The document discusses hyperuricemia and gout. It defines hyperuricemia as a plasma urate concentration greater than 7.0 mg/dl and can result from increased urate production, decreased urate excretion, or a combination. Gout is caused by the deposition of monosodium urate crystals in the joints and other tissues, which can cause acute inflammatory arthritis. The first metatarsophalangeal joint is commonly affected. Treatment involves medications like colchicine, NSAIDs, or glucocorticoids for acute attacks and urate-lowering therapies for long-term management.

1. Hyperuricemia and gout www.freelivedoctor.com

2. Uric Acid www.freelivedoctor.com

3. Uric Acid Is the final breakdown product of purine degradation in humans www.freelivedoctor.com

4. Urates The ionized forms of uric acid, predominante in plasma, extracellular fluid and synovial fluid. Approximately 98% existing as monosodium urate at pH 7.4 www.freelivedoctor.com

5. Plasma is saturated with monosodium urate at a concentration of 6.8 mg/dl. At higer concentrations, plasma is therfore supersaturated, creating the potential for urate crystal precipitation. www.freelivedoctor.com

6. Urate production varies with the purine content of the diet and the rates of purine biosyntesis, degradation and salvage. www.freelivedoctor.com

7. 2/3 to ¾ of urate is excreted by kidneys, and most of the remainer is eliminated through the intestines. www.freelivedoctor.com

8. Renal handling Glomerular filtration Tubular reabsorption Secretion Postsecretory reabsorption www.freelivedoctor.com

9. Uric acid is more soluble in urine than in water. The pH of urine greatly influences its solubility. pH 5 urine is saturated with uric acid at concentrations ranging from 6 to 15 mg/dl. At pH 7 saturation is reached at concentration between 158 and 200mg/dl www.freelivedoctor.com

10. Serum urate levels vary with age and sex. Children: 3 to 4 mg/dl Adult men: 6 to 6.8 mg/dl www.freelivedoctor.com

11. Hyperuricemia www.freelivedoctor.com

12. Hyperuricemia Defined as a plasma urate concentration > 7.0 mg/dl www.freelivedoctor.com

13. Hyperuricemia Can result from: Increased production of uric acid Decreased excretion of uric acid Combination of the two processes. www.freelivedoctor.com

14. Increased Urate Production Diet provides an exogenous source of purines and, accordingly, contributes to the serum urate in proportion to its purine content. www.freelivedoctor.com

15. Hyperuricemia Foods high in nucleic acid: liver, thymus and pancreas, kidney and anchovy. Restriction intake: reduces: 1 mg/dl www.freelivedoctor.com

16. Endogenous sources: De novo purine biosynthesis: 11 step Increased PRPP synthetase activity and HPRT deficiency are associated with overproduction of purine, hyperuricemia and hyperuricaciduria. www.freelivedoctor.com

17. Decreased Uric Acid Excretion Alterated uric acid excretion could result from decreased glomerular filtration, decreased tubular secretion or enhanced tubular reabsorption. www.freelivedoctor.com

18. Decreased tubular secretion of urate causes the secondary hyperuricemia of acidosis. Diabetic ketoacidosis, starvation, ethanol intoxication, lactic acidosis, and salicylate intoxication are accompanied by accumulations of organic acids (B-hydroxybutyrate, acetoacetate, lactate or salicylates) that compete with urate for tubular secretion. www.freelivedoctor.com

19. Combined Mechanisms Alcohol intake promotes hyperuricemia: Fast hepatic breakdown of ATP and increases urate production. Can induce hyperlacticacidemia, and inhibition of uric acid secretion. The higher purine content in some alcoholic beverages such as beer may also be a factor. www.freelivedoctor.com

20. Prevalence 2 and 13.2% www.freelivedoctor.com

21. Causes of hyperuricemia Primary No recognized cause Hypoxanthine phosphoribosyltransferase deficiency Increased phosphoribosyl pyrophosphatase activity. Secundary Hereditary fructose intolerance Mieloproliferative disease Linfoproliferative disease Hemolitic anemia Drugs: Low-doses salicylate, diuretis, pyrazinamide, ethambutol, nicotinamide, etanol www.freelivedoctor.com

22. Evaluation of Hyperuricemia Hyperuricemia does not represent a disease. Is not an specific indication for therapy. The finding of hyperuricemia is an indication to determine its cause. www.freelivedoctor.com

23. The hyperuricemia of individuals who excrete uric acid above this level while on a purine-free diet is due to purine overproduction, whereas it is due to decreased excretion in those who excrete lower amounts on the purine-free diet. www.freelivedoctor.com

24. Complications of Hyperuricemia The most recognized complication of hyperuricemia is gouty arthritis Nephrolithiasis Urate Nephropathy Uric Acid Nephropathy www.freelivedoctor.com

25. Nephrolithiasis The prevalence of nephrolithiasis correlates with the serum and urinary uric acid levels. Serum urate levels 13 mg/dl Urinary uric acid excretion > 1100 mg/d www.freelivedoctor.com

