Week 9 - bone pain Flashcards
1
Q
Describe the basic epidemiology of Paget’s disease. (LO1)
A
- Second most common metabolic bone disease.
- More common in males.
- Unusual in <40s.
2
Q
Describe the pathophysiology of Paget’s disease. (LO1)
A
- Increased bone cell activity.
- Osteoclasts are larger in size, therefore, resorb more bone.
- This leads to osteoblasts laying down bone in a haphazard way resulting in poor bone architecture.
- As a result, we see expansion of poor quality bone.
- The marrow is replaced with fibrous tissue (which isn’t as strong) and blood vessels - leading to the bone sometimes feeling warm due to increased blood flow.
3
Q
Which bones are usually affected by Paget’s disease? (LO1)
A
Normally only one bone is affected.
- Femur.
- Spine.
- Skull.
- Sternum.
- Pelvis.
- Any bone in the body can be affected.
4
Q
List some neurological symptoms of Paget’s disease. (LO1)
A
- Obstructive hydrocephalus - fluid not circulating around the brain.
- Cranial nerve palsies - nerve going through the skull not working.
- Deafness - if the skull expands.
- Paraplegia or quadriplegia - if the spine is affected.
- Tinnitus.
5
Q
List some investigations for Paget’s disease. (LO1)
A
- Plain radiographs.
- CT.
- MRI.
- PET CT.
- Isotope bone scans.
6
Q
List some presentations of Paget’s disease. (LO1)
A
On examination, the affected bone will be:
- Warm - due to increased blood flow.
- Tender - due to periosteum being stretched.
- Deformed.
7
Q
Briefly describe the genetic factor associated with Paget’s disease. (LO1)
A
- There is a small genetic link with a defect in the SQSTM1 gene.
- However, it is unknown what triggers this defect.
8
Q
List the complications caused by expansion of the pelvis due to Paget’s disease. (LO1)
A
- Pain in the hip joint.
- Bone deformity.
- Bone pain.
- Increased risk of fracture.
- Sclerotic and lytic areas on x-rays.
- Osteoarthritis in neighbouring joints.
Rare:
- Cardiovascular symptoms.
- Metabolic symptoms.
- Neoplasia.
9
Q
Describe the findings of an x-ray in Paget’s disease. (LO1)
A
- Bones expanded.
- Cortical thickening.
- Mixture of sclerotic and lytic areas.
10
Q
Describe the management of Paget’s disease. (LO1)
A
- Zoledronate 5mg - reduce osteoclast function.
- Analgesia - to relieve symptoms.
- Vitamin D.
- Physiotherapy.
- Surgery - to repair fractures, replace joints or for spinal stenosis.
11
Q
Describe the basic epidemiology of bone metastases. (LO2)
A
- 400,000 diagnoses of bony metastases are made in the US annually.
- The general incidence of advanced malignant tumours with bone metastasis is 30-75%.
- The presence of bone metastases indicates a poor prognosis.
12
Q
List the most common cancers to metastasise to bones. (LO2)
A
Most common primary tumours for bone metastases are organs that naturally lie near bone:
- Prostate cancer - 65-75% of prostate cancer cases will involve metastasis to the bone.
- Breast cancer - 65-75%.
- Thyroid cancer - 60%.
- Lung cancer - 30-40%.
- Bladder cancer - 40%.
- Renal cell carcinoma - 20-25%.
- Melanoma - 14-45%.
13
Q
List the three types of bone metastases. (LO2)
A
- Osteolytic.
- Osteoblastic.
- Mixed.
14
Q
Describe osteolytic bone metastases. (LO2)
A
- Mediated by osteoclasts which break down the bone matrix.
15
Q
Which cancers is osteolytic bone metastases more likely to be found in? (LO2)
A
- Multiple myeloma.
- Renal cell carcinoma.
- Melanoma.
- Breast cancer.
16
Q
Describe osteoblastic bone metastases. (LO2)
A
- New bone is laid down by osteoblasts, forming sclerotic lesions.
- This is not always preceded by bone resorption.
17
Q
Which cancers is osteoblastic bone metastases more likely to be found in? (LO2)
A
- Prostate cancer.
- Carcinoid.
- Small cell lung cancer.
18
Q
Describe mixed bone metastases. (LO2)
A
- Both destruction and deposition of bone.
19
Q
Which cancers is mixed (lytic+blastic) bone metastases more likely to be found in? (LO2)
A
- Breast cancer - 15-20% have a mixed type of bone metastasis.
- GI cancers.
- Squamous cancers.
20
Q
List the three mechanisms of spread of bone metastases. (LO2)
A
- Epithelial-mesenchymal transition.
- Micro-environmental support.
- Vascular adhesion and extravasation.
All of these work together to allow the tumour to spread.
21
Q
Describe epithelial-mesenchymal transition as a mechanism of spread for bone metastases. (LO2)
A
- Where epithelial cells transition into a mesenchymal cell.
- Epithelial cells have tight junctions which fix them to neighbouring cells.
- When they transition to mesenchymal cells, they lose the junctions making them more mobile, i.e. they can migrate.
22
Q
Describe micro-environmental support as a mechanism of spread for bone metastases. (LO2)
A
- The seed and soil hypothesis states that the “soil”, which is distant tissue, bone in this case, is fertile ground for growth of the “seed” which is the primary cancer.
23
Q
Describe vascular adhesion and extravasation as a mechanism of spread for bone metastases. (LO2)
A
- Cancer cells can interact with the endothelium, causing extravasation.
