MSK: Part 1 Flashcards
Characteristics of cortical bone
Compact
Dense
What are found in the spaces of cortical bone
Cells and Blood Vessels
Characteristics of trabecular bone
- Cancellous (spongy)
- Network of bony struts (Trabeculae)
- Looks like sponge, many holes with bone marrow
Where do cells of trabecular bones reside
Trabceulae
Where are blood vessels of the trabuclar bone found
Holes
Woven vs lamellar bone
Made quick vs made slow
Disorganised vs organised
No clear structure vs layered
What is the function of th hollow long bone
Keeps mass away from neutral axis and minimises deformation
Role of trabecular bone
Structural support and minimising mass
Role of wide ends of a long bone
Spreads load over weak, frictionless surface
Describe the bone composition
- 50-70% HYDROXYAPETITE
- 20-40% Organic matrix (Type I collagen and non-collagenous proteins)
- 5-10% water
Role of minerals
Stiffness
Role of collagen
Elasticity
What is hydroxyapatite
Crystalline form of calcium phosphate
What is the function of the joint
- Allow movement in 3d
- Bear weight
- transfer load evenly to MSK system
Where are fibrous joints found
teeth sockets
Where are cartilaginous joints found
Intervertebral discs
Where are synovial joints found
Metacarpophalngeal and knee joints
What separates most articulating joints
Fluid-filled cavity
What are the main features of a joint
- Articular cartilage
- Joint capsule
- Joint cavity
- Synovial fluid
- Reinforcing ligaments
What is the inner layer of the joint capsule
Synovial membrane
What is the joint cavity
Space filled with synovial fluid
What are bursae
Found in synovial joints - fluid filled acs
What are meniscis
In synovial joints:
Discs of fibrocartilage
What is osteoarthritis
- Cartilage loss of accompanying periarticular bone response
- Inflammation of articular and periarticular structure and alteration in cartilage structure
What structure of the joint is most affected in Non-inflammatory degenerative arthritis
ARTICULAR CARTILAGE
What is the most common type of arthritis
Non-inflammatory degenerative arthritis
What causes non-inflammatory degenerative arthritis
No obvious factor
What conditions can cause SECONDARY OA
Haemochromatosis
Obesity
Occupational
What gender is osteoarthritis most common
Females
Risk factors for OA
- Joint HYPERMOTILITY
- Insufficient joint repair
- Diabetes
- Increasing age:
Due to cumulative effect of traumatic insult
Decline in neuromuscular junction - Gender (more common in females)
- Genetic predisposition
- Obesity
- Local Trauma
- Inflammatory arthritis (Rheumatoid arthritis)
What genetic predisposition causes OA
- COL2A1 collagen type II gene
How does obesity cause OA
Pro-inflammatory state (increased release of IL-1 and TNF)
Where is OA in manual labour found
Small joints of th hand
Where is OA in farming found
Hips
Where is OA in footballing found
Knees
Pathophysiology of OA
- Progressive destruction and loss of articular cartilage with an accompanying periarticular bone responses
- Balance between collagen degradation and its production is lost and increased synthesis of extracellular matrix the cartilage becomes oedematous
- Focal erosion of cartilage develops and chondrocytes die - attempted repair from adjacent cartilage
- Process of repair is disorganised leading to failure of synthesis of extracellular matrix so that the surface is fibrillated and fissured
- Cartilage ulceration exposes underlying bones to increased stress producing micro-fractures and cysts + secondary inflammation
What is cartilage
Matrix of collagen fibres, enclosing a mixture of proteoglycans and water - it has a smooth surface and is shock-absorbing
Product of disorganised bone repair
Sclerotic subchondral bone forms and overgrowths as the joint margins become calcified (OSTEOPHYTES)
