22 - Introduction to Joint Disease Flashcards
What does mono, poly, and oligo mean in terms of joints?
Mono: one
Poly: 4 or more
Oligo: 2-3 joints (“pauci”)
What are the parts of the axial skeleton?
Skull, mandible, sternum, ribs, vertebral column, and sacrum.
Describe the hyaline cartilage of a synovial joint (diarthrodial joint)?
Hyaline cartilage on articular surface: for elastic shock absorber, spreads weight acress joint surface. Friction free.
- avascular, type II collagen, water, proteoglycans, and chondrocytes
Describe the synovial cavity of a synovial joint (diarthrodial joints)?
Synovial cells line synovial cavity: cuboidal cells (1-4 layers thick)
- make synovial fluid, remove debris, regulate movement of solutes, electrolytes and proteins from capillaries into fluid.
- NOT present over articular cartilage
Synovial fluid: viscous filtrate of plasma containing hyaluronic acid as a lubricant/provides nutrients to articular cartilage.
What would a normal femoral head look like grossly? What about on histology of the synovium and articular cartilage?
Blue/white shiney-ish appearance.
Articular cartilage: multiple layers of chondrocytes within the cartilage.
Synovium: under cuboidal cells are vessels and fibrous tissue
What are the six different patterns of arthritis?
- Inflamm vs non-inflamm
- Monoarthritis vs oligo vs polyarthritis
- Acute vs chronic
- Large joint vs small joint involvement
- Symmetric vs asymmetric
- Axial vs peripheral
What labratory testing would you do to identify arthritis?
1. “generic” markers of inflammation:
- Sed Rate
- CRP
- Anemia
- Leukocytosis (high WBC)
2. Serology: presence of autoantibodies: Rheumatoid factor, CCP antibody, antinuclear antigen (ANA).
3. Synovial joint fluid analysis.
What can Sed rate elevation result from? What can falsely elevate ESR? How do you adjust for age?
Infection (most common), malignancy, and autoimmune/inflamm conditions.
False elevation: end stage renal disease, anemia (fewer RBCs to bump each other to slow decent), obesity, and age.
Women: age + 10/2 = adjusted upper limit of normal
Men: age/2
What an decrease ESR?
- Low fibrogen (DIC)
- Polycythenia vera
- Sickle cell
- Spherocytosis
What is C-reactive protein? Where are they made and what do very high CRP levels indicate? What can be done to detect it?
Molecule binds dying cells/pathogens: Rapid ride in hours of tissue injury. Synthesized in liver.
Very high CRP suggests bacterial infection
High sensitivity CRP (hsCRP) measures CRP but can detect it in lower concentrations. Elevation linked to increased CV disease.
What is rheumatoid factor? What is anti-cyclic citrullinated peptide antibody (CCP)? What is each sensitive/specific for?
Rheumatoid factor: autoantibody that binds Fc of human IgG (70% sensitive for RA, 80% specific for RA).
- False + : chronic HepC, sjogrens, primary biliary cirrhosis, multiple myeloma, and ~4% of normal pop.
Anti-cyclic citrullinated peptide Ab (CCP): 70% sensitive for RA, >90% specific for RA.
These are both found on serology.
How do doctors look for ANA? What are the different types and what diseases are they associated with?
Immunofluorescence.
dsDNA - SLE
SSA (RO) - sjogrens, SLE
Smith - SLE
RNP - missed connective tissue disease (MCTD)
Scl-70 - scleromerma
Jo-1 - inflamm. myopathy
Histone - drug induced lupus
Not great because there’s MANY false positive results.
Inflammation causes synovial fluid to become _____ in character.
Less viscous - so it drips like water instead of showing a normal string sign
What WBC/mm^3 is seen in normal, non-inflamm, inflammatory, septic, and hemorrhagic synovial fluid?
Normal: <200
Non-inflamm: 200-2,000
Inflammatory: 2,000-10,000 (up to 100,000)
Septic: >80,000
Hemorrhagic: 200-2,000
What is gout? When it is more common?
Very inflamm. arthritis linked to metabolic disorder causing ^ in blood uric acid (hyperuricemia) and pro-inflamm crystals in the joint.
- in an acute attack uric acid levels may be falsely low (DO NOT CHECK SERUM LEVELS - IT IS NOT AN INDICATION OF GOUT).
