Pathology of Bone and Joints

Question 1

Where do osteocytes reside and how are they sustained?

Answer 1

In lacunae

Sustained via canaliculae

Question 2

What types of cells are osteoprogenitor cells?

Answer 2

Mesenchymal stem cells

Question 3

What is contained within the secretory vesicles of the osteoblasts?

Answer 3

Alkaline phosphatase

Pyrophosphatase

Question 4

What is the role of the components of the secretory vesicles of osteoblasts?

Answer 4

Increase concentration of Ca2+ and PO4- locally to cause precipitation of hydroxyapatite

Question 5

What is a comminuted fracture?

Answer 5

Fracture resulting in >2 separate bone components

Question 6

What is a compound fracture?

Answer 6

Open fracture (break in the skin around the bone)

Question 7

What causes a stress fracture?

Answer 7

Repeated low force injury to a normal bone

Question 8

What are the 4 phases of fracture healing?

Answer 8

Bleeding and inflammation (granulation tissue)
Reparative phase with soft callus
Reparative phase with hard callus
Remodelling

Question 9

What occurs with the formation of haematoma following fracture?

Answer 9

Fibrin mesh creates framework
Platelets and leukocytes release inflammatory cytokines
Granulation tissue forms
Bone cells are activated to start repair
There is variable necrosis of bone at the fracture

Question 10

How long does haematoma formation take?

Answer 10

Hours to days

Question 11

What changes occur with the formation of soft callus in the early reparative phase?

Answer 11

Fibrocartilage forms and holds the fractured ends together (but there is no structural rigidity)
Periosteum repairs itself over the outside

Question 12

When does the reparative phase with soft callus formation occur?

Answer 12

Within days (cartilage) to weeks (soft callus)

Question 13

What changes occur with the formation of hard callus in the late reparative phase?

Answer 13

Osteoid formation and cartilage removal (woven bone formation and endochondral ossification)
Thickened area of woven bone (rigid but not as strong)

Question 14

When does the reparative phase with hard callus formation occur?

Answer 14

Within weeks to months

Question 15

What changes occur with bone remodelling?

Answer 15

Woven bone remodelled to lamellar bone along lines of stress

Question 16

When does bone remodelling occur?

Answer 16

Within months to years

Question 17

How is fracture healing different if bone ends are closely opposed?

Answer 17

May not need soft callus at all
Healing will be faster but perhaps not as strong in early stages
More similar to intramembranous ossification

Question 18

What occurs with fracture non-union?

Answer 18

Pseudo-arthrosis

Question 19

What causes osteonecrosis? Give common examples

Answer 19

Fractures which interrupt the blood supply

E.g. NoF, scaphoid

Question 20

What is Paget’s disease? What is the pathogenesis?

Answer 20

Osteitis deformans
Large, overactive osteoclasts break down bone
There is then production of more bone by osteoblasts, resulting in thick soft cortical and coarse trabecular bone which is easily fractured and may compress nerves

Question 21

What are the 3 stages of Paget’s disease?

Answer 21

Osteolytic
Mixed
Osteosclerotic

Question 22

What causes osteomalacia and rickets?

Answer 22

Vitamin D deficiency

Question 23

What is the pathogenesis of osteomalacia/rickets?

Answer 23

Inadequate vitamin D means more PTH is required and phosphate is lost in urine, which leads to impaired bone mineralisation and increased osteoid production
There is an overall loss of structural integrity

Question 24

What are the causes of primary hyperPTH?

Answer 24

Parathyroid hyperplasia or tumour

Question 25

What are the causes of secondary hyperPTH?

Answer 25

Prolonged hypocalcaemia or hyperphosphataemia (e.g. in renal osteodystrophy)

Question 26

What are the effects of hyperPTH?

Answer 26

Increased osteoclastic activity via RANK-L | Associated compensatory increase in osteoblastic activity

Question 27

Name 2 conditions caused by hyperPTH and their features

Answer 27

Dissecting osteitis: osteoclasts in trabeculae | Osteitis fibrosa cystica: microfractures and granulation tissue

Question 28

Name 4 symptoms of bony mets

Answer 28

Pathological fracture Hypercalcaemia Bone marrow failure Bone pain

Question 29

How do bony mets break down bone?

