Underlined Stuff from Rheum Review Session (complete) Flashcards
Describe generally OA
- Degeneration of cartilage, hypertrophy of bone
- Involves DIP (Heberden), PIP (Bouchard), 1st CMC
How do sports affect OA?
- No increased risk
- Exercise may actually be protective
Describe the cartilage in OA
INCREASED METALLOPROTEINASES
- also increased chondrocytes, water content
- Decreased proteoglycan, TIMP
- non-inflammatory synovial fluid
Which types of cytokines/inflammatory mediators are produced in OA?
- IL-1
- NO
- Prostaglandins
- Others (TNF, IL-6, 17, 18)
Complement activation
Adipokines (why obese people have ^ risk of OA)
Describe knees of OA
1) Joint space loss
2) Sclerosis (bone remodeling)
3) Subcondral cysts
4) Osteophytes
Describe RA
- Systemic, inflammatory autoimmune
- Unknown cause
- peripheral, SYMMETRIC SYNOVITIS => cartilage & bone destruction
- Joint involvement: bilateral, symmetric small joints hands (SPARES DIPS)
Overall ^ of inflammatory/cytokines causes bone and cartilage erosion
What is the disease susceptibility and severity associated with in RA? (think immune)
- Shared epitope: short sequence in Ag binding groove
- Shared subsets: HLA-DR4 and HLA-DR1
What are RF-IgG immune complexes associated with?
They are PATHOGENIC
- Can cause vasculitis and rheumatoid nodules over extensor surfaces
What are the majority of lymphocytes in RA synovium?
- CD4+ T cells
- Th17 cells
Why are CD4+ memory T cells in the RA synovium?
Modulation and amplification of local immune response through Ag recognition
Describe THE gout
- Results from tissue deposition of monosodium urate (MSU)
- Due to hyperuricemia (MSU SUPERSATURATION of extracellular fluids)
- Joints involved: 1st MTP, other cool peripheral joints of extremities (more likely to saturate at low temps)
What is the most common cause of hyperuricemia?
UNDER-EXCRETION of uric acid (90% of pts w/ gout)
other 10% = over-production
Uric acid is a a product of what?
Purine metabolism
Which enzyme do humans lack? It breaks down uric acid
Uricase
- oxidizes uric acid to allantoin
What are two ways to overproduce uric acid?
1) PRPP synthetase overactivity
2) HGPRT deficiency
X-linked!!!
complete HGPRT deficiency is Lesch-Nyhan
How is crystal arthritis diagnosed?
Arthrocentesis
Crystals identified by polarized microscopy
What does protein coating of crystals modulate in cellular response?
- IgG coating promotes phagocytosis by PMNs
- IgG => not specific anti-crystal Abs
- Apolipoprotein B coating INHIBITS phagocytosis
What are the characteristics of spondyloarthropathies?
- Sacroiliitis (SI joints)
- Enthesis (inflammation where ligaments/tendons inset into bone)
- Synovium: increased expression of TNF-alpha
Unknown infectious trigger in genetically susceptible individual => disease!
Describe the chances of developing ankylosing spondylitis
THINK: HLA-B27
- 2% if HLA-B27 positive
- 20% if HLA-B27 positive w/ first degree relative w/ AS
Describe reactive arthritis
- H/o infectious diarrhea or urethritis
- Asymmetric, oligoarticular, LOWER EXTREMITY ARTHRITIS
Describe systemic lupus erythematosus (SLE)
- Chronic, systemic disease affecting multiple organs
- Defect: misdirected recognition of self as foreign!!!
- Results in autoimmune process => T cell AND B cell process
- Ab responses to auto Ags are Ag-driven and require CD4+ T cells
- Loss of T cell requires B cell stimulation => peripheral abnormality in self-reactive lymphocyte deletion/anergy
Describe the genetics of SLE
- POLYGENIC
- Associated with C4A null allele
C4A null allele shows greatest risk!!!!!
Describe antinuclear antibodies (ANA)
- In SLE: >95% of pts have positive ANAs
- Not specific for SLE
- Abs are directed to multiple nuclear Ags
Anti-phospholipid Abs in SLE are associated with what?
INCREASED clotting
- block prothrombin activation in coag cascade
