Extra MSK Flashcards
- What is the HLA-B27?
- What is the function?
It is the Human Leucocyte Antigen, which a class I surface antigen present on all cells except RBC. It plays a role in immunity and self-recognition as an antigen presenting cell. Essentially you are either HLA-B27 positive or negative.
What proportion of the UK population is HLAB27 positive?
9% in the UK, more common in the northern hemispheres.
Describe the basic concept behind the misfolding and the heavy chain homodimer hypothesis
the molecules in both can join together and accumulate in the ER which triggers an inflammatory response called the endoplasmic reticulum UPR response. This then triggers a cascade of inflammatory cytokines e.g. IL23 or IL17.
Give 9 Signs of spondyloarthritis. SPINEACHE
1) Sausage digits (dactylitis)
2) Psoriasis
3) Inflammatory back pain
4) NSAID good response
5) Enthesitis (particularly in the ankle tendons, plantar fasciitis
6) Arthritis
7) Crohn’s/ Colitis/elevated CRP
8) HLA-B27
9) Eye (Uveitis)
What clinical features do all the spondyloarthritis conditions share?
1) Axial inflammation
2) Asymmetrical peripheral arthritis
3) Absence of rheumatoid factor “seronegative”
4) Strong association with HLAB27
Ankylosis
Abnormal stiffening and immobility of joint due to new bone formation.
Pathophysiology behind Ankylosing Spondylitis
1) Repeated inflammation of the spine leads to erosive damage.
2) Lymphocyte and plasma infiltration occurs with local erosion of bone at the attachments of the intervertebral which heals with new bone formation. (SYNDESMOPHYTE)
3) This leads to Enthesitis and irreversible fusion of the spine
What is enthesitis?
Inflammation where tendons/ligaments insert into bone
What is syndesmophyte?
New bone formation and vertical growth from anterior vertebral corners.
Give two spinal abnormalities that is usually found in ankylosing spondylitis
1) Loss of lumbar lordosis and increased kyphosis.
2) Limitation of lumbar spine motility in both sagittal and frontal planes. (Schober test)
Schober test
A mark is made at the 5th lumbar spinous process and 10cm above, with the patient in the erect position.
On bending forward, the distance should increase to more than 15 cm in normal individuals.
What is the use of TNF- alpha blockers? When should they be used?
- Improves spinal and peripheral joint inflammation, the earlier you start the less syndesmophyte form.
What is asymmetrical oligoarthritis?
- Involves the knee or any large joint with a few small joints in the fingers and toes.
What is symmetrical seronegative polyarthritis?
Polyarthritis is any type of arthritis that involves 5 or more joints simultaneously.
What proportion of people with psoriatic arthritis are HLA-B27 positive?
50%
What is the most typical pattern of joint involvement in psoriatic arthritis?
Distal interphalangeal joint
What is dactylitis?
Sausage shaped fingers due to inflammation of the flexor tendons and synovium.
What is arthritis mutilans?
Destruction of the small bones in the hands and feet due to periarticular osteolysis and bone shortening
Name 5 hidden sites for psoriasis
1) Behind ear/inside ear
2) Scalp
3) Umbilicus
4) Natal cleft
5) Genitalia
What is the pathophysiology of reactive arthritis?
- Bacterial antigens or bacterial DNA have been found in the inflamed synovium of affected joints- suggesting that this persistent antigenic material is driving the inflammatory response.
SEPTIC ARTHRITIS
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Describe the tests that you would perform to find Staphylococcus aureus and what would the results be?
1) Gram stain and shape = Purple as gram +ve cocci
2) Clusters/Chains? = Clusters»_space;>staphylococcus
3) Coagulase test: +ve»_space;>aureus
Describe the tests that you would perform to find Streptococci and what would the results be?
1) Gram stain = purple as gram +ve cocci
2) Clusters/chains? = Chains»»streptococci
3) Haemolysis on blood agar and Lancefield grouping to see which type
Describe the tests that you would perform to find and Neisseria gonorrhoea what would the results be?
1) Gram staining and shape = pink as gram -ve cocci
Nesseria= N for negative
MOST COMMON CAUSE OF SEPTIC ARTHRITIS IN YOUNG SEXUALLY ACTIVE WOMEN AND MEN WHO HAVE SEX WITH MEN
Describe the tests that you would perform to find Haemophilus influenzae and what would the results be?
