Musculoskeletal 1 - Metabolic Bone Disease - Histopathology Flashcards

1
Q

What are 4 functions of bone

A
  1. Structure - gives structure and shape to body
  2. Mechanical - sites for muscle attachment
  3. Protective - vital organs and bone marrow
  4. Metabolic - Ca reserve and other minerals
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2
Q

Describe the composition of bone

A

65% Inorganic - calcium hydroxyapatite, stores 99% of Ca in body, and loads of P, Mg, Na

35% organic - bone cells and protein matrix

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3
Q

Describe bone geography

A

Split into Diaphysis (shaft part) and Epiphysis (articular part)

Diaphysis = medulla inside (bone marrow is in medullary cavity), then cortex, then periosteum

Epiphysis = articular cartilage, subchondral bone, epiphyseal line

Metaphysis = region between diaphysis and epiphysis

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4
Q

What are the 5 anatomical types of bone

A
  1. Flat - cranial bones, ribs, protective
  2. Long - tibia, femur, support weight and movement
  3. Short/cuboid - carpals/tarsals, stabilise and facilitate movement
  4. Irregular - vertebrae, pelvis, specific shape allowing to protect specific organ
  5. Sesamoid - patella, embedded in tendons, protective
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5
Q

Describe the macroscopic structure of bone

A
  1. Trabecular/spongy/cancellous bone

2. Cortical compact bone

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6
Q

Describe the microscopic structure of bone

A
  1. Woven bone (immature - low strength)

2. Lamellar bone (mature)

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7
Q

Describe the differences between cortical bone and cancellous(/trabecular/spongy) bone

A

Cortical = long bones, 80% of skeleton, appendicular, 80-90% calcified (as slow turnover so lots of time to get mineralised), structural, mechanical and protective function

Cancellous/Trabecular/Spongy - Vertebrae and pelvis, 20% skeleton, axial, 15-25% calcified (high turnover), mainly metabolic function (deposit minerals etc) and facilitated by large SA

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8
Q

Describe cortical bone microanatomy

A

Circular bones = osteons, consist of circular layers of lamellar bone. Centred around a Haversian canal with blood vessels.

Interstitial lamellae between circles

On the outside of bone - circumferential lamellae

Osteocytes with dendritic processes form a network

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9
Q

Do trabecular lamellae have a Haversian canal?

A

No, they form in layers instead

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10
Q

Mature lamellar bone has striations with lamellae. What about woven bone?

A

Has no lamellae, disorganised structure, collagen is disorganised - hence weaker

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11
Q

What are the 3 types of bone cells

A
  1. Osteoclasts - multinuclear cells part of macrophage family - they resorb bone
  2. Osteoblasts - produce osteoid which forms new bone
  3. Osteocytes - mechanosensory network embedded in mature bone
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12
Q

Explain the bone remodelling cycle

A
  1. Osteocyte apoptosis releases RANKL.
  2. RANKL binds to osteoclasts and stimulates resorption
  3. Reversal cells are put onto bone, signalling osteoblasts, and eventually osteoblasts lay down osteoid

Osteoblasts also produce RANKL and M-CSF which regulates/precurses osteoclasts.

Osteoblasts produce OPG - osteoprotegerin, which competitively binds RANKL and inhibits resorption

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13
Q

What do osteoblasts and osteocytes look like histologically

A

Osteoblasts = cuboid cells on lining of bone

Osteocytes = cells embedded in bone

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14
Q

What are the uses of bone biopsy

A
  1. Confirm diagnosis of bone disorder
  2. Find cause/evaluate ongoing bone pain/tenderness
  3. Investigate abnormality on Xray
  4. Bone tumour diagnosis
  5. Determine cause of unexplained infection
  6. Evaluate therapy performance
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15
Q

What are canaliculae

A

Channels that osteocytes use to communicate to bone surface

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16
Q

What is a Haversian canal

A

Channels in cortical canals that blood vessels travel through

17
Q

What are the 2 types of bone biopsy

A
  1. Closed biopsy - using needle, core biopsy (e.g. Jamshidi needle)
  2. Open biopsy - for sclerotic/inaccessible lesions
18
Q

What histological stains can be used?

