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Flashcards covering Rheumatoid Arthritis, Osteoarthritis, and related topics.
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Rheumatoid Arthritis (RA)
Chronic, systemic autoimmune disorder primarily affecting synovial joints, leading to bone erosion and joint deformity.
Target Tissue (RA)
Synovium, cartilage, and underlying bone
Osteon
Structural Unit of Bone
Organic Matrix Components
Collagen and reticular fibers
Inorganic Matrix Components
Hydroxyapatite (Ca & phosphate)
Concentric Lamellae
Matrix layers around a central (Haversian) canal.
Lacunae
Small cavities housing osteocytes.
Osteoblasts
Build bone, secrete matrix, become osteocytes
Osteocytes
Maintain matrix; communicate via canaliculi
Osteoclasts
Resorb bone, secrete H⁺ and proteases
Ruffled border
↑ surface area for resorption (osteoclasts)
PTH Effect on Bone
↑ Osteoclast activity (indirect)
Calcitonin Effect on Bone
↓ Osteoclast activity
Pro-inflammatory Cytokine Effects on Bone Cells
↓ Osteoblasts, ↑ Osteoclasts
Anti-inflammatory Cytokine Effects on Bone Cells
↑ Osteoblasts, ↓ Osteoclasts
IGF, BMP, TGF-β
Promote osteoblast differentiation
RANK
Found on the surface of osteoclast precursors (immature osteoclasts); stimulates osteoclast formation and activation, leading to bone resorption.
RANKL (RANK Ligand)
Made and released by osteoblasts and stromal cells; binds to RANK on osteoclast precursors, stimulating their differentiation, activation, and survival.
OPG (Osteoprotegerin)
Secreted by osteoblasts; acts as a “decoy receptor”, binding to RANKL and preventing it from activating RANK
RANKL → RANK
Stimulates osteoclasts; Increased bone Resorption
OPG → Binds RANKL
Blocks RANK activation; decreased bone resorption
Vitamin D Effect on Bone
↑ RANKL
Glucocorticoids Effect on Bone
↓ OPG
Immune Activation (RA Pathogenesis)
Self-antigens (Self-antigens e.g., citrullinated proteins like fibrinogen, collagen are misidentified as foreign are taken up by antigen-presenting cells (APCs like macrophages and dendritic)→ APCs (dendritic cells, macrophages) present via MHC II; Activation of Th1 and Th17 cells → produce RANKL, ↑ osteoclastogenesis.
Synovial Inflammation (RA Pathogenesis)
Synoviocytes + T cells produce cytokines (TNF-α, IL-1, IL-6), NF-κB (↑ COX enzymes → ↑ PGE2), MMPs (degrade cartilage/bone)
RF (Rheumatoid Factor)
IgM antibody targets region of IgG; creates immune complexes which are very inflammatory
Anti-CCP (ACPA)
Antibodies against citrullinated proteins; targets these altered self-proteins, thinking they’re foreign
Clinical Presentation of RA
Symmetric joint pain, morning stiffness >1 hr, fatigue, nodules
RF, anti-CCP Significance in diagnosing RA
Autoantibodies (Anti-CCP = early + specific)
ESR, CRP Significance in diagnosing RA
Inflammation markers
Imaging results - RA
Soft tissue swelling, tenosynovitis (early); Marginal erosions (esp. 2nd/3rd MCP & PIP), periarticular osteopenia (progression)
HLA-DRB1
Strongest genetic link to RA.
Synovitis Stage of RA
Inflamed synovial membrane
Pannus Formation Stage of RA
Invasive granulation tissue
Fibrous Ankylosis Stage of RA
Fibrous fusion of joint
Bony Ankylosis Stage of RA
Bone fusion, complete immobility
STAT4
T-cell activation, RA + lupus
TRAF1-C5
Cytokine signaling
Smoking Risk Factor for RA
↑ Citrullination, oxidative stress
Silica Risk Factor for RA
Immune activation
Oral contraceptives Risk Factor for RA
Protective against RA
NSAIDs Purpose in Treating RA
Symptom relief, no disease modification
Steroids Purpose in Treating RA
Short-term; suppress immune function
Methotrexate (DMARD) Mechanism
Inhibits DHFR (reductase) → ↓ folate → ↓ T/B cell proliferation; ↑ adenosine (anti inflamm effects)
Sulfasalazine (DMARD) Mechanism
Metabolites inhibit TNF-α, NF-κB, COX enzymes, and immune cells
Leflunomide (DMARD) Mechanism
Inhibits DHODH enzyme → blocks DNA synthesis in immune cells
Hydroxychloroquine (DMARD) Mechanism
↑ pH in lysosomes → interferes with antigen processing
↑ pH in lysosomes Effect
HCQ makes these compartments less acidic.
