L13 Gout "Disease of Kings"

Objectives

1. Identify Risk Factors

2. Understand how Purine Metabolism and Uric Acid Elimination contribute to Gout formation

   • Overproducers and Underexcretors

3. Factors and Process that predispose Acute Gouty Arthritis in Peripheral Joints of Lower Extremities

4. Understand Clinical Manifestations of Acute Gouty Arthritis, Tophaceous Gout, and Uric Acid Nephrolithiasis

Notes

1. What is a possible indicator of Gout

   • Hyperuricemia (excessive uric acid)

     • decline in urinary excretion of uric acid below the rate of production

2. Uric Acid is a byproduct (waste) of what

   • Purine Metabolism

     • mostly endogenous, some dietary (red meats, seafood, alcohol, etc)

3. What are the diagnostic factors of Hyperuricemia

   • < 7 mg/dL → < 1% risk

   • > 10 mg/dL → 30% risk

4. What can happen when there is excess uric acid in the blood

   • Uric Acid and Monosodium Urate can precipitate into crystal deposition → arthritis

5. T/F: The body uses Uricases to breakdown Uric Acid

   • False, converts into Allantoin to solubilize

6. What is Urate

   • anionic uric acid (more soluble)

7. Where is most of urate filtered through?

   • Kidney’s glomerulus

     • however, 90% is reabsorbed

8. What causes excess uric acid

   • Overproduction or Underexcretion

9. What are risk factors of Goat

   • Age

     • associated with decreased Kidney function

   • Elevated Serum Urate

   • Male

   • Postmenopausal Women

   • SCr, BUN

   • Obesity

   • Alcohol intake

   • High Purine intake (meat/fish)

10. What are key players mentioned within the Purine Metabolism Pathway

    • Ribose 5-Phosphate → PRPP Synthetase → PRPP → + Glutamine → Inosinic Acid → Hypoxanthine → Xanthine Oxidase → Xanthine → Xanthine Oxidase → Uric Acid → Renal Resorption or Excretion

      

11. What are Xanthine Oxidase Inhibitors used for

    • Prevents the formation of uric acid, likely to avoid excess production

12. Why is it important to keep a balance between uric acid production and excretion

    • Normal Levels are already near the limits of Urate Solubility

13. Is overproduction or underproduction of uric acid more common in goat?

    • Underproduction (90%)

14. What is categorized as overproduction

    • excrete > 600 mg on purine-free diet (> 1000 mg on a regular diet)

15. What is categorized as underproduction

    • excrete < 600 mg on a purine-free diet (< 1000 mg on a regular diet)

16. What can cause increased tissue breakdown and cell turnover → uric acid overproduction

    • Cytotoxic Meds

    • Hemolytic Anemia

    • Psoriasis

17. What enzymes can cause uric acid overproduction

    • Increased PRPP Synthase

    • Decreased HGPRT

18. What are possible causes of Underexcretion

    • Organic acids competing with urate for expression

    • Decreased kidney function

    • Medications

19. List the medications that decrease renal clearance

    • Diuretics, Ethanol

    • Nicotinic Acid, Pyrazinamide, Ethambutol, Testosterone, Salicylates, Cyclosporine, Cytotoxic meds

20. How is overproduction or underexcretion

    • 24 hour urine screening

21. What is Acute Gouty Arthritis

    • Rapid onset of pain, swelling, and inflammation often the big toe

      • Insteps (top of foot), Ankles, Heels, Knees, Wrists, Fingers, Elbows

    • Typically Monoarticular

22. What is Acute Gouty Arthritis a predisposition to?

    • Peripheral Joints in Lower Extremities

    • due to low temp and/or synovial fluid is a poor solvent

      • urate crystals are less soluble < 37 degrees C

23. When does AGA pain typically occurs

    • begins at night

      • synovial effusions (fluid accumulation) occur for a short period (transiently) during the day with routine activity

      • water is reabsorbed during the night

      • supersaturated solution of monosodium urate

24. What inflammatory responses are cause by Acute Gouty Arthritis Crystal Deposits

    • Vasodilation

    • increased Vascular Permeability

    • Complement Activation

    • Chemotactic activity

25. What are causes of AGA

    • Stress,

    • Trauma

    • Alcohol

    • Infection

    • Surgery

    • Rapid lowering of uric acid

    • Meds

26. How is AGA diagnose

    • Aspirate Synovial Fluid

      • not typically done but is best method

    • Clinical Triad

      • Inflammatory Monoarthritis

      • Elevated Serum Uric Acid Levels

      • Response to Colchicine

27. What are the criteria for clinical diagnosis

    1. One or more episodes of swelling, pain, tenderness

    2. Monosodium Urate Crystals

       • aspiration of joint

    3. Additional Criteria

       • Ankle or midfoot (monoarticular or oligoarticular)

       • First metatarsophalangeal joint (monoarticular or oligoarticular)

       • Redness over affected joint

       • Cannot bear to touch or put pressure on affected joint

       • Great difficulty walking or inability to use affected joint

       • Time to maximal pain < 24 hours

       • Resolution of symptoms ≤ 14 days

       • Complete resolution between episodes

       • Tophus

       • Hyperuricemia

       • Synovial fluid analysis

       • Imaging evidence of urate deposition

       • Imaging evidence of gout-related joint damage

28. What is Interval Gout

    • Asymptomatic periods between attacks

29. What is Tophaceous Gout

    • Urate deposits in soft tissue

30. What are complications of Tophaceous Gout

    • Soft tissue dmg

    • Deformity

    • Joint destruction

    • Nerve Compression Syndromes

31. What is Gouty Nephropathy

    • ACUTE renal failure → blocked urine flow → uric acid crystals in collecting ducts and ureters

      • Myeloproliferation or Lymphoproliferation

    • CHRONIC Urate Nephropathy → long-term urate crystal deposits in renal parenchyma

32. What is Uric Acid Nephrolithiasis

    • Uric acid Kidney stones

      • pH of 5 → 15 mg/dL uric acid level

      • pH of 7 → 200 mg/dL

33. Do stones form in more basic or acidic conditions?

    • acidic

34. What pH do most patients have for spontaneous precipitation (formation) of stones to occur

    • pH < 6