24
Q
Describe the presentation of bone metastases. (LO2)
A
- No specific presentation.
- Usually diagnosed on the staging scans/follow-ups for the primary cancer.
- Main symptom is non-specific pain.
- Neurological symptoms can also occur if the spine is involved.
- The severity of pain can be affected by:
- Is a nerve being compressed?
- Is the bone metastasis causing damage to a nearby structure?
- The location of the bone metastasis.
25
List the potential neurological symptoms from a bone metastases of the spine. (LO2)
- Motor weakness.
- Paralysis.
- Sensory dysfunction.
- Bowel and bladder dysfunction - incontinence.
- Ataxia.
26
Describe Cauda Equina syndrome. (LO2)
- Where the bone metastasis can compress part of the spinal cord called the cauda equina.
- This is an emergency requiring urgent surgery as if untreated, it can cause permanent paralysis or worse.
- Symptoms include: back pain, incontinence, saddle/perineal anaesthesia.
- Treatment is laminectomy or decompression/removal of whatever is compressing the cord.
27
Describe the investigations for bone metastases. (LO2)
- X-ray - first line - shows osteolytic lesions (black), osteoblastic lesions (white). Requires >50% trabecular injury before lesions appear on x-ray.
- CT - shows good detail of bone and soft tissue.
- MRI - best for spinal cord and axial skeleton.
- PET - shows metabolic activity by showing tissue uptake of a dye-tagged metabolite, e.g. glucose. Can show early metastatic multiple myeloma.
28
Describe the management of bone metastases. (LO2)
- Bisphosphonates - inhibits bone demineralisation.
- Denosumab - monoclonal antibody, RANK-L inhibitor.
- External radiotherapy - tumour may shrink or be less active. Effective for pain relief (few weeks after the procedure).
- Radionuclide therapy - more effective for osteoblastic metastasis.
- Ablation - tumours are detroyed using heat/cold or chemicals. Indicated for symptomatic tumours.
- Surgery - only if necessary, i.e. risk of fracture, spinal cord compression, hip + long bones are affected.
29
Describe the prognosis of bone metastases. (LO2)
- Presence of bone metastases is evidence of tumour spread so it is associated with a poor prognosis.
- The exact survival is tumour dependent (the type of primary cancer).
30
Define pathological fracture. (LO3)
Loss of continuity of the cortex of a bone that has been weaked by a pre-existing condition.
31
What are some underlying causes for pathological fractures? (LO3)
- Tumours.
- Paget's disease.
- Metabolic bone disease.
- Rheumatoid arthritis.
- Infection.
32
What is the most common cause of pathological fractures? (LO3)
- Osteoporosis followed by tumours.
- If a tumour is the cause of a pathological fracture, the tumour may be benign or malignant.
- If malignant, it is highly likely to be metastatic as opposed to a primary bone sarcoma.
33
Which areas are most commonly affected by pathological fractures? (LO3)
- Vertebrae of the thoracic and lumbar regions.
| - Proximal femur and distal radius.
34
Describe the investigations for pathological fractures. (LO3)
- X-ray.
- 25-hydroxyvitamin D concentrations.
- FBC.
- Tests for metabolic disorders.
- Biopsy.
- Urine examination.
- CRP.
- Alkaline phosphatase.
- Albumin adjusted calcium.
- DEXA scan.
35
List some presentations of pathological fractures. (LO3)
- New skeletal deformities.
- Painful bony areas, swelling or bruising.
- Behaviour changes.
- Changes in sleep pattern.
- Many pathological fractures are asymptomatic, however.
36
Describe the management of pathological fractures. (LO3)
- Surgical stabilisation of the fracture is common, however this supplements the treatment of the underlying pathology.
- In primary malignancy, treatment of the tumour is the priority and the prognosis is usually very poor.
- With metastatic tumours, treatment of the primary malignancy is key along with surgical stabilisation.
37
What is osteomalacia? (LO4)
- Osteomalacia is a disorder that arises as a result of vitamin D deficiency and means that our bones are unable to mineralise properly.
- The result is bones that are weak and soft and at greater risk of fractures than normal.
38
Describe the basic epidemiology of osteomalacia. (LO4)
- Osteomalacia affects adults as it only occurs in mature skeletal bones.
- Osteomalacia is a result of vitamin D deficiency and so those most at risk are those with a deficiency.
- This deficiency may have occurs for a number reasons such as:
1. Lack of sunshine.
2. Low vitamin D diet.
3. As a result of a medical condition that causes intestinal malabsorption.
4. A liver and kidney disease that prevents regulatory enzymes from working.
39
List the risk factors for developing osteomalacia. (LO4)
- Darker skin.
- Older in age.
- Infirm (inpatient at hospital).
- GI disorders.
- Chronic liver disease or renal failure.
- Those on anticonvulsant medications.
- Those on strict diets, e.g. lacto vegetarians.
- People who use excessive high factor sunblock.
- Rare hereditary disorders.
40
Describe the role of vitamin D in bone mineralisation. (LO4)
- Bone mineralisation is when calcium and phosphate are deposited into the osteoid framework by osteoblasts.
- In order to do this, vitamin D needs to be able to regulate the levels of calcium and phosphate in the blood.
- Vitamin D from our food and UV exposure is converted to 25-(OH)-vitamin D by the enzyme 25-hydroxylase.
