MSK Flashcards
What is the function of type A and type B cells in the sunovium?
Type A clear debris
Type B produce synovial fluid components
Describe osteoarthritis
Progressive loss of articular cartilage
Give the components of the extracellular matrix of a chondrocyte
Type II collagen
Proteoglycans
Give 6 risk factors for osteoarthritis
Age Inflammation Joint injury Mechanical stress and obesity Neurologic disorders Genetics Medications
How can articular damage to the chondrocytes cause a loss of elasticity and an inflammatory response?
Loss of polteoglycans and increase in type I collagen leads to loss of elasticity
Chondrocytes can undergo apoptosis and flake off into the synovial space
Type A cells bring in macrophages and lymphocytes which produce pro-inflammatory cytokines, causing synovitis
Give 3 bone changes as a result of osteoarthritis
Fibrillations: cracks on articular surface
Bone-bone contact: eburnation (looks like polished ivory)
Osteophytes: bone grows outwards, joints look wider
Where are Heberden nodes found?
Distal interphalangeal joints
Where are Bouchard nodes found?
Proximal interphalangeal joints
Describe the pattern of pain and stiffness in osteoarthritis
Stiffness: less than an hour in the morning, worsens at the end of the day
Pain: sharp ache/ burning, worse with activity
How would you treat osteoarthritis?
Losing weight Exercise Physical therapy Pharmacological: reduce pain/ inflammation Hyaluronic acid injections Surgery
Which human leukocyte antigens are genetic risk factors for rheumatoid arthritis?
HLA-DR1 and HLA-DR4
What is the role of environmental factors in rheumatoid arthritis?
Cigarette smoke/ pathogens can modify our own antigens
Give 3 proteins which can be modified through citrullination in rheumatoid arthritis
IgG antibodies
Type II collagen
Vimentin
What is the result of citrullination in rheumatoid arthritis?
Antigens are no longer recognised by immune cells and are taken to a lymph node and presented to CD4+ helper cells which present to B cells which proliferate and differentiate into plasma cells producing autoantibodies
What is a panus?
Thick, swollen synovial membrane with granulation tissue containing fibroblasts, myofibroblasts and inflammatory cells
Over time, what damage can the panus cause?
Damages other soft tissue, cartilage and can erode bone
Activated synovial cells release proteases which break down cartilage so exposed bone can rub against each other
What effect can inflammatory cytokines have on T-cels presenting RANK-L in rheumatoid arthritis?
T-cells present RANK L which binds to RANK on osteoclasts which are activated to break down bone
Give 2 antibodies produced in rheumatoid arthritis and state what they bind to
Rheumatoid factor (IgM) binds to Fc of altered IgG Anti-CCP binds to citrullinated proteins and forms immune complexes which activate the compliment system and cause inflammation
What is the result of immune complexes depositing in:
The brain
Skin nodules
Blood vessels
Brain: IL-1 or 6 causes pyrogens (fever)
Skin nodules: filled with macrophages and lymphocytes + with central necrosis
Blood vessels: Inflammation, so prone to atheromatous plaques
What is the result of immune complexes depositing in:
The lungs
Skeletal muscle
Liver
Lungs: pleural cavities fill with fluid: pleural effusion
fibroblasts form scar tissue in the interstitium
Skeletal muscle: Protein breakdown
Liver: Increased hepcidin, decreases iron by inhibiting absorption and trapping iron in macrophages/ liver cells
How many joints are typically affected in rheumatoid arthritis?
> 5
It there a symmetrical or asymmetrical pattern of join inflammation in rheumatoid arthritis?
Symmetrical
Which joints are commonly affected in rheumatoid arthritis?
MCP, PIP, MTP
Give 4 symptoms of rheumatoid flares
Swollen
Warm
Red
Painful
Describe the 3 specific deformities found with rheumatoid arthritis
Ulnar deviation
Boutonniere deformity: PIP flexion, DIP hyper-extension
Swan neck: PIP hyper-extension, DIP flexion
How can a Baker (popliteal) cyst form as a result of rheumatoid arthritis?
One way valve forms in the knee joint, causing fluid to fill the semi-membranous bursa
Synovial sack can bulge posteriorly into the popliteal fossa
Give 4 extra-articular symptoms of rheumatoid arthritis
Fever
Low appetite
Malaise
Weakness
Give the 3 conditions that make up Felty syndrome
Rheumatoid arthritis
Splenomegaly
Granulocytopoenia
How would you diagnose rheumatoid arthritis?
Blood tests: Rheumatic factor and anti-citrullinated peptide antibody (anti-CCP)
X-Ray: loss of bone density, bony erosions, soft tissue swelling, narrowing of joint space
How would you treat rheumatoid arthritis?
