Flashcards in Underlined Stuff from Rheum Review Session (complete) Deck (42):
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
- also increased chondrocytes, water content
- Decreased proteoglycan, TIMP
- non-inflammatory synovial fluid
Which types of cytokines/inflammatory mediators are produced in OA?
- Others (TNF, IL-6, 17, 18)
Adipokines (why obese people have ^ risk of OA)
Describe knees of OA
1) Joint space loss
2) Sclerosis (bone remodeling)
3) Subcondral cysts
- 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?
Which enzyme do humans lack? It breaks down uric acid
- oxidizes uric acid to allantoin
What are two ways to overproduce uric acid?
1) PRPP synthetase overactivity
2) HGPRT deficiency
complete HGPRT deficiency is Lesch-Nyhan
How is crystal arthritis diagnosed?
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
- 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
- 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?
- block prothrombin activation in coag cascade
Inflammation w/in or through blood vessel wall => damage to vessel integrity/flow
What are types of large vessel vasculitis?
1) Takayasu's arteritis
2) Giant cell arteritis
What are types of medium vessel vasculitis?
1) Polyarteritis nodosa
2) Kawasaki's disease
What are types of small vessel vasculitis that have c-ANCA?
2) Churg Strauss
3) Microscopic polyangiitis
What are types of small vessel vasculitis that have p-ANCA?
3) Cutaneous leukocytoclastic vasculitis
Describe the pathophysiology of immune complexes in vasculitis
- inflammation causes *increased vascular permeability* => IC deposition
- Leads to palpable purpura
Describe the pathophysiology of T cell dependent mediated endothelial cell injury in vasculitis
HLA-DR4 and giant cell arteritis
Suggests AG-DRIVEN vascular inflammation
What is associated with cytoplasmic ANCA (c-ANCA)?
- PROTEINASE-3 (PR3) in primary granules of PMNs
- GPA (Wegeners)
Think 3 looks like 2 Cs and 3 on its side is a W or Wegeners
What is associated with perinuclear ANCA (p-ANCA)?
-Myeloperoxidase (MPO) in 1ary granules
- Microscopic polyangiitis (MPA)
All the P's!!!
- Inflammatory myopathies
- Muscle weakness
- Gottron's papules
- Heliotrope rash (eyeshadow rash)
- V-sign and shawl sign
- Mechanic's hands
- Periungual changes/erythema
What is the most common presentation of anti-synthetase syndrome?
PM or DM presenting with:
INTERSTITIAL LUNG DISEASE (60%)
Where are anti-synthetase Abs found?
What's another word for Anti-Jo1?
Are anti-synthetase Abs pathologic?
NO! Not pathologic or myotoxic
They are just markers for disease
Which inflammatory cells are associated with Polymyositis?
CD8+ T cells
Which inflammatory cells are associated with dermatomyositis?
CD4+ T cells
What is important to keep in mind about evidence suggesting a viral cause for PM or DM?
By the time a pt comes in with a disease, the virus has already been eaten up by the immune system
You won't find the live virus, no culture
There can be evidence of the virus, but NO LIVE VIRUS