1. Four Stages of Gout  Asymptomatic hyperuricemia Elevated levels of uric acid in the blood but no other symptoms Does not require treatment  Acute gout/Acute gouty arthritis Hyperuricemia has caused the deposit of uric acid crystals in joint spaces Sudden onset of intense pain and swelling in the joints, which also may be warm and very tender Attack commonly occurs at night Triggered by ○ Stressful events, alcohol or drugs, or the presence of another illness Harrison’s Principles of Internal Medicine 17 th edition

2. Four Stages of Gout  Interval/Intercritical gout period between acute attacks no symptoms normal joint function  Chronic Tophaceous gout most disabling stage of gout over a long period (10 years) disease has caused permanent damage to the affected joints and sometimes to the kidneys Solid deposits of urate crystals in joints, usually in the big toe (Tophi) ○ Low grade pain and mild and acute inflammation ○ May progress to affect other joints Uric acid nephrolithiasis ○ Very painful Harrison’s Principles of Internal Medicine 17 th edition

3. Conditions which Contribute to Hyperuricemia ↑Production ↓ExcretionCombination Purine-rich dietRenal insufficiencyG6PD Alcohol Strenuous exerciseDiabetes insipidus Enzyme deficiencies (e.g Lesch-Nyhan and Kelley Seegmiller syndrome) Drugs: Salicylates (>2 g/d), diuretics, anti- TB,levodopa,nicotinic acid, cyclosporine Fructose-1-phosphate aldolase deficiency Lymphoproliferative & Myeloproliferative diseases Polycystic kidney diseaseShock Hemolytic diseasesAcidosis Polycythemia veraLead intoxication PsoriasisHyperparathyroidism; Hypothyroidism Paget's diseaseToxemia of pregnancy Glycogenosis III, V, and VIIDown syndrome Berylliosis;Sarcoidosis; Bartter's syndrome Hyperuricemia, Yasir Qazi, MD. Retrieved from http://emedicine.medscape.com/article/241767-overview Harrison’s Principles of Internal Medicine 17 th edition

4. Renal Involvement in Chronic Gout  Uric Acid Nephrolithiasis Occurs most commonly, but not exclusively, in individuals with gout In gout, prevalence correlates with the serum and urinary uric acid levels o ~50% with serum urate levels of 770 mol/L (13 mg/dL) or o Urinary uric acid excretion >6.5 mmol/d (1100 mg/d) Uric acid can also play a role in other types of kidney stones o May act as a nidus on which calcium oxalate can precipitate o Lower the formation product for calcium oxalate crystallization  Urate Nephropathy (Urate Nephrosis) Late manifestation of severe gout Characterized histologically by MSU crystal deposits surrounded by a giant cell inflammatory reaction in the medullary interstitium and pyramids Rare; cannot be diagnosed in the absence of gouty arthritis Lesions may be clinically silent or cause proteinuria, hypertension, and renal insufficiency Harrison’s Principles of Internal Medicine 17 th edition

5. Renal Involvement in Chronic Gout  Uric Acid Nephropathy Reversible cause of acute renal failure due to precipitation of uric acid in renal tubules and collecting ducts  obstruction to urine flow Dehydration and acidosis favor uric acid crystal formation Develops following sudden urate overproduction and marked hyperuricaciduria Uric acid : creatinine in random urine sample or 24-h specimen is >1 Hypertension Uric acid appears to activate the renin-angiotensin system and inhibit NO, leading to glomerular hypertension and renal injury Harrison’s Principles of Internal Medicine 17 th edition Teng, G.G., Nair, R. & Saag, K.G. (2006). Pathophysiology, clinical presentation and treatment of gout. Drugs. 66 (12), 1547-1563.

6. Outline Management of Uncomplicated Acute Gout. What analgesics are contraindicated in this patient? MMainstay of treatment during an acute attack is the administration of: Nonsteroidal anti-inflammatory drugs (NSAIDs) Colchicine Glucocorticoids In attacks involving one or two joints, intraarticular glucocorticoid injections may be preferable and effective. Ice pack applications and rest of the involved joints can be helpful. What analgesics are contraindicated in this patient? NSAIDS Ibuprofen Naproxen Diclofenac Licofelone Harrison’s Principles of Internal Medicine 17 th edition