1) Rheumatoid Arthritis Flashcards
What is rheumatoid arthritis?
Chronic, inflammatory disease mediated by the immune system that affects peripheral joints symmetrically, with the possibility of becoming a systemic disease.
Who does rheumatoid arthritis affect?
1 in 100 Canadians affected.
Affects women compared to men 3:1
Name 4 causes of RA.
- Genetics
- Smoking
- Infections
- Autoimmunity
What is a synovial membrane?
Thin layer of connective tissue between joint capsule and synovial cavity.
What is synovial fluid?
An ultra-filtrate of blood that diffuses across the synovial membrane and into the joint cavity composed of hyaluronan and lubrican
What is hyaluronan and lubrican?
Hyaluronan regulates cartilage viscosity and lubrican lubricates cartilage.
What is a joint composed of?
A normal synovium is composed of the synovial lining with an interstitium lying below with blood vessels but few cells.
It contains fibronectin which holds the collagen together and synoviocytes on the inner capsule that create synovial fluid
Signs of RA on the synovial membrane.
Pannus Formation (growth of fibrous tissue on the joint) causes the loss of bone and causes cartilage formation Activation of the inflammatory immune cells in synovial fluid
The 4 cells activated in immune response of RA
- Fibroblast -like synoviocytes
- Macrophage-like synoviocytes
- Macrophages
- T cells and B cells
How do mediators of inflammation enter the joint?
Mediators of inflammation enter the joint via the ultra- filtrate of blood that diffuses across the synovial membrane
What do osteoclasts do?
Break down bone (bone resorption)
Stimulates immune response
What is pannus formation caused by?
It is caused by fibroblasts which are activated by the immune response.
What percent of lymphocytes are TCells in RA synovium?
30- 50%
What occurs with the activation of TCells in the RA synovium?
• Production of prostaglandins, cytotoxins, and cytokines
• Release of inflammatory cytokines, matrix
metalloproteinases (degrade bone
matrix), osteoclasts, and B cells
What is IL-6?
It is the most abundant pro-inflammatory cytokine in the synovium and it stimulates the synthesis of acute-phase reactants from the liver, osteoclasts, T-lymphocytes, B lymphocytes
What are the 3 ways that B cells are thought to affect RA
- Produce auto-antibodies
- Stimulate cytotoxin and free radical release (RF, anti-CPP and ANA)
- Activate T cells
What do the auto antibodies RF, anti-CCP and ANA do?
They damage synovium and bone. Antibodies are involved in the phagocytosis of the cartilage and bone creating more inflammation of the joints
Name the three pro-inflammatory cytokines
IL-1, IL-6, TNF alpha
What are the four major symptoms of RA?
Symptoms progress over months
Pain and stiffness begin in 1 to 2 joints and progress to poly-articulate presentation
Pain persists for over an hour after waking
Systemic complaints can develop
What are the main clinical symptoms of RA?
Small joint stiffness that is typically worse in the morning. Inflammation is also associated with RA which results in muscle atrophy, weakness and deformity
Rheumatoid arthritis is the leading cause of disability in Canada.
True or False
True
Name the 6 lab tests that can be done (specific and nonspecific) that can be done to diagnose RA.
RF, anti-CPP, ESR, CRP, ANA and Fe
What is the most specific test for RA?
Anti-CPP, May be detected up to 15 years before onset of clinical symptoms of RA ***
Name two other diagnostic tests for RA.
Increased white blood cell count within joint fluid.
Joint space narrowing