1) Gram stain= pink as gram -ve coccobacillus
2) Blood culture on blood and chocolate agar:
No growth on blood agar as they need factor X(haem) and V (NAD).
Growth on chocolate agar as blood agar heated to release haem.
Name 3 different types of bacterial arthritis
1) Gonococcal arthritis
2) Meningococcal arthritis
3) Tuberculous arthritis
READ UP ON THESE
Pathophysiology of osteomyelitis: describe the 3 ways in which the pathogen can get into bone.
Is it polymicrobial or monomicrobial?
- Easy: DIRECT inoculation of infection into the bone e.g. trauma/open wound. POLY/MONOMICROBIAL
- Quite easy: contiguous spread of infection to bone from adjacent soft tissues. POLY/MONOMICROBIAL
- Difficult: hematogenous seeding, from skin to blood to bone e.g. due to cannula infection. MONOMICROBIAL
Why do long bones tend to be affected by hematogenous seeding in children?
In children the metaphysis of long bones has a slow blood flow, capillaries lack or have inactive phagocytic lining cells and endothelial BM is absent meaning bacteria can move from the blood to bone and predispose growth of bacteria in the bone.
Why do vertebrae tend to be affected by hematogenous seeding in adults?
With age, the vertebrae become more vascular meaning bacterial seeding and vertebral endplate is more likely.
In chronic histopathological changes of osteomyelitis, what is the name for new bone formation?
Involucrum
Why does chronic osteomyelitis lead to sequestra and new bone formation?
Inflammatory exudate( formed in response to bacteria in marrow)»>increased intamedullary pressure»ruptures through periosteum -> periosteum blood supply impaired -> necrosis -> pieces of separated bone known as sequestra -> new bone forms called involucrum.
OSTEOPOROSIS
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What is a DEXA scan?
Dual Energy X-ray Absorptiometry. Low energy x-rays to see how dense bone is. It is used to get the T-score.
What is the T-score for established osteoporosis?
Less than or equal to -2.5 + 1or more fragility fractures
Define osteopenia
Pre-cursor to osteoporosis characterised by low bone density, due to loss of calcium.
What age is peak bone mass achieved?
25 yrs
What is a Z-score?
How far this individual is from the gender AND age-matched mean BMD given in standard deviations.
Name some other drugs other than steroids that can cause osteoporosis
- Heparin
- Ciclosporin
- PPIs
- Anticonvulsants
- GnRH Analogues
- SSRI’s
- Depo-provera
How does a low BMI cause osteoporosis?
Reduced skeletal loading- increases bone resorption. low body weight and immobility so the body breaks it down as not using.
What has the single most significant influence on peak bone mass?
Genetic factors. e.g. genes involved in collagen type-1A1, Vit d receptor and oestrogen receptor genes.
Bone quality: Bone mineralisation what is the problem with too much and too little mineralisation?
Not enough: bone weak and break
Too much: bone is stiff and will shatter
Why are so many women over 50 affected by osteoporosis?
Women over 50 are likely to be post-menopausal; they, therefore, have less oestrogen and so
- Osteoclast action isn’t inhibited
- Premature arrest of osteoblast activity
- Perforation of trabeculae
There is a high rate of bone turnover -> more resorption than formation-»>bone loss and deterioration of -> fracture risk.
What is osteomalacia?
Poor bone mineralisation due to lack of Ca2+, before adulthood = RICKETS
PRIMARY AND SECONDARY BONE TUMOURS
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5 cancers that can metastasise to bone
1) Breast
2) Bronchus
3) Thyroid
4) Prostate
5) Kidney
What antibody would be raised in prostatic metastases?
PSA
Osteosarcoma:
- Who is it most common in?
- Peak onset age?
- Where does it occur?
- Common sites to be affected?
- Metastases?
- X-ray features
Most common primary bone tumour in children.
Peak onset 15-19yrs
Occurs in the metaphyses of long bones
Common sites are knees (75%) or proximal humerous
Rapidly metastasises to the lung
X-ray:
- Bone destruction and formation
- Soft tissue calcification —- SUNBURST APPEARANCE
Chondrosarcoma
- Where does it occur?
- Who does it affect?
- Sites affected?
Cancer of the cartilage
Most common adult none sarcoma
Common sites affected the pelvis, femur, humerus, scapula and ribs.
