Metabolic bone disease overview and histopathology Flashcards Preview

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Flashcards in Metabolic bone disease overview and histopathology Deck (77)
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1
Q

What is the definition of metabolic bone disease?

A

A group of diseases that cause a decrease in bone density and strength, either by increasing bone resorption or decreasing bone formation

2
Q

What are the main metabolic bone diseases?

A
Primary hyperparathyroidism
Rickets/osteomalacia
Osteoporosis
Paget's disease
Renal osteodystrophy
3
Q

What are the symptoms of metabolic bone disease? (metabolic and bone)

A
Metabolic-
Hypo/hypercalcaemia- hypo causes pins and needles, seizures and cardiac conduction problems
Hypo/hyperphosphataemia 
Bone-
Low phosphate - renal damage
High phosphate - precipitation with calcium to form calcium phosphate, causing widespread tissue damage including atherosclerosis
Pain
Deformity
Fractures
4
Q

What is calcium mainly stored as in bone?

A

Inorganic hydroxyapatite

5
Q

What type of bone is very metabolically active?

A

Cancellous (particularly in the vertebrae)

6
Q

What is the continuous remodelling of bone?

A

Bone is resorbed and replaced 5% at any time

7
Q

What does the continuous remodelling require?

A

Continuous exchange of ECF with bone fluid reserve

8
Q

In regards to clinical medicine, what is the main concern with bone?

A

Tendency to fracture

9
Q

What two aspects of bone are important in terms of bone strength and therefore possible fracture risk?

A

Quantity- Cortical thickness, mineral density, size
Quality- Architecture, bone turnover (low- no mending and high- too fragile), cortical porosity (holes mnade during remodelling are weak), trabecular connectivity (connections within cancellous bone)

10
Q

How is the tibia modelled during growth?

A

Bone is added, more in the anterior/posterior direction due to the stresses put on the tibia bone during walking- modelling occurs at areas of higher stress

11
Q

How do you assess bone structure and function? (4)

A

Bone histology
Biochemical tests
Bone mineral densitometry e.g. in osteoporosis
Radiology e.g. osteomalacia

12
Q

What is the function of bone? (3)

A

Mechanical- support and site for muscle attachment allowing movement and strength
Protective- vital organs, bone marrow
Metabolic- main reserve of calcium, allowing release and storage of calcium

13
Q

What is the difference between bone and all other organs?

A

It is naturally mineralised

14
Q

What is bone naturally comprised of?

A
Inorganic calcium hydroxyapatite (65%)
Organic (35%):
- Collagen matrix (type 1 mainly)
- Water
- Non-collagenous protein and carbohydrate
15
Q

What is calcium hydroxyapatite?

A

Inorganic salt formed by calcium and phosphate which acts as a storehouse for 99% of the Ca in the body, 85% of phosphate and 65% Na and Mg

16
Q

What are the two parts of a bone?

A

Diaphysis (long shaft)

Epiphysis (head of bone)

17
Q

What is a facet joint?

A

Small articular surfaces at synovial joints that enable bone to act as a lever in joints

18
Q

What does articular cartilage do?

A

Provide a frictionless surface

19
Q

What does periosteum do?

A

Surrounds bone, providing a protective covering as well as pathways for blood vessels to enter the bone itself

20
Q

What are condyles?

A

Knuckle shaped prominence at the end of the bone

21
Q

What is the cortex of the bone like and what does it do?

A

It is thick and strong and is the part of the bone to which muscles attach

22
Q

What is the medulla of the bone like and what occurs in the medulla?

A

Soft trabecular/cancellous bone where most metabolism occurs

23
Q

Where are cortical bones found?

A

They are usually long and form 80% of the human skeleton (appendicular)

24
Q

Where are cancellous/trabecular bones found?

A

Forms 20% of human skeleton (axial)- especially present in vertebrae and pelvis

25
Q

What are the indications for use of bone biopsy?

A

Investigating an abnormality seen on x-ray
Evaluate bone pain or tenderness
Bone tumour diagnosis
Determining the cause of unexplained infection
Evaluating the progress of therapy

26
Q

What are the two types of bone biopsy and when are they both used?

A

Closed (Jamshidi needle core biopsy in the iliac crest)- used most commonly as less risk
Open- for sclerotic or inaccessible lesions

27
Q

What is cartilage?

A

Load bearing tissue composed predominantly of type 2 collagen and a variable amount of elastic fibres

28
Q

Where is elastic cartilage found?

A

Ears, nose, epiglottis and larynx

29
Q

Where is hyaline cartilage found and what is it effective at?

A

It is present on the ends of long bones and is very effective as a shock absorber and resists large compressive forces generated by weight transmission

30
Q

What are osteoblasts?

A

Bone cells that build bone by laying down osteoid (uncalcified)

31
Q

What are osteoclasts?

A

Multinuclear bone cells of the macrophage family which resorb or chew bone

32
Q

What are osteocytes?

A

Osteoblast-like cells which sit in lacunae in bone

33
Q

What do osteocytes do after microdamage to bone, following mechanical stress, exposure to some cytokines or at random?

A

Secrete messages to the surface cells (stromal)

34
Q

What do stromal cells do once activated by messages from osteocytes?

A

Produce M-CSF (macrophage colony stimulating factor)- this causes differentiation of cells into pre-osteoclasts
Divide to produce pre-osteoblasts

35
Q

What do pre-osteoclasts have?

A

Membrane receptors called RANK (receptor activator for nuclear factor kB)

36
Q

What do pre-osteoblasts express?

A

RANK ligand

37
Q

What happens when RANK-L binds to RANK?

