Hyperuricemia and gout www.freelivedoctor.com
Uric Acid www.freelivedoctor.com
Uric Acid  <ul><li>Is the final breakdown product of purine degradation in humans </li></ul>www.freelivedoctor.com
Urates <ul><li>The ionized forms of uric acid, predominante in plasma, extracellular fluid and synovial fluid. </li></ul><...
<ul><li>Plasma is saturated with monosodium urate at a concentration of 6.8 mg/dl. </li></ul><ul><li>At higer concentratio...
<ul><li>Urate production varies with the purine content of the diet and the rates of purine biosyntesis, degradation and s...
<ul><li>2/3 to ¾ of urate is excreted by kidneys, and most of the remainer is eliminated through the intestines.  </li></u...
Renal handling <ul><li>Glomerular filtration </li></ul><ul><li>Tubular reabsorption </li></ul><ul><li>Secretion </li></ul>...
<ul><li>Uric acid is more soluble in urine than in water. </li></ul><ul><li>The pH of urine greatly influences its solubil...
<ul><li>Serum urate levels vary with age and sex. </li></ul><ul><li>Children: 3 to 4 mg/dl </li></ul><ul><li>Adult men: 6 ...
Hyperuricemia www.freelivedoctor.com
Hyperuricemia <ul><li>Defined as a plasma urate concentration > 7.0 mg/dl </li></ul>www.freelivedoctor.com
Hyperuricemia <ul><li>Can result from: </li></ul><ul><ul><li>Increased production of uric acid </li></ul></ul><ul><ul><li>...
Increased Urate Production <ul><li>Diet provides an exogenous source of purines and, accordingly, contributes to the serum...
Hyperuricemia <ul><li>Foods high in nucleic acid: liver, thymus and pancreas, kidney and anchovy. </li></ul><ul><ul><li>Re...
<ul><li>Endogenous sources: </li></ul><ul><ul><li>De novo purine biosynthesis: 11 step </li></ul></ul><ul><ul><li>Increase...
Decreased Uric Acid Excretion <ul><li>Alterated uric acid excretion could result from decreased glomerular filtration, dec...
<ul><li>Decreased tubular secretion of urate causes the secondary hyperuricemia of acidosis. </li></ul><ul><li>Diabetic ke...
Combined Mechanisms <ul><li>Alcohol intake promotes hyperuricemia:  </li></ul><ul><li>Fast hepatic breakdown of  ATP and i...
Prevalence <ul><li>2 and  13.2% </li></ul>www.freelivedoctor.com
Causes of hyperuricemia <ul><li>Primary </li></ul><ul><li>No recognized cause </li></ul><ul><li>Hypoxanthine phosphoribosy...
Evaluation of Hyperuricemia <ul><li>Hyperuricemia does not represent a disease.  </li></ul><ul><li>Is not an specific indi...
<ul><li>The hyperuricemia of individuals who excrete uric acid above this level while on a purine-free diet is due to puri...
Complications of Hyperuricemia <ul><li>The most  recognized complication of hyperuricemia is gouty arthritis </li></ul><ul...
Nephrolithiasis <ul><li>The prevalence of nephrolithiasis correlates with the serum and urinary uric acid levels. </li></u...
Urate Nephropathy <ul><li>Deposits of monosodium urate crystals surrounded by a giant cell inflammatory reaction in the me...
Uric acid nephropaty  <ul><li>Precipitation in renal tubules and collecting ducts cause obstruction to urine flow. </li></...
Treatment www.freelivedoctor.com
Asymptomatic Hyperuricemia <ul><li>Treatment with anthyperuricemic agents entails inconvenience, cost and potential toxici...
<ul><li>Treatment with anthyperuricemic agents in asymptomatic hyperuricemia is not recommended. </li></ul><ul><li>“ Treat...
Nephrolithiasis Prevention <ul><li>Fluid ingestion (urine >2 L/d) </li></ul><ul><li>Alcalinization of the urine (sodium bi...
Uric Acid Nephropathy <ul><li>Vigorous intravenous hydration and diuresis with furosemide. </li></ul><ul><li>Acetazolamide...
