Crystal Induced Arthritis

Question 1

Crystal Induced Arthritis - General

Answer 1

Endogenous Crystals

• Monosodium Urate (GOUT)
• Calcium Pyrophosphate (PSEUDOGOUT)
• Calcium Phosphate

Exogenous Crystals

• Corticosteroid Ester
• Talcum

Crystals cause disease by TRIGGERING CASCADE that results in CYTOKINE-mediated CARTILAGE DESTRUCTION

Question 2

Primary Gout - Classification

Answer 2

90% of cases
OVERPRODUCTION of URIC ACID
- Diet 
- Enzyme Defects
REDUCED EXCRETION

Question 3

Secondary Gout - Classification

Answer 3

10% of cases
OVERPRODUCTION w/ INCREASED EXCRETION
- Increased Nucleic Acid Turnover(Leuke)
- Inborn Metabolism error (HGPRT def)
DECREASED EXCRETION w/ NORMAL PRODUCTION
- Chronic Renal Disease

Question 4

Formation of Uric Acid ( 2 ways)

Answer 4

De Novo Pathway - Purines are synthesized from nonpurine precursors

Salvage Pathway - free purine bases derived from breakdown of nucleic acids are recaptured

• HGPRT is the gatekeeper enzyme
• Deficiency of HGPRT causes more product to push towards Uric Acid and results in more Purines being synthesized via the De Novo Pathway
• X-Linked Lesch Nyhan Syndrome –> defiecincy in HGPRT (causes retardation, self mutilation)

Question 5

Process of Gout

Answer 5

1. Monosodium Urate Crystals Precipitate in Joint
2. The urates in the joint fluid become supersaturated and crystals/microtophi develop
3. Crystals are “released” (possibly to a traumatic event) and initiate inflammatory response
   - chemotaxis and C3 and C5a generation
   - INCREASED Nuetrophils and Macrophages
4. Crystals are phagocytized
   - Free radicals and LTB4 released causing tissue injury and inflammation

Question 6

What factors help turn hyperuricemia (7mg/dL) into GOUT?

Answer 6

Age and Duration - usually older than 20-30
Genetic Predisposition - multifactorial
Heavy Alcohol Consumption
Obesity
Drugs - like thiazides (reduce excretion)
Lead toxicity

Question 7

For arthritis via crystals (gout) to occur - precipitation of MSU crystals is central to the disease process. What allows for crystalization?

Answer 7

1. Low temperatures - this is why extremities are more affected
2. High intra-articular concentration
3. Nucleating agents
   - insoluble collagen fibers
   - chondroitin sulfate
   - proteoglycans
   - cartilage fragments

Question 8

Gout - Morphology

Answer 8

Acute Arthritis

• Neutrophils with bifringent crystals permeate synovium and synovial fluid
• CRYSTALS ACTIVATE NUETROPHILS
• Synovial Fluid congested w/ various inflammatory cells
• Attacks stop when crystals are gone
• See PODAGRA here

Chronic Tophaceous Arthritis

• Repetative build-up of crystals in synovium and periarticular tissue during acute attacks
• TOPHI arise here (white/chalky and surrounded by fibrosis)
• PATHONOMONIC for gout

Question 9

Gout - Clinical

Answer 9

Acute Arthritis

• Podagra (first metatarsophalangeal joint)
• Sudden Joint Pain
• Warmth, Tenderness

Chronic Tophaceous Gout
- takes 12 years to develop

Question 10

Gout - Labs

Answer 10

Labs

• HYPERURICEMIA
• Athrocentesis
• High WBC
• NEGATIVE, LAY LOW, YELLOW, BIREFRINGENET NEEDLE-SHAPED INTRACELLULAR CRYSTALS

Question 11

Gout - Common Complications

Answer 11

Cardiovascular

Renal - 20% of chronic gout pts die of renal failure