- It then travels to the kidneys where an enzyme 1-α-hydroxylase converts 25-(OH)-vitamin D to 1,25-(OH)-vitamin D (calcitriol).
- Calcitriol is responsible for reabsorption of calcium in the kidneys to prevent it being excreted in the urine and phosphate absorption in the gut as well as preventing parathyroid hormone synthesis and secretion which resorbs calcium and some phosphate from the bone into the blood stream.
41
Describe the pathophysiology of osteomalacia. (LO4)
- Vitamin D is needed in order for osteoblasts to deposit calcium and phosphate into the osteoid framework of bone. This is known as bone mineralisation.
- Vitamin D, alongside parathyroid hormone, regulates calcium and phosphate in the blood.
- Vitamin D from food and UV is hydroxylated in the liver before being converted to its active form in the kidneys.
- Calcitriol regulates reabsorption of calcium and phosphate.
- When there is a lack of vitamin D, calcium and phosphate cannot be regulated correctly.
- Osteoblasts do not then have enough calcium and phosphate to deposit into the organic matrix.
42
Describe the presentation of osteomalacia. (LO4)
- Can exist with no symptoms.
- Chronic, non-specific widespread musculoskeletal pain.
- Aching.
- Weakness in hip or proximal leg.
- Increase in fractures, especially the vertebrae.
- Skeletal deformity (rickets).
- Waddling gait.
- Rare - hypocalcaemia seizures.
43
List the investigations for osteomalacia. (LO4)
- FBC.
- Serum calcium.
- Alkaline phosphatase.
- Liver function tests.
- Urea and electrolytes.
- X-rays.
44
Describe the management of osteomalacia. (LO4)
- Education of how to prevent osteomalacia is important, e.g. how to get sufficient vitamin D in your diet.
- Especially important to educate the at-risk groups.
- Lifestyle factors, e.g. improving diet and adding supplements if needed.
- Aiming to get at least 15 minutes of sun exposure to hands, forearms and face 3x a week. (Longer exposure for people with darker skin as it takes longer to absorb the same amount of vitamin D).
45
Describe the prognosis of osteomalacia. (LO4)
- Normally pretty good.
| - Unlike osteoporosis, it can be cured by replacing vitamin D through oral supplements.
46
List the most common causes of osteomyelitis. (LO5)
1. Post-trauma osteomyelitis - adults.
2. Post-surgery osteomyelitis - adults.
3. Acute haematogenous osteomyelitis - children.
4. Direct osteomyelitis - from nearby joint infection.
1 and 2 are types of 'exogenous' osteomyelitis, whereby infection is spread through inoculation. 3 is caused by blood-borne bacteria and is known as 'haematogenous' spread.
47
List the most causative organisms of osteomyelitis. (LO5)
- S. aureus.
- Streptococcus.
- Enterobacter spp.
- H. influenzae.
- P. aeruginosa - especially in intravenous drug users.
- Salmonella spp - especially in patients with sickle cell disease.
48
Describe the basic epidemiology of osteomyelitis. (LO5)
- Reported incidence of peripheral bone infection: 2% per year in developed countries.
- More likely in men than women.
- More likely as age increases - diabetes, falls, etc.
49
What are the two categories of osteomyelitis? (LO5)
- Congenital.
| - Acquired.
50
List the risk factors for acquired osteomyelitis. (LO5)
- Diabetes mellitus.
- Immunosuppression - due to long-term steroids/AIDS.
- Alcohol excess.
- Intravenous drug use.
- Penetrating injury.
- Recent surgery.
- Sickle cell anaemia.
- Rheumatoid arthritis.
- Chronic kidney disease/renal failure.
- Malnutrition.
51
Describe the risk factors for congenital osteomyelitis. (LO5)
- Sickle cell anaemia.
- Haemophilia.
- Rheumatoid arthritis.
52
Describe the general presentation of osteomyelitis. (LO5)
- Severe pain in the affected region.
- In patients with diabetic foot, pain may be absent due to peripheral neuropathy.
- Associated low-grade pyrexia.
- Pain is constant and worse at night.
- Can present with non-specific symptoms only.
- Possibly recent history of trauma.
- Site will be tender.
- Overlying swelling and erythema.
- If lower limb is affected, patient may not be able to weight bear.
53
What is acute-on-chronic osteomyelitis? (LO5)
- Adults most commonly present with this.
- An acute presentation may be the first presentation of chronic osteomyelitis.
- Previous infections may appear dormant for months or years before recurring.
54
Describe the presentation of acute osteomyelitis. (LO5)
- Local inflammation.
- Erythema.
- Tenderness.
- Swelling.
- Areas of point tenderness.
- Decreased range of motion above and below the affected area - this may be due to pain or indicate an associated septic arthritis.
- Torticollis and lower back pain may indicate axial osteomyelitis or lumbar discitis.
55
Describe the presentation of chronic osteomyelitis. (LO5)
- Typically low grade fever.
- Angular deformity or shortening of the limb - resulting from premature fusion of the physeal plate (particularly following childhood osteomyelitis).
- Acute or old healed sinuses.
- Fracture fixation.
- Evidence of previous operations, including scars and previous flap designs.
- Tenderness to percussion over the subcutaneous border of affected bones.
56
Describe the investigations for osteomyelitis. (LO5)
- Routine blood tests: FBC, CRP and ESR.
- Blood cultures - gram positive in around 60% of cases.
- Plain radiographs.
- MRI imaging - definitive diagnosis.
