What are synovial joints? and what are they also known as?
Allow for gliding movement facilitated by lubricated cartilagenous surfaces.
Also known as diarthrodial joints.
What comprises a synovial joint?
Hyaline cartilage on articular surface
What are the functions and components of hyaline cartilage?
-Elastic shock absorber spreading weight across surface of joint
-Friction-free surface (along with synovial fluid)
-Type 2 collagen (Tensile strength)
-Water and Proteoglycans (elasticity and decrease friction)
-Chondrocytes (Maintain cartilaginous matrix)
What are the components and function of the synovial cavity?
Synovial cells (1. Produce synovial fluid, 2. Remove debris (phagocytic fxn), 3. Regulate movement of solutes
Synovial fluid (Lubricant and provides nutrients to articular cartilage)
What are the categorizations or patterns of arthritis?
Inflammatory vs. non-inflammatory
Monoarthritis vs. polyarthritis
Acute vs Chronic
Large joint vs small joint involvement
Snyovial vs non-synovial
Axial vs. Peripheral Joints
What is the clinical assessment for inflammation?
Morning stiffness > 1 hr
Improves as the day goes on
-Erythema and warmth
-Synovitis - thickening of the synovium around joints; (tender and squishy w/ firm palpation)
- Serologies: markers present in serum: eg Rh factor
-Inflammatory markers (ESR and CRP, aka, Erythrocyte sedimentation rate and C reactive proteins, also anemia)
-Peripheral blood leukocytosis (septic arthritis)
-Joint fluid analysis
-X ray, erosions of bone at joint margins, MRI, CT
What are the categories for NON-INFLAMMATORY/INFLAMMATORY/SEPTIC in synovial fluid analysis?
WBC: <2000, >2000, >50000
PMNS: <10%, 50-90%, >90%
What is gout?
A metabolic disorder resulting in elevation of uric acid (hyperuricemia) beyond the level of saturation.
Plus presence of inflammatory microcrystals in the joint
What percent of gout is due to overproduction vs. underexcretion?
What is the male to female ratio for gout?
1.3 males : 0.5 females
What hormonal change can increase gout in females and why?
Increases in females after menopause because ESTROGEN PROMOTES URATE RENAL EXCRETION
What are specific causes for overproduction or underexcretion of urea (resulting in hyperuricemia)
-Increased cell turnover
-Drugs like diuretics or cyclosporine
How do we produce uric acid and what are the proportions of the total?
1/3: Dietary nucleotides and nucleoproteins we eat
2/3: internal turnover of cellular nucleotides and nucleoproteins
Would the breakdown of RBCs result in increase of uric acid?
No, because they are NOT NUCLEATED (like WBC)
Where is uric acid excreted and what are the proportions?
1/3 Gut excretion (200mgms/day)
2/3 Renal excretion (600 mgms/day), so 10% of filtered load
What are the 3 Ls of polarizing microscopy w/red compensator
Parallell, Allopurinol, Yellow=gout
negatively birefringent crystal
What can precipitate a gout attack?
Elevation of uric acid
Reduction of uric acid
Release of crystals from pre-formed deposits
How does monosodium urate crystals MSU crystals cause inflammation
1. Recognition by PAMPs
3. Inflammasome activation (capsase 1 activated)
4. IL-1beta release
5. Endothelium signal activation
6. Pro-inflammatory mediators release
7. Neutrophil recruitment
8. More IL-1beta release
What is CPPD?
Calcium pyrophosphate dihydrate crystal deposition
What is the prevalence of CPPD?
What is the etiology of CPPD?
What are mixed crystals?
What (again) does CPPD stand for?
12% of elderly, 5% at age 60 rising to 30% by age 90
Etiology unknown, but in most cases related to overproduction of PPi
Multiple different presentations, CPPD crystals may be found with urate cyrstals (mixed crystals)
Calcium pyrophosphate dihydrate crystal deposition
How does Calcium pyrophosphate dihydrate crystal deposition work?
1. Through ATP hydroysis to AMP, production of pyrophosphate PP
2. Goes through ank channel (can have genetic deffects)
3. PPi binds calcium easily and forms crystals
What are the colors of urate crystals and calcium pyrophosphate crystals when PARALLEL and PERPENDICULAR to the direction of the compensator?
Urate crystals: yellow parallel/blue perpendicular (Negatively birefringent, is gout)
Calcium crystals: blue parallel/white perpendicular (Positively birefringent, is CPPD)
What factors can evalulate CPPD for patients under 60?
Fe, TIBC- Hemochromatosis
What is pseudogout?
How is pseudogout diagnosed?
Attacks of acute arthritis similar to gout, but usually in larger joints: knee, wrist, shoulder
Diagnosed by rhomboidal shaped, positively birefringent crystals in joint fluid.
Also, diagnosis may be suggested by chondrocalcinosis, but not seen in all cases.
What are the different presentations of CPPD arthritis?
1. Asymptomatic- most common
3. Osteoarthritis (OA), may be assoc. with widespread OA including OA in atypical joints
4. RA-like (MCP joint enlargement)- may produce chronic low grade inflammation
What are the drugs used for Gout?
What are the drugs used for Rheumatoid Arthritis?
Disease-modifying Rheumatic Agents (DMARDs)
What are the therapeutic goals of Uric Acid Medications?
1. Increase excretion of uric acid
2. Inhibit inflammatory cells
3. Inhibit uric acid biosynthesis
4. Provide symptomatic relief (typically w/NSAIDS or steroids for short term)
What drugs provide symptomatic relief for gout?
NSAIDs and Steroids
NSAIDS (given within first 24 hours): Indomethacin and Naproxen
BUT NOT ASPIRIN
Steroids: most useful for patients with contraindict to NSAIDS, short term use only because adverse effects w/ extended use
For Colchicine, what is the MOA
-Antimitotic, arresting cell division in G1 by interfering with microtubule and spindle formation, specifically in inflammatory cells=neutrophils, inhibiting their activation and migration. This lessens symptoms of the inflammation.
- No effect on uric acid excretion