Rheumatology: Gout Flashcards
Pathophysiology of Gout
Gout is caused biochemically by extracellular urate supersaturation (uric acid becomes suprasaturated)
This can lead to:
Repeat attacks of acute inflammatory arthritis
Build up of urate crystals causing tophaceous/tophi (gritty) deposits
Uric acid nephrolithiasis
Nephropathy
Synthesis of Urate
End product of purine synthesis, interconversion, and degradation of DNA, RNA, Ribose-5-P, and Mg-ATP
Xanthine is converted to urate via xanthine oxidase
Movement of uric acid in and out of cells occurs on the proximal tubule via many types of transporters
2 Main Causes of Gout
15% of all patients with hyperuricemia develop gout- therefore, you can have high UA but not develop gout
Hyperuricemia is defined as serum uric acid concentrations >7 mg/dl in men and >6 mg/dl in women.
Gout has 2 main causes:
Over production
Under excretion
Causes of Overproduction
Ethanol HGPRT or G6PD deficiency Lesch-Nyhan PRPP synthetase overactivity Myeloproliferative disorders Cytotoxic chemotherapy Sickle-cell anemia Obesity Diet – high in purines B12 Deficiency Fructose Nicotinic Acid Cytotoxic Drugs Warfarin Psoriasis
Foods to Limit
Meat items that are particularly high in purines: beef, pork, lamb, and “organ meats” (such as liver, kidney, and brain).
Reduce or eliminate alcohol consumption, especially beer.
Reduce oatmeal, dried beans, peas, lentils, spinach, asparagus, cauliflower, and mushrooms.
Specific types of seafood found to be associated with higher levels of uric acid include: anchovies, sardines, roe (fish eggs), herring, mussels, codfish, scallops, trout, and haddock
Causes of Under-Excretion
ACBG abnormality URAT 1 abnormality Medullary Cystic Kidney Drugs Age and Gender Renal Insufficiency Renal insufficiency Lead nephropathy (saturnine gout) Diabetic ketoacidosis Lactic acidosis Preeclampsia Obesity Hyperparathyroidism Hypothyroidism Sarcoidosis
Drugs and Toxins that cause Under-Excretion
Diuretics (thiazides and loop diuretics) Ethanol Cyclosporine A Pyrazinamide Low-dose aspirin Levodopa Laxative abuse Salt Restriction
Test: Under-Excretion or Overproduction
Most of the time the case in under excretion
How to differentiate: 24 hour urine for uric acid and creatinine levels; if over 800 or more over producer, but under 800 patient is under excretion
Four Stages of Gouty Arthritis
- Asymptomatic hyperuricemia- gout crystals form at serum uric acid (sUA) level of 6.8
- Acute gouty arthritis
- Intercritical gout
- Chronic Tophaceous gout
Path to a Gout Flare
- Asymptomatic hyperuricemia
- Supersaturation
- Crystal Formation
- Microcrystal release
- Inflammatory Cascade
- Gout Flare!
Manifestation of Gout
Early attacks are usually monoarticular, beginning early am or during the night when body temperature is lower
The joint is red, warm, swollen and extremely painful.
Acute gout can occur in non-articular sites: bursa, Achilles tendon etc.
Early attacks spontaneously resolve in 3-10 days.
Subsequent attacks can become polyarticular and last longer
The 1st MTP of the great toe (podagra) is involved >50% in first attacks and >90% overall and is called podagra.
Gout can affect the instep, heels, knees, wrists, fingers and elbows; DIP joints in hands
From the 1st attack to the appearance of tophi can take on average 10years
Synovial Fluid Aspiration Findings
Inflammatory with 20,000-100,000 leukocytes/mm3
Uric acid crystals
Negatively birefringent; needle-shaped crystals under polarized light
Crystals appear yellow when parallel to axis of red compensator of polarized light, and blue when perpendicular
Lab Testing: UA Levels
Uric acid can be normal in up to @50% of acute attacks.
This is why it is important to check uric acid levels @2weeks after the flare during the intercritical period.
Most important: The fluid has to be looked at within the 1st hour from the tap as crystals dissolve at room temperature
X-Ray Findings: Gout
Soft tissue swelling
Tophi which can appear calcified
Bony erosions that appear “punched out” with sclerotic margins and overhanging edges – “rat bite erosions”.
Joint space early in gout is preserved and there is no osteopenia
UA Levels and Risk for Recurring Flare
UA of 10mg/dL = 90% UA of 9.0mg/dL = 65% UA of 8.0mg/dL = 65% UA of 7.0mg/dL = 20% UA of 6.0mg/dL = 10%