GOUT www.freelivedoctor.com
Crystal-induced arthritides <ul><li>MSU (monosodium urate) </li></ul><ul><li>CPPD (calcium pyrophosphate dihydrate) </li><...
Monosodiumurate Gout www.freelivedoctor.com
Monosodiumurate Gout <ul><li>Affecting middle-aged to elderly men. </li></ul><ul><li>Women represent only 5 to 17% of all ...
Monosodiumurate Gout <ul><li>Associated with an increased uric acid, hyperuricemia, episodic acute and chronic arthritis, ...
Acute and chronic arthritis <ul><li>Acute arthritis is the most frequent early clinical manifestation of MSU gout. </li></...
<ul><li>The metatarso phalangeal joint of the first toe is often involved. </li></ul><ul><li>Ankles, and knees are also co...
<ul><li>The first episode of acute gouty arthritis frequently begins at night. </li></ul><ul><li>With dramatic joint pain ...
<ul><li>Joints rapidly become warm, red, and tender, and the clinical appearence often mimics a cellulitis. </li></ul>www....
<ul><li>Early attacks tend to subside spontaneously within 3 to 10 days.  </li></ul><ul><li>Most  of the patients do not h...
<ul><li>Several events  may precipitate acute gouty arthritis: </li></ul><ul><ul><li>Dietary excess </li></ul></ul><ul><ul...
<ul><li>After many acute attacks, a portion of gouty patients may presents with a chronic  nonsymmetric synovitis.  </li><...
<ul><li>More rarely, the disease will manifest as inflamed or noninflamed periarticular tophaceous deposits in the absence...
Laboratory Diagnosis <ul><li>Even the clinical appearance strongly suggests gout. The diagnosis should be confirmed by nee...
<ul><li>Acute septic arthritis several of the other crystalline – associated arthropathies, and psoriatic arthritis may pr...
<ul><li>Effusion appear cloudy due to leukocytes and a large amounts crystals ocassionally produce a thick pasty or chalky...
Radiographic Features <ul><li>Cystic changes, well-defined erosions described as punched-out lytic lesion. </li></ul><ul><...
Treatment <ul><li>Acute attack: </li></ul><ul><li>Anti-inflammatory drug: </li></ul><ul><ul><li>Colchicine </li></ul></ul>...
<ul><li>Colchicine and NSAIDs may be quiet toxic in the elderly, particularly in the presence of renal insufficiency and g...
<ul><li>In elderly patients : </li></ul><ul><ul><li>Intraarticular glucocorticoid injections </li></ul></ul><ul><ul><li>Co...
<ul><li>Colchicine </li></ul><ul><ul><li>0.6 mg tablet every hour until relief of symptoms  </li></ul></ul><ul><ul><li>Gas...
<ul><li>Uricosuric agents  </li></ul><ul><ul><li>Probenecid 2oo mg  twice </li></ul></ul><ul><ul><li>Allopurinol 300 mg </...
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Hyperuricemia and gout

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Hyperuricemia and gout

  1. 1. Hyperuricemia and gout www.freelivedoctor.com
  2. 2. Uric Acid www.freelivedoctor.com
  3. 3. Uric Acid <ul><li>Is the final breakdown product of purine degradation in humans </li></ul>www.freelivedoctor.com
  4. 4. Urates <ul><li>The ionized forms of uric acid, predominante in plasma, extracellular fluid and synovial fluid. </li></ul><ul><li>Approximately 98% existing as monosodium urate at pH 7.4 </li></ul>www.freelivedoctor.com
  5. 5. <ul><li>Plasma is saturated with monosodium urate at a concentration of 6.8 mg/dl. </li></ul><ul><li>At higer concentrations, plasma is therfore supersaturated, creating the potential for urate crystal precipitation. </li></ul>www.freelivedoctor.com
  6. 6. <ul><li>Urate production varies with the purine content of the diet and the rates of purine biosyntesis, degradation and salvage. </li></ul>www.freelivedoctor.com