57
Why are plain radiographs not ideal for investigating osteomyelitis? (LO5)
- Performed often but they have a poor accuracy for osteomyelitis.
- Any visible signs tend to only be visible from ~7-10 days post-initial infection.
58
What are the potential findings from plain radiographs indicating osteomyelitis? (LO5)
- Osteopenia.
- Periosteal thickening.
- Endosteal scalloping.
- Focal cortical bone loss.
- Involucra.
- Sequestra.
59
What are the potential findings from MRIs indicating osteomyelitis? (LO5)
- Oedema.
- Cortical loss.
- Contrast enhancement of access rim.
60
Why is a bone biopsy done as part of investigations for osteomyelitis? (LO5)
- Gold standard diagnosis.
- Culture from bone biopsy at debridement (or curettage where there are associated ulcers).
- Has 90% sensitivity.
- Important to check for mycobacterium and fungal causes in relevant cases, such as immunosuppressed patients.
61
What is meant by involucra and why are these relevant? (LO5)
- Newly formed bone eveloping the sequestrum in infection of the bone.
- May start to appear in around day 7-10 post initial infection.
62
What is meant by sequestra and why are these relevant? (LO5)
- A fragment of necrosed bone that has been partially separated from the surrounding tissue.
- Can be seen on plain radiographs as early as 10 days post initial infection.
63
Describe the management of osteomyelitis. (LO5)
Depends on whether the patient is clinically well or deteriorating.
Clinically well:
- Analgesia.
- Splinting of limb.
- Long-term IV antibiotics >6 weeks, tailored to any cultures available, otherwise following local antimicrobial protocols.
- Usually this is all that's needed.
Deteriorating: surgical intervention
- Abscess drainage.
- Dead bone (sequestrum) removed (curettage).
- Extensive infection may require removal of bone.
64
What should you be looking out for when examining a patient with osteomyelitis? (LO5)
Potential source of the infection.
- Pock marks.
- Sinuses from IV drug abuse.
- Cellulitic areas.
- Penetrating wounds.
- Stigmata of concurrent infection in another body system.
65
What is meant by curettage in relation to osteomyelitis management? (LO5)
Surgical scraping of the lining, to clean it of foreign matter (dead matter).
66
List the potential complications of osteomyelitis. (LO5)
- Sepsis.
- Septic arthritis of the soft tissues (if it spreads to the joint).
- Deformity/growth inhibition (children) - as a result of premature physeal fusion.
- Recurrence/chronic osteomyelitis (often associated with premature cessation of antibiotics) - immunosuppressed patients, under-treated patients or with virulent/resistant organisms.
- Mortality.
- Amputation is rarely required in modern practice.
67
Describe the prognosis of acute osteomyelitis. (LO5)
- Good prognosis.
- Full recovery.
- If no complications occur.
68
Describe the prognosis of chronic osteomyelitis. (LO5)
- More difficult to treat and may remain dormant for many years.
- Flare-ups can occur, causing pain and loss of function. These can be managed with antibiotics.
Exogenous osteomyelitis:
- Many surgical procedures may follow.
- Amputation is not uncommon.
69
What is exogenous osteomyelitis? (LO5)
When bone extends out from the skin, allowing a potentially infectious organism to enter from an abscess, burn, puncture wound or an open fracture.
70
Where does the difficulty lie with prognosis of osteomyelitis? (LO5)
- Early diagnosis and intervention allows for better prognosis.
- BUT difficult to diagnose.
71
What is osteoporosis? (LO6)
A systemic skeletal disease characterised by low bone mass and deterioration of bone tissue, with consequent increase in bone fragility and susceptibility to fracture.
72
List the categories of causes of osteoporosis. (LO6)
- Non-modifiable risk factors.
- Lifestyle risk factors.
- Comorbidities.
- Medications.
73
List the non-modifiable risk factors of osteoporosis. (LO6)
- Increased age.
- Female sex.
- Previous fragility fracture at a site which is characteristic.
- Endocrine, e.g., early menopause.
- Parental history of hip fractures.
74
List the modifiable (lifestyle) risk factors of osteoporosis. (LO6)
- Low BMI.
- Smoking, alcohol intake.
- Low bone density.
75
List the comorbidities affecting osteoporosis. (LO6)
- Diabetes mellitus.
- Rheumatoid arthritis.
- Systemic lupus erythematosus.
- Epilepsy.
- HIV.
- Primary hyperparathyroidism.
- Liver and renal disease.
- Neurological.
- Asthma.
76
List the drugs that can increase the likelihood of developing osteoporosis. (LO6)
- Glucocorticoids.
- Epileptics.
- Aromatase inhibitors.
- Depot injection.
- GNRH in men.
- PPI.
- Thiazides.
77
What type of fracture affects the vertebra in osteoporosis? (LO6)
Wedge fractures, typically affecting T12.
78
Describe the pathophysiology of osteoporosis. (LO6)
An imbalance in the relationship between osteoblast and osteoclast activity.
79
What is a bone multicellular unit? (LO6)
A combination of osteoblast and osteoclast activity. When this is dysfunctional, osteopenia and osteoporosis can occur.
80
What is meant by peak bone mass? (LO6)
- This is when the bone is at it's densest/healthiest.
| - Rises to the peak in the first 30 years of our life. Plateaus between ages 30-45 and starts to decrease again.
81
List some key determinants of peak bone mass. (LO6)
- Genes.
- Skeletal geometry.
- Body weight.
- Sex hormones.
- Diet.
