Introduction to Rheumatology Flashcards
What is rheumatology?
medical specialty dealing with diseases of the musculoskeletal system
What are joints?
where 2 bone meets
What are tendons?
cords of strong fibrous collagen tissue attaching muscle to bone
What are ligaments?
flexible fibrous connective tissue which connect two bones
What are the components of a synovial joint?
- Bone
- Joint cavity containing synovial fluid
- Articular carilage
- Bone
What is synovium?
- 1-3 cell deep lining containing macrophage-like phagocytic cells (type A synoviocyte) and fibroblast-like cells that produce hyaluronic acid (type B synoviocyte)
- Type I collagen
What is synovial fluid?
Hyaluronic acid-rich viscous fluid
What is articular cartilage?
- Type II collagen
2. Proteoglycan (aggrecan)
What is arthritis?
disease of the joints
What are the two main divisions of arthritis?
- Osteoarthritis (degenerative arthritis)
2. Inflammatory arthritis (main type rheumatoid)
What is inflammation?
- a physiological response to deal with injury or infection
- aexcessive/inappropriate inflammatory reactions can damage the host tissues
How does inflammation manifest?
- RED (rubor)
- PAIN (dolor)
- HOT (calor)
- SWELLING (tumor)
- LOSS OF FUNCTION
What are the Physiological, cellular and molecular changes in inflammation?
- Increased blood flow
- Migration of white blood cells (leucocytes) into the tissues
- Activation/differentiation of leucocytes
- Cytokine production
E.g. TNF-alpha, IL1, IL6, IL17
What are the causes of joint inflammation?
- Crystal arthritis
- Immune mediated (“autoimmune”)
- Infection
What are examples of crystal arthritis?
- Gout
2. Pseudogout
What are the examples of immune-mediated joint inflammation?
E.g.
- Rheumatoid arthritis
- Seronegative spondyloarthropathies
- Connective tissue diseases
What are examples of infection that causes joint inflammation?
- Septic arthritis
2. Tuberculosis
What is gout?
Gout is a syndrome caused by deposition of urate (uric acid) crystals -> inflammation
What is a high risk factor for gout?
High uric acid levels (hyperuricaemia)
What are the causes of hyperuricaemia?
- Genetic tendency
- Increased intake of purine rich foods
- Reduced excretion (kidney failure)
What is pseudogout?
a syndrome caused by deposition of calcium pyrophosphate dihydrate (CPPD) crystal deposition crystals -> inflammation
What are the risk factors of pseudogout?
- background osteoarthritis
- elderly patients
- intercurrent infection
What is a good example of arthritis?
acute gout
What does a disease in which tissue deposition of monosodium urate (MSU) crystals occurs as a result of hyperuricaemia and lead to?
- Gouty arthritis
* Tophi (aggregated deposits of MSU in tissue)
What does gouty arthritis usually affect?
metatarsophalangeal joint of the big toe (‘1st MTP joint’) podagra
What are the symptoms of gouty arthritis?
- Abrupt onset
- Extremely painful
- Joint red, warm, swollen and tender
When does gout resolve?
spontaneously over 3-10 days
What are the investigations for gout?
oint aspiration – synovial fluid analysis
What is the management for an acute attack of gout?
colcihine, NSAIDs, Steroids
What is the management for chronic gout?
allopurinol
How is synovial fluid examined?
- Rapid Gram stain followed by culture and antibiotic sensitivity assays
- Polarising light microscopy to detect crystals which can be seen in arthritis due to gout or pseudogu
What is the crystal like the the synovial fluid of gout and psuedogout?
- gout: urate
- pseudogout: CPPD
What is the shape like the the synovial fluid of gout and psuedogout?
- gout: needle
- pseudogout: brick shaped
What is the birefringence (polarizing light microscopy) l like the the synovial fluid of gout and psuedogout?
- gout: negative
- pseudogout: positive
What is the most common form of immune mediated inflammatory joint disease?
rheumatoid arthritis (RA)
What is RA?
chronic autoimmune disease characterised by pain, stiffness and symmetrical synovitis
(inflammation of the synovial membrane) of synovial (diarthrodial) joints
What happen to the synovium in rheumatoid arthritis?
a proliferated mass of tissue (pannus)
Why does the synovium change?
- Neovascularisation
- Lymphangiogenesis
- Inflammatory cells:
What inflammatory cells are involved in RA?
- activated B and T cells
- plasma cells
- mast cells
- activated macrophages
How are these changes to synovium in RA controlled?
- Recruitment, activation and effector functions of these cells is controlled by a cytokine network
- There is an excess of pro-inflammatory vs. anti-inflammatory cytokines (‘cytokine imbalance’)
What is in a healthy synovial membrane?
- 1-3 cell layer than lines synovial joints
- contains macrophage-like (type A synoviocyte) and fibroblast-like (type B synoviocyte) cells and type 1 collagen
What is the function of a healthy synovial membrane
- Maintenance of the synovial fluid
- the hyaluronate rich viscous fluid within joint space
What does TNF alpha do in RA?
detrimental role
How is RA controlled?
TNF alpha inhibitors
How is TNF alpha inhibition achieved?
parenteral administration (most commonly sub-cutaneous injection) of antibodies or fusion proteins
What is the dominant pro-inflammatory cytokine in Rheumatoid synovium?
cytokine tumour necrosis factor-alpha (TNF alpha)
What does TNF alpha come from?
activated macrophage
What does TNF alpha do?
- Pro-inflammatory cytokine release (including Il-1, Il-6, Il-23 and GM-CSF)
- Hepicidin induction: acute phase response
- PGE2 production
- Osteoclast activation: bone resorption
- Chonrdocyte activation:
- metalloproteinase production
- cartilage destruction - Angiogenesis
- Leukocyte accumulation: induction/maintenance of HLA class II expression
- Endothelial cell activation: upregulation of E-selectin and VCAM-1, Leukocyte accumulation
- Chemokine release (including RANTES, MCP-1, IL-8 and SDF-1, leukocyte acitvation)
When are the key features of RA chronic arthritis?
- Polyarthritis - swelling of the small joints of the hand and wrists is common
- Symmetrical
- Early morning stiffness in and around joints
- May lead to joint damage and destruction - ‘joint erosions’ on radiographs
When can extra-articular disease can occur?
- Rheumatoid nodules
* Others rare e.g. vasculitis, episcleritis
How can rheumatoid ‘factor’ be detected in blood?
Autoantibody against IgG - should really call this rheumatoid ‘antibody’ not ‘factor’
What is the pattern of joint involvement in RA?
- Symmetrical
- Affects multiple joints (polyarthritis)
- Affects small and large joints, but particularly hands and feet
What is commonest affected joint in RA?
- Metacarpophalangeal joints (MCP)
- Proximal interphalangeal joints (PIP)
- Wrists
- Knees
- Ankles
- Metatarsophalangeal joints (MTP)
Where is the primary site of pathology in RA?
In the synovium
What does the synovium include?
- synovial joints
- tenosynovium surrounding tendons
- bursa
What synovial joints are affected in RA?
proximal inter-phalangeal joint synovitis
