Topic 5: Joint Disease Flashcards
What are some functions of synoviocytes?
- phagocytose dead/dying tissue
- secrete synovial fluid
- maintain homeostasis within joint
What are some functions of the synovial membrane?
- produce lubricin and hyaluronic acid (maintains integrity of AC)
- nutrient exchange
What are the functions of AC?
- frictionless motion
- even distribution of joint load
- disperse energy from loading
What are the properties of AC?
- avascular –> no inflammatory response
- aneural –> no source of pain
- alymphatic
- hypocellular –> low density of chondrocytes
What type of inflammation is OA?
dysregulated para-inflammation
What is the onset age of OA?
50-60yrs
What types of problems occur as a result of OA?
synovitis, alterations of joint capsule, degeneration of menisci and ligaments, AC breakdown, osteophyte formation, subchondral bone oedema + swelling
Role of synovium in OA
- decreased levels of HA and lubricin
- decreased cartilage protecting factors and increased degradation factors
- synovial inflammation precedes structural changes
Role of AC in OA
- over-expression of degradation enzymes
- fibrillation
Role of biomechanical influences in OA
- mal-alignment: abnormal load distribution
- loss of mensical tissue: alterations in load transmission, increased peak load stresses
- cartilage lesions: exposure of sub-chondral bone
- joint instability and ligament laxity: increased translation
Role of obesity in OA
adipokines - pro-inflammatory
Role of age-related changes in OA
- increased SASP secretion
- oxidative stress/damage
- decreased growth factors
- increased AGE formation (advanced glycation end-product)
Inducers of OA
Endogenous
- cell-derived alarmins
- tissue-derived metabolites
- ECM-derived
- AGEs
Sensors of OA
PRRs
- osteocytes and chondrocytes in sub-chondral bone
- tissue-resident macrophages
- synoviocytes
- chondrocytes
Effectors of OA
- AC chondrocytes
- tissue-resident macrophages and mast cells
- fibroblasts in ligament capsule
- osteocytes and chondrocytes in sub-chondral bone
- synoviocytes
Clinical features of OA
- crepitus
- decreased muscle strength
- joint instability
- deformities - genu varus/valgum
- pain in joint
- loss of ROM
- joint enlargement
Pathology of OA
- cartilage loss - decreased matrix material produced
- cartilage softening –> cracking, flaking, fibrillation, fissuring –> exposure of subchondral bone –> eburnation
- sunchondral cysts
- local muscle weakness
What is the onset age of RA?
25-50 years
What is the gender bias of RA?
females 2.5:1
What is an antigen?
cause immune response to produce antibodies
What is an antibody?
immunoglobulins, specific, adaptive immune system
What is an auto-antigen?
endogenous, body attacks self
Aetiology of RA
- Rh factors produce (auto-antibodies that react with immunoglobulins)
- immune complexes lodge in walls of synovial joints and blood vessels and attract immune cells
Inducers of RA
- endogenous - genetic factors
- PAMPs and DAMPs - cell-derived alarmins (Rh factors), tissue-derived inducers, pathogen-derived alarmins
- exogenous: microbial (PAMPs, virulence factors), non-microbial (allergens, irritants)
Sensors of RA
PRRs
- chondrocytes
- synoviocytes
- B + T cells
- osteocytes + condrocytes in sub-chondral bone
- tissue-resident macrophages
Effectors in RA
- AC chondrocytes
- tissue-resident macrophages
- synoviocytes
- osteocytes and chondrocytes in sub-chondral bone
- T + B cells
- antigen-antibody complexes
What is pannus?
- collection of fibroblasts, T + B lymphocytes
- fills joint space and contributes to fibrillation of AC
- releases cytokines and enzymes
What is the onset age of RA?
25-50yrs
What are some potential causes of RA?
stress, genetics
Does Rh trigger RA?
no, because not everyone with RA has Rh factors
Clinical features of RA?
- joint pain + tenderness
- swelling
- flu-like symptoms
- decreased ROM
- joint deformities
What are whole body features of RA?
-subcutaneous nodules, vasculitis, pericarditis, nodules in sclera, renal sclerosis, sleep disturbances
What is the pattern of joint involvement in RA?
bilateral, polyarticular
What is the pattern of joint involvement in OA?
weight-bearing synovial joints usually