- Exercise.
- Racial factors.
82
Describe the presentation of osteoporosis. (LO6)
- Osteoporosis is diagnosed by a fracture as usually this is the main way it presents.
- Presentation of osteoporosis is consistent with that of fractures: pain and reduced range of movement.
- Diagnosis is made when screening at-risk patients, e.g. those on long-term steroids.
83
What is FRAX? (LO6)
A method to calculate risk of fracture.
84
List the investigations for osteoporosis. (LO6)
- DXA scan.
- FBC.
- ESR/CRP.
- Serum calcium (albumin as a carrier for calcium).
- Alkaline phosphatase.
- Liver tests.
- Thyroid.
- Myeloma screen.
- 25-hydroxyvitamin D.
- PTH.
- Endocrine: sex hormones/diabetes/cortisol.
- Gastrointestinal: coeliac disease antibiotics, etc.
- Markers of bone turnover.
- Urine calcium excretion.
- Plain radiographs.
- MRI.
- Isotope bone scan.
85
What is the DXA scan? (LO6)
- Dual-energy x-ray absorptiometry scan - low dose of radiation.
- Used to screen for osteoporosis.
- Gives a t-score and z-score.
86
What is the difference between a t-score and a z-score? (DXA) (LO6)
- A t-score is the difference between the mean bone density of the patient and a healthy YOUNG woman.
- A z-score is the difference between the mean bone density of the patient and a healthy age-matched woman.
87
Explain the significance of the different t-scores. (DXA) (LO6)
>1.0 = normal, low fracture risk.
| -1.0 to -2.5 = osteopenia, above average risk of fracture.
88
Describe the general management of osteoporosis. (LO6)
- Diet - protein, vitamin D, calcium.
- Exercise.
- Lifestyle.
- Treat underlying diseases.
- Drug treatment.
- Falls intervention - medical, OT, physio.
89
What categories of drugs could be used to treat osteoporosis? (LO6)
- Anti-resorptive.
- Anabolic.
- Both (strontium ranelate has now been withdrawn).
90
List some examples of anti-resorptive therapy for osteoporosis. (LO6)
- Bisphosphonates - alendronate, ibandronate, risedronate, zoledronic acid.
- Calcium and vitamin D.
- Denosumab.
- Hormone replacement therapy.
- Calcitriol.
- Raloxifene.
91
Give an example of anabolic therapy for osteoporosis. (LO6)
Intermittent PTH - teraparatide.
92
Give an example of an osteoporosis therapy that combines both resorptive and anabolic treatment. (LO6)
Strontium ranelate - withdrawn.
93
Describe the prognosis of osteoporosis. (LO6)
- With preventative treatment, fragility fractures of the hip, vertebrae and wrist can be avoided.
- Prognosis is good for people at risk of osteoporosis if steps are taken to prevent decline in bone density and strength.
Duration of treatment:
- Uncertain.
- 3-5 years, 10 years with denosumab.
- Drug holidays - planned period of a patient ceasing a regular medication. Can be done to maintain sensitivity to the drug.
- Side effects of treatment - osteonecrosis of the joint, atypical fracture, atrial fibrillation, GI.
- Steroids - early bone loss.
94
List the consequences of a hip fracture as a result of osteoporosis. (LO6)
- 20% of patients die within a year.
- 50% of survivors are incapacitated.
- 20% require long-term residential care.
- High risk of future fracture or mortality.
95
List the most common fracture sites as a result of osteoporosis. (LO6)
- Hip: 3% of men, 14% of women.
- Vertebrae: 2% of men, 11% of women.
- Forearm: 2% of men, 13% of women.
- 8.9 million osteoporotic fractures occur worldwide with 1/3 in Europe. 18% of these are hip fractures.
- 180,000 in England and Wales per year.
96
List some indications for the use of paracetamol. (LO7)
- Cold.
- Flu.
- Fever/extremely high temperature.
- All sorts of pain (e.g. muscle pain, headache, earache, tooth pain, ligament, etc.)
97
List some contraindications for the use of paracetamol. (LO7)
- Liver disease.
- Severe malnutrition.
- Kidney disease.
- Alcohol addiction.
- Allergy to paracetamol.
- Other possible factors putting the patient at risk.
98
Describe the mechanism of paracetamol in the body. (LO7)
- Precise mechanism of drug action is still unclear.
- No real evidence of paracetamol having significant action on COX-1 and COX-2 enzymes.
- Is thought to work by inhibiting prostaglandin synthesis in the brain while having little effect on peripheral prostaglandin production.
99
List the potential routes of administration of paracetamol. (LO7)
- Oral (max. 4g daily) - most common, OTC.
- Rectal - use if difficulty swallowing an oral pill.
- Intravenous - short-term treatment of moderate pain, especially following surgery. Short-term treatment of fever, when i.v. route is clinically justified by an urgent need to treat pain or hyperthermia and/or when other routes are not possible.
100
List some indications for the use of NSAIDs. (LO7)
- Pain.
- Inflammation.
- E.g. menstrual pain, fever, swelling, etc.
101
List some contraindications for the use of NSAIDs. (LO7)
- Chronic kidney disease.
- Liver cirrhosis.
- Heart failure.
- Severe asthma - NSAID may exacerbate.
- Allergy to the particular NSAID.
- GI tract-related illness, e.g. Crohn's disease.
- Ulcerative colitis.
- Blood-clotting disorder.