Disease modifying anti-rheumatic drugs (DMARDs):
Methotrexate
Hydroxychloroquine
Sulfasalazine
Biologic response modifiers:
Abatacept (suppress T cells)
Rituximab (suppress B cells)
Describe gout
Monosodium urate crystals deposit in the joints which then become red, hot, swollen and tender
What is the cause of gout?
Hyperuricemia
What are purines and what are they converted to in the body?
N-containing, key components of DNA and RNA, covered to uric acid which has limited solubility in body fluid
What happens when uric acid levels are greater than 6.8mg/dL
Urate ion binds to sodium and forms monosodium urate crystals
Give 3 generic causes of monosodium rate crystal formation
Increased purine consumption
Decreased clearance of uric acid
Increased production of purines
Give 4 foods which are high in purines
Shellfish
Anchovies
Red meat
Organ meat
What may cause a decrease in clearance of uric acid?
Dehydration
What may cause an increase in the production of purines?
High-fructose corn syrup beverages
Give 6 risk factors of gout
Obesity Diabetes Chemo Genetic predisposition CKD Meds: thiazide diuretics and aspirin
What is the most commonly affected joint with gout?
First metatarsal joint of the big toe: podogra
What is the cause of inflammation in gout?
Leukocyte migration to site in order to eliminate uric acid
How would you treat gout?
Decrease pain and swelling: NSAIDs, corticosteroids and colchicine (inhibits WBC migration) Treat underlying cause: Diet modification Decrease uric acid levels: Xanthine oxidase inhibitors: Allopurinol
What causes chronic gout and what are the risks with this?
Repeated gouty attacks Risk of: Arthritis Tissue destruction Kidney stones and urate neuropathy Tophi (permanent nodules)
Describe pseudogout
Calcium pyrophosphate deposition
Describe the pattern of acute pseudogout
Monoarthropathy of larger joints in the elderly
Describe the pattern of chronic pseudogout
Inflammatory, symmetrical polyarthritis and synovitis
Give 3 potential causes of acute pseudogout
Illness
Surgery
Trauma
Give 4 risk factors of pseudogout
Old age
Hyperparathyroidism
Haemochromatosis
Hypophosphataemia
How would you diagnose pseudogout?
Polarised light microscopy of synovial fluid
X-Ray: soft tissue calcium deposition
How would you manage pseudogout?
Acute: cool packs, rest, aspiration, intra-articular steroids
Prophylaxis: NSAIDs and colchicine
Chronic: Methotrexate and hydrochloroquine
Describe osteoporosis
Age-related disorder causing gradual loss of bone density and strength
Give 5 modifiable risk factors for osteoporosis
Excess alcohol Vitamin D deficiency Smoking Malnutrition Underweight Heavy metals PPIs
Give 5 non-modifiable risk factors for osteoporosis
Female Age Menopause Ethnicity FHx Build
How would you diagnose osteoporosis?
X-Ray: cortical thinning, increased radiolucency, fractures
Dual-energy x-ray (DEXA)
Bone mineral density compared to that of a healthy (30-40y/o) adult population
Normal: > -1.0
Osteopenia -2.5< T score < -1.0
Osteoporosis:
How would you treat osteoporosis?
Weight-bearing/ resistance exercises
Fall prevention
Medications: bisphosphonates
Which human leukocyte antigen is associated with spondyloarthropathies?
HLA B27 (class I surface antigen)
What does SPINE ACHE stand for, in relation to spondyloarthropathies?
Sausage digits (dactylitis) Psoriasis Inflammatory back pain NSAIDs good response Enthesis
Arthritis
Chrons/ colitis
HLA B27
Eye (uveitis)
Describe ankylosing spondylitis
Inflammatory arthritis of the spine and rib cage, eventually leading to new bone formation and fusion of the joints
Give 5 factors which reflect a poor prognosis in ankylosing spondylitis
Male Smokers B27 +ve Syndesmophytes at presentation High CRP
Describe the signs and symptoms of ankylosing spondylitis
Gradual onset of lower back pain (worse at night)
Pain radiates to hip/ buttocks from the scaro-illiac joints
Spinal morning stiffness
Progressive loss of spinal movement
How would you manage ankylosing spondylitis?
Hip replacement Exercise NSAIDs TNF-alpha blockers Local steroid injections
Give the 5 types of psoriatic arthritis
Symmetrical polyarthritis DIP joints Spinal Asymmetrical oligoarthritis Psoriatic arthritis mutilans
What percentage of psoriasis cases also have psoriatic arthritis?
10-40%
What X-Ray changes would you see with psoriatic arthritis?
Erosive X-Ray changes “pencil in cup” appearance
How would you manage psoriatic arthritis?
