Introduction to Joint DIsease Flashcards
Define
mono
poly
oligo
mono-1 joint
oligo- 2-3 joint (Pauci)
poly-4 or more joints
What is the function of synovial joints?
allow gliding movement facilitated by lubricated cartilagenous surfaces
What tyoe of collagen is present in hyaline cartilage? what is the function of hyaline cartilage? where is it found?
- on articular surfaces
- function: elastic shock absorber spreads weight across surface of joint
- friction-free surface (along with synovial fluid)
- type 2 collagen: tensile strength
- chondrocytes maintain cartilagenous matrix
what is a synovial cavity? What is the function of synovial cavity?
- synovial cells line synovial cavity: cuboidal cells 1-4 layers thick
- function: produe synovial fluid, remove debris, regulate movement of solutes, electrolytes and proteins from capillaries into synovial fluid
- not present over articular cartilage
- contains synovial fluid
What is the function of synovial fluid?
viscous filtrate of plasma hyaluronic acid
functions as a lubricant and provides nutrients to articular cartilage
What features should be found grosly on a healthy synovial joint?
- blue/white transparency
What is the significance of timing when thinking about arthritis pain?
need to know if it is chronic or acute bc that helps you to decide if it is most likely infectious, inflammatory or non inflammaotry. acute is usually infectious
WHat things do you look for on physical exam for arthritis?
- observation
- deformities, redness, swelling, asymmetry
- palpation
- bony/hard, tender, warm, synovitis(thickening of synovium round joints leading to tender and “squishy” fell with firm palpation
- Function
- range of motion, pain with movement
What lab tests are done to assess for arthritis?
- Generic markers of inflammation
- Erythrocyte Sedimentation rate (“Sed rate”)
- C reactive protein
- anemia (of chronic disease)
- leukocytosis (high whit eblood cell count)
- Serology- ie presence of autoantibodies
- rheumatoid factor
- CCP Antibody
- Anti-nuclear antigen (ANA)
- Synovial (joint) fluid analysis
If inflammation is occuring will the sedimentation rate be high or low?
high!
what things raise the sedementation rate? do they change fast or slow? what things falsely elevate it?
- rasie:
- infection (most common)
- malignancy
- autoimmune/inflammatory conditions
- ****changes slowly****
- decrease:
- low fibrinogen
- polycythenia vera
- sickle cell
- sperocytosis
- artificially elevate sed rate
- ESRD
- Anemia
- Obesity
- Age
WHat is C reactive protein?
- small molecule that binds dying cells and/or pathogens
- rapid response within hours of tissue injury
- synthesized in liver
- very high C reactive protein level suggests bacterial infection
- High sensitivity CRP (hsCRP)
- measuring the exact same molceule, just an assay that can detect lower concentratios. hsCRP elevations linked to increased cardiovascular disease
What 2 factors are used serologically to look for rheumatoid arthritis and what are the differences between these two measures? which is a better predictor for RA
-
Rheumatoid factor
- autoantibosy that binds Fc region of human IgG
- 70% sensitivity for rheumatoid arthritis, 80% specificity
- false positive exist (hepC, sjorgen, primary biliary cirrhosis, multiple myeloma, healthy ppl)
-
Anti-Cyclic Citrillinated Peptide Antibody (CCP)
- 70% sensitivity for RA, >90% specificity. BETTER PREDICTOR
What doeas ANA stand for? WHat are the autoantibodies for
systemic lupus
sjogren’s
mixed connective tissue disease (MCTD)
Scleroderma
Inflammatory myopathy
Drug induced lupus
Antinuclear Antibody! Test looking for autoantibodies
- systemic lupus-Double stranded DNA, SSA (RO), Smith
- sjogren’s- SSA (RO), SSB (LA)
- mixed connective tissue disease (MCTD)- RNP
- Scleroderma-Scl-70
- Inflammatory myopathy-Jo-1
- Drug induced lupus-Histone
What is a string sign?
normal jont fluid should be viscous, if it is liek water then it is probably an inflammaed joitn
Depending on the clinical scenario, synovial fluid should be analyzed for:
If WBCs are over what value should we be alarmed?
cell count
crystals
culture and sensitivity (if septic arthritis is suspected)
cytology (if malignancy is suspected)
if WBCs are over 2000 we should think inflammation
What is gout? WHat percentage of the population has gout? what gender has more gout?