  7. 7. <ul><li>2/3 to ¾ of urate is excreted by kidneys, and most of the remainer is eliminated through the intestines. </li></ul>www.freelivedoctor.com
  8. 8. Renal handling <ul><li>Glomerular filtration </li></ul><ul><li>Tubular reabsorption </li></ul><ul><li>Secretion </li></ul><ul><li>Postsecretory reabsorption </li></ul>www.freelivedoctor.com
  9. 9. <ul><li>Uric acid is more soluble in urine than in water. </li></ul><ul><li>The pH of urine greatly influences its solubility. </li></ul><ul><li>pH 5 urine is saturated with uric acid at concentrations ranging from 6 to 15 mg/dl. </li></ul><ul><li>At pH 7 saturation is reached at concentration between 158 and 200mg/dl </li></ul>www.freelivedoctor.com
  10. 10. <ul><li>Serum urate levels vary with age and sex. </li></ul><ul><li>Children: 3 to 4 mg/dl </li></ul><ul><li>Adult men: 6 to 6.8 mg/dl </li></ul>www.freelivedoctor.com
  11. 11. Hyperuricemia www.freelivedoctor.com
  12. 12. Hyperuricemia <ul><li>Defined as a plasma urate concentration > 7.0 mg/dl </li></ul>www.freelivedoctor.com
  13. 13. Hyperuricemia <ul><li>Can result from: </li></ul><ul><ul><li>Increased production of uric acid </li></ul></ul><ul><ul><li>Decreased excretion of uric acid </li></ul></ul><ul><ul><li>Combination of the two processes. </li></ul></ul>www.freelivedoctor.com
  14. 14. Increased Urate Production <ul><li>Diet provides an exogenous source of purines and, accordingly, contributes to the serum urate in proportion to its purine content. </li></ul>www.freelivedoctor.com
  15. 15. Hyperuricemia <ul><li>Foods high in nucleic acid: liver, thymus and pancreas, kidney and anchovy. </li></ul><ul><ul><li>Restriction intake: reduces: 1 mg/dl </li></ul></ul>www.freelivedoctor.com
  16. 16. <ul><li>Endogenous sources: </li></ul><ul><ul><li>De novo purine biosynthesis: 11 step </li></ul></ul><ul><ul><li>Increased PRPP synthetase activity and HPRT deficiency are associated with overproduction of purine, hyperuricemia and hyperuricaciduria. </li></ul></ul>www.freelivedoctor.com
  17. 17. Decreased Uric Acid Excretion <ul><li>Alterated uric acid excretion could result from decreased glomerular filtration, decreased tubular secretion or enhanced tubular reabsorption. </li></ul>www.freelivedoctor.com
  18. 18. <ul><li>Decreased tubular secretion of urate causes the secondary hyperuricemia of acidosis. </li></ul><ul><li>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. </li></ul>www.freelivedoctor.com
  19. 19. Combined Mechanisms <ul><li>Alcohol intake promotes hyperuricemia: </li></ul><ul><li>Fast hepatic breakdown of ATP and increases urate production. </li></ul><ul><li>Can induce hyperlacticacidemia, and inhibition of uric acid secretion. </li></ul><ul><ul><li>The higher purine content in some alcoholic beverages such as beer may also be a factor. </li></ul></ul>www.freelivedoctor.com
  20. 20. Prevalence <ul><li>2 and 13.2% </li></ul>www.freelivedoctor.com
  21. 21. Causes of hyperuricemia <ul><li>Primary </li></ul><ul><li>No recognized cause </li></ul><ul><li>Hypoxanthine phosphoribosyltransferase deficiency </li></ul><ul><li>Increased phosphoribosyl pyrophosphatase activity. </li></ul><ul><li>Secundary </li></ul><ul><li>Hereditary fructose intolerance </li></ul><ul><li>Mieloproliferative disease </li></ul><ul><li>Linfoproliferative disease </li></ul><ul><li>Hemolitic anemia </li></ul><ul><li>Drugs: Low-doses salicylate, diuretis, pyrazinamide, ethambutol, nicotinamide, etanol </li></ul>www.freelivedoctor.com
  22. 22. Evaluation of Hyperuricemia <ul><li>Hyperuricemia does not represent a disease. </li></ul><ul><li>Is not an specific indication for therapy. </li></ul><ul><li>The finding of hyperuricemia is an indication to determine its cause. </li></ul>www.freelivedoctor.com
