GOUT LEARNING OBJECTIVES 1) RELATE THE METABOLIC ETIOLOGY OF GOUT TO ITS CLINICAL PRESENTATION

and UNDERSTAND EPIDEMIOLOGY OF HYPERURICEMIA AND GOUT AND ID PREDISPOSING FACTORS TO GOUT Hyperuricemia (high serum urate levels) does not necessarily lead to gout, but MANY of the patients with gout have hyperuricemia. Remember, they said that about 1/3 of the patients with gout had normal serum levels. Also, only about 10% of persons surveyed in the hospital had gout. There was hyperuricemia associated with a host of other conditions in the surveyed hospital patients, such as: Diuretic use (20%), azotemia (20%), HTN (18%), and Myeloproliferative disorders (2%). Where hyperuricemia is high serum urate levels, gout is considered a clinical syndrome due to the deposition of sodium urate crystals in joints. This can lead to acute inflammation and sudden onset arthritis. The sites of interest are the big toe, feet, ankles, knees, and hands. If the underlying conditions are not treated, then symptoms, episodes, and complications become more prominent. For instance, urate deposits can be seen in the soft tissue. These urate deposits are called tophi and are related to hyperuricemia.

Causes of Sustained Hyperuricemia

Division 1: Increased Urate Production Genetic Causes Enzyme Mutations: Lesch-Nyhan syndrome Acquired Causes Myeloproliferative disorder High Purine Intake- Meats, Yeast, Beans Obesity and High TG Alcohol consumption Fructose Consumption Exercise Division 2: Reduced Urate Excretion (90% here) Genetic Causes Reduced clearance or fractional excretion Acquired Causes (Potentially reversible) Intrinsic Renal Disease-Not reversible Drugs (Thiazides, Low dose salicylate) Metabolites (Lactate,Ketones,Angiotensin,ADH) Renal Cause- HTN, P-V contraction, Obesity Reduced Urine Flow x< 1ml/min

Causes of Acute and Chronic Gout

Acute Gouty Arthritis Joint Trauma, Surgery, Starvation or Dehydration, Acidosis, Alcohol or Purine Ingestion, Medications that increase or lower serum urate levels, and sudden changes in urate concentrations. Depositions of Urate in Joints and Tissues. This is especially evident in the kidneys and urinary tract. There is also usually both high serum levels of urate, as well as high total body pools.

Chronic Gout

2) LEARN THE LAB ABNORMALITIES, ICLUDING SYNOVIAL FLUID MICROSCOPY Lab Abnormalities: Normal serum urate is <7.2 Normal excretion of uric acid in 24 hr. urine collection is <10mg/kg i.e., 700mg/day for someone who weighs 70kg Excess excretion is considered 800 mg/day assuming normal diet Total body pool should be <2,000mg (about a 4-day supply) In gout patients, this might be 100-300 times normal

Synovial fluid analysis - Viscosity, color, cell count and differential, crystal analysis, & gram stain / culture - Color is separated into 2 main subtypes: hemorrhagic and non-hemorrhagic. The non-hemorrhagic subtype is divided into whether the fluid is cloudy or clear. Clear non-hemorrhagic synovial fluid suggests a NON-inflammatory process. Cloudy non-hemorrhagic synovial fluid suggests inflammation. WBC count < 200 WBC/cc <2000 WBC/cc 2000 20000 WBC/cc 20000 50000 WBC/cc Interpretation Normal synovial fluid Non-inflammatory fluid Mild Inflammation (ex. SLE) Moderated Inflammation (ex. RA & reactive arthritis)

> 50000 WBC/cc

> 100000 WBC/cc

Severe Inflammation (ex. Gout, sepsis)

Septic arthritis until proven otherwise

Clinical diagnosis a. Need to aspirate fluid from swollen joint (looks chalky grossly) b. Microscopically, you can see uric acid crystals (on a red plate background with polarizing scope) i. YUP yellow, urate, parallel ii. Axis of crystal is parallel to red plate iii. When perpendicular to the plate, they will appear BLUE iv. Do not confuse this with pseudogout, where there are yellow crystals when placed perpendicular to the plate. They quickly disappear though. v. Cells ingest this material (urate) and die 1. adding to the acidic milieu (attacks propagate themselves) vi. May see signs of acute inflammation in fluid 3) DISTINGUISH ACUTE FROM CHRONIC TREATMENT OF GOUT Acute gout arthritis how to treat? o Indocin (indomethacin) is drug of choice most potent NSAID Problem is that many of these patients are hypertensive and on many other drugs (careful with polypharmacy) NSAIDs are effective, especially if used early (but good for later, too) Colchicines old, effective drug (from bark of plant). Use on hourly basis to decrease severity of attack. Decreases recruitment of cells. Works early in attack. Best if used prophylactically (i.e., if someone is on a drug that decreases urate excretion) take BID x 1 year after last attack Glucocorticoids cortisone. Very effective (6 day treatment, helps within hours). ACTH patients on polypharmacy or with low Hct can tolerate ACTH (given IM) for a few days

o o

Chronic gout who to treat? o Patients with kidney stones (they dont want to go through that again) o Patients with tophus (total body pool = 50-200x normal to get a tophus need long-term therapy) o Patients with many attacks per year (3-4), or particularly severe attacks (need long-term therapy) o Patient with hyperuricemia and urine urea of 1,000 (very high) treat even if they have few attacks/stones/tophi

o Give allopurinol if overproduction of urate is the problem o Give benemid (probenecid) if underexcreting urate (increases excretion by one-third; old
o drug with few adverse effects) DONT treat asymptomatic hyperuricemia! even in the hospital, only 10% of these patients have gout allopurinol has risks, too (like Steven-Johnson Syndrome) dont use unnecessarily

Summary from Dr. Mendels Pharmacology Lecture to compare

Acute gout Use NSAID, injected steroid or colchicines. Must be followed by chronic treatment to prevent recurrences, normalize serum levels, reduce tophi formation, and limit renal involvement. - Chronic gout Use a Uricosuric and/or Allopurinol - Initial treatment of chronic Add colchicines or NSAID to prevent acute attack - Do not start chronic therapy until acute attack has subsided