26. Urate Nephropathy Deposits of monosodium urate crystals surrounded by a giant cell inflammatory reaction in the medullary intrerstitium and pyramids. Clinically: silent or cause proteinuria, hypertension and renal insufficiency. www.freelivedoctor.com

27. Uric acid nephropaty Precipitation in renal tubules and collecting ducts cause obstruction to urine flow. Following sudden urate overproduction and marked hyperuricaciduria: Dehydration and acidosis Lymphoma Cytolytic therapy www.freelivedoctor.com

28. Treatment www.freelivedoctor.com

29. Asymptomatic Hyperuricemia Treatment with anthyperuricemic agents entails inconvenience, cost and potential toxicity. “ Routine” treatment of asymptomatic hyperuricemia cannot be justified. www.freelivedoctor.com

30. Treatment with anthyperuricemic agents in asymptomatic hyperuricemia is not recommended. “ Treatment in special conditions” like patients during cytolytic therapy for neoplastic disease. Justification: prevent uric acid nephropathy. www.freelivedoctor.com

31. Nephrolithiasis Prevention Fluid ingestion (urine >2 L/d) Alcalinization of the urine (sodium bicarbonate or acetazolamide) to increase the solubility of uric acid. Allopurinol (Decrease the serum urate concentration) 300 mg/d www.freelivedoctor.com

32. Uric Acid Nephropathy Vigorous intravenous hydration and diuresis with furosemide. Acetazolamide and sodium bicarbonate (urine pH >7) Allopurinol www.freelivedoctor.com

33. GOUT www.freelivedoctor.com

34. Crystal-induced arthritides MSU (monosodium urate) CPPD (calcium pyrophosphate dihydrate) HA (calcium hydroxyapatite) Calcium oxalate (CaOx) www.freelivedoctor.com

35. Monosodiumurate Gout www.freelivedoctor.com

36. Monosodiumurate Gout Affecting middle-aged to elderly men. Women represent only 5 to 17% of all patients. www.freelivedoctor.com

37. Monosodiumurate Gout Associated with an increased uric acid, hyperuricemia, episodic acute and chronic arthritis, and deposition of MSU crystals in connective tissue tophi and kidneys. www.freelivedoctor.com

38. Acute and chronic arthritis Acute arthritis is the most frequent early clinical manifestation of MSU gout. Usually only one joint is affected initially Polyarticular acute gout is also seen in male hypertensive patients with ethanol abuse as well as in postmenopausal women. www.freelivedoctor.com

39. The metatarso phalangeal joint of the first toe is often involved. Ankles, and knees are also commonly affected. In elderly patients, finger joints may be inflamed. www.freelivedoctor.com

40. The first episode of acute gouty arthritis frequently begins at night. With dramatic joint pain and swelling. www.freelivedoctor.com

41. Joints rapidly become warm, red, and tender, and the clinical appearence often mimics a cellulitis. www.freelivedoctor.com

42. Early attacks tend to subside spontaneously within 3 to 10 days. Most of the patients do not have residual symptoms until next episode. www.freelivedoctor.com

43. Several events may precipitate acute gouty arthritis: Dietary excess Trauma Surgery Excessive ethanol ingestion Glucocorticoid withdrawal www.freelivedoctor.com

44. After many acute attacks, a portion of gouty patients may presents with a chronic nonsymmetric synovitis. Causing potential confusion with rheumatoid arthritis. www.freelivedoctor.com

45. More rarely, the disease will manifest as inflamed or noninflamed periarticular tophaceous deposits in the absence of chronic synovitis. www.freelivedoctor.com

46. Laboratory Diagnosis Even the clinical appearance strongly suggests gout. The diagnosis should be confirmed by needle aspiration of acute or chronically inflamed joints or tophaceous deposits. www.freelivedoctor.com

47. Acute septic arthritis several of the other crystalline – associated arthropathies, and psoriatic arthritis may present with similar clinical features. www.freelivedoctor.com

48. Effusion appear cloudy due to leukocytes and a large amounts crystals ocassionally produce a thick pasty or chalky joint fluid. www.freelivedoctor.com

49. Radiographic Features Cystic changes, well-defined erosions described as punched-out lytic lesion. Soft tissue calcified masses (chronic tophaceous gout) www.freelivedoctor.com

50. Treatment Acute attack: Anti-inflammatory drug: Colchicine Nonsteroidal anti-inflamtory drugs Glucocorticoids Depending on the age of the patient and comorbid conditions. www.freelivedoctor.com

51. Colchicine and NSAIDs may be quiet toxic in the elderly, particularly in the presence of renal insufficiency and gastrointestinal disorders. www.freelivedoctor.com

52. In elderly patients : Intraarticular glucocorticoid injections Cool aplications along with lower oral doses of colchicine. www.freelivedoctor.com

53. Colchicine 0.6 mg tablet every hour until relief of symptoms Gastrointestinal toxicity occurs ( never excede 4 mg) www.freelivedoctor.com

54. Uricosuric agents Probenecid 2oo mg twice Allopurinol 300 mg www.freelivedoctor.com