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review histopath > Histo: Bone Pathology > Flashcards

Histo: Bone Pathology Flashcards

1
Q

What are the main functions of bone?

A
  • Mechanical - support and site for muscle attachment
  • Protective - vital organs and bone marrow
  • Metabolic - store of calcium
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2
Q

Outline the composition of bone.

A

Inorganic (65%) - Calcium hydroxyapatite.
Storehouse of 99% of body calcium, 85% of the phosphorus, 65% of sodium and magnesium

Organic (35%) - bone cells and protein matrix (mainly type 1 collagen)

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3
Q

In which part of a bone is the growth plate found?

A

Metaphysis

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4
Q

What are the main features of cortical bones?

A
  • Long bones
  • 80% of skeleton
  • Appendicular
  • 80-90% calcified
  • Mainly mechanical and protective
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5
Q

What are the main features of cancellous bones?

A
  • Vertebrae and pelvis
  • 20% of skeleton
  • Mainly axial
  • 15-25% calcified
  • Mainly metabolic
  • Large surface

Cancellous bone is metabolically more active than cortical.

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6
Q

Describe the microanatomy of bone.

A
  • Made up of several micro-columns (osteon)
  • Haversian canals are found at the middle of each osteon and contain blood vessels
  • Volkmann canals are canals that connect adjacent Haversian canals
  • Around the Haversian canals are concentric ring of matrix called concentric lamellae and in between these units will be interstitial lamellae
  • Osteocytes are located in lacunae within the lamellae
  • Around the entire bone you will find circumferential lamellae
  • In the middle the bone will be trabecular lamellae
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7
Q

What are the three main types of bone cell and what are their roles?

A
  • Osteoblasts - build bone by laying down osteoid
  • Osteoclasts - multinucleate cells of the macrophage family that resorb bone
  • Osteocytes - osteoblasts-like cells that sit in the lacunae
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8
Q

How are osteoclasts regulated?

A

Osteoblasts produce RANKL and osteoprotegrin
- RANKL - stimulates osteoclast differentation and activity
- Osteoprotegerin - blocks RANK thus inhibiting osteoclast differentiation and activity

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9
Q

Define metabolic bone disease.

A

A group of diseases characterised by disordered bone turnover due to imbalance of various body chemicals.

NOTE: overall effect tends to be osteopaenia

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10
Q

What are the three main categories of metabolic bone disease?

A
  • Non-endocrine (e.g. age-related)
  • Endocrine (e.g. vitamin D, PTH)
  • Disuse osteopaenia
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11
Q

Where is bone usually sampled from for histological analysis of bone in metabolic bone disease?

A

Iliac crest

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12
Q

Which static parameters are measured in the histological analysis of bone in metabolic bone disease?

A
  • Cortical thickness and porosity
  • Trabecular bone volume
  • Thickness, number and separation of trabeculae
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13
Q

Which technique is used to measure histodynamic parameters when investigating metabolic bone disease?

A

Fluorescent tetracycline labelling

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14
Q

What are the most common causes of osteoporosis?

A

90% are due to insufficient calcium intake or post-menopausal oestrogen deficiency

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15
Q

List some primary and secondary causes of osteoporosis.

A
  • Primary - age, post-menopause
  • Secondary - medication (steroids), systemic disease
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16
Q

List some risk factors for osteoporosis

A
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17
Q

Describe the ways in which osteoporosis can present.

A

Asymptomatic - usually presents with pathological fractures

  • Wrist - Colles’
  • Hip - NoF and intertrochanteric
  • Pelvic
  • Vertebral (60% asymptomatic) - compression fractures in T11-L1
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18
Q

Which investigations may be used in a patient with suspected osteoporosis?

A

Biochemical

  • Serum calcium, phosphate and ALP (should be NORMAL)
  • Urinary calcium
  • Collagen breakdown products

Imaging

DEXA

  • Osteopenia = T score 1-2.5 SD below normal
  • Osteoporosis = T score >2.5 below normal
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19
Q

Which four organs are affected by PTH and have a role in calcium homeostasis?

A
  • Kidney
  • Bone
  • Proximal small intestine
  • Parathyroid gland
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20
Q

What is the most common cause of hypocalcaemia?

A

Vitamin D deficiency

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21
Q

Define osteomalacia.

A

Defective bone mineralisation

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22
Q

What two underlying abnormalities can cause osteomalacia?

A
  • Deficiency of vitamin D
  • Deficiency of phosphate
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23
Q

What is the main histological feature of osteomalacia?

A

Reduced amount of mineralised bone compared to the amount of osteoid

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24
Q

List some signs and symptoms of osteomalacia.

A
  • Bone pain/tenderness
  • Fracture
  • Proximal weakness
  • Bone deformity
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25
Q

Name some radiological features of osteomalacia.

A
  • Bowing of the legs (rickets)
  • Metaphysial cupping and fraying (rickets)
  • Horizontal pseudofractures (Looser zone)
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26
Q

Describe how the urine excretion of calcium and phosphate changes in primary hyperparathyroidism.

