Flashcards in 6.1. Rheumatology - The Science Deck (25):
What is Rheumatology?
The Medical Specialty that deals with Patients with Arthritis and other related Conditions
Note - this incorporates 200+ disorders
What is Arthritis?
Inflammation of a Joint or Joints
What are the Clinical Signs of Arthritis?
3. Restriction of Movement
6. Systemic Features
What are the Symptoms of Arthritis?
4. Functional Impairment
5. Systemic Symptoms
What are the main Rheumatic Diseases?
1. Rheumatoid Arthritis
2. Seronegative Arthritis
3. Crystal Arthritis
4. Connective Tissue Disease
5. Systemic Vasculitis
6. Bone Disease
What are the functions of the normal Synovium?
1. Maintenance of Intact Tissue Surface
2. Lubrication of Cartillage
3. Control of Synovial Fluid Volume and Composition
4. Nutrition of Chondrocytes within Joints
What is Rheumatoid Arthritis?
A Chronic, Symmetric, Polyarticular Inflammatory Joint Disease
Where does Rheumatoid Arthritis primarily affect?
Small Joints of the Hands and Feet
What characterises Rheumatoid Synovitis (Pannus)?
1. Inflammatory Cell Infiltration
2. Synoviocyte Proliferation
3. Synoviocyte neoangiogenesis
4. Synovial Fluid containing Neutrophils (particularly during acute flares of Rheumatoid Arthritis)
What does Synovial Pannus cause?
Bone and Cartilage Destruction
What auto-antibodies are associated with Rheumatoid Arthritis?
1. Rheumatoid Factors
2. Anti-Citrullinated Protein
What is the type of Rheumatoid Arthritis in which Autoantibody's are found?
Seropositive Rheumatoid Arthritis
What are the most common Autoantibodies found in Seropositive Rheumatoid Arthritis?
1. Rheumatoid Factor
2. Anti-Citrullinated Protein Antibody (ACPA)
3. Diagnostic Anti-CCP Assays (Recognise Self-Proteins)
Note - 3 recognises Alpha-enolase, fibrinogen, fibronectin, collagen, vimentin
How is the prognosis for anyone who is Anti-Cirullinated Protein Antibody Positive (ACPA+)?
What is the type of Rheumatoid Arthritis in which Autoantibody's are not found?
Seronegative Rheumatoid Arthritis
What plays a key role in Susceptibility to Rheumatoid Arthritis, and its Severity?
What genes are associated with Rheumatoid Arthritis?
1. HLA-DRB1 - role in promoting autoimmunity
Note - these are complex and may involve many genes, there are many more than these 3
Other than genetic, what factor can affect Rheumatoid Arthritis?
1. Smoking and Bronchial Stress
2. Infectious Agents
3. Repeated insults
What Infectious Agents (Environmental Factor) have been linked to Rheumatoid Arthritis?
1. Viruses (EBV, CMV)
2. E. Coli
4. Periodontal Disease
What do repeated insults in a genetically susceptible person lead to?
1. Formation of Immune Complexes and Rheumatoid Factor
2. Altered Citrullination (Deimination) of proteins and breakdown of tollerance (resulting in ACPA response)
What is the Pathology of Rheumatoid Arthritis?
1. a) Environmental Factors
1. b) Epigenetic Modification
1. c) Susceptibility Genes
1. Contribute to altered Post-Transcriptional Regulation
2. This causes Self-Protein Citrullination, and a loss of Tollerance in Immune Cells (B, T, Dendritic, and Lymphoid)
3. This then transitions to Arthritis
What is the Definition of Synovitis?
Inflammation of the Synovium
What is the Pathophysiology of Synovitis in Rheumatoid Arthritis?
1. Villous Hyperplasia leading to Infiltration of Plasma Cells, CD4, Macrophages, T-Cells, and B-Cells
2. This causes Intimal Cell Proliferation (Fibroblasts)
3. The Macrophages in the lining are Activated, resulting in the production of Cytokines and Proteases
4. Neoangiogenesis is induced by local hypoxic conditions and cytokines
5. There is insufficient Lymphangiogenesis so cellular egress is limited
6. This is a Self-Amplifying Process
What are the relative Levels of T-Cell Cytokines in the Rheumatoid Arthritis Synovium?
Relitively Low Levels