  23. 23. <ul><li>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. </li></ul>www.freelivedoctor.com
  24. 24. Complications of Hyperuricemia <ul><li>The most recognized complication of hyperuricemia is gouty arthritis </li></ul><ul><li>Nephrolithiasis </li></ul><ul><li>Urate Nephropathy </li></ul><ul><li>Uric Acid Nephropathy </li></ul>www.freelivedoctor.com
  25. 25. Nephrolithiasis <ul><li>The prevalence of nephrolithiasis correlates with the serum and urinary uric acid levels. </li></ul><ul><li>Serum urate levels 13 mg/dl </li></ul><ul><li>Urinary uric acid excretion > 1100 mg/d </li></ul>www.freelivedoctor.com
  26. 26. Urate Nephropathy <ul><li>Deposits of monosodium urate crystals surrounded by a giant cell inflammatory reaction in the medullary intrerstitium and pyramids. </li></ul><ul><li>Clinically: silent or cause proteinuria, hypertension and renal insufficiency. </li></ul>www.freelivedoctor.com
  27. 27. Uric acid nephropaty <ul><li>Precipitation in renal tubules and collecting ducts cause obstruction to urine flow. </li></ul><ul><li>Following sudden urate overproduction and marked hyperuricaciduria: </li></ul><ul><ul><ul><li>Dehydration and acidosis </li></ul></ul></ul><ul><ul><ul><li>Lymphoma </li></ul></ul></ul><ul><ul><ul><li>Cytolytic therapy </li></ul></ul></ul>www.freelivedoctor.com
  28. 28. Treatment www.freelivedoctor.com
  29. 29. Asymptomatic Hyperuricemia <ul><li>Treatment with anthyperuricemic agents entails inconvenience, cost and potential toxicity. </li></ul><ul><li>“ Routine” treatment of asymptomatic hyperuricemia cannot be justified. </li></ul>www.freelivedoctor.com
  30. 30. <ul><li>Treatment with anthyperuricemic agents in asymptomatic hyperuricemia is not recommended. </li></ul><ul><li>“ Treatment in special conditions” like patients during cytolytic therapy for neoplastic disease. </li></ul><ul><li>Justification: prevent uric acid nephropathy. </li></ul>www.freelivedoctor.com
  31. 31. Nephrolithiasis Prevention <ul><li>Fluid ingestion (urine >2 L/d) </li></ul><ul><li>Alcalinization of the urine (sodium bicarbonate or acetazolamide) to increase the solubility of uric acid. </li></ul><ul><li>Allopurinol (Decrease the serum urate concentration) 300 mg/d </li></ul>www.freelivedoctor.com
  32. 32. Uric Acid Nephropathy <ul><li>Vigorous intravenous hydration and diuresis with furosemide. </li></ul><ul><li>Acetazolamide and sodium bicarbonate (urine pH >7) </li></ul><ul><li>Allopurinol </li></ul>www.freelivedoctor.com
  33. 33. GOUT www.freelivedoctor.com
  34. 34. Crystal-induced arthritides <ul><li>MSU (monosodium urate) </li></ul><ul><li>CPPD (calcium pyrophosphate dihydrate) </li></ul><ul><li>HA (calcium hydroxyapatite) </li></ul><ul><li>Calcium oxalate (CaOx) </li></ul>www.freelivedoctor.com
  35. 35. Monosodiumurate Gout www.freelivedoctor.com
  36. 36. Monosodiumurate Gout <ul><li>Affecting middle-aged to elderly men. </li></ul><ul><li>Women represent only 5 to 17% of all patients. </li></ul>www.freelivedoctor.com
  37. 37. Monosodiumurate Gout <ul><li>Associated with an increased uric acid, hyperuricemia, episodic acute and chronic arthritis, and deposition of MSU crystals in connective tissue tophi and kidneys. </li></ul>www.freelivedoctor.com
  38. 38. Acute and chronic arthritis <ul><li>Acute arthritis is the most frequent early clinical manifestation of MSU gout. </li></ul><ul><li>Usually only one joint is affected initially </li></ul><ul><li>Polyarticular acute gout is also seen in male hypertensive patients with ethanol abuse as well as in postmenopausal women. </li></ul>www.freelivedoctor.com