102
Describe the mechanism of NSAIDs in the body. (LO7)
- NSAIDs inhibit the cyclo-oxygenase (COX) and prostaglandin H synthase enzymes.
- This inhibits the conversion of arachidonic acid into prostaglandins.
- The result: pain stimuli is inhibited to some extent as pain intensity is decreased. Inflammation is reduced as well as fever.
103
List the potential routes of administration of NSAIDs. (LO7)
- Oral - most common.
- Topical cream - for pain relief in osteoarthritis.
- Intravenous infusion - for acute-moderate pain or pyrexia in hospital.
- Rectal - when unable to take oral NSAIDs, e.g. constant vomiting.
104
List some indications for the use of opioids. (LO7)
- Severe acute pain.
- End-of-life pain.
- Pain which is not relieved by paracetamol or NSAIDs.
105
List some contraindications for the use of opioids. (LO7)
- Acute respiratory distress.
- Comatose patients.
- Head injury - opioids interfere with pupillary responses needed for neurological assessment.
- Raised intracranial pressure.
- Risk of paralytic ileus.
- History of addiction possibly.
106
Describe the mechanism of opioids in the body. (LO7)
- Opioid produces effects on neurons by acting on G receptors (3 types) located on neuronal cell membranes.
- They have an effect on ion channels on neuronal membranes through a direct G protein coupling to the channel.
- Opioids promote the opening of potassium channels and inhibit the opening of voltage-gates calcium channels.
- Decreases neuronal excitability and reduce transmitter release (due to inhibition of Ca2+ entry).
107
List the potential routes of administration of opioids. (LO7)
- Morphine - oral/intravenous/intrathecal/intramuscular.
- Codeine - oral.
- Diamorphine - oral/intravenous (in palliative care).
- Methadone - oral/intravenous.
- Remifentanil - intravenous infusion.
- Naloxone - intravenous.
- Fentanyl - intravenous/epidermal/transdermal patch.
- Buprenorphine - epidermal patch and intravenous/intramuscular injection.
108
Describe the basic epidemiology of spinal fractures. (LO8)
- Around 15 in 1,000,000 suffer a spinal injury in the UK every year.
- Road traffic accidents account for >50%.
- Other causes: accidents at home, falls, industrial accidents, sports injuries and assault.
- Most spinal fractures are vertebral compression fractures (VCF).
- Mid-thoracic and thoracolumbar spine are most susceptible.
- Osteoporosis is a risk factor (pathological fracture).
- Spinal fractures make up 46% of osteoporotic fractures.
- Nearly 90% of >80 year olds show radiological evidence of chronic vertebral fragility crush fracture.
- >50 years of age: 1 in 2 women and 1 in 5 men will suffer osteoporotic fracture.
109
What is a vertebral compression fracture (VCF)? (LO8)
- Wedge fracture.
- Where only the anterior portion of the vertebra is crushed.
- Causes kyphotic distortion and over time, "round shoulders".
110
Describe the presentation of spinal fractures. (LO8)
- Pain.
- Paraesthesia.
- Radiation down the arms.
- Muscle spasm.
- Localised tenderness.
- Weakness.
- Bowel/bladder changes - urinary retention.
- Transection above sympathetic outflow (4th dorsal vertebrae) causes bradycardia and hypotension.
- Multiple fractures over time = loss of height.
111
List the investigations for spinal fractures. (LO8)
- Estimated only 1/3 VCFs are diagnosed by physicians.
- Full history and neurological examination (muscle strength, tone, sensation).
- Lateral x-ray + through open mouth to show odontoid.
- CT.
- DEXA scan if suspected osteoporosis.
112
Describe the management of spinal fractures. (LO8)
- Assume it's a cervical spine injury until disproved.
- Immobilise the fracture if it's unstable.
- Fusion if non-union.
- Depending on height and fracture type, decompression and traction.
- Stable fractures - analgesia.
- Reduce future risk - bisphosphonates, observe and treat for spinal shock.
- Halo jacket - atlas (C1).
113
Describe the prognosis of spinal fractures. (LO8)
- Severity of loss of function depends on level of spinal cord injury.
- The patient with damage above C4 is unlikely to survive because of paralysis of all respiratory muscles.
- Spinal cord syndrome prognosis is better under the age of 50. 97% of patients recover. Only 17% of patients over 50 recover.
114
List the types of spinal fracture. (LO8)
- Compression: burst fracture (potentially unstable).
- Flexion compression: anterior wedge fracture. Possible disruption of posterior ligaments.
- Flexion rotation: shearing of all restraining ligaments. Unifacet or bifacet dislocations. These fractures are the commonest cause of neurological damage.
- Hyperextension: disruption of the anterior structures. These fractures may cause momentary cord compression leading to 'central cord syndrome'.
115
How do we obtain vitamin D? (LO9)
1. Diet (D3).
| 2. Synthesis from skin (D2).
116
How is vitamin D obtained from diet/skin converted to its active form? (LO9)
- 7-dehydrocholesterol interacts with UVB from sun exposure and is converted to cholecalciferol (D3) which is also obtained through our diet.
- D3 is hydroxylated to 25-hydroxycalciferol, 25(OH)D3 in the liver.
- 25(OH)D3 is hydroxylated further to 1,25-dihydroxycalciferol, 1,25(OH)D3 in the kidney.
117
List the functions of 1,25(OH)D3 (active form of vitamin D) in relation to bone. (LO9)
- MAIN FUNCTION: increased mineralisation of bone matrix. Part of this is due to the raised Ca2+ levels from the gut. Stimulates proliferation and activity of osteoblasts.
