YEAR 5: HISTOPATH > Histo: Bone Pathology > Flashcards

Histo: Bone Pathology Flashcards

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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 (and 85% of phosphorus, 65% of sodium and magnesium)
  • Organic (35%) - bone cells and protein matrix
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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
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6
Q

Describe the microanatomy of bone.

A
  • Made up of several micro-columns
  • Haversian canals are found at the middle of the micro-columns
  • Volkmann canals are canals that connect the Haversian canals
  • Around the Haversian canals are concentric lamellae and in between these units will be interstitial lamellae
  • Around the entire bone you will find circuferential lamellae
  • In the middle the bone will be trabecular lamellae
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7
Q

Describe the histological appearance of cancellous bone.

A

Trabeculae are dark pink areas and in between you will find adipose tissue with haemopoietic cells

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8
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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9
Q

Which protein is important in regulating the action of osteoclasts?

A

Osteoblasts produce osteoprotegrin which blocks the RANK-RANKL interaction which prevents the differentiation of an osteoclast precursor into a fully functioning osteoclast

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10
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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11
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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12
Q

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

A

Iliac crest

NOTE: the sample be processed and un-decalcified for histomorphometry

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13
Q

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

A
  • Cortical thickness
  • Trabecular bone volume
  • Thickness, number and separation of trabeculae
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14
Q

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

A

Tetracycline labelling

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15
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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16
Q

List some primary and secondary causes of osteoporosis.

A
  • Primary - age, post-menopause
  • Secondary - steroids, systemic disease
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17
Q

Broadly speaking, what are the two rutes by which disordered bone turnover can cause osteoporosis?

A
  • High turnover results in high bone resorption
  • Low turnover results in low bone formation
  • Both resulted in reduced bone mass
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18
Q

What are the effects of long-term steroid use on bone?

A
  • Affects all three bone cell types
  • Leads to decrease in bone quality
  • Ultimately results in osteonecrosis and fracture
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19
Q

Describe the ways in which osteoporosis can present.

A
  • Back pain
  • Pathological fractures
    • Wrist (Colles’)
    • Hip (NOF, intertrochanteric)
    • Pelvic
    • Vertebra (60% asymptomatic)
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20
Q

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

A
  • Serum calcium, phosphate and ALP (should be NORMAL)
  • Urinary calcium
  • Collagen breakdown products
  • Imaging
  • DEXA
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21
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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22
Q

Define osteomalacia.

A

Defective bone mineralisation

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23
Q

What two underlying abnormalities can cause osteomalacia?