NSAIDs, sulfasalazine, methotrexate
Anti-TNF
Describe reactive arthritis
Sterile inflammation of the synovial membrane, tendons and fascia, triggered by an infection at a distal site
Give 3 gut-associated causes of reactive arthritis
Salmonella
Shigella
Yersinia
Give 2 STIs which can cause reactive arthritis
Chlamydia
Ureaplasma urealyticum
Give 6 signs and symptoms of reactive arthritis
Arthritis
Conjunctivitis
Sterile urethritis
Circinate balanitis (painless penile ulceration)
Iritis
Keratoderma blenorrhagica (brown plaques on soles and palms)
How would you diagnose reactive arthritis?
High ESR, high CRP
Aspirate joint to exclude infection/ crystals
Urethral swab/ stool culture
How would you treat reactive arthritis?
Steroids (local injections)
NSAIDs
If symptoms >6moths: consider sulfasalazine/ methotrexate
What is the typical clinical presentation of septic arthritis?
Fever
Inflammation (warmth, red, effusion, pain)
Loss of function and range of movement
Give 3 causes of septic arthritis
Staphylococcus aureus
Group A streptococcus
Neisseriae Gonorrhoea
How might an infection be introduced into the synovium, causing septic arthritis?
URTI, LRTI, STI travels in blood
Osteomyelitis
Directly through procedures/ surgery
Skin infection
How would you diagnose septic arthritis?
FBC, CRP, ESR Joint aspiration with a microscopy culture sensitivity Blood cultures Electrolyte, urea, creatitnine US/X-Ray (joint space widening)
How would you treat septic arthritis?
Joint drainage: needle aspiration Broad spectrum IV Abx Once cultures come back: specific Abx IV: 2 weeks Oral: 4 weeks
How can osteomyelitis occur and what does it cause?
Bacterial infection of the bone, causing bone cell necrosis, pus formation and weak bones
What type of bone does osteomyelitis usually affect?
Long bones
Give 4 risk factors of osteomyelitis
Diabetes
IVDU
Prior splenectomy
Trauma
Give 4 symptoms of osteomyelitis
Pain
Redness
Fever
Weakness
How would you diagnose osteomyelitis?
FBC (Inflammation/ infection)
MRI
How would you treat osteomyelitis?
Prolonged antibiotic treatment
PICC line/ central venous catheter for long-term IV abx
In SLE, what is the role of susceptibility genes?
It is more likely for immune cells to attack nuclear antigens
They cause less effective clearance of apoptotic bodies, leading to a buildup of nuclear antigens
What is the consequence of a buildup of nuclear antigens in SLE?
They form antigen-antibody complexes with antinuclear antibodies
Where do antigen-antibody complexes deposit in SLE and what is the result of this?
Kidneys, skin, joints, heart
Type III hypersensitivity reaction
Cause a local inflammatory response, activating the complement system and an enzyme cascade, leaving cells with free channels so it bursts and dies
Give 5 tigers/ risk factors for SLE
Smoking Viruses Bacteria Sex hormones (oestrogen) Medications: Isoniazid Hydralazine Procainamide
Describe the type II hypersensitivity reaction in SLE
Antinuclear antibodies bind to RBCs, WBCs and phospholipids, marking them for phagocytosis and destruction
How many of the criteria must the patient meet to be diagnosed with SLE?
> 4
Give the 11 criteria for SLE
1: Malar (butterfly) rash
2: Discoid rash
3: Photosensitivity
4: Ulcers
5: Serositis
6: Arthritis
7: Renal disorders
8: Neurologic disorders
9: Haematologic disorders
10: Antinuclear antibodies
11: Other autoantibody
How would you prevent/ limit severity of SLE flare ups?
Avoid sunlight
Corticosteroids
Immunosuppressants
Describe an osteoid osteoma
Benign, bone-forming lesion in young patients causing localised pain
How would you diagnose and manage an osteoid osteoma?
CT/ X-Ray
NSAIDs, radiofrequency ablation
Describe an osteoblastoma
Bone producing tumour, causing pain
What would an X-Ray of an osteoblastoma show?
Bone destruction, surrounded by reactive new bone
Describe an osteochondroma
Metaphyseal lesion, covered by cartilage cap, grows away from growth plate- stops after puberty (painless lump)
Describe an osteosarcoma
spindle cell neoplasms that produce osteoid
Which mutation is associated with an osteosarcoma?
P53
Why does osteosarcoma have a poor prognosis?
Aggressive local growth
Rapid haematological spread
Poor response to chemo
Describe a Ewings sarcoma
Small round cell tumour that arises from neural crest cells characterised by a translocation mutation t(11;22)
What is the name of the neurotransmitter released by the cell body of an axon in response to nociceptor stimulation?
Substance P
Give the neurotransmitters released by the inhibitory neuron
Serotonin
Norepinephrine
What is the role of nearby epithelial cells in fibromyalgia?