A

Cells fuse and differentiate into mature multinucleated osteoclasts thus increasing bone resorption

38
Q

At the same time as Rank-L binding to RANK, what do mature osteoblasts make?

A

Free floating OPG (osteoprotegrin)

39
Q

What can OPG do?

A

It can bind to RANK-L allowing osteoblast activity to dominate -> increased bone build up

40
Q

Anatomically, what are the three types of bone?

A

Flat- scapula
Long- limbs
Cuboidal- vertebral

41
Q

What leads to flat bones?

A

Intramembranous ossification

42
Q

What leads to the development of long bones?

A

Endochondrial ossification

43
Q

Apart from anatomically, how else can bones be classified?

A

Their development:
Immature/woven
Mature/lamellar

44
Q

What is immature/woven bone like?

A

Lamellae are absent
Collagen fibres are disorganised; such as in states of high bone turnover (Paget’s, tumours) where they are in random bundles that are not closely packed

45
Q

Where is the only place in an adult that woven bone should be found?

A

Base of the tooth

46
Q

When is lamellar bone particularly evident?

A

When viewed under polarised light- collagen fibres are arranged in alternating orientations allowing for highest density

47
Q

What is metabolic bone disease caused by?

A

Disordered bone turnover due to imbalance of various chemicals in the body

48
Q

What is the overall effect of metabolic bone disease?

A

Reduced bone mass (osteopenia) leading to increased risk of fracture

49
Q

How is metabolic bone disease assessed?

A

Using histomorphology which requires un-decalcified bone

50
Q

What are the categories of metabolic bone disease?

A

Endocrine related- Vit D, PTH
Non-endocrine related- Age, iatrogenic
Disuse osteopenia

51
Q

What are the primary causes of osteoporosis?

A

Age

Post-menopausal

52
Q

What are secondary causes of osteoporosis?

A

Drugs and systemic disease

53
Q

What is the histopathology of a bone of someone with osteoporosis like?

A

Many holes and cysts

Mineralisation is normal but large marrow spaces

54
Q

What is very common with osteoporosis?

A

Neck and femur fractures

55
Q

What is osteomalacia?

A

Condition of defective bone mineralisation

56
Q

What can osteomalacia be caused by?

A

Vit D deficiency

Deficiency of phosphate usually related to chronic renal disease

57
Q

What is the mechanism of osteomalacia?

A

Vit D deficiency causes increase in PTH and subsequent increased bone resorption= hyperparathyroidism
Also causes hypocalcaemia

58
Q

What is the histology of a bone of someone with osteomalacia like?

A

No calcification of bone - more uncalcified osteoid (stains orange instead of green)- bones are very bendy so can’t carry musculature easily

59
Q

What are the sequelae (consequences) of osteomalacia?

A
Bending
Bone pain
Fracture
Proximal weakness
Bone deformity
60
Q

How can you investigate bone mineralisation?

A

Tetracycline fluorescent labelling which looks at mineralisation rate- Problems show fuzzy outline as opposed to distinct

61
Q

What does the excess PTH in hyperparathyroidism lead to?

A

Increased osteoclast activity > Increased bone resorption- osteitis fibrosis cystica
Increased calcium reabsorption and increased phosphate excretion- hypercalcaemia and hypophosphataemia
Increased absorption of dietary calcium via calcitriol production

62
Q

Which 4 organs are affected by hyperparathyroidism?

A

PT glands
Bone
Kidneys
Proximal small intestine

63
Q

What causes primary hyperparathyroidism?

A

PTH adenoma

Chief cell hyperplasia

64
Q

What causes secondary hyperparathyroidism?

A

Chronic renal disease

Vit D deficiency

65
Q

What are the symptoms of hyperparathyroidism?

A

Stones (kidney)
Bones (osteitis fibrosa cystica and bone resorption)
Abdominal groans (acute pancreatitis)
Psychic moans (psychosis and depression)

66
Q

What is the most important investigation for hyperparathyroidism?

A

XRAY of the hand

67
Q

What does an XRAY of the hand show in someone with hyperparathyroidism?

A

Sub-periosteal bone erosions

Small areas of resorption in the long bones of the fingers filled with osteoclasts- brown cell tumours

68
Q

What skeletal changes does renal osteodystrophy/chronic renal disease comprise?

A
Osteitis fibrosis cystica (increased bone resorption)
Osteomalacia
Osteosclerosis
Growth retardation
Osteoporosis
69
Q

What are the symptoms of renal osteodystrophy?

A
Hyperphosphataemia 
Hypocalcaemia resulting from decreased Vit D synthesis
Secondary hyperparathyroidism
Metabolic acidosis 
Aluminium deposition
70
Q

What is Paget’s disease?

A

Disorder of bone turnover due to lack of communication between cells

71
Q

What are the 3 stages of Paget’s?

A

Osteolytic whereby osteoclasts predominate -> bone resorption
Osteolytic-osteosclerotic- blasts fight back
Quiescent- osteosclerotic

72
Q

What is the epidemiology of Paget’s disease?

A

Middle aged

Common but rare in Asians and Africans

73
Q

Where is Paget’s normally found in the body?

A
Skull
Sternum
Spine
Humerus
Pelvis
Femur 
Tibia
74
Q

What are the clinical symptoms of Paget’s?

A
Pain
Microfractures
Nerve compression
Skull changes
Deafness
Haemodynamic changes
Cardiac failure
Hypercalcaemia
Development of sarcoma in area of involvement
75
Q

What is a haversian canal?

A

Channel that the blood vessels run in the bone

76
Q

What are caniculae important for?

A

They are routes for cell communication

77
Q

What are Howship’s lacunae?

A

Pits in the bone surface in which osteoclasts are found often called resorption bays