Answer 29

They produce RANK-L or PTHrP

Question 30

List 5 primary tumours which commonly give rise to bony mets and their effects on bone

Answer 30

``` Breast (osteolytic) Bronchus (lung; osteolytic) Thyroid Kidney Prostate (osteosclerotic) ```

Question 31

How is hyaline cartilage perfused?

Answer 31

By compression/decompression of cartilage e.g. with movement

Question 32

What are the type A cells in synovium?

Answer 32

Macrophage-like

Question 33

What are the type B cells in synovium?

Answer 33

Fibroblast-like

Question 34

Which joints are preferentially affected in OA?

Answer 34

Hard-working hands and weight-bearing or previously-injured joints

Question 35

What are the symptoms of OA?

Answer 35

Deep pain that gets worse with use (insidious onset) | Reduced RoM in joints, with crepitus and osteophyte formation

Question 36

How is OA treated?

Answer 36

Physiotherapy Pain relief Joint replacement

Question 37

Which joints are preferentially affected in RA?

Answer 37

Small joints of hands and/or feet | Symmetrical

Question 38

What are the symptoms of RA?

Answer 38

``` Morning stiffness (eases with activity) with systemic symptoms (fever, LOW, anaemia) Warm, swollen joints Rheumatoid nodules Eventual destruction and deformity of joints ```

Question 39

How is RA treated?

Answer 39

Using DMARDs (disease-modifying anti-rheumatic drugs)

Question 40

Which joints are preferentially affected in gout?

Answer 40

Big toe (podagra)

Question 41

What is the classical affected group in gout?

Answer 41

Male | Obesity

Question 42

What is gout associated with risk of?

Answer 42

T2DM Hypertension CVD

Question 43

How is gout treated?

Answer 43

Anti-inflammatory medication Urate-lowering therapy Lifestyle change

Question 44

Describe the pathogenesis of OA

Answer 44

Damage stimulates chondrocyte proliferation, enzyme/cytokine (e.g. IL-1) production by synovial cells and "unravelling" of cartilage matrix Release of enzymes (e.g. collagenases, MMPs) from cartilage matrix Loss of mechanical function Changes in bone (thickening and microfractures) Shedding of cartilage ("fibrillation" erosions) Bone-on-bone contact causes eburnation, production of cysts and osteophytes

Question 45

List 4 possible X-ray findings in OA

Answer 45

Loss of load-bearing joint space Subchondral cysts Osteophytes Subchondral sclerosis

Question 46

Describe the pathological process in RA

Answer 46

T-helper cells (TH1, TH17) release cytokines (IL-1, IL-6, IL-17, TNF-a) Induces fibroblasts, macrophages, osteoclasts and B cells, resulting in production of pannus Collagenases and MMPs breakdown cartilage and bone Eventual fibrous and then bony union of joints

Question 47

List 6 inflammatory changes seen in joints with RA

Answer 47

Mononuclear infiltrate in synovium with GCs Hyperplasia of synovium with villus formation (becomes pannus) PMNs and fibrin may be found within joint space Pannus invades and erodes bone and cartilage Weakening and destruction of ligaments Eventual fibrous and then bony union of joints

Question 48

What are 3 important morphological findings in RA

Answer 48

Villous hyperplasia Mononuclear infiltrate GCs

Question 49

What is a rheumatoid nodule?

Answer 49

Granulomatous inflammation | Central necrosis surrounded by epithelioid macrophages, and lymphocytes and fibrosis

Question 50

Name 2 specific tests used to diagnose RA

Answer 50

``` Rheumatoid factor (RF) Anti-cyclic citrulinated peptide (anti-CCP) ```

Question 51

List 3 X-ray findings in RA

Answer 51

Subchondral erosions Uniform joint space loss (not just weight-bearing) Juxta-articular osteopaenia (thin bone around joints)

Question 52

List some risk factors for RA

Answer 52

Genetic: HLA-DRB1, PTPN-22 Female Increasing age from 25-55 Smoking

Question 53

List 4 morphological features of gouty tophi

Answer 53

Granulomatous inflammation (foreign body type) with central urate deposits surrounded by epithelioid macrophages, multinucleate giant cells and fibrosis

Question 54

What is the gold standard for gout diagnosis?

Answer 54

Tophus aspiration demonstrating negatively birefringent crystals with PMNs

Question 55

List 3 late-stage findings of gout

Answer 55

Punched-out erosions with sclerotic, overhanging edges outside of the joint capsule Tophi may be visible (even calcified) Asymmetric distribution