They release nerve growth factor which attracts mast cells which release more nerve growth factors
This increases the growth and sensitivity of nociceptors, and therefore substance P
Give 3 causes of fibromyalgia
Low levels of serotonin
High levels of substance P
High levels of nerve growth factor
Give the 3 factors taken into account for the diagnosis of fibromyalgia
Pain location
Symptom severity score (fatigue, poor sleep, headache)
Duration
How would you treat fibromyalgia?
Exercise
Relaxation techniques
Meds:
Amitriptyline
Serotonin-Norepinephrine reuptake inhibitors (SNRIs)
Anticonvulsants: pregabalin and gabapentin
Describe the character of mechanical back pain
Better/ worse depending on position
Typically worse when moving
May be due to minor injury (sprain or strain)
Can be associated with stress
Give 5 symptoms of prolapsed/ herniated disc
Lower back pain Numbness/ tingling Neck pain Problems straightening your back Muscle weakness
Describe spondylolisthesis
A bone in the spine slips out of position
Give 5 symptoms of spondylolisthesis
Lower back pain: worse with activity/ standing Sciatica Tight hamstring muscles Stiffness/ back tenderness Kyphosis
Give 5 causes of mechanical back pain
Birth defect Repetitive spinal trauma Vertebral joints becoming worn and arthritic Sudden trauma/ spinal injury Bone abnormality
How would you treat mechanical back pain?
Rest NSAIDs Physio Corticosteroid injections Surgery
How does the parathyroid gland respond to low calcium?
Releases parathyroid hormone which causes osteoclasts to release HCl leading to bond breakdown and release of phosphate and calcium in the blood
Why does ionised calcium level not increase much with increased bone resorption in osteomalacia?
Phosphate and calcium ions bond to form calcium phosphate
Give 2 causes of excess loss of phosphate leading to osteomalacia
Primary hyperparathyroidism: excess phosphate lost in urine
Facing syndrome: PCT losing capacity to reabsorb a number of solutes
Give 5 causes of phosphate malabsorption in the GI tract leading to osteomalacia
Alcohol
Medications (antacids)
Not enough in the diet
Refeeding syndrome (phosphate moves from blood to cells since insulin draws phosphate into cells)
Respiratory alkalosis (increases pH in cell, triggering glycolysis)
Give 2 causes of insufficient calcium absorption leading to osteomalacia
Lack of dietary calcium
Resistance to action of vitamin D
Give 6 primary causes of osteomalacia
Renal tubular acidosis Malnutrition Malabsorption syndrome Chronic kidney failure Oncotic osteomalacia Coeliac disease
Describe degenerative disc disease
Natural breakdown of an intervertebral disc of the spine due to daily stresses
How does degenerative disc disease occur?
Daily stresses cause spinal discs to weaken and lose water as the annulus fibrosis weakens
As discs weaken and lose water, they begin to collapse
This results in pressure on the spinal nerves
Describe the symptoms of degenerative disc disease
Pain in the neck, hips, buttocks/ thighs
Commonly worse on movement
How would you diagnose degenerative disc disease?
Physical exam: muscle weakness, tenderness, poor range of motion
MRI: degenerative fibrocartilage and clusters of chondrocytes
How would you treat degenerative disc disease?
Physio Anti-inflammatories: NSAIDs Traction Steroid injection Surgery
Give 3 general symptoms of vasculitis
Fever
Weight loss
Fatigue
Who is most commonly affected by giant cell arteritis and which artery is affected?
> 50 y/o
Women > men
Affects carotid artery
What lab results would you see with giant cell arteritis?
High ESR
Granulomas in tunica intima
Which arteries are generally affected with medium vessel vasculitis?
Muscular arteries supplying the organs
How would you treat giant cell arteritis or medium vessel vasculitis?
Corticosteroids
Give a key complication of giant cell arteritis
Blindness
Give an example of medium vessel vasculitis and how it causes damage
Polyarteritis nodosa:
Immune cells attack endothelium and cause damage/ fibrosis, leading to organ ischaemia
Describe the mechanism of small vessel vasculitis
B-cells produce anti-neutrophilic cytoplasmic antibodies attack neutrophils in arterioles, capillaries and venuoles
Describe Paget’s disease
Disrupts normal cycle of bone renewal causing bones to become weakened and possibly deformed
Give 4 symptoms of Paget’s disease
Travelling shooting pain
Numbness and tingling
Joint pain, stiffness and swelling
Constant dull bone pain
How would you treat Paget’s disease?
Bisphosphonate medication/ vit D/ calcium supplements
Painkillers
Physio
Surgery
Give 6 potential complications of Paget’s disease
Bone cancer Breaks Enlarged/ misshapen bone Hearing loss Hypercalcaemia Heart problems