A

Both increase

NOTE: PTH causes a minor increase in reabsorption of calcium from the urine, however, as it causes a large increase in serum calcium concentration (and hence an increase in the calcium concentration of the glomerular filtrate) it causes an overall increase in urine calcium excretion

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27
Q

What skeletal change is seen in primary hyperparathyroidism?

A

Osteitis fibrosa cystica (brown tumours on X-ray)

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28
Q

List the main primary and secondary causes of hyperparathyroidism.

A

Primary

  • Parathyroid adenoma (90%)
  • Chief cell hyperplasia

Secondary

  • CKD
  • Vitamin D deficiency
  • Malabsorption
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29
Q

What histological feature is typically seen in hyperparathyroidism?

A

Brown cell tumour - several multinucleated giant cells (osteoclasts) on a background of fibrous stroma with haemorrhage

30
Q

Define renal osteodystrophy.

A

Term used to describe all the skeletal changes of chronic renal disease:

  • Increased bone resorption (osteitis fibrosa cystica)
  • Osteomalacia
  • Osteosclerosis
  • Osteoporosis
  • Growth retardation
31
Q

What is Paget’s disease and what are its three phases?

A

Disorder of bone turnover

Three phases:

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

NOTE: the combination of osteoblast and osteoclast activity results in new bone formation

NOTE: 85% are polyostotic

32
Q

Describe the histological appearance of Paget’s disease.

A

Mosaic pattern of randomly organised lamellar bone

33
Q

Which viruses are associated with Paget’s disease?

A

Paramyxoviruses

34
Q

Describe the presentation of Paget’s disease.

A
  • Pain
  • Microfractures
  • Deformity - bowing of tibia
  • Nerve compression - spinal nerves and cord
  • Skull changes - can put medulla at risk

Can also cause haemodynamic changes and high output heart failure

Development of sarcoma in area of involvement 1%

35
Q

Which bones are most affected by Paget’s?

A
36
Q

What are the four stages of fracture repair?

A
  • Organisation of a haematoma at the site of the fracture (pro-callus)
  • Formation of a fibrocartilaginous callus
  • Mineralisation of the fibrocartilaginous callus
  • Remodelling of the bone along weight-bearing lines
37
Q

List some factors that influence fracture healing.

A
  • Type of fracture
  • Presence of infection
  • Pre-existing systemic conditions (e.g. chronic conditions)
38
Q

Which sites are most commonly affected by osteomyelitis?

A
  • Vertebra
  • Jaw (secondary to dental abscess)
  • Toe (secondary to diabetic skin ulcer)
  • Long bones (usually metaphysis)
39
Q

Describe the typical presentation of osteomyelitis.

A

General - malaise, fever, rigors, leukocytosis

Local - pain, swelling, redness

40
Q

Which investigations may be used in suspected osteomyelitis?

A
  • Blood cultures (positive in 60%)
  • X-ray (will eventually show lytic areas)
41
Q

What are the routes of infection in osteomyelitis?

A
  • Haematogenous
  • Direct extension
  • Traumatic (penetrating injury)
42
Q

Which organisms can cause osteomyelitis?

A
  • Staphylococcus aureas (90%)
  • E. coli
  • Klebsiella
  • Salmonella (SCD)
  • Pseudomonas (IVDU)

Osteomyelitis is almost always bacterial (rarely fungal)

43
Q

When do X-ray changes appear in osteomyelitis and describe them?

A

Usually appear about 10 days after onset

  • Mottled rarefaction and lifting of periosteum
  • First week changes - involucrum formation
  • Later changes - irregular lytic destruction
  • Sequestra may form after 3-6 weeks
44
Q

What are involucrum and sequestra?

A

Involucrum - bone that has formed around an area of dead necrotic bone (analogous to an abscess in soft tissue)

Sequestra - a piece of dead bone that has been separated off (can be a foci of infection)

45
Q

What are the potential consequences of TB osteomyelitis of the vertebrae?

A
  • May result in psoas abscess or severe skeletal deformity
  • TB osteomyelitis tends to only occur in immunocompromised patients
  • Systemic amyloidosis may occur in some cases

Called Pott’s disease

46
Q

Describe the histological appearance of TB osteomyelitis.

A
  • Lots of inflammatory cells can be seen in between trabeculae
  • Langhans giant cells (with a horse-shoe nucleus) can be seen
47
Q

What congenital skeletal lesions are associated with syphilis?

A
  • Osteochondritis
  • Osteoperiositis
  • Diaphyseal osteomyelitis
48
Q

List some acquired skeletal lesions that are associated with syphilis.

A
  • Non-gummatous periostitis
  • Gummatous inflammation of joints and bones
  • Neuropathic joints (tabes dorsalis)
  • Neuropathic shaft fractures
49
Q

What is Lyme disease?