  39. 39. <ul><li>The metatarso phalangeal joint of the first toe is often involved. </li></ul><ul><li>Ankles, and knees are also commonly affected. </li></ul><ul><li>In elderly patients, finger joints may be inflamed. </li></ul>www.freelivedoctor.com
  40. 40. <ul><li>The first episode of acute gouty arthritis frequently begins at night. </li></ul><ul><li>With dramatic joint pain and swelling. </li></ul>www.freelivedoctor.com
  41. 41. <ul><li>Joints rapidly become warm, red, and tender, and the clinical appearence often mimics a cellulitis. </li></ul>www.freelivedoctor.com
  42. 42. <ul><li>Early attacks tend to subside spontaneously within 3 to 10 days. </li></ul><ul><li>Most of the patients do not have residual symptoms until next episode. </li></ul>www.freelivedoctor.com
  43. 43. <ul><li>Several events may precipitate acute gouty arthritis: </li></ul><ul><ul><li>Dietary excess </li></ul></ul><ul><ul><li>Trauma </li></ul></ul><ul><ul><li>Surgery </li></ul></ul><ul><ul><li>Excessive ethanol ingestion </li></ul></ul><ul><ul><li>Glucocorticoid withdrawal </li></ul></ul>www.freelivedoctor.com
  44. 44. <ul><li>After many acute attacks, a portion of gouty patients may presents with a chronic nonsymmetric synovitis. </li></ul><ul><li>Causing potential confusion with rheumatoid arthritis. </li></ul>www.freelivedoctor.com
  45. 45. <ul><li>More rarely, the disease will manifest as inflamed or noninflamed periarticular tophaceous deposits in the absence of chronic synovitis. </li></ul>www.freelivedoctor.com
  46. 46. Laboratory Diagnosis <ul><li>Even the clinical appearance strongly suggests gout. The diagnosis should be confirmed by needle aspiration of acute or chronically inflamed joints or tophaceous deposits. </li></ul>www.freelivedoctor.com
  47. 47. <ul><li>Acute septic arthritis several of the other crystalline – associated arthropathies, and psoriatic arthritis may present with similar clinical features. </li></ul>www.freelivedoctor.com
  48. 48. <ul><li>Effusion appear cloudy due to leukocytes and a large amounts crystals ocassionally produce a thick pasty or chalky joint fluid. </li></ul>www.freelivedoctor.com
  49. 49. Radiographic Features <ul><li>Cystic changes, well-defined erosions described as punched-out lytic lesion. </li></ul><ul><li>Soft tissue calcified masses (chronic tophaceous gout) </li></ul>www.freelivedoctor.com
  50. 50. Treatment <ul><li>Acute attack: </li></ul><ul><li>Anti-inflammatory drug: </li></ul><ul><ul><li>Colchicine </li></ul></ul><ul><ul><li>Nonsteroidal anti-inflamtory drugs </li></ul></ul><ul><ul><li>Glucocorticoids </li></ul></ul><ul><ul><li>Depending on the age of the patient and comorbid conditions. </li></ul></ul>www.freelivedoctor.com
  51. 51. <ul><li>Colchicine and NSAIDs may be quiet toxic in the elderly, particularly in the presence of renal insufficiency and gastrointestinal disorders. </li></ul>www.freelivedoctor.com
  52. 52. <ul><li>In elderly patients : </li></ul><ul><ul><li>Intraarticular glucocorticoid injections </li></ul></ul><ul><ul><li>Cool aplications along with lower oral doses of colchicine. </li></ul></ul>www.freelivedoctor.com
  53. 53. <ul><li>Colchicine </li></ul><ul><ul><li>0.6 mg tablet every hour until relief of symptoms </li></ul></ul><ul><ul><li>Gastrointestinal toxicity occurs ( never excede 4 mg) </li></ul></ul>www.freelivedoctor.com
  54. 54. <ul><li>Uricosuric agents </li></ul><ul><ul><li>Probenecid 2oo mg twice </li></ul></ul><ul><ul><li>Allopurinol 300 mg </li></ul></ul>www.freelivedoctor.com

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