More common with increased BMI. Somewhat more common in men, but increases in women post-menopause.
What are the two causes of hyperuricemia (increased uric acid in blood)?
10% overproduction
90% caused by underexcretion
What is the clinical presentation of acute gout?
- Abrupt obset of severe pain
- Usually monoarticular and in lower extremity
- Exam shows synovitis with redness, swelling,and extreme tenderness over join.
Self-limited and resolves in 8-10 days if left untreated.
What is the clinical presentation of chronic gout?
Polyarticular pattern and can be destructive.
Tophaceous pattern - nodular masses of uric acid in soft tissues
How would you detect gout?
Fluid aspiration: look for monosodium urate needle-shaped crystals.
They will be yellow and parall and negetively birefringement.
What is chronic tophaceous arthritis?
Repetitive episodes of gout, urates encrust articular surfaces and form depossits that destory cartilage.
Tophi are large aggreggates of urate crystals surrounded by lymphocytes, giant cells, and fibroblasts.
What are therapeutic goals when treating gout?
- Increased excretion of uric acid
- Inhibit inflamm cells
- Inhibit uric acid biosyn
- Produce symptom releif (NSAIDs or steroids short term)
When should NSAIDs be given to someone with gout? What are some examples? What are some things that need to be considered?
Within the first 24hrs; indomethacin or naproxen
DO NOT GIVE ASPIRIN
Contraindicitons: GI, platelet, renal, and hypersensitivity effects
Why shouldnt aspirins/salicylates be given to someone with gout?
Most urate is reabsorbed but a small secretory component in the tubule occurs and can be reabsorbed.
Aspirin blocks secretory components and thus decreases excretion - - > increase its presence in blood
Large doses increase excretion because it blocks transport.
How can corticosteroids be used to treat someone with gout?
Symptomas relief in pts that can’t take NSAIDs.
Short term use only.
What is the MOA for Colchicine? How is it given and what are some considerations when giving it?
ORAL antimitotic that treats acute gout attacks by binding to mts in inflammatory cells (PMNs) and ultimately inhibits activation and migration.
Can also be used prophylactically in pts with chronic gout.
Metabolized by CYP450; substrate for P-glycoprotein (pump that gets rid of drugs) - ie dont give to pts taking other cyp metabolized drugs or P-gp inhibitors.
What are adverse effects of colchicine?
Significant!
GI effects: nausea, vomiting, diarrhea, and abd. pain
Greatly limits use of the drug.
What non-pharmacological measures can be used to prevent gout?
Abstain from alcohol
Weight loss
Discontinue medicines that impair uric acid excreteion such as aspirin and thiazide diuretics.
What are some potential drug therapies to prevent gout flare and destructive effects on joints/kidneys?
- Allopurinol
- Febuxostate
- Probenecid
- Pegloticase
What is the MOA for allopurinol? What are some adverse effects?
Prodrug that prevents chronic gout by blocking xanthine oxidase, which causes plasma uric acid concentration to decrease and urid acid crystals to dissolve.
Hypersensitivity an d acute goet attack may occur due to mobilization of tissue stores of uric acid.
What is the MOA of Pegloticase? What are some adverse effects?
Recombinant form of urate-oxidase enzyme (uricase) used to prevent chronic gout attacks by converting uric acid to an inactive and water soluble metabolite.
Infusion site rxns, gout flare (need to provide prophylaxis for acute gout flares), and immune response b/c the portion of the molecule is foreign.
What are the major drug interactions of gout medication?
What is rheumatoid arthritis? Who is more likely to get it?
Inflamm symmetrical chronic polyarthritis
- Immune disease involv. both T and B cells
- Genetic predisposition (HLA-DR4 and HLA-DR1)
- First degree relatives have a 1.5x higher risk
1% worldwide. Women>Men 2.5:1
What is the pathogenesis of RA?
- APC phagocytose antigens and present to T cells
- Activated T cells stim. production of B and T cells
- B cells produce plasma cells that form Rheum. antibodies
- Helper Tcells activate macrohpages and CD8 T cells
- T cells, macrophages, and CD8 cells make TNFa, IL-1, and IL6, and prostaglandins that cause joint inflamm, synovial prolif, and bone and cartilage destruction.
