12. Degenerative vs Inflammatory conditions - Robson Flashcards
Give an overall summary of the pathogenesis of OA
Degenerative condition of the articular cartilage Chondrocytes that produce the cartilage are affected by age
The chondrocytes have a phenotypic alteration as they get old and they become stressed
The stressed chondrocytes do not produce as good quality proteoglycans and collagen as they used to when younger and so you have ECM degradation
This results in local low grade inflammation
And there is a vicious inflammatory cycle Proinflammatory cytokines
are released and this results in even more stress to chondrocytes and there is an even worse quality production of ECM
Eventually, the articular cartilage is lost and there is exposure of subchondral bone
The bone also erodes and so there is loss of subchondral bone
There is osteocyte formation and more inflammation and the joint continues to worsen
Give an overall summary of the pathogenesis of RA
RA is an autoimmune condition - the body’s own immune system attacks own tissue
There is a large inflammatory response within synovial joint
Massive release of pro-inflammatory cytokines (Th17 and IL17)
The synovial membrane is first effected
Fibroblast like synovial cells (synoviocytes) proliferate and grow
Results in the formation of a pannus
This pannus invades and degrades the ECM of the cartilage and the underlying subchondral bone so there is articular and bone erosion
There is instability within the joint due to the initial inflammatory process
What is more common out of OA and RA?
OA
What is the second most common form of arthritis in the UK?
Gout
What joints are generally affected in OA?
Weight bearing joints e.g. knees, hips, vertebral column
Which joints will be affected in the hand in OA?
Distal and proximal IP joints
Which joints will be affected in the feet in OA?
Distal and proximal IP joints
The big toe will be the most affected because it is carrying the most weight
Is OA bilateral or unilateral?
Can be either
Who will develop OA?
Everybody with increasing age - degenerative changes
Why does almost everyone develop OA?
Due to mechanical wear and tear on the joints
Which joints are generally affected in RA?
Can affect any joint in the body that is synovial
What is the prevalence of RA in the UK?
1% of the population
What joints are affected in the hands in RA?
Carpals - carpal tunnel syndrome
MCP joints
Proximal IP joints - nb. this is the furthest it will go in the hand
Is RA unilateral or bilateral and why?
RA is bilateral and symmetrical
System wide inflammation - systemic effects
Why are symptoms of OA unilateral and bilateral?
This is because symptoms will initially start on one side e.g. left knee is affected by OA
The individual will compensate by putting more weight on the right knee - this will then develop OA - has become bilateral
At what age does RA onset?
Can begin at any time
Peak age mid 20s to mid 40s
How fast is the speed of onset of RA?
Relatively rapid - weeks to months
What are the symptoms at the joints in RA?
Joints are painful and swollen and stiff due to massive joint effusion occurring from increased synovial fluid production
In RA, is synovial fluid production increased or decreased?
Increased
How long does morning stiffness of the joint last in someone with RA?
Why?
Morning stiffness will last longer than one hour
The synovial fluid is a gel first thing in the morning - will take a while for this gel to then break and be free flowing again - system wide gel so will take a while to resolve
What systemic symptoms are present in an individual with RA?
Frequent fatigue and general feeling of being ill
What is the age of onset of OA?
At what age may degeneration of the bone joint start to occur?
Usually begins later in life - very rare younger than 45 years of age
Degeneration may start to occur around 20 years
How fast is the speed of onset of OA?
Why?
Slow - over many years
This is because it takes a while for the degeneration to accumulate to a great enough amount for it to be noticed
What are the symptoms at the joints in OA?
The joints will ache and be tender
There will be little or no swelling - very mild inflammation for a long while
How long does morning stiffness of the joint last in someone with OA?
The morning stiffness will last less than one hour
Stiffness will then return at the end of the day or after periods of activity
What systemic symptoms are present in an individual with OA?
In OA, whole body symptoms are not present
Do females or males have more severe OA and why?
