GOUT

y Uric acid is the end product of the Purine metabolism.

y Hyperuricemia results from over production of uric

acid, inadequate elimination of uric acid by the kidney, or combination or both.

Manifestations of Hyperuricemia
y subcutaneous tophaceous deposits y urolithiasis y nephrolithiasis y renal diseases involving the tubules, interstitium, or

glomeruli

GOUT
y Gout is caused by disorders of purine metabolism

resulting in elevated levels of uric acid.

y > 7 mg/dl in men y > 6 mg/dl in women y prolonged hyperuricemia leads to formation of

monosodium urate crystals.

y Nodular masses of monosodium urate crystals are

deposited in soft tissue-tophi. This causes inflammation in joints resulting in painful Gouty Arthritis.
y Uric acid or sodium urate may also precipitate in

kidneys and ureters renal damage and stone formation.

Risk factors
y Genetics y Male sex y Older age y Overweight y y y y

Excessive alcohol consumption Eating foods rich in purines Exposure to lead Use of certain drugs: aspirin, diuretics, nicotinic acid, cyclosporine, L-DOPA

TYPES OF GOUT Primary Gout

y Primary gout Overproduction of uric acid due to inborn defects with either purine synthesis or its catabolism as in

PRPP synthase abnormality :

y X linked recessive condition y Enzyme not subject to normal allosteric control production

purine

PRPP glutamyl amido transferase abnormality : y Overactive & not subject to feedback inhibition production of purines

Deficiency of enzymes of salvage pathway : y HGPRT deficiency:Lesch Nyhan syndrome y utilisation of Purines(Hypoxanthine and guanine )by salvage pathway PRPP de novo synthesis
y Von Gierkes disease y Elevation of Glutathione reductase

Secondary gout
y Secondary gout results from a variety of diseases that

y y y y

cause an elevated destruction of cells or defective elimination of uric acid: Overproduction of urate:Increased destruction of cells or turn over of cells which occurs in : Leukemia Polycythemia Psoriasis

y Defective elimination of uric acid :occurs in

chronic renal disesase due to: Reduced glomerular filtration rate Reduced distal tubular secretion of uric acid y Hypercatabolic states and starvation-increased rate of cell destruction and impaired uric acid excretion due to : lactic acidosis ketoacidosis

Clinical Features
y y y y

Asymptomatic Hyperuricemia: >9 mg%. Normal: 3.5->7 mg%. Sudden, severe joint pain and swelling Shiny, red skin around the joint Extreme tenderness around the joint

Treatment
y Allopurinol : y Analogue of hypoxanthine. y Competitive inhibitor of xanthine oxidase.

in uric acid & in xanthine & hypoxanthine which are more soluble. y XO converts allopurinol to alloxanthine which is a more powerful inhibitor of XO. Thus this is an example of suicide inhibition.
y

y Uricosuric agents e.g. probenecid , sulfinpyrazone -

uric acid reabsorption and its excretion

y Colchicine -

movement of granulocytes into the affected area. Used to treat the arthritis in gout

y Aspirin & other anti-inflammatory agents y Reduced dietary intake of purine & restrict

alcohol