SM_234a: Rheumatoid Arthritis Flashcards
Rheumatoid arthritis is _____
Rheumatoid arthritis is a chronic inflammatory joint disease of autoimmune nature characterized by the development of autoantibodies
(more common in women, occurs earlier in women)
Risk factors for RA include ____, ____, ____, ____, ____, and ____
Risk factors for RA include genetic, epigenetic, female sex, smoking, dust inhalation, and microbiota (periodontal disease, gut microbiome)
Shared epitope is a ______
Shared epitope is a specific amino acid motif commonly encoded by alleles of the HLA-DR loci that confers genetic susceptibility to development of RA
(specific class II HLA antigen loci show strong association with RA, HLA-DRB1*01 and HLDRB1*04 are among strongest risk factors, many loci harbor RA susceptibility variants of variable strength)
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Locus involves in RA is _____
Locus involves in RA is HLA DR
Environmental risk factors for RA are ____, ____, and ____
Environmental risk factors for RA are smoking, dust inhalation, and microbiota
- Risk from smoking increases in a graded fashion
- Dust inhalation
- Periodontal disease increases risk of developing RA
- Gut microbiome changes in RA
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Healthy synovium has ____ and has a sublining of ____, ____, ____, and ____
Healthy synovium has an intimal lining of macrophage-like and fibroblast-like synoviocytes and sublining of fibroblasts, adipocytes, blood vessels, and immune cells
- Intimal lining is a delicate and leaky and allows free movement of cells and proteins into synovial fluid
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Healthy synovium functions to _____ and _____ during homeostasis
Healthy synovium functions to produce lubricants for cartilage and provide nutrients to cartilage during homeostasis
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In RA, pathological changes of the synovium include ____, ____, ____, and ____
In RA, pathological changes of the synovium include expansion of intimal lining with activated synoviocytes producing pro-inflammatory cytokines, infiltration of adaptive immiune cells into synovial sublining with hypervascularity, formation of a pannus, and activation of osteoclasts to degrade bone
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Pannus is an _____
Pannus is an invasive destructive front of synovial tissue attached to the articular surface
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Describe pathological changes in the RA synovium
RA synovium pathological changes
- Intimal lining greatly expands with activated synoviocytes producing pro-inflammatory cytokines
- Infiltration of adaptive immune cells into synovial sublining with hypervascularity
- Pannus: invasive, destructive front of synovial tissue attached to the articular surface
- Activated osteoclasts degrade bone
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Pannus is formed by ____, ____, and ____
Pannus is formed by the expansion of activated synoviocytes, infiltration of immune cells, and hypervascularity
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Describe the disease coure of RA
RA disease course
- Pre-clinical: citrullination
- Early: synovitis
- Established: joint damage
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Pre-clinical RA is characterized by _____
Pre-clinical RA is characterized by citrullination
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Early RA is characterized by _____
Early RA is characteirzed by synovitis
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Established RA is characterized by _____
Established RA is characterized by joint damage
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Describe the disease course and pathogenesis of RA
RA disease course and pathogenesis
- Pre-clinical RA: circulating autoantibodies and pro-inflammatory cytokines are detectable up to 10 years before clinical disease onset
- Citrullination is a key step in RA pathogenesis that leads to immune activation and production of RF and ACPAs
- Synovitis and joint damage are cardinal features of RA driven by pro-inflammatory cytokines IL-1, IL-6, and TNF
Describe the HPI of someone with RA and someone with OA
- RA: usually insidious onset of symmetric polyarthritis (>3 joints) especially in joints of hands and feet, joint swelling, decreased ROM in joints, pain and swelling worse in morning, morning stiffness lasting >1 hour, stiffness after rest (gelling)
- OA: insidious, bony enlargement of joints, morning stiffness lasting < 30=60 minutes, stiffness after rest (gelling)
RA involves joint _____, while OA involves _____ of joints
RA involves joint swelling, while OA involves bony enlargement of joints