A
  1. H & E stain
  2. Masson-Goldner trichrome stain - to tell between unmineralised and mineralised bone
  3. If you want to look at bone turnover, use tetracycline/calcein labelling
19
Q

What is metabolic bone disease

A

Group of diseases that reduces bone mass and strength

Caused by imbalance of various chemicals in the body

Causes altered bone cell activity, rate of mineralisation, or changes in bone structure

20
Q

Name 5 common metabolic bone diseases

A
  1. Osteoporosis
  2. Osteomalacia/Rickets
  3. Primary hyperparathyroidism
  4. Renal osteodystrophy
  5. Paget’s disease
21
Q

What is osteoporosis and what are the risk factors

What are the 2 types of osteoporosis

A

Osteoporosis = bone mineral density T-score of -2.5 or lower (BMD is 2.5 SDs below mean peak BMD for their sex)

Primary RF = age, post menopause

Secondary RF = drugs, systemic disease

2 types = high turnover (high osteoclast relative to osteoblast) and low turnover (low osteoblast relative to osteoclast)

22
Q

Which type of bone does osteoporosis affect most

A

Trabecular/cancellous/spongy bone - highly metabolic

23
Q

What is osteomalacia

What are the 2 types

A

Defective mineralisation of normally synthesised bone matrix (aka rickets in children)

Type 1 - caused by Vit D deficiency

Type 2 - caused by PO4 (phosphate) deficiency

24
Q

How does Vit D deficiency cause osteomalacia

A

Vit D acquired from sunlight or diet - activated in liver and kidney - causes Ca absorption in intestines and Ca reabsorption in kidney. Therefore a lack of it causes hypocalcaemia - causing osteomalacia

25
Q

What are the symptoms of osteomalacia

A
  1. bone pain/tenderness
  2. fracture
  3. Proximal weakness
  4. Bone deformity
26
Q

What are Loosers zone fractures?

A

Pseudo fractures that occur in areas of high tensile stress - typically at right angles to the cortex, occur partway into the bone and have symmetrical sclerotic margins

27
Q

How can hyperparathyroidism be a cause of MBD

A

Excess PTH

This causes increased PO4 and Ca excretion in urine - leading to hypercalcaemia and hypophosphatemia —> this may lead to skeletal changes of osteitis fibres cystica

28
Q

Which 4 organs are affected in hyperparathyroidism

A
  1. Parathyroid glands
    2 Bones
  2. Kidneys
  3. Proximal SI
29
Q

What are the primary and secondary causes of hyperparathyroidism

A

Primary -

  1. Parathyroid adenoma
  2. Chief cell hyperplasia

Secondary

  1. Chronic renal deficiency
  2. Vit D deficiency
30
Q

What is a useful mnemonic to remember the symptoms of hyperparathyroidism

A
  1. Stones - Ca oxalate renal stones
  2. Bones - osteitis fibrosa cystica, bone resorption
  3. Abdominal groans (acute pancreatitis)
  4. Psychic moans (psychosis and depression)

Stones, bones, groans and moans

31
Q

How may hyperparathyroidism present on an x ray, histologically,

A

X ray - lesions in hand

Histologically -

  1. tunnelling erosion in trabeculae - centre of trabeculae have been eaten away
  2. Brown cell tumour, giant cells surrounding blood vessels - causes a pattern of giant cells, fibrous tissue and reactive bone outside it
32
Q

What does renal osteodystrophy involve

A

All the skeletal changes resulting from chronic renal disease

Includes:

  1. Increased bone resorption
  2. Osteomalacia
  3. Osteosclerosis
  4. Growth retardation
  5. Osteoporosis
33
Q

What is Paget’s Disease

A

Disorder of bone turnover - >40y/o usually

Sometimes it can be mono-osmotic (15%) but usually multiple bones affected

3 stages:

  1. Osteolytic
  2. Osteolytic-osteosclerotic
  3. Quiescent osteosclerotic
34
Q

Which 2 genes may be affected that cause Paget’s disease

A
  1. RANK
  2. SQSTM1

Autosomal inheritance - incomplete penetrance

35
Q

What are the clinical symptoms of Paget’s disease

A
  1. Pain
  2. Microfractures
  3. Nerve compression
  4. Skull changes - may put medulla at risk
  5. Deafness
  6. Haemodynamic changes/Cardiac failure
  7. Hypercalcaemia
  8. Rare but sarcoma development
36
Q

What may Pagets disease look like x ray and histologically

A

X ray - thickened cortices, osteolytic black spots in medullary cavity

Histologically - usually see high turnover of bone with osteoclast resorbing bone. Later stages looks like disorganised bone with cement lines