- very inflammatory arthritis linked to metabolic disorders resulting in elevation of blood uric acid (hyperuricemia) and pro inflammaotry crystals in the joint (although in acute flare values are often low so don’t bother checking blood)
- 4% of pop but rising due to rising BMI. more men but after menopause pretty even
There are 2 main ways to get hyperuricemia. What are these 2 ways and what things can lead to these?
- overproduction (10%)
- inherited enzyme defects
- myeloproliferative disroders
- purin-rich diet
- alcohol
- underexcretion
- renal failure
- metabolic syndrome/obesity
- diuretics
- alcohol
what is the clinical presentation of acute gout?
- abrupt onset of severe pain
- most commonly monoarticular involving lower extremity
- exam shows synovitis with redness, swelling and extreme tenderness over the joint
- self-limited and resolves in 8-10 days untreated
- *
the triggers to an acute gout flare are not well understoof but what is thought to cause an acute flare?
- probably release of crystals from pre-formed deposits
- changes in temperature, fluid status, and purine load (steak and beer)
- use of diuretic, particularly thiazide diuretics
- often occur in setting of acute illness
What is Birefrgence?
a test to look for uric acid crystals. you are looking for monosodium crystals that shoul be needle shaped. if it is negatively bifringent and yellow and parallel to the light then it si gout
what is chronic tophaceous arthritis? what are tophi?
- repetitive episodes of gout where urates encrust articular surfaces and form deposits that destroy cartilage
- tophi are large aggregates of urate crystals that are surrounded by lymphocytes and giant cells and fibroblasts
WHat things are often seen with gout?
- chronic polyarticular pattern
- tophaceuous gout pattern
- invlvement of great toe
- bone and cartilage erosion by urate deposits forming a tophus
- Bifringence
what are the therapeutic goals for Gout?
increased excretion of uric acid
inhibit inflammatory cells
inhibit uric acid biosyntheis
provide symptomatic relief (typically with NSAIDS or steroids short term)
How shoudl NSADs be involved in the treatment of gout?
withing the first 24 hours
indomethacin and naproxen
NOT ASPIRIN
but remember that there are contraindications to NSAID (GI, platelets, renal, hypersensitivity)
why shouldn’t we use aspirin for gout?
Salicylic acid specific effect
- dose dependent effect: low doses of aspirin decrease uric acid excretion bc there is a small secretory component in the neprhon for urate and this secretory portion is sensitive to low doses of salicylates. meaning they stop secretion. this leads to a build up of salicylates
- large doses actually incerase excretion, but we still just don’t give aspriing in gout due to the low dose influence on uric acid secretion
How can low dose corticosteroids be involved in gout treatment?
symptomatic relief in patients that can’t take NSAID, short term use due to adverse effects that occur with extended use
WHat is the drug colchicine used for? what is its MOA? How is it given? How is it metabolized? how is it absorpbed?
- therapeutic use: Cochicine is used for acute gout attacks within hours or prophylactically in pts. with chronic gout
- MOA: anti-mitotic. binds to microtubules in inflammatory cell (PMNs) and inhibits neutrophil activation and migration by arresting cells division in G1 by interferring with microtubules. if inflammatory cells can’t respond then there is not as much inflammation!