- Stimulator of intestinal calcium and phosphate absorption (but only at high concentrations).
118
What characteristic condition develops with a vitamin D deficiency? (LO9)
Osteomalacia - due to insufficient bone mineralisation.
119
List the risk factors for vitamin D deficiency. (LO9)
20% of the general population has vitamin D deficiency status.
- Dark skin.
- Insufficient UVB exposure - e.g., concealing clothing.
- Obesity.
- Adolescents.
- Frail/elderly.
- Exclusively breast fed babies.
- Extras: renal disease, GI disorders, coeliac disease, ICU patients, severe liver disease, cystic fibrosis, TB, HIV.
120
Describe the presentation of vitamin D deficiency in adults and children. (LO9)
- Fatigue.
- Generalised muscle, joint and bone pain.
- Hyperalgesia (increased sensitivity to pain).
- Muscle weakness: especially extremities and pelvic region, manifesting in difficulty in rising from sitting/squatting or a waddling gait.
- Fragility fractures with prolonged bone loss.
- Very non-specific symptoms.
121
Describe the presentation of vitamin D deficiency ONLY occurring in children. (LO9)
- Bone deformities (rickets).
- Cardiac problems.
- Hypocalcaemic fits.
122
List the 10 hallmarks of a cancer cell. (LO10)
- Sustain proliferative signalling.
- Evade growth suppressors.
- Avoid immune destruction.
- Enable replicative immortality.
- Tumour-promoting inflammation.
- Activate invasion and metastasis.
- Induce angiogenesis.
- Genome instability and mutation.
- Resist cell death.
- Deregulating cellular energetics.
123
Describe what is meant by a dominant driver mutation in terms of a cancer genome. (LO10)
Activation of proto-oncogenes into oncogenes.
124
Describe what is meant by a recessive driver mutation in relation to a cancer genome. (LO10)
Inactivation of tumour suppressor genes.
125
Describe what is meant by a driver mutation in relation to a cancer genome. (LO10)
Alteration of the genome of a cancer cell which gives it a growth advantage.
126
Describe what is meant by a passenger mutation. (LO10)
- Has no effect on the fitness of the cell.
| - It just happens to be in the same cell as the mutation in the driver gene and therefore is also multiplied.
127
Describe what is meant by an oncogene. (LO10)
In a normal state, the cell has proto-oncogenes but in a cancerous cell, proto-oncogenes mutate and become oncogenes which drive uncontrolled cell growth.
128
List the 5 mechanisms of change in cancer genomes. (LO10)
- Substitutions.
- Deletions.
- Insertions.
- Translocations (break points).
- Copy number change.
129
Describe the role of TP53. (LO10)
- Codes for tumour suppressor protein P53 which stops cells growing or dividing in an uncontrolled way.
- It activates repair genes for DNA which is damaged, however if it is unrepairable, then it signals for apoptosis.
- There is inherited familial mutations of the TP53 gene in Li-Fraumeni syndrome which leads to early onset tumours.
130
What system is used to classify tumours and how are they categorised? (LO11)
The histogenetic classification system. This system classifies tumours based on the cell of origin as well as whether the tumour is malignant or benign.
131
What name is given to a tumour derived from epithelial cells? (LO11)
- Carcinoma.
- Suffix for malignant tumours: -carcinoma.
- Suffix for benign tumours: -oma.
132
What name is given to a tumour (benign and malignant) derived from glands or showing gland formation (form of epithelial cells)? (LO11)
- Malignant: adenocarcinoma.
| - Benign: adenoma.
133
What name is given to a malignant tumour derived from squamous epithelial cells? (LO11)
Squamous cell carcinoma.
134
What name is given to a tumour derived from connective/mesenchymal tissue? (LO11)
- Sarcoma.
- Suffix for malignant tumours: -sarcoma.
- Suffix for benign tumours: -oma.
135
List some common tissues of origin for connective/mesenchymal tissue tumours (6). (LO11)
- Adipose tissue.
- Blood vessels.
- Skeletal muscle.
- Smooth muscle.
- Schwann cells.
- Fibroblasts.
136
What name is given to a tumour (malignant and benign) derived from adipose tissue? (LO11)
- Malignant: liposarcoma.
| - Benign: lipoma.
137
What name is given to a tumour (malignant and benign) derived from blood vessels? (LO11)
- Malignant: angiosarcoma.
| - Benign: haemangioma.
138
What name is given to a tumour (malignant and benign) derived from skeletal muscle? (LO11)
- Malignant: rhabdomyosarcoma.
| - Benign: rhabdomyoma.
139
What name is given to a tumour (malignant and benign) derived from smooth muscle? (LO11)
- Malignant: leiomyosarcoma.
| - Benign: leiomyoma.
140
What name is given to a tumour (malignant and benign) derived from schwann cells? (LO11)
- Malignant: malignant peripheral nerve sheath tumour (MPNST).
- Benign: schwannoma.
141
What name is given to a tumour (malignant and benign) derived from fibroblasts? (LO11)
- Malignant: fibrosarcoma.
| - Benign: fibroma.
142
What name is given to a tumour derived from lymphocytes? (LO11)
- Lymphoma - malignant tumour of lymphocytes involving lymph nodes.
- Leukaemia - malignant lymphocytes present in the bone marrow or in peripheral blood.
- (leukaemia is also the name given to malignant tumours of haematopoietic cells.)