OSTEOMALACIA
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How does hypophosphataemia cause osteomalacia?
- Hypophosphataemia due to hyperparathyroidism
- Excess PTH results in decreased absorption of phosphate in the kidneys resulting in more excretion in urine
- Phosphate is needed for bone mineralisation
How does Vitamin D deficiency lead to osteomalacia?
Vit D low means calcium deficiency
How does renal failure lead to osteomalacia?
Renal failure means there is an inadequate conversion of 25-hydroxy vitamin D into 1,25-hydroxyvitamin D. Vit d low»»>calcium deficiency
How can drugs lead to osteomalacia?
Anticonvulsant may induce liver enzymes leading to increased breakdown of 25-hydroxy vitamin D.
Rifampicin (antibiotic) can also lead to this.
How can liver disease lead to osteomalacia?
Liver diease»>reduced hydroxylation o Vit D to 25-hydroxy vitamin D»_space;calcium deficiency
PAGET’S DISEASE
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What is the pathophysiology of Paget’s disease?
1) There is increased bone turnover due to overactive osteoclasts and osteoblasts.
2) There is increased osteoclastic bone resorption followed by the formation of WEAKER NEW BONE, increased local blood flow and fibrous tissue.
3) The new weaker bone means there is DEFORMITY and INCREASED FRACTURE RISK.
4) This also leads to patchy areas oh high-density bone (sclerosis) and low density (lysis).
OSTEOARTHRITIS
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Describe the dynamic balance in cartilage production around joint under normal conditions
- Cartilage is a matrix of collagen fibres, enclosing a mixture of proteoglycans and water.
- It has a smooth surface and is shock-absorbing.
- There is a dynamic balance between cartilage degradation by wear and its production by chondrocytes.
Describe the pathophysiology of osteoarthritis
- In OA the dynamic balance of chondrocytes is lost and despite increased synthesis of the extracellular matrix the cartilage becomes oedematous
- The focal erosion of cartilage develops and chondrocytes die
- Repair is attempted by adjacent cartilage, the process is disordered so you can’t synthesise EC matrix and the surface becomes fibrillated and fissured (instead of smooth like before).
- The ulcerated cartilage exposes the underlying bone to increased stress»>microfractures and cysts.
How does the exposed bone try to fix the situation?
The bone attempts to repair but instead produces abnormal SCLEROTIC SUBCHONDRAL BONE and overgrowth at the joint margin which becomes calcified.»_space;>osteophytes.
The exposed bone is: sclerotic, with increased vascularity and cyst formation.
What are the two main pathological features of OA?
Loss of cartilage
Disordered bone repair
What is crepitus?
- Crunching sensation when moving joint due to the disruption of the normally smooth articulating surfaces of the joints.
Rheumatoid arthritis
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What is rheumatoid factor?
IgM autoantibodies directed against the Fc portion of IgG by B cells
What does Anti-CCP stand for?
anti-cyclic citrullinated peptide
Why is the Rheumatoid factor not diagnostic?
Because it can be positive in Hep C and other diseases.
What does a positive Anti cyclic citrullinated peptide mean?
Worse prognosis
GOUT
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Pathophysiology of gout
Purines normally excreted. The last two steps of purine breakdown:
1) HYPOXANTHINE is converted to XANTHINE
2) XANTHINE converted into URIC ACID
Both under the action of XANTHINE OXIDASE
Uric acid is then excreted by the kidneys. HOWEVER, when there is an excess of purine and hence uric acid it is converted into MONOSODIUM URATE CRYSTALS.»_space;>which CAN lead to gout (not always)
Why is the big toe most commonly affected?
Crystals form at lower temperatures so makes sense for crystals to form at the most peripheral joint that is the coolest.
Name some triggers for gout
1) Direct trauma to the joint
2) Intercurrent illness
3) Alcohol or shellfish binge
4) Surgery
5) Dehydration
6) Starting hypouricaemic therapy
PSEUDOGOUT (CALCIUM PYROPHOSPHATE DEPOSITION)
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What is the pathophysiology of pseudogout?
Deposition of calcium pyrophosphate in articular cartilage and periarticular tissue producing the radiological appearance of chondrocalcinosis (linear calcification parallel to the articular surfaces.)
What is Haemochromatosis?
Haemochromatosis is an inherited condition where iron levels in the body slowly build up over many years.
What does birefringent mean?