What happens to the exposed underlying bone after cartilage ulceration
Becomes sclerotic (increased vascularity and cyst formation)
How do metalloproteinases cause OA
Degradation of collagen and proteoglycan
Name two metalloproteinases
Stromelysin
COllagenase
How does IL-1 and TNF-alpha cause OA
Stimulate metalloproteinase production
INHIBIT collagen production
How does GF deficiency cause OA
Impairs matrix repair (Insulin-like GF)
How does gene susceptibility cause OA
Mutations in type II collagen can cause polyarticular OA
Main features of OA
Loss of cartilage
Disordered bone repair
Clinical presentation of OA
- Mechanical pain in movement
- Symptoms are gradual
- Joint pain (worsened by movement and relieved on rest)
- Joint stiffness after rest
5 Only transient stiffness (30 mins) - Muscle wasting of surrounding groups
- Crepitus - crushing sensation when moving joints as smooth articulating surfaces are disrupted
- Joint effusions
- Heberden’s nodes (DIP)
- Bouchard’s nodes (PIP)
What joints are most commonly effected by OA
- DIPs (HEBEEDEN’S NODES) and first carpometacarpal joint thumb)
- First metatarsophalangeal joint of foot
- Weight-bearing joints (vertebra and hips)
Where are Bouchard’s nodes found
PIPs (B is before H so Bouchard’s are more proximal to Heberden’s)
Differential diagnosis of OA
- Rheumatoid arthritis
- Chronic tophaceaous gout
- Psoriatic arthritis affecting DIPs
How is OA differentiate from rheumatoid
Pattern of joint movement
No systemic features
Early morning stiffness is in rheumatoid
Diagnostics for OA
X-rays
FBC
MRI
Aspiration of synovial fluid
What would X-ray show in OA
1. LOSS L - Loss of joint space O - Osteophytes S - Subarticular sclerosis S - Subchondral cysts
What would FBC show for OA
- CRP
2. Rheumatoid factor and Antinuclear antibodies are NEGATIVE
What would an MRI show in OA
Early cartilage injury and subchondral bone marrow changes
What would aspiration of synovial fluid show in OA
Viscous fluid with few leucocytes
upon physical examination of OA what would we see
Deformity
Bone enlargement of joints
Non-medical treatment of OA
- Excercise to improve local muscle strength, improve mobility of weight bearing joints, general aerobic fitness (regardless of age, severity or comorbidity)
- Lose weight
- Local heat and ice packs
- Joint supports/insoles for joint stability and footwear with shock-absorbing properties for lower limb OA
- Acupuncture, physiotherapy and occupational therapy
Pharmacological treatment of OA
- Paracetamol prescribed before NSAIDs (IBUPROFEN)
- Weak opioids alongside paracetamol (DIHYDROCODEINE)
- Intra-articular corticosteroids reduce joint effusion
What corticosteroid is not used
Systemic
When do you not administer corticosteroids
if joint is going to be replaces (has immunosuppression properties)
Surgical interventions for OA
- Arthroscopy
- Arthroplasty
- Osteotomy
- Fusion
What is arthroscopy
Scope inserted into joint to assess damage and remove loose bodies (cartilage fragments causing knee lock)
What is arthroplasty
- Knee/hip replacement
Indications of arthroplasty
- Uncontrolled pain at night
2. Significant limitation of function
How long does a prosthetic joint last for
10-15 years and need a replacement
What is an osetotomy
Cut bone to change shape/length
What is fusion
- Usually of ankle and foot to prevent painful grinding of bones
- Loss of motility
What is rheumatoid arthritis
Autoimmune disorder causing SYMMETRICAL DEFORMING POLYARTHRITIS
Does RA have inflammation
Yes
Risk factors for RA
- Women
- Smoking
- Before menopause more common
- Family history
- Genetic factors
- Immune system
What genetic factors cause RA
- HLAs DR4 and DRB1 confer susceptibility to RA
What factors of the immune system contribute to RA
T cells : INF, IL-2 + IL-4