143
What name is given to a tumour derived from haematopoietic cells? (LO11)
Leukaemia.
144
What is the basis of tumour grading? (LO11)
Tumour grading tells us how closely the tumour resembles the tissue from which it's derived. This shows us how aggressive the tumour is likely to be. The higher the tumour grade, the more aggressive in behaviour and the faster it will grow and spread. Prognosis also worsens as tumour grade increases.
- Grade 1 tumour: well-differentiated, closely resembles parent tissue.
- Grade 3 tumour: poorly differentiated, not very similar to parent tissue.
145
What is the basis of tumour staging? (LO11)
Tumour staging tells us about the extent of tumour spread. We use the TNM system to describe this.
146
Describe the TNM system used for tumour staging. (LO11)
T:
- Size of the primary tumour or extent of invasion of the primary tumour.
- Suffixed by a number denoting the tumour size or extent. The number varies according to the organ concerned - e.g. T1, T2, T3.
N:
- Metastasis to the lymph nodes draining the organ where the tumour has originated.
- Suffixed by a number denoting the number of lymph nodes or groups of nodes containing metastases.
M:
- Anatomical extent of distant metastases.
T stage has the best prognosis, M stage has the worst.
147
BONUS: giving an example of oesophageal carcinoma, what does each of the tumour stages signify? (LO11)
T1: tumour has invaded the lamina propria, muscularis mucosae or submucosa.
T2: tumour invades the muscularis propria.
T3: tumour invades the adventitia.
T4: tumour invades adjacent structures such as the diaphragm for lower oesophageal tumours.
148
Describe the relationship between tumour stage and prognosis. (LO11)
As cancer stage progresses, patient survival decreases. Therefore, the benefit of adjuvant therapy (chemotherapy) increases.
149
List the 3 main models for healthcare funding. (LO12)
- Taxation.
- Private health insurance.
- Social health insurance.
150
Which of the healthcare models represents the NHS and how does it work? (LO12)
- NHS England is mostly funded through taxation and contributions from national insurance.
- The NHS is "free at the point of use".
- Some services must be paid for, e.g. prescriptions (£9.15 per item). However, due to exemptions, 90% of prescriptions are free of charge.
151
List some other countries that rely on taxation for funding. (LO12)
- Australia.
- New Zealand.
- Canada.
- However, none of these rely on taxation alone, e.g. 30% of Canada's healthcare funding originates directly from the patient and from health insurance.
152
Who would use private healthcare in the UK? (LO12)
Those in higher income groups for quicker access or access to better services.
153
Describe what is meant by social health insurance. (LO12)
- People generally contribute based on their salary as opposed to their health issue or other factors that affect private health insurance.
- Their employer will generally match their contribution.
- It is also possible to opt out of this in some countries, e.g. Germany if you earn over 57,600 euros and purchase private health insurance.
- In some countries, such as France, there are "sin taxes" on alcohol/tobacco which are contributed to the health care system.
154
How does private health insurance and funding work in the US? (LO12)
- Private health insurance is contributed to regularly by policy holder and varies based on age, family, history, pre-existing medical conditions, along with geographical location and job.
- In some countries such as Switzerland, public health insurance is mandatory.
- The majority of people in the US receive their cover through their employer, however they may also have to contribute through payments.
- There are also 2 publicly funded plans - Federal Medicare plan (for the old and disabled) and the state run Medicaid (for people on low-income).
- There are however a significant number of people without access to healthcare due this system.
155
Which systems do opioids have a pharmacological effect on? (LO13)
- CNS.
- GI.
- Respiratory.
156
List some adverse effects of opioid use. (LO13)
- Tolerance.
- Dependence.
- Chronic - constipation.
- Acute - sedation, respiratory difficulty, vomiting.
157
Briefly describe the uses of morphine. (LO13)
- Used to help with severe pain.
- Often prescribed with an anti-emetic.
- Often prescribed with laxatives for long-term use.
158
List the possible routes of administration for morphine. (LO13)
- Oral.
- Intravenous.
- Topical.
- Intramuscular.
- Best results when injected.
159
Briefly describe some features of morphine. (LO13)
- Short half-life.
| - Administered every 4 hours.
160
Describe the features of diamorphine. (LO13)
- More potent and soluble than morphine so only need half the dose.
- Used often in palliative care as it works best when patients need constant pain relief through syringe drivers.
- Used for analgesic effect for relief of pain associated with surgery, heart attack or for pain in terminally ill patients.
- A pro-drug (metabolised into active form once in the body).
- Active form is 6-monoacetylmorphine and morphine.
- Works quickly as it crosses the blood-brain barrier (BBB) easily.
161
Describe features of codeine. (LO13)
- A pro-drug that is demethylated in the liver by cytochrome P2D6 to become morphine.
- Often given in combination of paracetamol and codeine.
- Reasonably well-absorbed orally.
- Only a small part is converted to morphine at a time.
- Provides strong analgesia.
- Reaction to codeine is hard to predict.
162
What is codeine used for? (LO13)
- Mild to moderate pain.
- When NSAIDs are not appropriate.
- When patients may have chronic diarrhoea, e.g. chronic irritable bowel disease (IBD).
163
Describe features of methadone. (LO13)
- A synthetic opioid.
- Good oral absorption.
- Long half-life (>24 hours).
- Substitution therapy for IV drug addiction.
- Part of supervised regime.
- Long half-life means any overdose could be highly toxic.