A
  • Deficiency of vitamin D (causes low Ca2+)
  • Deficiency of phosphate
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24
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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25
List some consequences of osteomalacia.
* Bone pain/tenderness * Fracture * Proximal weakness * Bone deformity
26
Name some radiological features of osteomalacia.
* Bowing of the legs in Rickets * Horizontal pseudofractures in Looser's zones
27
Describe how the urine excretion of calcium and phosphate changes in primary hyperparathyroidism.
* 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
28
What skeletal change is seen in primary hyperparathyroidism?
Osteitis fibrosa cystica
29
List the main primary and secondary causes of hyperparathyroidism.
**Primary** * Parathyroid adenoma (90%) * Chief cell hyperplasia **Secondary** * Chronic renal deficiency * Vitamin D deficiency * Malabsorption
30
What histological feature is typically seen in hyperparathyroidism?
Brown cell tumour - several multinucleated giant cells on a background of fibrous stroma with haemorrhage
31
Define renal osteodystrophy.
Term used to describe all the skeletal changes of chronic renal disease: * Increased bone resorption (osteitis fibrosa cystica) * Osteomalacia * Osteosclerosis * Osteoporosis * Growth retardation
32
What is Paget's disease and what are its three phases?
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
33
Describe the histological appearance of Paget's disease.
Lines will be seen between areas of new bone formation so it looks like a mosaic/jigsaw puzzle.
34
Which virus is associated with Paget's disease.
Parvomyxovirus
35
Describe the presentatino of Paget's disease.
* Most lesions affect the skull and lumbar spine * Pain * Microfractures * Nerve compression * Skull changes (can put the medulla at risk leading to haemodynamic changes) * Sarcoma * Paget's disease of the tibia can cause bowing
36
What are the four stages of fracture repair?
* 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
List some factors that influence fracture healing.
* Type of fracture * Presence of infection * Pre-existing systemic conditions (e.g. chronic conditions)
38
Which sites are most commonly affected by osteomyelitis?
* Vertebra * Jaw (secondary to dental caries) * Toe * Long bones (usually metaphysis)
39
Describe the typical presentation of osteomyelitis.
General - FLAWS Local - pain, swelling, redness
40
Which investigations may be used in suspected osteomyelitis?
* Blood cultures (positive in 60%) * X-ray (will eventually show lytic areas) NOTE: osteomyelitis is almost always bacterial
41
What are the routes of infection in osteomyelitis?
* Haematogenous * Direct extension * Traumatic (penetrating injury)
42
Which organisms can cause osteomyelitis?
* *Staphylococcus aureas* (90%) * *E. coli* * *Klebsiella* * *Pseudomonas* (IVDU)
43
Which bacterium is associated with osteomyelitic in patients with sickle cell disease?
*Salmonella*
44
Describe the X-ray changes seen in osteomyelitis.
* Usually appear about 10 days after onset * Mottled rarefaction and lifting of periosteum * First week changes - irregular sub-periosteal new bone formation (involucrum - layer of new bone that forms around dead bone) * Later changes - irregular lytic destruction * Some areas of the necrotic cortex may become detached (sequestra). This takes 3-6 weeks
45
What are the potential consequences of TB osteomyelitis of the vertebrae?
* aka Pott's disease * May result in psoas abscess or skeletal deformity e.g. kyphosis from vertebral body collapse NOTE: TB osteomyelitis tends to only occur in immunocompromised patients NOTE: systemic amyloidosis may occur in some cases
46
Describe the histological appearance of TB osteomyelitis.
* Lots of inflammatory cells can be seen in between trabeculae * Langerhans-type giant cells (with a horse-shoe nucleus) will be seen
47
What congenital skeletal lesions are associated with syphilis?
* Osteochondritis * Osteoperiositis * Diaphyseal osteomyelitis
48
List some acquired skeletal lesions that are associated with syphilis.
* Non-gummatous periostitis * Gummatous inflammation of joints and bones * Neuropathic joints (tabes dorsalis) - degeneration of dorsal columns - loss of proprioception + vibration * Neuropathic shaft fractures
49
What is lyme disease?
* Inflammatory arthropathy that occurs as part of a complex multisystem illness from a tick bite
50
What is the organism and vector in lyme disease?
Organism: *Borrelia burgdorferi* Vector: *Ixodus dammini* - tick
51
What is the skin rash that is classically associated with lyme disease?
Erythema chronicum migrans
52
Describe the clinical features of lyme disease.
* **Early localised** - 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
Outline the treatment of lyme disease.
* Aim for prevention * Antibiotics - doxycycline * No effective prophylaxis -remove tick * Diagnosis is clinical
54
What is the difference between primary and secondary osteoarthritis?
* **Primary** - age-related * **Secondary** - can occur at any age, occurs in a previously damaged or congenitally abnormal joint
55
What are the main sites affected by osteoarthritis?
* Vertebrae * Hips * Knees * DIP and PIP of the hand NOTE: the synovium becomes very inflamed with lots of inflammatory cells (lymphocytes)
56
What are the HLA associations of rheumatoid arthritis?
HLA DR4 and HLA DR1 (Chr6p21) Other alleles: TFNA1P3, STAT4
57
What is rheumatoid factor and what proportion of patient's with rheumatoid arthritis are rheumatoid factor positive?
* IgM antibody against IgG * 80% positive * May be responsible for extra-articular disease
58
Which sites tend to be affected by rheumatoid arthritis?
* Small joints of the hand and feet (except DIP) * Wrists, elbows, ankles and knees
59
List some characteristic deformities associated with rheumatoid arthiritis.
* Radial deviation of the wrist * Ulnar deviation of the fingers * Swan neck and Boutonnier deformity * Z-shaped thumb
60
Describe the histological features of rheumatoid arthritis.
* 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)
61
Which type of multinucleate giant cell may be seen in rheumatoid arthritis?
Grimley-Sokoloff cell (like a Langerhans cell but does not have horseshoe nuclei)
62
What type of crystals cause gout?
Needle-shaped negatively birefringent urate crystals NOTE: big toe is involved in 90% of cases NOTE: a tophus is pathognomonic of gout
63
Which crystals cause pseudogout?
* Calcium crystals * Calcium pyrophosphate - mainly knees * Calcium phosphate (hydroxyapatite) - knees and shouldrs * Rhomboid-shaped positively birefringent crystals
64
Which tumours most commonly metastasis to the bone in: 1. Adults 2. Children
**Adults:** * Breast * Prostate * Lung * Kidney * Thyroid **Children:** * Neuroblastoma * Wilm's tumour * Osteosarcoma * Ewing's * Rhabdomyosarcoma
65
Name three types of primary malignant bone tumours.
* Osteosarcoma * Chondrosarcoma * Ewing's sarcoma/PPNET
66
What are the key clinical and radiological features of osteosarcoma?
* Peak in adolescence * 60% around the knee * X-ray: usually metaphysial, lytic, permeative, elevated periosteum (Codman's triangle)
67
Describe the histological appearanc of osteosarcoma.
Malignant mesenchymal cells with or without bone and cartilage formation
68
What are the main clinical, radiological and histological features of chondrosarcoma?
* Malignant cartilage producing tumour * Affects axial skeleton, proximal femur and proximal tibia * X-ray: lytic with fluffy calcification * Histology: malignant chondrocytes with or without chondroid matrix
69
What are the main clinical, radiological and histology features of Ewing's sarcoma?
* Highly malignant small round cell tumour * Occurs in \<20 years * Mainly affect diaphysis and metaphysis of long bones * X-ray: onion skinning of the periosteum, lytic with or withour sclerosis * Histology: sheets of small round cells
70
Which chromosomal translocation is associated with Ewing's sarcoma?
11;22 (ESWR1:Fli1)
YEAR 5: HISTOPATH
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