Macrophages: IL-1, 8 and TNF-alpha
Mast Cells: Histamine + TNF-alpha
Fibroblasts: IL-6
What maintains the chronic inflammation of RA
Local production of rheumatoid factor by B cells and formation of IMMUNE COMPLEXES with complement activate
What is rheumatoid factor
Autoantibodies directed against Fc portion of immunoglobulin
What does RA effect
Synovial joints
What is synovitis
Inflammation of synovial lining
When does synovitis occur in RA
When chemoattractants produced in the joint recruit circulating inflammatory cells
What chemoattractant causes synovitis and joint destruction
TNF-alpha
What drives overproduction of TNF-alpha
Interaction between macrophages, T and B cells
What happens to the synovium in RA
Becomes greatly thickened and infiltrated in inflammatory cells
Describe what happens in RA after synovium thickens
- Generation of new synovial blood vessels by angiogenic cytokines
- Activated endothelial cells produce adhesion molecules which force leucocytes into synovium = inflammation
- SYnovium proliferates and grows out over surface of the cartilage (past joint margins) producing a pannus
- Pannus of inflamed synovium damages underlying cartilage blocking route for nutrition and effects of cytokines by chondrocytes
- Cartilage thins and underlying bone exposed
- Pannus destroys articular cartilage and subchondral bone = bony erosions
What parts of the body are effected by RA
- Slowly progressive, SYMMETRICAL swollen, painful and stiff
- DIPs are SPARED
- MTP of feet
- Wrist, elbows, shoulders, knees and ankles
Clinical presentation of RA
- Joints warm and tender
- Symptoms worse in morning and in cold
- Morning stiffness lasting more than 30 mins
- SYMMETRICAL peripheral polyarthritis
- Joints swollen, tender and WARM
- Movement limitation and muscle wasting
- Fatigue, sleep disturbed and pain + stiffness are significantly worse in morning
- Shoulder and elbows swollen and stiff
- Feet pain in MTP joints, foot broadens and hammer toe deformity leads to ulcers and callouses
- Synovitis and effusion in knees
- Tenosynovitis (inflammation of knees)
What hand deformities are seen in RA
- Ulnar deviation (swelling of MCP and PIPs)
- Swan neck (Z-thumb)
- Boutonniere deformity
How does Ra effect the lungs
- Pleura effusions
- Fibrosing alveoli’s
- Pneumoconiosis (miners)
- Interstitial lung disease
- Bronchiectasis
How does Ra effect the heart
- Pericarditis
- Raynauds
- Pericardial effusion
How does Ra effect the eyes
- Dry eyes
- Episcleritis (redness of eyes)
- Scleritis (severe pain - can’t look at bright lights)
Neurological effects by RA
- Peripheral sensory neuropathies
- Compression/entrapment neuropathies
- Cord compression
What is entrapment neuropathies
Soft tissue swelling due to inflammation at site where rigid structures contain nerves (wrist and elbow - carpal tunnel syndrome)
What is cord compression
Due to instability of cervical spine, we get sensory loss, weakness and disturbed bladder function
How does Ra effect the kidneys
- Amyloidosis (proteinuria and renal impairment)
- Nephrotic syndrome
- CKD
How does RA effect the skin
Subcutaneous nodules
How is RA diagnosed
- Normochromic normocytic anaemia
- ESR and raised CRP = inflammation
- Positive Rheumatoid factor
- Positive Anti-cyclic citrullinated peptide
- X-ray
- MRI and ultrasound
What is Positive Anti-CCP
- Marker of the disease
- Presents earlier in the disease and inflammatory arthritis and indicates likelihood of progression to RA
Positive = worst prognosis
What is X-ray used for in RA
- Soft tissue swelling in early disease
- Joint space narrowing in late disease
- PERI-ARTICULAR EROSIONS
What is MRI and ultrasound used for in RA
- Erosions at joint margins and bones
If effusion present then aspiration of joint - will be cloudy due to high White cells
