Pathophysiology of joint disease Flashcards
What is rheumatoid arthritis?
An auto-immune disease where you have inflammation of the lining layer of joints = synovium
- Combination of genetic predisposition and environmental trigger
Which joints are primarily affected in RA?
MCPs, MTPs and wrists
Wrist joints
Elbow joints
At what age are you more susceptible to RA, if any?
It may begin at any time in life
Symptoms of RA
- Insidious onset
- Joint swelling
- Early morning stiffness >30mins
- MCPs, MTPs and wrists
- Dramatic NSAID response
Pathophysiology of RA?
- The trigger event (smoking etc) sets off a cascade of immune system activation, primarily delivered by T-cells. The T-cells will either:
1. Directly activate cytokines through the activation of macrophages and fibroblasts, this will activate both activating and inhibiting cytokines, where the activating cytokine effects predominate in RA, these are TNF-alpha, IL-1 and IL-6. These cytokines potentiate the process of cell activation, they will also increase enzyme formation which perpetuates the inflammatory activity inside the synovium ultimately leading to tissue damage.
2. Activate B-cells which are important for antibody production such as rheumatoid factor, which we can measure in the clinic as a marker for positive RA, they lead to ongoing inflammation and tissue damage
What is pannus in RA?
A type of extra growth in joints that can cause pain, swelling, and damage to your bones, cartilage and other tissue
What happens at the joint level in RA?
- The synovial membrane thickens
- A new network of blood vessels is formed - bringing in T cells, B cells and neutrophils
- Synovial membrane invades cartilage in early RA
- In established RA, we get pannus which destroys the cartilage and bone, leading to irreversible damage, bone and joint damage
What is the S factor for RA?
- Stiffness: early morning and >30mins
- Swelling: persistent swelling of one joint or more, especially hand joints
- Squeezing: squeezing the joints is painful in RA
Risk factors for RA
- Age
- Sex
- FHx
- Smoking
- Obesity
- Prev. joint injury
How is RA diagnosed?
- Blood tests: rheumatoid factor, anti-ccp antibodies, CRP, ESR
- X-rays
- Examination of joint fluid
Treatment of RA?
- DMARDs: methotrexate, hydroxychloroquine
- Cytokine targeting drugs : adalimumab, infliximab = TNFa blockers
- NSAIDs
- Corticosteroids: prednisone, dexamethasone, betamethasone, beclamethasone, fluticasone
What is osteoarthritis?
Osteoarthritis (OA) is the most common form of arthritis.
- A degenerative joint disease or “wear and tear” arthritis.
Which joints are primarily affected in OA?
- DIP, PIP, CMC, MTP1
- Large weight bearing joints
- Axial skeleton: spine (particularly cervical and lumbar spine), the neck
Signs and symptoms of OA?
- Nodular, boney, hard swelling affecting smaller joints of hands (DIP and PIP), knees, hips and lower back.
- Symptoms worse after activity
- Early morning stiffness <30 minutes
- LESS inflammation than RA
Risk factors for OA? General and biomechanical
- Depend on the site
- General:
1. Older age
2. Female sex
3. Genetic - FHx
4. Obesity
5. Oestrogen deficiency
6. BMD - Local/biomechanical:
1. Occupation
2. Pre-existing joint abnormality
3. Past trauma
Diagnosis of OA
- X-ray - look for 4 features:
1. Loss of joint space
2. Subchondral cysts
3. Subchondral sclerosis
4. Osteophyte formation
What are the causes of pain in OA?
- Prostaglandins
- Synovitis
- Cytokines
- Subchondral fractures
- Periosteal elevation
- Muscle spasm - atrophy, sarcopenia etc
- Venous congestion
- Biomechanical effects: favouring one leg over another etc
What are the management objectives for OA?
THERE IS NO CURE
- Pain relief
- Patient education and information access
- Optimisation of function
- Exercise and strengthening
- Weight loss
- Surgery
What are the two types of crystal arthritis?
- Gout
2. Calcium phosphate disease
What is the difference between gout and calcium phosphate disease?
The crystals which form as part of the disease process are: uric acid for gout, and calcium pyrophosphate dihydrate crystals for calcium phosphate disease
What is the consequence of crystal presence in crystal arthritis?
They provoke an acute inflammatory reaction in and around the joint which can cause chronic joint damage with recurrent episodes of inflammation over time
Epidemiology of gout - Age?
Incidence increases with age
Comorbidities common in gout patients?
- Renal impairment
- Coronary heart disease
- Metabolic syndrome
- Obesity
- Dyslipidaemia
- Hypertension
- Type 2 diabetes
Risk factors for gout: modifiable vs non-modifiable
- Modifiable:
1. HYPERURICAEMIA - MAIN CAUSE
2. High-purine diet
3. Alcohol consumption
4. Obesity
5. Certain medications e.g. diuretics - Non-modifiable:
1. Age
2. Male gender
3. Race
4. Genetic factors
5. Impaired renal function
Which medications act as modifiable risk factors for gout?
- Low dose aspirin
- Thiazides
- Furosemide
- Cyclosporin and other cytotoxic/cytostatic drugs
- Ethambutol
- Levdopa
- Nicotinic acid
Pathophysiology of gout
- Gout occurs when urate crystals (monosodium urate) precipitate either on articular cartilage or on tendons in and around soft tissues
- They provoke an acute inflammatory reaction
Where does urate come from?
