Rheum Flashcards
Joint involvement of OA
Hips and knees
Spine: cervical and lumbar
1st MTP, 1st CMC
DIP (Heberden’s), PIP (Bouchard’s)
OA Occupational risks:
Miners: OA hips, knees, shoulders
Weavers: OA hands
Do sports increase your risk of getting OA?
NO!
no increased risk; exercise may be protective
Secondary OA
Inflammatory
Metabolic: hemochromatosis,
Wilson’s disease,
ochronosis
What makes up Cartilage
- Collagen: predominantly type II
- Proteoglycans (chondroitin and keratin sulfate) linked to hyaluronic acid
- Matrix proteins
- Chondrocytes
- Water: 70% weight of intact cartilage
Cartilage in early Osteoarthritis
↑ chondrocytes
↑ metalloproteinases
↑ water content
↓ proteoglycan (proton weave that loves water)
↓ TIMP
Synovial fluid of OA
noninflammatory, type I fluid (200-2000 WBC/mm3)
Cytokines and inflammatory mediators implicated in articular cartilage destruction in OA
- Interleukin-1: stimulates MMP production, PGE2, nitric oxide (NO), IL-6
- Nitric oxide: increases MMP production, inhibits proteoglycan synthesis, induces chondrocyte apoptosis
- Prostaglandins (PGE): ↑ production and activation of MMPs
- Other cytokines: TNF, IL-6, IL-17, and IL-18
Aside from IL-1, NO, PGE, and other cytokines, what else plays a role in OA pathogenesis?
Complement activation
Adipokines
characteristics of OA in x rays
Joint space loss
Sclerosis
Subchondral cysts
Osteophytes
Which one is symmetric, RA or OA?
RA is.
RA Joint involvement:
Bilateral, symmetric - small joints hands + feet sparing the DIPs
Medium and large joints can be involved
X-rays: marginal joint erosions and deformities
Disease susceptibility of RA
Disease susceptibility and severity associated with shared epitope in subtypes of HLA-DR4 and HLA-DR1
RF
Anti-CCP
Rheumatoid factor (RF):
Usually IgM Antibody directed against the Fc portion of IgG
- RF-IgG immune complexes are pathogenic
Anti-Cyclic Citrullinated Peptide Antibodies (Anti-CCP)
Autoantibodies reactive with synthetic peptides containing the unusual amino acid citrulline (modified arginine residue)
Even though RF isn’t specific for RA, A-CCP sure as hell is.
- If you have both RF AND A-CCP, hell yea, you prob gots RA
Pannus
- what is it,
- Which disorder is it usually seen in
Infiltrating butt ton of cells
- Lymphocytes, macrophages ect.
RA (systemic inflammatory auto imm. disorder.
Lymphocytes in RA synovium:
Majority are CD4+ T cells
- Th17 cells
- B cells and plasma cells are present (RF, anti-CCP); no PMNs
CD4+ memory T cells fxn in rheumatoid arthritis
modulation and amplification of local immune response through antigen recognition
(query altered proteoglycans or collagen; citrullinated peptides)
The Gout
The result of tissue deposition of monosodium urate (MSU) crystals due to hyperuricemia (MSU supersaturation of extracellular fluids)
Gout joint involvement
- 1st MTP (podagra)
- Cool, peripheral joints of lower and upper extremities
- remember OA is 1st MTP too! (and 1st CMC)
What type of Hyperuricemia is most common in Gout?
underexcretors (90%)
- make it just fine, but cant get rid of it bc we lack uricase! which oxidizes uric acid into allantoin
Uric acid is a product of what?
purine metabolism:
Overproduction of uric acid
- what is it?
- type of genetic disorder?
- whats wrong with the enzymes?
Less common type of gout
X-linked
PRPP synthetase OVERACTIVITY
HGPRT DEFICIENCY
= high uric acid
*note: the common underexcretors also result in high uric acid content
How do you diagnose crystal arthritis in gout?
arthrocentesis (polarized microscopy)
aspirate or litigate!
How would you describe MSU crystals in Gout?
needle-shaped, negatively birefringent (blue outline)
Endogenous MSU crystals may act as a “danger signal”, how?
- Initial recognition of naked MSU crystals by TLR2 / TLR4 critical to the inflammatory response
- MSU crystals engage the caspase-1 activating NLRP3 inflammasome resulting in IL-1β production
Self-limited nature of acute gouty arthritis
- Proteins coating the crystals modulate the cellular response:
- Phagocytosis of crystals ↓ concentration
- Local heat of inflammation ↑ MSU solubility
- ACTH secretion suppresses inflammation
- IL-1 and TNF are modulated by inhibitors
How do proteins coating the crystals in gout modulate the cellular response?
- IgG-coating promotes phagocytosis by PMNs
- IgG: not specific anti-crystal antibodies
Apolipoprotein B-coating inhibits phagocytosis
Calcium Pyrophosphate Dihydrate Deposition Disease
Pseudogout
pathology of pseudogout (whats wrong?)
Abnormal pyrophosphate (PPi) metabolism – not purine like gout (uric acid)– crystals are naturally in your joint and shed
What is making more abnormal pyrophosphate (PPi) in pseudogout (CPPD)?
ANK and NTPPPH metabolism of nucleoside triphosphate (NTPs) from chondrocytes
How would you describe CPPD crystals?
rhomboid, positively birefringent (blue outline)
Remember, in gout, crystals are needle-shaped, negatively birefringent
