Rheumatology Flashcards

Flashcards covering Rheumatoid Arthritis, Osteoarthritis, and related topics.

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