanthine
Xanthine oxidase
Uric acid
 Urate anabolism
• Some xanthine, hypoxanthine and
guanine can be resynthesized to
purines.
• Enzyme concerned may be deficient –
• Lesch-Nyhan syndrome
disease of young males. Very rare.
Mentally deficient, self mutilate,
aggressive, involuntary hand wringing
(athetosis), spastic paraplegia.
 Urate synthesis
Diet Tophi
20%/day
urate pool

Faeces
urine filtration
secretion

Urine
 Gout – heterogeneous
group of diseases
• All patients with gout have
hyperuricaemia.
• People with hyperuricaemia < 15%
have gout.
• Primary gout means that it is the
only disease
• Secondary gout - another disease
causes the hyperuricaemia.
 Hyperuricaemia’s causes:
• Endogenous + obesity
Overproduction of urate
Increased catabolism - ATP turnover
• Exogenous (diet)
• Secondary:
• Renal: under excretion (75-90% of
cases)
• Cell breakdown (e.g. Cytotoxic
therapy)
 Hyperuricaemia,
secondary:
• Lead poisoning
• Hypothyroidism
• Leukaemia
• Diabetes mellitus (diabetic ketoacidosis)
• Cirrhosis
• Myocardial infarction
• Stress
• Idiopathic.
 Hyperuricaemia,
secondary (2):
• Glucose-6-phosphate deficiency
• Myeloproliferative diseases
• Lymphoproliferative diseases
• Multiple myeloma
• Secondary polycythaemia
• Pernicious anaemia
• Haemoglobinopathies
• Cancers
• Psoriasis
• Starvation, radiation, chemotherapy
Hyperuricaemia caused by
drugs:

• Ethanol
• Vitamin C
• Aspirin
• Caffeine
• Diuretics
• Nicotinic acid
• Theophylline.
Hyperuricaemia caused by
hypoxia:
1. Intense physical activity
2. Starvation
3. Glycogen storage diseases
4. Fructose intolerance
5. Alcoholic intoxication
6. Adult respiratory distress syndrome
7. Haemorrhagic shock and similar
conditions.
 Hyperuricaemia and
hypoxia
• Cell is energy starved
• Calcium gets in and
• changes a protein.
• This protein converts xanthine
dehydrogenase to xanthine
oxidase and
• makes “FREE RADICALS”
 Renal handling of urate
• Filtered 98%
• Proximal reabsorption 95%
• Distal secreted 50%
• Distal reabsorbed 90%
• Urine 10% of that filtered.
Hyperuricaemia: impaired
excretion
• Renal failure
• Organic acid overproduction
• Drug therapies:
• Diuretics
• Salicylates.

• Gout, 80% are underexcreters.

Gout, long needle shaped
crystals in tissue:
• Acute: intense pain and swelling in
joint of hand or foot. Attacks begin
at night often after big meal or
alcohol binge. Self limiting disease.
Tophi in outer ear, elbow
and tendons.
• Chronic: deforming arthritis of
joints.
 Gout:
• Incidence 0.2-0.35/1,000.
• Prevalence 0.13-0.37% in a
lifetime.
• Males to females 20:1.
• Hyperuricaemia without gout
2-18% of the population.
 Hyperuricaemia and gout:
Males: Hyperuricaemia Gout
Framingham 5 0.4%
“ >14years 9 2.3%
Finland 5 0.1%
Maori 40 10%
Females:
Framingham >14years 0.4%
Maori 1.8%
 Gout
Supersaturation with urate/uric acid.

Crystals formed

Phagocytosis,
Cell damage chemicals,
Acidosis: urate to uric acid

Renal function altered.

 Gout precipitated by:
• Psychic stress.
• Surgery.
• Alcohol.
• Blood loss.
• Myocardial infarction.
• Penicillin.
• Chlorothiazides.
 Hyperuricaemia:
laboratory work
• Serum urate increased
• Urate crystals in
synovial fluid
• Neutrophils increased
• Urine urate increase
 Pseudogout – usually
elderly.
• Calcium pyrophosphate
crystals in synovial fluid
• Serum urate normal
• Aspirate joint fluid and
carry out microscopy.
 Renal urate calculi

•10% of kidney stones in

North America.
•25% of patients with
primary or secondary
gout.
 Hyperuricaemia:
treatment
• Attack: colchicine
• Later:
• Diet
• No alcohol
• Reduce weight
• High fluid intake
• Urine made alkaline
• Allopurinol (inhibit xanthine oxidase)
 55 year old man
• Obese
• Red-faced
• Pain, redness, swelling of the big toe
joint
• Fever
• Tophi on ear
Laboratory work: uric acid, urea,
creatinine, complete blood count, ESR,
Liver Function Tests, synovial fluid, X
ray of feet, rheumatic factor.
 55 year old man
(continued)
• Check for aspirin use
• Check for thyroid problem
• Alcohol consumption
• Hyperlipidaemia
• Obesity
• Non Insulin Dependant Diabetes
Mellitus.
 55 year old man,
differential diagnosis:
• Gout
• Acute septic arthritis
• Acute osteoarthritis
• Pyrophosphate arthropathy
• Rheumatoid arthritis
• Reactive arthritis to one joint
55 year old man,
treatment
•Diet
•Allopurinol.
 74 year old man
• COPD, CHF, NIDDM, post MI, ARDS now
flushed and coughing sputum
Laboratory work:
Serum creatinine 180 umol/L (50-120)
Serum urea 11 mmol/L (3-7)
Plasma glucose 12 mmol/L (3-5.5)
Serum uric acid 700 umol/L (<450)
 6 year old boy
• Appetite decreased
• Weakness
• Pain in joints
• Fever
• Enlarged spleen, liver, lymph
nodes.
• Diagnosis: acute leukaemia (by
bone marrow aspirate).
6 year old boy (continued)
• Treatment:
• Chemotherapy,
• Radiation,
• Allopurinol

• After chemotherapy treatment:

serum urate 2,000 umol/L (<450)