A
  • Inflammatory arthropathy that occurs as part of a complex multisystem illness from a tick bite
50
Q

What is the organism and vector in lyme disease?

A

Organism: Borrelia burgdorferi

Vector: Ixodus dammini

51
Q

What is the skin rash that is classically associated with lyme disease?

A

Erythema chronicum migrans

52
Q

Describe the clinical features of Lyme disease at different stages

A
  • Early localised - flu-like symptoms with rash (90%) often on thigh, groin or axilla, 1-50 cm in diameter
  • Early disseminated - affects many organs (musculoskeletal, heart, nervous system)
  • Late, persistent - dominated by arthritis
53
Q

Outline the diagnosis and treatment of lyme disease.

A
  • Diagnosis is often clincial but can use ELISA if there is no erythema migrans
  • Treat with antibiotics (doxycycline)
54
Q

What is the difference between primary and secondary osteoarthritis?

A

Primary - age-related

Secondary - can occur at any age, occurs in a previously damaged or congenitally abnormal joint

55
Q

What happens to the joint in OA?

A
  • Cartilage degeneration
  • Fissuring
  • Abnormal matrix calcification
  • Osteophyte formation

Synovium becomes inflamed with inflammatory cell infiltrate

56
Q

What are the main sites affected by osteoarthritis?

A
  • Vertebrae
  • Hips
  • Knees
  • DIP and PIP of the hand
57
Q

What are the HLA associations of rheumatoid arthritis?

A

HLA DR4 and HLA DR1 (Chr6p21)

58
Q

What is rheumatoid factor and what proportion of patient’s are rheumatoid factor positive?

A
  • IgM antibody against IgG
  • 80% of patients are RF positive
  • Circulating immune complexes may be responsible for extra-articular disease
59
Q

Which sites tend to be affected by rheumatoid arthritis?

A
  • Small joints of the hand and feet (sparing the DIP)
  • Wrists, elbows, ankles and knees

Patients can also get rheumatoid nodules in the skin (25%)

60
Q

List some characteristic deformities associated with rheumatoid arthiritis.

A
  • Radial deviation of the wrist
  • Ulnar deviation of the fingers
  • Swan neck and Boutonnier deformity
  • Z-shaped thumb
61
Q

Describe the histological features of rheumatoid arthritis.

A
  • Proliferative synovitis with thickening of synovial membranes, hyperplasia of surface synoviocytes, intense inflammatory cell infiltrate and fibrin deposition and necrosis
  • A pannus can form (exuberant inflamed synovium)
62
Q

Which type of multinucleate giant cell may be seen in rheumatoid arthritis?

A

Grimley-Sokoloff cell (like a Langhans giant cell but does not have horseshoe nuclei)

63
Q

What type of crystals cause gout?

A

Needle-shaped negatively birefringent urate crystals

NOTE: big toe is involved in 90% of cases

NOTE: a tophus is pathognomonic of gout

64
Q

Which crystals cause pseudogout? Describe them

A

Calcium crystals

  • Calcium pyrophosphate - mainly knees
  • Calcium phosphate (hydroxyapatite) - knees and shouldrs

Crystals are rhomboid-shaped and positively birefringent

65
Q

Which tumours most commonly metastasis to the bone in:

  1. Adults
  2. Children
A

Adults:

  • Breast
  • Prostate
  • Lung
  • Kidney
  • Thyroid

Children:

  • Neuroblastoma
  • Wilm’s tumour
  • Osteosarcoma
  • Ewing’s
  • Rhabdomyosarcoma
66
Q

Name three types of primary malignant bone tumours.

A
  • Osteosarcoma
  • Chondrosarcoma
  • Ewing’s sarcoma/PPNET
67
Q

What are the key epidemiological and radiological features of osteosarcoma?

A

Most common primary bone tumour

Incidence peaks in adolescence

60% of cases affect the knee

X-ray: usually metaphysial, lytic, permeative, elevated periosteum (Codman’s triangle)

68
Q

Describe the histological appearance of osteosarcoma.

A

Malignant mesenchymal cells with or without bone and cartilage formation

69
Q

What are the main epidemiological, clinical, radiological, and histological features of chondrosarcoma?

A

Malignant cartilage producing tumour

Typically affects >40 years

Affects axial skeleton, proximal femur and proximal tibia

X-ray: lytic with fluffy calcification

Histology: malignant chondrocytes with or without chondroid matrix

70
Q

What are the main epidemiological, clinical, radiological, and histological features of Ewing’s sarcoma?

A

Highly malignant small round cell tumour

Typically affects <20 years

Mainly affect diaphysis and metaphysis of long bones, pelvis

X-ray: onion-skinning of the periosteum, lytic with or withour sclerosis

Histology: sheets of small round cells

Specific chromosomal translocation - 11;22 (EWS/FLI1)

71
Q

Which chromosomal translocation is associated with Ewing’s sarcoma?

A

11;22 (ESWR1:Fli1)

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