Females - especially of the hand and the knee
This is because their medial compartments are taking more of their body weight due to their wider pelvis
Does OA have genetic influences? Give examples
Yes
OA of hips uncommon in Africans and Asians
Polyarticular OA of the hands rare in Africans and Malaysians
Why are the rates of OA increasing in the UK?
Due to ageing population
What are the individual risk factors for OA?
Age over 50 years
Weight greater than 23 BMI
Genetic disorders e.g. deformed legs or knees
Habitual floor activities of kneeling, squatting
High impact physical activity
Any tears of the ACL, PCL, menisci of the knee - changes the mechanical load on this joint
Other arthritic conditions
What is primary OA?
Idiopathic OA
What is secondary OA?
Due to mechanical stress on joint or inflammatory disease, endocrine disorders or metabolic disorders etc.
What are the physical signs of OA?
Crepitus in the joint Bony enlargement - due to osteophytes Formation of nodes Deformity Instability Restricted movement at the joint Effusion - mild Muscle weakness or wasting
What are Heberdens nodes?
These are nodes formed in OA at the distal IP joints
What are Bouchards nodes?
Nodes formed in OA at the proximal IP joints
What is meant by ‘pseudolaxity’ and explain what this is
This is instability
The bones get closer together due to a lack of cartilage BUT the ligaments are still at their normal working distance
So the ligaments of the joint become loose and do not work to their optimal level - joint is less stable
Where is pseudolaxity a major problem in the body?
At the knee joint - stability of this joint is heavily dependant on the ligaments
What is the best investigation for the assessment of OA?
Plain radiograph
What are the four signs of OA that are visible on a plain radiograph?
Loss of joint space
Development of osteophytes
Subchondral sclerosis
Trabecular fractures/subchondral cysts
When does OA often start in women?
Around the time of the menopause
OA often starts around the time of the menopause. Is it hormone related?
No - HRT does not help - just happens at the same time
What is erosive OA?
Primary form of OA
Inflammatory form of OA similar to RA
There are erosions at the centre of the bone but there are osteophytes at the edges - get a gull winging
How does erosive OA present?
Gull winging - due to erosion at the centre of the bone and osteophytes at the edges
What is the prevalence of RA?
1% of the population in the UK
What is the relation of autoantibodies to RA?
Autoantibodies are found in 96% of patients with RA - high specificity but not necessary for a patient to have autoantibodies to have RA
What is the autoantibody present in RA?
Rheumatoid factor IgM to Fc portion of IgG
Anti-citrullinated peptide antibodies
What impact does the IL17 have on the synovial macrophages (type a synoviocytes) in RA?
Seems to result in switch of phenotype from synovial macrophages to osteotype macrophages
What is ‘anaemia of chronic disease’?
Hypochromic normocytic anaemia seen in chronic immune activation due to over production of IL-6
Due to iron dysregulation
These people are fatigued and tired all the time
How does RA show on a plain radiograph?
The fingers tend to sublux off of the MCP joints into ulnar deviation
Pencil cup deformity - the whole bone essentially erodes
Three components of neurofibrillary tangles in RA are?
Hyaluronic acid
Albumin protein
Globulin protein
Swelling of the joint occurs in RA or OA?
RA
Heberden’s nodes - OA or RA?
OA
Bouchard’s nodes - OA or RA?
OA
Heberden’s nodes - proximal or distal IP?
Distal
Bouchard’s nodes - proximal or distal IP?
Proximal
Characteristic feature of the erosions in OA (x-ray) are?
Gull winging
Characteristic feature of the erosions in gout (x-ray) are?
Rat bites (check)
Synovial macrophages are type a or type b synoviocytes?
Type a
Characteristic features of the erosions in RA (x-ray) are?
Pencil in cup deformity
Nodules of the pannus in RA are composed of what cells? x3
B-lymphocytes
CD4 T-lymphocytes (Th17)
Macrophages