End product of purine metabolism
- Normal urate level is close to the limit of solubility, so it is more likely to form into crystals when there is hyperuricaemia
- YOU CAN HAVE HYPERURICAEMIA AND NOT HAVE GOUT
Which enzyme is responsible for the breakdown of hypoxanthine and xanthine into uric acid?
Xanthine oxidase
What are the two mechanisms for hyperuricaemia?
- Overproduction of urate/uric acid
2. Underexcretion of urate/uric acid
Explain how an overproduction of urate can take place?
- Increased nuclear protein turnover in certain haematological diseases such as lymphoma, leukaemia, haemolytic anaemia where you have an increased risk of breakdown products HIGH IN PURINE resulting in hyperuricaemia
- Conditions where there are increased rates of cellular proliferation and cell death e.g. psoriasis, chemotherapy, radiotherapy
Explain how an underexcretion of urate can take place? This is the most common cause of hyperuricaemia
- Hereditary
- Patients taking diuretic drugs
- Patients with diseases affecting GFR
- Alcohol use
- Cyclosporin use
How can alcohol use cause an underexcretion of urate?
increases purine catabolism in liver which increases lactic acid formation that blocks urate secretion by renal tubules
Triggers of ‘gouty attacks’
Presence of crystals followed by mobilisation of urate due to changes in serum water level followed by either:
- Direct trauma
- Intercurrent illness/surgery that triggers acute phase response
- Dehydration/acidosis (incl. alcohol binge)
- Medications (including initiation of urate lowering drugs)
- Rapid weight loss
Give an example of a medication used to lower urate levels
Allopurinol
Clinical manifestation/picture of gout?
- Recurrent attacks of acute, very painful, monoarticular inflammation
- Typical rapid development of severe pain, swelling and tenderness
- Attacks often start at night or early in the morning
- Attacks usually resolve within 7-10 days without specific treatment
Common sites of acute gout attacks
- MTP1 (first toe)
- Midfoot, ankle, knee
- Wrist
- Finger joints
- Olecranon bursae
Risk factors for gout
- Alcohol use
- Red meat consumption
- Age
- Diuretics: THIAZIDES
- Hereditary
- Diseases affecting GFR
- Cyclosporin use
- Post-menopausal women
- Diabetes
- OA
- Hypertension
- High cholesterol
- Conditions with increased nuclear turnover such as lymphoma, leukaemia, haemolytic anaemia which gives increased breakdown products high in purine
- Conditions with increased cellular proliferation e.g. psoriasis, chemotherapy, radiotherapy
Who is at risk of gout being polyarticular rather than monoarticular?
High risk patients: alcoholic, postmenopausal women
Gout diagnosis
- Demonstration of monosodium urate crystals by microscopic examination for negatively birefringent crystals in synovial fluid or tophus aspirates permits a definitive diagnosis of gout
- Urate crystals are intra- or extracellular
- Crystals examined under a polarising filter will be:
- Yellow when aligned parallel to the axis of the red compensator
- Blue when aligned perpendicular to the direction of polarisation
Treatment for gout
Allopurinol - lowers urate levels
NSAIDs
Steroids
Ice pack
Men with gout have a two-fold increase of…
Kidney stones
What is high CRP evidence of?
Acute inflammatory response
What is the presence of anti-ccp antibodies indicative of?
Auto-immune disease - the immune system attacking healthy tissues, and cells such as joints
What is septic arthritis?
Joint infection
- A MSK emergency as it causes rapid destruction of cartilage and bone, and systemic sepsis may be life-threatening
How can septic arthritis occur?
- If you have an injury or accident to a joint such as a dog bite or a bad cut, causing the bacteria to get into the joint
- If bacteria from somewhere else in the body spread into the blood and then into a joint
- As a complication of surgery
Clinical presentation of septic arthritis? History
- Joint pain
- Joint swelling
- Inability to bear weight or move joint
- Recent increase/acute presentation (symptoms present for <2 weeks)
- Systemic symptoms: fever, sweats, rigors, confusion (raised WCC/ESR/CRP)
Clinical presentation of septic arthritis? Examination
- Joint effusion / heat / erythema / restriction of movement = PRISH. If all 4 signs are present then sepsis is likely
Which joints are more commonly affected in septic arthritis?
Large joints such as hip or knee
For each of the following patient groups, which organism is the most likely causative agent of sepsis?
- Infant
- Adolescent to adult
- Sexually active
- Sickle cell anaemia
- IV drug users
- Infant
- Streptococcus
- Haemophilus (*unvaccinated) - Adolescent to adult
- Staphylococcus - Sexually active
- Gonococcus - Sickle cell anaemia
- Salmonella - IV drug users
- Staphylococcus
- Peudonomas
Investigations with regards to septic arthritis?
- Joint aspiration
- ALL SPECIMENS TAKEN PRIOR TO ANTIBIOTIC TREATMENT
- Blood: FBC, ESR/CRP, U&Es, LFTs
- Microbiology
- Imaging: X-ray
Antibiotic treatment for septic arthritis: No risk factors for atypical organisms
Flucloxacillin
Antibiotic treatment for septic arthritis: high risk of gram negative sepsis
2nd or 3rd gen cephalosporin
Antibiotic treatment for septic arthritis: MRSA risk
Vancomycin
How can you reduce the risk of permanent cartilage damage in septic arthritis?
- Prolonged treatment
- Recurrent aspiration/washout of infected joints