Having different refractive index depending on the polarisation and direction of light. YELLOW/BLUE CRYSTALS.
MECHANICAL BACK PAIN
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Name 3 sinister causes of back pain
- Malignancy
- Infection
- Inflammatory causes
Serious spinal injury RED FLAGS (9)
- AGE onset <20yrs or >50yrs
- Violent trauma
- Constant, progressive non-mechanical pain
- Thoracic pain
- Drug abuse, systemic steroids, HIV
- Weight loss, systemically unwell
- Persisting severe restriction of lumbar flexion
- Widespread neurology
- Structural deformity
What are the main causes of mechanical back pain?
- Lumbar disc prolapse
- Osteoarthritis
- Fractures
- Spondylolisthesis
- Heavy manual handling
- Stooping and twisting whilst lifting
- Exposure to whole-body vibration
Risk factors for recurrent back pain
- Female
- Increasing age
- Pre-existing chronic widespread pain
- Fibromyalgia
- Psychosocial factors e.g. psychological distress, poor self-rated health, disatisfacton with work
Symptoms of mechanical back pain
- Back stiffness
- Scoliosis
- Local pain and tenderness- lessens when sitting or lying
- Sudden onset
- Worse in the evening and with exercise
- Morning stiffness absent
Pathophysiology of mechanical lower back pain
Spinal movement occurs at the disc and the posterior facet joints. Stability is normally achieved by a complex mechanism of spinal ligaments and muscles. Damage to any of these structures may be the source of the pain. Different syndromes for this.
Pathophysiology of Lumbar spondylosis
- Main lesion occurs in an intervertebral disc
- The disc allows rotation and bending
- Initially asymptomatic but visible on MRI as decreased hydration.
- Later the discs become thinner and less compliant causing circumferential bulging of intervertebral ligaments
- Reactive changes on adjacent vertebrae- osteophytes.
- Young people= Schmorl’s node
Name some syndromes that can cause lower back pain
- Fibrotitic nodulosis
2. Postural back pain and sway back pregnancy
How can you diagnose mechanical lower back pain?
- Spinal x-ray
- MRI
- Bone scans
Treatment for mechanical lower back pain
- URGENT NEUROSURGICAL REFERAL if any neurological deficit.
- Analgesia: NSAID’s, Paracetamol, Codeine
- Physiotherapy
- Acupuncture helps
- Re-education
VASCULITIS
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What is the difference between ENDOthelial and EPIthelial cells?
Endothelial cells are specialized type of epithelial cells. The main difference between epithelial and endothelial cells is that epithelial cells line both internal surfaces and external surfaces of the body whereas endothelial cells line the internal surfaces of the components of the circulatory system.
What is vasculitis? What are the consequences?
A histological term describing the inflammation of the vessel wall. Inflammation and necrosis of vessels walls cause reduced blood flow resulting in:
- Vessel wall destruction → aneurysms, stenosis and rupture → haemorrhage and perforation into tissues
- Endothelial injury → thrombosis and ischemia/ infarction of dependant tissues.
Name the 6 AUTOIMMUNE rheumatological disorders
- SLE
- Sjogrens
- Systemic sclerosis
- CREST syndrome
- Antiphospholipid syndrome
- Polymyositis and Dermatomyositis
Clinical presentation of vertebral disc degeneration
- Sudden onset of severe back pain (often following strenuous activity)
- Pain aggravated by movement
- Sideways tilt due to muscle spasms when standing up
ROOT LESION: S1
- Pain
- Reflex lost
- Other signs
pain: buttock down back of the thigh to ankle/foot
reflex: ankle jerk
other: diminished straight leg raising
Root lesion: L5
- Pain
- Reflex lost
- Other signs
pain: buttock to the lateral aspect of leg and top of the foot
reflex: none
other: diminished leg raise
ROOT LESION: L4
- Pain
- Reflex lost
- Other signs
pain: lateral aspect of the thigh to the medial side of the calf
reflex: knee jerk
other: positive femoral stretch test
What is the treatment of vertebral disc degeneration?
Acute stage: bed rest, analgesia and epidural corticosteroid injection
Surgery –only if severe
Physio in the recovery phase
What type of drug is Denosumab?
It is a monoclonal antibody which binds and neutralizes the activity of human RANKL to inhibit bone resorption and may also prevent the progression of bone erosion.
Used to reduce osteoporotic fractures