How is RA treated
- No cure
- Smoking cessation to reduce risk of CV disease
- Reduce weight
- Exercise
- Surgery (synovectomy to reduce bulk of inflamed tissue + prevent damage)
- Analgesics
- Corticosteroids
- Biological therapy
How is pain in RA managed
- NSAIDs - IBUPROFEN and COX inhibitors (ASPIRIN) for pain + stiffness
- Paracetamol with DIHYDROCODEINE
What corticosteroids are prescribed for RA
- ORAL PREDNISOLONE
2. drug while DMARDs kick in - IM METHYLPREDNISOLONE
How are corticosteroids delivered
Intra-articular injection (short-lived but rapid effect)
Role of corticosteroids
Suppress disease activity but risk of long-term toxicity
Side-effects of corticosteroids
Causes osteoporosis (most common cause of osteoporosis) and increases risk of fracture
What are DMARds
Inhibit inflammatory cytokines - suppress immune system and carry risk of infection
Why are DMARDs used
Early to reduce inflammation and slow development of joint erosions and irreversible damage
How long does it take for DMARDs to work
6 weeks
Why do we monitor DMARD use with blood tests
All DMARDs have serious side effects
Name the gold standard drug for DMARDs
METHOTREXATE
When is METHOTREXATE contraindicated
Pregnancy
Side-effects of methotrexate
- Nausea
- Mouth ulcers
- Diarrhoea
- Abnormal LFTs
- Neutropenia
- Thrombocytopenia
- Renal impairment
Alternative DMARDs to METHOTREXATE
SULFASALAZINE
LEFLUNOMIDE
When is SULFASALAZINE given
Mild/moderate disease
When is SUlfasalazine given
Young and women
Side-effects of SULFASALAZINE
- Nausea
- Skin rashes
- Mouth Ulcers
- Neutropenia
- thrombocytopenia
- abnormal LFTs
How does Leflunomide work
- Blocks T cell proliferation
Side-effects of Leflunomide
- Diarrhoea
- Neutropenia
- Thrombocytopenia
- Alopecia
- Hypertension
What biological therapy is used for RA
- TNF-alpha blockers:
Halts erosion formation
What are TNF-alpha blockers given alongside with
METHOTREXATE
Name a TNF-alpha blocker
Infliximab
Side-Effects of imfliximab
Demyelination
Autoimmune syndromes
What is Imfliximab
Monoclonal antibodies
How is Imfliximab delivered into the body
IV
What is Etanercept
Receptor fusion protein
Side-effects of TNF-alpha blocker Etanerept blockers
Infections
Hypersensitivity reaction
Other than IMfliximab and Etanercept what other TNF-alpha blocker is used for RA
ADALIMUMAB
What is ADALIMUMAB
Monoclonal antibodies
Side-effects of ADALIMUMAB
Hypersensitivity reaction
Heart failure
What are B-cell inhibitors
They stop production of rheumatoid factors
How does Rituximab function
Monoclonal antibod that targets CD20 on B cells
Side-effect of RITUXIMAB
Hypo/hypertension skin rash nausea pruritus back pain
When is Rituximab given
When anti-TNF agents fails
Name two interleukin blockers
TOCILIZUMAB
ANAKINRA
What is TOCILIZUMAB
Monoclonal antibody that binds to IL-6 cytokine before target receptor
What are the most common joint inflammation cytokines present
IL1
IL6
Along what medication is TOCILIZUMAB given with
METHOTREXATE
What interleukin blocker antagonises IL-1
ANAKINRA
Name a T-cell activation blocker
ABATACEPT
Role of ABATACEPT
Blocks T cell activation which means macrophages and B cells can’t be activated thus reducing inflammation
RHEUMATOID vs OSTEOARTHRITIS
- Begins at any time vs begins later
- Rapid onset vs Slow (over years)
- Joints are painful, swollen and stiff vs Joints ache and may be tender but no swelling
- Effects small and large joints on both sides of the body vs one side of the body
- Morning stiffness lasts longer than 30 mins vs morning stiffness lasts less than 30 mins
- Frequent fatigue vs whole body symptoms
X-ray results for RA
Juxta-articular osteoporosis
Soft Tissue Swelling
Joint Deformity
Loss of Joint Space
GI effects of RA
- FELTY’S SYNDROME: Seropositive RA + Splenomegaly + Neutropenia