↓ Antigen processing Effect
Enzymes can't break down proteins properly.
↓ MHC-II antigen presentation Effect
T-cells are less activated
↓ Inflammation Effect
Less immune system overactivity.
TNF-α inhibitors (Biologic DMARDs)
Etanercept, Infliximab, Adalimumab, target TNF-α
IL-6 inhibitors (biologic DMARDs)
Tocilizumab, Sirukumab, target IL-6
B-cell depletion
Rituximab, target CD20 B cells
T-cell co-stimulation block (biologic DMARDs)
Abatacept, target CTLA-4
Synovial Fluid Function
Lubricates and nourishes cartilage.
RA Takeaways
autoimmune → joint destruction; Central: T cells, synoviocytes, RANKL, MMPs, cytokines
RA Diagnosis
Clinical + serological + imaging
RA Treatment
Immune modulation with DMARDs, focus on preventing long-term joint damage
Osteoarthritis (OA) Definition
degenerative joint disease, especially common with aging; knee joint
Periosteum
Pain-sensitive outer covering of bones.
Articular Cartilage
Hyaline cartilage; shock absorption and smooth movement.
Fibrous Capsule
Encloses synovial membrane; together they form the articular capsule
Ligaments
Provide joint stability.
Meniscus
Fibrocartilage for stability and shock absorption (knee)
Osteocytes Function
Mature bone cells.
Osteoblasts Function
Build bone.
Osteoclasts Function
Break down bone.
Synovial Macrophages Function
Immune cells involved in inflammation.
Key Features of OA
Articular cartilage degeneration, joint space narrowing, Osteophytes (bone spurs), Subchondral sclerosis (bone hardening below cartilage)
Primary OA
Idiopathic, age-related
Secondary OA
Due to trauma, congenital abnormalities, or inflammatory diseases
Risk Factors for OA
Aging, female sex (hip OA), obesity, joint injury, deformity (genu varus/valgus), rheumatic disease, genetics
OAPathophysiology Macrophages
Macrophages in synovium stimulated by risk factors; release cytokines (TNF-α, IL-1β, IL-6), VEGF, E-selectin
Cartilage Breakdown Leading to Bone Changes in OA
Damaged cartilage releases IL-1β, IL-6, and TNF-α, stimulating osteoblasts to lay down new bone
Dysregulation Process in OA
Leads to bony overgrowths (osteophytes) and subchondral sclerosis (thickening/hardening of the bone below cartilage)
Pain Mechanism in OA
Cytokines, prostaglandins, bradykinin stimulate sensory nerves; Pain increases with activity, relieved by rest; severe OA can cause night/rest pain.
Clinical Presentation of OA
Pain (activity-related → rest/night), stiffness, malalignment (genu valgus/varus), muscle wasting, tenderness, possible osteophytes (bone spurs), joint effusion, crepitus, reduced movement.
first line and 2nd option for RA
Methotrexate | First-line for most patients |
Hydroxychloroquine | Mild RA or add-on |
X-ray Findings (OA)
Loss of joint space Osteophytes, Subchondral sclerosis, Subchondral cysts
Joint Aspiration (Arthrocentesis) for OA
Synovial fluid WBC ≤ 2000/uL
ESR, CRP (Blood Work) Meaning
Rule out inflammatory disease
RF, Anti-CCP (Blood Work) Meaning
Rule out RA
ANA (Blood Work) Meaning
Autoimmune screen
CBC (Blood Work) Meaning
Anemia, WBC, PLT status
Hb/Hgb (Blood Work) Meaning
Anemia evaluation
WBC (Blood Work) Meaning
Infection/inflammation
PLT (Blood Work) Meaning
Thrombocytosis
LFTs (Blood Work) Meaning
Baseline for medication use
U&E / RFT (Blood Work) Meaning
Kidney health before NSAID use
TSH (Blood Work) Meaning
Rule out thyroid-related symptoms
HLA-B27 (Blood Work) Meaning
Spondyloarthropathy marker
Serum uric acid - (Blood Work) Meaning
Elevated in gout
Non-Pharmacological Management (OA)
Weight loss, education, physiotherapy, walking aids, knee braces, good footwear, acupuncture, heat/cold
Pharmacological Management (OA)
paracetamol aka acetaminophen; Topical NSAIDs or capsaicin; Oral NSAIDs + PPI; Glucocorticoid injections; Viscosupplementation; Opioids; Glucosamine, chondroitin, turmeric, fish oil
Swelling
Hallmark feature of RA
Rheumatoid Arthritis (RA) Overview Definition
Chronic, systemic autoimmune inflammatory disease targeting joints, especially synovium.
Clinical Presentation - RA
Symmetrical arthritis Pain, swelling, and stiffness Subcutaneous nodules
RA Joints
MCP, PIP, wrist
OA Joints
DIP, PIP