StagesClinical Features (1)Asymptomatic hyperuricemiahigh uric acid level is present but without symptoms (2) Acute Gouty Arthritishigh uric acid level with crystal deposits in joint spaces, causing severe pain, swelling, warmth and tenderness. Usually occurring at night may subside spontaneously-> 3-10 days Precipitated by dietary excess, trauma, surgery, ethanol, serious illness, smoking (3) Intercritical Goutsilent period between attacks, pain-free joints functioning normally (4) Chronic Tophaceous Goutwith permanent damage to the affected joints and to the kidneys Spreading to tendons, tophi of the ears and fingers, hands, and also the elbows and knees, in the cartilage, and the flexors in the forearms Early and proper treatment can prevent the onset of advanced stage gout. Harrison’s Principles of Internal Medicine 17 th Edition;

Urate OverproductionDecreased Uric Acid ExcretionCombined Mechanism Primary Idiopathic HPRT deficiency PRPP synthetase overactivity Hemolytic processees Lymphoproliferative diseases Myeloproliferative Diseases Polycythemia Vera Psoriasis Paget’s Disease Glycogenosis III, V and VII Rhabdomyolysis Exercise Alcohol Obesity Purine-rich Diet Primary Idiopathic Renal insufficiency Polycystic Kidney Disease Diabetes insipidus Hypertension Lactic acidosis Diabetic ketoacidosis Starvation ketosis Sarcoidosis Lead intoxication Hyperparathyroidism Hypothyroidism Toxemia of pregnancy Bartter’s syndrome Down Syndrome Drug ingestion: Salicylates (>2g/d) Diuretics Alcohol Levodopa Ethambutol Pyrazinamide Nicotinic acid cyclosporine Glucose-6-phosphatase deficiency Fructose-1-phosphatase aldolase deficiency Alcohol Shock Harrison’s Principles of Internal Medicine 17 th Edition

NEPHROLITHIASIS -Occurs most commonly but not exclusively in patients with gout -Serum urate level of 770umol/L (13mg/dL) or urinary excretion >6.5mmol/d (1100mg/d) URATE NEPHROPATHY(Urate nephrosis) -Rare cause of renal insufficiency attributed to monosodium urate crystal deposition in the renal interstitium URIC ACID NEPHROPATHY -Reversible cause of renal of acute renal failure resulting from deposition of large amounts of uric acid crystals in the renal collecting ducts, pelvis and ureters Harrison’s Internal Medicine17 th ed vol 2

MANAGEMENT OF UNCOMPLICATED ACUTE GOUTY ARTHRITIS NSAIDs Colchicine Glucocorticoids ACTH Reduce inflammation: Pharmacologic Ice packs Rest of involved joints Reduce inflammation: Non-pharmacologic NSAID choice are those of propionic acid derivatives which have short half-life i.e. ibuprofen, diclofenac, sulindac, naproxen Harrison’s Principle of Internal Medicine 17 th edition

MANAGEMENT OF UNCOMPLICATED ACUTE GOUTY ARTHRITIS Probenecid Allopurinol Losartan, fenofibrate, amlodipine Control hyperuricemia: Pharmacologic Low purine diet Increased fluid intake Prevent diuretics Control body weight Limit ethanol consumption Control hyperuricemia: Non- pharmacologic Harrison’s Principle of Internal Medicine 17 th edition

CONTRAINDICATED ANALGESICS TO THE PATIENT Salicylates (aspirin): blocks action of probenecid Acetaminophen: renal tubular necrosis NSAIDs progressive renal insufficiency Allopurinol proteinuria, hematuria, tubular necrosis Colchicine