Disease caused by tissue deposition of Monosodium urate crystals as a result of supersatuaration of extra cellular fluid with MSU.

Urate:

end product of purine metabolism

Hyperuricemia:

serum urate > urate solubility (> 6.8 mg/dl) deposition of monosodium urate crystals in tissues

Gout:

 Hyperuricemia

caused by Overproduction Underexcretion Gout w/o crystal deposition

No

Biologically significant hyperuricemia (6.8 mg/dL) is less than laboratory defined hyperuricemia (8.0 mg/dL)

The Hyperuricemia Cascade

Tissue nucleic acids Dietary purines

Endogenous purine synthesis

Urate

Overproduction

Underexcreti on Hyperuricemia 6.8 mg/dL

Silent tissue deposition

Gout

Associated Renal manifestations cardiovascular events and mortality

Group of conditions which may be characterized by

An elevation of serum uric acid (usually) Recurrent attacks (flares) of an acute inflammatory arthritis with monosodium urate crystals demonstrated in synovial fluid leukocytes Bone and joint destruction in some cases Aggregates of uric acid crystals (tophi) in and around joints, soft tissues, and various organs Tophus in bone leading to erosions in some cases Kidney disease and stones

1.

2.

Image reprinted with permission. American College of Rheumatology. ACR Clinical Slide Collection on the Rheumatic Diseases. Atlanta, Ga.: American College of Rheumatology; 1998. http://www.healthinplainenglish.com/health/musculoskeletal/gout/index.htm

Obesity,

metabolic syndrome

Ethanol
Diuretics Fructose

ingestion Excessive purine ingestion

Underexcretors (80%) Male gender Postmenopausal females Obesity, metabolic synd. Ethanol Renal insufficiency Plumbism Medications Dehydration/low flow Filipino ancestry Fructose ingestion Uromodulin kidney dis.

Overproducers (20%) Ethanol High cell turnover states (psoriasis, myeloprolif. disorders) Excessive purine ingestion PRPP overactivity (x-linked) HGPRT underactivity (x-linked) Beta aldolase deficiency Sarcoidosis B12 deficiency Down syndrome Glycogen storage dis. 3, 5, 7 Fever, post-op state

 Asymptomatic

hyperuricemia

Acute

Flares of crystallization
between flares Gout & Complications

Intervals

Advanced

 Abrupt

onset of severe joint inflammation, often nocturnal; Warmth, swelling, erythema, & pain; Possibly fever Untreated? Resolves in 3-10 days 90% 1st attacks are monoarticular 50% are podagra

 90%

of gout patients eventually have podagra : 1st MTP joint

 Can

occur in other joints, bursa & tendons

 Asymptomatic
If

untreated, may advance

Intervals

may shorten Crystals in asx joints Body urate stores increase

 Silent

tissue deposition & Hidden Damage

 Chronic
X-ray Tophi Acute

Arthritis

Changes Develop Flares continue

 Chronic

Arthritis Polyarticular acute flares with upper extremities more involved

 Solid

urate deposits in tissues

 Irregular

& destructive

 Long

duration of hyperuricemia

Higher Long

serum urate

periods of active, untreated gout

Dr. Alka Stoelinga

2/26/2013

26

Pseudogout - acute symptoms of joint inflammation or synovitis:

Red, tender, and swollen joints that may resemble gouty arthritis

Chondrocalcinosis - radiographic evidence of calcification in hyaline and/or fibrocartilage Pyrophosphate arthropathy - term that may refer to either of the above Statistically, the knee joint is the most commonly affected
Dr. Alka Stoelinga 2/26/2013

27

Calcium pyrophosphate deposition disease (CPDD) - metabolic arthropathy caused by the deposition of calcium pyrophosphate dihydrate (CPPD) in and around joints, especially in hyaline and fibrocartilage of joints

often asymptomatic, with only radiographic changes (i.e., chondrocalcinosis), various clinical manifestations may occur,

Including acute (pseudogout) and chronic arthritis.

Dr. Alka Stoelinga

2/26/2013

28

Acute synovitis (Pseudogout)

Most common cause of acute monoarthritis in elderly Most common site: Knee F/B Wrist, shoulder, ankle and elbow Triggering factors: Direct trauma Intercurrent illness/ Any surgery Typical attack: Resembles gout Rapidly developing Severe pain, stiffness and swelling within 6-24hrs Overlying erythema Examination: Very tender joint, held in loose pack position Signs of marked synovitis Large/ tense effusion, warmth, restricted movement and stress pain Fever, confusion, ill looking

Dr. Alka Stoelinga

2/26/2013

29

Chronic (Pyrophosphate) arthritis Mostly elderly female Most common site: Knee F/B Wrist, shoulder, elbow, hips and midtarsals Hand 2nd and 3rd metacarpophalangeal joints are most commonly affected Typical symptoms: Chronic pain Variable early morning and inactivity stiffness Functional impairment Acute attacks may superimpose in chronic h/o pain Examination: Features of osteoarthritis (Bony swelling, crepitus, restriction) Synovitis Wrist involvement Carpal tunnel syndrome Large/ tense effusion, warmth, restricted movement and stress pain Heberdens nodes
Dr. Alka Stoelinga 2/26/2013

30

 Wrist:

triangular ligament Pelvis: symphysis pubis Knee: menisci

Also:

annulus fibrosis, articular capsules, bursae, ligaments, tendons

Knees
Pelvis

Hands

 Gout

hallux, ankle, knee, hand younger, male knee, wrist, ankle older, female

Pseudogout

Almost

any joint can be affected by either disease!

Drugs used for Hyperuricemia

 Colchicine

decreases leucocyte chemotaxis and phagocytosis and thereby inhibits the formation and release of a chemotactic glycoprotein that is produced during the phagocytosis of urate crystals.

 Inhibits

the tubular reabsorption of urate. Reduce plasma binding of urate and inhibit renal secretion of uric acid at subtherapeutic concentrations.

Allopurinol

is a purine analog of hypoxanthine

Isomer

Inhibitor

of the enzyme xanthine oxidase.

It

is a nonsteroidal anti-inflammatory drug (NSAID) with a highly selective (COX-2) inhibitory action. It possesses antiinflammatory, analgesic, and antipyretic activities.

Adjunctive treatment for Chemotherapy

Called cytoprotective (cell-protecting) agent. This helps prevent kidney damage Tumor Lysis Syndrome

complication of anticancer treatment numbers of neoplastic cells are killed rapidly. of intracellular ions and metabolic byproducts.

Large

Release