Pathology of Bone and Joints Flashcards
Where do osteocytes reside and how are they sustained?
In lacunae
Sustained via canaliculae
What types of cells are osteoprogenitor cells?
Mesenchymal stem cells
What is contained within the secretory vesicles of the osteoblasts?
Alkaline phosphatase
Pyrophosphatase
What is the role of the components of the secretory vesicles of osteoblasts?
Increase concentration of Ca2+ and PO4- locally to cause precipitation of hydroxyapatite
What is a comminuted fracture?
Fracture resulting in >2 separate bone components
What is a compound fracture?
Open fracture (break in the skin around the bone)
What causes a stress fracture?
Repeated low force injury to a normal bone
What are the 4 phases of fracture healing?
Bleeding and inflammation (granulation tissue)
Reparative phase with soft callus
Reparative phase with hard callus
Remodelling
What occurs with the formation of haematoma following fracture?
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
How long does haematoma formation take?
Hours to days
What changes occur with the formation of soft callus in the early reparative phase?
Fibrocartilage forms and holds the fractured ends together (but there is no structural rigidity)
Periosteum repairs itself over the outside
When does the reparative phase with soft callus formation occur?
Within days (cartilage) to weeks (soft callus)
What changes occur with the formation of hard callus in the late reparative phase?
Osteoid formation and cartilage removal (woven bone formation and endochondral ossification)
Thickened area of woven bone (rigid but not as strong)
When does the reparative phase with hard callus formation occur?
Within weeks to months
What changes occur with bone remodelling?
Woven bone remodelled to lamellar bone along lines of stress
When does bone remodelling occur?
Within months to years
How is fracture healing different if bone ends are closely opposed?
May not need soft callus at all
Healing will be faster but perhaps not as strong in early stages
More similar to intramembranous ossification
What occurs with fracture non-union?
Pseudo-arthrosis
What causes osteonecrosis? Give common examples
Fractures which interrupt the blood supply
E.g. NoF, scaphoid
What is Paget’s disease? What is the pathogenesis?
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
What are the 3 stages of Paget’s disease?
Osteolytic
Mixed
Osteosclerotic
What causes osteomalacia and rickets?
Vitamin D deficiency
What is the pathogenesis of osteomalacia/rickets?
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
What are the causes of primary hyperPTH?
Parathyroid hyperplasia or tumour
What are the causes of secondary hyperPTH?
Prolonged hypocalcaemia or hyperphosphataemia (e.g. in renal osteodystrophy)
What are the effects of hyperPTH?
Increased osteoclastic activity via RANK-L
Associated compensatory increase in osteoblastic activity
Name 2 conditions caused by hyperPTH and their features
Dissecting osteitis: osteoclasts in trabeculae
Osteitis fibrosa cystica: microfractures and granulation tissue
Name 4 symptoms of bony mets
Pathological fracture
Hypercalcaemia
Bone marrow failure
Bone pain
How do bony mets break down bone?
They produce RANK-L or PTHrP
List 5 primary tumours which commonly give rise to bony mets and their effects on bone
Breast (osteolytic) Bronchus (lung; osteolytic) Thyroid Kidney Prostate (osteosclerotic)
How is hyaline cartilage perfused?
By compression/decompression of cartilage e.g. with movement
What are the type A cells in synovium?
Macrophage-like
What are the type B cells in synovium?
Fibroblast-like
Which joints are preferentially affected in OA?
Hard-working hands and weight-bearing or previously-injured joints
What are the symptoms of OA?
Deep pain that gets worse with use (insidious onset)
Reduced RoM in joints, with crepitus and osteophyte formation
How is OA treated?
Physiotherapy
Pain relief
Joint replacement
Which joints are preferentially affected in RA?
Small joints of hands and/or feet
Symmetrical
What are the symptoms of RA?
Morning stiffness (eases with activity) with systemic symptoms (fever, LOW, anaemia) Warm, swollen joints Rheumatoid nodules Eventual destruction and deformity of joints
How is RA treated?
Using DMARDs (disease-modifying anti-rheumatic drugs)
Which joints are preferentially affected in gout?
Big toe (podagra)
What is the classical affected group in gout?
Male
Obesity
What is gout associated with risk of?
T2DM
Hypertension
CVD
How is gout treated?
Anti-inflammatory medication
Urate-lowering therapy
Lifestyle change
Describe the pathogenesis of OA
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
List 4 possible X-ray findings in OA
Loss of load-bearing joint space
Subchondral cysts
Osteophytes
Subchondral sclerosis
Describe the pathological process in RA
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
List 6 inflammatory changes seen in joints with RA
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
What are 3 important morphological findings in RA
Villous hyperplasia
Mononuclear infiltrate
GCs
What is a rheumatoid nodule?
Granulomatous inflammation
Central necrosis surrounded by epithelioid macrophages, and lymphocytes and fibrosis
Name 2 specific tests used to diagnose RA
Rheumatoid factor (RF) Anti-cyclic citrulinated peptide (anti-CCP)
List 3 X-ray findings in RA
Subchondral erosions
Uniform joint space loss (not just weight-bearing)
Juxta-articular osteopaenia (thin bone around joints)
List some risk factors for RA
Genetic: HLA-DRB1, PTPN-22
Female
Increasing age from 25-55
Smoking
List 4 morphological features of gouty tophi
Granulomatous inflammation (foreign body type) with central urate deposits surrounded by epithelioid macrophages, multinucleate giant cells and fibrosis
What is the gold standard for gout diagnosis?
Tophus aspiration demonstrating negatively birefringent crystals with PMNs
List 3 late-stage findings of gout
Punched-out erosions with sclerotic, overhanging edges outside of the joint capsule
Tophi may be visible (even calcified)
Asymmetric distribution