-
pharmacokinetics: oral, rapid absorption but variable, deposits in tissue stores/forms complex w tubulin (large volume of distribution),
- metabolized by :CYP450s, substrate for P-glycoprotein which is a transmembrane ptoein that eliminates drugs) so think about drug drug interactiosn w colchcine
What is P-glycoprotein pump?
a pump (transmembrane protein) that eliminates drugs
What are the adverse effects and contraindications for colchicine?
-
adverse efffects: significant! narrow therapeutic toxicity window.
- GI (nausea, vominiting, diarrhes, abdominal pain)
- usually a latent period before symptoms but it effects the rapid proliferatin cells of the GI
- these GREATLY limit the use of the drug
-
contraindications
- hepatic or renal disease (decrease dose or less frequent doses), elderly patients,
- especially if they are tkainf a CYP3A4 or P-gp inhibitor bc it would increase the concentration of colchicine
what are some non-pharmacological measures to prevent/treat gout?
- abstain from alcohol
- weight loss
- discontinue medicines that impair uric acid excretion like aspirin or thiazide diuretics
what 4 drugs (besides colchine) can be used to PREVENT gout flare and destructive effects on joint snd kidneys
allopurinol
febuxostat
probenecid
pegloticase
what is the pathogenesis of rheumatoid arthritis?
- dendritic (antigen-presenting) cells phagocytose anitgens and present them to T cells
- activated T cells stimulate the production of B and T cells
- B cells produce plasma cells that form rheumatoid antibodies
- Helper T cells activate macrophages and cytotoxic T cells
- Togteher, T cells, macrophages, and cytotoxic T cells produce cytoxic cytokines (TNFa, IL1, IL6 and others) and prostaglandins that cause joint inflammation, synovial proliferation and bone and caritlage destruction
What is a panus?
- a covering that grows and covers up the cartilgae and the synvoium within it are inflammatory cells there are aslo inflammatory cells in the snovial fluid
- papillary strucutres composed of synovial hyperplasia, lymphoid infiltrates, and fibrin
What are rheumatoid nodules?
- develop most commonly on skin (subcutaneous) in areas exposed to pressure (extensor surface of forearm and elbow)
- less than 25% (severe disease)
- less commonly in viscera
- grossly: non-tender, firm, oval.round
- microscopically: central zone of fibrinoid necrosis surrounded by rim of epithelail histocytes and then lymphocytes and plasma cells
- causes of nodules: necrosis secondary to vascular damage possibly secondary to vasculitis (inflammation of the vessel walls) associated with RA
What are the therapeutic indications for Adalimumab? MOA> half-life? adverse effects?
- TI: active moderate to severe RA, junvenile idiopathic arthritis, alone or in combo with methotrexate
- MOA: binds to soluble and transmembrane forms of TNFa to prevent binding of TNFa to its receptor (remember etanercept was just the soluble form)
- long half-life
- adverse effects: injection site recations, infections
what are features of late stage osteoarthritis vs late stage RA?
- Osteo:
- fusiform swelling of joint
- Herden’s nodes (bony enlargement of DIP joints. remember RA spares DIP)
- RA:
- Boutonniere deformity of thumb
- ulnar deviation of metacarophalngeal joints
- swan nech deformities
what are the early changes seen with osteo arthritis?
- superficial layers of cartilage are destroyed fibrilation and crackling of the cartilage matrix
- limited chondrocyte proliferation and new matrix formation
what happen with osteoarthritis? physical changes/pathology?
- absence of articular cartilage; polished appearance of exposed bone (eburnation)
- subchondral sclerosis: more dense bone develops underneath areas where cartilage is gone
- subchondral cyst: formed by break in cartilage; this allows synovial fluid to be forced into subchondral space, forming fibrous walled cyst
-
osteophyte formation: bony outgrowth develops at margins of articular surface in characteristic locations fo specific joints; results in increased joint size
- hip joint: all around entire joint margin, typically flat ostephyte on medial surfac extending to fovea
- distal interphalangeal joint: Heberden nodes
- proximal interphalangeal joint: Bouchard nodes