What is the pathology of RA?
Chronic papillary synovitis: chronic inflamm of the synovium; accompanied by synovial cell hyperplasia that results in pappillary pattern on surface of synovium.
PMNs and fibrin on joint surfaces in acute phase.
Hyperplastic inflammed synovium extends over the articular surface surface, forming a pannus which fills the joint space.
What is this an image of?
Lymphoid follicles in papillary synovitis (arrows are pointing to papillary structures)in rheumatoid arthritis.
What syptes of cells are present in RA?
Hyperplastic synovial cells and lymphocytes.
Synovium demonstrates papillary hyperplasia caused by dense inflamm infiltrate.
Where do rheumatoid nodules occur? What do they look like grossly and on histology? What causes them?
Usually skin(subQ), in areas exposed to pressure (extensor of forearm/elbow). Occurs in ~25% of those with severe disease.
Grossly: non tender firm, round, oval
Hist.: central zone of fibrinoid necrosis surrounded by rim of epithelioid histiocytes, and then lymphocytes and plasma cells.
Necrosis secondary to vascular damage
What is the MOA of Etanercept (enbrel)? What is the half life, adverse effects, and therapetuic indications?
Inhibits ability of soluble TNFa to bind its receptor (TNFa is a pre-inflamm cytokine).
Long half-life.
Injection-site reactions and infections.
Indicated in mod-severe RA, juvenile RA, and early stage.
What is the MOA of Adalimumab (humira)? What is the half life, adverse effects, and therapetuic indications?
Binds soluble AND transmembrane forms of TNFa to prevent TNFa binding to its receptor.
Long half life.
Injection site rxns and infections.
Mod-severe RA, active mod-severe juvenile arthritis, may be used alone or with methotrexate.
What is the MOA of rituximab (rituxan)? What is the half life, adverse effects, and therapeutic use?
B cell depleting monoclonal anti-CD20 antibody (CD20 normally responds to complement activation).
Long half life
Injection site reactions and inreased risk of infections.
Mod-severe active RA in combo with methotrexate in those with inadequate resposne to one or more anti-TNF aget.
What is the MOA of abatacept (orencia)? What is the half life, adverse effects, and therapeutic use?
Fusion protein that inhibits the binding to CD28 and prevents the activation of T cells.
Long half life.
Injection site reaction and infections.
Mod-severe active RA in adults with inadequate response to one or more DMARDs or anto-TNF agents.
What is the clinical presentation of OA?
Non-inflammatory joint pain
- worse with activity
- minites of morning stiffness (as opposed to 1+ hour with RA)
- brief stiffness after prolonged immobility (gelling)
- “crunching”
How does OA differ from RA?
OA: fusiform swelling of joints, heberden’s nodules (boney swellings), DIP joints affected.
RA: swan neck and boutonniere deformitiy, ulnar deviation, DIP joints spared.
How would you diagnose OA? What may be seen on radiology?
Based on joint distribution, character of pain, and exam findings.
- blood tests usually not helpful
- X rays not required (controversial)
- Synovial fluid aspiration may rule out other arthritis
Xray: narrowing of joint space, osteophytes (bony outgrowth associated with degen of cartilage at joints).
What ist the early pathology of OA?
Superficial layers of catilage are destroyed: fibrillation and cracking of the matrix
Limited chondrocyet proliferation and new matrix formation
Describethe femoral head in pts with more advaced OA?
What is the differene between a RA and OA joint?
RA: pannus formation, inflammation
OA: subchondral cyst, bony spur
What is the MOA of capsaicin? How is it given, what are the adverse effects, and what does it treat?
Agonist for TRPV1 receptor ion channel - induces release of SubP (mediator of pain from periphery to CNA). After repeated application, it depletes the neuron of SubP and prevents reaccumulation.
Topical; local transient application site pain and erythema.
OTC for minor pain (OA)
What is the MOA of hyaluronic acid (HA)? How is it given? what are adverse effects?
Injection of polysaccharice made of glucosamine and glucuronic acid:
- Inhibits inflamm mediators
- Decreases cartilage degradation
- Promotes cartilage matrix synthesis
Can cause joint inflammation; small risk of infection. No evidence that it slosw disease progression but may help reduce pain.
