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Musculoskeletal pathology quiz
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What bone tumour is associated with lifting of periosteum off bone producing the Codman triangle and a sunburst appearance on X-ray?
Question 1 Explanation:
An osteosarcoma is a malignant proliferation of osteoblasts. The clinical features include bone pain with swelling. It is prevalent in teens and the elderly. Risk factors include Paget's disease, familial retinoblastoma and radiation. It usually manifests in the region of the knee. Imaging reveals the Codman triangle and sunburst appearance.
Acute gout presents as painful inflammation of the big toe which is referred to as podagra. What is an acute treatment for gout?
Question 2 Explanation:
Colchicine inhibits microtubule polymerization by binding tubulin. This impairs neutrophil chemotaxis and degranulation. In acute gout, monosodium urate crystals are deposited in joint generating an inflammatory response. Colchicine can therefore treat this condition by reducing inflammation by impairing neutrophil response. Other drugs used for acute treatment are glucocorticoids and NSAIDs (e.g. naproxen).
Allopurinol, febuxostat and probenecid are chronic gout drugs (preventative).
On biopsy, a mosaic pattern of lamellar bone is revealed. What disease is associated with these results?
Sickle cell disease
Paget's disease of bone
Question 3 Explanation:
Paget's disease is possibly caused by a paramyxovirus infection of the osteoclasts of the affected bone. It can be monostotic or polyostotic. It is characterized by an imbalance between osteoclasts and osteoblasts. There are 3 phases- an osteoclastic phase, a mixed osteoclastic- osteoblastic phase followed by an osteoblastic phase. This will result in abnormally thick bone that fractures easily. Biopsy shows the ‘mosaic pattern of lamellar bone’ which resembles puzzles pieces put together.
Clinical findings include bone pain, lion-like facies, hearing loss and increasing hat size. The complications are osteosarcoma as osteoblasts can get mutated in the disorder and high output cardiac failure as AV shunts are formed in the bone.
What is the pathogenesis of osteopetrosis (marble bone disease)?
Poor osteoclast function due to a carbonic anhydrase II mutation
Defective mineralization of osteoid
Reduction in trabecular bone mass
Imbalance between osteoclast and osteoblast activity with an osteoclastic phase, a mixed osteoclastic- osteoblastic phase followed by an osteoblastic phase
Question 4 Explanation:
An acidic environment is needed for osteoclasts to remove calcium from bone. A defect in maintaining this acidic environment, leads to poor bone resorption by osteoclasts resulting in overgrowth and sclerosis of cortical bone. This abnormally thick bone fractures easily. Clinical features include bone fractures, anaemia, thrombocytopenia (due to bony replacement of marrow) and visual/ hearing loss due to cranial nerve compression. The patient can also develop renal tubular acidosis (defect in carbonic anhydrase leads to decreased reabsorption of bicarbonate) and hydrocephalus (narrowing of foramen magnum).
Achondroplasia is a disorder of bone whereby there is a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene leading to impaired cartilage proliferation in the growth plate.
Why is it that affected children have a normal sized head and vertebral column whilst arms and legs are shortened?
Growth hormone and insulin like growth factor 1 levels only affect long bones
Intramembranous bone formation (flat bones) vs endochondral bone formation (long bones)
Flat bones are less susceptible to fracture
Difference in bone density
Question 5 Explanation:
In achondroplasia, there is poor endochondral bone formation but intramembranous bone formation is unaffected. Endochondral bone formation is the mechanism by which long bones grow, cartilage matrix is formed and is then replaced by bone. However, in intramembranous bone formation, the mechanisms by which flat bones grow (e.g. rib cage, skull) there is no pre-existing cartilage matrix. Note that growth hormone and insulin-like growth factor 1 levels are normal in this disease.
Which joint disease is associated with morning stiffness that improves with activity?
Rheumatoid arthritis (RA)
Question 6 Explanation:
RA is a systemic and autoimmune disorder associated with chronic joint inflammation. HLA-DR4 link. An important clinical feature to distinguish it from osteoarthritis is the morning stiffness that improves with use. With osteoarthritis, a degenerative joint disease, the joint stiffness worsens during the day.
Synovial fluid was sampled for a joint condition and rhomboid shaped crystals with weak positive birefringence under polarised light were found.
What joint disease is this an indicator of?
Question 7 Explanation:
Pseudogout has a similar presentation to gout clinically but it is due to deposition of calcium pyrophosphate dihydrate (CPPD) in tissues especially the joint, unlike the deposition of monosodium urate crystals seen in gout. Synovial fluid analysis will reveal rhomboid crystals with weak positive birefringence under polarized light compared to gout for which there are needle-shaped crystals with negative birefringence under polarised light (yellow when parallel) in synovial fluid.
What bone disorder is caused by an autosomal dominant defect in the synthesis of collagen type 1?
Question 8 Explanation:
Osteogenesis imperfecta is also known as ‘brittle bone disease’. It is a congenital defect of bone formation. Clinical findings include multiple pathologic fractures (often child abuse suspected), blue sclera due to thin scleral collagen revealing the underlying choroidal veins and deafness due to fracture of bones in the middle ear.
What are the key lab features in osteomalacia?
Normal serum calcium, normal serum phosphate, normal PTH, normal alkaline phosphatase
Active vitamin D is responsible for raising serum calcium and phosphate levels by acting on the kidney (↑ reabsorption of calcium and phosphate), intestine (↑ absorption of calcium and phosphate) and bone (↑ resorption of calcium and phosphate). Thus if vitamin D is reduced, serum calcium and phosphate will also be reduced. Parathyroid hormone (PTH) is increased to compensate for the low calcium level. Alkaline phosphatase is increased as there is osteoblast hyperactivity- osteoblasts produce osteoid but there is defective mineralization of the osteoid and the mineralization is needed to form bone, so there is an excess of osteoid.
Select the cause/s of vitamin D deficiency.
Minimal sun exposure
Liver failure and renal failure
A patient presents with a heliotrope rash, a malar rash and Gottron's papules on the elbows and knees. She cannot comb her hair or climb the stairs due to muscle weakness. Lab results show an increased creatine kinase, positive antinuclear antibody (ANA) and anti-Jo-1 antibody. Biopsy reveals perimysial inflammation with perifascicular atrophy. She is treated with corticosteroids.
What disease does the patient have?
X- linked muscular dystrophy
Question 11 Explanation:
The patient has dermatomyositis which is an inflammatory disorder affecting the skin and skeletal muscle. This clinical scenario highlights important characteristics of the disease presentation, investigations and management.
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